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

• 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
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2010.11.104

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]