Isotope effects and the distinction between synchronous, asynchronous, and stepwise Diels±Alder reactions Daniel A. Singleton, p Brian E. Schulmeier, Chao Hang, Allen A. Thomas, Shun-Wang Leung and Steven R. Merrigan Department of Chemistry, Texas A & M University, P.O. Box 30012, College Station, TX 77842-3012, USA Dedicated to Professor Barry M. Trost and his inspiring enthusiasm for chemistry on the occasion of his 60th birthday Received 5 February 2001; revised 28 February 2001; accepted 1 March 2001 Abstract ÐA variety of symmetrical or nearly symmetrical Diels±Alder reactions are studied by a combination of experimental isotope effects, theoretical calculations, and rate observations. Becke3LYP calculations predicted highly asynchronous transition structures for Diels±Alder reactions of bisboryl)acetylenes, dialkyl acetylenedicarboxylates, triazolinediones, and dialkyl maleates. Rate observations and kinetic isotope effects are consistent with these predictions, though the experimental support for the calculated structures is notably ambiguous in some cases. A concerted mechanism is supported for the retro-Diels±Alder reaction of norbornene. Overall, Diels±Alder reactions appear to be only very weakly biased toward synchronous transition states. q 2001 Elsevier Science Ltd. All rights reserved. 1. Introduction It is widely accepted that most Diels±Alder reactions occur by concerted mechanisms, and the common understanding of the facility of Diels±Alder reactions centers on the idea of an aromatic transition state with synchronous formation of the two new carbon±carbon bonds. In the past there has been some controversy over these ideas, with highly asynchronous `biradicaloid' transition states or stepwise mechanisms being favored at times by some groups. 1 However, the view that Diels±Alder reactions intrinsically prefer synchronous transition states has prevailed in later studies. Reactions of unsymmetrical dienes or dienophiles necessarily involve unsymmetrical transition states, but Diels±Alder reactions of symmetrical addends are thought to usually involve synchronous or nearly synchronous C±C bond formation. The evidence for this proposition has come mainly from ab initio calculations, 2±4 substituent effects on the rate, 5 and deuterium kinetic isotope effects KIEs). 6 Recently the argument over the nature of Diels±Alder reactions was brie¯y rekindled by Zewail and coworkers' femtosecond time-resolved observation of an intermediate in the retro-Diels±Alder reaction of norbornene. 7 Notably this intermediate's short lifetime was thought to allow a stereospeci®c stepwise mechanism. 8 Nevertheless, calculations predict a synchronous concerted transition state for this reaction, 9 and Zewail and Houk have found that the femtosecond norbornene observations are consistent with reactions on the excited-state energy surface. 10 We have been intrigued by calculations predicting highly asynchronous transition states for some Diels±Alder reactions, 11±13 and we present here our studies of several symmetrical or nearly symmetrical Diels±Alder reactions. A key tool in these investigations is the comparison of experimental and theoretically predicted 2 H and 13 C KIEs. In several studies we have recently shown that high-level Tetrahedron 57 2001) 5149±5160 Pergamon TETRAHEDRON 0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved. PII: S0040-402001)00354-4 Keywords: Diels±Alder reaction; isotope effect; asynchronous transition state. p Corresponding author. Tel.: 11-409-845-9166; fax: 11-409-845-4719; e-mail: singleton@chemvx.tamu.edu