Catalytic Asymetric Reactions with Novel Chiral Catalysts Bearing a Flexible Chiral Reaction Field around the Metal Atom

手性催化剂柔韧性较弱，有望在催化不对称反应中提供更有效的立体控制。本研究制备了具有柔性伯烷基的新型光活性双膦化合物（TRAP），并将其应用于不饱和杂环的对映选择性加氢。以旋光性N，N-二甲基-1-二茂铁乙胺为原料，经4步合成了手性双膦化合物TRAP。TRAP配体通常以反式螯合方式与金属原子配位，但与PtCl_2(MeCN)_2反应得到反式和顺式螯合铂配合物的混合物。i-Pr-和i-BuTRAP仅以反式方式与铂原子螯合。相反，MeTRAP只形成顺式螯合络合物。TRAP配体在1,4,5,6-四氢吡嗪-2-羧酰胺的不对称加氢反应中是有效的（等式1）。（R，R）-(S，S)-i- butrap对映体选择性最高，为97% ee (S)。有趣的是，（R，R）-(S，S)- metrap表现出与其他（R，R）-(S，S)- trap配体相反的手性对映体选择，使加氢产物具有85%的ee (R)。杂芳烃化合物的不对称氢化反应虽有其应用价值，但尚未得到研究。本文研究了吲哚的不对称氢化反应。由Rh(acac)（cod）和各种市售的手性双膦制备的铑配合物可以催化2-取代吲哚的加氢，但导致非对映选择性加氢（0-1% ee）。然而，PhTRAP对氢化反应表现出较高的对映选择性（85% ee）。[Rh(nbd)_2]SbF_6-PhTRAP-Cs_2CO_3催化剂是最有效的催化剂，得到了具有94% ee的光学活性的2-取代吲哚（eq.2）。

Less flexibility of chiral catalyst is expected to provide more effective stereocontrol in catalytic asymmetric reactions. In this study, we prepared new optically active bisphosphines (TRAP) bearing flexible primary alkyl groups on the phosphorus atoms, and applied the chiral bisphosphines into enantioselective hydrogenation of unsaturated heterocycles.The chiral bisphosphines TRAP were synthesized from optically active N,N-dimethyl-1-ferrocenylethylamine in 4 steps. TRAP ligands generally coordinate to a metal atom in trans-chelate fashion, but the reaction with PtCl_2(MeCN)_2 gave the mixture of trans- and cis-chelating platinum complex. i-Pr- and i-BuTRAP chelated to platinum atom in only trans-manner. By contrast, MeTRAP formed only cis-chelating complex.TRAP ligands were effective in the asymmetric hydrogenation of 1,4,5,6-tetrahydropyrazine-2-carboxamide (eq.1). (R,R)-(S,S)-i-BuTRAP exhibited the highest enantioselectivity, 97% ee (S). Interestingly, (R,R)-(S,S)-MeTRAP showed a chiral sense of enantioselection opposite to other (R,R)-(S,S)-TRAP ligands, giving the hydrogenation product with 85% ee (R).Asymmetric hydrogenation of heteroaromatic compounds has been unexplored in spite of its usefulness. Herein, we examined the asymmetric hydrogenatipn of indoles. The rhodium complexes prepared from Rh(acac)(cod) and various commercially available chiral bisphosphines were possible to catalyze the hydrogenation of 2-substituted indole, but resulting in non-enantioselective hydrogenation (0-1% ee). However, PhTRAP showed high enantioselectivity (85% ee) for the hydrogenation. [Rh(nbd)_2]SbF_6-PhTRAP-Cs_2CO_3 catalyst was found to be the most effective catalyst, giving optically active 2-substituted indolines with 94% ee (eq.2).