Hydrothiolation, alkynes

These inherent difficulties have elicited considerable attention, which has led to the emergence of synthetically viable protocols. The first catalytic alkyne hydrothiolation was reported by Ogawa in 1992 [151]. A number of late transition metal salts were found to be effective. In particular, Pd(OAc)2 demonstrated excellent selectivity for the branched olefin. High yields were obtained even with stericaUy demanding substrates and potentially reactive functional groups (19). 

Equation 19 Observed regioselectivity in the Pd (OAc)2 catalyzed alkyne hydrothiolation [151]... 

A number of similar transformations of allenes have been reported. As with alkyne hydrothiolation, the key to the utility of this process is the ability to control regio-and stereoselectivity. A few key recent discoveries are highlighted below. For related reactions, see the following references [165, 168, 197, 236-243]. 

The addition of sulfur-hydrogen bonds to alkynes (hydrothiolation) is a valuable and popular approach to the synthesis of vinyl sulfides [23], Some of the earliest reports of this chemistry involved the use of molybdenum [77] and palladium complexes [78]. While discussions of the challenges encountered when trying to design an effective cross-coupling reactions often focus on concerns about reactivity and substrate scope, hydroelementation reactions introduce further complications due to regio- and stereoselectivity issues, hi many... 

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. 

Cao C, Fraser LR, Love JA. Rhodium-catalyzed alkyne hydrothiolation with aromatic and aliphatic thiols. J. Am. Chem. Soc. 2005 127 17614-17615. 

Shoai S, Bichler P, Kang B, Buckley H, Love JA. Catalytic alkyne hydrothiolation with alkanethiols using Wilkinson s catalyst. Organometallics 2007 26 5778-5781. 

Recently, Tang and coworkers also succeeded in developing the polyhydrothiolation reaction using Diynes (AA-type) with Dithiols (BB-type) (Figure 8.4) [17]. Moreover, the alkyne hydrothiolation reaction proceeded in a linear manner, and no branched isomer was obtained at all. More importantly, they found that both regioselectivity and stereoselectivity of the polyhydrothiolation reaction can be well controlled in the presence of the Rh catalyst (Rh(PPh3)3Cl) [17]. 

Gerber R, Freeh CM (2012) Alkyne hydrothiolation catalyzed by a dichlorobis (aminophosphine) complex of palladium selective formation of cis-conflgured vinyl thioethers. Chem Fur J 18(29) 8901-8905... 

Sabarre A, Love J (2008) Synthesis of 1,1-disubstituted olefins via catalytic alkyne Hydrothiolation/Kumada cross-coupling. Org Lett 10 3941-3944... 

Yang J, Sabarre A, Fraser LR, Patrick BO, Love JA (2009) Synthesis of 1,1-disubstituted alkyl vinyl sulfides via rhodium-catalyzed alkyne hydrothiolation scope and limitations. J Org Chem 74 182-187... 

A variety of alkynes undergo regio- and stereoselective hydrothiolation with arenethiols in the presence of RhCl(PPh3)3. Ethanol and dichlorometane is suitable solvents for this hydrothiolation. This hydrothiolation proceeds well, even when galvinoxyl as a radical inhibitor is added to the reaction system. Recently, Wilkinson s catalyst is reported to be an excellent catalyst for alkyne hydrothiolation with alkanethiols to provide -isomers of anri-Markovnikov-type addition products 3 selectively [54]. 

Hydrothiolations (addition of H-SR across the CC multiple bond) of alkynes, electron-deficient aUcenes and electron-deficient vinyl arenes have been catalysed by NHC complexes of Ni and Cu, respectively [Scheme 2.17a-c],... 

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

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. 

The thiolato complex 97 that was postulated as the active catalytic species in the reaction was prepared from 96 and the thiol in the presence of NEtj. Certain analogues of 97 (NHC = Mes, SIMes, IPr, SIPr R = Ph) have also been independently synthesised, isolated and fully characterised. A plausible mechanism for the hydrothiolation involves insertion of the alkyne into the Ni-SR bond forming the (non-isolable) p-thioalkenyl complex, from which the product can be released via alkanolysis of the Ni-C bond by the thiol and regeneration of the active catalyst 97 [84]. 

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

Although the path (a) has been verified by a stoichiometric reaction [23], the details of exact reaction mechanism remain unsettled. Triggered by this publication [and the Pd-catalyzed doublethiolation of alkynes described in Eq. (7.7) in Section 7-3], a number of transition metal-catalyzed additions of S-X or Se-X bonds to C-C unsaturated organic compounds started to be published. In 1994, BackvaU et al. applied the Pd(OAc)2-catalyzed hydrothiolation to conjugated enynes and obtained 17,... 

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]. 

Since this initial report, significant advances have been made with Ni [121, 152-159], Pd [160-189], Pt [187, 190-201], Rh [202-212] and Ir [204, 211]. In general, group 10 metals generate the branched isomer and proceed by syn-insertion of the alkyne into an M-S bond, followed by protonolysis of the resulting M-C bond, although this is dependent on the reaction conditions. Eor example, under photolytic conditions, certain Pt complexes react through a trans-insertion mechanism [192, 200]. Likewise, Pd-catalyzed reactions of thiols with 1-alkynyl-phosphines proceeds by anfi-hydrothiolation (20) [213]. 

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...

Kinetic analysis of the reaction between 60 and 110°C yields = +9.1(0.7) kcal/mol and AS - —45(2) eu, suggesting a highly ordered transition state and an intermolecular, turnover-limiting step. The hydrothiolation processes exhibits a high Markovnikov selectivity. This is presumably reflecting a four-membered transition state with the alkyne insertion regio-chemistry dictated by the transition state steric hindrance and the bond polarity orientation. 

It is interesting to point out that the thiol nature has a major influence on the hydrothiolation rates. Hence, changing the aliphatic thiol from primary to secondary resulted in signiflcant rate depression, consistent with a steric impediment at the turnover-limiting alkyne insertion (step ii. Scheme 14). The use of benzyl mercaptan allows an increase of the rate by nearly three times. The effect on the alkyne was found to be minor and by increasing the alkyne steric encumbrance minor changes in rates were observed. 

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