A Direct Organocatalytic Enantioselective Route to Functionalizedtrans‐Diels–Alder Products Having the Norcarane Scaffold

Abstract

An enantioselective methodology to construct trans‐Diels–Alder scaffolds by organocatalysis with excellent selectivity, high yield and up to five contiguous stereocenters is presented. The reaction concept integrates the halogen effect and a novel discovered pseudo‐halogen effect to direct an endo‐selective, secondary‐amine catalyzed Diels–Alder reaction allowing for the subsequent formation of trans‐Diels–Alder cycloadducts featuring the norcarene scaffold. The methodology relies on the reaction between an in situ generated trienamine and an α‐brominated or α‐pseudo‐halogenated enone to form a fleeting cis‐Diels–Alder intermediate. The endo‐transition state‐enhanced by the (pseudo‐)halogen effect‐sets the stereochemistry that allows for a subsequent SN2‐like reaction at a tertiary center to obtain the trans‐Diels–Alder scaffold. The mechanism was investigated and supported by experimental results as well as computational studies.