Catalyst‐Free Formal Thioboration to Synthesize Borylated Benzothiophenes and Dihydrothiophenes

Abstract

The first ring-forming thioboration reaction of C-C π bonds is reported. This catalyst-free method proceeds in the presence of a commercially available external electrophilic boron source (Bchlorocatecholborane) in good to high yields. The method is scalable and tolerates a variety of functional groups that are intolerant of other major borylation methods. The resulting borylated benzothiophenes participate in a variety of in situ derivatization reactions, showcasing that these borylated intermediates do not need to be isolated prior to downstream functionalization. This methodology has been extended to the synthesis of borylated dihydrothiophenes. Mechanistic experiments suggest that the operative mechanistic pathway is through boron-induced activation of the alkyne followed by electrophilic cyclization, as opposed to S-B σ bond formation, providing a mechanistically distinct pathway to the thioboration of C-C π bonds. Borylative CyclizationsThe first ring-forming thioboration reaction of C-C π bonds is reported. The resulting borylated benzothiophenes participate in a variety of in situ derivatization reactions, showcasing that these borylated intermediates do not need to be isolated prior to downstream functionalization. Mechanistic experiments suggest that the operative mechanistic pathway is through boron-induced activation of the alkyne followed by electrophilic cyclization. KeywordsBoron; C-C Activation; Sulfur Heterocycles; Sulfur; Cyclization Thioboration, the addition of sulfur and boron across C-C π bonds, holds promise as an efficient route to synthesize functionalized thioethers. [1] This area of research has focused on Correspondence to: Suzanne A. Blum. HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript reagents containing B-S σ bonds that are capable of adding in a direct fashion to π systems. In 2015, Bo, Fernández, and Westcott demonstrated the ability of B-S σ bonds from inhouse synthesized reagents to add across Michael acceptors through boron activation of the carbonyl oxygen (Figure 1a, top), but without generation of a B-C bond for downstream functionalization. [2] In 1993, Miyaura and Suzuki developed a thioboration reaction of B-S σ bonds across alkynes. [3,4] This method similarly employed in-house synthesized reagents containing B-S σ bonds, however it used a carbophilic palladium catalyst to activate the C-C π bond. Protodeboration and in situ Suzuki cross-coupling reactions of these thioboration products were demonstrated, establishing the utility of such synthetic intermediates ( Figure 1a, bottom).In contrast, formal thioboration, wherein the equivalents of boron and sulfur add across a C-C π bond, is underexplored, despite the potential advantages of employing commercially available boron reagents as opposed to the thioboration reagents requiring synthesis, and the plausibility of avoiding a palladium catalyst as previously required in the direct thioboration of alkynes. [3,4] Although little is known about the thiophilicity versus ca...