(1S,3R,4S)-1-ethenyl-3-(methoxymethoxy)-7,7-dimethylbicyclo[2.2.1]heptan-2-one | 162790-59-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1S,3R,4S)-1-ethenyl-3-(methoxymethoxy)-7,7-dimethylbicyclo[2.2.1]heptan-2-one
• CAS: 162790-59-2
• 化学式: C₁₃H₂₀O₃
• 分子量: 224.3
• InChiKey: OZUANHDRHUNQMR-BREBYQMCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 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：

  (1S,3R,4S)-1-ethenyl-3-(methoxymethoxy)-7,7-dimethylbicyclo[2.2.1]heptan-2-one 在 二甲基硫 、 臭氧 作用下， 生成 (1R,3R,4S)-3-(methoxymethoxy)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-carbaldehyde
  参考文献：
  名称：

  Stereocontrolled Oxygenation of Camphor Derivatives as a Prelude to the Complete .beta.-Ring Functionalization of Potential Precursors to Taxol and Structural Analogs Thereof

  摘要：

  The possibility of realizing the predominant exo a-hydroxylation of camphor-related ketones is described. Both the direct oxidation of enolate anions with 1-phenyl-N-(phenylsulfonyl)oxaziridine or exposure of the derived silyl enol ethers to dimethyl dioxirane are conducive to exo attack. Following conversion to MOM derivatives, the acidity of the alpha-carbonyl proton is reduced sufficiently to allow direct condensation of these hindered ketones with cyclohexenyllithium reagents. The subsequent anionic oxy-Cope rearrangement of the resulting exo carbinols results in direct conversion to tricyclic products that feature the characteristic C-2,C-9,C-10 B-ring oxygenation pattern resident in taxol. Further, the stereogenic centers are introduced in their proper absolute configuration. The steric demands of the [3,3] sigmatropic shift are discussed and the stereochemical features conducive to the minimization of steric compression subjected to experimental verification.

  DOI：

  10.1021/jo00109a020
• 作为产物：
  描述：

  氯甲基甲基醚 、 (1S,4S)-3-Hydroxy-7,7-dimethyl-1-vinyl-2-norbornanone 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (1S,3R,4S)-1-ethenyl-3-(methoxymethoxy)-7,7-dimethylbicyclo[2.2.1]heptan-2-one 、 (1S,3S,4S)-3-(Methoxymethoxy)-7,7-dimethyl-1-vinyl-2-norbornanone
  参考文献：
  名称：

  Stereocontrolled Oxygenation of Camphor Derivatives as a Prelude to the Complete .beta.-Ring Functionalization of Potential Precursors to Taxol and Structural Analogs Thereof

  摘要：

  The possibility of realizing the predominant exo a-hydroxylation of camphor-related ketones is described. Both the direct oxidation of enolate anions with 1-phenyl-N-(phenylsulfonyl)oxaziridine or exposure of the derived silyl enol ethers to dimethyl dioxirane are conducive to exo attack. Following conversion to MOM derivatives, the acidity of the alpha-carbonyl proton is reduced sufficiently to allow direct condensation of these hindered ketones with cyclohexenyllithium reagents. The subsequent anionic oxy-Cope rearrangement of the resulting exo carbinols results in direct conversion to tricyclic products that feature the characteristic C-2,C-9,C-10 B-ring oxygenation pattern resident in taxol. Further, the stereogenic centers are introduced in their proper absolute configuration. The steric demands of the [3,3] sigmatropic shift are discussed and the stereochemical features conducive to the minimization of steric compression subjected to experimental verification.

  DOI：

  10.1021/jo00109a020

文献信息

• Evaluation of D-Ribose as an Enantiopure Building Block for Construction of the C-Ring of Taxol and Its Congeners
  作者：Leo A. Paquette、Simon Bailey

  DOI：10.1021/jo00129a026

  日期：1995.12

  The enantiomerically pure Z vinyl iodide 20 is shown to be readily available from D-ribose via a sequence involving zinc-promoted reductive unmasking of an aldehyde and homologation with (iodomethylene)triphenylphosphorane. The vinyl anion produced by halogen-metal exchange adds from the endo direction to an enantiopure ketone prepared from D-camphor. The resulting carbinol undergoes anionic oxy-Cope rearrangement and C-methylation with complete stereocontrol to set the appropriate C-3 stereochemistry of taxol. Dihydroxylation of this intermediate brings about facile transannular hemiketalization. DIBAL-H reduction of this intermediate does not affect the hemiketal, but does reduce the acetonide regiospecifically. An unusual transannular hydride shift occurs during subsequent heating with dibutyltin oxide, as confirmed by X-ray crystallography. When transannular hemiketalization is skirted, hydroboration-oxidation of the side chain leads to an acetaldehyde which is notably prone to beta-elimination. Treatment with potassium carbonate in methanol does eventuate in ring closure via an aldol addition reaction, but only after methanol has been added in Michael fashion to the alpha,beta-unsaturated aldehyde.
• An Abbreviated, Highly Stereocontrolled Route to Precursors of Taxol. Elaboration of a Fully Functionalized C Ring by Means of Intramolecular Aldol Cyclization
  作者：Leo A. Paquette、Francis J. Montgomery、Ting-Zhong Wang

  DOI：10.1021/jo00129a027

  日期：1995.12

  The asymmetric synthesis of an advanced taxol precursor is reported. The scheme involves the conversion of (R)-glyceraldehyde acetonide into the Q-vinyl iodide 2, transmetalation of this intermediate, and 1,2-addition to the D-camphor derivative 11 from the endo direction. This convergent coupling gives rise to exo alcohol 12, which undergoes anionic oxy-Cope rearrangement at low temperatures. In situ methylation of the resulting enolate anion delivers 13, which is chemoselectively transformed into aldehyde 18. In a key step, the aldol cyclization of 18 proceeds without beta-elimination to deliver a tricyclic product in which proper absolute configuration is adopted at the two stereogenic centers being newly introduced. Following protection of the hydroxyl substituent as in 19b,the alpha-hydroxy ketone 21 is heated with aluminum tri-tert-butoxide in benzene in order to effect near-quantitative rearrangement to the taxol-like isomer 22.
• Bicyclic Systems Related to Taxol. A Direct Means for Implementing C-2 Oxygenation and Demonstration of the Feasibility of α-Ketol Equilibration in a Fully Oxygenated B-Ring Setting
  作者：Qingbei Zeng、Simon Bailey、Ting-Zhong Wang、Leo A. Paquette

  DOI：10.1021/jo971592f

  日期：1998.1.1

  The feasibility of alpha-ketol equilibration in a fully oxygenated B-ring setting for the rapid, enantioselective construction of an A/B bicyclic model related to Taxol has been examined. The key elements associated with this successful venture include selection of a proper array of protecting groups for the four hydroxyl groups present, suitable catalysis of the 1,2-pinacol-like shift, and an intrinsic dependence on the thermodynamic stabilities of the two alpha-ketol isomers. The key conversion of 13 to 14 is seen to be unidirectional and consequently to offer useful potential serviceability as more advanced thrusts toward Taxol are mounted.
• Stereochemical Models for the Enantiocontrolled Construction of Fully Functionalized C Rings via Intramolecular Aldolization in Advanced Precursors to Paclitaxel
  作者：Leo A. Paquette、Qingbei Zeng、Hon-Chung Tsui、Jeffrey N. Johnston

  DOI：10.1021/jo981749j

  日期：1998.11.1

  Six transition-state models for intramolecular aldol C-ring annulation in suitably substituted bicyclo-[6.2.1]undecanones have been defined. The first consideration is the inherent conformational flexibility of the nine-membered ketonic ring which does not limit effective deprotonation to a single C-8 epimer. When the oxygen substituents at C-4 and C-5 are not covalently linked, the configuration at C-5 defines the stereochemical course of the ring closure, with only the beta series being amenable to the proper elaboration of paclitaxel. When C-4 and C-5 are incorporated into a 1,3-dioxane ring instead, the principal stereocontrol element is translocated into the aryl-substituted carbon of the cyclic acetal. To the extent that the Ar group remains equatorially disposed, then proper aldolization will materialize in only one of the four possible diastereomers. Experimental tests that are provided for three of the models are shown to conform to expectations. This analysis of the origin of stereoselectivity has, for the first time, defined the scope and limitations associated with C-ring closure by means of the aldol protocol.
• Evaluation of 2-Bromocyclohexenone Acetals as Vehicles for the Introduction of C-7 Oxygen Preliminary to the Synthesis of Taxane Diterpenes
  作者：Leo A. Paquette、Zhuang Su、Simon Bailey、Francis J. Montgomery

  DOI：10.1021/jo00109a021

  日期：1995.2

  The coupling of an optically pure, camphor-derived, beta,gamma-unsaturated, bicyclic ketone with a suitable vinyl organometallic is recognized to result in 1,2-addition from the endo face. Anionic oxy-Cope rearrangement of these carbinols proceeds via an ''endo-chair'' transition state to deliver a strained and reactive enolate that is formed regioselectively and is amenable to alpha-methylation from the top face. These steps, which are preliminary to a broad-based approach to the taxane diterpenes, had not yet accommodated suitable introduction of a C-7 oxygen substituent as required of taxol. Typically, an ether substituent at this site experiences beta-elimination once the enolate anion intermediate is accessed. Herein it is demonstrated that the parent 2-bromocyclohexenone acetal is well suited to resolving this complication. Halogen-metal exchange proceeds well to provide a suitably nucleophilic building block. Direct charge-accelerated sigmatropic rearrangement of the carbinol products does proceed with beta-elimination, but under the present circumstances the second C-O bond remains in the form of a vinylogous ester. Alternatively, the carbinols are amenable to chemoselective hydrolysis of the acetal, thereby unmasking a conjugated cyclohexenone part structure. These intermediates have been found to rearrange along completely analogous reaction trajectories to provide enolates of a beta-diketone subunit. The extent to which these anions undergo C- versus O-methylation under various conditions has been examined. When O-methylation does occur, it is the C-7 oxygen (and not the one at C-9) that is engaged in reaction.