(1S,2R)-1-(tert-butyldiphenylsilyloxy)methyl-2-formyl-2-phenylcyclopropane | 625389-74-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1S,2R)-1-(tert-butyldiphenylsilyloxy)methyl-2-formyl-2-phenylcyclopropane
• 英文别名: (1R,2S)-2-[[tert-butyl(diphenyl)silyl]oxymethyl]-1-phenylcyclopropane-1-carbaldehyde
• CAS: 625389-74-4
• 化学式: C₂₇H₃₀O₂Si
• 分子量: 414.62
• InChiKey: MUHBNFOGEYNUOA-KCWPFWIISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.72
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1S,2R)-1-(tert-butyldiphenylsilyloxy)methyl-2-formyl-2-phenylcyclopropane 在 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 作用下， 以 水 、 丙酮 为溶剂， 反应 12.0h， 以86%的产率得到(1R,2S)-2-((tert-butyldiphenylsilyloxy)methyl)-1-phenylcyclopropanecarboxylic acid
  参考文献：
  名称：

  通过还原性自由基脱羧反应构建顺式环丙烷。对映选择性合成顺式和反式-1-芳基哌嗪基-2-苯基环丙烷，用作抗多巴胺能药物。

  摘要：

  （1S，2S）-，（1S，2R）-和（1R，2S）-1-（2,4-二甲基苯基）哌嗪基-2-苯基环丙烷（分别为2a，3和ent-3）以Barton还原性自由基脱羧为关键步骤，从手性表氯醇合成了被设计为氟哌啶醇（1）（一种临床有效的抗精神病药）的受构象限制的类似物。由（S）-表氯醇（（S）-7）制得的（1S，2R）-1-（叔丁基二苯基甲硅烷氧基）甲基-2-羧基-2-苯基环丙烷（5）被转化为其N-羟基吡啶-2-硫酮酸酯12，为还原性自由基脱羧的底物。当在Et3B或AIBN存在下用TMS3SiH处理12时，发生了从大体积甲硅烷氧基甲基部分相反的一侧对环丙基自由基中间体进行脱羧和随后的氢化物攻击，导致选择性地形成具有顺式-环丙烷结构的相应的还原性脱羧产物4-顺式。由4-顺式容易地合成出顺式-环丙烷型目标化合物3。从（R）-表氯醇（（R）-7）开始，类似地合成了ent-3。用由Bu2Mg和i-Pr2N

  DOI：

  10.1021/jo0302206
• 作为产物：
  描述：

  (+)-(1R,2S)-(2-hydroxymethyl-1-phenyl-cyclopropyl)-methanol 在 咪唑 、 草酰氯 、 二甲基亚砜 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.17h， 生成 (1S,2R)-1-(tert-butyldiphenylsilyloxy)methyl-2-formyl-2-phenylcyclopropane
  参考文献：
  名称：

  通过还原性自由基脱羧反应构建顺式环丙烷。对映选择性合成顺式和反式-1-芳基哌嗪基-2-苯基环丙烷，用作抗多巴胺能药物。

  摘要：

  （1S，2S）-，（1S，2R）-和（1R，2S）-1-（2,4-二甲基苯基）哌嗪基-2-苯基环丙烷（分别为2a，3和ent-3）以Barton还原性自由基脱羧为关键步骤，从手性表氯醇合成了被设计为氟哌啶醇（1）（一种临床有效的抗精神病药）的受构象限制的类似物。由（S）-表氯醇（（S）-7）制得的（1S，2R）-1-（叔丁基二苯基甲硅烷氧基）甲基-2-羧基-2-苯基环丙烷（5）被转化为其N-羟基吡啶-2-硫酮酸酯12，为还原性自由基脱羧的底物。当在Et3B或AIBN存在下用TMS3SiH处理12时，发生了从大体积甲硅烷氧基甲基部分相反的一侧对环丙基自由基中间体进行脱羧和随后的氢化物攻击，导致选择性地形成具有顺式-环丙烷结构的相应的还原性脱羧产物4-顺式。由4-顺式容易地合成出顺式-环丙烷型目标化合物3。从（R）-表氯醇（（R）-7）开始，类似地合成了ent-3。用由Bu2Mg和i-Pr2N

  DOI：

  10.1021/jo0302206

文献信息

• Synthesis of 1-arylpiperazyl-2-phenylcyclopropanes designed as antidopaminergic agents: Cyclopropane-based conformationally restricted analogs of haloperidol
  作者：Kazuya Yamaguchi、Yuji Kazuta、Kazufumi Hirano、Shizuo Yamada、Akira Matsuda、Satoshi Shuto

  DOI：10.1016/j.bmc.2008.08.061

  日期：2008.10

  A series of the cyclopropane-based conformationally restricted analogs of haloperidol were designed as potential antidopaminergic agents and were effectively synthesized using highly stereoselective Grignard reaction with tert-butanesulfinyl imines as the key step. Pharmacological evaluation of the compounds showed that the conformational restriction method can effectively work for improving the pharmacological

  氟哌啶醇的一系列基于环丙烷的构象受限的类似物被设计为潜在的抗多巴胺能药物，并通过高度立体选择性格氏试剂与叔丁烷亚磺酰基亚胺作为关键步骤有效合成。化合物的药理评价表明，构象限制方法可以有效地改善母体化合物的药理选择性，也可以用于研究生物活性构象。
• The unusual 1,4-chelation-controlled nucleophilic addition to aldehydes with high stereoselectivity. A systematic study of stereoselectivity in the addition reaction of carbon nucleophiles to cis-substituted cyclopropanecarbaldehydes
  作者：Yuji Kazuta、Hiroshi Abe、Tamotsu Yamamoto、Akira Matsuda、Satoshi Shuto

  DOI：10.1016/j.tet.2004.05.063

  日期：2004.7

  The addition reaction of carbon nucleophiles to cis-substituted cyclopropanecarbaldehydes was systematically investigated. Ab initio calculations of model cyclopropanecarbaldehydes suggested that the bisected s-cis and s-trans conformers are the only two minimum energy conformers, which are stabilized due to the pi-donating stereoelectronic effect of the cyclopropane ring. The experimental results of a series of substrates, that is, cyclopropanecarbaldehydes 1-5 bearing a cis-(tert-butyldiphenyisilyloxy)methyl group, a cis-benzyloxymethyl group, a cis-(p-methoxybenzyloxy)methyl group, cis-N,N-diethylcarbamoyl and trans-phenyl groups, and cis-(tert-butyldiphenylsilyloxy)methyl and trans-phenyl groups, respectively, showed that highly anti-selective Grignard additions could be realized. It turned out that it occurred via an unusual 7-membered 1,4-chelation-controlled pathway. Highly stereoselective Grignard addition via the chelation-controlled pathway occurred even in the reaction of the usually non-chelating silyl ether-type substrate 5. The results have great importance because the 1,4-chelation-controlled stereoselective addition reactions can indeed be realized. Under non-chelation conditions, the syn-products were produced with moderate stereoselectivity, which are likely to be formed via the bisected s-cis conformation-like transition state stabilized by the characteristic orbital interaction. These reactions, especially the chelation-controlled reaction, should be useful because of their t stereoselectivity and stereochemical predictability. (C) 2004 Elsevier Ltd. All rights reserved.
• Construction of a <i>cis</i>-Cyclopropane via Reductive Radical Decarboxylation. Enantioselective Synthesis of <i>cis-</i> and <i>trans-</i>1-Arylpiperazyl-2-phenylcyclopropanes Designed as Antidopaminergic Agents
  作者：Kazuya Yamaguchi、Yuji Kazuta、Hiroshi Abe、Akira Matsuda、Satoshi Shuto

  DOI：10.1021/jo0302206

  日期：2003.11.1

  Barton reductive radical decarboxylation as the key step. (1S,2R)-1-(tert-Butyldiphenylsilyloxy)methyl-2-carboxy-2-phenylcyclopropane (5), which was prepared from (S)-epichlorohydrin ((S)-7), was converted into its N-hydroxypyridine-2-thione ester 12, the substrate for the reductive radical decarboxylation. When 12 was treated with TMS3SiH in the presence of Et3B or AIBN, the decarboxylation and subsequent

  （1S，2S）-，（1S，2R）-和（1R，2S）-1-（2,4-二甲基苯基）哌嗪基-2-苯基环丙烷（分别为2a，3和ent-3）以Barton还原性自由基脱羧为关键步骤，从手性表氯醇合成了被设计为氟哌啶醇（1）（一种临床有效的抗精神病药）的受构象限制的类似物。由（S）-表氯醇（（S）-7）制得的（1S，2R）-1-（叔丁基二苯基甲硅烷氧基）甲基-2-羧基-2-苯基环丙烷（5）被转化为其N-羟基吡啶-2-硫酮酸酯12，为还原性自由基脱羧的底物。当在Et3B或AIBN存在下用TMS3SiH处理12时，发生了从大体积甲硅烷氧基甲基部分相反的一侧对环丙基自由基中间体进行脱羧和随后的氢化物攻击，导致选择性地形成具有顺式-环丙烷结构的相应的还原性脱羧产物4-顺式。由4-顺式容易地合成出顺式-环丙烷型目标化合物3。从（R）-表氯醇（（R）-7）开始，类似地合成了ent-3。用由Bu2Mg和i-Pr2N