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【结 构 式】 
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【分子编号】60352 【品名】10,10-dibromo-3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-N,2,6-trimethyl-N-(methyloxy)-6,9-decadienamide 【CA登记号】 |
【 分 子 式 】C20H37Br2NO3Si 【 分 子 量 】527.41222 【元素组成】C 45.55% H 7.07% Br 30.3% N 2.66% O 9.1% Si 5.33% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Preparation of fragment (VIII) is illustrated in Scheme 24509401a. Aldol condensation of aldehyde (I) with (R)-4-benzyl-3-propionyl-2-oxazolidinone (II) mediated by dibutylboron triflate gives the syn aldol adduct (III). This is converted to the Weinreb amide (IV) by treatment with N,O-dimethyl hydroxylamine in the presence of trimethylaluminium. After silylation of the secondary hydroxyl group of (IV), the resultant bis-silyl ether (V) is selectively desilylated at the primary hydroxyl group with p-toluenesulfonic acid and tetrabutylammonium bisulfate, to afford alcohol (VI). Dess-Martin oxidation of (VI) gives the aldehyde (VII), which is then subjected to Corey-Fuchs olefination with CBr4 and PPh3 to produce the gem-dibromo olefin (VIII)
| 【1】 Evans, D.A.; Starr, J.T.; A cascade cycloaddition strategy leading to the total synthesis of (-)-FR182877. Angew Chem. Int Ed 2002, 41, 10, 1787. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 60194 | 7-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-4-methyl-4-heptenal | C14H28O2Si | 详情 | 详情 | |
| (II) | 25713 | (4S)-4-benzyl-3-propionyl-1,3-oxazolidin-2-one | C13H15NO3 | 详情 | 详情 | |
| (III) | 60195 | (4R)-4-benzyl-3-((2R,3S,6E)-9-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxy-2,6-dimethyl-6-nonenoyl)-1,3-oxazolidin-2-one | C27H43NO5Si | 详情 | 详情 | |
| (IV) | 60196 | 9-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-hydroxy-N,2,6-trimethyl-N-(methyloxy)-6-nonenamide | C19H39NO4Si | 详情 | 详情 | |
| (V) | 60197 | 3,9-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-N,2,6-trimethyl-N-(methyloxy)-6-nonenamide | C25H53NO4Si2 | 详情 | 详情 | |
| (VI) | 60198 | 3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-9-hydroxy-N,2,6-trimethyl-N-(methyloxy)-6-nonenamide | C19H39NO4Si | 详情 | 详情 | |
| (VII) | 60199 | 3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-N,2,6-trimethyl-N-(methyloxy)-9-oxo-6-nonenamide | C19H37NO4Si | 详情 | 详情 | |
| (VIII) | 60352 | 10,10-dibromo-3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-N,2,6-trimethyl-N-(methyloxy)-6,9-decadienamide | C20H37Br2NO3Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)Suzuki coupling of vinyl bromide (VIII) with boronic acid (XVI) gives bromotetraene (XVII). The methoxyamide function of (XVII) is then reduced to aldehyde (XVIII) employing DIBAL in THF. Two carbon homologation of aldehyde (XVIII) with ethyl diazoacetate leads to keto ester (XIX). Selective removal of the primary tert-butyl diphenylsilyl ether of (XIX) with tetrabutylammonium fluoride affords the allylic alcohol (XX), which is then converted into iodide (XXI) by means of I2 and PPh3.
| 【1】 Evans, D.A.; Starr, J.T.; A cascade cycloaddition strategy leading to the total synthesis of (-)-FR182877. Angew Chem. Int Ed 2002, 41, 10, 1787. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 15911 | Ethyldiazoacetate; ethyl 2-diazoacetate | 623-73-4 | C4H6N2O2 | 详情 | 详情 |
| (VIII) | 60352 | 10,10-dibromo-3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-N,2,6-trimethyl-N-(methyloxy)-6,9-decadienamide | C20H37Br2NO3Si | 详情 | 详情 | |
| (XVI) | 60358 | 3,5-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-8-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-4-methyl-1,6-octadienylboronic acid | C37H63BO5Si3 | 详情 | 详情 | |
| (XVII) | 60422 | 10-bromo-3,13,15-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-18-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-N,2,6,14-tetramethyl-N-(methyloxy)-6,9,11,16-octadecatetraenamide | C57H98BrNO6Si4 | 详情 | 详情 | |
| (XVIII) | 60423 | 10-bromo-3,13,15-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-18-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-2,6,14-trimethyl-6,9,11,16-octadecatetraenal | C55H93BrO5Si4 | 详情 | 详情 | |
| (XIX) | 60424 | ethyl 12-bromo-5,15,17-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-20-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-4,8,16-trimethyl-3-oxo-8,11,13,18-icosatetraenoate | C59H99BrO7Si4 | 详情 | 详情 | |
| (XX) | 60425 | ethyl 12-bromo-5,15,17-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-20-hydroxy-4,8,16-trimethyl-3-oxo-8,11,13,18-icosatetraenoate | C43H81BrO7Si3 | 详情 | 详情 | |
| (XXI) | 60426 | ethyl 12-bromo-5,15,17-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-20-iodo-4,8,16-trimethyl-3-oxo-8,11,13,18-icosatetraenoate | C43H80BrIO6Si3 | 详情 | 详情 |