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

The direct transformation of a benzylic C(sp 3 )–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)