(4R,6R)-4-羟基-6-甲基四氢-2H-吡喃-2-酮 | 27751-97-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 中文名称: (4R,6R)-4-羟基-6-甲基四氢-2H-吡喃-2-酮
• 英文名称: cis-4-hydroxy-6-methyl-3,4,5,6-tetrahydro-2H-pyran-2-one
• 英文别名: (4RS,6SR)-4-hydroxy-6-methyltetrahydro-2H-pyran-2-one；cis-4-hydroxy-6-methyltetrahydro-2-pyrone；cis-3-Hydroxy-5-hexanolid；(4S,6R)-4-hydroxy-6-methyloxan-2-one
• CAS: 27751-97-9；33275-54-6；74282-23-8；87172-73-4；87172-74-5；121843-07-0；121843-08-1；130857-41-9；147921-49-1
• 化学式: C₆H₁₀O₃
• 分子量: 130.144
• InChiKey: KKZQBMBBMJKIRQ-UHNVWZDZSA-N

物化性质

• 沸点：
  284.4±23.0 °C(Predicted)
• 密度：
  1.172±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4R,6R)-4-羟基-6-甲基四氢-2H-吡喃-2-酮 在 palladium on activated charcoal 、 对甲苯磺酸 氢气 作用下， 以 乙酸乙酯 、 苯 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 生成 丁位己内酯
  参考文献：
  名称：

  三乙酸内酯的氢化。木蜂（Xylocopa hirsutissima）性信息素的新合成

  摘要：

  在各种催化条件下，三乙酸内酯（Ⅰ）已被氢化成不同氧化态的内酯（Ⅱ，Ⅲ和Ⅴ）。其中一个（II）的C-甲基化是方便制备木匠蜂性信息素的关键步骤。

  DOI：

  10.1016/s0040-4039(01)85553-2
• 作为产物：
  描述：

  4-羟基-6-甲基-2-吡喃酮 在 palladium on activated charcoal 、 Ra-Ni 氢气 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 生成 (4R,6R)-4-羟基-6-甲基四氢-2H-吡喃-2-酮
  参考文献：
  名称：

  三乙酸内酯的氢化。木蜂（Xylocopa hirsutissima）性信息素的新合成

  摘要：

  在各种催化条件下，三乙酸内酯（Ⅰ）已被氢化成不同氧化态的内酯（Ⅱ，Ⅲ和Ⅴ）。其中一个（II）的C-甲基化是方便制备木匠蜂性信息素的关键步骤。

  DOI：

  10.1016/s0040-4039(01)85553-2

文献信息

• Assembly intermediates in polyketide biosynthesis: enantioselective syntheses of β-hydroxycarbonyl compounds
  作者：Christine Le Sann、Dulce M. Muñoz、Natalie Saunders、Thomas J. Simpson、David I. Smith、Florilène Soulas、Paul Watts、Christine L. Willis

  DOI：10.1039/b419492f

  日期：——

  versatile approach for the enantioselective synthesis of functionalised beta-hydroxy N-acetylcysteamine thiol esters has been developed which allows the facile incorporation of isotopic labels. It has been shown that a remarkable reversal of selectivity occurs in the titanium mediated aldol reaction of acyloxazolidinone using either (S)- or (R)-tert-butyldimethylsilyloxybutanal. The aldol products are valuable

  已经开发了用于对映选择性合成官能化的β-羟基N-乙酰半胱胺硫醇酯的通用方法，该方法允许容易地掺入同位素标记。已经显示出在使用（S）-或（R）-叔丁基二甲基甲硅烷基氧基丁醛的钛介导的恶唑烷酮的羟醛缩醛反应中，选择性的显着逆转发生。醛醇缩合产物是合成4-羟基-6-取代的δ-内酯的有价值的中间体。
• Synthese vonrac-Detoxinin
  作者：Johannes Häusler

  DOI：10.1002/jlac.198319830611

  日期：1983.6.15

  Versuche zur Synthese des 3-Oxoesters 5 aus N-Boc-3-Hydroxyprolin (1) werden beschrieben. Acylierung von Meldrumsäure (2,2-Dimethyl-1,3-dioxan-4,6-dion) mit dem Pyrrolidin-2,3-carbolacton 8 in Gegenwart von 4-(Dimethylamino)pyridin liefert die Acylmeldrumsäure 7, die thermisch zum 4-Hydroxy-2-pyron 9 cyclisiert wird. Reduktion von 9 mit Amin-Boran-komplexen im schwach Sauren führt zu den isomeren Hydroxypyronen

  描述了从N -Boc-3-羟基脯氨酸（1）合成3-氧代酸酯5的尝试。麦德鲁姆酸（2,2-二甲基-1,3-二恶烷-4,6-二酮）与吡咯烷-2,3-羧内酯的酰化8在4-（二甲氨基）吡啶存在下使酰基meldrum酸7，这是热转化为4-羟基-2-吡喃酮9的环化。在弱酸性环境中用胺-硼烷络合物还原9会生成羟基吡喃酮10和11异构体。以16产生17和18的类似转换（在每种情况下异构体比率约为1：2）。Boc残基分离后，10和11个内酯环开口形成标题氨基酸19或其异构体20。类似地，21可以对不饱和氨基酸22开放。
• In search of open-chain 1,3-stereocontrol
  作者：Asun Barbero、David C. Blakemore、Ian Fleming、Robert N. Wesley

  DOI：10.1039/a607545b

  日期：——

  Methylation of methyl 4-phenylpentanoate 25 gives the diastereoisomers methyl (2RS,4SR )-2-methyl-4-phenylpentanoate 26 and methyl (2RS,4RS)- 2-methyl-4-phenylpentanoate 27 in a ratio of 44∶56. The aldehydes 3-dimethyl(phenyl)silylbutanal 28, 3-dimethyl(phenyl)silyl-3-phenylpropanal 32 and 3-dimethyl(phenyl)silyl-4-methylpentanal 36, each of which has a stereogenic centre on C-3 carrying a silyl group and successively also a methyl, a phenyl and an isopropyl group, react with a range of methyl, phenyl and isopropyl nucleophiles to give pairs of diastereoisomeric secondary alcohols 40–42, 47–49 and 54–56 having 1,3 related stereocentres. The same alcohols 43–45, 50–52 and 57–59 are also prepared by reduction of the corresponding ketones 29–31, 33–35 and 37–39 with a range of hydride reagents, and three of the ketones, 31, 35 and 39, react with phenyllithium to give mixtures of the tertiary alcohols 46, 53 and 60. The (E)- and (Z)-α,β-unsaturated methyl esters, 61, 62, 64, 65, 67 and 68, prepared from the same three aldehydes with methoxycarbonylmethyltriphenylphosphorane, react with the phenyldimethylsilyl-cuprate and -zincate reagents to give diastereoisomeric pairs of 1,3-disilylated esters. Likewise, the α,β-unsaturated dimethyl diesters, 63, 66 and 69, prepared from the same three aldehydes with dimethyl malonate, react with phenyldimethylsilyllithium and the corresponding cuprate and zincate reagents to give diastereoisomeric pairs of 1,3-disilylated diesters, and with various methyl and phenyl nucleophiles to give the corresponding pairs of diastereoisomeric diesters with stereogenic centres at C-3 and C-5. The relative stereochemistry of all but two of the products having 1,3-related stereocentres has been proved by silyl-to-hydroxy conversion using mercuric acetate and peracetic acid to give the corresponding alcohols or their derived lactones.An attempt to identify a purely steric rule by which it might be possible to predict which diastereoisomer would be the major product in each of these reactions was based on arguments about, and molecular mechanics calculations of, the lowest-energy conformations of the starting materials. The only rule that emerges is that ketones are regularly attacked in sense B, defined in the drawings 21 and 23, in a conformation that minimises the interaction between the group M on the stereogenic centre and the group R1 on the other side of the ketone, but even within this group of reactions, phenyl groups in either or both locations sometimes lead to anomalies.Krapcho reactions take place more rapidly and in higher yield using four equivalents of lithium chloride in place of the usual sodium chloride, and adding two equivalents of water to the DMSO.

  将 4-苯基戊酸甲酯 25 甲酯化，得到非对映异构体(2RS,4SR )-2-甲基-4-苯基戊酸甲酯 26 和(2RS,4RS)-2-甲基-4-苯基戊酸甲酯 27，比例为 44∶56。3-二甲基（苯基）硅基丁醛 28、3-二甲基（苯基）硅基-3-苯基丙醛 32 和 3-二甲基（苯基）硅基-4-甲基戊醛 36，每种醛的 C-3 上都有一个带有硅基的立体中心，并先后带有一个甲基、一个苯基和一个异丙基、与一系列的甲基、苯基和异丙基亲核物反应，得到一对非对映异构的仲醇 40-42、47-49 和 54-56，它们具有 1,3 个相关的立体中心。同样的醇 43-45、50-52 和 57-59 也可以通过相应的酮 29-31、33-35 和 37-39 与一系列氢化物试剂发生还原反应来制备，其中三个酮 31、35 和 39 与苯基锂发生反应，得到叔醇 46、53 和 60 的混合物。 (E)-和(Z)-α,β-不饱和甲基酯 61、62、64、65、67 和 68 由相同的三种醛与甲氧羰基甲基三苯基膦制备而成，它们与苯基二甲基硅琥珀酸酯试剂和锌酸试剂反应，得到非对映异构的 1,3-二硅烷化酯对。同样，由相同的三种醛与丙二酸二甲酯制备的 α、β-不饱和二甲基二酯 63、66 和 69 与苯基二甲基硅烷基锂及相应的铜酸盐和锌酸盐试剂发生反应，生成一对非对映异构的 1,3-二硅烷基二酯，与各种甲基和苯基亲核剂发生反应，生成相应的一对非对映异构的二酯，其立体中心位于 C-3 和 C-5。除了两种具有 1,3 相关立体中心的产物外，其他所有产物的相对立体化学性质都已通过使用乙酸巯基和过乙酸进行硅基-羟基转换而得到相应的醇或其衍生内酯得到证实。出现的唯一规则是，酮在图 21 和图 23 中定义的 B 意义上经常被攻击，其构象使立体中心上的基团 M 与酮另一侧的基团 R1 之间的相互作用最小，但即使在这组反应中，苯基在任一位置或两个位置有时也会导致异常。
• Model studies towards the synthesis of aplysiatoxin. Spiro-conformational control in the reactivity of C2-oxidized spiroketals.
  作者：David A. Stolze、Françoise Perron-Sierra、Mary Jane Heeg、Kim F. Albizati

  DOI：10.1016/s0040-4039(00)79868-6

  日期：1991.8

  The strategy of pre-foming a highly functionalized C2-oxidized spiroketal prior to utilizing the steric and stereoelectronic biases of the ring system to direct the introduction of further functionality is an attractive method for complex spiroketal synthesis. By such an approach, aplysiatoxin-oscillatoxin models have been constructed, in which non-chair conformation have been discovered.

  在利用环系统的空间和立体电子偏压来直接引入其他功能之前，预先形成高度官能化的C 2-氧化螺环酮的策略对于复杂的螺环酮合成来说是一种有吸引力的方法。通过这种方法，已经构建了aplysiatoxin-oscillatoxin模型，其中发现了非椅子的构象。
• Asymmetric Hydrogenation of Substituted 2-Pyrones
  作者：Matthias J. Fehr、Giambattista Consiglio、Michelangelo Scalone、Rudolf Schmid

  DOI：10.1021/jo982215l

  日期：1999.8.1

  Various substituted 2-pyrones have been hydrogenated with high enantioselectivity (up to 97% ee) to the corresponding 5,6-dihydropyrones using cationic ruthenium catalysts containing the (6,6'-dimethoxybiphenyl-2,2'diyl)bis[3,5-di(tert-butyl)phenylphosphine] ligand. When substituents at position 3 are absent, 5,6-dihydropyrones are further hydrogenated to the fully saturated delta-lactones. In the case of 4,6-dimethyl-2H-pyran-2-one, the diastereoselectivity of the second hydrogenation step was determined by the chirality of the applied catalyst, while for the 4,5,6-trimethyl-2H-pyran-2-one a double asymmetric induction effect was observed. Other cyclic substrates with endo- or exocyclic double bonds were hydrogenated, although with substantially lower enantioselectivity with respect to the 2-pyrones.