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

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* = C5Me5; Ln = La, Sm, Lu), Ln[N(TMS)(2)](3) (Ln = La, Nd, Y), Cp*(2)An(CH2TMS)(2), and Me2SiCp ''(2)An(CH2R)(2) (Cp '' = C5Me4; 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*2SmCH(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*2SmCH(TMS)(2) and Me2SiCp '' Th-2(CH2TMS)(2) argues for a metal-alkynyl reversible arrow 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 gamma-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.