C-10b Functionalized 5,6-dihydropyrrolo[2,1-a]isoquinolines as intermediates in the synthesis of erythrinane systems. Intra- vs. intermolecular conjugate addition based strategies

Abstract

C-10b Functionalized 5,6-dihydropyrrolo[2,1-a]isoquinolines have been prepared via Parham cyclization and α-amidoalkylation reactions, using functionalized organolithium reagents. Their utility as intermediates in the synthesis of erythrinanes via intra or intermolecular conjugate addition reactions has been studied. Thus, a protocol for preparing the erythrinane skeleton through a Parham cyclization−intermolecular α-amidoalkylation−intermolecular conjugate addition−ring-closing metathesis process has been described.

New approaches for the synthesis of erythrinan alkaloids

“…We were also aware that, in the aforementioned access to lactam 16, Lete and co-workers had found very similar problems and had resorted to incorporation of a further carboxymethyl group to activate the Michael addition process. 42 Instead we returned to the use of radical chemistry, and adopted a method described by Clive and co-workers for the synthesis of functionalised ring-fused bicyclic compounds. 43 The method involves the radical cyclisation of a b-hydroxyselenide, which in our case was readily available by addition to the unsaturated sidechain appendage, Scheme 23.…”