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. 2010 Feb 3;132(4):1267-9.
doi: 10.1021/ja9098643.

Indolyne and aryne distortions and nucleophilic regioselectivites

Paul H-Y Cheong  1 , Robert S Paton, Sarah M Bronner, G-Yoon J Im, Neil K Garg, K N Houk
Affiliations

Indolyne and aryne distortions and nucleophilic regioselectivites

Paul H-Y Cheong et al. J Am Chem Soc. .

Abstract

Density functional theory computations reproduce the surprisingly high regioselectivities in nucleophilic additions and cycloadditions to 4,5-indolynes and the low regioselectivities in the reactions of 5,6-indolynes. Transition-state distortion energies control the regioselectivities, activating the 5 and 6 positions over the 4 and 7 positions, leading to high preferences for 5- and 6-substituted products from 4,5- and 6,7-indolynes, respectively. Orbital and electrostatic interactions have only minor effects, producing low regioselectivities in the reactions of 5,6-indolynes. The distortion model predicts high regioselectivities with 6,7-indolynes; these have been verified experimentally. The regioselectivities found with other arynes are explained on the basis of distortion energies that are reflected in reactant geometries.

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Figures

Figure 1
Figure 1
B3LYP/6-31G(d) optimized 4,5-indolyne and TSs for aniline addition. Energies in kcal/mol.
Figure 2
Figure 2
B3LYP/6-31G(d) optimized benzyne and TS for aniline addition. Energies in kcal/mol.
Figure 3
Figure 3
B3LYP/6-31G(d) optimized 5,6-indolyne and TSs for aniline addition. Energies in kcal/mol.
Figure 4
Figure 4
B3LYP/6-31G(d) optimized 6,7-indolyne and TS for aniline addition. Energies in kcal/mol.
Figure 5
Figure 5
B3LYP/6-31G(d) optimized structures of benzynocyclo-n-alkenes (n=4,5,6), naphthalyne and 3-methoxybenzyne. TS (with aniline) distortion energies (activation energies) in kcal/mol.
Figure 6
Figure 6
Distortion model for regioselective nucleophilic addition to fused benzynes (X = electron-withdrawing group). The effect of X is larger than the more remote X’.
See this image and copyright information in PMC

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    1. Also known as deformation energy:Nagase S, Morokuma K. J. Am. Chem. Soc. 1978;100:1666–1672.

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