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

Abstract

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.

Catalytic enantioselective synthesis of indanes by a cation-directed 5-endo-trig cyclization

“…The electrocyclic pathway [27][28][29][30] necessitates that the pentadienyl anion achieve near-planarity in order to maximize orbital overlap with the π-system. Alternatively, this process could involve a stereoelectronically challenging 5-endo-trig Michael reaction [31][32][33][34][35][36][37][38] in which facial selectivity of addition to the α,β-unsaturated ester is directed by the chiral cation. [39][40][41][42] To probe the electronic requirements of this cyclization we examined the reaction of a derivative 36 bearing a single anion-stabilizing group at the benzylic position ( Figure 2).…”

Allenes and computational chemistry: from bonding situations to reaction mechanisms

“…According to calculations (CAM-B3LYP/6-311+G(d,p)/CPCM), 2,3-dihydro-thiophene 154 can be formed in three steps from allenyl species 153, including base 155, which undergoes a 5-endo-trig cyclization to 156 (Scheme 28). 192…”

Propargylic Sulfides: Synthesis, Properties, and Application

“…Schwan and co-workers described transition-metal-free cyclization of benzyl 1-alkynyl sulfides. This base-induced reaction proceeded without the necessity for activating the electron-withdrawing substituents which are directly bonded to the carbon skeleton.…”