Alkyl C-O ring cleavage of bicyclic beta-lactones with Normant reagents: synthesis of a Merck IND intermediate.
Highly diastereoselective Cu(I)-mediated, bicyclic beta-lactone ring cleavage reactions with either alkyl or aryl cuprates proceeded with inversion of stereochemistry to give optically active trans-substituted cyclopentanes and cyclohexanes. Optimization of typically problematic aryl cuprate additions was made possible by minimization of a competing bromide-induced ring cleavage process. The utility of this process was demonstrated by an efficient synthesis of a Merck investigational new drug (IND) intermediate for an anti-HIV CCR5 antagonist.
Zhang
Wei
W
Department of Chemistry, Texas A&M University, P.O. Box 30012, College Station, Texas 77842-3012, USA.
Matla
Andrea S
AS
Romo
Daniel
D