Asymmetric synthesis of a β-lactam framework via the conjugate addition of amidocuprates(I) to chiral enoates

Amidocuprate(I) reagents {Li[Cu(NR₂)₂]} and higher order cyanocuprates(I) {Li₂[Cu(CN)(NR₂)₂]} have been developed as a new class of nitrogen nucleophiles. These reagents underwent regioselective 1,4-additions to α,β:γ,δ-dienoates, whereas NHR₂ gave a 1,6-addition product and the lithium reagent LiNR₂ afforded a mixture of 1,4- and 1,2-addition products. The amidocuprates(I) were added to chiral α,β:γ,δ-dienones having a 8-phenyl-p-menth-3-yl or a 10,2-bornanesultam chiral auxiliary in order to produce 1,4-adducts in good to high diastereoselectivity. The addition of Li[Cu{N(Bn)(TMS)}₂] and Li₂[Cu(CN){N(Bn)(TMS)}₂] to 8-phenyl-p-menth-3-yl 5-phenyl-2,4-pentadienoate or N-(5-phenyl-2,4-pentadienoyl)-10,2-bornanesultam produced an (R)-chirality at the β-position. The 1,4-addition of Li₂[Cu(CN){N(Bn)(TMS)}₂] to the bornanesultam, followed by trapping with acetaldehyde, gave the α-(1-hydroxyethyl)-β-amino derivative as a single isomer in good yield. This three-component coupling was used in an asymmetric synthesis of a β-lactam.