1-哌啶羧酸,2-甲基-6-丙基-,1,1-二甲基乙基酯,(2R,6S)-rel- | 132410-23-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 中文名称: 1-哌啶羧酸,2-甲基-6-丙基-,1,1-二甲基乙基酯,(2R,6S)-rel-
• 英文名称: N-Boc-dihydropinidine
• 英文别名: tert-butyl (2S,6R)-2-methyl-6-propylpiperidine-1-carboxylate
• CAS: 132410-23-2
• 化学式: C₁₄H₂₇NO₂
• 分子量: 241.374
• InChiKey: VUYCICJKIMXBKT-NWDGAFQWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  17
• 可旋转键数：
  4
• 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：

  1-哌啶羧酸,2-甲基-6-丙基-,1,1-二甲基乙基酯,(2R,6S)-rel- 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以90%的产率得到(2S,6R)-dihydropinidine hydrochloride
  参考文献：
  名称：

  对映选择性合成2-烷基-和2,6-二烷基哌啶生物碱：（-）-coniine，（-）-solenopsin A和（-）-dihydropinidine盐酸盐的制备。

  摘要：

  [反应：见正文]锂化-取代，对映选择性氢化和非对映选择性锂化-取代的序列提供了2-取代的和顺式和反式2,6-二取代的哌啶的高效高对映选择性的合成。该方法论通过合成（-）-芥氨酸，（-）-血脂素A和（-）-二氢吡啶为盐酸盐来证明。

  DOI：

  10.1021/ol9912534
• 作为产物：
  描述：

  4-氯吡啶 在 palladium on activated charcoal 正丁基锂 、 氢气 、 lithium carbonate 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 3.83h， 生成 1-哌啶羧酸,2-甲基-6-丙基-,1,1-二甲基乙基酯,(2R,6S)-rel-
  参考文献：
  名称：

  Stereocontrolled preparation of cis- and trans-2,6-dialkylpiperidines via 1-acyldihydropyridine intermediates. Synthesis of (.+-.)-solenopsin A and (.+-.)-dihydropinidine

  摘要：

  The stereoselective reduction of 1-(tert-butoxycarbonyl)-4-chloro-2,6-dialkyl-1,2-dihydropyridines 6 and 22 was studied. Reduction of 6 with Et3SiH/TFA gave the cis-2,6-dialkyl-1,2,5,6-tetrahydropyridine 7 as the major product. The stereoselectivity was reversed by reducing 6 with NaBH3CN/TFA, which gave predominantly the trans-2,6-dialkyltetrahydropyridine 10. Catalytic hydrogenation of 7 and 10 gave the corresponding N-Boc-cis(or trans)-2,6-dialkylpiperidines. Regioselective hydrogenation of 6 gave the 1,2,3,4-tetrahydropyridine 18, which on treatment with NaBH3CN/TFA provided a 90:10 mixture of trans- and cis-piperidines 15 and 16. More vigorous hydrogenation of 6 afforded the cis-piperidine 15 with 96% stereoselectivity. Similar stereoselective reductions of dihydropyridine 22 were carried out. Stereoselective reductions of dihydropyridines 6 and 22 were utilized in the synthesis of (+/-)-solenopsin A and (+/-)-dihydropinidine from 4-chloropyridine in six and five steps, respectively.

  DOI：

  10.1021/jo00007a044

文献信息

• A highly regioselective indium-mediated allylation of pyridine derivatives: synthesis of (±)-dihydropinidine from pyridine
  作者：Teck-Peng Loh、Pek-Ling Lye、Rui-Bin Wang、Keng-Yeow Sim

  DOI：10.1016/s0040-4039(00)01332-0

  日期：2000.9

  The preparation of various 1-acyl-1,2-dihydropyridines with high regioselectivity by indium-mediated allylation of the corresponding 1-acylpyridinium salts is demonstrated. This is applied to the synthesis of (±)-dihydropinidines.

  证明了通过铟介导的相应的1-酰基吡啶鎓盐的烯丙基化制备具有高区域选择性的各种1-酰基-1,2-二氢吡啶。这适用于（±）-二氢吡啶的合成。
• Diastereoselectively Complementary C–H Functionalization Enables Access to Structurally and Stereochemically Diverse 2,6-Substituted Piperidines
  作者：Gang Wang、Ying Mao、Lei Liu

  DOI：10.1021/acs.orglett.6b03372

  日期：2016.12.16

  The preparation of 2,6-substituted piperidine derivatives through diastereoselective C–H functionalization of corresponding nitrogen heterocycles represents an appealing protocol and yet remains a formidable challenge. Here, we describe a stereochemically complementary oxidative C–H functionalization of N-carbamoyl tetrahydropyridines with a wide variety of building blocks, providing either the cis-

  通过相应的氮杂环的非对映选择性CH官能团制备2，6-取代的哌啶衍生物是一个有吸引力的方案，但仍然是一个艰巨的挑战。在这里，我们描述了N-氨基甲酰基四氢吡啶的立体化学互补氧化C–H功能化，具有多种结构单元，可为顺式-或反式-2,6-取代的哌啶提供多种功能模式。不含金属的温和工艺具有极佳的区域选择性和非对映选择性，以及对官能团的耐受性。还描述了天然产物和类似物合成中的合成用途。
• 1,5-Asymmetric induction in addition reaction of aldehydes with chiral allyltitaniums having an amino group at the stereogenic center. Synthesis of optically active 2,6-cis-disubstituted piperidines
  作者：Teng Xin、Sentaro Okamoto、Fumie Sato

  DOI：10.1016/s0040-4039(98)01455-5

  日期：1998.9

  Chiral allyltitaniums prepared from cyclic carbamate of optically active 4-aminoalk-1-en-3-ols and a reagent react with aldehydes with good to excellent regio- and stereoselectivity to afford optically active 1,5-amino alcohols, from which optically active 2,6-cis-disubstituted piperidines are synthesized.

  由旋光性4-氨基烷基-1-en-3-醇的环状氨基甲酸酯制得的手性烯丙基铝鎓盐与一种试剂，具有良好至极佳的区域选择性和立体选择性的醛反应，可制得旋光性1,5-氨基醇，旋光性2 ，6-顺式二取代的哌啶进行合成。
• .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.