Synthesis and reactivity of hydroindole enelactams leading to densely functionalized scaffolds

Org Biomol Chem. 2021 Mar 18;19(10):2284-2301. doi: 10.1039/d1ob00060h.

Abstract

The 5-endo-trig radical cyclization of N-benzyl-N-[(2-substituted)cycloalkenyl] trichloroacetamides (tetrasubstituted enamides) using Bu3SnH and AIBN is a reliable synthetic procedure giving access to 3a-methyl- and 3a-methoxycarbonyl enelactams. The substrate-controlled diastereoselective enolate alkylation of these enelactams resulted in the synthesis of a set of 3-substituted derivatives that upon reduction furnished polyfunctionalized cis-octahydroindoles. The latter building blocks, which embody three consecutive stereocenters at C-3, C-3a, and C-7a, were also synthesized through an initial reductive radical cyclization using (carbo-substituted)dichloroacetamides.

Publication types

  • Research Support, Non-U.S. Gov't