Organozirconium Complexes as Catalysts for Markovnikov-Selective Intermolecular 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 CGCZrMe(2) (CGC = Me2SiCp '' NCMe3, Cp '' = C5Me4), (CpZrBn3)-Zr-star (Cp-star = C5Me5, Bn = benzyl), (CpZrCl2NMe2)-Zr-star, (Cp2ZrMe2)-Zr-star, and Zr(NMe2)(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 CGCZrMe(2)-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(2)-mediated 1-pentanethiol hydrothiolation of 1-hexyne measured over the temperature range of 50-80 degrees C are Delta H-double dagger = +18.1(1.2) kcal/mol and Delta S-double dagger = -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 dimers in the reaction medium suggest instances of dimeric catalyst resting states and possible aggregated, hydrothiolation-active species.