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【结 构 式】 
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【分子编号】42629 【品名】(1-bromo-2-propenyl)(trimethyl)silane 【CA登记号】94397-40-7 |
【 分 子 式 】C6H13BrSi 【 分 子 量 】193.15872 【元素组成】C 37.31% H 6.78% Br 41.37% Si 14.54% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)The intermediate (XXI) has been obtained as follows: The condensation of the chiral benzylated hydroxypentanone (XII) with the chiral aldehyde (XIII) by means of DCHBCl gives the chiral hydroxyheptanone (XIV), which is protected at the OH group with p-methoxybenzyl trichloroacetimidate (Pmb-Tca), yielding the expected benzyl ether (XV). The reduction of the CO group of (XV) by means of LiAlH4, with simultaneous debenzylation affords the alpha-diol (XVI), which is oxidized with NaIO4 to provide the aldehyde (XVII). The condensation of (XVII) with the allyl compound (XVIII) by means of CrCl2 and KH in THF gives the octadiene compound (XIX), which is desilylated with camphorsulfonic acid (CSA) to yield the unsaturated alcohol (XX). Finally, this alcohol is oxidized with DMP to the desired intermediate aldehyde (XXI).
| 【1】 Paterson, I.; Florence, G.J.; Synthesis of (+)-discodermolide and analogues by control of asymmetric induction in aldol reactions of gamma-chiral (Z)-enals. Tetrahedron Lett 2000, 41, 35, 6935. |
| 【2】 Paterson, I.; et al.; Total synthesis of the antimicrotubule agent (+)-discodermolide using boron-mediated aldol reactions of chiral ketones. Angew Chem. Int Ed Engl 2000, 39, 2, 377. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 42623 | (1S)-1-methyl-2-oxobutyl benzoate | C12H14O3 | 详情 | 详情 | |
| (XIII) | 42624 | (2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropanal | C10H22O2Si | 详情 | 详情 | |
| (XIV) | 42625 | (1S,3R,4R,5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-4-hydroxy-1,3,5-trimethyl-2-oxohexyl benzoate | C22H36O5Si | 详情 | 详情 | |
| (XV) | 42626 | (1S,3R,4R,5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4-methoxybenzyl)oxy]-1,3,5-trimethyl-2-oxohexyl benzoate | C30H44O6Si | 详情 | 详情 | |
| (XVI) | 42627 | (2S,4S,5R,6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-5-[(4-methoxybenzyl)oxy]-4,6-dimethyl-2,3-heptanediol | C23H42O5Si | 详情 | 详情 | |
| (XVII) | 42628 | (2R,3R,4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanal | C21H36O4Si | 详情 | 详情 | |
| (XVIII) | 42629 | (1-bromo-2-propenyl)(trimethyl)silane | 94397-40-7 | C6H13BrSi | 详情 | 详情 |
| (XIX) | 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 | |
| (XX) | 42631 | (2S,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadien-1-ol | C18H26O3 | 详情 | 详情 | |
| (XXI) | 42632 | (2R,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadienal | C18H24O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXV)The intermediate (XLI) has been obtained as follows: The condensation of the silylated propionic aldehyde (I) with the chiral allene (XXIII) by means of BF3/Et2O gives the acetylenic alcohol (XXIV), which is desilylated with TBAF, yielding the diol (XXV). The reaction of (XXV) with p-methoxybenzaldehyde dimethyl acetal (XXVI) affords the cyclic ketal (XXVII), which is treated with Red-Al to provided the primary alcohol (XXVIII). The asymmetric Sharpless epoxidation of the double bond of (XXVIII) gives the epoxide (XXIX), which is methylated with Me2CuCNLi2, yielding the chiral diol (XXX). The regioselective acylation of (XXX) with pivaloyl chloride affords the monopivalate (XXXI), which is silylated with Tes-Otf, providing the silyl ether (XXXII). The reductive cleavage of the pivalate ester of (XXXII) with Red-Al furnishes the primary alcohol (XXXIII), which is oxidized with DMP to the aldehyde (XXXIV). The condensation of (XXXIV) with the bromoallyl compound (XXXV) gives the homoallyl alcohol (XXXVI), which is treated with NaH in THF to afford the conjugated diene (XXXVII) (2). The reductive cleavage of the cyclic ketal group of (XXXVII) with iBu2AlH gives the primary alcohol (XXXVIII), which is treated with I2 and PPh3 to yield the iodo derivative (XXXIX). Finally, this compound is condensed with 9-methoxy-9-borabicyclo[3,3,1]nonane (XL) by means of BuLi in THF/ethyl ether to furnish the desired intermediate, the lithium salt (XLI).
| 【1】 Marshall, J.A.; Hohns, B.A.; Total synthesis of (+)-discodermolide. J Org Chem 1998, 63, 22, 7885. |
| 【2】 Marsshall, J.A.; et al.; Synthesis of discodermolide subunits by SE2' addition of nonracemic allenylstannanes to aldehydes. J Org Chem 1998, 63, 3, 817. |
| 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) | 42735 | (2S)-2-methyl-3-[(triethylsilyl)oxy]propanal | C10H22O2Si | 详情 | 详情 | |
| (XXIII) | 42756 | 2-(tributylstannyl)-2,3-pentadienyl pivalate | C22H42O2Sn | 详情 | 详情 | |
| (XXIV) | 42757 | (4R,5S,6S)-5-hydroxy-4,6-dimethyl-7-[(triethylsilyl)oxy]-2-heptynyl pivalate | C20H38O4Si | 详情 | 详情 | |
| (XXV) | 42758 | (4R,5S,6S)-5,7-dihydroxy-4,6-dimethyl-2-heptynyl pivalate | C14H24O4 | 详情 | 详情 | |
| (XXVI) | 26485 | 1-(dimethoxymethyl)-4-methoxybenzene | 2186-92-7 | C10H14O3 | 详情 | 详情 |
| (XXVII) | 42759 | (4R)-4-[(2R,4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2-pentynyl pivalate | C22H30O5 | 详情 | 详情 | |
| (XXVIII) | 42760 | (E,4R)-4-[(2R,4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2-penten-1-ol | C17H24O4 | 详情 | 详情 | |
| (XXIX) | 42761 | ((2S,3R)-3-[(1R)-1-[(2R,4R,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]oxiranyl)methanol | C17H24O5 | 详情 | 详情 | |
| (XXX) | 42762 | (2S,3S,4R)-4-[(2R,4R,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2-methyl-1,3-pentanediol | C18H28O5 | 详情 | 详情 | |
| (XXXI) | 42763 | (2S,3S,4R)-3-hydroxy-4-[(2R,4R,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2-methylpentyl pivalate | C23H36O6 | 详情 | 详情 | |
| (XXXII) | 42764 | (2S,3S,4S)-4-[(2R,4R,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2-methyl-3-[(triethylsilyl)oxy]pentyl pivalate | C29H50O6Si | 详情 | 详情 | |
| (XXXIII) | 42765 | (2S,3S,4S)-4-[(2R,4R,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2-methyl-3-[(triethylsilyl)oxy]-1-pentanol | C24H42O5Si | 详情 | 详情 | |
| (XXXIV) | 42766 | (2R,3R,4S)-4-[(2R,4R,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2-methyl-3-[(triethylsilyl)oxy]pentanal | C24H40O5Si | 详情 | 详情 | |
| (XXXV) | 42629 | (1-bromo-2-propenyl)(trimethyl)silane | 94397-40-7 | C6H13BrSi | 详情 | 详情 |
| (XXXVI) | 42767 | (3S,4R,5S,6S,7S)-7-[(2R,4R,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-5-methyl-6-[(triethylsilyl)oxy]-3-(trimethylsilyl)-1-octen-4-ol | C30H54O5Si2 | 详情 | 详情 | |
| (XXXVII) | 42768 | triethyl[((1S,2S,3Z)-1-[(1S)-1-[(2R,4R,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2-methyl-3,5-hexadienyl)oxy]silane; 4-((2R,4R,5S)-4-[(1S,2S,3S,4Z)-1,3-dimethyl-2-[(triethylsilyl)oxy]-4,6-heptadienyl]-5-methyl-1,3-dioxan-2-yl)phenyl methyl ether | C27H44O4Si | 详情 | 详情 | |
| (XXXVIII) | 42769 | (2S,3R,4S,5S,6S,7Z)-3-[(4-methoxybenzyl)oxy]-2,4,6-trimethyl-5-[(triethylsilyl)oxy]-7,9-decadien-1-ol | C27H46O4Si | 详情 | 详情 | |
| (XXXIX) | 42770 | triethyl[((1S,2S,3Z)-1-[(1S,2S,3R)-4-iodo-2-[(4-methoxybenzyl)oxy]-1,3-dimethylbutyl]-2-methyl-3,5-hexadienyl)oxy]silane; (1S,2S,3Z)-1-[(1S,2S,3R)-4-iodo-2-[(4-methoxybenzyl)oxy]-1,3-dimethylbutyl]-2-methyl-3,5-hexadienyl triethylsilyl ether | C27H45IO3Si | 详情 | 详情 | |
| (XL) | 42771 | 9-methoxy-9-borabicyclo[3.3.1]nonane | 38050-71-4 | C9H17BO | 详情 | 详情 |
| (XLI) | 42772 | C36H62BLiO4Si | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XX)Chiral octadienoic aldehyde intermediate (XXV): The reaction of the silylated allyl bromide (XX) with CrCl2 in THF gives the Cr derivative (XXI), which is condensed with the chiral pentanoic aldehyde intermediate (XIX) to yield the secondary alcohol (XXII). Elimination of the Tms group of (XXII) by means of KH in THF affords the desired (Z)-diene (XXIII), which is desilylated by means of CSA in methanol/dichloromethane to provide the primary alcohol (XXIV). Finally this compound is oxidized by means of DMP in dichloromethane to furnish the target, chiral octadienoic aldehyde intermediate (XXV).
| 【1】 Paterson, I.; Florence, G.J.; Gerlach, K.; Scott, J.P.; Sereinig, N.; A practical synthesis of (+)-discodermolide and analogues: Fragment union by complex aldol reactions. J Am Chem Soc 2001, 123, 39, 9535. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIX) | 42628 | (2R,3R,4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanal | C21H36O4Si | 详情 | 详情 | |
| (XX) | 42629 | (1-bromo-2-propenyl)(trimethyl)silane | 94397-40-7 | C6H13BrSi | 详情 | 详情 |
| (XXI) | 62840 | chloro[(E)-3-(trimethylsilyl)-2-propenyl]chromium | C6H13ClCrSi | 详情 | 详情 | |
| (XXII) | 62841 | (3R,4S,5S,6R,7S)-8-{[tert-butyl(dimethyl)silyl]oxy}-6-[(4-methoxybenzyl)oxy]-5,7-dimethyl-3-(trimethylsilyl)-1-octen-4-ol | C27H50O4Si2 | 详情 | 详情 | |
| (XXIII) | 46630 | 2,4,4-trimethyl-5,6-dihydro-4H-1,3-oxazine | C7H13NO | 详情 | 详情 | |
| (XXIV) | 42631 | (2S,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadien-1-ol | C18H26O3 | 详情 | 详情 | |
| (XXV) | 42632 | (2R,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadienal | C18H24O3 | 详情 | 详情 |