Electrophilic Zinc Homoenolates: Synthesis of Cyclopropylamines from Cyclopropanols and Amines
journal contributionposted on 15.08.2017, 13:18 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.
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cyclopropylaminepresencelysine demethylase 1 inhibitorGSKstrategycarbonyl-electrophilediastereoselectivitienucleophilic aminescarbonyl derivativesCyclopropanolsynthesisElectrophilic Zinc Homoenolatesβ-nucleophilecyclopropanolzinc homoenolatesCyclopropylaminetrancell lung carcinomaHereinyieldcleavageSynthesiAmines Metal homoenolatesbond