Palladium hydrothiolation

Interception of reactive intermediates provides access to an even broader range of products. For example, insertion of CO leads to conjugated lactones and thioe-sters (Scheme 4). A wide variety of sulfur derivatives can be used in these processes producing an array of interesting synthetic intermediates. These organosulfur compounds can be free thiol [164, 167-170, 175, 190, 193, 197, 202, 204], disulfide [160, 165, 183, 207], thiocyanate [179, 182, 186], thioborate [161], thiostannane [196], sulfenamide [180], and thioester [187, 189, 191, 194, 195]. Palladium catalyzed thiocarbonylation, and the development of multicomponent reactions centering on hydrothiolation with free thiols and disulfides has been reviewed extensively [19, 20, 23-26, 167, 227-231]. 

SCHEME 5.2 Palladium-catalyzed hydrothiolation of vinyl ethers [2],... 

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... 

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

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. 

Kondoh A, Yorimitsu H, Oshima K. Palladium-catalyzed a ri-hydrothiolation of 1-alkynylphosphines. Org. Lett. 2007 9 1383-1385. 

In 1996, Ogawa et al. reported the hydrothiolation of an allene catalyzed by Pd(OAc)2 to provide 32, whose formation can be explained as follows (1) insertion of the allene into the Pd-S bond of Pd(SPh)2 to give a it-allyl palladium thiolate 33, and (2) protolysis by PhSH to form 32 and Pd(SPh)2 (Eq. 7.24) [35]. The authors proposed the direct reaction of a a-aUyl palladium with PhSH before the formation of 33. 

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... 

Scheme 5 Catalytic activity of palladium sulfide for hydrothiolation...

The structures of the palladium sulfides have been confirmed clearly by scanning electron microscopy (SEM) study [26]. When Pd(OAc)2 dissolved in alkyne in the presence of y-terpinene is allowed to react with cyclohexanethiol upon microwave heating, nanostructured Pd species (Pd nanobelts) is formed in 85% yield. y-Terpinene acts as an excellent radical trapper and suppresses the formation of anfi -Markovnikov addition product 3 by radical pathway. On the other hand, the addition of thiols to Pd(OAc)2 followed by addition of alkyne leads to amorphous particles in the pm-size region. The formed Pd nanobelts exhibits excellent catalytic activity toward the hydrothiolation of aUcynes. In particular, the hydrothiolation with aUcanethiols proceeds efficiently with excellent regioselectivity upon microwave heating (Scheme 6). 

Catalytic hydrothiolation and hydroselenation reactions are very useful for providing a wide variety of functionalized organosulfur and selenium compounds. For example, the palladium-catalyzed hydrothiolation of conjugated enynes affords a series of 2-(phenylsulfanyl)-1,3-dienes regioselectively in good yields (Scheme 29) [100]. 

Palladium-catalyzed hydrothiolation of alkynylphosphines proceeds via anti-addition process, yielding the corresponding (Z)-l-phosphino-2-thioalkenes regio-and stereoselectively. The coordination of the phosphino group to the palladium induces the rare example of catalytic anti-addition of thiols to alkynes (Scheme 30)... 

Scheme 29 Palladium-catalyzed hydrothiolation of conjugated enynes...

The palladium-catalyzed intramolecular hydrothiolation of (Z)-2-en-4-yne-1-thiols, followed by double-bond-isomerization successfully provides substituted thiophenes in good yields. The hydrothiolation step may involve the nucleophilic attack of the sulfanyl group to the carbon-carbon triple bond coordinated by palladium (Scheme 31) [103]. 

Scheme 31 Thiophene synthesis by palladium-catalyzed hydrothiolation...

Mitamura T, Daitou M, Nomoto A, Ogawa A (2011) Highly regioselective double hydrothiolation of terminal acetylenes with thiols catalyzed by palladium diacetate. Bull Chem Soc Jpn 84 413 15... 

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