(Z)-(2S,3S,5S)-2-bromomethyl-1-[bromo(trimethylsilyl)methylene]-3,5-bis(tert-butyldimethylsilyloxy)cyclohexane | 643025-35-8

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: (Z)-(2S,3S,5S)-2-bromomethyl-1-[bromo(trimethylsilyl)methylene]-3,5-bis(tert-butyldimethylsilyloxy)cyclohexane
• 英文别名: [(Z)-bromo-[(2S,3S,5S)-2-(bromomethyl)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene]methyl]-trimethylsilane
• CAS: 643025-35-8
• 化学式: C₂₃H₄₈Br₂O₂Si₃
• 分子量: 600.697
• InChiKey: SJKLFVNVCZUUTD-KKITZDHISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.1
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 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：

  (Z)-(2S,3S,5S)-2-bromomethyl-1-[bromo(trimethylsilyl)methylene]-3,5-bis(tert-butyldimethylsilyloxy)cyclohexane 在 caesium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 (Z)-(3S,5S)-1-bromomethylene-3,5-bis(tert-butyldimethylsilyloxy)-2-methylenecyclohexane
  参考文献：
  名称：

  New Convergent Synthesis of 1α,25-Dihydroxyvitamin D₃ and Its Analogues by Suzuki−Miyaura Coupling between A-Ring and C,D-Ring Parts

  摘要：

  A new convergent method for the synthesis of 1alpha,25-dihydroxyvitamin D-3 and its analogues has been developed that involves efficient preparation of the A-ring part la, (Z)-(3S,5R)-1-bromomethylene-3,5-bis(tert-butyldimethylsilyloxy)-2-methylenecyclohexane, starting from epichlorohydrin (4) and its Suzuki-Miyaura coupling reaction with the C,D-ring part 12. Thus, (R)-4 was converted to (3S,5R)-5-(tert-butyldimethylsilyloxy)-8-(trimethylsilyl)-oct-1-en-7-yn-3-ol (3a) through a ten-step reaction sequence in 49% overall yield. Compound 3a thus obtained was treated with a Ti(O-i-Pr)(4)/2 i-PrMgCl reagent and then with NBS to afford (Z)-(1S,2S,5R)-2-bromomethyl-3-[bromo(trimethylsilyl)methylene]-5-(tert-butyldimethylsilyloxy)cyclohexanol (10a) in 51% yield, from which la was obtained in 87% yield by sequential treatment with TBSCl/imidazole, DBU, and Cs2CO3. The resulting A-ring intermediate la was reacted with alkenylboronate 12 in the presence of a PdCl2(dppf) catalyst to furnish 1alpha,25-dihydroxyvitamin D-3 in 82% yield after protodesilylation. Similarly, all of the other three possible stereoisomers of A-ring parts 1b, 1c, and 1d were prepared, from which 1-epi-, 3-epi-, and 1,3-di-epi-1alpha,25-dihydroxyvitamin D-3 were synthesized by coupling with 12 in excellent yield, respectively. Starting from la and 1c, des-C,D-I(x,25-dihydroxyvitamin D-3 analogues, retiferol 13 and its 3-epi derivative, were also prepared, respectively.

  DOI：

  10.1021/jo0353435
• 作为产物：
  描述：

  (R,E)-5-(tert-butyldimethylsilyloxy)-8-(trimethylsilyl)oct-2-en-7-yn-1-ol 在 咪唑 、 titanium(IV) isopropylate 、 叔丁基过氧化氢 、 diisopropyl (L)-tartrate 、 异丙基氯化镁 、 碳酸氢钠 、 溶剂黄146 、 三乙胺 、 sodium iodide 、 锌 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 生成 (Z)-(2S,3S,5S)-2-bromomethyl-1-[bromo(trimethylsilyl)methylene]-3,5-bis(tert-butyldimethylsilyloxy)cyclohexane
  参考文献：
  名称：

  New Convergent Synthesis of 1α,25-Dihydroxyvitamin D₃ and Its Analogues by Suzuki−Miyaura Coupling between A-Ring and C,D-Ring Parts

  摘要：

  A new convergent method for the synthesis of 1alpha,25-dihydroxyvitamin D-3 and its analogues has been developed that involves efficient preparation of the A-ring part la, (Z)-(3S,5R)-1-bromomethylene-3,5-bis(tert-butyldimethylsilyloxy)-2-methylenecyclohexane, starting from epichlorohydrin (4) and its Suzuki-Miyaura coupling reaction with the C,D-ring part 12. Thus, (R)-4 was converted to (3S,5R)-5-(tert-butyldimethylsilyloxy)-8-(trimethylsilyl)-oct-1-en-7-yn-3-ol (3a) through a ten-step reaction sequence in 49% overall yield. Compound 3a thus obtained was treated with a Ti(O-i-Pr)(4)/2 i-PrMgCl reagent and then with NBS to afford (Z)-(1S,2S,5R)-2-bromomethyl-3-[bromo(trimethylsilyl)methylene]-5-(tert-butyldimethylsilyloxy)cyclohexanol (10a) in 51% yield, from which la was obtained in 87% yield by sequential treatment with TBSCl/imidazole, DBU, and Cs2CO3. The resulting A-ring intermediate la was reacted with alkenylboronate 12 in the presence of a PdCl2(dppf) catalyst to furnish 1alpha,25-dihydroxyvitamin D-3 in 82% yield after protodesilylation. Similarly, all of the other three possible stereoisomers of A-ring parts 1b, 1c, and 1d were prepared, from which 1-epi-, 3-epi-, and 1,3-di-epi-1alpha,25-dihydroxyvitamin D-3 were synthesized by coupling with 12 in excellent yield, respectively. Starting from la and 1c, des-C,D-I(x,25-dihydroxyvitamin D-3 analogues, retiferol 13 and its 3-epi derivative, were also prepared, respectively.

  DOI：

  10.1021/jo0353435

文献信息

• New Convergent Synthesis of 1α,25-Dihydroxyvitamin D₃ and Its Analogues by Suzuki−Miyaura Coupling between A-Ring and C,D-Ring Parts
  作者：Takeshi Hanazawa、Akiko Koyama、Kunio Nakata、Sentaro Okamoto、Fumie Sato

  DOI：10.1021/jo0353435

  日期：2003.12.1

  A new convergent method for the synthesis of 1alpha,25-dihydroxyvitamin D-3 and its analogues has been developed that involves efficient preparation of the A-ring part la, (Z)-(3S,5R)-1-bromomethylene-3,5-bis(tert-butyldimethylsilyloxy)-2-methylenecyclohexane, starting from epichlorohydrin (4) and its Suzuki-Miyaura coupling reaction with the C,D-ring part 12. Thus, (R)-4 was converted to (3S,5R)-5-(tert-butyldimethylsilyloxy)-8-(trimethylsilyl)-oct-1-en-7-yn-3-ol (3a) through a ten-step reaction sequence in 49% overall yield. Compound 3a thus obtained was treated with a Ti(O-i-Pr)(4)/2 i-PrMgCl reagent and then with NBS to afford (Z)-(1S,2S,5R)-2-bromomethyl-3-[bromo(trimethylsilyl)methylene]-5-(tert-butyldimethylsilyloxy)cyclohexanol (10a) in 51% yield, from which la was obtained in 87% yield by sequential treatment with TBSCl/imidazole, DBU, and Cs2CO3. The resulting A-ring intermediate la was reacted with alkenylboronate 12 in the presence of a PdCl2(dppf) catalyst to furnish 1alpha,25-dihydroxyvitamin D-3 in 82% yield after protodesilylation. Similarly, all of the other three possible stereoisomers of A-ring parts 1b, 1c, and 1d were prepared, from which 1-epi-, 3-epi-, and 1,3-di-epi-1alpha,25-dihydroxyvitamin D-3 were synthesized by coupling with 12 in excellent yield, respectively. Starting from la and 1c, des-C,D-I(x,25-dihydroxyvitamin D-3 analogues, retiferol 13 and its 3-epi derivative, were also prepared, respectively.