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

金属原子周围具有灵活手性反应场的新型手性催化剂的催化不对称反应

基本信息

批准号：
10208207
负责人：
KUWANO Ryoichi
金额：
$ 6.98万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

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).

手性催化剂的较低灵活性有望在催化不对称反应中提供更有效的立体控制。本研究制备了磷原子上带有柔性伯烷基的新型光学活性双膦(TRAP)，并将该手性双膦应用于不饱和杂环的对映选择性加氢反应。 1-二茂铁基乙胺分 4 步。 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 仅形成顺式螯合复合物。TRAP 配体在 1,4,5,6-四氢吡嗪-2-甲酰胺（eq.1）的不对称氢化中有效。 (R,R)-(S,S)-i-BuTRAP 表现出最高的对映选择性，97% ee (S)。有趣的是，(R,R)-(S,S)-MeTRAP 显示出与其他 (R,R)-(S,S)-TRAP 配体相反的手性对映选择，使氢化产物具有 85% ee (R)尽管杂芳族化合物的不对称氢化有其用途，但尚未对其进行探索。在此，我们研究了吲哚的不对称氢化。由Rh(acac)(cod)和各种市售手性双膦制备的铑配合物可以催化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 对氢化表现出高对映选择性 (85% ee)。 [Rh(nbd)_2]SbF_6-PhTRAP-Cs_2CO_3 催化剂被发现是最有效的催化剂，产生具有 94% ee 的光学活性 2-取代二氢吲哚（eq.2）。