Synthesis of Novel D ‐Secoestrone Isoquinuclidines by an Unpredicted Iminium Ion‐Induced 1,5‐Hydride Shift

Unique 9,13‐bridged D ‐secoestrone alkaloids have been synthesized and structurally characterized. Treatment of 3‐methoxy‐16,17‐secoestra‐1,3,5(10)‐trien‐17‐al ( 6a ) with aniline ( 7 ) or substituted aniline derivatives 8 − 28 in the presence of different Lewis and Brønsted acids produces the bridged azaestrone derivatives 51 − 67 and the alkenes 68 − 73 in high yields in a domino‐type process. The imines 29 − 50 are proposed as intermediates, undergoing 1,5‐hydride shifts via the iminium ion salts 75 to give the cations 77 , which, depending on the substitution pattern on the aniline moiety, either afford the bridged compounds through a nucleophilic addition of the formed secondary amine to the benzylic carbocation or give the alkenes through the abstraction of a proton at C‐8. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)