Electrophilic Zinc Homoenolates: Synthesis of Cyclopropylamines from Cyclopropanols and Amines.
L Reginald MillsLuis Miguel Barrera ArbelaezSophie A L RousseauxPublished in: Journal of the American Chemical Society (2017)
Metal homoenolates, produced via C-C bond cleavage of cyclopropanols, have been extensively investigated as nucleophiles for the synthesis of β-substituted carbonyl derivatives. Herein, we demonstrate that zinc homoenolates can react as carbonyl-electrophiles in the presence of nucleophilic amines to yield highly valuable trans-cyclopropylamines in good yields and high diastereoselectivities. GSK2879552, a lysine demethylase 1 inhibitor currently in clinical trials for the treatment of small cell lung carcinoma, was synthesized using this strategy.