Nickel-catalysed selective migratory hydrothiolation of alkenes and alkynes with thiols

Abstract

Direct (utilize easily available and abundant precursors) and selective (both chemo- and regio-) aliphatic C–H functionalization is an attractive mean with which to streamline chemical synthesis. With many possible sites of reaction, traditional methods often need an adjacent polar directing group nearby to achieve high regio- and chemoselectivity and are often restricted to a single site of functionalization. Here we report a remote aliphatic C–H thiolation process with predictable and switchable regioselectivity through NiH-catalysed migratory hydrothiolation of two feedstock chemicals (alkenes/alkynes and thiols). This mild reaction avoids the preparation of electrophilic thiolation reagents and is highly selective to thiols over other nucleophilic groups, such as alcohols, acids, amines, and amides. Mechanistic studies show that the reaction occurs through the formation of an RS-Bpin intermediate, and THF as the solvent plays an important role in the regeneration of NiH species.

Nickel-Catalyzed Removal of Alkene Protecting Group of Phenols, Alcohols via Chain Walking Process

“…Other nickel sources such as zero valent Bis(1,5-cyclooctadiene)nickel (Ni(COD) 2 , entry 2, Table 1) or less soluble NiCl 2 (entry 3, Table 1) diminished the yield. Similar to the previous reports [31][32][33][34][35][36], more bulky ligand was critical for the reaction and probably facilitate the chain walking process (entry 4-5, Table 1). Other common phosphine ligands such as triphenylphosphine (entry 6, Table 1) and tricyclohexylphosphine (entry 7, Table 1) were all low efficient.…”

“…Other common phosphine ligands such as triphenylphosphine (entry 6, Table 1) and tricyclohexylphosphine (entry 7, Table 1) were all low efficient. Nickel(I) was proposed as the active spices in the chain walking reactions [31][32][33][34][35][36], so we tested some reductant to generate of nickel(I) spices. B 2 pin 2 in combination of base was reported as efficient reductant in nickel-catalyzed reductive reactions [47], to our pleased moderated yield was observed (entry 8, Table 1).…”

“…Meanwhile, chain walking strategy in bond construction has been emerging as a powerful tool utilizing alkene as feedstock in synthetic chemistry [22][23][24][25]. Hu [26,27], Martin [28][29][30], Zhu [31][32][33][34][35][36], and Hartwig [37] recently demonstrated that nickel was a prominent catalyst in chain walking chemistry. Streuff reported a zirconium catalyzed deallylation through chain walking mechanism [38].…”

Nickel‐Catalyzed Regioselective Hydroalkylation and Hydroarylation of Alkenyl Boronic Esters

“…Thus the Ni‐catalyzed hydrocarbonation of both terminal and internal alkenes shows linear selectivity (Scheme b). To achieve branch selectivity in NiH‐mediated alkene functionalization, an aryl directing group next to the alkenyl moiety is required (Scheme c) –. The aryl group cannot be easily removed and offers limited opportunities for further functionalization.…”

Ligand‐Enabled Nickel‐Catalyzed Redox‐Relay Migratory Hydroarylation of Alkenes with Arylborons

“…Given the abundance and easy accessibility of alkene feedstock, remote functionalization through alkene isomerization and sequential selective cross‐coupling has recently emerged as an attractive alternative in which a non‐polar C=C double bond in an arbitrary position is used as a traceless directing group and the distant C−H bond is selectively functionalized . Previously, starting from isomeric olefins and a wide variety of electrophilic coupling partners, nickel catalyzed reductive remote hydrofunctionalization has been developed via proposed nickel hydride intermediates (Figure a). Despite robust investigation, these methods are generally limited by the need of a stoichiometric amount of extra reductant.…”