Reduction of an enaminone: Synthesis of the diamino alcohol core of ritonavir

The reduction of (SS)-2-amino-5-dibenzylamino-4-oxo-1,6-diphenylhex-2-ene w as optimized for diastereoselectivity and overall conversion to (2S,3S,5S)- 5-amino-2-dibenzylamino-3-hydroxy-1,6-diphenylhexane (2a), A two-step reduc tion sequence is described wherein the enamine is reduced with a borane-sul fonate derivative followed by reduction of the resulting ketone with sodium borohydride. The desired 2a was obtained with 84% diastereoselectivity and an acyclic 1,4 stereoinduction ratio of 14:1, This methodology has been us ed to produce multikilogram quantities of the diamino alcohol core of Riton avir and should be general to the synthesis of related diamino hydroxyethyl ene isosteres.