(2S)-3-(1,3-benzodioxole-5-yl)-2-methylpropanal | 737776-68-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (2S)-3-(1,3-benzodioxole-5-yl)-2-methylpropanal
• 英文别名: (S)-2-methyl-3-(3,4-methylenedioxyphenyl)-1-propanal；(S)-tropional；(R)-3-benzo[1,3]dioxol-5-yl-2-methyl-propionaldehyde；(S)-3-(benzo[d][1,3]dioxol-5-yl)-2-methylpropanal；(S)-3-(1,3-benzodioxol-5-yl)-2-methylpropanal；(S)-Helional；(2R)-3-(1,3-benzodioxol-5-yl)-2-methylpropanal；(2S)-3-(1,3-benzodioxol-5-yl)-2-methylpropanal
• CAS: 737776-68-0
• 化学式: C₁₁H₁₂O₃
• 分子量: 192.214
• InChiKey: BOPPSUHPZARXTH-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S)-3-(1,3-benzodioxole-5-yl)-2-methylpropanal 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 反应 0.75h， 生成 (2S)-3-(1,3-benzodioxole-5-yl)-2-methylpropan-1-ol
  参考文献：
  名称：

  First asymmetric synthesis of both enantiomers of Tropional® and their olfactory evaluation

  摘要：

  The first asymmetric synthesis of both enantiomers of Tropional(R) is accomplished by asymmetric alkylation by employing the SAMP/RAMP-hydrazone method, respectively. The alkylated hydrazones were oxidatively cleaved with magnesium-monoperoxyphthalate (MMPP). Subsequent reduction of the resulting nitriles with diisobutyl aluminium hydride (DIBAL-H) led to the desired aldehydes in good overall yields (52-53%) and enantiomeric excesses (ee = 90%). Furthermore, the olfactory evaluation of both enantiomers showed remarkable differences in odour quality and intensity. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.04.026
• 作为产物：
  描述：

  [3-Benzo[1,3]dioxol-5-yl-2-methyl-prop-(E)-ylidene]-((S)-2-methoxymethyl-pyrrolidin-1-yl)-amine 在 二异丁基氢化铝 、 magnesium monoperoxyphthalate hexahydrate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (2S)-3-(1,3-benzodioxole-5-yl)-2-methylpropanal
  参考文献：
  名称：

  First asymmetric synthesis of both enantiomers of Tropional® and their olfactory evaluation

  摘要：

  The first asymmetric synthesis of both enantiomers of Tropional(R) is accomplished by asymmetric alkylation by employing the SAMP/RAMP-hydrazone method, respectively. The alkylated hydrazones were oxidatively cleaved with magnesium-monoperoxyphthalate (MMPP). Subsequent reduction of the resulting nitriles with diisobutyl aluminium hydride (DIBAL-H) led to the desired aldehydes in good overall yields (52-53%) and enantiomeric excesses (ee = 90%). Furthermore, the olfactory evaluation of both enantiomers showed remarkable differences in odour quality and intensity. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.04.026

文献信息

• Bioreduction of α-Acetoxymethyl Enones: Proposal for an S_N2′ Mechanism Catalyzed by Enereductase
  作者：Bruno R. S. Paula、Davila Zampieri、J. Augusto R. Rodrigues、Paulo J. S. Moran

  DOI：10.1002/adsc.201600601

  日期：2016.11.17

  acylated Morita–Baylis–Hillman adduct 1‐acetoxy‐2‐methylene‐1‐phenylbutan‐3‐one produced a mixture of products, with and without the acetoxy group, via three different reaction pathways. In addition to experiments employing whole cells, those in which isolated enereductases were used suggested that the main pathway through which the loss of the acetoxy group occurs during the biocatalytic cascade is an SN2′‐type

  （Z）-3-乙酰氧基甲基-4-R-3-丁烯-2-酮（R =芳基，烷基）和（Z）-3-甲基-4-R-3-丁烯-2-丁烯（R =芳基）合成并通过酿酒酵母进行还原，分别产生（R）-和（S）-4-R-3甲基丁烷-2-。这种立体化学控制策略适用于对映体过量至中度过量的（R）-和（S）-Tropional®的合成。其他（Z）-3-酰氧基甲基-4-苯基-3-丁烯-2-酮的行为与（Z）-3-乙酰氧基甲基对应物和酰化的Morita-Baylis-Hillman加合物1-乙酰氧基-2-亚甲基-1-苯基丁烷-3-酮通过三种不同的反应途径生成了带有或不带有乙酰氧基的产物混合物。除了使用全细胞的实验外，使用分离的烯还原酶的实验还表明，在生物催化级联反应中发生乙酰氧基丢失的主要途径是S N 2'型反应，而不是正式的氢加成反应。消除乙酸。最后，相关的乙基烯酮被酵母白色念珠菌对映体选择性还原，产生（R）-和（S）还原产物，取决于起始原料中乙酰氧基的存在。
• Acid promoted CIDT for the deracemization of dihydrocinnamic aldehydes with Betti's base
  作者：Goffredo Rosini、Claudio Paolucci、Francesca Boschi、Emanuela Marotta、Paolo Righi、Francesco Tozzi

  DOI：10.1039/c0gc00013b

  日期：——

  Racemic α-epimerizable and unfunctionalized aldehydes have been converted into enantiomerically enriched mixtures through a sequence of (i) a conversion into the diastereoisomeric 3-substituted 1-phenyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines by reaction with the (R)- or (S)-1-(α-aminobenzyl)-2-naphthol (Betti's base), (ii) an acid promoted crystallization-induced diastereoisomer transformation (CIDT), and (iii) a clean cleavage of the dihydro-1,3-naphthoxazinic ring of the enriched diastereoisomer, easily collected by filtration, allowing the recovery of the enantiomerically enriched aldehydes and the chiral auxiliary.

  对映体的α-可互变和未功能化的醛通过以下步骤转化为富含对映体的混合物：(i) 与(R)-或(S)-1-(α-氨基苄基)-2-萘酚（Betti碱）反应，转化为二面体异构体的3-取代1-苯基-2,3-二氢-1H-萘并[1,2-e][1,3]氧杂啉；(ii) 促酸的结晶诱导二面体异构体转化（CIDT）；(iii) 清洁地切割富集的二面体异构体的二氢-1,3-萘氧杂烯环，易于过滤收集，从而回收富含对映体的醛和手性辅助剂。
• Deracemization through photochemical <i>E</i> / <i>Z</i> isomerization of enamines
  作者：Mouxin Huang、Long Zhang、Tianrun Pan、Sanzhong Luo

  DOI：10.1126/science.abl4922

  日期：2022.2.25

  pharmaceutical applications. Here, we report a photochemical E / Z isomerization strategy for the deracemization of α-branched aldehydes by using simple aminocatalysts and readily available photosensitizers. A variety of racemic α-branched aldehydes could be directly transformed into either enantiomer with high selectivity. Rapid photodynamic E / Z isomerization and highly stereospecific iminium/enamine

  α-支链醛的催化去外消旋是构建对映体纯 α-叔羰基化合物的直接策略，这对药物应用至关重要。在这里，我们报告了一种光化学物质乙/Z通过使用简单的氨基催化剂和容易获得的光敏剂对 α-支链醛进行去外消旋的异构化策略。多种外消旋α-支链醛可以直接转化为任一对映异构体，具有高选择性。快速光动力乙/Z异构化和高度立体定向的亚胺/烯胺互变异构是对映富集的两个关键因素。这项研究提出了一种独特的光化学乙/Z用于外部调节烯胺催化的异构化策略。
• Bioreduction of α-methylcinnamaldehyde derivatives: chemo-enzymatic asymmetric synthesis of Lilial™ and Helional™
  作者：Clemens Stueckler、Nicole J. Mueller、Christoph K. Winkler、Silvia M. Glueck、Karl Gruber、Georg Steinkellner、Kurt Faber

  DOI：10.1039/c002971h

  日期：——

  Nonracemic aryl-substituted α-methyldihydrocinnamaldehyde derivatives employed as olfactory principles in perfumes (Lilial™, Helional™) were obtained via enzymatic reduction of the corresponding cinnamaldehyde precursors using cloned and overexpressed ene-reductases. (R)-Enantiomers were obtained using the old-yellow-enzyme (OYE) homolog YqjM from Bacillus subtilis and 12-oxophytodienoic acid reductase isoenzyme OPR1 from tomato (e.e.max 53%), and (S)-aldehydes were furnished in up to 97% e.e. using isoenzyme OPR3, nicotinamide 2-cyclohexene-1-one reductase NCR from Zymomonas mobilis and yeast OYE isoenzymes 1–3 under optimised reaction conditions in the presence of t-butyl methyl ether as the co-solvent. The stereochemical outcome of the reduction of α-methylcinnamaldehyde using NCR and OYEs 1–3 [previously reported to be (R)] was unambiguously corrected to be (S).

  在香水中用作嗅觉原理的非外消旋芳基取代的α-甲基二氢肉桂醛衍生物（Lilial™、Helional™）是通过使用克隆和过表达的烯还原酶酶促还原相应的肉桂醛前体而获得的。使用来自枯草芽孢杆菌的老黄酶 (OYE) 同源物 YqjM 和来自番茄的 12-氧代植物二烯酸还原酶同工酶 OPR1（e.e.max 53%）获得 (R)-对映体，并且 (S)-醛提供最多97% 有效量使用同工酶 OPR3、来自运动发酵单胞菌的烟酰胺 2-环己烯-1-酮还原酶 NCR 和酵母 OYE 同工酶 1–3，在叔丁基甲基醚作为共溶剂的情况下，在优化的反应条件下进行。使用 NCR 和 OYE 1–3 还原 α-甲基肉桂醛的立体化学结果 [之前报告为 (R)] 明确更正为 (S)。
• [EN] PROCESS FOR PREPARING HYDROCINNAMIC ALDEHYDES IN ENANTIOPURE OR ENANTIOMERICALLY ENRICHED FORM<br/>[FR] PROCÉDÉ DE PRÉPARATION D'ALDÉHYDES HYDROCINNAMIQUES DE FORME ÉNANTIOPURE OU ÉNANTIOMÉRIQUEMENT ENRICHIE
  申请人：ENDURA SPA

  公开号：WO2010131274A1

  公开（公告）日：2010-11-18

  A process is described for preparing hydrocinnamic aldehydes in enantiopure or enantiomerically enriched form of Formula I, in which R is isopropyl or tert-butyl and R' is hydrogen, or R and R' when taken together are a methylenedioxolyl group, comprising the following steps: a) reacting the hydrocinnamic aldehyde of Formula I with the alcohol of Formula Il in enantiopure or enantiomerically enriched form to give the crystallized hemiacetal of Formula III, in which R, R' have the same meaning as Formula I and (*) indicates a stereogenic centre in the absence of a solvent or in one or more aprotic solvents or mixtures thereof with apolar solvents; b) recovering the hydrocinnamic aldehyde of Formula I in enantiopure or enantiomerically enriched form from the crystallized hemiacetal of Formula III and the aldehyde of opposite configuration in enantiopure or enantiomerically enriched form from the hemiacetal crystallization mother liquors. The invention also concerns a process for preparing the alcohol of Formula Il to be introduced into step a).

  描述了一种制备式I的羟基肉桂醛的过程，其中R是异丙基或叔丁基，R'是氢，或者当一起时R和R'是一个亚甲二氧苯基团，包括以下步骤：a)将式I的羟基肉桂醛与式II的醇在对映纯或对映富集形式中反应，得到结晶的半缩醛III的结晶体，其中R，R'的含义与式I相同，(*)表示在无溶剂或一个或多个无极性溶剂或与极性溶剂混合物中具有立体异构中心；b)从半缩醛III的结晶体中以对映纯或对映富集形式回收式I的羟基肉桂醛，同时从半缩醛结晶母液中回收对映纯或对映富集形式的相反构型的醛。该发明还涉及一种制备式II醇的过程，以引入到步骤a)中。