NOVEL ELECTRONIC EFFECTS OF REMOTE SUBSTITUENTS ON THE OXAZABOROLIDINE-CATALYZED ENANTIOSELECTIVE REDUCTION OF KETONES

A new class of highly enantioselective oxazaborolidine-catalyzed reductions of achiral ketones is reported which depends on stereoelectronic effects involving p-substituted non-planar aromatic ketones, or pi-coordinated transition-metal containing ketones, or strained ring ketones, as exemplified in Table 1. The discovery of these reactions was guided by the transition-state model 1, for which they provide experimental support. Because high enantioselectivities (> 30:1) are achievable, these reductions define an excellent method for the synthesis of for example, chiral benzhydrols, chiral propargylic, or chiral allylic alcohol. Lower enantioselectivities observed with CH2Cl2 as solvent, relative to toluene as solvent, are consistent with the transition-state model I and indicate that CH2Cl2 hydrogen bonds to the donor groups in the pi-electron-rich carbonyl substituent (R(L) in 1) thereby diminishing electron supply.