Reversal of enantioselectivity using tethered bisguanidine catalysts in the aza-Henry reaction

A series of chiral guanidines were synthesized and shown to efficiently catalyze the aza-Henry reaction. Modifications of the catalyst structure revealed important selectivity trends as well as an intriguing reversal in stereoselectivity with bisguanidine variants. These compounds were applied to the aza-Henry reaction between N-Boc imines and nitroalkanes generating the β-nitroamines in up to 77% ee and up to 20:1 diastereoselectivity.

Graphical abstractA series of chiral guanidines were synthesized and shown to efficiently catalyze the aza-Henry reaction. Modifications of the catalyst structure revealed important selectivity trends including an intriguing reversal of stereoselectivity with bisguanidine variants.Download full-size image