2-[Benzyl-((R)-3-hydroxy-3-phenyl-propyl)-amino]-1-phenyl-ethanone | 185376-71-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[Benzyl-((R)-3-hydroxy-3-phenyl-propyl)-amino]-1-phenyl-ethanone
• 英文别名: 2-[benzyl-[(3R)-3-hydroxy-3-phenylpropyl]amino]-1-phenylethanone
• CAS: 185376-71-0
• 化学式: C₂₄H₂₅NO₂
• 分子量: 359.468
• InChiKey: JGWJTPBRLZEPEZ-HSZRJFAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[Benzyl-((R)-3-hydroxy-3-phenyl-propyl)-amino]-1-phenyl-ethanone 在 R-Alpine-Hydride< 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 (1R)-3-[benzyl-[(2R)-2-hydroxy-2-phenylethyl]amino]-1-phenylpropan-1-ol 、 (R)-3-[Benzyl-((S)-2-hydroxy-2-phenyl-ethyl)-amino]-1-phenyl-propan-1-ol
  参考文献：
  名称：

  通过双环螯合控制，在无环酮底物的氢化物还原中具有较高的1,6非对映选择性

  摘要：

  无环ε羟基酮的还原3与ř -Alpine -氢化物®在二氯甲烷中提供的强大优势抗的非对映体4（反：顺式= 12：1）。这种令人印象深刻的1,6立体选择性归因于氢化物添加的双环螯合控制。

  DOI：

  10.1016/0040-4039(96)01767-4
• 作为产物：
  描述：

  (R)-(+)-3-氯-1-苯基-1-丙醇 在 potassium carbonate 、 N,N-二异丙基乙胺 、 potassium iodide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 72.0h， 生成 2-[Benzyl-((R)-3-hydroxy-3-phenyl-propyl)-amino]-1-phenyl-ethanone
  参考文献：
  名称：

  Stereocontrol between Remote Atom Centers in Acyclic Substrates. Anti Addition of Hydride to 1,5-, 1,6-, and 1,7-Hydroxy Ketones

  摘要：

  For conformationally unconstrained, acyclic organic compounds, the control of stereogenic centers at remote positions of a chain, that is, at a distance of four or more atom centers, remains a challenging problem in asymmetric synthesis. We report on our studies of 1,5, 1,6, and 1,7 diastereoselectivity in hydride reductions of acyclic hydroxy amino ketones and related compounds, which were sparked by our discovery of high 1,5 diastereocontrol (>10:1) with substrates such as 17 and 23. We have been able to achieve both high 1,5- and 1,6-anti diastereocontrol in the reduction of 1,5- and 1,6-hydroxy ketone substrates, respectively. However, the level of 1,7-anti diastereocontrol with 1,7-hydroxy ketones was only moderate. More specifically, reduction of 23 to 24 with R-alpine-hydride or Zn(BH4)(2) in CH2Cl2 (predominantly) at -78 degrees C gave high 1,5-anti stereoselectivity (anti/syn = 10:1 or 13:1, respectively), and reduction of 34 to 35 with R-alpine-hydride (CH2Cl2) gave high 1,6-anti selectivity (anti/syn = 12:1, respectively), whereas reduction of 46 to 44 with R-alpine-hydride (CH2Cl2) gave only moderate 1,7-anti stereoselectivity (anti/syn = 3:1). Results for reductions of 1,5- and 1,6-hydroxy ketone substrates having the N-benzyl structural subunit replaced (i.e., 27 --> 28, 29 --> 30, 31 --> 32, 52 --> 53, 54a --> 55a, 54b --> 55b, 54c --> 55c, and 56 --> 57) clearly indicate that the stereoelectronic character of this subunit plays a critical. role in the attainment of high anti asymmetric induction. Thus, while we obtained exceptionally high 1,6-anti stereoselectivity in the reduction of the N-mesitylmethyl substrate, 54c, to 1,6-diols 55c (anti/syn = 22:1) with R-alpine-hydride at -78 degrees C in CH2Cl2, the N-methyl substrate, 54b, gave a relatively modest anti/syn ratio of 3:1. The diminished anti/syn ratio of 4:1 in the R-alpine-hydride reduction of methoxy amino ketone 50 to 51 also indicates the importance of the free hydroxyl group for attaining high 1,6-anti stereoselectivity. To rationalize the high remote anti stereocontrol in such acyclic systems, we discuss a chelation-controlled mechanism, involving external hydride addition to a bicyclic metal complex with a coordinated ketone carbonyl (e.g., 33) vs internal hydride addition to a monocyclic metal complex with an uncoordinated ketone carbonyl (e.g., 58).

  DOI：

  10.1021/jo981341m

文献信息

• High 1,6 diastereoselectivity in the hydride reduction of an acyclic ketone substrate via bicyclic chelation control
  作者：Han-Cheng Zhang、Bruce D. Harris、Cynthia A. Maryanoff、Bruce E. Maryanoff

  DOI：10.1016/0040-4039(96)01767-4

  日期：1996.10

  Reduction of acyclic ε-hydroxy ketone 3 with R-Alpine-Hydride® in methylene chloride provided a strong preponderance of the anti diastereomer of 4 (anti:syn = 12:1). This impressive 1,6 stereoselectivity is attributed to bicyclic chelation control of hydride addition.

  无环ε羟基酮的还原3与ř -Alpine -氢化物®在二氯甲烷中提供的强大优势抗的非对映体4（反：顺式= 12：1）。这种令人印象深刻的1,6立体选择性归因于氢化物添加的双环螯合控制。
• Stereocontrol between Remote Atom Centers in Acyclic Substrates. Anti Addition of Hydride to 1,5-, 1,6-, and 1,7-Hydroxy Ketones
  作者：Han-Cheng Zhang、Bruce D. Harris、Michael J. Costanzo、Edward C. Lawson、Cynthia A. Maryanoff、Bruce E. Maryanoff

  DOI：10.1021/jo981341m

  日期：1998.10.1

  For conformationally unconstrained, acyclic organic compounds, the control of stereogenic centers at remote positions of a chain, that is, at a distance of four or more atom centers, remains a challenging problem in asymmetric synthesis. We report on our studies of 1,5, 1,6, and 1,7 diastereoselectivity in hydride reductions of acyclic hydroxy amino ketones and related compounds, which were sparked by our discovery of high 1,5 diastereocontrol (>10:1) with substrates such as 17 and 23. We have been able to achieve both high 1,5- and 1,6-anti diastereocontrol in the reduction of 1,5- and 1,6-hydroxy ketone substrates, respectively. However, the level of 1,7-anti diastereocontrol with 1,7-hydroxy ketones was only moderate. More specifically, reduction of 23 to 24 with R-alpine-hydride or Zn(BH4)(2) in CH2Cl2 (predominantly) at -78 degrees C gave high 1,5-anti stereoselectivity (anti/syn = 10:1 or 13:1, respectively), and reduction of 34 to 35 with R-alpine-hydride (CH2Cl2) gave high 1,6-anti selectivity (anti/syn = 12:1, respectively), whereas reduction of 46 to 44 with R-alpine-hydride (CH2Cl2) gave only moderate 1,7-anti stereoselectivity (anti/syn = 3:1). Results for reductions of 1,5- and 1,6-hydroxy ketone substrates having the N-benzyl structural subunit replaced (i.e., 27 --> 28, 29 --> 30, 31 --> 32, 52 --> 53, 54a --> 55a, 54b --> 55b, 54c --> 55c, and 56 --> 57) clearly indicate that the stereoelectronic character of this subunit plays a critical. role in the attainment of high anti asymmetric induction. Thus, while we obtained exceptionally high 1,6-anti stereoselectivity in the reduction of the N-mesitylmethyl substrate, 54c, to 1,6-diols 55c (anti/syn = 22:1) with R-alpine-hydride at -78 degrees C in CH2Cl2, the N-methyl substrate, 54b, gave a relatively modest anti/syn ratio of 3:1. The diminished anti/syn ratio of 4:1 in the R-alpine-hydride reduction of methoxy amino ketone 50 to 51 also indicates the importance of the free hydroxyl group for attaining high 1,6-anti stereoselectivity. To rationalize the high remote anti stereocontrol in such acyclic systems, we discuss a chelation-controlled mechanism, involving external hydride addition to a bicyclic metal complex with a coordinated ketone carbonyl (e.g., 33) vs internal hydride addition to a monocyclic metal complex with an uncoordinated ketone carbonyl (e.g., 58).