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

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)