Hydrothiolation, terminal alkynes

The products of standard hydrothiolation processes are capable of further undergoing subsequent transformations, such as Pt-catalyzed Heck reactions with appropriately tethered alkyne acceptors (23) [235]. Furthermore, Beletskaya demonstrated that following the organometallic intermediates formed in addition of disulfides to terminal alkynes may be intercepted these were found to undergo further carbon-carbon bond formation in the presence of a suitable ligand and excess alkyne (24) [158],... 

Catalytic Hydrothiolation of Terminal Alkynes Promoted by Organoactinide Complexes... 

Scheme 14 Proposed catalytic cycle for the hydrothiolation of terminal alkynes promoted by an organoactinide complex...

Regioselective hydrothiolation of terminal alkynes RC=CH with sulfonyl hydrazides R S02NHNH2, mediated by (DBU " OAc) and AcOH at 120 °C in a microwave, to afford vinyl sulfides RCH=CHSR, has been attained. A mechanism, involving a gradual loss of N2 and the two oxygens from the sulfur atom, has been proposed. ... 

The sulfur-hydrogen bond addition to alkynes represents a convenient access to vinyl sulfides. Nolan, Beletskaya and co-workers reported a new selective hydrothiolation process induced by homogeneous NHC-Ni complexes." They showed that [(IMes)Ni(Cp)Cl] was effective in catalyzing the reaction of terminal alkynes and various aryl thiols (Equation (10.10)). The process was found highly selective and the classical transfer of two thioaryl groups did not... 

The palladium-catalyzed hydrothiolation of terminal alkynes has been achieved using a metallocycle catalyst that was generated through the treatment of palladium acetate with phosphinic acids (Scheme 5.53) [79], Using this catalyst system, benzenethiol was added to 1-octyne in moderate yield with high selectivity for the Markovnikov-isomer. While only a single hydrothiolation example was reported, this chemistry provides the foundation for the design of additional palladium-catalyzed reactions. 

SCHEME 5.58 Overall Z-selective hydrothiolation of internal and terminal alkynes [88],... 

While terminal alkynes are typically used for metal-catalyzed hydrothiolation reactions, the treatment of 1-alkynylphosphines 18 with a variety of thiols in the presence of Pd(OAc)2 resulted in (Z)-isomers 19 through a preferential coordination of the substrate phosphine to a Pd metal center 20 followed by nucleophilic attack of thiol and protonolysis.In 2010, Liu and co-workers reported on the Cu-catalyzed decarboxylative cross-coupling of arylpropiolic acids 21 with thiols for the synthesis of vinyl sulfides 22 with high stereoselectivity for (Z)-isomers. ... 

Wang ZL, Tang RY, Luo PS, Deng SL, Zhong P, Li JH. Hydrothiolation of terminal alkynes with diaryl disulfides and diphenyl diselenide selective synthesis of (Z)-l-alkenyl sulfides and selenides. Tetrahedron 2008 64 10670-10675. 

Weiss CJ, Marks TJ. Organozirconium complexes as catalysts for Markovnikov-selective intermolecular hydrothiolation of terminal alkynes scope and mechanism. J. Am. Chem. Soc. 2010 132 10533-10546. 

Weiss CJ, Wobser SD, marks TJ. Lanthanide and actinide-mediated terminal alkyne hydrothiolation for the catalytic synthesis of Markovnikov vinyl sulfides. Organometallics 2010 19 6308-6320. 

Marks and coworkers also reported in detail the Markovnikov-selective lanthanide-mediated, intermolecular hydrothiolation of terminal alkynes by aliphatic, benzylic, and aromatic thiols using Cp 2LnCH(TMS>2 (Cp = CsMes Ln = La, Sm (16), and Lu) as precatalysts [34]. The Markovnikov selectivity and conversion rate of this transformation depend on the bulkiness of substituents of thiols and alkynes (10). 

Weiss CJ, Wobser SD, Marks TJ (2009) Organoactinide-mediated hydrothiolation of terminal alkynes with aliphatic, aromatic, and benzylic thiols. J Am Chem Soc 131 2062-2063... 

Tp Rh(PPh3)2 [Tp =hydrotris(3,5-dimethylpyrazolyl)borate] displays high catalytic performance in hydrothiolation of alkynes to afford branched adducts. The complex and a related complex Tp Rh(cod) (Scheme 25) have proved to be linear-selective in the addition reaction of HP(0)Ph2 to terminal alkynes [33]. Their activity is somewhat low as compared with Rha(PPh3)3, giving, for instance, 51% yield in the reaction with 1-octyne (3 mol% of Tp Rh(cod), 110°C, 3 h). When Tp Rh(PPh3)2 is exposed to 10 equiv. of HP(0)Ph2 for 12 h at room temperature, an unusual dinuclear complex is generated. However, its role in the catalysis is ambiguous. 

RS-M" L c-i)- The other is the oxidative addition of thiols to low-valent transition metals (M"L ) to give the corresponding transition metal complexes bearing both hydride and thiolate ligands (RS-M" L c 2-H). The reaction of the former complexes (RS-M" L c-i) with carbon-carbon unsaturated compounds such as alkynes may proceed via thiometallation, in which relatively more bulky is bonded at the terminal carbon of alkynes. On the other hand, in the reaction of the latter complexes (RS-M" L c-2 H) with alkynes both hydrometallation and thiometallation processes are possible. These processes proceed via sy -addition. Alternative pathway for the addition of thiols to alkynes involves coordination of alkynes to transition metals and then nucleophilic addition of thiols (or thiolate anions) to the alkynes. These processes take place via a f -addition. By controlling these pathways, regio- and stereoselective hydrothiolation of alkynes is expected to be attained successfully. 

Scheme 2 Product selectivity in hydrothiolation of terminal alkynes...

In the transition-metal-catalyzed addition reactions of thiols to terminal alkynes, several addition products, i.e., Markovnikov-type adduct 1, Markovnikov addition and then double-bond-isomerization product 2, a n -Markovnikov adduct 3, double hydrothiolation product 4, and bisthiolation product 5, may be formed (Scheme 2). Controlling the product selectivity can be attained by the selection of transition metal complexes as catalysts, the use of additives, and/or the optimization of the reaction conditions (solvent, temperature, molar ratios of the starting materials, and so on). 

To ascertain the stereochemistry of this Pd(OAc)2-catalyzed hydrothiolatiOTi of terminal alkynes, the reaction of PhSH with 1-octyne-l-d (containing 93% d) is monitored by H NMR spectroscopy. The E Z ratio of the thiolation products is 100 0 at the initial stage, and then -isomer as the kinetic product gradually isomerized to Z-isomer. These results clearly indicate that the hydrothiolation proceeds via yn-addition at least at the initial stage (Scheme 4). 

Hydrothiolation of terminal alkynes is investigated by using Tp Rh(SPh)2 as the catalyst [41]. This hydrothiolation also affords Markovnikov-type addition products as the major product. Mechanistic aspects are shown in Scheme 12. 

The Markovnikov-selective lanthanide-mediated hydrothiolation of terminal alkynes with ahphatic, benzyhc, and aromatic thiols also proceeds by using Cp 2LnCH (TMS)2 (Cp = CgMes Ln = La, Sm, Lu) and Ln[N(TMS)2l3 (Ln = La, Nd, Y) as precatalysts [44, 45],... 

The hydrothiolation of terminal alkyl alkynes with 96 (Fig. 2.17) proceeds with good degree of regio- and chemo-selectivity, especially with thiophenol and p-methoxy-thiophenol as substrates. Isomerisation to the internal alkenyl thiolates accounts for less than 9% of the thiolated products under the reaction conditions. In addition, further hydrothiolation of the vinyl thioether product is not observed. Typical conversions of 70-85% at 1 mol% loading at 80°C within 5 h are observed. Arylthiols substituted with electron-withdrawing groups afford lower conversions. 

This reaction exemplified that the regiochemistry of RS and H introduced by car-bonylahve addition differed from that of those by simple hydrothiolation. In the Rh-catalyzed hydrothiolation, the ArS group added to the terminal carbon and H to the internal carbon (Eq. 7.12). On the other hand, in the Rh-catalyzed thioformylation, RS was placed at internal carbon and formyl at the terminal carbon in spite of using the same catalyst precursor, [RhCljPPhsjs], which was also active for the thioformylation shown in Eq. (7.17). In 1997, the Pt-catalyzed hydrothiocarboxylation using RSH, alkyne and CO was reported to furnish 24 (Eq. 7.18), which showed the same regiochemistry as the Ni-catalyzed reaction shown in Eq. (7.1) [28]. 

Further exploration of the higher activity of the Ni complexes compared to Pd analogs led to the discovery of a novel nano-sized catalytic system with superior performance for hydrothiolation and hydroselenation reactions of alkynes [ 152,153]. Furthermore, it was found that with a simple catalyst precursor - Ni(acac)2 - the reaction was carried out with excellent yields and excellent selectivity, even at room temperature. Both terminal and internal alkynes were successfully involved in the addition reaction. This catalytic system was tolerant to various functional groups in alkynes and was easily scaleable for the synthesis of 1-50 g of product (Scheme 3.85) [152, 153]. The proposed mechanism of the catalytic reaction involved (i) catalyst self organization with nano-sized particles formation, (ii) alkyne insertion into the Ni—Z bond and (iii) protonolysis with RZH (Scheme 3.86). 

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