Premium
Internal Nucleophilic Catalyst Mediated Cyclisation/Ring Expansion Cascades for the Synthesis of Medium‐Sized Lactones and Lactams
Author(s) -
Lawer Aggie,
RossiAshton James A.,
Stephens Thomas C.,
Challis Bradley J.,
Epton Ryan G.,
Lynam Jason M.,
Unsworth William P.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201907206
Subject(s) - chemistry , nucleophile , ring (chemistry) , catalysis , transition state , nucleophilic addition , chirality (physics) , cascade , amine gas treating , combinatorial chemistry , lactam , stereochemistry , organic chemistry , physics , chiral symmetry breaking , chromatography , quantum mechanics , nambu–jona lasinio model , quark
Abstract A strategy for the synthesis of medium‐sized lactones and lactams from linear precursors is described in which an amine acts as an internal nucleophilic catalyst to facilitate a novel cyclisation/ring expansion cascade sequence. This method obviates the need for the high‐dilution conditions usually associated with medium‐ring cyclisation protocols, as the reactions operate exclusively via kinetically favourable “normal”‐sized cyclic transition states. This same feature also enables biaryl‐containing medium‐sized rings to be prepared with complete atroposelectivity by point‐to‐axial chirality transfer.