Organozirconium complexes as catalysts for markovnikov-selective lntermolecular hydrothiolation of terminal alkynes: Scope and mechanism

The efficient and selective organozirconium(IV)-mediated, intermolecular hydrothiolation of terminal alkynes by aliphatic, benzylic, and aromatic thiols using CGCZrMe2 (CGC = Me2SiCp" NCMe3, Cp" = C5Me4), Cp*ZrBn ₃ (Cp* = C5Me5, Bn = benzyl), Cp*ZrCI ₂NMe ₂, Cp* ₂ZrMe ₂, and Zr(NMe ₂) ₄ precatalysts is reported, These transformations are shown to be highly Markovnikov-selective, with selectivities up to 99%, and typically in greater than 90% yields. The reaction has been demonstrated on the preparative scale with 72% isolated yield and 99% Markovnikov selectivity. A mixture of anti-Markovnikov products is occasionally observed as a result of a known, non-organometallic, radical mechanism, which can be suppressed by addition of a radical inhibitor. Kinetic investigations show that the CGCZrMe2-mediated reaction between 1-pentanethiol and 1-hexyne is first-order in catalyst concentration, first-order in alkyne concentration, and also first-order in thiol at lower concentrations but transitions to zero-order at concentrations > 0.3 M, Deuterium labeling of the alkyne yields K _H/K _D = 1.3(0.1), along with evidence of thiol-mediated protonolytic detachment of product from the Zr center. Activation parameters for CGCZrMe ₂mediated 1-pentanethiol hydrothiolation of 1-hexyne measured over the temperature range of 50-80 0C are AhP = +18.1(1.2) kcal/mol and δS‡ = -20.9(2.5) e.u. for [alkyne] and [thiol] at 0.2 M. These and other findings are consistent with turnover-limiting alkyne insertion into the Zr-SR bond, followed by a thiol-induced Zr-C protonolysis. Observed zirconium-thiolate dinners in the reaction medium suggest instances of dimeric catalyst resting states and possible aggregated, hydrothiolation-active species.