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Electrophilic Zinc Homoenolates: Synthesis of Cyclopropylamines from Cyclopropanols and Amines

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journal contribution
posted on 15.08.2017 by L. Reginald Mills, Luis Miguel Barrera Arbelaez, Sophie A. L. Rousseaux
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.