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【结 构 式】 
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【分子编号】44490 【品名】tert-butyl(dimethyl)silyl (1S,2E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-1-vinyl-2-propenyl ether; 4-((1E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,4-pentadienyl)-2-methyl-1,3-thiazole 【CA登记号】 |
【 分 子 式 】C16H27NOSSi 【 分 子 量 】309.54802 【元素组成】C 62.08% H 8.79% N 4.52% O 5.17% S 10.36% Si 9.07% |
合成路线1
该中间体在本合成路线中的序号：(XXI)Synthesis of the thiazole intermediate (XXVI): The Grignard reaction of 2-methyl-3-(2-methylthiazol-4-yl)-2(E)-propenal (XVII) with vinylmagnesium bromide (XVIII) in THF gives the racemic secondary alcohol (XIX), which is submitted to enzymatic optical resolution with Pseudomonas AK lipase and vinyl acetate to yield the desired (S)-secondary alcohol (XX) along with the (R)-acetate, which is easily separated by chromatography. The silylation of (XX) with Tbdms-Cl and imidazole in DMF affords the silyl ether (XXI). The selective hydroboration of the terminal double bond of (XXI) with dicyclohexylborane followed by oxidation with H2O2 provided the primary alcohol (XXII), which is oxidized with DMP in dichloromethane to give the corresponding aldehyde (XXIII). The reaction of (XXIII) with the iodomethyl phosphonium salt (XXIV) by means of NaHMDS in THF yields the cis-iodovinyl compound (XXV), which is desilylated with aqueous HF in acetonitrile, affording the corresponding alcohol (XXVI). Finally, this alcohol is treated with acetic anhydride, TEA and DMAP to provide the desired thiazole intermediate (XXVII).
| 【1】 Panek, J.S.; Zhu, B.; Total synthesis of apothilone A. Org Lett 2000, 2, 17, 2575. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVII) | 44456 | (E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal | C8H9NOS | 详情 | 详情 | |
| (XVIII) | 16524 | bromo(vinyl)magnesium | 1826-67-1 | C2H3BrMg | 详情 | 详情 |
| (XIX) | 44488 | (1E)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,4-pentadien-3-ol | C10H13NOS | 详情 | 详情 | |
| (XX) | 44489 | (1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,4-pentadien-3-ol | C10H13NOS | 详情 | 详情 | |
| (XXI) | 44490 | tert-butyl(dimethyl)silyl (1S,2E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-1-vinyl-2-propenyl ether; 4-((1E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,4-pentadienyl)-2-methyl-1,3-thiazole | C16H27NOSSi | 详情 | 详情 | |
| (XXII) | 40821 | (3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-penten-1-ol | C16H29NO2SSi | 详情 | 详情 | |
| (XXIII) | 40822 | (3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenal | C16H27NO2SSi | 详情 | 详情 | |
| (XXIV) | 42718 | (iodomethyl)(triphenyl)phosphonium iodide | n/a | C19H17I2P | 详情 | 详情 |
| (XXV) | 44491 | 4-((1E,3S,5Z)-3-[[tert-butyl(dimethyl)silyl]oxy]-6-iodo-2-methyl-1,5-hexadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl ether | C17H28INOSSi | 详情 | 详情 | |
| (XXVI) | 44492 | (1E,3S,5Z)-6-iodo-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol | C11H14INOS | 详情 | 详情 | |
| (XXVII) | 44493 | (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate | C13H16INO2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXI)Synthesis of the thiazole intermediate (XXVI): The Grignard reaction of 2-methyl-3-(2-methylthiazol-4-yl)-2(E)-propenal (XVII) with vinylmagnesium bromide (XVIII) in THF gives the racemic secondary alcohol (XIX), which is submitted to enzymatic optical resolution with Pseudomonas AK lipase and vinyl acetate to yield the desired (S)-secondary alcohol (XX) along with the (R)-acetate, which is easily separated by chromatography. The silylation of (XX) with Tbdms-Cl and imidazole in DMF affords the silyl ether (XXI). The selective hydroboration of the terminal double bond of (XXI) with dichlohexylborane followed by oxidation with H2O2 provides the primary alcohol (XXII), which is oxidized with DMP in dichloromethane to give the corresponding aldehyde (XXIII). The reaction of (XXIII) with the iodomethyl phosphonium salt (XXIV) by means of NaHMDS in THF yields the cis-iodovinyl compound (XXV), which is desilylated with aqueous HF in acetonitrile affording the corresponding alcohol (XXVI). Finally, this alcohol is treated with acetic anhydride, TEA and DMAP to provide the desired thiazole intermediate (XXVII).
| 【1】 Panek, J.S.; Zhu, B.; Total synthesis of apothilone A. Org Lett 2000, 2, 17, 2575. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVII) | 44456 | (E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal | C8H9NOS | 详情 | 详情 | |
| (XVIII) | 16524 | bromo(vinyl)magnesium | 1826-67-1 | C2H3BrMg | 详情 | 详情 |
| (XIX) | 44488 | (1E)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,4-pentadien-3-ol | C10H13NOS | 详情 | 详情 | |
| (XX) | 44489 | (1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,4-pentadien-3-ol | C10H13NOS | 详情 | 详情 | |
| (XXI) | 44490 | tert-butyl(dimethyl)silyl (1S,2E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-1-vinyl-2-propenyl ether; 4-((1E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,4-pentadienyl)-2-methyl-1,3-thiazole | C16H27NOSSi | 详情 | 详情 | |
| (XXII) | 40821 | (3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-penten-1-ol | C16H29NO2SSi | 详情 | 详情 | |
| (XXIII) | 40822 | (3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenal | C16H27NO2SSi | 详情 | 详情 | |
| (XXIV) | 42718 | (iodomethyl)(triphenyl)phosphonium iodide | n/a | C19H17I2P | 详情 | 详情 |
| (XXV) | 44491 | 4-((1E,3S,5Z)-3-[[tert-butyl(dimethyl)silyl]oxy]-6-iodo-2-methyl-1,5-hexadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl ether | C17H28INOSSi | 详情 | 详情 | |
| (XXVI) | 44492 | (1E,3S,5Z)-6-iodo-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol | C11H14INOS | 详情 | 详情 | |
| (XXVII) | 44493 | (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate | C13H16INO2S | 详情 | 详情 |