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. 2009 Feb 11;131(5):1947-57.
doi: 10.1021/ja8079548.

Diels-Alder exo selectivity in terminal-substituted dienes and dienophiles: experimental discoveries and computational explanations

Yu-hong Lam  1 , Paul Ha-Yeon Cheong, José M Blasco Mata, Steven J Stanway, Véronique Gouverneur, K N Houk
Affiliations

Diels-Alder exo selectivity in terminal-substituted dienes and dienophiles: experimental discoveries and computational explanations

Yu-hong Lam et al. J Am Chem Soc. .

Abstract

The Diels-Alder reactions of a series of silyloxydienes and silylated dienes with acyclic alpha,beta-unsaturated ketones and N-acyloxazolidinones have been investigated. The endo/exo stereochemical outcome is strongly influenced by the substitution pattern of the reactants. High exo selectivity was observed when the termini of the diene and the dienophile involved in the shorter of the forming bonds were both substituted, while the normal endo preference was found otherwise. The exo-selective asymmetric Diels-Alder reactions using Evans' oxazolidinone chiral auxiliary furnished a high level of pi-facial selectivity in the same sense as their well-documented endo-selective counterparts. Computational results for these Diels-Alder reactions were consistent with the experimental endo/exo selectivity in most cases. A twist-asynchronous model accounts for the geometries and energies of the computed transition structures.

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Figures

Scheme 1
Scheme 1
Selected Examples of Substrate- and Catalyst-Controlled Exo-Selective Intermolecular Diels–Alder Reactions.
Scheme 2
Scheme 2
Stereochemical Dependence on Substitution Pattern of Starting Materials.
Chart 1
Chart 1
Structure of Dienes 1−2 and Dienophiles 3−6.
Figure 1
Figure 1
Numbering of Cycloadducts.
Figure 2
Figure 2
Rationalization of the Sense of Asymmetric Induction in the 1a–1c + 3* Cycloadditions.
Figure 3
Figure 3
Key NMR Coupling Constants for Stereochemical Assignments Illustrated for Endo- and Exo-15.
Figure 4
Figure 4
Endo and Exo TSs of the 2c+A2 Cycloadditions. Gas-phase enthalpies of activation computed at the B3LYP/6−31G(d) level. Free energies of activation computed by B3LYP/6−31G(d), corrected for solvent effects by PCM single-points at HF/6−31+G(d,p). Interatomic distances around the forming ring in Å and angles of pyramidalization at the termini of the partially formed bonds are labeled.
Figure 5
Figure 5
Side View of A2 Dienophile Fragment in (a) the Endo 2c+A2 TS, and (b) the Exo 2c+A2 TS. (c) Overlay of A2 Dienophile Fragments in TSs of 2c+A2 (Green: Endo, Other-Colored Atoms: exo).
Figure 6
Figure 6
Schematic Illustration of the Two Modes of Asynchronicity at the Transition State of a Diels–Alder Reaction.
Figure 7
Figure 7
A Twist-Asynchronicity Model Delineating the Origin of Exo Selectivity in Diels–Alder Reactions Involving Oxygenated Dienes.
Figure 8
Figure 8
The B3LYP/6−31G(d) Endo TSs for the Reaction of Isoprene with Acrolein•AlMe2Cl Obtained by Singleton/Houk and Evanseck.
Figure 9
Figure 9
Endo and Exo TSs of the 1d and 1e+A2 Cycloadditions. Gas-phase enthalpies of activation computed at the B3LYP/6−31G(d) level. Free energies of activation computed by B3LYP/6−31G(d), corrected for solvent effects by PCM single-points at HF/6−31+G(d,p). Interatomic distances around the forming ring in Å and angles of pyramidalization at the termini of the partially formed bonds are labeled.
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