ASYMMETRIC-SYNTHESIS OF A BETA-LACTAM FRAMEWORK VIA THE CONJUGATE ADDITION OF AMIDOCUPRATES(I) TO CHIRAL ENOATES

Amidocuprate(I) reagents {Li[Cu(NR(2))(2)]} and higher order cyanocuprates(I) {Li-2[Cu(CN)(NR(2))(2)]} have been developed as a new class of nitrogen nucleophiles. These reagents underwent regioselective 1,4-additions to alpha,beta:gamma,delta-dienoates, whereas NHR(2) gave a 1,6-addition product and the lithium reagent LiNR(2) afforded a mixture of 1,4- and 1,2-addition products. The amidocuprates(I) were added to chiral alpha,beta:gamma,delta-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 Li-2[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 beta-position. The 1,4-addition of Li-2[Cu(CN)(N(Bn)(TMS))(2)] to the bornanesultam, followed by trapping with acetaldehyde, gave the alpha-(1-hydroxyethyl)-beta amino derivative as a single isomer in good yield. This three-component coupling was used in an asymmetric synthesis of a beta-lactam.