Nucleophile-Assisted Alkene Activation: Olefins Alone Are Often Incompetent

Ashtekar, Kumar Dilip; Vetticatt, Mathew J.; Yousefi, Roozbeh; Jackson, James E.; Borhan, Babak

doi:10.1021/jacs.6b02877

Cited by 80 publications

(101 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…34 Indeed, the entire spectrum of Ad type reactions from Ad E 2 to Ad N 2 (electrophile initiated, nucleophile initiated, and of course, synchronous in between) is treated in many advanced textbooks on physical organic chemistry. 35,36 …”

Section: Resultsmentioning

confidence: 99%

Toward Catalytic, Enantioselective Chlorolactonization of 1,2-Disubstituted Styrenyl Carboxylic Acids

et al. 2016

View full text Add to dashboard Cite

An investigation into the use of Lewis base catalysis for the enantioselective chlorolactonization of 1,2-disubstituted alkenoic acids is described. Two mechanistically distinct reaction pathways for catalytic chlorolactonization have been identified. Mechanistic investigation revealed that tertiary amines predominately operate as Brønsted rather than Lewis bases. Two potential modes of activation have been identified that involve donation of electron density of the carboxylate to the C=C bond as well hydrogen bonding to the chlorinating agent. Sulfur- and selenium-based additives operate under Lewis base catalysis; however, due to the instability of the intermediate benzylic chloriranium ion, chlorolactonization suffers from low chemo-, diastereo-, and enantioselectivities. Independent generation of the benzylic chloriranium ion shows that it is in equilibrium with an open cation, which leads to low specificities in the nucleophilic capture of the intermediate.

show abstract

Section: Resultsmentioning

confidence: 99%

Toward Catalytic, Enantioselective Chlorolactonization of 1,2-Disubstituted Styrenyl Carboxylic Acids

et al. 2016

View full text Add to dashboard Cite

show abstract

“…[3,4] Although little is known about the thiophilicity versus carbophilicity of boron reagents in synthesis, such knowledge would facilitate the development of thioboration reactions by indicating when B–S σ bonds are necessary and when such bonds can be avoided, aiming instead for previously unknown carbophilic activation of the C–C π bond by boron with simultaneous attack by sulfur via an Ad E 3 or Ad E 2 reaction mechanism (Figure 1b). [5,6] Herein the first formal thioboration of C–C π bonds is reported, concurrently developing fundamental knowledge about guiding principles of relative carbophilicity and thiophilicity. The experiments were motivated by a broader study on gold-catalyzed and catalyst-free oxyboration and aminoboration (B–O and B–N addition) reactions in our research group.…”

mentioning

confidence: 99%

Catalyst‐Free Formal Thioboration to Synthesize Borylated Benzothiophenes and Dihydrothiophenes

et al. 2016

View full text Add to dashboard Cite

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.

show abstract

“…Treatment of diphenylacetylene 16, which is the no-sulfur analogue of substrate 1b, under the otherwise standard thioboration conditions resulted in no reaction by 1 H (>95% 16 remaining using mesitylene as an internal standard) or 11 B NMR spectroscopy (only signal detected at δ = 28.6 ppm, corresponding to unreacted ClBcat) in 4 h. This demonstrated that chloroboration product 17 did not form, and thus is an unlikely operative pathway in this thioboration reaction. On the basis of these mechanistic experiments, a role for boron as a carbophilic Lewis acid in this cyclization is proposed, plausibly through an Ad E 2/Ad E 3 mechanism [5,6] (Scheme 2, bottom). Subsequent attack by the sulfur via transition state 13 generates sulfonium intermediate 12.…”

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

confidence: 99%

“…On the basis of these mechanistic experiments, a role for boron as a carbophilic Lewis acid in this cyclization is proposed, plausibly through an Ad E 2/Ad E 3 mechanism [5,6] (Scheme 2, bottom). Subsequent attack by the sulfur via transition state 13 generates sulfonium intermediate 12.…”

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

confidence: 99%

Catalyst‐Free Formal Thioboration to Synthesize Borylated Benzothiophenes and Dihydrothiophenes

et al. 2016

View full text Add to dashboard Cite

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...

show abstract

Nucleophile-Assisted Alkene Activation: Olefins Alone Are Often Incompetent

Cited by 80 publications

References 40 publications

Toward Catalytic, Enantioselective Chlorolactonization of 1,2-Disubstituted Styrenyl Carboxylic Acids

Toward Catalytic, Enantioselective Chlorolactonization of 1,2-Disubstituted Styrenyl Carboxylic Acids

Catalyst‐Free Formal Thioboration to Synthesize Borylated Benzothiophenes and Dihydrothiophenes

Catalyst‐Free Formal Thioboration to Synthesize Borylated Benzothiophenes and Dihydrothiophenes

Contact Info

Product

Resources

About