|
【结 构 式】 
|
【分子编号】62115 【品名】5-(trimethylsilyl)-4-pentynal 【CA登记号】 |
【 分 子 式 】C8H14OSi 【 分 子 量 】154.28406 【元素组成】C 62.28% H 9.15% O 10.37% Si 18.2% |
合成路线1
该中间体在本合成路线中的序号：(VII)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：(II)The oxidation of 5-(trimethylsilyl)-4-pentyn-1-ol (I) with oxalyl chloride in dichloromethane gives the corresponding aldehyde (II),which is condensed with furan (III) by means of BuLi in THF, yielding 1-(2-furyl)-5-(trimethylsilyl)-4-pentyn-1-ol (IV). The optical resolution of (IV) by means of diisopropyl-L-tartrate affords the (R)-isomer (V), which is treated with NBS and sodium acetate in THF to provide the dihydropyranone derivative (VI). The reaction of (VI) with ethyl vinyl ether (VII) by means of PPTS gives the 1-ethoxyethyl ether as a diastereomeric mixture that is separated by column chromatography affording the desired isomer (VIII). The reduction of the carbonyl group of (VIII) by means of LAH in ethyl ether provides alcohol (IX) along with minor amounts of its diastereomer that is separated by column chromatography. The dihydroxylation of (IX) by means of OsO4 in ethyl ether proceeded diastereoselectively giving triol (X), which is treated with 2,2-dimethoxypropane (XI) and PPTS in acetone to yield the acetonide (XII). The reaction of (XII) with thiocarbonyl diimidazole (TCDI) in dichloroethane affords intermediate (XIII), which is submitted to a radical cyclization by means of Bu3SnH and AIBN in benzene to provide the exomethylene derivative (XIV). The oxidation of the vinylsilane (XIV) by means of NaIO4 and OsO4 in t-butanol/pyridine gives the ketone (XV), which is submitted to a Birch reduction with Na in liquid ammonia to yield alcohol (XVI) along with some of its diastereomer that is separated by chromatography. The reaction (XVI) with benzyl bromide and NaH in THF affords the benzyl ether (XVII), which is treated with HCl in THF to provide the lactol (XVIII). The reduction of (XVIII) with NaBH4 in methanol/dichloromethane gives the diol (XIX), which is selectively monosilylated with Tbdms-Cl, yielding the primary silyl ether (XX). The oxidation of the secondary OH group of (XX) by means of TPAP in dichloromethane affords the cyclopentanone (XXI), which is treated with hydroxylamine and pyridine in methanol to provide the corresponding oxime (XXII). The oxime (XXII) was subjected to a Beckmann rearrangement by means of SOCl2 to give the lactam (XXIII), which is finally desilylated by means of TBAF in THF to yield the primary alcohol (XXIV).
| 【1】 Honda, T.; et al.; Enantioselective synthesis of indolizidine alkaloids: Formal synthesis of (-)-swainsonine and of (+)-pumiliotoxin 251D. J Chem Soc - Perkins Trans I 1994, 15, 2091. |
| 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) | 62628 | 5-(trimethylsilyl)-4-pentyn-1-ol | C8H16OSi | 详情 | 详情 | |
| (II) | 62115 | 5-(trimethylsilyl)-4-pentynal | C8H14OSi | 详情 | 详情 | |
| (III) | 22372 | Furan | 110-00-9 | C4H4O | 详情 | 详情 |
| (IV) | 62629 | 1-(2-furyl)-5-(trimethylsilyl)-4-pentyn-1-ol | C12H18O2Si | 详情 | 详情 | |
| (V) | 62630 | (1R)-1-(2-furyl)-5-(trimethylsilyl)-4-pentyn-1-ol | C12H18O2Si | 详情 | 详情 | |
| (VI) | 62631 | (2R)-6-hydroxy-2-[4-(trimethylsilyl)-3-butynyl]-2H-pyran-3(6H)-one | C12H18O3Si | 详情 | 详情 | |
| (VII) | 62632 | 1-propoxyethylene; propyl vinyl ether | C5H10O | 详情 | 详情 | |
| (VIII) | 62633 | (2R,6R)-6-(1-propoxyethoxy)-2-[4-(trimethylsilyl)-3-butynyl]-2H-pyran-3(6H)-one | C17H28O4Si | 详情 | 详情 | |
| (IX) | 62634 | (2R,3S,6R)-6-(1-propoxyethoxy)-2-[4-(trimethylsilyl)-3-butynyl]-3,6-dihydro-2H-pyran-3-ol | C17H30O4Si | 详情 | 详情 | |
| (X) | 62635 | (2R,3S,4S,5S,6R)-2-(1-propoxyethoxy)-6-[4-(trimethylsilyl)-3-butynyl]tetrahydro-2H-pyran-3,4,5-triol | C17H32O6Si | 详情 | 详情 | |
| (XI) | 10722 | 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane | 77-76-9 | C5H12O2 | 详情 | 详情 |
| (XII) | 62636 | (3aS,4R,6R,7R,7aS)-2,2-dimethyl-4-(1-propoxyethoxy)-6-[4-(trimethylsilyl)-3-butynyl]tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-ol | C20H36O6Si | 详情 | 详情 | |
| (XIII) | 62637 | O-{(3aS,4R,6R,7R,7aR)-2,2-dimethyl-4-(1-propoxyethoxy)-6-[4-(trimethylsilyl)-3-butynyl]tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-yl} 1H-imidazole-1-carbothioate | C24H38N2O6SSi | 详情 | 详情 | |
| (XIV) | 62638 | (3aS,4R,5aR,8aS,8bS)-2,2-dimethyl-8-[(E)-(trimethylsilyl)methylidene]hexahydrocyclopenta[b][1,3]dioxolo[4,5-d]pyran-4(4H)-yl 1-propoxyethyl ether; {[(3aS,4R,5aR,8aS,8bS)-2,2-dimethyl-4-(1-propoxyethoxy)hexahydrocyclopenta[b][1,3]dioxolo[4,5-d]pyran-8(4H)-ylidene]methyl}(trimethyl)silane | C20H36O5Si | 详情 | 详情 | |
| (XV) | 62639 | (3aS,4R,5aR,8aS,8bS)-2,2-dimethyl-4-(1-propoxyethoxy)hexahydrocyclopenta[b][1,3]dioxolo[4,5-d]pyran-8(4H)-one | C16H26O6 | 详情 | 详情 | |
| (XVI) | 62640 | (3aS,4R,5aR,8R,8aS,8bS)-2-ethyl-2-methyl-4-(1-propoxyethoxy)octahydrocyclopenta[b][1,3]dioxolo[4,5-d]pyran-8-ol | C17H30O6 | 详情 | 详情 | |
| (XVII) | 62641 | (3aS,4R,5aR,8R,8aS,8bS)-8-(benzyloxy)-2,2-dimethyloctahydrocyclopenta[b][1,3]dioxolo[4,5-d]pyran-4-yl 1-propoxyethyl ether; (3aS,4R,5aR,8R,8aS,8bS)-8-(benzyloxy)-2,2-dimethyl-4-(1-propoxyethoxy)octahydrocyclopenta[b][1,3]dioxolo[4,5-d]pyran | C23H34O6 | 详情 | 详情 | |
| (XVIII) | 62642 | (3aS,4S,5aR,8R,8aS,8bS)-8-(benzyloxy)-2,2-dimethyloctahydrocyclopenta[b][1,3]dioxolo[4,5-d]pyran-4-ol | C18H24O5 | 详情 | 详情 | |
| (XIX) | 62643 | (1R,2R,3R)-3-(benzyloxy)-2-[(4S,5R)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]cyclopentanol | C18H26O5 | 详情 | 详情 | |
| (XX) | 62644 | (1R,2R,3R)-3-(benzyloxy)-2-[(4S,5R)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-1,3-dioxolan-4-yl]cyclopentanol | C24H40O5Si | 详情 | 详情 | |
| (XXI) | 62645 | (2R,3R)-3-(benzyloxy)-2-[(4S,5R)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-1,3-dioxolan-4-yl]cyclopentanone | C24H38O5Si | 详情 | 详情 | |
| (XXII) | 62646 | (2R,3R)-3-(benzyloxy)-2-[(4S,5R)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-1,3-dioxolan-4-yl]cyclopentanone oxime | C24H39NO5Si | 详情 | 详情 | |
| (XXIII) | 62647 | (5R,6R)-5-(benzyloxy)-6-[(4S,5R)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-piperidinone | C24H39NO5Si | 详情 | 详情 | |
| (XXIV) | 62648 | (5R,6R)-5-(benzyloxy)-6-[(4S,5R)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-piperidinone | C18H25NO5 | 详情 | 详情 |