{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang W"],"funding":["NIGMS NIH HHS"],"pagination":["292-297"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9016776"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["604(7905)"],"pubmed_abstract":["Recent research in medicinal chemistry has suggested that there is a correlation between an increase in the fraction of sp<sup>3</sup> carbons-those bonded to four other atoms-in drug candidates and their improved success rate in clinical trials<sup>1</sup>. As such, the development of robust and selective methods for the construction of carbon(sp<sup>3</sup>)-carbon(sp<sup>3</sup>) bonds remains a critical problem in modern organic chemistry<sup>2</sup>. Owing to the broad availability of alkyl halides, their direct cross-coupling-commonly known as cross-electrophile coupling-provides a promising route towards this objective<sup>3-5</sup>. Such transformations circumvent the preparation of carbon nucleophiles used in traditional cross-coupling reactions, as well as stability and functional-group-tolerance issues that are usually associated with these reagents. However, achieving high selectivity in carbon(sp<sup>3</sup>)-carbon(sp<sup>3</sup>) cross-electrophile coupling remains a largely unmet challenge. Here we use electrochemistry to achieve the differential activation of alkyl halides by exploiting their disparate electronic and steric properties. Specifically, the selective cathodic reduction of a more substituted alkyl halide gives rise to a carbanion, which undergoes preferential coupling with a less substituted alkyl halide via bimolecular nucleophilic substitution to forge a new carbon-carbon bond. This protocol enables efficient cross-electrophile coupling of a variety of functionalized and unactivated alkyl electrophiles in the absence of a transition metal catalyst, and shows improved chemoselectivity compared with existing methods."],"journal":["Nature"],"pubmed_title":["Electrochemically driven cross-electrophile coupling of alkyl halides."],"pmcid":["PMC9016776"],"funding_grant_id":["R01 GM134088"],"pubmed_authors":["Zhang W","Lu L","Lehnherr D","Mondragon J","Lin S","Strotman N","Wang Y","Rein J","See KA","Ware SD"],"additional_accession":[]},"is_claimable":false,"name":"Electrochemically driven cross-electrophile coupling of alkyl halides.","description":"Recent research in medicinal chemistry has suggested that there is a correlation between an increase in the fraction of sp<sup>3</sup> carbons-those bonded to four other atoms-in drug candidates and their improved success rate in clinical trials<sup>1</sup>. As such, the development of robust and selective methods for the construction of carbon(sp<sup>3</sup>)-carbon(sp<sup>3</sup>) bonds remains a critical problem in modern organic chemistry<sup>2</sup>. Owing to the broad availability of alkyl halides, their direct cross-coupling-commonly known as cross-electrophile coupling-provides a promising route towards this objective<sup>3-5</sup>. Such transformations circumvent the preparation of carbon nucleophiles used in traditional cross-coupling reactions, as well as stability and functional-group-tolerance issues that are usually associated with these reagents. However, achieving high selectivity in carbon(sp<sup>3</sup>)-carbon(sp<sup>3</sup>) cross-electrophile coupling remains a largely unmet challenge. Here we use electrochemistry to achieve the differential activation of alkyl halides by exploiting their disparate electronic and steric properties. Specifically, the selective cathodic reduction of a more substituted alkyl halide gives rise to a carbanion, which undergoes preferential coupling with a less substituted alkyl halide via bimolecular nucleophilic substitution to forge a new carbon-carbon bond. This protocol enables efficient cross-electrophile coupling of a variety of functionalized and unactivated alkyl electrophiles in the absence of a transition metal catalyst, and shows improved chemoselectivity compared with existing methods.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2025-04-03T22:45:06.394Z","creation":"2024-10-16T10:48:56.295Z"},"accession":"S-EPMC9016776","cross_references":{"pubmed":["35189623"],"doi":["10.1038/s41586-022-04540-4"]}}