Organothorium-Catalyzed Hydroalkoxylation/Cyclization of Alkynyl Alcohols. Scope, Mechanism, and Ancillary Ligand Effects

Organothorium complexes bearing amide or alkyl proligands are active toward the highly selective hydroalkoxylation/cyclization of alkynyl alcohols. Substrates include primary and secondary alcohols, as well as terminal and internal alkynes. Catalysts with strongly binding ligation such as pentamethylcyclopentadienyl (Cp* = C₅Me₅) or “constrained geometry catalysts” (CGC = Me₂Si­(η⁵-Me₄C₅)­(^<i>t</i>BuN)) remain soluble throughout the reaction, with the more sterically open (CGC)­Th­(NMe₂)₂ (<b>1</b>) exhibiting higher activity than Cp*₂Th­(CH₂TMS)₂ (<b>2</b>). The use of precatalyst [(Me₃Si)₂N]₂Th­[κ²-(<i>N</i>,<i>C</i>)-CH₂Si­(CH₃)₂N­(SiMe₃)] (<b>3</b>) leads to precipitation upon the addition of alcohol substrates, although catalytic activity is retained. The substrate scope for <b>1</b> includes primary and secondary alcohols as well as terminal and internal alkynes. <i>In situ</i> ¹H NMR spectroscopic monitoring indicates that the rate law is zero-order in [substrate] and first-order in [catalyst]. The rates of primary alcohols and terminal alkynes are significantly more rapid than their more sterically hindered counterparts, suggesting that steric demands dominate the hydroalkoxylation/cyclization transition state. Turnover frequencies as high as 49 h^–1 at 60 °C are observed, producing exclusively the <i>exo</i>-methylene products. For internal alkyne substrates, alkenes with <i>E</i>-orientation are formed with complete selectivity. Activation parameters Δ<i>H</i>^‡ = 27.9(0.4) kcal/mol, Δ<i>S</i>^‡ = −3.0(1.1) eu, and <i>E</i>_a = 28.6(0.4) kcal/mol are largely in accord with observations for other f-element-mediated insertive hydroelementation processes, and an ROH/ROD kinetic isotope effect of 0.97(0.02) is observed. The reactivity patterns, kinetics, and activation parameters are consistent with a pathway proceeding via turnover-limiting alkyne insertion into the Th–O bond, with subsequent, rapid Th–C protonolysis, regenerating the initial Th–OR species

Organoactinide-Mediated Hydrothiolation of Terminal Alkynes with Aliphatic, Aromatic, and Benzylic Thiols

Organoactinide-Mediated Hydrothiolation of Terminal Alkynes with Aliphatic, Aromatic, and Benzylic Thiol

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*2LnCH(TMS)2 (Cp* = C5Me5; Ln = La, Sm, Lu), Ln[N(TMS)2]3 (Ln = La, Nd, Y), Cp*2An(CH2TMS)2, and Me2SiCp′′2An(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 kH/kD = 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′′2Th(CH2TMS)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

Carbostannolysis Mediated by Bis(pentamethylcyclopentadienyl)lanthanide Catalysts. Utility in Accessing Organotin Synthons

Facile carbon–tin bond activation in the reaction of 2-(trimethylstannyl)­pyridine (<b>1</b>) with the organolanthanide complexes Cp*₂LaCH­(TMS)₂ (<b>2a</b>) and [Cp*₂LaH]₂ (<b>2b</b>) yields Cp*₂La­(2-pyridyl) (<b>3</b>), as well as Me₃SnCH­(TMS)₂ and Me₃SnH, respectively. At room temperature, ethylene then undergoes insertion into the resulting La–C­(pyridyl) bond followed by carbostannolysis to catalytically generate 2-(2-(Me₃Sn)­ethyl)­pyridine (<b>4</b>) or, with extended reaction times, 6-ethyl-2-(2-(trimethylstannyl)­ethyl)­pyridine (<b>5</b>). In contrast to <b>1</b>, 6-methyl-2-(trimethylstannyl)­pyridine (<b>6</b>) is unreactive, likely reflecting steric constraints. With terminal alkynes, this catalytic heterocycle–SnMe₃ activation/carbostannylation process affords tin-functionalized conjugated enynes. Thus, at 60 °C <b>2b</b> catalyzes the conversion <b>1</b> + 1-hexyne to yield (<i>E</i>)-2-butyl-1-(Me₃Sn)-oct-1-en-3-yne in a 60:1 ratio <i>E</i>:<i>Z</i> isomer ratio. This reaction is available to α-monosubstituted and α-disubstituted terminal alkynes, while α-trisubstituted alkynes are too hindered for reaction. The catalytic cycle is proposed to proceed via a spectroscopically detectable Me₃Sn–alkynyl intermediate which undergoes insertion into a Cp*₂La–alkynyl bond to produce the conjugated alkynyl product, which is subsequently protonolyzed from the Cp*₂La center by a new terminal alkyne substrate molecule. NMR spectroscopic and kinetic data support the proposed pathway and indicate turnover-limiting alkyne insertion