Catalytic Generation of Borenium Ions by Cooperative B–H Bond Activation: The Elusive Direct Electrophilic Borylation of Nitrogen Heterocycles with Pinacolborane

Stahl, Timo; Müther, Kristine; Ohki, Yasuhiro; Tatsumi, Kazuyuki; Oestreich, Martin

doi:10.1021/ja405925w

Cited by 172 publications

(92 citation statements)

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“…Recently, Oestreich, Tatsumi and co-workers developed a route to dehydroborate activated heteroarenes directly using pinacol-ligated borenium cations [73]. In contrast to previous studies using amine-ligated pinacol borenium cations that were ineffective for dehydroborations, they used a cationic Ru(II)-SR compound that was bound to [PinB] + through sulphur.…”

Section: Intermolecular Electrophilic Aromatic Borylationmentioning

confidence: 99%

Fundamental and Applied Properties of Borocations

Ingleson

2015

Synthesis and Application of Organoboron Compounds

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Section: Intermolecular Electrophilic Aromatic Borylationmentioning

confidence: 99%

Fundamental and Applied Properties of Borocations

Ingleson

2015

Synthesis and Application of Organoboron Compounds

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“…Obtaining insights into the turnover-limiting step and nature of catalyst deactivation pathways in this class of C−H functionalization reaction is crucial for the rational design of next generation catalysts. Information on the speciation of iridium, 17,18 ruthenium, 19 iron, 6a,d heterobimetallic copper, 6c,20 and frustrated Lewis pair (FLP) 21 catalysts in the presence of HBPin have been reported; however, the turnover-limiting step and possible catalyst deactivation pathways have not been identified, and principles for future catalyst development are not evident.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic Studies of Cobalt-Catalyzed C(sp²)–H Borylation of Five-Membered Heteroarenes with Pinacolborane

Obligacion

Chirik

2017

ACS Catal.

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Studies into the mechanism of cobalt-catalyzed C(sp2)−H borylation of five-membered heteroarenes with pinacolborane (HBPin) as the boron source established the catalyst resting state as the trans-cobalt(III) dihydride boryl, (iPrPNP)Co(H)2(BPin) (iPrPNP = 2,6-(iPr2PCH2)2(C5H3N)), at both low and high substrate conversions. The overall first-order rate law and observation of a normal deuterium kinetic isotope effect on the borylation of benzofuran versus benzofuran-2-d1 support H2 reductive elimination from the cobalt(III) dihydride boryl as the turnover-limiting step. These findings stand in contrast to that established previously for the borylation of 2,6-lutidine with the same cobalt precatalyst, where borylation of the 4-position of the pincer occurred faster than the substrate turnover and arene C−H activation by a cobalt(I) boryl is turnover-limiting. Evaluation of the catalytic activity of different cobalt precursors in the C−H borylation of benzofuran with HBPin established that the ligand design principles for C− H borylation depend on the identities of both the arene and the boron reagent used: electron-donating groups improve catalytic activity of the borylation of pyridines and arenes with B2Pin2, whereas electron-withdrawing groups improve catalytic activity of the borylation of five-membered heteroarenes with HBPin. Catalyst deactivation by P−C bond cleavage from a cobalt(I) hydride was observed in the C−H borylation of arene substrates with C−H bonds that are less acidic than those of five-membered heteroarenes using HBPin and explains the requirement of B2Pin2 to achieve synthetically useful yields with these arene substrates.

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Section: Mechanistic Studies: Boron As a Thiophilic Or Carbophilic Lementioning

confidence: 98%

“…This lack of chemical shift change in the 11 B NMR spectrum also ruled out formation of detectable amounts of sulfur-based borenium species. [33,34] This mechanistic control reaction demonstrated that demethylation of 1 is too slow relative to the timescale of the overall thioboration reaction (4 h) to be a step in the operative pathway and therefore ruled out the thiophilic activation pathway.Next, two pathways were considered in which the ClBcat acts as a carbophilic Lewis acid by activating the C-C π system. [34] The first is through a haloboration/cyclization pathway proceeding through a chloroboration reaction analogous to that reported for alkynes, [30] generating intermediate 11 (Scheme 2, middle).…”

mentioning

confidence: 98%

Catalyst‐Free Formal Thioboration to Synthesize Borylated Benzothiophenes and Dihydrothiophenes

et al. 2016

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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...

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Catalytic Generation of Borenium Ions by Cooperative B–H Bond Activation: The Elusive Direct Electrophilic Borylation of Nitrogen Heterocycles with Pinacolborane

Cited by 172 publications

References 35 publications

Fundamental and Applied Properties of Borocations

Fundamental and Applied Properties of Borocations

Mechanistic Studies of Cobalt-Catalyzed C(sp²)–H Borylation of Five-Membered Heteroarenes with Pinacolborane

Catalyst‐Free Formal Thioboration to Synthesize Borylated Benzothiophenes and Dihydrothiophenes

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Catalytic Generation of Borenium Ions by Cooperative B–H Bond Activation: The Elusive Direct Electrophilic Borylation of Nitrogen Heterocycles with Pinacolborane

Cited by 172 publications

References 35 publications

Fundamental and Applied Properties of Borocations

Fundamental and Applied Properties of Borocations

Mechanistic Studies of Cobalt-Catalyzed C(sp2)–H Borylation of Five-Membered Heteroarenes with Pinacolborane

Catalyst‐Free Formal Thioboration to Synthesize Borylated Benzothiophenes and Dihydrothiophenes

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Mechanistic Studies of Cobalt-Catalyzed C(sp²)–H Borylation of Five-Membered Heteroarenes with Pinacolborane