(4RS,6SR)-4,6-dimethyltetrahydro-2H-pyran-2-one | 24405-13-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (4RS,6SR)-4,6-dimethyltetrahydro-2H-pyran-2-one
• 英文别名: (4R*,6R*)-4,6-dimethyltetrahydropyran-2-one；cis-5-hydroxy-3-methylhexanoic acid lactone；(+/-)-cis-3,5-Dimethylvalerolacton；(4S,6R)-4,6-dimethyloxan-2-one
• CAS: 24405-13-8
• 化学式: C₇H₁₂O₂
• 分子量: 128.171
• InChiKey: KSFJZYURRNSMGO-NTSWFWBYSA-N

物化性质

• 沸点：
  77-78 °C(Press: 2 Torr)
• 密度：
  0.956±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4RS,6SR)-4,6-dimethyltetrahydro-2H-pyran-2-one 在 lithium aluminium tetrahydride 、 对甲苯磺酸 作用下， 以 乙醚 为溶剂， 反应 74.0h， 生成 cis-2-methoxy-4,6-dimethyltetrahydropyran
  参考文献：
  名称：

  Anomeric effect in 2-alkoxytetrahydropyrans studied by carbon-13 and oxygen-17 NMR chemical shifts

  摘要：

  DOI：

  10.1021/jo00337a025
• 作为产物：
  描述：

  4,6-二甲基-2-吡喃酮 在 palladium on activated charcoal 氢气 作用下， 以 叔丁醇 为溶剂， 反应 19.0h， 以93.9%的产率得到(4RS,6SR)-4,6-dimethyltetrahydro-2H-pyran-2-one
  参考文献：
  名称：

  Anomeric effect in 2-alkoxytetrahydropyrans studied by carbon-13 and oxygen-17 NMR chemical shifts

  摘要：

  DOI：

  10.1021/jo00337a025

文献信息

• A Synthesis of Jaspamide Based on 1,2-Metallate Rearrangements of α-Heteroalkenylmetal Derivatives
  作者：Philip Ashworth、Brian Broadbelt、Pawel Jankowski、Philip Kocienski、Austen Pimm、Richard Bell

  DOI：10.1055/s-1995-3870

  日期：1995.2

  Jaspamide (Jasplakinolide), a marine cyclodepsipeptide, was synthesised from tripeptide fragment 4 and (2S,4E,6R,8S)-8-benzoyloxy-2,4,6-trimethylnon-4-enoic acid (3). The tripeptide fragment was prepared from β-tyrosine derivative 6, Boc-2-bromoabrine (8), and alanine. β-Tyrosine derivative 6 was prepared by asymmetric conjugate amination of methyl p-hydroxycinnamate. Bromabrine derivative 8 was prepared from tryptophan. Key steps in the synthesis of the polyketide fragment 3 include 1,2-metallate rearrangement of a metallated dihydropyran and a metallated enol carbamate derivative.

  由三肽片段 4 和 (2S,4E,6R,8S)-8-苯甲酰氧基-2,4,6-三甲基壬-4-烯酸 (3) 合成了海洋环肽 Jaspamide (Jasplakinolide)。三肽片段是由δ-酪氨酸衍生物 6、Boc-2-溴肾上腺素（8）和丙氨酸制备而成。δ-酪氨酸衍生物 6 是通过对羟基肉桂酸甲酯的不对称共轭胺化反应制备的。溴苦参碱衍生物 8 由色氨酸制备。合成多酮片段 3 的关键步骤包括金属化二氢吡喃和金属化烯醇氨基甲酸酯衍生物的 1,2-金属化重排。
• 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。
• Palladium-catalyzed enantioselective hydrogenation of 2-pyrones: evidence for competing reaction mechanisms
  作者：W.-R Huck、T Bürgi、T Mallat、A Baiker

  DOI：10.1016/s0021-9517(03)00166-0

  日期：2003.10.1

  reactant–modifier interactions. These interactions may involve the OH function and the quinuclidine N of the alkaloid modifier. When the reactant possesses an acidic OH group (1a and 2a), the reaction via the energetically most stable bidentate complex controls the enantioselectivity. Protic or basic solvents diminish the ee in these reactions by stabilizing a single-bonded (acid–base type) interaction. Different

  4-羟基-6-甲基-2-吡喃酮（1a），3,6-二甲基-4-羟基-2-吡喃酮（2a），4-甲氧基-6-甲基-2-吡喃酮（3a）的对映选择性氢化，并且在5wt％的Pd / TiO 2催化剂上研究了4，6-二甲基-2-吡喃酮（4a）。各种金鸡纳生物碱及其O-和N-甲基衍生物被用作手性改性剂。催化实验与FTIR，NMR和NOESY-NMR光谱分析以及从头算计算相结合，揭示了反应的一个有趣特征：ee由竞争的反应物-修饰剂相互作用决定。这些相互作用可能涉及生物碱改性剂的OH功能和奎尼丁N。当反应物具有酸性OH基团（1a和2a），通过能量上最稳定的双齿配合物的反应控制了对映选择性。质子或碱性溶剂通过稳定单键（酸碱型）相互作用来减少这些反应中的ee。对于非酸性吡喃酮3a和4a的氢化，提出了不同的机理。这些模型可以很好地解释催化结果，但需要进一步确认。此外，这些研究为手性修饰的Pd的固有速率加速和对映微分过程提供了第一个实验证据。
• Heterogeneous enantioselective hydrogenation of 2-pyrones over cinchona-modified palladium
  作者：Wolf-Rüdiger Huck、Tamas Mallat、Alfons Baiker

  DOI：10.1039/b108944g

  日期：2002.1.24

  Asymmetric hydrogenation of 4-alkoxy and 4-methyl derivatives of 2-pyrones to the corresponding dihydro- or tetrahydropyrones over cinchona-modified Pd/TiO2 is fast under ambient conditions and affords good yields and high ee. cis-Tetrahydropyrones are obtained with 98–99% de. The ee can be further increased by kinetic resolution.

  不对称 氢化在环境条件下，在金鸡纳改性的Pd / TiO 2上2-吡喃酮的4-烷氧基和4-甲基衍生物转化为相应的二氢-或四氢吡喃酮是快速的并且提供了良好的产率和高ee。顺式-四氢吡喃酮的de含量为98-99％。ee可以通过动力学拆分进一步提高。
• A method for the chromatographic resolution of tetrahydropyran-2-ones
  作者：Philip Ashworth、Shiddappa L. Belagali、Sharon Casson、Anna Marczak、Philip Kocieński

  DOI：10.1016/s0040-4020(01)80729-8

  日期：1991.12

  The spirocyclic ortholactones prepared from certain tetrahydropyran-2-ones (valerolactones) and (1R)-1-phenylpropan-1,3-diol are readily separable by flash chromatography on silica gel. Hydrolysis of the resolved ortholactones then provides the pure homochiral lactones.

  由某些四氢吡喃-2-酮（戊内酯）和（1R）-1-苯基丙烷-1,3-二醇制备的螺环原内酯很容易通过硅胶快速色谱分离。然后水解分解的原内酯，得到纯的手性内酯。