BCl<sub>3</sub>‐Induced Annulative Oxo‐ and Thioboration for the Formation of C3‐Borylated Benzofurans and Benzothiophenes

Warner, Andrew J.; Churn, Anna; McGough, John S.; Ingleson, Michael J.

doi:10.1002/anie.201610014

Cited by 83 publications

(50 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9 Unlike our proposed intermediate 4 , 11 did not spontaneously demethylate. Instead, the neutral product 12 was produced after sequential treatment with Et 3 N for demethylation and AlCl 3 to remove the chloride.…”

Section: Resultsmentioning

confidence: 53%

“…Notably, this reagent has the potential to display similar reactivity to ClBcat in the initial alkyne activation step, but lacks the bifunctional ability to dissociate an anionic ligand and thus lacks the ability to induce subsequent demethylation. Thus, this reagent may permit “freezing” of the reaction pathway at zwitterionic intermediate 19 , 9 which in turn would permit the study of its structure and of its fundamental reactivity independent of the borylative heterocyclization step. Indeed, after 1 h at 20 °C in CH 2 Cl 2 the 1-methyl-1-benzothiophenium borate intermediate 19 was isolated in 81% yield (Scheme 3).…”

Section: Resultsmentioning

confidence: 99%

“…Subsequently, Ingleson found that BCl 3 was sufficiently electrophilic to bring about oxyboration and thioboration reactions of alkynes at 20 °C, albeit with additional reagents to promote thioboration (Figure 1c). 8,9 …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mechanistic Studies of Formal Thioboration Reactions of Alkynes

et al. 2017

View full text Add to dashboard Cite

Several formal heteroborylative cyclization reactions have been recently reported, but little physical-organic and mechanistic data is known. We now investigate the catalyst-free formal thioboration reaction of alkynes to gain mechanistic insight into B-chlorocatecholborane (ClBcat) in its new role as an alkynophilic Lewis acid in electrophilic cyclization/dealkylation reactions. In kinetic studies, the reaction is second order globally; first order with respect to both the 2-alkynylthioanisole substrate and the ClBcat electrophile, with activation parameters of ΔG‡ = 27.1 ± 0.1 kcal mol−1 at 90 °C, ΔH‡ = 13.8 ± 1.0 kcal mol−1 and ΔS‡ = −37 ± 3 cal mol−1 K−1, measured over the range of 70–90°C. Carbon kinetic isotope effects supported a rate-determining AdE3 mechanism wherein alkyne activation by neutral ClBcat is concerted with cyclative attack by nucleophilic sulfur. A Hammett study found a ρ+ of −1.7, suggesting cationic charge buildup during the cyclization and supporting rate-determining concerted cyclization. Studies of the reaction with tris(pentafluorophenyl)borane (B(C6F5)3), an activating agent capable of cyclization but not dealkylation, resulted in the isolation of a post-cyclization zwitterionic intermediate. Kinetic studies via UV-vis spectroscopy with this boron reagent found second order kinetics, supporting the likely relevancy of intermediates in this system to the ClBcat system. Computational studies comparing ClBcat with BCl3 as an activating agent showed why BCl3, in contrast to ClBcat, failed to mediate the complete the cyclization/demethylation reaction sequence by itself. Overall, the results support a mechanism in which the ClBcat reagent serves a bifunctional role by sequentially activating the alkyne, despite being less electrophilic than other known alkyne-activating reagents, then providing chloride for post-rate-determining demethylation/neutralization of the resulting zwitterionic intermediate.

show abstract

Section: Resultsmentioning

confidence: 53%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Mechanistic Studies of Formal Thioboration Reactions of Alkynes

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Substituents at the benzene moiety often originate from the synthetic precursor used to construct the benzofuran scaffold. Synthetic methods for assembling the benzofuran scaffold have typically involved acid-catalyzed cyclizations [11][12][13][14][15][16][17], carbonylative cyclizations via Sonogashira reactions [18][19][20][21][22][23][24], Heck-type cyclizations [25][26][27][28][29], photocyclizations [30][31][32][33][34], radical cyclizations [35][36][37][38][39], and other types of transition-metal catalyzed transformations [40][41][42][43][44][45]. When it comes to the functionalization of the furan part, there exists a considerable number of methods for directly functionalizing either the C2 or C3 position [46][47][48][49][50][51][52][53][54][55][56].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Elaborate Benzofuran-2-Carboxamide Derivatives through a Combination of 8-Aminoquinoline Directed C–H Arylation and Transamidation Chemistry

et al. 2020

View full text Add to dashboard Cite

Herein, we present a short and highly modular synthetic route that involves 8-aminoquinoline directed C–H arylation and transamidation chemistry, and which enables access to a wide range of elaborate benzofuran-2-carboxamides. For the directed C–H arylation reactions, Pd catalysis was used to install a wide range of aryl and heteroaryl substituents at the C3 position of the benzofuran scaffold in high efficiency. Directing group cleavage and further diversification of the C3-arylated benzofuran products were then achieved in a single synthetic operation through the utilization of a one-pot, two-step transamidation procedure, which proceeded via the intermediate N-acyl-Boc-carbamates. Given the high efficiency and modularity of this synthetic strategy, it constitutes a very attractive method for generating structurally diverse collections of benzofuran derivatives for small molecule screening campaigns.

show abstract

“…We first turned our attention to the recently reported cyclization of 2i to the borylated benzofuran 7 (Scheme 3A). [18] Thea uthors proposed that alkyne activation by BCl 3 is followed by nucleophilic attack of the oxygen atom and the formation of chloromethane.I nterestingly,when BCl 3 was added to amixture of 1 and 2i,the only product detected was that of chlorocyanation 4i.M oreover, when 1 was added to solutions of 7 generated in situ, no cyanation was observed. Hence, 4i is not likely to be formed by the addition of Cl 2 B À Cl to 2i,f ollowed by BCl 2 /CN displacement.…”

mentioning

confidence: 99%

Regio‐ and Stereoselective Chlorocyanation of Alkynes

et al. 2017

View full text Add to dashboard Cite

Av ariety of terminal and internal alkynes were converted regio-and stereoselectively into (Z)-3-chloroacrylonitriles by treatment with BCl 3 in the presence of stoichiometric amounts of imidazolium thiocyanates.These products could be readily functionalizedt op rovide useful building blocks,t hus demonstrating the synthetic value of the method. Preliminary mechanistic studies suggest initial activation of the cationic thiocyanate by the Lewis acid, followed by electrophilic attack of the alkyne.The syn addition of achloride to the vinyl cation intermediate and final elimination of the thiourea unit afford the desired chloroacrylonitriles.Scheme 1. Synthesis of substituted acrylonitriles from alkynes.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

show abstract

BCl₃‐Induced Annulative Oxo‐ and Thioboration for the Formation of C3‐Borylated Benzofurans and Benzothiophenes

Cited by 83 publications

References 32 publications

Mechanistic Studies of Formal Thioboration Reactions of Alkynes

Mechanistic Studies of Formal Thioboration Reactions of Alkynes

Synthesis of Elaborate Benzofuran-2-Carboxamide Derivatives through a Combination of 8-Aminoquinoline Directed C–H Arylation and Transamidation Chemistry

Regio‐ and Stereoselective Chlorocyanation of Alkynes

Contact Info

Product

Resources

About

BCl3‐Induced Annulative Oxo‐ and Thioboration for the Formation of C3‐Borylated Benzofurans and Benzothiophenes

Cited by 83 publications

References 32 publications

Mechanistic Studies of Formal Thioboration Reactions of Alkynes

Mechanistic Studies of Formal Thioboration Reactions of Alkynes

Synthesis of Elaborate Benzofuran-2-Carboxamide Derivatives through a Combination of 8-Aminoquinoline Directed C–H Arylation and Transamidation Chemistry

Regio‐ and Stereoselective Chlorocyanation of Alkynes

Contact Info

Product

Resources

About

BCl₃‐Induced Annulative Oxo‐ and Thioboration for the Formation of C3‐Borylated Benzofurans and Benzothiophenes