Motto John M, Castillo Alvaro, Greer Alexander, Montemayer Laura K, Sheepwash Erin E, Schwan Adrian L
Department of Chemistry, University of Guelph, Guelph, ON Canada, N1G 2W1.
Tetrahedron. 2011 Feb 4;67(5):1002-1010. 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.
我们展示了一项关于芳基取代苄基1-炔基硫醚与醇钾在乙腈中反应的实验和计算研究，该反应能以低至良好的产率生成2-芳基2,3-二氢噻吩。芳环上带有吸电子基团时，环化反应效率最高。有证据表明，在环化之前，炔基单元存在质子的快速交换和互变异构现象。我们还进行了理论计算，以帮助解释苄基1-丙炔基硫醚（1a）的碱诱导5-内型环化反应。计算了苄基1-丙炔基硫醚（1a）与甲醇钾反应生成2,3-二氢噻吩的势能面。使用CAM-B3LYP/6-311+G(d,p)方法，在带有CPCM溶剂模型的乙腈中对几何结构进行了优化。值得注意的是，苄基丙-1,2-二烯-1-基硫烷（6）的苄基质子亲和力低于苄基丙-2-炔-1-基硫烷（8），因此有利于前者的碱诱导反应。从苄基（丙-1,2-二烯-1-基硫烷（6）可以通过共轭碱形成2,3-二氢噻吩，该共轭碱先进行5-内型-三取代环化，然后进行质子化步骤。
