GYOUNG Young Soo Kangnung University, Kangnung大学化学科, 教授
NAKAMURA Hiroyuki Kyushu University, 有機化学基礎研究センター, 助手 (30274434)
KADOTA Isao Tohoku University, 大学院・理学研究科, 助手 (30250666)
ASAO Naoki Hokkaido University, 理学部, 講師 (60241519)
NEMOTO Hisao Tokushima University, 薬学部, 助教授 (30208293)
Amide cuprate reagents, (R_2N)_2CuLi and higher order cyano cuprates (R_2N)_2Cu(CN)Li_2, have been developed as a new class of nitrogen nucleophiles. These reagents underwent regioselective 1,4-addition to alpha, beta, gamma, delta-dienoates whereas R_2NH gave a 1,6-addition product and the lithium reagent R_2NLi afforded a mixture of 1,4-and 1,2-addition products. The amide cuprates were added to chiral alpha, beta, gamma, delta-dienoates having a 8-phenylmenthyl or bornanesultam chiral auxiliary to produce 1,4-adducts in good to high diastereoselectivity. The addition of [BnN(TMS)]_2CuLi and [BnN(TMS)]_2Cu(CN)Li_2 to 8-phenylmenthyl 5-phenyl-2,4-pentadienoate or 5-phenyl-2,4-pentadienoylbornanesultam produced (R) -chirality at the beta-position. The 1,4-addition of [BnN(TMS)]_2Cu(CN)Li_2 to the bornanesultam followed by trapping withacetaldehyde 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.
Conjugate addition of N-benzyl-N-((R)-1-Phenylethyl)amine to (R)-(E)-tert-butyl 5-((tert-butyldimethylsilyl)oxy)-4-methyl-2-pentenoate produced the (3S,4R)-syn-adduct with essentially 100% de in 84% yield, whereas the addition of (S)-amine to the pentenoate afforded the (3R,4R) -anti-adduct with essentially 100% de in 95% yield. The syn adduct was converted upon sequential treatment with lithium diisopropylamide-methylaluminum dichloride-acetaldehyde to the key intermediate ; the diastereoisomer ratio of the key intermediate : the diastereoisomer ratio of the key intermediate to other diasteroisomers was 80 : 20. Conversion to a 1beta-methylcarbapenem key intermediate was carried out readily according to the known procedures.