Premium
Stereocontrol of the Intramolecular Diels−Alder Reaction by Internal Hydrogen Bonding
Author(s) -
Cayzer Tory N.,
PaddonRow Michael N.,
Sherburn Michael S.
Publication year - 2003
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200300414
Subject(s) - intramolecular force , chemistry , hydroxymethyl , diels–alder reaction , hydrogen bond , bicyclic molecule , diene , stereochemistry , covalent bond , medicinal chemistry , transition state , molecule , organic chemistry , catalysis , natural rubber
Abstract A novel approach for exo / endo stereocontrol of intramolecular Diels−Alder reactions is described. Substrates carrying a hydroxymethyl group attached to the diene and an ester group attached to the dienophile participate in hydrogen bonding in the transition state. This non‐covalent interaction causes either a significant enhancement or diminution in the observed kinetic endo / exo product ratio. Thus, the parent pentadienyl maleate 12 undergoes intramolecular Diels−Alder reaction to give an approx. 5:1 mixture of trans ‐ and cis ‐fused bicyclic cycloadducts, whereas the C 2‐hydroxymethyl analogue 1 delivers a 1:1 ratio of products. In contrast, the parent pentadienyl fumarate 13 gives a 3:2 trans : cis ratio, which is improved to 9:1 in the C 2‐hydroxymethyl analogue 4 . These stereoselectivities are accurately predicted from transition structure populations calculated using B3LYP/6‐31+G(d) theory. The presence of an intramolecular H‐bond confers a transannular Diels−Alder‐like appearance upon the transition states of these reactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)