Carbon-Carbon Bond Forming Reactions of α-Aminonitriles Under Dissolving Metal Conditions: Synthesis of Gephyrotoxin-167B

Abstract
Intra- and/or intermolecular alkylations of the bicyclic α-aminonitriles 6 and 17 (6-cyanohexahydropyrido[2,1-b][1,3]-oxazines) and monocyclic α-aminonitrile 8 (a 2-cyanopiperidine derivative) were achieved under dissolving metal conditions (sodium/liquid ammonia; potassium/tetrahydrofuran/18-crown-6; lithium/4,4′-di-tert-butylbiphenyl). These reactions form the basis of a four step synthesis of Gephyrotoxin-167B, and provide access to the spirocyclic piperidine intermediate 18 (2-iminospiro-[cyclohexane-1,6′-hexahydropyrido[2,1-b][1,3]oxazine]).

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