Intramolecular Dehydrative Coupling of Tertiary Amines and Ketones Promoted by KO-t-Bu/DMF: A New Synthesis of Indole Derivatives

Abstract

A new synthesis of indole derivatives has been achieved through intramolecular dehydrative coupling of tertiary amines and ketones promoted by KO-t-Bu/DMF. The reaction probably proceeds via an α-amino alkyl radical pathway.

Transition‐Metal‐Free α‐Arylation of Enolizable Aryl Ketones and Mechanistic Evidence for a Radical Process

“…The hypothesis25 of Yan and co‐workers, namely that an electron‐rich carbamoyl anion is generated by the deprotonation of DMF with KO t Bu, seems more reasonable to explain the experimental observations. The formation of this intermediate was first reported by Reeves and co‐workers 26.…”

Synthesis of Dihydroindoloisoquinolines through Copper‐Catalyzed Cross‐Dehydrogenative Coupling of Tetrahydroisoquinolines and Nitroalkanes

“…However, the installation of an ortho acyl group on the N‐aryl moiety is mandatory to accomplish the corresponding dehydrative coupling (Figure ). This transformation has been promoted by stoichiometric amounts of a base or catalyzed by iridium complexes under thermal of photoredox conditions ,…”

Sequential Nucleophilic C(sp3)‐Benzylation/C(sp2)–H Arylation for the Synthesis of Spiro[oxindole‐3,5′‐pyrrolo[2,1‐a]isoquinolines]

“…The indolizidine framework, characterized by fused six‐ and five‐membered rings with a bridgehead nitrogen atom, constitutes an important nitrogen‐containing heterocyclic motif that is present in many alkaloids that have been shown to have various biological activities (Figure ), Accordingly, interest in their diverse activity and the abundance of this core structure in nature is the motivation behind the development of creative methods for the synthesis of such bicyclic systems. These strategies mainly rely on the intramolecular cyclization reactions based on pyrrole/isoquinoline skeletons, cascade cyclization of pyrrole/unsaturated amine derivatives, and the hydrogenation of aromatic indolizine precursors . Despite these efforts, concise and highly efficient methods for the expeditious construction of the indolizidine core unit that incorporates other structures remain a desirable and challenging goal.…”