Corey-Itsuno Reduction - Scope and Limitations - Stereo and Chemoselectivity

Stereo and Chemoselectivity

The CBS reduction has proven to be an effective and powerful method to reduce a wide range of different types of ketones in both a stereoselective and chemoselective manner. Substrates include a large variety of aryl-aliphatic, di-aliphatic, di-aryl, α,β unsaturated enone and ynone systems, as well as ketones containing heteroatoms. Combinations of different derivatives of the CBS catalyst and borane reducing agents have been employed to optimize enantioselectivity.

Several interesting cases are worth noting in this selection of substrates. First, in the case of the diaryl system 9, relatively high stereoselectively is achieved despite the isosteric nature of the ketone substituents, suggesting that electronics in addition to sterics may play a role in the stereoselectivity of the CBS reduction. Differences in the substitution of the alkyne moieties in ynones 11 and 12 result in a change of selectivity for the alkyne to function as the more sterically bulky substituent rather than the smaller one. For the α,β unsaturated systems 10-12, efficient reduction of the ketone occurs despite the possible side reaction of hydroboration of the C-C unsaturated bond. The CBS reduction has also been shown to tolerate the presence of heteroatoms as in ketone 13, which is capable of coordinating to the borane.