3-(2-hydroxy-2-phenylethylamino)-1-phenylpropanol

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-(2-hydroxy-2-phenylethylamino)-1-phenylpropanol
• 英文别名: (1S)-3-[[(2S)-2-hydroxy-2-phenylethyl]amino]-1-phenylpropan-1-ol
• 化学式: C₁₇H₂₁NO₂
• 分子量: 271.359
• InChiKey: AOFCNAQIVRMQNV-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  52.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氨基-1-苯乙醇 在 R-Alpine-Hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 9.5h， 生成 3-(2-hydroxy-2-phenylethylamino)-1-phenylpropanol
  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

• Remote stereocontrol in acyclic systems. Hydride addition to 1,5- and 1,6-hydroxy ketones mediated by metal chelation
  作者：Edward C. Lawson、Han-Cheng Zhang、Bruce E. Maryanoff

  DOI：10.1016/s0040-4039(98)02501-5

  日期：1999.1

  Acyclic 1,6-hydroxy amino ketones can be reduced to either the anti or syn diols with high 1,6 diastereoselectivity by sequential treatment with a Lewis acid and a borohydride reagent, with the direction of stereocontrol depending on the Lewis acid complexant used. For example, with 1aanti:syn ratios of >100:1 [Ti(OiPr)4/K-Selectride] and 1:7 [Al(OEt)3/K-Selectride] were realized. 1,5-Hydroxy amino

  通过用路易斯酸和硼氢化物试剂进行顺序处理，视立体控制的方向而定，取决于所使用的路易斯酸络合剂，无环1,6-羟基氨基酮可还原为具有高1,6-非对映选择性的抗或顺二醇。例如，以> 100：1 [Ti（OiPr）4 / K-Selectride]和1：7 [Al（OEt）3 / K-Selectride]的1a反：syn比率实现。1,5-羟基氨基酮4a以高的syn 1,5非对映选择性被还原[ anti：syn = 1:18（Al（OEt）3 / K-Selectride）。
• 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).