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

在不对称催化反应中，手性催化剂的柔性越小，立体控制效果越好。本论文以N，N-二甲基-1-二茂铁基乙胺为原料，经4步反应合成了手性双膦（TRAP），并将其应用于不饱和杂环的不对称氢化反应。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。相比之下，MeTRAP仅形成顺式螯合络合物。TRAP配体在1，4，5，6-四氢吡嗪-2-甲酰胺（eq.1）的不对称氢化中是有效的。（R，R）-（S，S）-i-BuTRAP具有最高的对映选择性，97%ee（S）。有趣的是，（R，R）-（S，S）-MeTRAP具有与其它（R，R）-（S，S）-TRAP配体相反的手性对映选择性，氢化产物的ee（R）为85%。本文研究了吲哚的不对称氢化反应。由Rh（acac）（cod）和各种市售手性双膦制备的铑配合物可催化2-取代吲哚的氢化，但导致非对映选择性氢化（0- 1%ee）。然而，PhTRAP显示出高的对映体选择性（85%ee）的氢化。[Rh（nbd）_2]SbF_6-PhTRAP-Cs_2CO_3催化剂是最有效的催化剂，得到光学活性的2-取代吲哚啉，其ee值为94%（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).