Conjugate addition–enolate-trapping reactions

Abstract

Abstract Enolate anions are one of the most widely used nucleophilic species in organic synthesis. Organocopper conjugate addition to α,β-unsaturated carbonyl compounds generates in situ metal enolates under mild conditions with the incorporation of an organic group to the β-position. Therefore, the organocopper-mediated reaction followed by the regioselective enolate trapping provides an extremely powerful tool for controlled construction of organic frameworks (see Scheme 9.1). The organocopper reagents commonly used for this tandem reaction can be divided into four general classes: (1) Grignard reagents plus catalytic amounts of copper salts (RMgX + cat. CuX; X = Cl, Br, or I); (2) complexed mono-organocopper compounds (RCu complexed with phosphine, phosphite, or sulfide ligand); (3) homocuprates or mixed cuprates [MCuR2, MCuRR1, or MCuR(Z); M = Li or MgX, Z = C≡CPr or CN]; and (4) higher order cuprates [Li2CuR2(CN) or Li2CuRR1(CN)]. Homocuprates and higher order cuprates also include silylcuprates [Li2Cu(SiR3)2(CN)], stannylcuprates [Li2CuSnMe3(2-thienyl)(CN)], and aminocuprates ﹛LiCu[NSiMe3(CH2Ph)]2 and Li2Cu[NSiMe3(CH2Ph)2(CN)﹜. Although the combination of Grignard reagents and copper catalysts is often the first choice, lithium diorganocuprates and higher order cuprates have been used more widely in view of the higher efficiency, selectivity, and reproducibility of the conjugate addition reactions and the enhanced reactivity of the resulting enolate intermediates.