(3S,4S)-3-<(R)-1-(Formyloxy)ethyl>-1-<(4-methoxyphenyl)methyl>-4-<(phenylthio)methyl>-2-azetidinone | 161806-11-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (3S,4S)-3-<(R)-1-(Formyloxy)ethyl>-1-<(4-methoxyphenyl)methyl>-4-<(phenylthio)methyl>-2-azetidinone
• 英文别名: [(1R)-1-[(3S,4S)-1-[(4-methoxyphenyl)methyl]-2-oxo-4-(phenylsulfanylmethyl)azetidin-3-yl]ethyl] formate
• CAS: 161806-11-7
• 化学式: C₂₁H₂₃NO₄S
• 分子量: 385.484
• InChiKey: DNMJCGLOLYTOCU-CDHQVMDDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  81.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,4S)-3-<(R)-1-(Formyloxy)ethyl>-1-<(4-methoxyphenyl)methyl>-4-<(phenylthio)methyl>-2-azetidinone 在 咪唑 、 2,6-二甲基吡啶 、 盐酸 、 potassium permanganate 、 碳酸氢钠 、 potassium carbonate 、 间氯过氧苯甲酸 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.5h， 生成 (3R,4R)-4-Acetoxy-3-<(R)-1-<(tert-butyldimethylsilyl)oxy>ethyl>-1-<(4-methoxyphenyl)methyl>-2-azetidinone
  参考文献：
  名称：

  Sulfur-Directed Regioselective Radical Cyclization Leading to .beta.-Lactams: Formal Synthesis of (.+-.)-PS-5 and (+)-Thienamycin

  摘要：

  A new method for the synthesis of beta-lactams by tributyltin hydride (Bu(3)SnH)-mediated radical cyclizations of N-ethenyl-alpha-bromo amides bearing sulfur-substituent(s) at the terminus of the N-vinylic bond is described. N-[2-(Phenylthio)ethenyl]-alpha-bromoacetamide (11), upon treatment with Bu(3)SnH in the presence of azobis(isobutyronitrile) (AIBN) in boiling toluene, underwent radical cyclization in a 4-exo-trig manner to give beta-lactam 13, but in low yield (22%), whereas N-[2,2-bis(phenylthio)ethenyl] congener 23 cyclized with a high degree of efficiency to give beta-lactam 25 and a partially desulfurized lactam 13 in 70% combined yield. The effectiveness of the 4-exo cyclization of 23 can be explained in terms of the high stability of the intermediate of radical 19b. Similar treatment of alpha-bromobutanamide 24 with Bu(3)SnH afforded, in 58% yield, beta-lactam 26, which was transformed, via aldehyde 31, into the key intermediate 35 for the synthesis of(+/-)-PS-5 (36). 1,2-Asymmetric induction in radical cyclizations leading to beta-lactams was then examined. Cyclization of (2S,3R)-3-acetoxy-2-bromo-N-[2-(phenylthio)ethenyl]butanamide (38) proceeded with no diastereoselectivity to give beta-lactams 40a and 40b in approximately equal amounts. However, 2,2-bis(phenylthio) congener 39 provided (3R,4R)-2-azetidinone 41a and its (3S,4S)-isomer 41b in a ratio of ca. 2:1. Similarly, (2R,3S)-butanamide 47 afforded 48a as a major product. Saponification of 48a followed by partial desulfurization of 49 gave alcohol 50, which was then subjected to Mitsunobu inversion to afford 52. This compound was converted into the key intermediate 56 for the synthesis of (+)-thienamycin (58). Reversibility of the radical cyclization leading to the beta-lactams is discussed.

  DOI：

  10.1021/jo00110a035
• 作为产物：
  描述：

  (3SR,4SR)-3-<(S)-1-Acetoxyethyl>-1-<(4-methoxyphenyl)methyl>-4--2-azetidinone 在 sodium hydroxide 、 偶氮二异丁腈 、 偶氮二甲酸二异丙酯 、 三正丁基氢锡 、 三苯基膦 作用下， 以 四氢呋喃 、 吡啶 、 甲苯 为溶剂， 反应 16.0h， 生成 (3S,4S)-3-<(R)-1-(Formyloxy)ethyl>-1-<(4-methoxyphenyl)methyl>-4-<(phenylthio)methyl>-2-azetidinone
  参考文献：
  名称：

  Sulfur-Directed Regioselective Radical Cyclization Leading to .beta.-Lactams: Formal Synthesis of (.+-.)-PS-5 and (+)-Thienamycin

  摘要：

  A new method for the synthesis of beta-lactams by tributyltin hydride (Bu(3)SnH)-mediated radical cyclizations of N-ethenyl-alpha-bromo amides bearing sulfur-substituent(s) at the terminus of the N-vinylic bond is described. N-[2-(Phenylthio)ethenyl]-alpha-bromoacetamide (11), upon treatment with Bu(3)SnH in the presence of azobis(isobutyronitrile) (AIBN) in boiling toluene, underwent radical cyclization in a 4-exo-trig manner to give beta-lactam 13, but in low yield (22%), whereas N-[2,2-bis(phenylthio)ethenyl] congener 23 cyclized with a high degree of efficiency to give beta-lactam 25 and a partially desulfurized lactam 13 in 70% combined yield. The effectiveness of the 4-exo cyclization of 23 can be explained in terms of the high stability of the intermediate of radical 19b. Similar treatment of alpha-bromobutanamide 24 with Bu(3)SnH afforded, in 58% yield, beta-lactam 26, which was transformed, via aldehyde 31, into the key intermediate 35 for the synthesis of(+/-)-PS-5 (36). 1,2-Asymmetric induction in radical cyclizations leading to beta-lactams was then examined. Cyclization of (2S,3R)-3-acetoxy-2-bromo-N-[2-(phenylthio)ethenyl]butanamide (38) proceeded with no diastereoselectivity to give beta-lactams 40a and 40b in approximately equal amounts. However, 2,2-bis(phenylthio) congener 39 provided (3R,4R)-2-azetidinone 41a and its (3S,4S)-isomer 41b in a ratio of ca. 2:1. Similarly, (2R,3S)-butanamide 47 afforded 48a as a major product. Saponification of 48a followed by partial desulfurization of 49 gave alcohol 50, which was then subjected to Mitsunobu inversion to afford 52. This compound was converted into the key intermediate 56 for the synthesis of (+)-thienamycin (58). Reversibility of the radical cyclization leading to the beta-lactams is discussed.

  DOI：

  10.1021/jo00110a035

文献信息

• Sulfur-Directed Regioselective Radical Cyclization Leading to .beta.-Lactams: Formal Synthesis of (.+-.)-PS-5 and (+)-Thienamycin
  作者：Hiroyuki Ishibashi、Chisato Kameoka、Hiroko Iriyama、Kazuya Kodama、Tatsunori Sato、Masazumi Ikeda

  DOI：10.1021/jo00110a035

  日期：1995.3

  A new method for the synthesis of beta-lactams by tributyltin hydride (Bu(3)SnH)-mediated radical cyclizations of N-ethenyl-alpha-bromo amides bearing sulfur-substituent(s) at the terminus of the N-vinylic bond is described. N-[2-(Phenylthio)ethenyl]-alpha-bromoacetamide (11), upon treatment with Bu(3)SnH in the presence of azobis(isobutyronitrile) (AIBN) in boiling toluene, underwent radical cyclization in a 4-exo-trig manner to give beta-lactam 13, but in low yield (22%), whereas N-[2,2-bis(phenylthio)ethenyl] congener 23 cyclized with a high degree of efficiency to give beta-lactam 25 and a partially desulfurized lactam 13 in 70% combined yield. The effectiveness of the 4-exo cyclization of 23 can be explained in terms of the high stability of the intermediate of radical 19b. Similar treatment of alpha-bromobutanamide 24 with Bu(3)SnH afforded, in 58% yield, beta-lactam 26, which was transformed, via aldehyde 31, into the key intermediate 35 for the synthesis of(+/-)-PS-5 (36). 1,2-Asymmetric induction in radical cyclizations leading to beta-lactams was then examined. Cyclization of (2S,3R)-3-acetoxy-2-bromo-N-[2-(phenylthio)ethenyl]butanamide (38) proceeded with no diastereoselectivity to give beta-lactams 40a and 40b in approximately equal amounts. However, 2,2-bis(phenylthio) congener 39 provided (3R,4R)-2-azetidinone 41a and its (3S,4S)-isomer 41b in a ratio of ca. 2:1. Similarly, (2R,3S)-butanamide 47 afforded 48a as a major product. Saponification of 48a followed by partial desulfurization of 49 gave alcohol 50, which was then subjected to Mitsunobu inversion to afford 52. This compound was converted into the key intermediate 56 for the synthesis of (+)-thienamycin (58). Reversibility of the radical cyclization leading to the beta-lactams is discussed.