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【结 构 式】 
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【分子编号】46122 【品名】ethyl(triphenyl)phosphonium iodide 【CA登记号】 |
【 分 子 式 】C20H20IP 【 分 子 量 】418.257032 【元素组成】C 57.43% H 4.82% I 30.34% P 7.41% |
合成路线1
该中间体在本合成路线中的序号：(XXIX)Synthesis of the thiazole intermediate (XXXIII): The reaction of 2-methyl-3-(2-methylthiazol-4-yl)-2(E)-propenal (XXII) with trimethylsilyl cyanide and Et2AlCl catalyzed by a chiral bidentate phosphine oxide catalyst gives the chiral alpha-hydroxybutenenitrile (XXIII), which is hydrolyzed to the corresponding carboxylic ester (XXIV) by means of HCl in hot ethanol/water. The reaction of (XXIV) with Tbdms-Cl and imidazole yields the silylated hydroxyester (XXV), which is reduced with DIBAL in toluene, affording the aldehyde (XXVI). The reaction of (XXVI) with phosphonium salt (XXVII), LHMDS, Hg(OAc)2 and tetrabutylammonium iodine (TBAI) in THF provides the olefin (XXX), which is iodinated with I2 and NaHMDS in THF to give the iodinated olefin (XXXI). The desilylation of (XXXI) with HF and pyridine in THF yields the secondary alcohol (XXXII), which is acylated with Ac2O, TEA and DMAP in dichloromethane to afford the target thiazole intermediate (XXXIII).
| 【1】 Sawada, D.; et al.; Enantioselective total synthesis of epothilones A and B using multifunctional asymmetric catalysis. J Am Chem Soc 2000, 122, 43, 10521. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXII) | 44456 | (E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal | C8H9NOS | 详情 | 详情 | |
| (XXIII) | 44520 | (2R,3E)-2-hydroxy-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenenitrile | C9H10N2OS | 详情 | 详情 | |
| (XXIV) | 44521 | ethyl (2R,3E)-2-hydroxy-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenoate | C11H15NO3S | 详情 | 详情 | |
| (XXV) | 44522 | ethyl (2R,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenoate | C17H29NO3SSi | 详情 | 详情 | |
| (XXVI) | 44523 | (2R,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenal | C15H25NO2SSi | 详情 | 详情 | |
| (XXVII) | 39163 | (methoxymethyl)(triphenyl)phosphonium chloride | 4009-98-7 | C20H20ClOP | 详情 | 详情 |
| (XXVIII) | 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 | |
| (XXIX) | 46122 | ethyl(triphenyl)phosphonium iodide | C20H20IP | 详情 | 详情 | |
| (XXX) | 46123 | tert-butyl(dimethyl)silyl (1S,3E)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl ether; 4-((1E,3S,5E)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,5-heptadienyl)-2-methyl-1,3-thiazole | C18H31NOSSi | 详情 | 详情 | |
| (XXXI) | 26246 | tert-butyl(dimethyl)silyl (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl ether; 4-((1E,3S,5Z)-3-[[tert-butyl(dimethyl)silyl]oxy]-6-iodo-2-methyl-1,5-heptadienyl)-2-methyl-1,3-thiazole | C18H30INOSSi | 详情 | 详情 | |
| (XXXII) | 46124 | (1E,3S,5Z)-6-iodo-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-heptadien-3-ol | C12H16INOS | 详情 | 详情 | |
| (XXXIII) | 46125 | (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl acetate | C14H18INO2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXIX)Synthesis of the thiazole intermediate (XXXIII): The reaction of 2-methyl-3-(2-methylthiazol-4-yl)-2(E)-propenal (XXII) with trimethylsilyl cyanide and Et2AlCl catalyzed by a chiral bidentate phosphine oxide catalyst gives the chiral alpha-hydroxybutenenitrile (XXIII), which is hydrolyzed to the corresponding carboxylic ester (XXIV) by means of HCl in hot ethanol/water. The reaction of (XXIV) with Tbdms-Cl and imidazole yields the silylated hydroxyester (XXV), which is reduced with DIBAL in toluene, affording the aldehyde (XXVI). The reaction of (XXVI) with phosphonium salt (XXVII), LHMDS, Hg(OAc)2 and tetrabutylammonium iodine (TBAI) in THF provides the olefin (XXX), which is iodinated with I2 and NaHMDS in THF to give the iodinated olefin (XXXI). The desilylation of (XXXI) with HF and pyridine in THF yields the secondary alcohol (XXXII), which is acylated with Ac2O, TEA and DMAP in dichloromethane to afford the target thiazole intermediate (XXXIII).
| 【1】 Sawada, D.; et al.; Enantioselective total synthesis of epothilones A and B using multifunctional asymmetric catalysis. J Am Chem Soc 2000, 122, 43, 10521. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXII) | 44456 | (E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal | C8H9NOS | 详情 | 详情 | |
| (XXIII) | 44520 | (2R,3E)-2-hydroxy-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenenitrile | C9H10N2OS | 详情 | 详情 | |
| (XXIV) | 44521 | ethyl (2R,3E)-2-hydroxy-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenoate | C11H15NO3S | 详情 | 详情 | |
| (XXV) | 44522 | ethyl (2R,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenoate | C17H29NO3SSi | 详情 | 详情 | |
| (XXVI) | 44523 | (2R,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenal | C15H25NO2SSi | 详情 | 详情 | |
| (XXVII) | 39163 | (methoxymethyl)(triphenyl)phosphonium chloride | 4009-98-7 | C20H20ClOP | 详情 | 详情 |
| (XXVIII) | 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 | |
| (XXIX) | 46122 | ethyl(triphenyl)phosphonium iodide | C20H20IP | 详情 | 详情 | |
| (XXX) | 46123 | tert-butyl(dimethyl)silyl (1S,3E)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl ether; 4-((1E,3S,5E)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,5-heptadienyl)-2-methyl-1,3-thiazole | C18H31NOSSi | 详情 | 详情 | |
| (XXXI) | 26246 | tert-butyl(dimethyl)silyl (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl ether; 4-((1E,3S,5Z)-3-[[tert-butyl(dimethyl)silyl]oxy]-6-iodo-2-methyl-1,5-heptadienyl)-2-methyl-1,3-thiazole | C18H30INOSSi | 详情 | 详情 | |
| (XXXII) | 46124 | (1E,3S,5Z)-6-iodo-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-heptadien-3-ol | C12H16INOS | 详情 | 详情 | |
| (XXXIII) | 46125 | (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl acetate | C14H18INO2S | 详情 | 详情 |