(1R,5R)-6,6-Dimethyl-3-(phenylthio)bicyclo<3.1.1>hept-3-en-2-one | 128261-64-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (1R,5R)-6,6-Dimethyl-3-(phenylthio)bicyclo<3.1.1>hept-3-en-2-one
• 英文别名: 3-(phenylthio)apoverbenone；(1R,5R)-6,6-Dimethyl-3-(phenylthio)bicyclo[3.1.1]hept-3-en-2-one；(1R,5R)-6,6-dimethyl-3-phenylsulfanylbicyclo[3.1.1]hept-3-en-2-one
• CAS: 128261-64-3
• 化学式: C₁₅H₁₆OS
• 分子量: 244.357
• InChiKey: PVMOXUXEQOMBAP-PWSUYJOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,5R)-6,6-Dimethyl-3-(phenylthio)bicyclo<3.1.1>hept-3-en-2-one 在 copper(l) iodide 、 copper(I) bromide dimethylsulfide complex 、 甲烷磺酸 、 氨 、 乙酸酐 、 lithium 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 39.0h， 生成 (1R,4R,5R)-4-(3-Butenyl)-4,6,6-trimethylbicyclo<3.1.1>heptan-2-one
  参考文献：
  名称：

  The use of 4,4-disubstituted nopinones for natural-product synthesis. Synthesis of elemanoid sesquiterpenes

  摘要：

  A general and convenient synthetic route to 4,4-disubstituted nopinones 14 from (+)-nopinone (1) is developed and applied to the asymmetric synthesis of some representative elemanoid sesquiterpenes. Phenylsulfenylation of 1 provided sulfide 6 in high yield. A convenient transformation of 6 to 3-(phenylsulfonyl)-4,4-disubstituted-nopinones 13 was accomplished by (i) m-CPBA oxidation of a sulfide compound followed by the Pummerer rearrangement and (ii) the conjugate addition of carbon nucleophiles to the resulting enones, 6 --> 8 --> 9 and 9 --> 10,11 --> 13. Subsequent reductive desulfurization of the adducts 13 provided 14 in good overall yield from 1. Bicyclic ketones 14 are envisioned as promising intermediates for natural product synthesis. As examples, syntheses of two elemanoid sesquiterpenes, beta-elemenone (16) and eleman-8-beta,12-olide (17) in optically active form from (1R,4S,5S)-4,6,6-trimethyl-4-vinylbicyclo[3.1.1]heptan-2-one (14a) were carried out.

  DOI：

  10.1021/jo00025a023
• 作为产物：
  描述：

  beta-pinene 在 甲醇 、 甲烷磺酸 、 乙酸酐 、 臭氧 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 二氯甲烷 为溶剂， 反应 56.33h， 生成 (1R,5R)-6,6-Dimethyl-3-(phenylthio)bicyclo<3.1.1>hept-3-en-2-one
  参考文献：
  名称：

  The use of 4,4-disubstituted nopinones for natural-product synthesis. Synthesis of elemanoid sesquiterpenes

  摘要：

  A general and convenient synthetic route to 4,4-disubstituted nopinones 14 from (+)-nopinone (1) is developed and applied to the asymmetric synthesis of some representative elemanoid sesquiterpenes. Phenylsulfenylation of 1 provided sulfide 6 in high yield. A convenient transformation of 6 to 3-(phenylsulfonyl)-4,4-disubstituted-nopinones 13 was accomplished by (i) m-CPBA oxidation of a sulfide compound followed by the Pummerer rearrangement and (ii) the conjugate addition of carbon nucleophiles to the resulting enones, 6 --> 8 --> 9 and 9 --> 10,11 --> 13. Subsequent reductive desulfurization of the adducts 13 provided 14 in good overall yield from 1. Bicyclic ketones 14 are envisioned as promising intermediates for natural product synthesis. As examples, syntheses of two elemanoid sesquiterpenes, beta-elemenone (16) and eleman-8-beta,12-olide (17) in optically active form from (1R,4S,5S)-4,6,6-trimethyl-4-vinylbicyclo[3.1.1]heptan-2-one (14a) were carried out.

  DOI：

  10.1021/jo00025a023

文献信息

• Preparation of Optically Active Apoverbenone and Verbenone from Nopinone by Use of the Sulfenylation−Dehydrosulfenylation Method. Stability and Reactivity Attributable to Absolute Configuration at the Sulfur Atom in Sulfoxides
  作者：Hiroshi Kosugi、Jaseung Ku、Michiharu Kato

  DOI：10.1021/jo9807316

  日期：1998.10.1

  with 19a. As a result, it was proved that, in 3-(phenylsulfinyl)nopinones, thermodynamic stability of isomers is dependent on absolute configuration at the sulfur center; that is, the trans-isomer 10a possesses an R(s)-phenylsulfinyl group and the cis-isomer 10b possesses an S(s)-phenylsulfinyl group, and it was proved that, in (4R)-4-methyl-3-(phenylsulfinyl)nopinones, both cis-isomers 18a,b are stable

  旋光形式的Apoverbenone（4）和verbenone（5）作为对映选择性合成中的手性来源，可能是有用的化合物。以易于从（-）-β-pine烯，（+）-apoverbenone（4a）和（+）-verbenone（5a）购得的（+）-nopinone（1）开始，以合成上令人满意的总收率制备，通常使用亚磺酰化-脱氢亚磺酰化方法涉及烯酮官能团的构建。该方法学可适用于从（-）-去甲酮开始制备其对映体（-）-4b和（-）-5b。虽然亚砜10a，b和18a，b中的苯亚磺酰基的构型是通过（1）H NMR光谱和NOE相关性确定的，但通过在（1）H NMR光谱中比较它们的同系物，可以得出硫原子的绝对构型绝对配置明确的 即10a与13a，10b与13b，18a与19b和18b与19a。结果证明，在3-（苯基亚磺酰基）nopinones中，异构体的热力学稳定性取决于硫中心的绝对构型；即，反式异构体10a
• Extracyclic stereocontrolled alkylation of (1R,5S)-4-ethyl-6,6-dimethyl-3-(phenylsulfonyl)bicyclo[3.1.1]hept-3-en-2-one. A highly stereocontrolled synthesis of (-)-kanshone A
  作者：Michiharu Kato、Masataka Watanabe、Bahlul Z. Awen

  DOI：10.1021/jo00071a025

  日期：1993.9

  (1R,5S)-4-Ethyl-6,6-dimethyl-3-(phenylsulfonyl)bicyclo[3.1.1]hept-3-en-2-one (7) was prepared from (+)-nopinone (1) in six steps and 70% overall yield via (1R,5R)-6,6-dimethyl-3-(phenylthio)bicyclo-[3.1.l]hept-3-en-2-one (2). Alkylation reactions of 7 with alkyl bromides 16 (a, allyl; b, 3-methyl-2-butenyl; c, propargyl; d, benzyl bromide) in the presence of K2CO3 in MeCN proceeded in regio- and extracyclic stereocontrolled fashion to give, as the major product, mixtures of gamma-alkylated products 17a-d possessing a new chiral center of R configuration adjacent to a ring and 18a-d possessing that of S configuration, whose ratios are 17a-18a, 10:1, 17b-18b, 7:1; 17c-18c, 13:1; and 17d-18d, 18:1, along with alpha-alkylated products 19a-d and 0-alkylated products 20a,b on reactions with 16a,b. In addition, reaction of 7 with methyl bromoacetate (16e) provided 17e as the sole product. In the presence of a combined reagent, K2CO3-Cs2CO3 (9:1), in MeCN, considerably high diastereoselection was detected, i.e., reactions of 7 with 16a,b produced mixtures of 17a and 18a, and 17b and 18b, in 20:1 and 12:1 ratios, respectively. Reaction products were separated by chromatography on silica gel, while the major diastereomers 17a,c-e, highly crystalline themselves, were readily obtained as pure crystals by recrystallization. Mechanism of diastereoselection and the scope and limitations of the extracyclic stereocontrolled alkylation are briefly discussed. In the application of 17 as the synthetic intermediate for the asymmetric synthesis, starting with (1R,5S)-6,6-dimethyl-4-[(1R)-1-methyl-3-butenyl]-3-(phenylsulfonyl)bicyclo[3.l.l]hept-3-en-2-one (17a), (-)-kanshone A (8), a nardosinane sesquiterpene, was synthesized in a highly stereoselective fashion in 12 steps via (1R,4R,5R)-4,6,6-trimethyl-4-[(1R)-l-methyl-3-butenyl]bicyclo[3.1.1]heptan-2-one (30) and its cyclobutane-ring opening product, (4S,4aR,5R)-1-acetoxy-4-isopropenyl-4a,5-dimethyl-3,4,4a,5,6,7-hexahydronaphthalene (34).

  (1R,5S)-4-乙基-6,6-二甲基-3-(苯基亚砜基)双环[3.1.1]庚-3-烯-2-酮 (7) 由 (+)-诺蒎酮 (1) 经过六步反应和 70% 总收率制得，其中关键中间体为 (1R,5R)-6,6-二甲基-3-(苯硫基)双环[3.1.1]庚-3-烯-2-酮 (2)。在甲基乙腈 (MeCN) 中以 K₂CO₃ 为碱的条件下，化合物 7 与不同烷基溴 (16，a： allyl；b： 3-甲基-2-丁烯基；c： 丙炔基；d： 苯甲基溴；e： 甲基溴乙酸酯) 进行烷基化反应，分别以区域和全环立体受控的方式进行，主要生成含有 R 型新手性中心（邻近环）的 γ-烷基化产物 17a-d 和含有 S 型手性中心的 18a-d，它们的比例分别为：17a-18a，10:1；17b-18b，7:1；17c-18c，13:1；17d-18d，18:1。此外，反应还生成少量的 α-烷基化产物 19a-d 和 β-烷基化产物 20a,b。当使用 16a 和 16b 作为反应物时，烷基化反应主要生成 γ-烷基化产物。值得注意的是，当使用甲基溴乙酸酯 (16e) 进行反应时，仅生成 17e 作为唯一产物。在 MeCN 中使用 K₂CO₃ 和 Cs₂CO₃ (9:1) 的混合碱时，观察到较高的对映体选择性，即化合物 7 与 16a 和 16b 的反应分别以 20:1 和 12:1 的比例生成对映体混合物 17a-18a 和 17b-18b。 反应产物通过硅胶柱色谱分离，其中主要的对映异构体 17a、17c 和 17e，由于其高度结晶性，可通过重结晶直接获得纯晶体。文中简要讨论了对映体选择性的机制以及全环立体受控烷基化的范围和限制。 在将 17 作为不对称合成的合成中间体应用于天然产物合成时，以 (1R,5S)-6,6-二甲基-4-[(1R)-1-甲基-3-丁烯基]-3-(苯基亚砜基)双环[3.1.1]庚-3-烯-2-酮 (17a) 为起始原料，通过 12 步反应，以高立体选择性合成了 (-)-kanshone A (8)，一种nardosinane型倍半萜。其合成过程中依次通过 (1R,4R,5R)-4,6,6-三甲基-4-[(1R)-1-甲基-3-丁烯基]双环[3.1.1]庚烷-2-酮 (30) 和其环丁烷开环产物 (4S,4aR,5R)-1-乙酰氧基-4-异丙烯基-4a,5-二甲基-3,4,4a,5,6,7-六氢萘 (34) 完成。
• Kato, Michiharu; Kido, Fusao; Watanabe, Masataka, Journal of the Chemical Society. Perkin transactions I, 1993, # 22, p. 2831 - 2836
  作者：Kato, Michiharu、Kido, Fusao、Watanabe, Masataka、Masuda, Yoshiaki、Awen, Bahlul Z.

  DOI：——

  日期：——
• Efficient synthesis of (1S,5S)-4-alkyl-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-ones from (1R,5S)-(+)-nopinone and preparation of some chiral building blocks suitable for the asymmetric synthesis
  作者：Masataka Watanabe、Bahlul Z. Awen、Michiharu Kato

  DOI：10.1021/jo00067a026

  日期：1993.7

  A general and convenient transformation of (1R,5S)-(+)-nopinone (1) into (1S,5S)-4-alkyl-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-ones, i.e., (-)-verbenone (6a) as the simplest compound and its C(4)-alkyl homologs 6b-f, via (+)-apoverbenone (7) is developed and applied, starting with 6a,e, to the syntheses of (4R,5R)-1-acetoxy-4-isopropenyl-5-methyl-5-vinyl-1-cyclohexene (12a) and (4R,5S)- and (4R,5R)-1-acetoxy-5-(3-butenyl)-4-isopropenyl-5-methyl-1-cyclohexene (12b and 12c), in connection with a search for chiral building blocks suitable for the asymmetric synthesis. Preparation of 12a indicates the formal synthesis of the elemanoid sesquiterpenes (-)-beta-elemenone and (-)-eleman-8beta,12-olide.
• Kato, Michiharu; Vogler, Bernhard; Tooyama, Youichi, Chemistry Letters, 1990, p. 151 - 154
  作者：Kato, Michiharu、Vogler, Bernhard、Tooyama, Youichi、Yoshikoshi,Akira

  DOI：——

  日期：——