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【结 构 式】 
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【分子编号】62124 【品名】(2R,3R,5S,6S)-6-[(E)-3-iodo-2-butenyl]-2,5-dimethyltetrahydro-2H-pyran-3-yl azide; (2R,3R,5S,6S)-3-azido-6-[(E)-3-iodo-2-butenyl]-2,5-dimethyltetrahydro-2H-pyran 【CA登记号】 |
【 分 子 式 】C11H18IN3O 【 分 子 量 】335.18801 【元素组成】C 39.42% H 5.41% I 37.86% N 12.54% O 4.77% |
合成路线1
该中间体在本合成路线中的序号：(XVI)Hetero Diels-Alder reaction between diene (VI) and aldehyde (VII) in the presence of chiral chromium complex furnishes the optically active dihydropyran compound (VIII). Subsequent oxidation of the silyl enol ether moiety of (VIII) with m CPBA under Rubottom conditions affords the alpha-hydroxy ketone (IX). Reduction of ketone (IX) is accomplished via the tosyl hydrazone (X), which is then reduced to (XI) employing NaBH3CN. Desilylation of (XI) with tetrabutylammonium fluoride gives the terminal acetylene (XII), which is further isomerized to the thermodynamically more stable internal alkyne (XIII) in the presence of potassium tert-butoxide in DMSO. Treatment of (XIII) with Schwartz's reagent, followed by quenching of the vinylzirconium intermediate with I2 leads to the vinyl iodide (XIV). After conversion of alcohol (XIV) into the chloromethanesulfonate (XV), displacement with LiN3 provides azide (XVI).
| 【1】 Thompson, C.F.; Jamison, T.F; Jacobsen, E.N.; Total synthesis of FR901464. Convergent assembly of chiral componenents prepared by asymmetric catalysis. J Am Chem Soc 2000, 122, 45, 10482. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 62114 | triethyl({(E)-1-[(Z)ethylidene]-2-butenyl}oxy)silane; (E)-1-[(Z)ethylidene]-2-butenyl triethylsilyl ether | C12H24OSi | 详情 | 详情 | |
| (VII) | 62115 | 5-(trimethylsilyl)-4-pentynal | C8H14OSi | 详情 | 详情 | |
| (VIII) | 62116 | (2S,3R,6R)-3,6-dimethyl-2-[4-(trimethylsilyl)-3-butynyl]-3,6-dihydro-2H-pyran-4-yl triethylsilyl ether; (4-{(2S,3R,6R)-3,6-dimethyl-4-[(triethylsilyl)oxy]-3,6-dihydro-2H-pyran-2-yl}-1-butynyl)(trimethyl)silane | C20H38O2Si2 | 详情 | 详情 | |
| (IX) | 62117 | (2R,3R,5R,6S)-3-hydroxy-2,5-dimethyl-6-[4-(trimethylsilyl)-3-butynyl]tetrahydro-4H-pyran-4-one | C14H24O3Si | 详情 | 详情 | |
| (X) | 62118 | N'-{(2R,3S,5S,6S)-3-hydroxy-2,5-dimethyl-6-[4-(trimethylsilyl)-3-butynyl]tetrahydro-4H-pyran-4-ylidene}-4-methylbenzenesulfonohydrazide | C21H32N2O4SSi | 详情 | 详情 | |
| (XI) | 62119 | (2R,3S,5S,6S)-2,5-dimethyl-6-[4-(trimethylsilyl)-3-butynyl]tetrahydro-2H-pyran-3-ol | C14H26O2Si | 详情 | 详情 | |
| (XII) | 62120 | (2R,3S,5S,6S)-6-(3-butynyl)-2,5-dimethyltetrahydro-2H-pyran-3-ol | C11H18O2 | 详情 | 详情 | |
| (XIII) | 62121 | (2R,3S,5S,6S)-6-(2-butynyl)-2,5-dimethyltetrahydro-2H-pyran-3-ol | C11H18O2 | 详情 | 详情 | |
| (XIV) | 62122 | (2R,3S,5S,6S)-6-[(E)-3-iodo-2-butenyl]-2,5-dimethyltetrahydro-2H-pyran-3-ol | C11H19IO2 | 详情 | 详情 | |
| (XV) | 62123 | (2R,3S,5S,6S)-6-[(E)-3-iodo-2-butenyl]-2,5-dimethyltetrahydro-2H-pyran-3-yl chloromethanesulfonate | C12H20ClIO4S | 详情 | 详情 | |
| (XVI) | 62124 | (2R,3R,5S,6S)-6-[(E)-3-iodo-2-butenyl]-2,5-dimethyltetrahydro-2H-pyran-3-yl azide; (2R,3R,5S,6S)-3-azido-6-[(E)-3-iodo-2-butenyl]-2,5-dimethyltetrahydro-2H-pyran | C11H18IN3O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVI)Enantioselective cycloaddition of dienyne (XVII) with aldehyde (XVIII) affords dihydropyran (XIX). Subsequent Rubottom oxidation of the silyl enol ether (XIX) gives a mixture of epimeric alpha-hydroxy ketones (XX), which is further equilibrated to the desired stereoisomer (XXI) in the presence of K2CO3 in MeOH. After protection of the hydroxyl group of (XXI) as the triisopropylsilyl ether (XXII), Wittig reaction with methylene triphenylphosphorane provides the exocyclic olefin (XXIII). Replacement of the silylated primary hydroxyl of (XXIII) with a iodide group to yield (XXIV) is accomplished by treatment with I2 and PPh3. Removal of the remaining silyl group of (XXIV) with tetrabutylammonium fluoride and acetic acid yields the allylic alcohol (XXV), which can be diastereoselectively epoxidized with t butyl hydroperoxide and vanadyl acetylacetonate, producing (XXVI) as a single isomer. Reprotection of (XXVI) with triisopropylsilyl triflate affords the corresponding silyl ether (XXVII). Hydrozirconation of acetylene (XXVII), followed by Negishi coupling with the vinyl iodide (XVI) furnishes the diene system (XXVIII). Subsequent azido group reduction in (XXVIII) with trimethylphosphine in moist THF provides amine (XXIX).
| 【1】 Thompson, C.F.; Jamison, T.F; Jacobsen, E.N.; Total synthesis of FR901464. Convergent assembly of chiral componenents prepared by asymmetric catalysis. J Am Chem Soc 2000, 122, 45, 10482. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVI) | 62124 | (2R,3R,5S,6S)-6-[(E)-3-iodo-2-butenyl]-2,5-dimethyltetrahydro-2H-pyran-3-yl azide; (2R,3R,5S,6S)-3-azido-6-[(E)-3-iodo-2-butenyl]-2,5-dimethyltetrahydro-2H-pyran | C11H18IN3O | 详情 | 详情 | |
| (XVII) | 62125 | triethyl{[(E)-1-methylene-2-penten-4-ynyl]oxy}silane; (E)-1-methylene-2-penten-4-ynyl triethylsilyl ether | C12H20OSi | 详情 | 详情 | |
| (XVIII) | 61170 | 2-{[tert-butyl(dimethyl)silyl]oxy}acetaldehyde；tert-butyldimethylsilyloxy acetaldehyde | 102191-92-4 | C8H18O2Si | 详情 | 详情 |
| (XIX) | 62126 | tert-butyl(dimethyl)silyl {(2R,6S)-6-ethynyl-4-[(triethylsilyl)oxy]-3,6-dihydro-2H-pyran-2-yl}methyl ether; tert-butyl({(2R,6S)-6-ethynyl-4-[(triethylsilyl)oxy]-3,6-dihydro-2H-pyran-2-yl}methoxy)dimethylsilane | C20H38O3Si2 | 详情 | 详情 | |
| (XX) | 62127 | (2R,6R)-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-ethynyl-3-hydroxytetrahydro-4H-pyran-4-one | C14H24O4Si | 详情 | 详情 | |
| (XXI) | 62128 | (2R,3R,6R)-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-ethynyl-3-hydroxytetrahydro-4H-pyran-4-one | C14H24O4Si | 详情 | 详情 | |
| (XXII) | 62129 | (2R,3R,6R)-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-ethynyl-3-[(triisopropylsilyl)oxy]tetrahydro-4H-pyran-4-one | C23H44O4Si2 | 详情 | 详情 | |
| (XXIII) | 62130 | tert-butyl(dimethyl)silyl {(2R,5S,6R)-6-ethynyl-4-methylene-5-[(triisopropylsilyl)oxy]tetrahydro-2H-pyran-2-yl}methyl ether; tert-butyl({(2R,5S,6R)-6-ethynyl-4-methylene-5-[(triisopropylsilyl)oxy]tetrahydro-2H-pyran-2-yl}methoxy)dimethylsilane | C24H46O3Si2 | 详情 | 详情 | |
| (XXIV) | 62131 | (2R,3S,6R)-2-ethynyl-6-(iodomethyl)-4-methylenetetrahydro-2H-pyran-3-yl triisopropylsilyl ether; {[(2R,3S,6R)-2-ethynyl-6-(iodomethyl)-4-methylenetetrahydro-2H-pyran-3-yl]oxy}(triisopropyl)silane | C18H31IO2Si | 详情 | 详情 | |
| (XXV) | 62132 | (2R,3S,6R)-2-ethynyl-6-(iodomethyl)-4-methylenetetrahydro-2H-pyran-3-ol | C9H11IO2 | 详情 | 详情 | |
| (XXVI) | 62133 | (3R,4R,5R,7R)-5-ethynyl-7-(iodomethyl)-1,6-dioxaspiro[2.5]octan-4-ol | C9H11IO3 | 详情 | 详情 | |
| (XXVII) | 62134 | (3R,4R,5R,7R)-5-ethynyl-7-(iodomethyl)-1,6-dioxaspiro[2.5]oct-4-yl triethylsilyl ether; triethyl{[(3R,4R,5R,7R)-5-ethynyl-7-(iodomethyl)-1,6-dioxaspiro[2.5]oct-4-yl]oxy}silane | C15H25IO3Si | 详情 | 详情 | |
| (XXVIII) | 62135 | (3R,4R,5R,7R)-5-{(1E,3E)-5-[(2S,3S,5R,6R)-5-azido-3,6-dimethyltetrahydro-2H-pyran-2-yl]-3-methyl-1,3-pentadienyl}-7-(iodomethyl)-1,6-dioxaspiro[2.5]oct-4-yl triethylsilyl ether; {[(3R,4R,5R,7R)-5-{(1E,3E)-5-[(2S,3S,5R,6R)-5-azido-3,6-dimethyltetrahydro-2H-pyran-2-yl]-3-methyl-1,3-pentadienyl}-7-(iodomethyl)-1,6-dioxaspiro[2.5]oct-4-yl]oxy}(triethyl)silane | C26H44IN3O4Si | 详情 | 详情 | |
| (XXIX) | 62136 | (2R,3R,5S,6S)-6-((2E,4E)-5-{(3R,4R,5R,7R)-7-(iodomethyl)-4-[(triethylsilyl)oxy]-1,6-dioxaspiro[2.5]oct-5-yl}-3-methyl-2,4-pentadienyl)-2,5-dimethyltetrahydro-2H-pyran-3-amine; (2R,3R,5S,6S)-6-((2E,4E)-5-{(3R,4R,5R,7R)-7-(iodomethyl)-4-[(triethylsilyl)oxy]-1,6-dioxaspiro[2.5]oct-5-yl}-3-methyl-2,4-pentadienyl)-2,5-dimethyltetrahydro-2H-pyran-3-ylamine | C26H46INO4Si | 详情 | 详情 |