cis-4-tert-butyl-2-methylpiperidine-1-carboxyclic acid tert-butyl ester | 126503-07-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: cis-4-tert-butyl-2-methylpiperidine-1-carboxyclic acid tert-butyl ester
• 英文别名: N-(tert-butoxycarbonyl)-2-methyl-4-tert-butylpiperidine；N-Boc-2-methyl-4-tert-butylpiperidine；tert-butyl (2R,4R)-4-tert-butyl-2-methylpiperidine-1-carboxylate
• CAS: 126503-07-9；133165-19-2
• 化学式: C₁₅H₂₉NO₂
• 分子量: 255.401
• InChiKey: LABFHTAJVLWYLX-VXGBXAGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  cis-4-tert-butyl-2-methylpiperidine-1-carboxyclic acid tert-butyl ester 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 以47%的产率得到cis-4-tert-butyl-1,2-dimethylpiperidine
  参考文献：
  名称：

  构象锁定的α-氨基有机锡烷和α-氨基有机锂的合成和反应性。发现了一种令人惊讶的过渡金属构造要求。

  摘要：

  [方程式-见正文]在重金属化反应（Sn-Li交换）和与亲电试剂的反应中，评估了被4-叔丁基取代基构象锁定的2-三丁基锡烷基-N-甲基哌啶。当锡是赤道的时，与羰基亲电试剂的反应一样，过渡金属化反应会平稳进行。卤代烷似乎经历了单电子转移反应，提供了非选择性烷基化产物以及自由基歧化产物。出乎意料的是，轴向取向的锡未能进行金属转移，这表明氮孤对与碳-锡键之间的倾斜关系是金属转移的必要条件。

  DOI：

  10.1021/ol005770u
• 作为产物：
  描述：

  4-叔丁基哌啶 在 四甲基乙二胺 、 仲丁基锂 作用下， 以 乙醚 、 二氯甲烷 、 环己烷 为溶剂， 反应 33.0h， 生成 cis-4-tert-butyl-2-methylpiperidine-1-carboxyclic acid tert-butyl ester
  参考文献：
  名称：

  构象锁定的α-氨基有机锡烷和α-氨基有机锂的合成和反应性。发现了一种令人惊讶的过渡金属构造要求。

  摘要：

  [方程式-见正文]在重金属化反应（Sn-Li交换）和与亲电试剂的反应中，评估了被4-叔丁基取代基构象锁定的2-三丁基锡烷基-N-甲基哌啶。当锡是赤道的时，与羰基亲电试剂的反应一样，过渡金属化反应会平稳进行。卤代烷似乎经历了单电子转移反应，提供了非选择性烷基化产物以及自由基歧化产物。出乎意料的是，轴向取向的锡未能进行金属转移，这表明氮孤对与碳-锡键之间的倾斜关系是金属转移的必要条件。

  DOI：

  10.1021/ol005770u

文献信息

• .alpha.-Lithioamine synthetic equivalents: syntheses of diastereoisomers from the Boc-piperidines
  作者：Peter Beak、Won Koo Lee

  DOI：10.1021/jo00296a008

  日期：1990.4
• .alpha.-Lithioamine synthetic equivalents: syntheses of diastereoisomers from Boc derivatives of cyclic amines
  作者：Peter Beak、Won Koo Lee

  DOI：10.1021/jo00057a024

  日期：1993.2

  Sequences of alpha'-lithiations and electrophilic substitutions of Boc-pyrrolidines, Boc-piperidines, and Boc-hexahydroazepines that provide compounds which are substituted adjacent to nitrogen are reported, and the pathways of the reactions are discussed. By this methodology monosubstituted 2 and disubstituted 2,4,2,6, and 2,5 Boc-piperidines are obtained as single or separable diastereoisomers consistent with equatorial lithiations and retentive electrophilic substitution in chair conformations. Both cis and trans 2,6-disubstituted diastereoisomers can be prepared, and control of diastereoselectivity is demonstrated by syntheses of solenopsin A, a 2,6-trans-disubstituted piperidine, and of Boc-dihydropinidine, a 2,6-cis-disubstituted piperidine. In the case of 3-methoxy-Boc-piperidine elimination of methoxide occurs upon lithiation, and with cis-2,4-disubstituted Boc-piperidines the electrophile is introduced with trans stereochemistry at C-6. These reactions are suggested to involve twist boat conformations consistent with an X-ray crystal structure of 2-methyl-6-(trimethylstannyl)-4-phenyl-N-Boc-piperidine. Boc-pyrrolidine lithiates more rapidly than Boc-piperidine, provides 2-substituted products with electrophiles, and on further lithiation-substitution gives 2,5-cis- and -trans-substituted products. Boc-perhydroazepine provides 2-substituted products by the sequence and on further lithiation-substitution gives 2,7-trans-disubstituted products.
• Stereochemistry of alkylation of .alpha.-lithio piperidines: differing effects of formamidine and urethane activating groups
  作者：Thomas T. Shawe、A. I. Meyers

  DOI：10.1021/jo00008a033

  日期：1991.4

  The stereochemistry of alkylation of alpha-lithio-N-(N'-tert-butylformimidoyl)-4-tert-butylpiperidines was studied. Monoalkylation proceeded to give equatorial 2-substituted piperidines, which in turn gave diequatorial 2,6-disubstituted piperidines when subjected to a second lithiation-alkylation procedure. The stereochemical result of the second alkylation is in contrast to alpha-lithio-2-substituted piperidines that are stabilized by the N-(tert-butoxycarbonyl) group; these gave the axial 6-substituted piperidine on treatment with electrophiles. A mechanistic rationalization of these results is given that invokes nonbonding interactions between the stabilizing groups and piperidine ring substituents.
• BEAK, PETER;LEE, WON KOO, J. ORG. CHEM., 55,(1990) N, C. 2578-2580
  作者：BEAK, PETER、LEE, WON KOO

  DOI：——

  日期：——