(6Z,8E,10E)-(S)-5-Benzyloxy-7-bromo-12-hydroxy-dodeca-6,8,10-trienal | 132047-80-4

• 分子结构分类: 有机化合物
• 英文名称: (6Z,8E,10E)-(S)-5-Benzyloxy-7-bromo-12-hydroxy-dodeca-6,8,10-trienal
• 英文别名: (5S,6Z,8E,10E)-7-bromo-12-hydroxy-5-phenylmethoxydodeca-6,8,10-trienal
• CAS: 132047-80-4
• 化学式: C₁₉H₂₃BrO₃
• 分子量: 379.294
• InChiKey: FNHYSCPOZNZWCS-DSDDWADBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.32
• 重原子数：
  23.0
• 可旋转键数：
  11.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (6Z,8E,10E)-(S)-5-Benzyloxy-7-bromo-12-hydroxy-dodeca-6,8,10-trienal 以 二氯甲烷 为溶剂， 生成 methyl 1α-(benzyloxy)-8-bromo-6β-(3'-hydroxy-prop-2'-en-1'-yl)-5β-methyl-1,2,3,4aα,5,6,8aα-octahydronaphthalene-5α-carboxylate
  参考文献：
  名称：

  Enantioselective synthesis of the bottom half of chlorothricolide. 3. Studies of the steric directing group strategy for stereocontrol in intramolecular Diels-Alder reactions

  摘要：

  The intramolecular Diels-Alder reactions of a series of C(7)-alkoxy-substituted 2(E),8(Z),10(E)-undecatrienoates and trienals containing removable C(9)-Br or C(9)-SiMe3 substituents (11, 12, 13, 33, 42, 43, 44, 45) were studied as part of a program directed toward the total synthesis of the bottom half of chlorothricolide. The IMDA reaction of trienoate 3 that lacks a C(9) substituent had previously been shown to cyclize with poor stereoselectivity to a mixture of four cycloadducts. It was expected that the IMDA reactions of trienes containing C(9) substituents (i.e., steric directing groups) would proceed with substantially enhanced stereoselectivity via trans-fused transition state A owing to nonbonded interactions that the steric directing groups experience in the competitive transition states B-D. Cis-fused transition states C and D suffer from serious interactions between C(9)-X and the axial C(6)-H, while trans-fused transition state B is destabilized by a 1,3-eclipsing interaction with the C(7)-alkoxyl group. Only the desired transition state, trans-fused transition state A, suffers from no serious interactions involving the C(9) steric directing group. These predictions were verified experimentally: the trans-fused cycloadduct deriving from A was the major product in all cases. Stereoselectivity for trans-fused cycloadducts was consistently greater, using C(9)-TMS directing groups compared to C(9)-Br substituted systems (for IMDA reactions under analogous conditions), but the C(9)-Br group appeared to have a greater influence on the partition between transition states A and B (see Table I). A surprising aspect of this study, however, is that significant amounts of cis-fused cycloadducts were obtained from the thermal cyclizations of the above-named trienes (12-45%), and this pathway was not entirely suppressed even in the Lewis acid catalyzed cycloadditions of trienals 44 and 45 (5-9% of cis fused cycloadduct). The results with TMS-substituted trienes 33, 42, and 44 thus are in disagreement with an earlier report by Boeckman and Barta (ref 5f) that the IMDA reaction of 33 gives ''a single cycloadduct (> 100:1).'' The cis-fused diastereomers most probably arise via boat-like transition state E rather than the chair-like transition state C. Cis-fused cycloadducts were not observed in the IMDA reaction of TMS-substituted triene 61 that lacks a C(7)-alkoxy substituent, suggesting that the C(7)-alkoxy groups electronically deactivate trans-fused transition state A such that boat-like transition state E is competitive only with substrates containing such C(7)-alkoxy substituents. Data are also presented that show that the C(9)-TMS substituents lead to an increase in reactivity (e.g., the IMDA reaction of 61 that proceeds at ambient temperature and the acid-catalyzed cyclocondensation of TMS diene aldehyde 63). This study defines bromo trienoate 43 as the optimal precursor to the bottom half unit (2) of chlorothricolide, even though the IMDA reaction of 43 is less selective than that of TMS-substituted trienes 42 and 44. The synthesis of 43 (Figure 4) involving the Pd0-catalyzed cross-coupling reaction of dibromo olefin 35 and vinylboronate 37 is shorter and considerably more efficient than the syntheses of TMS trienes 42 and 44, and this compensates for the fact that 43 is the least selective IMDA substrate.Syntheses that proceed by way of TMS trienoates like 42 or TMS trienals like 44 become competitive only if a more efficient triene synthesis is devised.

  DOI：

  10.1021/jo00003a049
• 作为产物：
  描述：

  (E)-(S)-5-Benzyloxy-8-oxo-oct-6-enenitrile 在 吡啶 、 溴-1,4-二氧六环复合物 、 二异丁基氢化铝 、 lithium diisopropyl amide 作用下， 以 正己烷 、 甲苯 为溶剂， 反应 8.0h， 生成 (6Z,8E,10E)-(S)-5-Benzyloxy-7-bromo-12-hydroxy-dodeca-6,8,10-trienal
  参考文献：
  名称：

  Enantioselective synthesis of the bottom half of chlorothricolide. 3. Studies of the steric directing group strategy for stereocontrol in intramolecular Diels-Alder reactions

  摘要：

  The intramolecular Diels-Alder reactions of a series of C(7)-alkoxy-substituted 2(E),8(Z),10(E)-undecatrienoates and trienals containing removable C(9)-Br or C(9)-SiMe3 substituents (11, 12, 13, 33, 42, 43, 44, 45) were studied as part of a program directed toward the total synthesis of the bottom half of chlorothricolide. The IMDA reaction of trienoate 3 that lacks a C(9) substituent had previously been shown to cyclize with poor stereoselectivity to a mixture of four cycloadducts. It was expected that the IMDA reactions of trienes containing C(9) substituents (i.e., steric directing groups) would proceed with substantially enhanced stereoselectivity via trans-fused transition state A owing to nonbonded interactions that the steric directing groups experience in the competitive transition states B-D. Cis-fused transition states C and D suffer from serious interactions between C(9)-X and the axial C(6)-H, while trans-fused transition state B is destabilized by a 1,3-eclipsing interaction with the C(7)-alkoxyl group. Only the desired transition state, trans-fused transition state A, suffers from no serious interactions involving the C(9) steric directing group. These predictions were verified experimentally: the trans-fused cycloadduct deriving from A was the major product in all cases. Stereoselectivity for trans-fused cycloadducts was consistently greater, using C(9)-TMS directing groups compared to C(9)-Br substituted systems (for IMDA reactions under analogous conditions), but the C(9)-Br group appeared to have a greater influence on the partition between transition states A and B (see Table I). A surprising aspect of this study, however, is that significant amounts of cis-fused cycloadducts were obtained from the thermal cyclizations of the above-named trienes (12-45%), and this pathway was not entirely suppressed even in the Lewis acid catalyzed cycloadditions of trienals 44 and 45 (5-9% of cis fused cycloadduct). The results with TMS-substituted trienes 33, 42, and 44 thus are in disagreement with an earlier report by Boeckman and Barta (ref 5f) that the IMDA reaction of 33 gives ''a single cycloadduct (> 100:1).'' The cis-fused diastereomers most probably arise via boat-like transition state E rather than the chair-like transition state C. Cis-fused cycloadducts were not observed in the IMDA reaction of TMS-substituted triene 61 that lacks a C(7)-alkoxy substituent, suggesting that the C(7)-alkoxy groups electronically deactivate trans-fused transition state A such that boat-like transition state E is competitive only with substrates containing such C(7)-alkoxy substituents. Data are also presented that show that the C(9)-TMS substituents lead to an increase in reactivity (e.g., the IMDA reaction of 61 that proceeds at ambient temperature and the acid-catalyzed cyclocondensation of TMS diene aldehyde 63). This study defines bromo trienoate 43 as the optimal precursor to the bottom half unit (2) of chlorothricolide, even though the IMDA reaction of 43 is less selective than that of TMS-substituted trienes 42 and 44. The synthesis of 43 (Figure 4) involving the Pd0-catalyzed cross-coupling reaction of dibromo olefin 35 and vinylboronate 37 is shorter and considerably more efficient than the syntheses of TMS trienes 42 and 44, and this compensates for the fact that 43 is the least selective IMDA substrate.Syntheses that proceed by way of TMS trienoates like 42 or TMS trienals like 44 become competitive only if a more efficient triene synthesis is devised.

  DOI：

  10.1021/jo00003a049

文献信息

• ROUSH, WILLIAM R.;KAGEYAMA, MASANORI;RIVA, RENATA;BROWN, BRADLEY B.;WARMU+, J. ORG. CHEM., 56,(1991) N, C. 1192-1210
  作者：ROUSH, WILLIAM R.、KAGEYAMA, MASANORI、RIVA, RENATA、BROWN, BRADLEY B.、WARMU+

  DOI：——

  日期：——