Here, we demonstrate that a metallaphotoredox-catalyzed cross-electrophile coupling mechanism provides a unified method for the α-arylation of diverse activated alkyl chlorides, including α-chloroketones, α-chloroesters, α-chloroamides, α-chlorocarboxylic acids, and benzylic chlorides. This strategy, which is effective for a wide variety of aryl bromide coupling partners, is predicated upon a halogen atom abstraction/nickel radical-capture mechanism that is generically successful across an extensive range of carbonyl substrates. The construction and use of arylacetic acid products have further enabled two-step protocols for the delivery of valuable building blocks for medicinal chemistry, such as aryldifluoromethyl and diarylmethane motifs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764888 | PMC |
| http://dx.doi.org/10.1002/anie.201909072 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
One-Pot Chlorination and Cross-Electrophile Coupling of Alcohols with Aryl Chlorides.
Org Lett
January 2025
Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave, Madison, Wisconsin 53706, United States.
Although alkyl alcohols and aryl chlorides are the two most abundant substrate pools for cross-electrophile coupling, methods to couple them remain limited. Herein we demonstrate a simple procedure for the in situ deoxychlorination of alcohols followed by XEC with aryl chlorides. A broad substrate scope can be achieved by tuning the rate of the reaction via halide exchange.
View Article and Find Full Text PDFNickel-Catalyzed Cross-Electrophile Coupling of Aryl Triflates with Alkyl Halides: Mechanism-Informed Design of More General Conditions.
J Am Chem Soc
January 2025
Department of Chemistry, University of Wisconsin─Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.
Aryl triflates make up a class of aryl electrophiles that are available in a single step from the corresponding phenol. Despite the known reactivity of nickel complexes for aryl C-O bond activation of phenol derivatives, nickel-catalyzed cross-electrophile coupling using aryl triflates has proven challenging. Herein, we report a method to form C(sp)-C(sp) bonds by coupling aryl triflates with alkyl bromides and chlorides using phenanthroline (phen) or pyridine-2,6-bis(-cyanocarboxamidine) (PyBCam)-ligated nickel catalysts.
View Article and Find Full Text PDFBenzothiazolium salts as versatile primary alcohol derivatives in Ni-catalyzed cross-electrophile arylation/vinylation.
Org Biomol Chem
January 2025
Center for Supramolecular Chemistry and Catalysis and Department of Chemistry, Shanghai University, 99 Shang-Da Road, Shanghai 200444, China.
Herein, we report a Ni-catalyzed cross-electrophile coupling of aryl/vinyl halides with benzothiazolium salts derived from alcohols. Our findings demonstrate that primary alkyl benzothiazolium salts serve as effective C(sp)-O substrates, facilitating coupling with aryl and vinyl halides. This method not only enables the formal functionalization of primary alcohols but also provides experimental support for previously established sequential alcohol halogenation and Ni-catalyzed reductive coupling platforms.
View Article and Find Full Text PDFCobalt-Catalyzed Enantioselective Reductive Coupling of Imines and Internal Alkynes.
Angew Chem Int Ed Engl
January 2025
Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, 741246, West Bengal, India.
Chiral allylamines are important structural components in natural products, pharmaceuticals, and chiral catalysts. Herein, we report a cobalt-catalyzed enantioselective reductive coupling of imines with internal alkynes to synthesize chiral allylamines. The reaction is catalyzed by a cobalt complex derived from commercially available bisphosphine ligand utilizing zinc as the electron donor.
View Article and Find Full Text PDFSelective Ni-Catalyzed Cross-Electrophile Coupling of Heteroaryl Chlorides and Aryl Bromides at 1:1 Substrate Ratio.
J Am Chem Soc
January 2025
Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Nickel-catalyzed cross-electrophile coupling (XEC) reactions of (hetero)aryl electrophiles represent appealing alternatives to palladium-catalyzed methods for biaryl synthesis, but they often generate significant quantities of homocoupling and/or proto-dehalogenation side products. In this study, an informer library of heteroaryl chloride and aryl bromide coupling partners is used to identify Ni-catalyzed XEC conditions that access high selectivity for the cross-product when using equimolar quantities of the two substrates. Two different catalyst systems are identified that show complementary scope and broad functional-group tolerance, and time-course data suggest that the two methods follow different mechanisms.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!