New Synthetic Method for Chiral B-Lactams

手性B-内酰胺的新合成方法

• 批准号: 07044305
• 负责人: YAMAMOTO Yoshinori
• 金额: --
• 依托单位: Tohoku Univ., Granduate School of Sciencw
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for International Scientific Research.
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07044305/
• 关键词: Organometallics; beta-Lactan; 1beta-Methylcarbapenem; Aldol Reaction; Asymmetric Synthesis; Enolate; Imine; Metal Amide

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.

酰胺铜酸盐试剂(R_2N)_2CuLi和高阶氰基铜酸盐(R_2N)_2Cu(CN)Li_2是一类新型氮亲核试剂。这些试剂对α、β、γ、δ-二烯酸酯进行区域选择性1,4-加成，而R_2NH给出1,6-加成产物，锂试剂R_2NLi提供1,4-和1,2-加成产物的混合物。将酰胺铜酸盐添加到具有8-苯基薄荷基或冰片磺内坦手性助剂的手性α、β、γ、δ-二烯酸酯中，以产生良好至高非对映选择性的1,4-加合物。 [BnN(TMS)]_2CuLi 和 [BnN(TMS)]_2Cu(CN)Li_2 与 5-苯基-2,4-戊二烯酸 8-苯基薄荷酯或 5-苯基-2,4-戊二烯酰基冰磺内酰胺加成生成 (R) - β位的手性。将[BnN(TMS)]_2Cu(CN)Li_2 1,4-加成到冰片磺内酰胺中，然后用乙醛捕获，以良好的产率得到作为单一异构体的α-(1-羟乙基)-β-氨基衍生物。这种三组分偶联用于 β-内酰胺的不对称合成。 N-苄基-N-((R)-1-苯乙基)胺与 (R)-(E)-叔丁基 5-( (叔丁基二甲基甲硅烷基)氧基)-4-甲基-2-戊烯酸酯产生了 (3S,4R)-顺式加合物，其产率基本上为 100%，产率为 84%，而添加(S)-胺与戊烯酸酯反应得到(3R,4R)-反加合物，基本上100% de，产率95%。顺式加合物经二异丙基酰胺锂-二氯化甲基铝-乙醛连续处理后转化为关键中间体；关键中间体的非对映异构体比率：关键中间体与其他非对映异构体的非对映异构体比率为80:20。根据已知的程序容易地进行向1β-甲基碳青霉烯关键中间体的转化。

项目成果

浅尾直樹,上原忠夫,山本嘉則: "Asymmetric Synthesis of a β-Lactan Framework via the Confugate Addition" Bull.Chem.Soc.Jpn.68. 2103-2111 (1995)

Naoki Asao、Tadao Uehara、Yoshinori Yamamoto：“通过共轭加法不对称合成 β-内聚糖框架”Bull.Chem.Soc.Jpn.68 (1995)。

根本尚夫,J.Cai,浅尾直樹,岩本聡,山本嘉則: "Synthesis and Biological Properties of Water Soluble BPA" J.Med.Chem.38. 1673-1678 (1995)

Nao Nemoto、J.Cai、Naoki Asao、Satoshi Iwamoto、Yoshinori Yamamoto：“水溶性 BPA 的合成和生物特性”J.Med.Chem.38（1995）。

中村浩之,浅尾直樹,山本嘉則: "Palladium and Platinum-catalyzed Addition of Aldehydes" J.Chem.Soc.Chem.Commun.1271-1272 (1995)

Hiroyuki Nakamura、Naoki Asao、Yoshinori Yamamoto：“钯和铂催化的醛加成”J.Chem.Soc.Chem.Commun.1271-1272 (1995)

N.Tsukada, T.Shimada, Y.S.Gyoung, N.Asao, Y.Yamamoto: "A Three Component Coupling Approach to a chiral" J.Org. Chem.60. 143-148 (1995)

N.Tsukada、T.Shimada、Y.S.Gyoung、N.Asao、Y.Yamamoto：“手性的三组分耦合方法”J.Org。

門田功,小林克,浅尾直樹,山本嘉則: "Asymmetric Diels-Alder Reactions of TMHD-acrylate" J.Chem.Soc.Chem.Commun.1273-1274 (1995)

Isao Kadota、Katsu Kobayashi、Naoki Asao、Yoshinori Yamamoto：“TMHD-丙烯酸酯的不对称 Diels-Alder 反应” J.Chem.Soc.Chem.Commun.1273-1274 (1995)