[(2R,3R,5S)-5-bromo-3-chloro-2,6,6-trimethyloxan-2-yl]methoxy-tert-butyl-dimethylsilane | 204918-30-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: [(2R,3R,5S)-5-bromo-3-chloro-2,6,6-trimethyloxan-2-yl]methoxy-tert-butyl-dimethylsilane
• CAS: 204918-30-9
• 化学式: C₁₅H₃₀BrClO₂Si
• 分子量: 385.844
• InChiKey: LOKVZDSHXRGIHC-YWPYICTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.34
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [(2R,3R,5S)-5-bromo-3-chloro-2,6,6-trimethyloxan-2-yl]methoxy-tert-butyl-dimethylsilane 在 草酰氯 、 四丁基氟化铵 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 24.5h， 生成 (2R,3R,5S)-5-bromo-3-chloro-2,6,6-trimethyltetrahydropyran-2-carboxaldehyde
  参考文献：
  名称：

  Total Syntheses of the Cytotoxic Marine Natural Product, Aplysiapyranoid C¹

  摘要：

  The first total syntheses of the cytotoxic marine natural product, aplysiapyranoid C, 1c, are reported. The Wittig reaction of 4-methyl-3-pentenyltriphenylphosphorane with the THP ether of hydroxyacetone gave in 88% yield the Z-alkene 4 which was hydrolyzed to the alcohol 5 in 72% yield. Sharpless asymmetric epoxidation of 5 afforded the epoxy alcohol 6 in 91% yield and 81% ee, Opening of the epoxide of 6 with ammonium chloride in DMSO gave in 76% yield the chloro diol 7 which was converted to the primary TBS ether 8 in 95% yield. Opening of the epoxy alcohol 6 with HCl and Ti(OiPr)(4) afforded the desired chloro diol 7 as the minor product along with the rearranged chloromethyl diol 9. This compound is presumably formed by opening of the protonated epoxide to give a butenyl cation which rearranges to the cyclopropylcarbinyl cation and is then trapped by chloride ion at the unsubstituted cyclopropyl carbon, regenerating the alkene. Cyclization of the TBS ether 8 with tetrabromocyclohexadienone (TBCO) afforded a mixture of all four possible cyclization products, the desired tetrahydropyrans 11a,b and the tetrahydrofurans 12a,b with the former being isolated in 70% yield. Hydrolysis of the TBS ether afforded the primary alcohols from which the desired isomer, 13, could be isolated (24% overall from 8), Swern oxidation furnished the aldehyde 14 which was subjected to the Takai chlorovinylation to give a mixture of aplysiapyranoid C Ic and the reduced product, dechloroaplysiapyranoid C 15. This dechlorination under these conditions is quite unusual. A second synthesis of aplysiapyranoid C avoided this problem. Selective protection of the more hindered tertiary alcohol of the chloro diol 7 afforded the primary alcohol 16 in which the tertiary alcohol was protected as the triethylsilyl ether. Swern oxidation, Takai reaction, and desilylation gave the dichloro alkenol 17 in 52% overall yield. In this case, only a small amount of the corresponding dechlorinated product was obtained. Final cyclization of 17 with TBCO afforded aplysiapyranoid C Ic as the major product in an isolated yield of 43%. Thus we have completed two total syntheses of aplysiapyranoid C Ic from the simple bromide 2 in eight or nine steps and good overall yield.

  DOI：

  10.1021/jo972228j
• 作为产物：
  描述：

  (2R,3R)-3-chloro-2,6-dimethyl-1-[(1,1-dimethylethyl)dimethylsilyloxy]-5-hepten-2-ol 在 四溴环己二烯-1-酮 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 [(2R,3R,5S)-5-(1-Bromo-1-methyl-ethyl)-3-chloro-2-methyl-tetrahydro-furan-2-ylmethoxy]-tert-butyl-dimethyl-silane 、 [(2R,3R,5R)-5-(1-Bromo-1-methyl-ethyl)-3-chloro-2-methyl-tetrahydro-furan-2-ylmethoxy]-tert-butyl-dimethyl-silane 、 ((2R,3R,5R)-5-Bromo-3-chloro-2,6,6-trimethyl-tetrahydro-pyran-2-ylmethoxy)-tert-butyl-dimethyl-silane 、 [(2R,3R,5S)-5-bromo-3-chloro-2,6,6-trimethyloxan-2-yl]methoxy-tert-butyl-dimethylsilane
  参考文献：
  名称：

  Total Syntheses of the Cytotoxic Marine Natural Product, Aplysiapyranoid C¹

  摘要：

  The first total syntheses of the cytotoxic marine natural product, aplysiapyranoid C, 1c, are reported. The Wittig reaction of 4-methyl-3-pentenyltriphenylphosphorane with the THP ether of hydroxyacetone gave in 88% yield the Z-alkene 4 which was hydrolyzed to the alcohol 5 in 72% yield. Sharpless asymmetric epoxidation of 5 afforded the epoxy alcohol 6 in 91% yield and 81% ee, Opening of the epoxide of 6 with ammonium chloride in DMSO gave in 76% yield the chloro diol 7 which was converted to the primary TBS ether 8 in 95% yield. Opening of the epoxy alcohol 6 with HCl and Ti(OiPr)(4) afforded the desired chloro diol 7 as the minor product along with the rearranged chloromethyl diol 9. This compound is presumably formed by opening of the protonated epoxide to give a butenyl cation which rearranges to the cyclopropylcarbinyl cation and is then trapped by chloride ion at the unsubstituted cyclopropyl carbon, regenerating the alkene. Cyclization of the TBS ether 8 with tetrabromocyclohexadienone (TBCO) afforded a mixture of all four possible cyclization products, the desired tetrahydropyrans 11a,b and the tetrahydrofurans 12a,b with the former being isolated in 70% yield. Hydrolysis of the TBS ether afforded the primary alcohols from which the desired isomer, 13, could be isolated (24% overall from 8), Swern oxidation furnished the aldehyde 14 which was subjected to the Takai chlorovinylation to give a mixture of aplysiapyranoid C Ic and the reduced product, dechloroaplysiapyranoid C 15. This dechlorination under these conditions is quite unusual. A second synthesis of aplysiapyranoid C avoided this problem. Selective protection of the more hindered tertiary alcohol of the chloro diol 7 afforded the primary alcohol 16 in which the tertiary alcohol was protected as the triethylsilyl ether. Swern oxidation, Takai reaction, and desilylation gave the dichloro alkenol 17 in 52% overall yield. In this case, only a small amount of the corresponding dechlorinated product was obtained. Final cyclization of 17 with TBCO afforded aplysiapyranoid C Ic as the major product in an isolated yield of 43%. Thus we have completed two total syntheses of aplysiapyranoid C Ic from the simple bromide 2 in eight or nine steps and good overall yield.

  DOI：

  10.1021/jo972228j

文献信息

• Total Syntheses of the Cytotoxic Marine Natural Product, Aplysiapyranoid C¹
  作者：Michael E. Jung、Bruce T. Fahr、Derin C. D'Amico

  DOI：10.1021/jo972228j

  日期：1998.5.1

  The first total syntheses of the cytotoxic marine natural product, aplysiapyranoid C, 1c, are reported. The Wittig reaction of 4-methyl-3-pentenyltriphenylphosphorane with the THP ether of hydroxyacetone gave in 88% yield the Z-alkene 4 which was hydrolyzed to the alcohol 5 in 72% yield. Sharpless asymmetric epoxidation of 5 afforded the epoxy alcohol 6 in 91% yield and 81% ee, Opening of the epoxide of 6 with ammonium chloride in DMSO gave in 76% yield the chloro diol 7 which was converted to the primary TBS ether 8 in 95% yield. Opening of the epoxy alcohol 6 with HCl and Ti(OiPr)(4) afforded the desired chloro diol 7 as the minor product along with the rearranged chloromethyl diol 9. This compound is presumably formed by opening of the protonated epoxide to give a butenyl cation which rearranges to the cyclopropylcarbinyl cation and is then trapped by chloride ion at the unsubstituted cyclopropyl carbon, regenerating the alkene. Cyclization of the TBS ether 8 with tetrabromocyclohexadienone (TBCO) afforded a mixture of all four possible cyclization products, the desired tetrahydropyrans 11a,b and the tetrahydrofurans 12a,b with the former being isolated in 70% yield. Hydrolysis of the TBS ether afforded the primary alcohols from which the desired isomer, 13, could be isolated (24% overall from 8), Swern oxidation furnished the aldehyde 14 which was subjected to the Takai chlorovinylation to give a mixture of aplysiapyranoid C Ic and the reduced product, dechloroaplysiapyranoid C 15. This dechlorination under these conditions is quite unusual. A second synthesis of aplysiapyranoid C avoided this problem. Selective protection of the more hindered tertiary alcohol of the chloro diol 7 afforded the primary alcohol 16 in which the tertiary alcohol was protected as the triethylsilyl ether. Swern oxidation, Takai reaction, and desilylation gave the dichloro alkenol 17 in 52% overall yield. In this case, only a small amount of the corresponding dechlorinated product was obtained. Final cyclization of 17 with TBCO afforded aplysiapyranoid C Ic as the major product in an isolated yield of 43%. Thus we have completed two total syntheses of aplysiapyranoid C Ic from the simple bromide 2 in eight or nine steps and good overall yield.