Figure 1 |. Cross-coupling reactions using configurationally stable, optically active secondary alkyl nucleophiles.

a, Proposed catalytic cycle for the Pd-catalysed cross-coupling of secondary nucleophiles and aryl electrophiles. It is necessary for reductive elimination to occur in the absence of the competing β-hydride elimination pathway to avoid the formation of isomeric by-products. b, Inverse relationship between configurational stability and nucleophilicity in secondary alkyl organometallic nucleophiles. c, Recent advances in Pd-catalysed cross-coupling reactions between isolable, optically active organometallic nucleophiles and aryl halides. The groups of Hoppe²⁹, Crudden²², Ohmura and Suginome³², Molander^31,37, Hall³⁵ and Falck²⁸ have demonstrated the use of isolable, optically active organometallic nucleophiles in cross-coupling reactions. However, nucleophiles in these examples require activation via the presence of a C(sp²) α-carbon, heteroatomic α-carbon and/or a strongly coordinating β-carbonyl group. DMF, dimethylformamide; THF, tetrahydrofuran; CPME, cyclopentyl methyl ether; dba, dibenzylideneacetone; XPhos, 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl.