Intramolecular Hydro‐N‐alkylation of Hydrazones and Oxime Ethers: Synthesis of Novel D‐Secoestrone Isoquinuclidines via Domino 1,5‐Hydride Shift/Cyclization

Abstract

AbstractThe direct transformation of a benzylic C(sp3)–H bond into a C–N bond from steroidal hydrazones 10b, 10f–l and oxime ethers 28b–d under the action of a stoichiometric amount of Lewis acid is reported. The mechanism of functionalization to give novel types of isoquinuclidine derivatives 25b, 25f–l and 32b–d is assumed to involve an intramolecular domino 1,5‐hydride transfer/cyclization sequence. Azomethine imines 23b, 23f–l and oxyiminium ions 29b–d are proposed as intermediates, which undergo 1,5‐hydride shift to give the tertiary carbocation 24b, 24f–l or 31b–d. The nucleophilic addition of the hydrazine or hydroxylamine moiety to the benzylic C‐9 carbon led to bridged azaestrone derivatives. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)