Hydrothiolation of alkynes

Scheme 2.17 Product formation in the hydrothiolation of alkynes and alkenes...

Scheme 7-1 A proposed reaction path of Pd(OAc)2-catalyzed hydrothiolation of alkyne...

Hydrothiolation of unsaturated compounds is an atom economical process, especially the formation of C—S bonds, which are present in many biologically active molecules [146]. Moreover, vinyl sulfides are very convenient synthetic intermediates in organic reactions. Despite the existence of several active catalysts, the stereo- and regioselective controk remain a challenge [147]. Castarle-nas and coworkers reported the selective hydrothiolation of alkynes catalyzed by NHC-based rhodium complexes 62 and 63 (Scheme 10.6) imder mild reaction conditions [147]. A regioselective switch from linear to branched vinyl sulfides was observed when mononuclear compound 62 was used. The authors proposed... 

SCHEME 5.53 E-selective palladium-catalyzed hydrothiolation of alkynes [79]. 

SCHEME 46.1. Hydrothiolation of alkynes under radical conditions. 

SCHEME 46.3. Stereoselective hydrothiolation of alkynes under metal catalysis. 

Kondoh A, Takami K, Yorimitsu H, Oshima K. Stereoselective hydrothiolation of alkynes catalyzed by cesium base facile access to (Z)-l-aIkenyl sulfides. J. Org. Chem. 2005 70 6468-6473. 

Corma A, Gonzalez-Arellano C, Iglesias M, Sanchez R Efficient synthesis of vinyl and alkyl sulfides via hydrothiolation of alkynes and electron-deficient olefins using soluble and hetereogeneous gold complexes catalysts. Appl. Catal. A 2010 375 49-54. 

Ogawa A, Ikeda T, Kimura K, Hirao T. Highly regio- and stereocontrolled synthesis of vinyl sulfides via transition-metal-catalyzed hydrothiolation of alkynes with thiols. J.Am. Chem. Soc. 1999 121 5108-5114. 

Field LD, Messerle BA, Vuong KQ, Turner P. Rhodium(I) and iridium(I) complexes containing bidentate phosphine-imidazolyl donor ligands as catalysts for the hydroamination and hydrothiolation of alkynes. Dalton Trans. 2009 3599-3614. 

Manarin F, Roehrs JA, Prigol M, Alves D, Nogueira CW, Zeni G. Regio and stereoselective synthesis of vinyl sulfides via PhSeBr-catalyzed hydrothiolation of alkynes. Tetrahedron Lett. 2007 48 4805 808. 

C-S bond formation through reaction between aryl halide (Cl, Br, I) and aromatic or aliphatic thiols has been catalysed by a Ni-NHC complex under basic conditions. The reaction is of wide scope and high efficiency. Vinyl sulfides have been synthesized by hydrothiolation of alkynes catalysed by Rh-NHC complexes. Mechanistic investigations have established that the catalysis proceeds via an oxidative addition of the S-H bond to Rh(I) followed by alkyne insertion and reductive elimination. Interestingly, the regioselectivity could be controlled by the nature of the complex (mono or dinuclear precursors), and the use of a strong donor such as the NHC prevents the deactivation of the catalyst. 

Rhodium-NHC complexes [Rh( <-Cl)(IPr)( -olefin)]2 and RhCl(IPr)(py)(t/"-olefin) (IPr= l,3-bis(2,6-diisopropylphenyl)imidazol-2-carbene, py = pyridine, olefin = cyclooctene) have been designed as highly active catalysts for hydrothiolation of alkynes RC=CH with R SH. The dinuclear catalyst was found to promote the formation of the linear product RCH=CHSR, whereas the mononuclear catalyst favoured the branched isomer R(R S)C=CH2- A complex interplay between electronic and steric effects exerted by the carbene (IPr), pyridine, and hydride ligands accounts for the observed regioselectivity. DFT calculations suggested that migratory insertion of the alkyne into the rhodium-thiolate bond is the rate-determining step. ... 

Di Giuseppe A, Castarlenas R, Perez-TOTrente JJ, Crucianelli M, Polo V, Sancho R, Lahoz FJ, Oro LA (2012) Ligand-controlled regioselectivity in the hydrothiolation of alkynes by rhodium N-heterocyclic carbene catalysts. J Am Chem Soc 134(19) 8171-8183... 

Scheme 7 Catalytic cycle for PdCl2(PhCN)2-catalyzed hydrothiolation of alkynes followed by isomerization of the resulting Markovnikov-type adduct...

Scheme 10 Catalytic cycle for CpNi(lMes)Cl-calalyzed hydrothiolation of alkynes...

Homogeneous hydrothiolation of alkynes was achieved by using CpNi(IMes)Cl (IMes = A, M-bis(2,6-diisopropylphenyl)imidazol-2-ylidene). Under the optimized conditicHis (8), CpNi(IMes)Cl catalyzed the reaction of PhSH with 1-heptyne in the presence of Et3N in toluene-tfg to give 9 (66%) and 11 (8%) without other byproducts. This catalytic reaction (Scheme 10) starts from the formaticm of the thiolato Ni(II)... 

In 2007, Love and coworkers reported the hydrothiolation of alkynes with alkanethiol using RhCl(PPh3)3 [62], Under optimized conditirais (in 1,2-dichloro-ethane at room temperature), the reaction of CF3CH2SH with phenylacetylene in the presence of 3 mol% of RhCl(PPh3)3 furnished anfi-Markovnikov (56) and Markovnikov (57) adducts in a ratio of 9 1 in 90% yield (27), the regioselectivity of which is similar to the case of PhSH [see (28)]. 

Ananikov VP, Malyshev DA, Beletskaya IP, Aleksandrov GG, Eremenko IL (2005) Nickel(II) chloride-catalyzed regioselective hydrothiolation of alkynes. Adv Synth Catal 347 1993-2001... 

Malyshev DA, Scott NM, Marion N, Stevens ED, Ananikov VP, Beletskaya IP, Nolan SP (2006) Homogeneous nickel catalysts for the selective transfer of a single arylthio group in the catalytic hydrothiolation of alkynes. Organometallics 25 4462-4470... 

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. 

Hydroamination of aUcynes using gold catalysts has also attracted considerable interest [155-158]. hi this context, triazole-Au(l) complexes, which show improved thermal stability, are active catalysts for the hydroamination of alkynes [159]. The hydrothiolation of alkynes using soluble and heterogenized gold complex catalysts was reported by Corma and co-workers [160]. 

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. 

---