2-chloro-N-methyl-N-(2-phenylcyclohex-2-en-1-yl)-2-phenylsulfanylacetamide | 147949-58-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-chloro-N-methyl-N-(2-phenylcyclohex-2-en-1-yl)-2-phenylsulfanylacetamide
• CAS: 147949-58-4
• 化学式: C₂₁H₂₂ClNOS
• 分子量: 371.931
• InChiKey: VUMDYLVFIYMERE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-N-methyl-N-(2-phenylcyclohex-2-en-1-yl)-2-phenylsulfanylacetamide 在 tris(triphenylphosphine)ruthenium(II) chloride 作用下， 以 苯 为溶剂， 反应 2.0h， 以48%的产率得到(3R^*,3aR^*,4R^*,7aS^*)-4-Chlorooctahydro-1-methyl-3a-phenyl-3-(phenylthio)indol-2-one
  参考文献：
  名称：

  Ruthenium-catalyzed chlorine atom transfer cyclizations of N-allylic .alpha.-chloro-.alpha.-thioacetamides. Synthesis of (-)-trachelanthamidine and formal total synthesis of (.+-.)-haemanthidine and (.+-.)-pretazettine

  摘要：

  A new method for the synthesis of five-membered lactams by ruthenium-catalyzed chlorine atom transfer cyclizations of N-allylic alpha-chloro-alpha-thioacetamides and the application of the method to the synthesis of the title alkaloids are described. A benzene solution of N-allyl-N-methyl-alpha-chloro-alpha-(phenylthio)acetamide (6) was heated at 140-degrees-C in the presence of RuCl2(PPh3)3 to give alpha-thio-beta-(chloromethyl)-substituted gamma-lactam 8 as a mixture of cis and trans isomers in a ratio of ca. 3:7. NH congener 11, however, gave no cyclization product. Heating chloro sulfides 18 and 19, prepared from L-prolinol, with RuCl2(PPh3)3 afforded bicyclic lactams 20 and 21, respectively. Treatment of 20 with cesium propanoate gave predominantly cyclopropane derivative 25, whereas S-methyl congener 21 provided esters 24 in good yield. Desulfurization of 24 with Raney nickel followed by reduction with LiAlH4 furnished (-)-trachelanthamidine (28). On the other hand, N-(cyclohex-2-en-1-yl) derivative 30, when heated with RuCl2(PPh3)3, afforded octahydroindol-2-ones 31a,b. The formation of 31a,b indicated that the intramolecular addition of the chloro sulfide of 30 to the olefinic bond proceeded in an anti-mode. By contrast, 2-phenyl-substituted derivative 38 gave syn-addition product 39. The difference between the modes of cyclization of 30 and 38 can be explained by assuming the intermediacy of radical 34. When R = H, the chlorine atom attacks the convex face of the fused bicyclic system of 34 to lead to 31a,b, whereas the steric bulk of the angular phenyl group (R = Ph) is apparently sufficient to direct the chlorine atom to the concave face. Heating chloro sulfide 48, prepared in a highly stereocontrolled manner from cyclohexene 42, with RuCl2(PPh3)3 afforded bicyclic lactam 49. Oxidation of 49 with m-CPBA followed by Pummerer rearrangement/hydrolysis gave keto lactam 51, which was dehydrochlorinated with DBU to give olefin 52. LiAlH4 reduction of 52 and acylation with pivaloyl chloride provided ester 54, a key intermediate in Martin's total synthesis of (+/-)-haemanthidine (41) and (+/-)-pretazettine (40).

  DOI：

  10.1021/jo00061a005
• 作为产物：
  描述：

  (1R^*,2S^*)-2-(methylamino)-1-phenylcyclohexane-1-ol 在 N-氯代丁二酰亚胺 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氯化碳 、 二氯甲烷 、 苯 为溶剂， 反应 18.5h， 生成 2-chloro-N-methyl-N-(2-phenylcyclohex-2-en-1-yl)-2-phenylsulfanylacetamide
  参考文献：
  名称：

  Ruthenium-catalyzed chlorine atom transfer cyclizations of N-allylic .alpha.-chloro-.alpha.-thioacetamides. Synthesis of (-)-trachelanthamidine and formal total synthesis of (.+-.)-haemanthidine and (.+-.)-pretazettine

  摘要：

  A new method for the synthesis of five-membered lactams by ruthenium-catalyzed chlorine atom transfer cyclizations of N-allylic alpha-chloro-alpha-thioacetamides and the application of the method to the synthesis of the title alkaloids are described. A benzene solution of N-allyl-N-methyl-alpha-chloro-alpha-(phenylthio)acetamide (6) was heated at 140-degrees-C in the presence of RuCl2(PPh3)3 to give alpha-thio-beta-(chloromethyl)-substituted gamma-lactam 8 as a mixture of cis and trans isomers in a ratio of ca. 3:7. NH congener 11, however, gave no cyclization product. Heating chloro sulfides 18 and 19, prepared from L-prolinol, with RuCl2(PPh3)3 afforded bicyclic lactams 20 and 21, respectively. Treatment of 20 with cesium propanoate gave predominantly cyclopropane derivative 25, whereas S-methyl congener 21 provided esters 24 in good yield. Desulfurization of 24 with Raney nickel followed by reduction with LiAlH4 furnished (-)-trachelanthamidine (28). On the other hand, N-(cyclohex-2-en-1-yl) derivative 30, when heated with RuCl2(PPh3)3, afforded octahydroindol-2-ones 31a,b. The formation of 31a,b indicated that the intramolecular addition of the chloro sulfide of 30 to the olefinic bond proceeded in an anti-mode. By contrast, 2-phenyl-substituted derivative 38 gave syn-addition product 39. The difference between the modes of cyclization of 30 and 38 can be explained by assuming the intermediacy of radical 34. When R = H, the chlorine atom attacks the convex face of the fused bicyclic system of 34 to lead to 31a,b, whereas the steric bulk of the angular phenyl group (R = Ph) is apparently sufficient to direct the chlorine atom to the concave face. Heating chloro sulfide 48, prepared in a highly stereocontrolled manner from cyclohexene 42, with RuCl2(PPh3)3 afforded bicyclic lactam 49. Oxidation of 49 with m-CPBA followed by Pummerer rearrangement/hydrolysis gave keto lactam 51, which was dehydrochlorinated with DBU to give olefin 52. LiAlH4 reduction of 52 and acylation with pivaloyl chloride provided ester 54, a key intermediate in Martin's total synthesis of (+/-)-haemanthidine (41) and (+/-)-pretazettine (40).

  DOI：

  10.1021/jo00061a005

文献信息

• Ruthenium-catalyzed chlorine atom transfer cyclizations of N-allylic .alpha.-chloro-.alpha.-thioacetamides. Synthesis of (-)-trachelanthamidine and formal total synthesis of (.+-.)-haemanthidine and (.+-.)-pretazettine
  作者：Hiroyuki Ishibashi、Nahoko Uemura、Hiroshi Nakatani、Mika Okazaki、Tatsunori Sato、Nobuyuki Nakamura、Masazumi Ikeda

  DOI：10.1021/jo00061a005

  日期：1993.4

  A new method for the synthesis of five-membered lactams by ruthenium-catalyzed chlorine atom transfer cyclizations of N-allylic alpha-chloro-alpha-thioacetamides and the application of the method to the synthesis of the title alkaloids are described. A benzene solution of N-allyl-N-methyl-alpha-chloro-alpha-(phenylthio)acetamide (6) was heated at 140-degrees-C in the presence of RuCl2(PPh3)3 to give alpha-thio-beta-(chloromethyl)-substituted gamma-lactam 8 as a mixture of cis and trans isomers in a ratio of ca. 3:7. NH congener 11, however, gave no cyclization product. Heating chloro sulfides 18 and 19, prepared from L-prolinol, with RuCl2(PPh3)3 afforded bicyclic lactams 20 and 21, respectively. Treatment of 20 with cesium propanoate gave predominantly cyclopropane derivative 25, whereas S-methyl congener 21 provided esters 24 in good yield. Desulfurization of 24 with Raney nickel followed by reduction with LiAlH4 furnished (-)-trachelanthamidine (28). On the other hand, N-(cyclohex-2-en-1-yl) derivative 30, when heated with RuCl2(PPh3)3, afforded octahydroindol-2-ones 31a,b. The formation of 31a,b indicated that the intramolecular addition of the chloro sulfide of 30 to the olefinic bond proceeded in an anti-mode. By contrast, 2-phenyl-substituted derivative 38 gave syn-addition product 39. The difference between the modes of cyclization of 30 and 38 can be explained by assuming the intermediacy of radical 34. When R = H, the chlorine atom attacks the convex face of the fused bicyclic system of 34 to lead to 31a,b, whereas the steric bulk of the angular phenyl group (R = Ph) is apparently sufficient to direct the chlorine atom to the concave face. Heating chloro sulfide 48, prepared in a highly stereocontrolled manner from cyclohexene 42, with RuCl2(PPh3)3 afforded bicyclic lactam 49. Oxidation of 49 with m-CPBA followed by Pummerer rearrangement/hydrolysis gave keto lactam 51, which was dehydrochlorinated with DBU to give olefin 52. LiAlH4 reduction of 52 and acylation with pivaloyl chloride provided ester 54, a key intermediate in Martin's total synthesis of (+/-)-haemanthidine (41) and (+/-)-pretazettine (40).