Asymmetric Rh-Catalyzed Hydrogenation of Enamides with a Chiral 1,4-Bisphosphine Bearing Diphenylphosphino Groups

Abstract

Much effort has been devoted to the development of efficient asymmetric synthetic methods for the preparation of enantiomerically enriched compounds.1,2 Among various methods for the enantiomerically selective synthesis of chiral organic compounds from prochiral precursors, enantioselective catalytic hydrogenation of dehydro precursors has been extensively developed.3 In fact, asymmetric hydrogenation is one of the most practical methods in asymmetric synthesis, accounting for 70% of all procedures used on a commercial scale.4 However, most asymmetric catalytic hydrogenation systems only hydrogenate electron-deficient olefins with high enantioselectivity and high reactivity. In contrast, electronrich olefins, such as simple enamides5 and enolates,6 are generally poor substrates for asymmetric hydrogenation with most known systems. Since enamides and enolates upon asymmetric hydrogenation can be converted to enantiomerically pure amines and alcohols,7 it would be extremely desirable to have a general and efficient method for this transformation. Recently, Burk and coworkers have reported that Rh complexes bearing the electron-rich DuPhosand BPE-type ligands were efficient catalysts for the asymmetric hydrogenation of enamides8 and enolates.9 They reported that analogous Rh-chiral bisphosphines bearing diphenylphosphino groups (e.g., BINAP, DIOP, and CHIRAPHOS) led to significantly lower enantioselectivities in the reduction of enamides (<60% ee).8 We have been interested in elucidating the steric and electronic effects10 of various diphenylphosphino-bearing chiral ligands in asymmetric hydrogenation processes. Recently a new chiral 1,4-bisphosphine, 2(R),2′(R)-bis(diphenylphosphino)-1(R),1′(R)-dicyclopentane ((R,R)BICP, Figure 1), was reported from our laboratory as an excellent ligand for the Rh-catalyzed asymmetric hydrogenation of dehydroamino acids.11 The key feature of this new ligand is that four stereogenic centers are introduced in a conformationally rigid bicyclic backbone, which is fundamentally different from either axially dissymmetric BINAP or bisphosphines with two stereogenic centers. Herein, we describe the highly enantioselective Rhcatalyzed hydrogenation of enamides using the BICP ligand. Among the known chiral bisphosphines with diphenylphosphino groups, the BICP ligand gives the highest enantioselectivity for the rhodium-catalyzed asymmetric hydrogenation of simple enamides.