Synthetic scope, computational chemistry and mechanism of a base induced 5- endo cyclization of benzyl alkynyl sulfides

We present an experimental and computational study of the reaction of aryl substituted benzyl 1-alkynyl sulfides with potassium alkoxide in acetonitrile, which produces 2-aryl 2,3-dihydrothiophenes in poor to good yields. The cyclization is most efficient with electron withdrawing groups on the arom...

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Bibliographic Details
Published in:Tetrahedron 2011-02, Vol.67 (5), p.1002-1010
Main Authors: Motto, John M., Castillo, Álvaro, Greer, Alexander, Montemayer, Laura K., Sheepwash, Erin E., Schwan, Adrian L.
Format: Article
Language:English
Subjects:
Acetonitrile
Aromatic compounds
Carbanions
chemical reactions
chemical structure
Chemistry
Computational chemistry
Conjugates
Cyclization
Dihydrothiophenes
energy
Exact sciences and technology
Exchange
Heterocyclic compounds
Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives
Kinetics and mechanisms
Mathematical models
Organic chemistry
Potassium
Preparations and properties
protons
Reactivity and mechanisms
Solvents
Sulfides
Tautomerism
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Summary:We present an experimental and computational study of the reaction of aryl substituted benzyl 1-alkynyl sulfides with potassium alkoxide in acetonitrile, which produces 2-aryl 2,3-dihydrothiophenes in poor to good yields. The cyclization is most efficient with electron withdrawing groups on the aromatic ring. Evidence indicates there is rapid exchange of protons and tautomerism of the alkynyl unit prior to cyclization. Theoretical calculations were also conducted to help rationalize the base induced 5- endo cyclization of benzyl 1-propynyl sulfide ( 1a). The potential energy surface was calculated for the formation of 2,3-dihydrothiophene in a reaction of benzyl 1-propynyl sulfide ( 1a) with potassium methoxide. Geometries were optimized with CAM-B3LYP/6-311+G(d,p) in acetonitrile with the CPCM solvent model. It is significant that the benzyl propa-1,2-dien-1-yl sulfane ( 6) possessed a lower benzylic proton affinity than the benzyl prop-2-yn-1-yl sulfane ( 8) thus favoring the base induced reaction of the former. From benzyl(propa-1,2-dien-1-yl sulfane ( 6), 2,3-dihydrothiophene can be formed via a conjugate base that undergoes 5- endo- trig cyclization followed by a protonation step. [Display omitted]
ISSN:0040-4020
1464-5416
DOI:10.1016/j.tet.2010.11.104