(R)-2-chloro-2,2-difluoro-1-phenylethanol | 119454-39-6

• 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: (R)-2-chloro-2,2-difluoro-1-phenylethanol
• 英文别名: (1R)-2-chloro-2,2-difluoro-1-phenylethanol
• CAS: 119454-39-6
• 化学式: C₈H₇ClF₂O
• 分子量: 192.593
• InChiKey: FMOACCSFYBBLBO-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  一氯二氟苯乙酮 在 吡啶 、 sodium tetrahydroborate 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 18.5h， 生成 (R)-2-chloro-2,2-difluoro-1-phenylethanol
  参考文献：
  名称：

  A microbially-based approach for the synthesis of chiral secondary alcohols bearing the difluoromethyl or chlorodifluoromethyl group

  摘要：

  A synthetic approach to both enantiomers of the secondary alcohols [Ph(CH2)n CH(OH)CXF2 (n = 0-2) C6H13(CH2)n CH(OH)CFX2 (n = 0 or 2) and CXF2CH(OH)CH2CO2Et [X = H or Cl], involving the stereoselective hydrolysis of ester derivatives, is described. The absolute configurations of these difluoromethylated or chlorodifluoromethylated molecules were determined.

  DOI：

  10.1016/s0022-1139(00)81174-4

文献信息

• Two Classes of Enzymes of Opposite Stereochemistry in an Organism:  One for Fluorinated and Another for Nonfluorinated Substrates
  作者：Tomoko Matsuda、Tadao Harada、Nobuyoshi Nakajima、Toshiyuki Itoh、Kaoru Nakamura

  DOI：10.1021/jo991283k

  日期：2000.1.1

  observed in the reduction of hindered ketones such as isopropyl ketone, while the stereoselectivity was inverted in the reduction of ketones with electron-withdrawing atoms such as chlorine. The mechanism for the inversion in stereochemistry was investigated by enzymatic studies. Several enzymes with different stereoselectivities were isolated; one of them catalyzed the reduction of methyl ketones, and another

  用白色假单胞菌干燥细胞还原甲基酮可得到对映体过量（ee）极好的（S）-醇，而三氟甲基酮的还原也可得到ee极佳的相反构型的相应醇。用三氟甲基取代甲基部分改变了体积和电子性质，检查了其对立体选择性的影响。在受阻酮（如异丙基酮）的还原中未观察到立体化学的反转，而在具有吸电子原子（如氯）的酮的还原中，立体选择性被反转。通过酶学研究了立体化学转化的机理。分离出了几种具有不同立体选择性的酶。它们之一催化甲基酮的还原，而另一种具有相反的立体选择性催化三氟甲基酮的还原。此外，将APG4和分离的酶均应用于制备规模的氟化酮还原反应，从而合成了具有优异ee的手性氟化醇。
• Molecular Basis for the High Activity and Enantioselectivity of the Carbonyl Reductase from <i>Sporobolomyces salmonicolor</i> toward α-Haloacetophenones
  作者：Xi Chen、Hongliu Zhang、Jinhui Feng、Qiaqing Wu、Dunming Zhu

  DOI：10.1021/acscatal.8b00591

  日期：2018.4.6

  2-Trifluoro-1-phenylethanol was prepared in excellent isolated yield and enantiomeric excess from the reduction of α,α,α-trifluoroacetophenone with mutant T209A. These results suggest that tuning the interactions between the halogen atoms/phenyl group of the substrate and the amino acid residues of the enzyme would lead to valuable mutants for the practical synthesis of β-haloalcohols.

  在努力开发一种实用的方法来合成光学纯的2,2,2-三氟-1-苯基乙醇时，我们发现来自鲑鱼孢菌的羰基还原酶（SSCR）具有出色的活性和对卤代苯乙酮的对映选择性。特别是，SSCR对α，α，α-三氟苯乙酮的活性比未取代的苯乙酮高出1000倍以上，这与先前研究的来自短乳杆菌的醇脱氢酶（LBADH）截然不同。酶-底物对接和定点诱变研究揭示了SSCR对α-卤代苯乙酮的高酶活性和对映选择性的分子基础。Asn207侧链与底物卤原子的氢键以及底物苯基与Ser222 / Thr223侧链的XH /π相互作用导致在活性位点中形成高反应性的α-卤代苯乙酮构象酶。（S）-2,2,2-三氟-1-苯基乙醇的制备具有优异的分离收率和对映体过量，其原因是用突变体T209A还原了α，α，α-三氟苯乙酮。这些结果表明，调节底物的卤素原子/苯基与酶的氨基酸残基之间的相互作用将导致有价值的突变体，用于实际合成β-卤代醇。
• Chemo- and Enantioselective Addition and β-Hydrogen Transfer Reduction of Carbonyl Compounds with Diethylzinc Reagent in One Pot Catalyzed by a Single Chiral Organometallic Catalyst
  作者：Huayin Huang、Hua Zong、Guangling Bian、Ling Song

  DOI：10.1021/acs.joc.5b01871

  日期：2015.12.18

  as the catalyst, the asymmetric β-H transfer reduction of aromatic α-trifluoromethyl ketones and enantioselective addition of aromatic aldehydes with Et2Zn in one pot were successfully realized, affording the corresponding additive products of secondary alcohols in high yields (up to 99%) with excellent enantioselectivities (up to 98% ee) and the reduction products of α-trifluoromethyl alcohols in good

  以单一手性磷酰胺-Zn（II）配合物为催化剂，成功实现了芳族α-三氟甲基酮的不对称β-H转移还原和在一个罐中与Et 2 Zn对映体选择性加成芳族醛，从而提供了相应的添加剂产品高收率（高达99％）的仲醇，具有出色的对映选择性（高达98％ee），α-三氟甲基醇的还原产物，收率高达77％ee，优良至优异。
• Catalytic asymmetric β-hydrogen transfer reduction of α-trifluoromethyl aromatic ketones with diethylzinc
  作者：Huayin Huang、Hua Zong、Guangling Bian、Ling Song

  DOI：10.1016/j.tetasy.2015.06.017

  日期：2015.8

  The catalytic asymmetric β-hydrogen transfer reduction of α-trifluoromethyl ketones using diethylzinc as the β-hydrogen donor was developed with the use of phosphinamide chiral ligand. The corresponding alcohol products were afforded in good yields with up to 73% ee. This method was successfully applied to the chemo- and enantioselective reduction of α-methyl/trifluoromethyl diketone, affording 88%

  利用次膦酰胺手性配体，开发了以二乙基锌为β-氢供体的α-三氟甲基酮的催化不对称β-氢转移还原反应。以高达73％ee的高收率提供相应的醇产物。该方法成功应用于α-甲基/三氟甲基二酮的化学和对映选择性还原，提供了88％的收率和70％ee的氟化羟基酮产物。
• Biocatalytic asymmetric reduction of fluoroalkyl ketones to access enantiopure fluoroalkyl secondary alcohols
  作者：Yahan Wu、Kaiji Wang、Xia Wang、Jingjing Wu、Fanhong Wu

  DOI：10.1039/d3ob00193h

  日期：——

  An efficient biocatalytic reduction of difluoroalkyl ketones for accessing chiral fluoroalkyl secondary alcohols is reported using commercial NADPH-dependent ketoreductase K234 with 2-propanol as a co-substrate for NADPH regeneration. This bioreduction reaction could be applied to a broad range of prochiral fluoroketones including aryl difluoroketones, aliphatic difluoroketones, and trifluoroacetophenones

  据报道，使用商业 NADPH 依赖性酮还原酶 K234 和 2-丙醇作为 NADPH 再生的共底物，可有效生物催化还原二氟烷基酮以获得手性氟烷基仲醇。这种生物还原反应可应用于广泛的前手性氟酮，包括芳基二氟酮、脂肪族二氟酮和三氟苯乙酮，在高底物浓度（100 g L -1). 这些结果表明 K234 在工业生产有价值的手性氟代醇方面具有潜力。此外，该生物催化方案在不添加外部烟酰胺辅助因子的情况下也可以有效，这为酮还原酶 K234 在手性仲醇不对称合成中的进一步应用提供了有用的指导。