ChemRxiv 2017,DOI: 10.26434/chemrxiv.5715106.v1
◆Cross-coupling reactions, wherein a catalyst brings together molecular partners to forge a new bond, are powerful transformations that are among the most used tools in synthesis. For decades, researchers have mined this area of chemistry, developing methods for a litany of coupling partners. Now chemists have found a novel, and valuable, pairing.
◆A team of researchers led by Phil Baran at Scripps Research Institute, California, has introduced alkylsulfones as coupling partners for radical cross-coupling reactions, providing access to fluorinated structures that would be cumbersome to make with typical alkyl coupling partners. Where as classic cross-couplings conjoin two aryl partners, this type of cross-couplingis particularly well-suited for threading together aryl and alkyl partners.
◆With the help of a nickel catalyst and bipyridine ligand, the reaction couples arylzinc compounds with special alkylsulfone reagents. The researchers demonstrated the scope of the reaction with more than 60 examples containing a variety of substitution patterns and by synthesizing biologically relevant molecules to highlight the shortened synthetic routes enabled by the technique.
◆Notably, the sulfone reagents let researchers directly install fluorine atoms at the alkyl coupling site, whereas previously chemists would have had to run difficult deoxyfluorination reactions to make the requisite fluorinated coupling partner, says Scott Denmark of the University of Illinois, Urbana-Champaign. 「The unique reactivity of the N-phenyltriazolylsulfones is surpassed only by their practicality as bench stableand odorless, crystalline compounds,」 he says. 」There is no doubt that this workis going to be game-changing and illustrates that there is still much to do in the field of cross-coupling,」 say Cathleen Crudden of Queen’s University in Ontario and Masakazu Nambo of the Institute of Transformative Bio-Molecules at Nagoya University.