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 (B-chlorocatecholborane) 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.

Mechanistic Studies of Formal Thioboration Reactions of Alkynes

“…Previous experiments ruled out alternative mechanistic pathways that proceed through either B–S σ-bond formation/cyclization or haloboration/cyclization routes when ClBcat is the boron electrophile. 6 …”

“…N,N-Dimethyl-4-((2-(methylthio)phenyl)ethynyl)aniline was synthesized using a literature procedure 34 in 97% yield. 1 H NMR (CDCl 3 , 600 MHz): δ7.47 (d, J = 10.9 Hz, 3H), 7.26 (t, J = 9.5 Hz, 1H), 7.16 (d, J = 9.3 Hz, 1H), 7.10 (t, J = 9.0 Hz, 1H), 6.66 (d, J = 10.7 Hz, 2H), 2.99 (s, 6H), 6.51 (s, 3H).…”

“…(2-(Hex-1-yn-1-yl)phenyl)(methyl)sulfane was synthesized using a literature procedure 34 in 92% yield. 1 H NMR (CDCl 3 , 600 MHz): δ 7.36 (d, J = 7.6 Hz, 1H), 7.24 (t, J = 7.9 Hz, 1H), 7.12 (d, J = 7.5 Hz, 1H), 7.05 (t, J = 7.5 Hz, 1H), 2.50 (t, J = 7.0 Hz, 2H), 2.47 (s, 3H), 1.64 (quin, J = 7.9 Hz, 2H), 1.60–1.50 (m, 2H), 1.25 (t, J = 7.4 Hz, 3H).…”

“…Hept-3-yn-1-yl(methyl)sulfane was synthesized using a literature procedure 34 in 14% yield. 1 H NMR (CDCl3, 600 MHz): δ 2.63 (t, J = 8.0 Hz, 2H), 2.47–2.44 (m, 2H), 2.14–2.11 (m, 5H), 1.50 (sext., J = 7.3 Hz, 2H), 0.96 (t, J = 7.3 Hz, 3H).…”

Theoretical Investigation on the ClBcat‐Promoted Synthesis of Heterocyclic Boronic Esters

“…In general, this metal-free strategy developed by Blum and co-workers could be used as ag eneral way to synthesize heterocyclic boronic esters withoutt he risk of hydrolysis, given the fact that the heteroatom is nucleophilica tabalanced point. [26] The nucleophilicity of the heteroatom should be neither too weak nor too strong. If it is weakly nucleophilic,t he cyclization will not occur;i fi ti st oo nucleophilic, the RDS will shift to the demethylations tep, whichc ould have an inaccessibly high barrier, although our calculations on an aniline system showedt hat the demetylation on the nitrogen remains possible.…”