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【结 构 式】 
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【分子编号】42718 【品名】(iodomethyl)(triphenyl)phosphonium iodide 【CA登记号】n/a |
【 分 子 式 】C19H17I2P 【 分 子 量 】530.126682 【元素组成】C 43.05% H 3.23% I 47.88% P 5.84% |
合成路线1
该中间体在本合成路线中的序号：(XXXVI)The intermediate (XLIII) has been obtained in two related ways: 1) The protection of (2S,3S,4S)-2,4-dimethyl-1-(tert-butyldimethylsilyloxy)-5-hexen-3-ol (I) with p-methoxybenzyl bromide and NaH gives the benzyl ether (XXXIV) which is ozonolyzed with O3, yielding the aldehyde (XXXV), which is condensed with the phosphonium salt (XXXVI) by means of KHMDS to afford the iodovinyl derivative (XXXVII). The homologation of (XXXVII) with vinylzinc bromide (XXXVIII) provides the octadiene derivative (XXXIX), which is desilylated with TFA, furnishing the primary alcohol (XL). The oxidation of (XL) with DMP gives the aldehyde (XLI), which is treated with CH3-MgBr, yielding the secondary alcohol (XLII). Finally, this alcohol is oxidized with DMP to the target intermediate ketone (XLIII). 2) The protection of (2S,3R,4S)-2,4-dimethyl-1-(tert-butyldimethylsilyloxy)-5-hexen-3-ol (XVII) with p-methoxybenzyl bromide and NaH gives the benzyl ether (XLIV), which is ozonolyzed with O3, yielding the aldehyde (XLV). The reaction of (XLV) with CH3-MgBr affords the secondary alcohol (XLVI), which is desilylated with TFA.
| 【1】 Hung, D.T.; et al.; Syntheses of discodermolides useful for investigating microtubule binding and stabilization. J Am Chem Soc 1996, 118, 45, 11054. |
| 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) | 42608 | [(1R,3S,4S)-4-aminospiro[2.2]pent-1-yl]methanol | C6H11NO | 详情 | 详情 | |
| (XXXIV) | 42717 | tert-butyl([(2S,3S,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-hexenyl]oxy)dimethylsilane; tert-butyl(dimethyl)silyl (2S,3S,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-hexenyl ether | n/a | C22H38O3Si | 详情 | 详情 |
| (XXXV) | 42628 | (2R,3R,4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanal | C21H36O4Si | 详情 | 详情 | |
| (XXXVI) | 42718 | (iodomethyl)(triphenyl)phosphonium iodide | n/a | C19H17I2P | 详情 | 详情 |
| (XXXVII) | 42719 | tert-butyl([(2S,3S,4S,5Z)-6-iodo-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-hexenyl]oxy)dimethylsilane; tert-butyl(dimethyl)silyl (2S,3S,4S,5Z)-6-iodo-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-hexenyl ether | n/a | C22H37IO3Si | 详情 | 详情 |
| (XXXVIII) | 42720 | bromo(vinyl)zinc | n/a | C2H3BrZn | 详情 | 详情 |
| (XXXIX) | 42630 | tert-butyl([(2S,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadienyl]oxy)dimethylsilane; tert-butyl(dimethyl)silyl (2S,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadienyl ether | C24H40O3Si | 详情 | 详情 | |
| (XL) | 42631 | (2S,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadien-1-ol | C18H26O3 | 详情 | 详情 | |
| (XLI) | 42632 | (2R,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadienal | C18H24O3 | 详情 | 详情 | |
| (XLII) | 42721 | (3S,4S,5S,6Z)-4-[(4-methoxybenzyl)oxy]-3,5-dimethyl-6,8-nonadien-2-ol | C19H28O3 | 详情 | 详情 | |
| (XLIII) | 42722 | (3R,4S,5S,6Z)-4-[(4-methoxybenzyl)oxy]-3,5-dimethyl-6,8-nonadien-2-one | C19H26O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXVI)The diol (XLVII) has been obtained as follows: The Swern oxidation of the OH groups of (XLVII) gives the 5-oxohexanal derivative (XLVIII), which is condensed with the phosphonium salt (XXXVI) to yield the iodovinyl derivative (XLIX). Finally, this compound is homologated with vinylzinc bromide (XXXVIII) to afford the target intermediate ketone (XLIII).
| 【1】 Hung, D.T.; et al.; Syntheses of discodermolides useful for investigating microtubule binding and stabilization. J Am Chem Soc 1996, 118, 45, 11054. |
| 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) | 42701 | (2S,3R,4S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2,4-dimethyl-5-hexen-3-ol | C14H30O2Si | 详情 | 详情 | |
| (XXXVI) | 42718 | (iodomethyl)(triphenyl)phosphonium iodide | n/a | C19H17I2P | 详情 | 详情 |
| (XXXVIII) | 42720 | bromo(vinyl)zinc | n/a | C2H3BrZn | 详情 | 详情 |
| (XLIII) | 42722 | (3R,4S,5S,6Z)-4-[(4-methoxybenzyl)oxy]-3,5-dimethyl-6,8-nonadien-2-one | C19H26O3 | 详情 | 详情 | |
| (XLIV) | 42723 | tert-butyl(dimethyl)silyl (2S,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-hexenyl ether; tert-butyl([(2S,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-hexenyl]oxy)dimethylsilane | C22H38O3Si | 详情 | 详情 | |
| (XLV) | 42724 | (2R,3S,4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanal | C21H36O4Si | 详情 | 详情 | |
| (XLVI) | 42725 | (3S,4S,5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4-methoxybenzyl)oxy]-3,5-dimethyl-2-hexanol | n/a | C22H40O4Si | 详情 | 详情 |
| (XLVII) | 42726 | (2S,3S,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-1,5-hexanediol | n/a | C16H26O4 | 详情 | 详情 |
| (XLVIII) | 42727 | (2R,3S,4R)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-oxohexanal | C16H22O4 | 详情 | 详情 | |
| (XLIX) | 42728 | (3R,4S,5S,6Z)-7-iodo-4-[(4-methoxybenzyl)oxy]-3,5-dimethyl-6-hepten-2-one | C17H23IO3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XXIV)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4
该中间体在本合成路线中的序号：(XXIV)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 |