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

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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).