An azapentacyclic
compound with the daphenylline ACDEF ring framework
was synthesized from a benzo[e]indole intermediate
efficiently obtained by a 5-endo-trig radical cyclization of a bicyclic trichloroenamide. Stereocontrolled
processes were used to generate the three stereogenic methine carbons
in the pyrrolidine C ring including the all-carbon quaternary stereocenter
at C5. Ring closure to build both seven- and five-membered rings was
achieved by Friedel–Crafts reactions.
A general procedure is reported for the synthesis of cis ring fused azapolycyclic compounds bearing an all‐carbon quaternary stereocenter at the ring fusion and an adequate functionalization for the assembly of new rings leading to advanced synthetic intermediates for Daphniphyllum alkaloid synthesis. The key carbon−carbon bond‐forming step in this approach is a radical cyclization of an N‐cycloalkenyl trichloroacetamide derivative involving a tetrasubstituted enamide to achieve polyfunctionalized lactams.
Three approaches to the stereoselective synthesis of 3‐methyl‐cis‐octahydroindoles through a 5‐endo‐trig radical cyclization are described. First, starting from an N‐vinyl‐α‐chloroacetamide, the cyclization was followed by lactam methylenation and hydrogenation. Second, starting from an alkyne‐tethered enamide, the cyclization was promoted by Bu3SnH, and this was followed by protonolysis of the vinylstannane and hydrogenation of the exocyclic alkene. Third, through a 2,2‐dichloropropanamide cyclization onto an alkenyl bond, and hydrogenation of the resulting endocyclic double bond; this represents the most efficient sequence to form the target compounds. 1,5‐Enyne cyclizations through a 5‐endo‐trig process are reported. Here, a remote functional group (ketal or ketone), allowed the diastereoselectivity of the octahydroindole ring formation to be reversed through steric control of the facial selectivity in the hydrogen radical delivery step.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.