Homoproline homologation by enolate Claisen rearrangement or direct allylation: syntheses of (-)-trachelanthamidine, (-)-isoretronecanol and (+/-)-turneforcidine

The pyrrolizidine precursors 13 and 14 are obtained both by enolate Claisen rearrangement of the homoproline allyl ester 12 and by direct allylation of N-protected homoproline ethyl ester 15. In both cases, the reactions show poor levels of stereoselectivity. Reduction gives the corresponding alcohols 2Oa and 21a which are separated and subsequently elaborated to (-)-trachelanthamidine 24 and (-)-isoretronecanol 25 respectively via reductive alkene cleavage, mesylation and spontaneous cyclisation following N-deprotection. The chiral integrity of the original proline-derived asymmetric centre is preserved throughout. A similar enolate allylation gives, with high stereoselectivity, the homologue 34 of the Geissman-Waiss lactone 32, which is similarly transformed into (+/-)-turneforcidine 31.