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A Direct Organocatalytic Enantioselective Route to Functionalized trans ‐Diels–Alder Products Having the Norcarane Scaffold
Author(s) -
Barløse Casper L.,
Østergaard Niklas L.,
Bitsch René S.,
Iversen Marc V.,
Jørgensen Karl Anker
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202106598
Subject(s) - stereocenter , enantioselective synthesis , chemistry , organocatalysis , diels–alder reaction , amine gas treating , selectivity , cycloaddition , yield (engineering) , combinatorial chemistry , catalysis , organic chemistry , materials science , metallurgy
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 S N 2‐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.