A nickel-catalyzed cross-electrophile coupling of allylic acetates and -difluorovinyl tosylate is presented, which first achieves allylic -difluoroolefins via C(sp)-C(sp) cross-electrophile coupling. In addition, this protocol was performed under mild reaction conditions, affording a variety of allylic -difluorovinyl arenes in moderate to good yields. Moreover, both linear and branched allylic acetate could produce a linear cross-coupling product exclusively. Mechanistic studies reveal that the reaction involves two different Ni(0)/Ni(II) catalytic cycles.
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http://dx.doi.org/10.1021/acs.orglett.2c01245 | DOI Listing |
J Am Chem Soc
December 2024
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 PDFAngew Chem Int Ed Engl
December 2024
Xi'an Jiaotong University, School of Chemical Engineering & Technology, Xingqing Road 28, 710049, Xi'an, CHINA.
The nickel catalyzed multi-component cross-electrophile carbonylation which emerges as a powerful and efficient method for constructing diverse ketones has attracted increasing attention of organic chemists. However, the selectivity of this reaction poses a significant challenge. In this work, we have developed a current-regulated selective nickel-catalyzed electroreductive cross-electrophile carbonylation, which offers a direct convergent synthesis of β/γ-hydroxy ketones, which represent pivotal structural motifs found in numerous natural products, bioactive molecules, pharmaceutical compounds, and essential building blocks.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China.
Ni-catalyzed multicomponent cross-couplings have emerged as a powerful strategy for efficiently constructing complex molecular architectures from a diverse array of organic halides. Despite its potential, selectively forming multiple chemical bonds in a single operation, particularly in the realm of cross-electrophile coupling catalysis, remains a significant challenge. In this study, we have developed a consecutive open-shell reductive Ni catalysis, enabling the formation of two geminal C(sp)-C(sp) bonds from two stereoelectronically similar C(sp)-I reactants in conjunction with a methylene electrophile.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.
Chemically modified oligonucleotides have garnered significant attention in medicinal chemistry, chemical biology, and synthetic biology due to their enhanced stability in vivo compared to naturally occurring oligonucleotides. However, current methods for synthesizing modified nucleosides, particularly at the C2'-position, are limited in terms of efficiency, modularity, and selectivity. Herein, we report a new approach for the synthesis of highly functionalized C2'-α-aryl/alkenyl nucleosides via an electrochemical nickel-catalyzed cross-coupling of 2'-bromo nucleosides with a variety of (hetero)aryl and alkenyl iodides.
View Article and Find Full Text PDFChem Rev
December 2024
Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Cross-electrophile coupling (XEC), defined by us as the cross-coupling of two different σ-electrophiles that is driven by catalyst reduction, has seen rapid progression in recent years. As such, this review aims to summarize the field from its beginnings up until mid-2023 and to provide comprehensive coverage on synthetic methods and current state of mechanistic understanding. Chapters are split by type of bond formed, which include C(sp)-C(sp), C(sp)-C(sp), C(sp)-C(sp), and C(sp)-C(sp) bond formation.
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