炭素－水素結合など不活性結合の直接的な官能基化は、原子効率、工程数の削減から理想的な合成変換であるが、望みの不活性結合を位置選択的に活性化するためには、反応部位に金属触媒を接近させる「配向基」が一般に用いられる。私は、「配向基」を単なる「活性化基」として用いるのではなく、生成物の付加価値を高め、その後の多彩な合成変換を可能にする「機能性基」として位置づけ触媒反応の開発を行った。
まず私は、カチオン性イリジウム触媒を用いることで、配向基（DG）を有するフェロセン化合物に対し、酸化的C-H結合開裂を起点とするアルキル化、アルケニル化を行った。その結果、2-pyridyl基を配向基を用いた場合、三置換、一方1-isoquinolyl基を用いた場合、二置換フェロセン化合物が選択的に得られた。
次にカチオン性イリジウム触媒を用いたアルケン類との反応により、インドールの2位選択的なアルキル化を達成した。さらに、窒素上の置換基（Ac基とBz基）と、触媒に用いるホスフィン配位子（SEGPHOSとSDP）の適切な組み合わせにより、直鎖型（linear）と分岐型（branched）アルキル化体の選択的な合成に成功した。複素環であるインドールは多くの生理活性化合物の母骨格あり、位置選択的な炭素鎖や官能基の導入法の開発が望まれている。3位は電子豊富でありFriedel-Crafts反応に対する活性部位であるが、2位のC-H結合の直接的なアルキル化の例は、本例が初めてである。
そして、新形式のC-H結合活性化を伴う反応として“ロールオーバー”を経る反応を目指し、3-アルキニル-2-アリールピリジンの反応を検討した。様々な遷移金属触媒の検討の結果、ロジウム触媒[Cp*RhCl2]2に触媒量の銅塩Cu(OAc)2を添加することで効率よく反応が進行し、4-アザフルオレン誘導体が得られた。

I reported an enantioselective ortho-lithiation of achiral paracyclophanes with oxygen atoms as directed moieties at both ends of ansa-chain using a chiral lithium reagent. The reaction of an unflippable 1,n-dioxa[n]paracyclophane (n?□11) with sec- utyllithium and (-)-sparteine gave the chiral mono-lithiated product. Additional amount of sec-butyllithium gave C_2-symmetric dilithiated product. The quenching of these lithium salts by appropriate electrophiles gave various planar-chiral aracyclophanes with excellent ee. The planar-chiral mono- and diphosphines, which were prepared by the above protocols, were used as chiral ligands in transition metal-catalyzed reactions.

Biologically related compounds such as L-amino acids are composed of one of the enantiomers. The phenomenon is called biological homochirality, and the origin of homochirality has attracted broad interest. Asymmetric autocatalysis, i.e., Soai reaction, is a reaction in which chiral product acts as a chiral catalyst for its own production. It was found that chiral isotopomers of carbon, hydrogen and oxygen, spontaneous absolute asymmetric synthesis, chiral crystals formed from achiral organic compounds such as nucleic acid base act as chiral initiators of asymmetric autocatalysis. Highly enantioenriched chiral compounds withthe corresponding absolute configurations with those of chiral initiators are obtained.

Transition metal catalyzed-reactions realize efficient and useful synthetic transformations. In particular, transition metals with chiral ligands can induce high enantioselectivity, and various types of chiral skeletons can be synthesized. I have focused on the development of chiral transition metal-catalyzed cycloadditions in this project. For example, consecutive inter- and intramolecular [2+2+2] cycloadditions of two o-phenylene-tethered triynes provided highly enantioselective synthesis of chiral substituted tetraphenylenes. The present protocol is a new and facile approach to the construction of chiral tetraphenylene skeleton. We also reported the enantioselective synthesis of the tripodal cage-type compounds with planar chirality. Intramolecular [2+2+2] cycloaddition of branched triynes, where diyne and alkyne moieties were connected by 2-aminophenol linkage, gave tripodal cyclophanes with almost perfect enantioselectivity.

報告者は、キラルイリジウム触媒を用い、「アルキンの三量化によるベンゼン環の構築とともに軸不斉を創製する」というコンセプトで総括的に研究を行っている。今回は、複数の反応点をもつ連続反応に焦点を当て、軸不斉ビアリール骨格の構築を検討した。
まず、1,3-ジイン部分により二つの1,6-ジイン部分が連結されたテトラインと、アルキンの分子間連続的[2+2+2]付加環化反応を検討した。その結果、従来の1,6-ジインとアルキンの反応の場合と異なり、アルキンの嵩高さがエナンチオ選択性に影響を及ぼすことがわかった。例えば2-ブチン-1,4-ジオールを嵩高いシリル基で保護したアルキンを用いることにより、90%前後の高い不斉収率で、ビアリール誘導体を得ることができた。
次に、1,3-ジイン部分により二つのトリイン部分が連結されたヘキサインの分子内連続的[2+2+2]付加環化反応を検討した。その結果、両末端にアリール基、あるいは嵩高いイソプロピル基を導入した基質を用いることにより、対応するビアリール誘導体を高不斉収率で得た。
さらに、ベンゼン環により架橋された1,7-ジインを出発物質として、アルキンとの分子間[2+2+2]付加環化反応、生成物の1,4-シクロヘキサジイン部分の酸化による芳香化を二回繰り返すことにより、軸不斉を有する光学活性なペンタセン骨格の合成に初めて成功した。
これらの結果は、アルキン類の[2+2+2]付加環化反応による軸不斉の創製というコンセプトの汎用性を示すとともに、芳香環を含む多縮環型光学活性化合物の合成手法を提供したと言える。

Pyrimidyl alkanol was found to act as an asymmetric autocatalysis in the reaction between pirimidine-5-carbaldehyde and diisopropylzinc, affording highly enantioenriched pyrimidyl alkanol with the same structure and absolute configuration. When asymmetric autocatalyst with very low enantiomeric excess (ee) was employed, significant amplification of ee was observed. Starting from asymmetric autocatalyst with very low ee, three consecutive asymmetric autocatalysis afforded practically enantiopure (>99.5% ee) pyrimidyl alkanol. Asymmetric autocatalysis has been employed to examine the validity of the origin of chirality. It was found that chiral inorganic crystal such as sodium chlorate act as chiral initiator of asymmetric autocatalysis. Direct irradiation of circularly polarized light (CPL) to racemic pyrimidyl alkanol and the subsequent asymmetric autocatalysis gave highly enantioenriched pyrimidyl alkanol with the related configuration to that of the direction of CPL. In addition, certain ketoolefin to which CPL induces the enantioenrichment by asymmetric photoequilibrium can act as a chiral initiator of asymmetric autocatalysis. Chiral crystals of achiral organic compound such as cytosine acts as chiral initiator of asymmetric autocatalysis. Spontaneous absolute asymmetric synthesis in the presence of achiral silica gel was achieved without adding chiral initiator in the reaction between pyrimidine-5-carbaldehyde and diisopropylzinc. Chiral discrimination of cryprochiral compound such as satirated quaternary hydrocarbon was achieved by using asymmetric autocatalysis. As described, we have found highly efficient asymmetric autocatalysis with amplification of enantioenrichment and applied the reaction to elucidate the origin of chirality and chiral discrimination.

1,6 Coordinate perphosphoranide anion (12-P-6) are usually unstable and difficult to be isolated. In order to stabilize the anion, two equivalents of the bidentate Martin ligand (hexafluorocumyl alcohol) were reacted with phosphorus trichloride to generate 4 coordinate phosphoranide anion (10-P-4) in situ. Conjugate aldehydes and 1,2-diketones were reacted with the anion (10-P-4) to effect Diels-Alder type 1,4-cycloadditon to synthesize 6 coordinate perphosphoranide anions (12-P-6). The anion (12-P-6) was isolated stable and the structure was determined by X-ray analysis when phenanhrenequinone was used as a 1,2-diketone. Gnerally, the anions (12-P-6) were hydrolyzed to give 5 cordinate phosphoranes (10-P-5) bearing ethylene aldehyde group and the aldehydes were characterixed as their 2,4-dinitrophenylhydrazones.
2,Syntheses and structure determination by X-ray analysis of a variety of 5 coordinate hypervalent carbon species (10-C-5) were reported as full papers in the fiscal year of 2005. In 2006, we challenged to synthesize 6 coordinate hypervalent carbon species (12-C-6). Because of the new and unique idea to prepare 12-C-6 species, several attempts were tried. Finally, an allene compound which bears thioxanthene skeleton at the terminal 1,3-carbons was prepared and the two sulfur atoms were methylated to yield the 6 coordinate carbon species. For the methylation, only the strongest methylation reagent, i.e., carborane reagent, could lead to success. The reagent was developed by Professor C. Reed group of Riverside, California, USA.
3,Syntheses, crystal and solution structures, ligand exchange and ligand coupling reactions of mixed pentaarylantimony compounds were reported as a full paper in 2007. The experiments were quite complicated and contained a variety of aspects of hypervalent pentacoordinate compounds and had been completed several years before. By analyzing the total experimental results, it was concluded that the reaction proceeded through the two apical ligands which was termed as "memory effect".

There are many reactions of 1, 2-propadienes(allenes), which have cumulated double bond moieties, as unique synthetic reagents. Among them, the features of the cumulated double bond are effectively utilized, that cannot be achieved by simple double or triple bond. In this research, I recognize vinylidene and allenylidene complexes as metal analogue of 1, 2-propadienes and 1, 2, 3-butatriene, respectively, and pay attention to the reactivity of carbon-carbon double bond in metallacumulenes. I plan to search for synthetic reactions that make the best use of their characteristics, and that use metallacumulenes as two or three carbon unit.
I first examined the synthesis of vinylidene complexes from rhodium and iridium ones, which are known to be relatively electron-rich metals. According to the conventional methods, I tried to prepare them from low valent rhodium complexes and terminal alkynes via isomerization along with a hydrogen transfer. I failed but obtained multicyclic compounds by cycloaddition of alkyne moieties. Thus, I focused on the development of low valent late transition metal catalyzed-cycloaddition of alkynes and alkenes, especially enantioselective reaction using chiral metal catalysts.
For example, transition metal-catalyzed[2+2+2] cycloaddition is a well-established protocol for the construction of six-membered ring systems. I developed a new type of enantioselective[2+2+2] cycloaddition for the synthesis of quaternary carbon stereocenters. The intramolecular reaction of various 1, 4-diene-ynes proceeded using a chiral rhodium catalyst and tricyclic compounds possessing a strained bicyclo[2.2.1] heptene skeleton or bicyclic cyclo-1, 3-dienes were obtained, depending on the substituent on the 1, 4-diene moiety.

報告者は、イリジウム錯体を用いる触媒的かつエナンチオ選択的[4+2]付加環化反応について検討した。その結果、置換基を持たないジエンとアルキンとの分子内反応が進行し、キラルイリジウム錯体を用いた場合には、対応するシクロヘキサ-1,4-ジエンが高不斉収率で得られことを見いだした。
これまで数多くの報告例があるルイス酸触媒を用いる[4+2]付加環化反応(Diels-Alder反応)では、不斉場構築において、反応点近傍にあるヘテロ原子官能基へのルイス酸の配位が足がかりとなる。一方、メタラサイクルを経由する遷移金属錯体を触媒とする反応では、ヘテロ原子官能基をもたない不活性な基質間でも反応が進行するという特徴をもつ。分子内[4+2]付加環化反応は、Ni、Pd、Rh触媒などを用いる反応が知られており、カチオン性キラルRh錯体を用いる不斉反応も報告されている。しかしながら、これまで用いられている基質は、置換基を有する(主にsorbic alcohol、ヘキサ-2,4-ジエン-1-オール由来の)ジエンとアルキンあるいはアルケンとの分子内不斉反応のみであった。
報告者は既に、[2+2+1]付加環化反応において、イリジウム錯体が有効な触媒として機能することを見いだし、不斉反応へも展開している。今回、末端ジエンとアルキンとの分子内[4+2]付加環化反応においても、イリジウム錯体が触媒として働くことを見いだした。特にキラルなジホスフィンBDPPを不斉配位子とし、溶媒として酢酸tert-ブチルを用いた場合、非カチオン性イリジウム錯体によって極めて高エナンチオ選択的に反応が進行し、対応するシクロヘキサ-1,4-ジエンが得られた。

遷移金属触媒を用いる付加環化反応は、環状化合物合成において最も汎用な手法である。中でも、一酸化炭素やイソシアニドの挿入を伴う反応は、環内に合成上有用なカルボニル基、イミノ基をもつ環化生成物を与える。しかしながらこれまで、触媒的アルキン-アルキンカップリング反応によるシクロペンタジエノンの一般的な合成法はなく、また、イソシアニドの挿入を伴う反応は、基質に対し等量の遷移金属錯体を用いる例しか報告されていない。
報告者は、イリジウム-ホスフィン錯体を用いることにより、一酸化炭素の挿入を伴う触媒的分子内アルキン-アルキンカップリング反応が進行することを見いだした。その後に他の研究者により報告されたコバルト三核カルボニル錯体を用いる高一酸化炭素圧下の触媒的アルキン-アルキンカップリングと異なり、本反応は、一酸化炭素常圧下、さらには低分圧下(0.2atm)においても効率的に進行することがわかった。また、生成物のシクロペンタジエノンは、酸処理により、容易に二重結合の異性化が進行し、さらなる合成変換が可能な二環性ジエノンが得られる。
さらに、これまで等量のNi(O)錯体を用いる例しか知られていない、イソシアニドの挿入を伴うアルキン-アルキンカップリングについて検討した結果、ロジウム錯体を用いることにより触媒反応を達成した。本反応は、ホスフィン配位子をもたないロジウム錯体を用い、溶媒としてジブチルエーテルを選択し、かつイソシアニドを少量ずつ適切な時間間隔で添加することにより、速やかに反応が進行し、良好な収率でイミノシクロペンタジエンを与えることを見いだした。

2つの二重結合が連続した構造を持つアレンは、オレフィンやアセチレンにない特有の反応性を持ち、合成上有用な三炭素合成素子として用いられている。例えば、アリールパラジウム(II)種に対してアレン化合物を作用させると速やかに挿入反応が進行し、π-アリルパラジウム中間体を与えることが知られている。
そこで筆者は、一酸化炭素雰囲気下、アレニルアミン化合物を用いれば、分子内のアミノ基がπ-アリルパラジウム中間体へ求核付加し、引き続き一酸化炭素の挿入を伴ってパラジウムが還元的脱離すれば、β-ラクタムが得られると考えた。実際に触媒としてPd(PPh_3)_4、塩基として炭酸カリウム用い、加熱条件によりα-アレニルアミンとヨードベンゼンの反応を行うと、予期に反してカルボニル基を環外にもつ含窒素五員環生成物が得られた。この結果は、系中で生成するフェニルパラジウム種が、アレンに挿入する前にカルボニル化され、ベンゾイルパラジウム種となり、その後アミンの求核付加により閉環したと考えられる。従って、アルゴン雰囲気下で反応を行うと、環状にフェニル基をもつ含窒素複素環であるピロール誘導体が得られた。
反応条件を精査した結果、トルエン溶媒中、嵩高い有機塩基であるエチルジイソプロピルアミン(Hunig base)を用いた場合、反応は効率的に進行し、高収率でジヒドロピロール誘導体を与えた。本反応は、ベンゼン環上に電子吸引性基、電子供与性基いずれの置換基をもつヨー化アリールを基質として用いても進行し、対応するアリール置換複素環化合物を与えた。

Asymmetric autocatalysis has been developed. Chiral 2-alkynyl-5-pyrimidyl alkanol was found to be a highly enantioselective asymmetric autocatalyst in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde. PracticaUy perfect asymmetric autocatalysis(>99%. >99.5% ee) is achieved. The product has been used as asymmetric autocatalyst for the next asymmetric autocatalysis. During the ten consecutive asymmetric autocatalyses, the initial pyrimidyl alkanol has automultiplied by a factor of 60 million. It was also found that the enantiomeric excess is enhanced in the asymmetric autocatalysis. When the asymmetric autocatalyst with only 0.1% ee was employed, the ee was enhanced up to >99.5% ee. In the presence of L-leucine with only 2% ee, the reaction between pyrimidine-5-carbaldehyde and diisopropylzinc afforded pyrimidyl alkanol with higher ee. This is the first example of the correlation of the chirality of circularly polarized light (CPL) with a chiral organic compound with high ee. Chiral hydrocarbon, i. e., hexahelicene, serves as a chiral initiator, and pyrimidyl alkanol with high ee was obtained. Chral inorganic crystals such as quartz and sodium chlorate work as chiral initiators. In the presence of d-quartz, (S)-pyrimidyl alkanol with 98% ee was obtained. On the other hand, in the presence of I-quartz, (R)-alkanol with 98% ee was formed. As described, we found asymmetric autocatalysis in which the ee of organic compound increases without the need for any other chiral auxiliary. Amplification from 0.1% ee to>99.5% ee has been achieved. Chiral organic compounds with low ee work as chiral initiators to afford pyrimidyl alkanol with higher ee. By using asymmetric autocatalysis, chirality of CPL is correlated with organic compound of high ee. Chiral inorganic crystals act as chiral initiators in asymmetric autocatalysis, and pyrimidyl alkanol with very high ee was formed. This is the first example of a highly enantioselective synthesis induced by chiral inorganic crystal.

報告者は、用いる不斉触媒と得られる生成物の構造ならびに絶対構造が同一である「不斉自己触媒反応」の開発を行っている。不斉触媒と生成物の構造が異なる従来の不斉反応とは異なり、不斉自己触媒系では、微量の不斉源から得られた生成物を次の反応の触媒として用いる連続反応により、触媒の劣化を考慮することなく、大量のキラル化合物が得られる。報告者は既に、ピリミジン-5-カルバルデヒドのジアルキル亜鉛による不斉イソプロピル化反応においてほぼ定量的(>99%)、かつほぼ完全にエナンチオ選択的(>99.5%e.e.)に進行する完全不斉自己触媒反応系を見いだした。さらに、最初に用いる不斉自己触媒として極めて低鏡像体過剰率のピリミジルアルカノールを用いても、連続反応によりほぼ一方の鏡像体のみが得られることを報告した。
今回、上記不斉自己触媒系の応用、実用化を目指し、始めに添加するキラル化合物として、不斉自己触媒であるピリミジルアルカノールではなく、それ以外の構造の異なる化合物をキラル開始剤として用いて同条件下反応を試みた。その結果、極めて低鏡像体過剰率(0.1%e.e.以下)のアルコール、アミン、カルボン酸などがキラル開始剤として作用し、高い鏡像体過剰率のピリミジルアルカノールが生成した。得られるピリミジルアルカノールが、その鏡像体過剰率を保ったまま、α-ヒドロキシカルボン酸あるいはα-アミノ酸誘導体へと変換できることを見いだしたことから、本結果は、種々の低鏡像体過剰率の有機化合物が、有用なキラルプールの供給源となりうることを意味している。

私は用いる不斉配位子と得られる生成物の構造、ならびに絶対配置が同一である自己完結型不斉反応の開発を行った。従来型不斉反応、すなわち用いる不斉配位子と生成物とが全く異なる構造を有する不斉反応と比べ、自己完結型不斉反応は、1)反応後両者を分離精製する必要がない、2)得られた生成物を次の反応で不斉配位子として用いる連続反応が可能である、などの利点を持つ。
平成9、10年度の研究により、上記自己完結型不斉反応をα-アミノケトンの不斉還元反応において実現した。すなわち、不斉配位子としてβ-アミノアルコール、還元剤として水素化アルミニウムリチウム、補助配位子としてN-エチルアニリンを用い、対応するα-アミノケトンの不斉還元反応を行ったところ、用いた不斉配位子と同一な構造、絶対配置を有するβ-アミノアルコールが高不斉収率で得られた。
さらに平成10年度において、触媒的自己完結型不斉還元反応の開発を目指し研究を進めた。従来型触媒的不斉還元反応として、基質に対し触媒量の不斉配位子を用いるケトン、あるいはケトイミンのボラン還元反応が知られている。そこで予備的実験として等量のアミノアルコールを不斉配位子として対応するα-アミノケトン、ケトイミンの自己完結型不斉還元反応をボラン錯体を還元剤として用い行った。その結果、ボラン還元反応においても自己完結型不斉還元反応は達成されるが、上記したアルミニウムヒドリドを用いる場合と比べ一般に不斉収率が低い結果を与えた。例えば、窒素上に嵩高い2級アルキル基であるジフェニルメチル基を持つアミノアルコールを不斉配位子とするケトイミンの不斉還元反応で、不斉配位子と同一の絶対配置を持つアミノアルコールが得られたが、その不斉収率は最高11%e.e.であり、さらなる検討を要するを言える。

従来の不斉合成反応では、不斉配位子と生成物の構造は異なり、異型の不斉配位子および、反応後の不斉配位子と生成物との分離操作が必要であった。これに対し、本研究では不斉配位子と生成物の構造が同一で、異型不斉配位子が不要かつ不斉配位子と生成物との分離操作が不要である省エネ・省資源型の不斉自己増殖反応の開発および関連する不斉合成法の開拓を目的とする。
キラルなβ-アミノアルコールを不斉配位子とする水素化アルミニウムリチウムによるα-アミノケトンの不斉還元により、β-アミノアルコールである不斉配位子が最高90%e.e.で不斉自己増殖することを世界で最初に見出した。すなわち、光学的にほぼ純粋な(S)-フェニル-2-ピロリジニルエタノールを不斉配位子に用い、N-エチルアニリン存在下で水素化アルミニウムリチウムとキラルな錯体を形成させ、2-ピロリジニルアセトフェノンを不斉還元したところ、不斉配位子と同一構造同一絶対配置の(S)-フェニル-2-ピロリジニルエタノールが収率82%、不斉収率90%e.e.で得られた。さらに、ピペリジンあるいはモルフォリン骨格を有するアミノアルコールを不斉配位子に用いた場合も、不斉還元において78-84%e.e.で自己増殖することを明らかにした。以上のように異型の不斉源が不要、かつ不斉配位子と生成物とが同一であるのでこれらの分離が不要である次世代の不斉合成反応を開発した。
また、新規の不斉配位子の開発として、キラルなデンドリマ-およびアミノアルコールを不斉配位子とするN-Dppイミンのジアルキル亜鉛による不斉アルキル化反応により、対応するDppアミンが良好ないし高いエナンチオ選択性で得られた。

We have developed a method for the synthesis of dihydroquinoxalinones via intramolecular N–H/C–H coupling using hypervalent iodine. The starting materials were prepared from inexpensive and readily available aniline and amino acid derivatives. Various functional groups were tolerated to give multisubstituted dihydroquinoxalinones in moderate to excellent yields. The chirality of the amino acid was transferred to the desired target compound without a loss of enantiomeric excess. Preliminary mechanistic studies indicated that the reaction proceeds via an ionic mechanism.

The rhodium-catalyzed enantioselective intramolecular cycloaddition of triynes connected by sulfur-containing tethers gave tribenzothiepins and a tribenzodithiocin in high yields with good-to-excellent enantiomeric excesses. The present protocol generated axial chiralities fused with medium-ring heterocycles. In particular, this is the first example of the catalytic and highly enantioselective construction of a tribenzodiheterocin skeleton.

Sulfur-directed sp C-S bond cleavage along with a regioselective reaction with alkynes proceeded to give (Z)-enyne sulfides in high to excellent yields. Mechanistic studies were conducted, including characterization of an intermediate. An intramolecular variant realized the construction of a dibenzodithiepin skeleton, which is a seven-membered ring with two sulfur atoms.

The synthesis and characterization of thermally stable monosubstituted thiophene 1-oxide and 1-imides stabilized by EMind (1,1,7,7-tetraethyl-3,3,5,5-tetramethyl-s-hydrindacen-4yl) group on the 3-position are described. In addition to the molecular structures determined by X-ray crystallography, inversion barriers at the three-coordinated sulfur atoms have been determined by a coalescence method using diastereotopic C-3 and C-5 indacene carbon atoms as a (CNMR)-C-13 probe.

The intramolecular reaction of 3-acetyl-N-alkynylindoles proceeded via C-H bond cleavage at the C2 position. Iridium and rhodium catalysts selectively promoted 6-exo-dig and 7-endo-dig cyclization, respectively, and N-fused tricyclic compounds were obtained.

A facile two-step synthesis of aza[7]helicenes possessing a 6-5-6-6-6-5-6 skeleton from commercially available 2,9-dichloro-1,10-phenanthroline via double amination with aniline derivatives followed by hypervalent iodine reagent-mediated intramolecular double-NH/CH couplings was developed. Single-crystal X-ray analyses of the helicenes revealed unique structures, including both a significantly twisted center and planar terminals of the skeleton. The azahelicenes show high fluorescent quantum yields (Fs) under both neutral (Phi: 0.25-0.55) and acidic conditions (Phi: up to 0.80). An enantiomerically pure aza[7] helicene showed high circularly polarized luminescence (CPL) activity under both neutral and acidic conditions (g(lum): up to 0.009).

An intramolecular reaction of N-(2-alkynylphenyl)indolines proceeded efficiently to give indolo[1,7-ab][1]benzazepine derivatives in high to excellent yields by cationic Au(I)-catalyzed 7-endo-dig selective cycloisomerization along with DDQ oxidation. The present transformation could be used for the intramolecular reaction of N-(2-alkynylphenyl)-1,2,3,4-tetrahydroquinoline and N-(2-alkynylphenyl)-N-methylaniline, and construction of a dibenzazepine skeleton was achieved.

The Ir-catalyzed enantioselective reaction of substituted acetanilides with beta-substituted alpha,beta-unsaturated esters provided chiral 3,3-disubstituted propanoates in high yield with good-to-excellent enantiomeric excess (up to 99% ee). This transformation, initiated by sp(2) C-H bond activation, is the first example of enantioselective formal C-H conjugate addition to beta-substituted alpha,beta-unsaturated carbonyl compounds. The starting materials are commercially available and/or readily accessible.

An ultra-remote intramolecular (point-to-point) asymmetric control through 38 bonds (1,39-asymmetric induction) has been achieved by using the principle of direct supramolecular orientation of catalytic and reactive moieties in asymmetric autocatalysis. We found the highly stereoselective diisopropylzinc addition reaction using designed molecules possessing pyrimidine sites at each terminal of a conformationally flexible simple methylene chain.

A new pi-conjugated system of nitrogen-containing polycyclic compounds was constructed by cationic Au-I-catalyzed cycloisomerization. Intramolecular reaction of 9-(2-alkynylphenyl)-9H-carbazole derivatives gave a variety of penta- and hexacyclic compounds possessing a dibenzazepine skeleton. The rigid carbazole structure was responsible for efficient 7-endo-dig cycloisomerization.

A library of bench-stable planar-chiral 1,11-dioxa[11]paracyclophane-derived phosphoramidites was synthesized by a three step procedure: enantioselective ortho-lithiation, reductive amination and coupling with phosphorochloridites. The efficacy of these phosphoramidite as chiral ligands was tested in the Pd-catalyzed allylic alkylation of dimethyl malonate and the Cu-catalyzed ethylation of chalcone under the reported conditions, with moderate enantioselectivity being obtained. (C) 2016 Elsevier Ltd. All rights reserved.

Enantioselective cycloisomerization of 2-ethynyl-1-ferrocenylbenzene derivatives proceeded by using a chiral cationic platinum catalyst at room temperature. The intramolecular reaction gave planar-chiral naphthalene-and anthracene-fused ferrocene derivatives with high to excellent ee.

Various planar-chiral 1,n-dioxa[n]paracyclophanes possessing a phenolic hydroxyl group have been synthesized via enantioselective ortho-lithiation. Subsequent reaction with 2,2-biarylene phosphorochloridites gave a new family of chiral phosphites. These phosphites were then used as chiral ligands in the enantioselective palladium-catalyzed allylic alkylation of dimethyl malonate with (E)-1,3-diphenylallyl acetate and the rhodium-catalyzed 1,4-addition of phenylboronic acid to cyclohex-2-enone.

We measured 785 nm excited Raman and infrared spectra of pentacene-d(14). The observed spectra were assigned on the basis of the Raman and infrared spectra calculated by the density functional theory (DFT) method at the B3LYP/6-311 + G** level. We measured 785 nm excited Raman spectrum of a pentacne-d(14): C-60 bulk heterojunction film. The spectrum was assigned on the basis of the wavenumber shifts upon deuteration of pentacene. The assignments of the 1462 and 493 cm(-1) A(g) bands of C-60 were confirmed. The 511, 453, and 256 cm(-1) bands, which were observed only in pentacene:C-60 bulk heterojunction films, did not show large deuteration shifts. This result indicates that the 511, 453, and 256 cm(-1) bands are attributed to activation of the silent modes of C-60 due to symmetry lowering. (C) 2016 Elsevier B.V. All rights reserved.

Clavicipitic acid is an ergot alkaloid, which was isolated from Claviceps strain and Claviceps fusiformis. Its unique tricyclic azepinoindole skeleton has attracted synthetic chemists, and various strategies have been developed for its total synthesis. These strategies can be generally categorized into two types based on the synthetic intermediates, namely, 4-substituted gramine derivatives and 4-substituted tryptophan derivatives. This Minireview summarizes the reported total syntheses from the point of these two key intermediates

An Ir-catalyzed intermolecular reaction of biphenylenes as a C4 unit with various alkenes as a Cl unit gave 9,9-disubstituted fluorenes in moderate to high yields. Preliminary mechanistic studies revealed that this formal [4 + I] cycloaddition probably proceeds via C-C bond cleavage, alkene insertion, beta-hydrogen elimination, intramolecular alkene insertion, and then reductive elimination. An example of enantioselective reaction was also disclosed.

The enantioselective synthesis of aminoindan carboxylic acid (Aic) derivatives was achieved by Rh-catalyzed intramolecular [2+2+2] cycloaddition of amino-acid-tethered triynes. This reaction, along with recrystallization, gave chiral tethered Aic derivatives with excellent enantiomeric excess. Subsequent hydrolysis of the tethered Aic compounds afforded chiral Aic derivatives, which were further transformed into a free Aic and its dimethyl ester in good yields.

The first catalytic and highly enantioselective synthesis of tribenzothiepin derivatives was achieved. Two types of intermolecular cycloadditions using either diphenyl-sulfide-tethered diynes or 2-phenyl sulfanylbenzene-tethered diynes with a monoalkyne successfully gave chiral multisubstituted tribenzothiepins in good to excellent eevalues under mild conditions. The inversion energy of this saddle-shaped molecule was calculated by measurement of the racemization rate of chiral tribenzothiepins using the Eyring kinetic equation under heating conditions. The present protocol could also be used to prepare a chiral tribenzoselenepin.

Rhodium-catalyzed intermolecular [2+2+2] cycloaddition of phosphorylbenzene-tethered 1, 6-diynes with alkynes gave dibenzophosphole oxide derivatives. Various monoalkynes were applicable in this reaction as coupling partners, and dibenzophosphole oxide derivatives substituted with aromatic ring(s) including dibenzothiophene(s) were obtained. The asymmetric desymmetrization of a prochiral phosphorylbenzene-tethered triyne gave a chiral dibenzophosphole oxide derivative with high ee.

4-Substituted tryptophan derivatives and the total synthesis of cis-clavicipitic acid were achieved in reactions in which Ir-catalyzed CH bond activation was a key step. The starting material for these reactions is asparagine, which is a cheap natural amino acid. The reductive amination step from the 4-substituted tryptophan derivative gave cis-clavicipitic acid with perfect diastereoselectivity.

The reaction of 2-arylmethyl-, 2-aryl-, and 2-alkyl substituted pyridine N-oxides with acrylates proceeded in the presence of a cationic Ir-rac-BINAP catalyst under heating conditions. Various 2,6-disubstituted pyridine N-oxides were obtained by C-H alkylation at the C6-position.

Intramolecular enantioselective alkylation of N-alkenylindoles proceeded via C-H bond cleavage at the C-2 position in the presence of a cationic iridium catalyst with a diphosphine ligand. Aroyl groups at the C-3 position of the indoles operated as effective directing groups, and chiral 1-substituted-2,3-dihydro-1H-pyrrolo[1,2-a] indoles were obtained in high yield with excellent ee.

An intermolecular [2+2+2] cycloaddition of sulfanyl- and sulfonylbenzene-tethered 1,6-diynes with alkynes using rhodium catalysts gave dibenzothiophene derivatives in moderate to excellent yields. The consecutive reaction of tetraynes with an alkyne gave an axially chiral 1,1'-bi(dibenzothiophenyl) and its tetraoxide with up to excellent ee.

Ir-catalyzed sp(3) C-H alkylation of gamma-butyrolactam with alkenes was used for the highly enantioselective synthesis of 5-substituted gamma-lactams, which were readily converted into chiral 4-substituted gamma-amino acids. A broad scope of alkenes was amenable as coupling partners, and the alkylated product using acrylate could be transformed into the key intermediate of pyrrolam A synthesis.

This paper presents the numerical evaluation of the strength and stability of a ground improved via vacuum consolidation combined with a preloading embankment. To assess the stability of soft grounds, the undrained shear strength is definitely required. A numerical analysis is desirable for predicting the strength of the improved ground, and the elasto-plastic FEM for soil-water coupled problems, incorporating the SYS Cam-clay model, is adopted in two dimensions. The compression index of clay and the coefficient of permeability of organic soil, which are the primary factors for evaluating the ground behavior, are identified through an inverse analysis from the measured settlements. As the inverse approach, the particle filter is employed to account for the strong nonlinearity of the ground behavior. A stability analysis of the slip surface method is performed based on the evaluated undrained shear strength to assess the effect of the ground improvement on the construction of earth structures. The results show the validity of the ground improvement using vacuum consolidation with a preloading embankment.

Enantioselective alkynylation of 1,5-dibromoanthracene-9,10-dione by alkynyllithium reagents prepared from alkynes, n-BuLi, and sparteine gave chiral cis-diols possessing two alkyne moieties with moderate ee. Subsequent Ru-catalyzed [2+2+2] cycloaddition of the diol with alkynes afforded chiral 1,5-dibromotriptycenes. (C) 2014 Elsevier Ltd. All rights reserved.

The first synthesis of planar-chiral benzosiloloferrocenes was achieved by the intramolecular reaction of 2-(dimethylhydrosilyl)-arylferrocenes. The enantioselective cross dehydrogenative coupling of an sp(2) C-H bond of ferrocene with a Si-H bond proceeded efficiently with the use of a Rh-chiral diene catalyst.

Various multicyclic heterocycles were synthesized via rollover as the key pathway using a Rh(III) catalyst with a catalytic amount of sodium pivalate or copper(II) acetate. 3-Alkynyl-2-heteroarylpyridines were transformed into tri- or tetracyclic heterocycles containing two heteroatoms via an intramolecular alkyne insertion. 3-Aryloyl-2-arylpyridines were derived into 4-azafluoren-9-ols via the intramolecular carbonyl insertion.

Consecutive inter- and intramolecular [2+2+2] cycloadditions of various thiophenylene-tethered triynes were comprehensively studied by using chiral Rh catalysts. When we started from 2,3- and 3,4-thiophenylene-tethered substrates, dimerization proceeded and chiral tetraheteroarylenes were obtained. In contrast, reactions of 2,5-thiophenylene-tethered substrates gave hexaheteroarylenes as trimers. When bis- and tris(2,5-thiophenylene)-tethered triynes were used, mixtures of dimers and trimers were obtained, which included macrocyclic systems that contained up to 12 aromatic rings, and their photophysical properties were measured. (C) 2014 Elsevier Ltd. All rights reserved.

A Rh-catalyzed intermolecular [2 + 2 + 2] cycloaddition of the 2,3-double bond of benzothiophene dioxides with a,?-diynes gave sulfone-containing cycloadducts in high yields. This is the first example of a catalytic [2 + 2 + 2] cycloaddition that uses the 2,3-double bond of a heterole as an ene moiety. The consecutive reaction of benzodithiophene tetraoxide with 2,3-naphthylene-tethered 1,7-diyne gave an 11-ring condensed polycyclic compound in one pot.

The one-pot palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of a diborylmethane with bromothiophene derivatives realized the synthesis of various dithienylmethane derivatives. Cyclopentadithiophenes, which are promising compounds in material science, can be obtained in good yields. The in situ generation of an unstable thienylmethylboronate is a key step for the present reaction.

A highly chemo-, enantio-, and regioselective synthesis of furanones bearing an alpha,alpha- disubstituted quaternary stereogenic center is reported. The Cu-catalyzed enantioselective conjugate addition of organoaluminum reagents to unsaturated ketoesters at room temperature and subsequent lactonization took place. Synthetic transformations of furanones represent facile approaches to various cyclic or acyclic compounds bearing a quaternary stereogenic center.

An efficient method for C7-position-selective alkenylation of N-substituted indolines with alkenes is reported. Various 7-alkenylindolines were obtained in moderate to excellent yields in air in the presence of catalytic amounts of [Cp*IrCl2](2), AgOTf, and Cu(OAc)(2). The protocol relies on the use of a carbonyl or carbamoyl group on the nitrogen atom of indoline as a directing group and is potentially applicable to the synthesis of 7-alkenylindoles and 7-alkylindoles.

The cationic rhodium-catalyzed alkenylation proceeds at the C-8 position of quinoline N-oxides. Regioselective CH bond activation was achieved by the directing effect of the anionic oxygen of an N-oxide moiety, which can be readily removed by reductive treatment. A variety of 8-alkenylated quinoline N-oxides was obtained in moderate to high yields.

The first catalytic and enantioselective CH alkylation of ferrocene derivatives with various alkenes was achieved. A cationic iridium complex, having a chiral diene ligand, and an isoquinolyl moiety as a directing group are essential for regioselective and enantioselective CH bond activation.

A cationic iridium-catalyzed C-7 alkylation of N-substituted indoline derivatives with various alkenes has been developed. A variety of 7-alkylindolines were obtained in moderate to high yields. This protocol relies on the use of the carbonyl group on the nitrogen atom of indoline as a directing group and it is potentially applicable to the large-scale synthesis of 7-alkylindoles.

A new family of chiral phosphines based on planar-chiral 1,n-dioxa[n]paracyclophane scaffold was created. They were synthesized with excellent enantioselectivity via asymmetric ortho-lithiation using sec-butyllithium and (-)-sparteine. These phosphines were used as 'chiral ligands in three reactions: Ag-catalyzed allylation of imines, Pd-catalyzed,asymmetric Sonogashira coupling of diiodoparacyclophanes, and Pd-catalyzed asymmetric Suzuki-Miyaura coupling of tricarbony1(eta(6)-ortho-dich1orobenzene)chromium.

This chapter summarizes the recent work (published after 2000) of enantioseletive cycloadditions catalyzed by chiral Lewis acids and chiral transition metal complexes. The cycloaddition is categorized as [4+2], [5+2], [2+2], [2+2+2], [3+2], and [4+3] cycloadditions. These reactions provide efficient protocols for the construction of various chiral cyclic skeletons, which include central, axial, planar, and helical chiralities. © 2013 Elsevier Ltd. All rights reserved.

The readily functionalized ligands, BINAM-PHOS, participate in the copper-catalyzed asymmetric conjugate addition of organozinc reagents to enones. The incorporation of benzoyl derivatives on nitrogen atoms was crucial to promote the reaction. Notably, BINAM-PHOS derivatives gave the opposite major enantiomers to that obtained using BINOL-PHOS derivatives, which we have developed for the construction of multinuclear catalysts.

Functionalization of BINOL-mono-PHOS achieved the Cu-catalyzed highly asymmetric conjugate addition of organozinc reagents to enones. The incorporation of a bulky hydroxy group at the 3'-position of BINOL-mono-PHOS dramatically improved the yield and enantioselectivity. The present novel BINOL-mono-PHOS ligands are effective in the Cu-catalyzed asymmetric conjugate addition of organozinc reagents in both acyclic enones and cyclohexenone.

Over the past few years, iridium complexes have been widely used in the direct functionalization of unactivated bonds. In the presence of iridium catalysts, inactive C-H and N-H bonds have been transformed into C-C and N-C bonds in dehydrative alkylation using alcohols, allylation using allyl carbonates, and alkylation using alkenes. Enantioselective variants of some reactions have also been reported.

A cationic Ir(I) complex-catalyzed O-to-N-alkyl migration in 2-alkoxypyridines bearing a secondary alkyl group on the oxygen atom by C-O bond cleavage is described. The present transformation gave various N-alkylpyridones in moderate to good yields. The addition of sodium acetate played a key role in suppressing beta-hydrogen elimination.

Al and friends: Asymmetric conjugate addition of Me3Al to β,β-disubstituted α,β-unsaturated ketones in the presence copper and L1 leads to a highly efficient construction of an all-carbon-substituted chiral quaternary center. This result is the first example of an asymmetric conjugate addition of Me3Al to acyclic enones to give a chiral quaternary carbon center with excellent yield and enantioselectivity under mild reaction conditions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The direct functionalization of inactive bonds is an ideal transformation in organic synthesis because the introduction of activating groups, such as halogens and metals, to substrates is unnecessary and by-products derived from them are not formed. This report describes several types of cationic iridium-catalyzed reactions that occur through C-H, N-H, or C-O bond cleavage. The carbonyl-directed sp2 C-H bond activation of aryl ketones realized new approaches to benzofulvene, benzofuran and indole synthesis, as well as the C2-position-selective alkylation of N-acyl-protected indoles. The enantioselective sp3 C-H alkylation of 2-(alkylamino)pyridines and the intermolecular enantioselective hydroamination of heteroaromatic amines gave various chiral amines. 0-to-7V-alkyl migration in 2-alkoxypyridines gave 7V-alkylpyridones via C-O bond cleavage.

Consecutive inter-and intramolecular [2+2+2] cycloadditions of various phenylene-tethered triynes were comprehensively studied by using chiral rhodium catalysts. ortho-Phenylene-tethered triynes gave chiral o,o,o,o-tetraphenylenes in high-to-excellent enantiomeric excess as dimers. meta-Phenylene-tethered triynes gave chiral o,m,o,m-tetraphenylenes in moderate enantiomeric excess as dimers along with hexaphenylenes as trimers. This is the first synthesis of cis-o,m,o,m-tetraphenylenes; one structure was ascertained by X-ray crystal structure analysis. para-Phenylene-tethered triynes gave o,p,o,p,o,p-hexaphenylenes as trimers along with the formation of o,p,o,p,o,p,o,p-octaphenylenes as tetramers.
1 Introduction
2 Results and Discussion
2.1 ortho-Phenylene-Tethered Triynes
2.2 Naphthylene-Tethered Triynes
2.3 meta-Phenylene-Tethered Triynes
2.4 para-Phenylene-Tethered Triynes
3 Conclusion

A cationic Ir(I)-tolBINAP complex catalyzed an enantioselective C-C bond formation, which was initiated by secondary sp(3) C-H bond cleavage adjacent to nitrogen atom. A wide variety of 2-(alkylamino) pyridines and alkenes were selectively transformed into the corresponding chiral amines with moderate to almost perfect enantiomeric excesses. Alkynes were also investigated as coupling partners. The effect of alkyl structure in substrates and directing groups were studied. This transformation represents the first example of a highly enantioselective C-H bond activation of a methylene group, not at allylic or benzylic position. (c) 2012 Elsevier Ltd. All rights reserved.

An intramolecular reaction of 3-alkynyl and 3-alkenyl-2-arylpyridines selectively gave 4-azafluorene compounds in the presence of a catalytic amount of [Cp*RhCl2](2) and Cu(OAc)(2). Pyridine-directed C-H bond activation along with "rollover" are likely to be key steps of this transformation.

A cationic iridium-catalyzed C2-alkylation of N-substituted indole derivatives with various alkenes has been developed, which selectively gives linear or branched 2-alkylindoles in high to excellent selectivity. This protocol relies on the use of the carbonyl group on the nitrogen atom of indole as a directing group: a linear product was predominant when an acetyl group was used as a directing group, and a branched product was predominant with a benzoyl group.

[RhCp*(OAc)(2)(H2O)] [Cp* = pentamethylcyclopentadienyl] catalyzed the C-H bond amidation of ferrocenes possessing directing groups with isocyanates in the presence of 2 equiv/Rh of HBF4 center dot OEt2. A variety of disubstituted ferrocenes were prepared in high yields, or excellent diastereoselectivities.

A one-pot synthesis of diarylmethanes from air-stable diborylmethane via the Suzuki-Miyaura cross-coupling reaction is described. The present approach realizes the synthesis of various symmetrical and unsymmetrical diarylmethanes in good to excellent yields.

A reversal in enantioselectivity was observed by the combination of a chiral diol and achiral alcohols as a chiral initiator in the asymmetric alkylation of a pyrimidine-5-carbaldehyde using diisopropylzinc. (2S,3S)-Butane-2,3-diol alone induced (R)-pyrimidyl alkanol, while a mixture of the chiral diol and phenol derivatives induced (S)-pyrimidyl alkanol. The effect of achiral alcohols is also discussed. (c) 2012 Elsevier Ltd. All rights reserved.

[Ir(cod)(2)]BARF [BARF = tetrakis(3,5-trifluoromethylphenyl)borate] catalyzed the directed alkenylation and alkylation of ferrocenes to form a variety of tri- and disubstituted ferrocenes. Mechanistic investigation revealed several putative intermediates along with the importance of COD (1,5-cyclooctadiene), as a diene ligand, and a possible catalyst deactivation pathway. On the basis of the mechanistic investigation, catalytic activity was further improved.

The asymmetric induction of chiral centers bearing a methyl group is a fundamental protocol for the synthesis of valuable molecules in biologically active compounds. However, the direct asymmetric methylation is typically difficult to achieve. The present review describes recent representatives of detour and direct approaches to the construction of methyl-containing chiral centers via catalytic C-H or C-C bond formation.

Multinuclear Cu/Zn complex-catalyzed efficient asymmetric conjugate addition of organozinc reagents to acyclic and cyclic enones has been developed in the presence of a wide variety of regioisomeric chiral diols bearing phosphorus moieties as ligands. The regioisomeric SPINOL-PHOS ligands based on a SPINOL architecture showed an unexpected inversion of stereoselectivity.

A novel example of the Suzuki-Miyaura cross-coupling reaction between sp(3)-carbon and sp(3)-carbon is described. The reaction of a diborylmethane derivative with allyl halides or benzyl halides proceeded efficiently in the presence of appropriate Pd-catalysts at room temperature. The present approaches provide functionalized homoallylboronates and alkylboronates with excellent regio- and chemoselectivities.

An enantioselective intramolecular [2+2+2] cycloaddition of 2-aminophenol-tethered triynes and diyne-nitriles proceeded using the chiral Rh catalysts, and tripodal cyclophanes and pyridinophanes with a long ansa chain (up to [16]pyridinophane) were obtained in acceptable yield with high to almost perfect ee. In the reaction of triynes, we elucidated that the oxygen atom at the alkyne terminus is essential for the excellent enantioselectivity. For the construction of cage-type molecule, the choice of rigid tether, which connects 1,6-diyne moiety with a side carbon chain having alkyne or cyano group on its terminus, was important, and 8-amino-2-naphthol moiety was also a preferable tether. (C) 2012 Elsevier Ltd. All rights reserved.

A cationic Ir(I)-C-3-TUNEPHOS complex catalyzed an intermolecular hydroamination of styrene derivatives with various heteroaromatic amines. The reaction gave Markovnikov products with perfect regioselectivity and good enantioselectivity under solvent-free conditions.

The asymmetric induction of planar chirality in 1,n-dioxa[n]paracyclophane derivatives via asymmetric ortho-lithiation is described. Enantioselective ortho-lithiation of unflippable 1,n-dioxa[n]paracyclophanes (n <= 11) using sec-BuLi-(-)-sparteine at -78 degrees C and subsequent treatment with electrophiles gave the corresponding planar-chiral monosubstituted paracyclophanes with excellent ee. Further lithiation of these compounds and treatment with electrophiles gave planar-chiral paracyclophanes with two different substituents. Dilithiation of unflippable 1,n-dioxa[n]paracyclophanes gave the corresponding C(2)symmetrical disubstituted products with almost perfect ee. In the case of flippable 1,n-dioxa[n]paracyclophanes (n >= 12), a stepwise reaction was required for the highly enantioselective formation of disubstituted products. (C) 2011 Elsevier Ltd. All rights reserved.

Silahelicenes, which contain two silole moieties in a helically chiral structure, were synthesized by a chiral Ir-catalyzed intermolecular [2 + 2 + 2] cycloaddition of tetraynes with diynes along with a Ni-mediated intramolecular [2 + 2 + 2] cycloaddition. The photophysical properties of the obtained highly enantiomerically enriched silahelicenes (up to 93% ee) were also measured.

A catalytic beta-selective addition of amines to styrenes proceeded in the presence of cationic Ru complexes combined with diphosphine ligands. In the reaction of alpha-methylstyrene, an enantioselective addition was achieved by using xylylBINAP.

The regio- and stereoselective synthesis of allylsilane derivatives bearing a tetrasubstituted olefin was achieved using 2,2-diborylethylsilane as a key intermediate. The regioselective deprotonation of a 2,2-diborylethylsilane with LTMP and the subsequent nucleophilic addition to ketones gave corresponding allylsilanes in good to excellent yield with excellent stereoselectivity.

Cyclodehydration of various alpha-aryloxy ketones proceeded to give various multisubstituted benzofurans by using an Ir(III) catalyst, which was prepared from [Cp*IrCl2](2), AgSbF6, and Cu(OAc)(2). The use of the cationic iridium complex with a carboxylate salt realized the efficient transformation at ambient temperature.

Secondary sp(3) C-H bond activation of ureas was achieved by a cationic Ir(I)-JOSIPHOS catalyst. Regioselective C-H bond cleavage adjacent to the nitrogen atom in N-benzylureas and an N-allyl urea possessing a 2-alkynylphenyl group, and subsequent intramolecular reaction with an alkyne along with double-bond isomerization provided 2,3-disubstituted indoles.

A cationic Ir(1)-tolBINAP complex catalyzed an enantioselective C-C bond formation initiated by secondary sp(3) C-H bond cleavage adjacent to a nitrogen atom. The reaction of 2-(alkylamino)pyridines with various alkenes gave chiral amines In good yields with high enantiomeric excesses.

The chemoselective Pd-catalyzed Suzuki-Miyaura cross-coupling reaction using a diborylmethane is reported. The use of an equimolar amount of base with a diborylmethane realized chemoselective coupling for the synthesis of various benzylboronate derivatives. Sterically hindered aryl bromides can give products in moderate to excellent yields.

(Styrene)Cr(CO)(3) complexes underwent the addition of various heteronucleophiles such as alcohols, amines, and thiols, in the presence of KOH, and the beta-addition products were selectively obtained in moderate to excellent yields. The structural details and features of the product complexes were also elucidated.

A multinuclear palladium catalyst can be used to realize the efficient catalytic asymmetric alkylative ring-opening reaction of oxabicyclic alkenes using dimethylzinc. The use of (R)-BINOL-PHOS bearing bisphosphine and diol moieties is essential for achieving excellent catalytic performance; the corresponding monophosphine and hydroxy-protected derivatives showed lower catalytic activities and/or enantioselectivities. The generation of Pd/Zn-multinuclear complexes is a key feature of the present catalysis.

Two types of enantioselective [2 + 2 + 2] cycloadditions of triynes using chiral rhodium catalysts are disclosed. The intramolecular reaction of ortho-aminophenol-tethered triynes provides chiral tripodal compounds. Consecutive inter- and intramolecular reactions of ortho-phenylene-tethered triynes provide chiral tetraphenylenes.

Enantioselective intramolecular cycloaddition of hexaynes with 1,3-diyne moiety was examined. Chiral Rh catalyst provided axially chiral 1,1'-bis(biphenylenyl) derivatives by consecutive [2 + 2 + 2] cycloaddition. In contrast, chiral Ir catalyst provided axially chiral macrocyclic compounds with 1,3-diyne moiety by single [2 + 2 + 2] cycloaddition. (C) 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:363-370, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20691

Catalytic SNAr reaction of fluoroarenes possessing no electron-withdrawing group(s) with cyclic amines was achieved using a readily accessible Ru catalyst, which was prepared from [Ru(benzene)Cl-2](2), AgOTf, and P(p-FC6H4)(3). The coexistence of molecular sieves MS4A realized high conversion and various substituted aryl amines were obtained in good to high yields.

The palladium-catalyzed Suzuki-Miyaura cross-coupling on a multisubstituted sp(3)-carbon in 1,1-diborylalkanes was achieved at room temperature. The generation of a monoborate intermediate by virtue of the adjacent B atom could result in the chemoselective coupling reaction under ambient conditions.

Highly enantioselective ortho-lithiation and dilithiation of 1,n-dioxa[n]paracyclophanes were realized with the use of see-butyllithium and a catalytic or stoichiometric amount of sparteine. Quenching with various electrophiles, such as iodine, iodomethane, and chlorodiphenylphosphine, afforded chiral mono- and disubstituted paracyclophanes with good to excellent ee.

A chiral rhodium catalyst realized the first intramolecular [2+2+2] cycloaddition of yne-ene-enes, and chiral multicyclic cyclohexenes with adjacent three chiral centers were afforded with high to excellent ee.

The stereoselective synthesis of tetrasubstituted alkenylboronates was established via the lithiation/nucleophilic addition reaction of 1,1-orizanodiboronates to carbonyl compounds. The present approach enables the facile and practical synthesis of tetrasubstituted olefins, which are useful synthetic intermediates for further functionalizations.

Ru-catalyzed SNAr reaction of non-activated fluoroarenes with secondary amines proceeded through eta(6)-arene complexes to give aminated products in up to 79% yield.

(Figure Presented) A whole lot o' metal: An efficient copper-catalyzed asymmetric conjugate addition was achieved using a binol-derived ligand. The catalytic system has a turnover number of 2000, and the excellent cata-lytic performance could be attributed to the generation of a multinuclear complex such as 1. binol = 2, 2'-dihydroxy-l, 1'-binaphthyl. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

The cationic iridium complex ([Ir(cod)(2)]OTf + rac-BINAP) efficiently catalyzed a sequential process of ortho-C-H bond functionalization, cyclization and dehydration, leading to a concise preparation of 1-methylene indene (benzofulvene) derivatives. The iridium complex operated as a catalyst in the ortho-C-H bond alkenylation of aryl ketones with alkynes and as a Lewis acid catalyst in the cyclization of the alkenylated product and the subsequent dehydration.

A directed cyclization-dehydration cascade of alpha-aryloxy ketones and alpha-arylamino ketones was efficiently catalyzed by a cationic iridium-BINAP complex, which afforded various types of 4-substituted benzofurans and indoles in high yields with complete regioselectivity. The newly developed protocol also enabled the enantioselective preparation of chiral 4-acetyloxindole using a chiral iridium catalyst.

Cyclotrimerization of triynes branched by a nitrogen atom of 2-aminophenol yielded planar-chiral tripodal cage compounds. When a cationic Rh-Me-DUPHOS catalyst was used, the cycloadducts were obtained in high yield and excellent ee, and a macrocyclic compound with a [15]cyclophane system was also obtained. This method can be further applied to the synthesis of a triarmed pyridinophane by the intramolecular reaction of a diyne-nitrile.

A Rh(I)Cl-DPPB-complex-catalyzed sequential hydroboration of aryl alkynes and aliphatic alkynes was achieved. The reaction proceeded with almost perfect regioselectivity to afford 1,1-organodiboronate compounds in moderate to good yield.

A cationic Ir(I)-BINAP catalyst cleaved sp(3) C-H bonds of arylamides rather than sp(2) C-H bonds, which was followed by alkenylation with alkynes to give allylamides. Several types of amides and alkynes were suitable as substrates, and the corresponding allylamides were obtained in moderate to good yield. We also demonstrated that carbonyl-directed sp(3) C-H bond cleavage would be an initial step in the present reaction by a deuterium-labeling experiment.

The double Sonogashira coupling of diiodoparacyclophanes with alkynes proceeded to give planarly chiral dialkynylparacyclophanes; a chiral Pd catalyst, which was prepared in situ from PdCl(2)(CH(3)CN)(2) and Taniaphos, realized the first asymmetric Sonogashira coupling with up to ca. 80% ee.

Triynes having a phenylene-bridged 1,5-diyne moiety were transformed into substituted tetraphenylenes by the title sequence. A cationic Rh-ligand species catalyzed this highly enantioselective reaction. This protocol is a new and easy approach to the construction of the tetraphenylene skeleton and enables an efficient asymmetric synthesis (see scheme; R=H; Z=NTs, C(CO2Me) 2, O). © 2009 Wiley-VCH Verlag.

Cationic Ir complex ([Ir(cod)(2)]BF(4) + BINAP) catalyzed the addition of ortho-C-H bonds in aryl ketones to alkynes, which gave alkenylated products in good to high yield. Styrene derivatives were good substrates, and the enantioselective addition to norbornene was also described. (C) 2008 Elsevier B. V. All rights reserved.

Regioselective hydroboration of vinylarenes catalyzed by a Rh(I)-DPPB complex proceeded rapidly when DMAP was used as an additive. The catalyst loading could be reduced to 0.4 mol% Rh(I) to furnish the desired products in good to excellent yield with high regioselectivity.

In the presence of a catalytic amount of RhCl(PPh(3))(3), an intramolecular cycloaddition of cyclopropene-yne proceeded along with carbon-carbon bond cleavage of cyclopropene ring to give various bicyclic cyclopentadiene derivatives in good to high yield.

(RhOAc)-O-I shows a remarkably high catalytic activity for the hydroboration of vinylarenes with pinacolborane. The reaction was complete within 10 min to give the Markovnikov product.

Chiral iridium complex catalyzed a formal [4+2] cycloaddition of biphenylene with disubstituted alkynes, which was initiated by carbon-carbon bond cleavage. Axially chiral 9, 10-disubstituted phenanthrenes were enantiomerically obtained.

The intramolecular cycloaddition of 1,n-diene-ynes (n = 4-6), where alkyne and alkene moieties are connected by a 1,1-disubstituted alkene, was examined using a chiral rhodium catalyst, and various types of cycloadducts with quaternary carbon stereocenter(s) were obtained in high to excellent enantiomeric excess. In the case of 1,4-diene-ynes, tricyclic, bicyclic, and spirocyclic compounds were obtained depending upon the substituents at the 2-position of the 1,4-diene moiety and those at their alkyne termini. On the other hand, 1,5- and 1,6-diene-ynes gave tricyclic and bicyclic compounds, which included medium-sized ring systems. The mechanistic considerations for different reaction pathways and the synthetic transformation of tricyclic products into functionalized spirocyclic compounds are also described. The reaction of enediynes, where two alkyne moieties are connected by a 1,1-disubstituted alkene, was also examined, and sterically strained tricyclic compounds with two carbon stereocenters were obtained.

A rhodium complex, [Rh(acac)(CO)(2)], has been identified to catalyze the cyclization of various 1,5-diynes with hydrosilanes under an atmospheric pressure of carbon monoxide at room temperature. The cyclization of 1,5-diynes proceeds along with hydrosilylation and carbonylation to give derivatives of 2,5-dialkylidenecyclopentanone.

A Rh-BINAP complex catalyzed an intermolecular and enantioselective [4 + 2] cycloaddition of 1-monosubstituted, 1, 1- or 1,2-disubstituted buta-1,3-dienes with dimethyl acetylenedicarboxylate to give chiral cyclohexa-1,4-dienes.

A chiral iridium complex catalyzed a consecutive and enantioselective [2+2+2] cycloaddition of polyynes to give axially chiral compounds. Intermolecular reaction of tetraynes, possessing aryl groups on their termini, with protected but-2-yne-1,4-diols gave C-2-symmetrical quateraryl compounds. Intramolecular reaction of hexaynes, possessing aryl or alkyl groups on their termini gave C-2-symmetrical biaryl compounds. The catalytic synthesis of a pentacene derivative with axial chiralities is also discussed. (c) 2007 Published by Elsevier Ltd.

Enantioselective cycloaddition using chiral transition metal catalysts is an atom-economical and efficient synthetic tool for the construction of chiral carbo- and heterocyclic skeletons. This short account discloses our recent results of inter- and intramolecular enantioselective [2 + 2 + 2] cycloadditions of alkyne and/or alkene moiety(ies). Chiral iridium complexes catalyzed the alkyne trimerization for the generation of axial chirality(ies), and chiral rhodium ones catalyzed alkyne-alkyne-alkene cyclization for the generation of a quaternary carbon including spirocyclic system.

The cationic Rh-SEGPHOS complex catalyzed an intermolecular [2 + 2 + 2] cycloaddition of enynes, possessing an ortho-substituted aryl group on their alkyne terminus, with acetylenedicarboxylates. Bicyclic cyclohexa-1,3-dienes with both central and axial chiralities were obtained in extremely highly diastereo- and enantioselective manner.

A chiral rhodium complex catalyzed an enantioselective [2+2+2] cycloaddition of unsymmetrical diynes with norbornene, and tetracyclic products were obtained in good to excellent cc. The cycloaddition of a symmetrical diyne with styrene derivatives as coupling partners gave bicyclic products in good cc. (c) 2007 Elsevier Ltd. All rights reserved.

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The Rh-catalyzed hydroarylative and hydrovinylative cyclization of diynes with aryl ketones or enones gave monocyclic 1,3-dienes. Enynes also underwent the same reaction and chiral products were obtained with high ee using a chiral Rh catalyst. Carbonyl-directed activation of aromatic and vinylic C-H bonds is likely the initial step in the present transformation.

In the presence of various chiral secondary alcohols as chiral initiators, an enantioselective alkylation of a pyrimidine-5-carbaldehyde using diisopropylzinc was examined: a pyrimidyl alkanol was obtained in high yield and enantiomeric excess. The correlation between the absolute configuration of the chiral secondary alcohols and the pyrimidyl alkanol is discussed. (C) 2007 Elsevier Ltd. All rights reserved.

The enantioselective intramolecular [2 + 2 + 2] cycloaddition of various enediynes, where two acetylenic moieties are connected by a traps-olefinic moiety, gave chiral tricyclic cyclohexa-1,3-dienes using Rh-H-8-BINAP catalyst. In the case of carbon-atom-tethered enediynes, enantioselectivity was generally good-to-high regardless of the substituents on their alkyne termini. In contrast, with heteroatom-tethered enediynes, appropriate substituents were required to induce the oxidative coupling of alkyne and alkene moieties before that of two alkyne moieties, which would be important for highly enantioselective intramolecular cycloaddition.

A Rh-BINAP complex was used to catalyze the hetero-[2+2+2] cycloaddition of symmetrical 1,6-diynes and carbonyl moiety of ketoesters, a diketone, and an aldehyde to give bicyclic alpha-pyrans, which were readily transformed into monocyclic compounds via the following electrocyclic ring opening. In the reaction of an unsymmetrical 1,6-diyne and a 1,7-diyne, alpha-pyrans with a quaternary carbon stereocenter were obtained in moderate to excel lent ee using a chiral rhodium catalyst.

A highly enantioselective intermolecular [2+2+2] cycloaddition of alkynes was catalyzed by a chiral iridium complex. Symmetrical and unsymmetrical diynes, and monoalkynes possessing functional group(s) were subjected to the reaction and various types of axially chiral compounds possessing biaryl skeletons were obtained in good to excellent enantiomeric excesses.

The Pauson-Khand-type reaction is formally a [2 + 2 + 1] cycloaddition involving an alkyne, an alkene and carbon monoxide catalyzed or mediated by transition metal complexes. This review focuses on the catalytic reaction and describes the recent research on the Pauson-Khand-type reaction.

The enantioselective [2 + 2 + 2] cycloaddition of 1,6-diynes with α-methylene lactones and cyclic ketones gave various chiral spirocyclic compounds. The reaction proceeded with high enantioselectivity when the rhodium-xylylBINAP complex was used as a chiral catalyst. Not only exo-methylene cyclic compounds but also exo-methylene acyclic compounds could be used as coupling partners for diynes. The present protocol provides access to a new chiral library possessing a quaternary carbon center, including a spirocyclic system. Copyright © 2006 American Chemical Society.

The intramolecular [2 + 2 + 2] cycloaddition of various 1,4-diene-ynes was examined using a chiral rhodium catalyst. In the case of 1,4-diene-ynes with a substituent at the 2-position of the 1,4-diene moiety, tricyclic compounds possessing a strained bicyclo[2.2.1]heptene skeleton with two quaternary carbon stereocenters were obtained in high enantiomeric excess. On the other hand, in the case of 1,4-diene-ynes with no substituent at this position, bicyclic cyclohexa-1,3-dienes with a quaternary carbon stereocenter were obtained probably by carbon-carbon bond cleavage of the reaction intermediate. Copyright © 2006 American Chemical Society.

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Rh-dppf was found to be an efficient catalyst for the cross-coupling between primary alkyl halides bearing beta-hydrogens and arylzinc compounds possessing carbonyl groups such as ester, amide, or ketone at the ortho position. Various functional groups such as ester, nitrile, or acyloxylate moieties on the halides were tolerated under the catalysis conditions. Arylzinc compounds free of ortho-carbonyl groups reacted well with ethyl 3-iodopropanoate, suggesting that the essential intramolecular interaction between carbonyl groups and Rh promotes the reductive elimination.

The silylation of alcohols using allylsilanes was catalyzed by cationic Au(I) and Pt(II) species, which were prepared in situ from the metal chlorides ([AuC(PPh3)] PtCl2) and a silver salt. TBS-, TES-, and TIPS-protections of various alcohols and carboxylic acids could be possible.

The enantioselective [2 + 2] cycloaddition of alkynes possessing an ester functionality and norbornene derivatives proceeded efficiently using a chiral rhodium catalyst. The chiral tri- and tetracyclic cyclobutenes were obtained in moderate to high ee.

A cationic Au(I) complex catalyzed the cycloisomerization of aromatic enynes that possess a substituent on their alkyne terminus. Cyclization of the 6-endo-dig type proceeded dominantly to give 1,3-di- and 1,2,3-tri substituted naphthalenes.

An iridium-chiral diphosphine complex was used to catalyze an enantioselective [2+2+2] cycloaddition of oxygen- and nitrogen-bridged triynes with ortho-substituted aryl groups on their termini. ortho-Diarylbenzenes with atropisomeric chiralities were obtained in high yield and enantiomeric excess. (c) 2006 Elsevier Ltd. All rights reserved.

Transition metal-catalyzed cycloaddition is an atom-economical and powerful synthetic tool for the construction of cyclic carbon skeletons. Various types of cycloadditions, including [2 + 2 + 1], [2 + 2 + 2], [4 + 2] cycloaddition, etc., have been reported. Their asymmetric versions using chiral transition metal catalysts have also been reported to give enantiomerically-enriched multi-cyclic compounds. First, an iridium-catalyzed enantioselective Pauson-Khand-type reaction is summarized. Pauson-Khand(-type) reaction is a [2 + 2 + 1] cycloaddition of an alkyne, alkene and carbon monoxide, and gives synthetically useful cyclopentenones. Rhodium- and iridium-catalyzed Pauson-Khand-type reactions using an aldehyde as a CO source were also mentioned. Second, two types of enantioselective [2 + 2 + 2] cycloadditions are described: One is an iridium-catalyzed [2 + 2 + 2] cycloaddition of diynes and monoalkynes for the synthesis of chiral teraryls with two axial chiralities. Another is a rhodium-catalyzed [2 + 2 + 2] cycloaddition of enynes and monoalkynes for the synthesis of bicyclic cyclohexa-1, 3-dienes with a chiral quaternary carbon center. Third, a rhodium-catalyzed enantioselective [2 + 2] cycloaddition of alkynes and alkenes for the synthesis of chiral cyclobutenes is mentioned.

The organic field-effect transistors based on polydiacetylene as an active semiconductor have been made. The hole mobility and the on/off ratio have been determined to be 1.3 x 10(-3) cm(2)/V s and 1.0 x 10(4), respectively, for the transistor based on the blue phase of polydiacetylene prepared from 10, 12-pentacosadiynoic acid. The gate-voltage-induced infrared absorption spectrum has been attributed to the positive carriers injected by field effect. The spectrum shows a remarkable electron-molecular vibration coupling between vibration levels and an electronic transition.

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The catalytic activity of a Rh complex in cross-coupling between ArZnI and TMSCH2I was examined in which the Rh complex, generated in situ from [RhCl(1,5-cyclooctadiene)](2) and 1,1'-bis(diphenylphosphino)ferrocene, exhibited excellent catalytic activity for the production of various functionalized benzylsilanes in good yields. From P-31 NMR studies of various solutions containing several of the reaction components, confirmation of the rapid and quantitative transfer of aryl groups from ArZnI to the Rh complex to form arylrhodium species was ascertained. A catalytic cycle, commencing with the transmetalation, was thus proposed for the reaction.

Wilkinson's catalyst [RhCl(PPh3)3] catalyzed a cycloisomerization of allenynes which possess geminal methyls on the allene terminus and an intramolecular ene-type reaction proceeded to give various cross-conjugated trienes. Thermal Diels-Alder reaction of the obtained triene was examined to give a bicyclic compound in a high yield.

The Pauson-Khand(-type) reaction is a [2+2+1] cycloaddition of an alkyne, alkene and carbon monoxide, which gives synthetically useful cyclopentenones. The carbonylative coupling is mediated or catalyzed by various transition metal complexes. This review summarizes the recent advances in the catalytic Pauson-Khand(-type) reaction.

Palladium-catalyzed cyclization of dimethyl-substituted allene possessing amino functionality with aryl iodides efficiently proceeded in the presence of diisopropylethylamine to give 2,2-dimethyl-3-aryl-3-pyrrolines. Under an atmospheric pressure of carbon monoxide, 3-aroyl-3-pyrrolines are provided in good yield.

The asymmetric autocatalysis is an enantioselective synthesis where the asymmetric catalyst and the product possess the same structure and the same absolute configuration. We disclosed chiral α-isopropyl-3-pyridinemethanols, α-isopropyl-5-pyrimidinemethanols, and α-isopropyl-3-quinolinemethanols operate as asymmetric autocatalysts in the enantioselective additions of i-Pr2Zn to 3-pyridinecarbaldehyde, 5-pyrimidinecarbaldehyde and 3-quinolinecarbaldehyde, respectively. Especially, practically perfect asymmetric autocatalysis (&gt
99% yield and &gt
99.5%e.e.) is attained by using 2-(3,3-dimethyl-1-butynyl)-α-isopropyl-5-pyrimidinernethanol as an asymmetric autocatalyst. Moreover, consecutive asymmetric autocatalytic reaction enables α-isopropyl-5-pyrimidine- and α-isopropyl-3-quinolinemethanols as well as 5-(1-hydroxy-2-methylpropyl)pyridine-3-carboxamides with extremely low e.e. to automultiply with dramatic amplification of e.e. without any assistance of other chiral auxiliaries. It was also found that various chiral compounds can operate as chiral initiators in the enantioselective addition of i-Pr2Zn to 5-pyrimidinecarbaldehydes and α-isopropyl-5-pyrimidinemethanols with high e.e. were obtained. For example, in the presence of L-leucine with 2%e.e., asymmetric autocatalysis affords an (R)-α-isopropyl-5-pyrimidinemethanol with high e.e. It is known that asymmetric degradation of racemic leucine using circularly polarized light (CPL) gives chiral leucine (ca. 2%e.e.). Thus, asymmetric autocatalysis with amplification of e.e. serves as a correlation between CPL and highly enantiomerically enriched organic molecules. Moreover, enantiomorphic inorganic crystals such as quartz (SiO2) and sodium chlorate (NaClO3) can be utilized as chiral initiators and an α-isopropyl-5-pyrimidinemethanols with high e.e. was obtained in high yields.

Homo-coupling reactions of aryl- or alkynylzinc iodides were achieved by the use of N-chlorosuccinimide as an oxidant of zinc compounds in the presence of a catalytic amount of Pd.

Acetates of chiral 5-pyrimidylalkanols are transformed into chiral a acetoxy-N-acetylamides and alpha-acetoxyamides without racemization in high total yields by the oxidative cleavage of pyrimidine ring using ruthenium tetroxide.

Chiral N-diphenylphosphiny 1-3-quinoly lamines (DPP amines) with up to 74.9% e.e. were obtained by the enantioselective alkylation using dialkylzincs in the presence of various chiral amino alcohols. The acidic hydrolysis of the chiral DPP amine afforded optically active chiral 3-quinolylamine without racemization.

Enantioselective cyclopropylation of various aldehydes proceeds using dicyclopropylzine in the presence of a catalytic amount of chiral amino alcohol or thiophosphoramidate with Ti(OPri)(4) to provide enantiomerically enriched cyclopropyl alkanols (up to 96.6% ee).

Chiral N,N-dialkylnorephedrines supported on polystyrene resin catalyse the enantioselective addition of dialkylzincs to N-diphenylphosphinylimine, affording optically active N-diphenylphosphinylamines with high enantiomeric excess, The influence on the enantioselectivity of the carbon-chain spacer between the chiral function and polymer resin has been examined. Reaction temperature- and solvent-dependency on the chiral polymer-catalysed reaction has also been examined.

[4+2] Cycloaddition reaction proceeds between N-aryl Schiff's bases and I-alkenyl sulfides, a 1,2-propadienyl sulfide, or 1-alkynyl sulfides in the presence of BF3.OEt2 to provide 2-substituted quinoline derivatives. A 2-alkyl-4-quinolone alkaloid, leptomerine, is prepared by applying the present cycloaddition reaction.

遷移金属錯体による炭素－炭素結合開裂を起点とする反応は、比較的単純な化合物から複雑な炭素骨格を構築できる原子効率が高い合成変換である。炭素－炭素結合活性化の手法として最も汎用されるのが、小員環の環歪みの解消を駆動力とする方法であり、例えば、四員環のシクロブタジエンに2つのベンゼン環が縮環したビフェニレンは、典型的な基質である。本研究では、配向基かつ反応部位としてアルケン部位を有するビフェニレンを用いた分子内反応を検討した。その結果ロジウム触媒を用いることで、所望のより混み合った炭素−炭素結合が開裂し、引き続きアルケンが挿入することで分子内[4+2]付加環化反応が進行することを見出した。

本研究は、ヘテロ元素を導入した縮合多環π共役系の中で、特に非平面π共役系を有する化合物とその光基礎物性の評価を目的とする。具体的には、環内に一つのヘテロ原子を有する共役七員環骨格であるヘテロピンに、3つベンゼン環が縮環したトリベンゾヘテロピンに注目した。報告者は既に、ロジウム触媒を用いた不斉[2+2+2]付加環化により、硫黄原子を有するトリベンゾチエピンの触媒的不斉合成を達成した。本研究では、イリジウム触媒を用いた脱水素型Si-H/C-Hカップリングを用いることにより、ケイ素を有するトリベンゾシレピンの触媒的合成法を見出した。さらに、構造解析、光学分割による不斉合成、熱的安定性について調査を行った。

炭素−水素結合の開裂を起点とする合成変換は、官能基の事前導入が不要であり、その事前導入した官能基に由来する副生成物が生成しないため、原子効率の点で理想的な合成変換である。一方、不活性な炭素−水素結合を開裂するためには、反応点に触媒を近づけるために配向基が重要である。実際に、遷移金属触媒による炭素−水素結合の活性化において配向基の導入により様々な形式の合成変換が報告されている。しかしながら炭素−水素結合活性化を起点とする不斉反応の報告例は未だ少ない。今回報告者は、イリジウム錯体と光学活性ホスフィンから調製される不斉触媒により、高エナンチオ選択的な不斉C-H共役付加反応を達成した。

本研究では、堅固な構造を有する三次元骨格として、配位子の母骨格や高分子の基本ユニットとして活用されながら、キラル素子として利用されていなかったトリプチセン骨格に注目する。中でも2つの橋頭位に窒素原子を有する置換ジアザトリプチセンは、窒素原子上に中心不斉を有する過去の合成例がない新規なキラル骨格である。本年度はその予備的な研究として、窒素原子を環内に有する七員環の8π系化合物であるアゼピンに2つのベンゼン環が縮環したジベンザゼピン骨格の効率的な構築を目指した。アゼピンに代表されるヘテロピンは三次元の桶型構造であるため、置換基の導入によりキラリティの導入が可能である。

 ヘテロ元素を含んだ縮合多環式化合物が機能性材料として注目されている。中でも中員環を導入した化合物は歪んだ骨格を有し、平面構造を有するアセン類とは異なる新規な物性が期待される。今回我々は、ジフェニルチオエーテルで架橋された1,8-ジインあるいは、2-スルファニルビフェニルで架橋された1,8-ジインとモノアルキンとの[2+2+2]付加環化を検討したところ、キラルなカチオン性ロジウム触媒を用いることで、効率的に反応が進行し、異なる置換形式の多置換トリベンゾチエピン誘導体が高鏡像体過剰率で得られた。本反応では、ヘテロ元素として硫黄に加え、セレンあるいは酸素架橋の1,8-ジインを用いた際にも高鏡像体過剰率で目的の環化体であるトリベンゾヘテロピンが得られた。

　窒素を含む七員環化合物であるアゼピンに2つのベンゼン環が縮環したジベンゾアゼピンは、多くの医薬品の部分骨格として知られている重要な構造である。我々は、原子効率が高い環化異性化に着目し、ジベンゾアゼピン誘導体の合成を試みた。七員環を構築するためには、進行し易い6-exo-dig型環化ではなく、7-endo-dig型環化を選択的に進行させるため、基質の剛直性と高い求核性を期待しカルバゾール骨格を含む基質を反応に用い検討を行った。その結果、金触媒存在下、所望の7-endo-dig型の環化異性化が選択的に進行し、目的の置換ジベンザゼピン誘導体を高収率で得ることができた。

　環状ペプチドは直鎖ペプチドと比較して標的タンパク質と相互作用しやすく、またタンパク質分解酵素によって分解されにくいなどの特徴を有している。一方我々は、分子内[2+2+2]付加環化反応による分岐型トリインを用いた三脚型シクロファン、およびアミノ酸架橋トリインを用いたアミノインダンカルボン酸誘導体の高エナンチオ選択的合成を達成している。そこで本研究では、分子内[2+2+2]付加環化反応による環状ペプチドの触媒的合成を試みた。その結果、1,6-ジインとアルキン部分がペプチド鎖で架橋されたトリインの分子内[2+2+2]付加環化反応が進行し、種々の環状ペプチドを得ることに成功した。さらに塩基性、酸性アミノ酸を含む環状ペプチドの合成も達成した。

アミノ酸誘導体は、生命維持機能や生体調節機能に加え、生理活性や医薬品の部分構造に含まれるなど、それらの機能は多岐にわたっている。特に非天然のアミノ酸は医薬品のビルディングブロックとしての利用や、未知なる機能が期待されている。そこで我々は炭素－水素結合活性化を起点とし、キラルな4位置換γ-アミノ酸誘導体の不斉合成を目指した。その結果、カチオン性イリジウム錯体とキラル二座リン配位子から調製される触媒存在下、配向基としてピリジル基を導入したγ-ラクタムと種々のアルケンの反応が進行し、キラルなγ-ラクタム誘導体が得られた。引き続き、水素添加、還元で配向基の除去、加水分解によりキラルな4位置換γ-アミノ酸誘導体を得た。

　新規かつ種々の誘導体の合成が容易な不斉配位子群の合成手法の開発は、多彩な不斉炭素骨格の構築に直結する極めて重要な課題である。不斉配位子の不斉要素として、BINAPに代表される軸不斉、SDP、QuinoxP*に代表される中心不斉が挙げられる。一方、「面不斉」リン配位子として、二置換フェロセニル骨格を有する化合物が研究されており、市販の化合物も多い。さらに、面不斉「パラシクロファン骨格」を有する二座配位子としてPHANEPHOS (bis(diphenylphosphino)[2.2]paracyclophane)が市販されているが、BINAP誘導体や二置換フェロセン誘導体と比較して研究が立ち後れている。その理由は、効率的かつ汎用な不斉合成法が少ないのが一因である。　今回我々は、当研究室が開発した不斉オルトリチオ化による面不斉パラシクロファンの高エナンチオ選択的手法により、 [1,n]パラシクロファン骨格を有するモノホスフィン化合物、ならびにジホスフィン化合物を高鏡像体過剰率で不斉合成した。本法により、架橋部の炭素数、構造、あるいはリン上の置換基など、多彩な面不斉リン化合物を得ることが出来る。　さらに、これらの面不斉リン化合物の不斉配位子としての適用として、まず当研究室で開発したパラジウム触媒を用いる連続的不斉Sonogashiraカップリングの不斉配位子として用いた。その結果、これまでに検討した全てのリン化合物よりも高いエナンチオ選択性を達成した（最高90% ee）。また、同様にパラジウム触媒を用いる反応として、Suzukiカップリングを検討した。過去において、中程度のエナンチオ選択性であり、しかも塩基として有毒な水酸化タリウムを用いることが必須であったジクロロフェロセン化合物の非対称化による不斉Suzukiカップリングをモデル反応として検討した結果、通常の無機塩基である炭酸ナトリウムを用い、80% eeを越える高エナンチオ選択的にモノアリール化生成物が得られた。　上記の通り、我々が独自開発した手法により不斉合成したオリジナルなリン化合物の不斉配位子として有効性を実証できた。今後、パラジウム以外の金属触媒の不斉配位子として、さらにはそれ自体を不斉有機触媒として検討する予定である。

　金属が2つのシクロペンタジエニル基によりサンドウィッチ状に挟まれたメタラロセン化合物の中で、金属が鉄であるフェロセンとその誘導体は、その特徴的な構造と化学的・熱力学的・酸化還元的安定性から様々な分野で応用されている。その代表例が不斉リン配位子であり、例えば、フェロセン骨格を持つキシリホス（xyliphos）は除草剤(S)-Metolachlorの年10000トン以上のスケールでの工業的な不斉合成に用いられており、工業的な利用に耐えうる数少ない不斉リン配位子の一つである。しかしながら、このようなキラルな1,2-二置換フェロセンの合成には、化学量論量の有機金属試薬を用いるジアステレオ選択的な手法が多く用いられていた。一方、当研究室ではこれまでにカチオン性イリジウム、ロジウム触媒を用いて配向性置換基を持つ反応基質の炭素－水素結合活性化反応を利用した炭素－炭素結合生成反応の開発を行った。そこで本研究では、配向性置換基を利用した炭素－水素結合の活性化により、直接的な炭素－炭素結合生成反応によって、フェロセン誘導体の合成およびその不斉合成を目指した。　配向基としてイミノ基を有するフェロセン用い、三価ロジウム触媒存在下、イソシアナートとの反応を試みたところ、イミノ基のα位がアミド化された二置換体フェロセン誘導体が得られた。反応条件の最適化の結果、対アニオンとしてテトラフルオロホウ酸（BF4）を用いることで、電子求引性あるいは供与性置換基を有するフェニルイソシアナート、あるいはアルキルイソシアナートとの反応が進行し、対応する二置換体フェロセン誘導体が得られた。　そこで次に、本系を不斉反応へ展開し、キラルな配向基としてオキサゾリン環を用いて検討を行った。その結果イミノ基を配向基とするフェロセンと同様にアリールイソシアナート、アルキルイソシアナートに対しても反応が進行した。また、いずれの反応においても生成物は単一のジアステレオマーとして得られ、特にパラクロロフェニルイソシアナートとの反応生成物は単結晶であり、X線による結晶構造解析により立体構造を確定できた。　上記のように、カチオン性ロジウム触媒を用いることにより、炭素―水素の直接的な官能基化によるキラル二置換フェロセン化合物の合成を達成した。今後、プロキラルなフェロセン化合物のエナンチオ選択的な不斉合成を目指す。

　シクロファンとは、広義で芳香族化合物を含む大環状架橋型化合物である。これまで架橋構造により歪みをもつシクロファン類や、多数の環状構造を架橋部に有する複雑な骨格のシクロファン類の合成が達成された。近年では、シクロファン類のもつ機能性に注目が集まり、ホスト－ゲスト化学のゲスト化合物として多くの研究例がある。中でも、ベンゼン環のパラ位の2つの置換基を環構造で連結した化合物をパラシクロファンと言い、架橋鎖が短い場合にはベンゼン環が自由回転できないために、面不斉を生じ鏡像異性体が存在する。これまで既に、パラシクロファン化合物の面性キラリティを利用し、キラル認識剤、キラルポリマー、不斉配位子などとしての応用が報告されているが、それらは光学分割や不斉結晶化などで合成された。一方、パラシクロファン化合物のエナンチオ選択的不斉合成は僅か3例のみであり、しかも不斉収率の最高値は、我々が報告した79% eeであった。　そこで本研究では、ベンゼン環と架橋鎖を酸素原子により連結したヒドロキノン型のパラシクロファンを用い、酸素への配位を利用した不斉オルトリチオ化を検討した。その結果、sec-BuLiとキラルジアミン配位子であるsparteineを作用させたところ、高エナンチオ選択的にモノリチオ化が進行し、キラルなアリールリチウム試薬が得られた。さらに、過剰量のsec-BuLiを加えた場合、パラ位で位置選択的かつ高エナンチオ選択的（99% ee）にジリチオ化が進行し、C2対称を有するキラルなアリールジリチウム試薬が得られた。得られたキラルなモノリチオ化、ジリチオ化体を種々の求電子剤と反応させることにより、種々の長さの架橋鎖、種々の官能基を１つないし２つ有する面不斉パラシクロファンが極めて高不斉収率で得られた。

「環境にやさしい化学 (Green Chemistry)」の達成が求められる今日、従来のように効率的に目的化合物を合成するだけでなく、反応、後処理、精製の全ての過程を通して環境負荷を低減させたシステムの構築が求められている。その対策として、(1) 等量反応から触媒反応へ、(2) 副生成物が少ない反応系の開発、(3) 回収再利用可能な反応媒体（溶媒）の利用、などが挙げられる。本研究では、遷移金属”触媒”を用いる反応において、”副生成物の低減化”を実現するC-H結合活性化反応、ならびに”反応媒体と不斉触媒を兼ね備えた”機能性分子の創製を目指した。　C-H結合の活性化を伴う直接的な変換反応は、従来の官能基を起点とする反応と異なり、反応点への官能基の導入が不要でありことから反応工程数を減ずることができ、さらには反応の進行に伴って生成する官能基に由来した副生成物も低減できる。報告者は、カチオン性イリジウム錯体に注目し、アリールケトンのカルボニル基への配位により、そのオルトのsp2C–H結合活性化を起点する種々の触媒反応を開発した。すなわち、アリールケトンのアルケニル化、さらには引き続く環化反応によりベンゾフルベンの合成を達成した。また、分子内に求核付加を受ける別のカルボニル基を導入することで、分子内環化反応が進行し、4-置換ベンゾヘテロールの合成を達成し、またアミドに隣接したsp3C–H結合のアルケニル化も達成した。　一方、反応媒体に不斉触媒能を付与する試みとして、報告者が開発したイリジウム触媒によるエン型反応において、イリジウム錯体の対アニオンとして天然物由来の安価な不斉源を検討した。すなわち、反応媒体としてイオン性液体への展開を視野に入れ、種々のアミノ酸塩を検討したが、反応は進行するものの、不斉誘起されなかった。

　報告者は既に、キラルイリジウム触媒を用いる対称ジインと対称モノアルキンとのエナンチオ選択的分子間[2+2+2]付加環化反応を報告した。本反応は、軸不斉をもつC2対称キラルテルアリール化合物を高収率かつ極めて高い不斉収率で与える。これまでに報告したジインのカップリングパートナーは、両プロパルギル位に酸素官能基を有するアルキンのみであった。そこで本研究で一つあるいは二つの官能基をもつ種々のモノアルキンの検討、さらには炭素-炭素多重結合に替え、炭素－ヘテロ元素多重結合をもつ化合物を検討した。　まずプロパルギル位に、一つの水酸基、アミノ基、ホスフィニル基を有するアルキンとジインとの反応を行った結果、いずれの場合も環化生成物であるテルアリール化合物が、単一ジアステレオマー、かつほぼ一方の鏡像異性体のみで得られた。さらに、アミノ基と水酸基をともに有するアルキンでも反応が進行し、ほぼ光学的純粋なアミノアルコールが得られた。これらの結果は、エナンチオ選択的[2+2+2]付加環化反応により種々の官能性基を有する軸不斉化合物が得られるたこと意味する。　次に、ジカルボニル化合物とジインの反応を検討した結果、ロジウム錯体を用いることにより、ヘテロ[2+2+2]付加環化反応が進行することを見いだした。1,6-ジインとピルビン酸エステルの反応では、環化体として二環性2H-ピラン化合物の生成を確認できたが、単離精製する過程で不安定な2H-ピラン環が開環し、ジエノン体として得られた。不斉反応へ展開するため1,7-ジインを用いたところ、二環性2H-ピラン化合物を単離同定することができた。現在のところ中程度（50% ee）の不斉収率を達成できたが、今後エナンチオ選択性を向上させ、不斉ヘテロ[2+2+2]付加環化反応による不斉炭素を有する複素環化合物の合成を目指す。

「環境にやさしい化学 (Green Chemistry)」の理論化と実践が求められる今日、反応媒体として基質に対し大量に用いられる有機溶媒が大きな問題となっている。本研究は、不斉触媒と反応媒体の２つの機能を兼ね備えた高分子触媒の創製が最終目標である。溶媒を用いないことで、生成物と触媒の分離精製が容易になるだけでなく、触媒の再利用が可能であり、環境負荷が小さく、かつ経済効率の高い不斉触媒システムの構築が可能となる。　本年度は、予備的実験として、近年注目されている新反応媒体の一つである有機イオン性液体中での触媒反応を検討した。有機イオン性液体は、(1) 大きな装置が不要、(2) 安価かつ取扱いが容易、(3) 目的に合わせて違う骨格をもつ物質の合成が可能、などの利点をもつ。　その結果、イリジウム触媒を用いる1,6-エンインの環化異性化反応が、通常用いる有機溶媒であるトルエン中より、有機イオン性液体であるイミダゾリウム塩中で加速され、高効率的に生成物を与え、また反応媒体の再利用も可能であることを見いだした。これまで、水素化反応、カップリングなどの遷移金属錯体を用いる触媒反応で、イオン性液体が利用された例は知られているが、環化異性化反応では初めての例である。　現在、無溶媒化反応へのステップとして、イリジウム錯体のイミダゾリウム塩への担持、さらには不斉反応への検討を行っている。

「環境にやさしい化学 (Green Chemistry)」を達成する上で、反応媒体として基質に対し大量に用いられる有機溶媒が大きな問題となっている。一方不斉触媒反応では、立体選択性(不斉収率)、反応効率(TOF)、触媒活性(TON)などの点で実用性の高い反応系を構築するために、溶媒選択は極めて重要なファクターである。本研究は、新たな反応媒体の探索という従来のアプローチではなく、反応媒体を必要としない無溶媒型触媒システムの開発、特に不斉触媒系に焦点をあて、研究を行った。　その結果報告者は、Pauson-Khand型反応で無溶媒型不斉触媒反応を見いだした。Pauson-Khand型反応は、一酸化炭素挿入を伴うアルケン-アルキンカップリング反応であり、シクロペンテノン骨格を構築する有用な反応のひとつである。従来の不斉Pauson-Khand型反応は、有機溶媒を用い、一酸化炭素源としてCOガスを用いており、報告者も、同条件下、キラルイリジウム錯体により、高エナンチオ選択的な反応を既に発表している。そこで、遷移金属錯体によるカルボニル化合物の脱カルボニル化反応に着目し、アルデヒドのカルボニル部位を一酸化炭素源として活用する触媒系を検討した。その結果、無溶媒条件下、a,b-不飽和アルデヒドであるシンナムアルデヒドを用い、光学活性ロジウム触媒を用いることで、高エナンチオ選択的な不斉カルボニル化反応が進行し、高い鏡像体過剰率のシクロペンテノン誘導体が得られた。　従来、遷移金属錯体を用いる反応では、触媒サイクルを効率的に回すために、反応溶媒の使用が必要とされてきた。本研究により、反応系の巧みな設計が無溶媒系の構築を可能にすることがわかったことから、遷移金属触媒を用いる他の有用な合成反応における無溶媒系の設計を目指す。