SYNTHESIS OF ANALOGS OF IBOGA ALKALOIDS - INVESTIGATION OF ELECTROPHILIC, PALLADIUM-CATALYZED, AND RADICAL CYCLIZATIONS FOR THE PREPARATION OF 5,6-HOMOIBOGA DERIVATIVES

The Diels-Alder adducts formed from l-(benzyloxycarbonyl)-l,2-dihydropyridine or l-(benzyloxycarbonyl)-4-methoxy-l,2-dihydropyridine by reaction with methyl 2-[l-(phenylsulfonyl)-l/f-indol-2-yl]-2-propenoate can serve as precursors of the 5,6-homologues of the iboga alkaloid skeleton. The eight-membered C-ring can be closed by introduction of a three-carbon bridge between the isoquinuclidine nitrogen and the 3-position of the indole ring. Electrophilic cyclization proceeds in modest yield. Intramolecular Heck reactions involving a 3-iodinated indole ring and N-acryloyl or N-allyl derivatives of the isoquinuclidine ring are efficient only when the indole ring is N-methylated. Intramolecular radical addition of a 3-iodinated indole occurs when a 2-eth-oxycarbonyl, 2-phenylsulfonyl, or 2-phenylsulfinyl substituent is present on an N-allyl isoquinuclidine substituent. The cyclization products from the 2-phenylsulfonyl case can be converted to various homoiboga derivatives. © 1990, American Chemical Society. All rights reserved.