We describe the formation of a bis-cyclopropane product, a tricyclic[4.1.0.02,4]heptane, that is formed during a Johnson-Corey-Chaykovsky reaction on a cyclopentenone. Two (of four possible) bicyclic products are selectively formed by addition of a COOEt-stabilized sulfur ylide onto the Michael acceptor. The tricyclic product is formed subsequently via a retro Michael elimination of a hindered ether followed by addition of a further cyclopropyl moiety, affecting only one of the two bicyclic products initially formed. The experimental reaction outcome was rationalized using density functional theory (DFT), investigating the different Michael-addition approaches of the sulfur ylide, the transition state (TS) energies for the formation of possible zwitterionic intermediates and subsequent reactions that give rise to cyclopropanation. Selective formation of only two of the four possible products occurs due to the epimerization of unreactive intermediates from the other two pathways, as revealed by energy barrier calculations. The formation of the tricyclic product was rationalized by evaluation of energy barriers for proton abstraction required to form the intermediate undergoing the second cyclopropanation. The selectivity-guiding factors discussed for the single and double cyclopropanation of this functionalized Michael-acceptor will be useful guidelines for the synthesis of future singly and doubly cyclopropanated compounds.

Observation of a Tricyclic[4.1.0.0 2,4]heptane During a Michael Addition-Ring Closure Reaction and a Computational Study on Its Mechanism of Formation / M. Farren-Dai, J.R. Thompson, A. Bernardi, C. Colombo, A.J. Bennet. - In: JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1520-6904. - 82:23(2017 Oct 30), pp. 12511-12519. [10.1021/acs.joc.7b02218]

Observation of a Tricyclic[4.1.0.0 2,4]heptane During a Michael Addition-Ring Closure Reaction and a Computational Study on Its Mechanism of Formation

A. Bernardi;C. Colombo;
2017-10-30

Abstract

We describe the formation of a bis-cyclopropane product, a tricyclic[4.1.0.02,4]heptane, that is formed during a Johnson-Corey-Chaykovsky reaction on a cyclopentenone. Two (of four possible) bicyclic products are selectively formed by addition of a COOEt-stabilized sulfur ylide onto the Michael acceptor. The tricyclic product is formed subsequently via a retro Michael elimination of a hindered ether followed by addition of a further cyclopropyl moiety, affecting only one of the two bicyclic products initially formed. The experimental reaction outcome was rationalized using density functional theory (DFT), investigating the different Michael-addition approaches of the sulfur ylide, the transition state (TS) energies for the formation of possible zwitterionic intermediates and subsequent reactions that give rise to cyclopropanation. Selective formation of only two of the four possible products occurs due to the epimerization of unreactive intermediates from the other two pathways, as revealed by energy barrier calculations. The formation of the tricyclic product was rationalized by evaluation of energy barriers for proton abstraction required to form the intermediate undergoing the second cyclopropanation. The selectivity-guiding factors discussed for the single and double cyclopropanation of this functionalized Michael-acceptor will be useful guidelines for the synthesis of future singly and doubly cyclopropanated compounds.
Michael Addition-Ring Closure Reaction; cyclopropane; cyclopropanation; density functional theory (DFT); sulfur ylide
Settore CHIM/06 - Chimica Organica
Design, synthesis and evaluation of potential group-1 and group-2 neuraminidase inhibitors
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/534308
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