Lanthanide- and Actinide-Mediated Terminal Alkyne Hydrothiolation for the Catalytic Synthesis of Markovnikov Vinyl Sulfides

Abstract

The Markovnikov-selective lanthanide- and actinide-mediated, intermolecular hydrothiolation of terminal alkynes by aliphatic, benzylic and aromatic thiols using Cp* 2 LnCH(TMS) 2 (Cp* = C 5 Me 5; Ln = La, Sm, Lu), Ln[N(TMS) 2 ] 3 (Ln = La, Nd, Y), Cp* 2 An(CH 2 TMS) 2, and Me 2 SiCp′′ 2 An(CH 2 R) 2 (Cp′′ = C 5 Me 4; An = Th, R = TMS; An = U, R = Ph) as precatalysts is studied in detail. These transformations are shown to be Markovnikov-selective, with selectivities as high as >99%. Kinetic investigations of the Cp* 2 SmCH(TMS) 2 -mediated reaction between 1-pentanethiol and 1-hexyne are found to be first-order in catalyst concentration, first-order in alkyne concentration, and zero-order in thiol concentration. Deuterium labeling of the alkyne −C≡C−H position reveals k H /k D = 1.40(0.1) and 1.35(0.1) for the organo-Sm- and organo-Th-catalyzed processes, respectively, along with evidence of thiol-mediated protonolytic detachment of the vinylic hydrothiolation product from the Sm center. Mechanistic findings indicate turnover-limiting alkyne insertion into the Sm−SR bond, followed by very rapid, thiol-induced M−C protonolysis to yield Markovnikov vinyl sulfides and regenerate the corresponding M−SR species. Comparisons of different substrates and metal complexes in catalyzing hydrothiolation reveal a strong dependence of hydrothiolation activity on the steric encumbrance in the insertive transition state. Observed deuterium exchange between alkyne −C≡C−H and thiol RS−H in the presence of Cp* 2 SmCH(TMS) 2 and Me 2 SiCp′′ 2 Th(CH 2 TMS) 2 argues for a metal−alkynyl ⇌ metal−thiolate equilibrium, favoring the M−SR species under hydrothiolation conditions. A mixture of free radical-derived anti-Markovnikov vinyl sulfides is occasionally observed and can be suppressed by γ-terpinene radical inhibitor addition. Previously reported metal thiolate complex aggregation to form insoluble species is observed and can be delayed kinetically by Cp-based ligation.