Modular mesoionics: understanding and controlling regioselectivity in 1,3-dipolar cycloadditions of Münchnone derivatives

Morin, Marie S. T., St-Cyr, Daniel J., Arndtsen, Bruce A., Krenske, Elizabeth H. and Houk, K. N. (2013) Modular mesoionics: understanding and controlling regioselectivity in 1,3-dipolar cycloadditions of Münchnone derivatives. Journal of the American Chemical Society, 135 46: 17349-17358. doi:10.1021/ja406833q

Author Morin, Marie S. T.
St-Cyr, Daniel J.
Arndtsen, Bruce A.
Krenske, Elizabeth H.
Houk, K. N.
Title Modular mesoionics: understanding and controlling regioselectivity in 1,3-dipolar cycloadditions of Münchnone derivatives
Journal name Journal of the American Chemical Society   Check publisher's open access policy
ISSN 0002-7863
Publication date 2013-11-20
Year available 2013
Sub-type Article (original research)
DOI 10.1021/ja406833q
Open Access Status
Volume 135
Issue 46
Start page 17349
End page 17358
Total pages 10
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Subject 1503 Catalysis
1600 Chemistry
1303 Biochemistry
1505 Colloid and Surface Chemistry
Abstract 1,3-Dipolar cycloadditions of mesoionic 1,3-dipoles (Münchnones, imino-Münchnones, and phospha-Münchnones) with alkynes offer versatile, modular synthetic routes to pyrroles. Reactivity and regioselectivity differ markedly for different members of this series, and we report here the first general rationale for differences in reactivity by means of a systematic investigation of 1,3-dipolar cycloadditions involving electron-poor and electron-rich alkynes. Competition kinetic measurements indicate that Münchnones and phospha-Münchnones are nucleophilic 1,3-dipoles that react most rapidly with electron-poor alkynes. However, the regioselectivities of cycloadditions are found to undergo an inversion as a function of alkyne ionization potential. The exact point at which this occurs is different for the two dipoles, allowing rational control of the pyrrole formed. The origins of these reactivities and regioselectivities are examined computationally. Frontier molecular orbital predictions are found not to be accurate for these reactions, but transition state calculations give correct predictions of reactivity and selectivity, the origins of which can be analyzed using the distortion/ interaction model of reactivity. Cycloadditions with electron-poor alkynes are shown to favor the regioisomer that has either the most favorable TS interaction energy (Münchnones or imino-Münchnones) or the smallest TS distortion energy (phospha-Münchnones). Cycloadditions with more electron-rich aryl-substituted alkynes, on the other hand, generally favor the regioisomer that has the smaller TS distortion energy. These insights delineate the synthetically important distinctions between Münchnones and phospha-Münchnones: phospha-Münchnones undergo highly regioselective cycloadditions with electron-poor alkynes that do not react selectively with Münchnones, and the reverse is true for cycloadditions of Münchnones with electron-rich alkynes.
Keyword Chemistry, Multidisciplinary
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID CHE-0548209
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
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