Palladium-Catalyzed Regio- and Stereoselective Carbothiolation of Terminal Alkynes with Azolyl Sulfides

Abstract

Palladium-catalyzed carbothiolation of terminal alkynes with azolyl sulfides affords various 2-(azolyl)alkenyl sulfides with perfect regio-and stereoselectivities. The present addition reaction proceeded through a direct cleavage of carbon-sulfur bonds in azolyl sulfides. The resulting adducts that are useful intermediates in organic synthesis are further transformed to multi-substituted olefins containing azolyl moieties.Carbothiolation of alkynes has been regarded as the most ideal approach to the highly substituted alkenyl sulfides in organic synthesis, which can generate carboncarbon and carbon-sulfur bonds simultaneously. 1 Regioand stereoselective addition of various carbon-sulfur bonds to alkynes has been achieved by using transition metal catalysts; thioesterification, 2 cyanothiolation, 3 allylthiolation, 4 alkenylthiolation, 5 acylthiolation, 6 iminothiolation, 7 alkynylthiolation, 8 and alkylthiolation. 9,10 Although only decarbonylative addition reaction of thioesters is known, 11 the atom-economical arylthiolation across alkynes has yet to be disclosed to date because carbon-sulfur bonds in aryl sulfides tend to cause a reversible oxidative addition. 12 While it was previously found that aryl sulfides underwent cross-coupling with organometallic reagents 13 probably because of the high reactivity of the once formed oxidative adducts for subsequent transmetalation, arylthiolation of alkynes is unprecedented.Recently, Weller and Willis have reported rhodiumcatalyzed addition of aryl sulfides bearing unique activating groups to terminal alkynes as a specific case. 14 On the other hand, addition reaction of heteroaryl sulfides to alkynes, which can construct the ubiquitous skeletons in pharmaceuticals and agrochemicals, 15 is significantly limited despite its utility. Although platinum-catalyzed furylthiolation, 11b,16 thienylthiolation, 17 and pyridylthiolation 18 of terminal alkynes with thioesters or with heteroaryl halides and arenethiolate salts are only known, those reactions produce toxic carbon monoxide or undesired by-products. We have recently disclosed the regioand stereocontrolled chlorothiolation of alkynes with transition metal catalysts through the chlorine-sulfur bond cleavage of sulfenyl chlorides. 19 During the course of our research on selective addition of organosulfur compounds to alkynes, we investigated carbothiolation with a direct activation of heteroaryl sulfides. Herein, we report that a palladium complex ligated with Nheterocyclic carbene (NHC) catalyzed regio-and stereoselective addition of azolyl sulfides to terminal alkynes.

Recent developments in palladium-catalyzed C–S bond formation

“…After that, the same group described an atom-economical protocol for palladium-catalyzed carbothiolation of azolyl sulfides (55) with terminal alkynes (56) for constructing various 2-(azolyl)alkenyl sulfides (58) with good regio-and stereoselectivities (Scheme 23). 47 The optimization of reaction conditions showed that the conventional palladium/phosphine catalytic systems were found to be less active for this chemical transformation, and the palladium catalysts Pd-PEPPSI-IPr (57) and ([1,3-bis(2,6-diisopropylphenyl)imidazol-2ylidene](3-chloropyridine) palladium(II) dichloride) were superior to the others. Further screening of reaction conditions revealed that both nBuLi and MeOH were indispensable for this protocol.…”

2-(Octadecylsulfanyl)-1,3-thiazole

“…For the synthesis and applications of alkylated thiazoles, see: Iwasaki et al, (2016). For an example of alkylated thiazoles as metal ligands, see: Artem'ev et al (2018).…”

Electrochemical Oxidation Cross Dehydrogenative Coupling of Enamines and Thiophenols for the Synthesis of Vinyl Sulfides

“…Over the past decades, the construction of vinyl sulfide motifs has received considerable attention, [2] and subsequently the C−H/S−H cross coupling [3] has emerged as a more privileged approach to the formation of C−S bond. However, harsh reaction conditions, [2c,f,h–l,3b,e] such as the addition of external oxidants and catalysts, as well as the environmental pollution and atomic economy issues have severely restricted the synthesis of vinyl sulfides. Therefore, developing more efficient, green, and atomic economy methods for the preparation of organic sulfides continue to be highly attractive.…”