Stereocontrol of the Intramolecular Diels−Alder Reaction by Internal Hydrogen Bonding

✍ Scribed by Tory N. Cayzer; Michael N. Paddon-Row; Michael S. Sherburn

• Book ID: 102170003
• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 223 KB
• Volume: 2003
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.200300414

✦ Synopsis

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)