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【结 构 式】 
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【分子编号】61304 【品名】Trimethylsilylmethylmagnesium Chloride; (Trimethylsilyl)methylmagnesium chloride Solution; Chloro[(trimethylsilyl)methyl]magnesium; (TRIMETHYLSILYLMETHYL)MAGNESIUM CHLORIDE; (TRIMETHYLSILYL)METHYLMAGNESIUM CHL. SOL 【CA登记号】13170-43-9 |
【 分 子 式 】C4H11ClMgSi 【 分 子 量 】146.97454 【元素组成】C 32.69% H 7.54% Cl 24.12% Mg 16.54% Si 19.11% |
合成路线1
该中间体在本合成路线中的序号：(A)The synthesis of the dihydropyranyl acetaldehyde intermediate (XVII) has been obtained as follows: The reduction of the pentanedioic acid monoethyl ester (I) with BH3 gives the hydroxyester (II), which is oxidized with DMP to yield the aldehyde (III). The reaction of (III) with the chiral borane (IV) affords the 5-hydroxyoctenoic ester (V), which is treated with dimethylamine to provide the corresponding amide (VI). The reaction of (VI) with propenal diethylacetal (VII) gives ether (VIII), which is submitted to a ring closing metathesis reaction catalyzed by a Ru catalyst to yield the dihydropyran derivative (IX). The reaction of (IX) with tert-butyldimethylsilyloxy ethylene (X) catalyzed by LiClO4 affords the dihydropyranyl acetaldehyde (XI), which is reduced with NaBH4 and protected with Tes-Cl to provide the butyramide (XII). The reaction of (XII) with MeLi gives the pentanone (XIII), which is treated with Ph-NTf2 and KHMDS to yield the enol triflate (XIV). The reaction of (XIV) with Tms-CH2-MgCl affords the methylene derivative (XV), which is selectively desilylated with K2CO3 to provide the dihdyropyranyl ethanol compound (XVI). Finally, this compound is oxidized with DMP to obtain the target dihydropyranyl acetaldehyde intermediate (XVII).
| 【1】 Ahmed, A.; Hoegenauer, E.K.; Enev, V.S.; Hanbauer, M.; Kaehlig, H.; Ohler, E.; Mulzer, J.; Total synthesis of the microtubule stabilizing antitumor agent laulimalide and some nonnatural analogues: The power of Sharpless' asymmetric epoxidation. J. Org. Chem. 2003, 68, 8, 3026. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 61304 | Trimethylsilylmethylmagnesium Chloride; (Trimethylsilyl)methylmagnesium chloride Solution; Chloro[(trimethylsilyl)methyl]magnesium; (TRIMETHYLSILYLMETHYL)MAGNESIUM CHLORIDE; (TRIMETHYLSILYL)METHYLMAGNESIUM CHL. SOL | 13170-43-9 | C4H11ClMgSi | 详情 | 详情 |
| (I) | 61124 | (3R)-3-methyl-5-oxo-5-propoxypentanoic acid | C9H16O4 | 详情 | 详情 | |
| (II) | 61125 | propyl (3R)-5-hydroxy-3-methylpentanoate | C9H18O3 | 详情 | 详情 | |
| (III) | 61126 | propyl (3R)-3-methyl-5-oxopentanoate | C9H16O3 | 详情 | 详情 | |
| (IV) | 61128 | C4H8 | 详情 | 详情 | ||
| (V) | 61127 | propyl (3R,5S)-5-hydroxy-3-methyl-7-octenoate | C12H22O3 | 详情 | 详情 | |
| (VI) | 61129 | (3R,5S)-5-hydroxy-N,N,3-trimethyl-7-octenamide | C11H21NO2 | 详情 | 详情 | |
| (VII) | 61131 | 1-propoxy-2-propenyl propyl ether; 3,3-dipropoxy-1-propene | C9H18O2 | 详情 | 详情 | |
| (VIII) | 61130 | (3R,5S)-N,N,3-trimethyl-5-[(1-propoxy-2-propenyl)oxy]-7-octenamide | C17H31NO3 | 详情 | 详情 | |
| (IX) | 61132 | (3R)-N,N,3-trimethyl-4-[(2S)-6-propoxy-3,6-dihydro-2H-pyran-2-yl]butanamide | C15H27NO3 | 详情 | 详情 | |
| (X) | 61133 | tert-butyl(dimethyl)(vinyloxy)silane; tert-butyl(dimethyl)silyl vinyl ether | C8H18OSi | 详情 | 详情 | |
| (XI) | 61134 | (3R)-N,N,3-trimethyl-4-[(2S,6R)-6-(2-oxoethyl)-3,6-dihydro-2H-pyran-2-yl]butanamide | C14H23NO3 | 详情 | 详情 | |
| (XII) | 61135 | (3R)-N,N,3-trimethyl-4-((2S,6R)-6-{2-[(triethylsilyl)oxy]ethyl}-3,6-dihydro-2H-pyran-2-yl)butanamide | C20H39NO3Si | 详情 | 详情 | |
| (XIII) | 61136 | (4R)-4-methyl-5-((2S,6R)-6-{2-[(triethylsilyl)oxy]ethyl}-3,6-dihydro-2H-pyran-2-yl)-2-pentanone | C19H36O3Si | 详情 | 详情 | |
| (XIV) | 61137 | 1-[(2R)-2-methyl-3-((2S,6R)-6-{2-[(triethylsilyl)oxy]ethyl}-3,6-dihydro-2H-pyran-2-yl)propyl]vinyl trifluoromethanesulfonate | C20H35F3O5SSi | 详情 | 详情 | |
| (XV) | 61138 | 2-((2R,6S)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)ethyl triethylsilyl ether; trimethyl{2-[(2S)-2-methyl-3-((2S,6R)-6-{2-[(triethylsilyl)oxy]ethyl}-3,6-dihydro-2H-pyran-2-yl)propyl]-2-propenyl}silane | C23H46O2Si2 | 详情 | 详情 | |
| (XVI) | 61139 | 2-((2R,6S)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)-1-ethanol | C17H32O2Si | 详情 | 详情 | |
| (XVII) | 61140 | 2-((2R,6S)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)acetaldehyde | C17H30O2Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIX)The synthesis of the dihydropyran intermediate (XX) has been performed as follows: The reduction of the known aldehyde (XIV) with NaBH4 in methanol, followed by reaction with Tbdms-Cl and imidazole in DMF gives the silyl ether (XV), which is selectively deprotected with DDQ in dichloromethane and treated with TsCl and TEA to yield the tosylate (XVI). The reaction of (XVI) with NaCN in hot DMSO, followed by reaction with MeLi in ethyl ether affords the methyl ketone (XVII), which is treated with KHMDS and Ph-NTf2 in THF to provide the enol triflate (XVIII). Finally, this compound is treated with Tms-CH2-MgCl , Pd(PPh3)4 and LiCl in ethyl ether to furnish the target dihydropyran intermediate (XX).
| 【1】 Mulzer, J.; Hanbauer, M.; Total synthesis of the antitumor agent (-)-laulimalide. Tetrahedron Lett 2002, 43, 18, 3381. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 61207 | 2-((2R,6S)-6-{(2R)-3-[(4-methoxybenzyl)oxy]-2-methylpropyl}-5,6-dihydro-2H-pyran-2-yl)acetaldehyde | C19H26O4 | 详情 | 详情 | |
| (XV) | 61208 | tert-butyl(dimethyl)silyl 2-((2R,6S)-6-{(2R)-3-[(4-methoxybenzyl)oxy]-2-methylpropyl}-5,6-dihydro-2H-pyran-2-yl)ethyl ether; tert-butyl[2-((2R,6S)-6-{(2R)-3-[(4-methoxybenzyl)oxy]-2-methylpropyl}-5,6-dihydro-2H-pyran-2-yl)ethoxy]dimethylsilane | C25H42O4Si | 详情 | 详情 | |
| (XVI) | 61301 | (2R)-3-[(2S,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl 4-methylbenzenesulfonate | C24H40O5SSi | 详情 | 详情 | |
| (XVII) | 61302 | (4R)-5-[(2R,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-4-methyl-2-pentanone | C19H36O3Si | 详情 | 详情 | |
| (XVIII) | 61303 | 1-{(2R)-3-[(2R,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl}vinyl trifluoromethanesulfonate | C20H35F3O5SSi | 详情 | 详情 | |
| (XIX) | 61304 | Trimethylsilylmethylmagnesium Chloride; (Trimethylsilyl)methylmagnesium chloride Solution; Chloro[(trimethylsilyl)methyl]magnesium; (TRIMETHYLSILYLMETHYL)MAGNESIUM CHLORIDE; (TRIMETHYLSILYL)METHYLMAGNESIUM CHL. SOL | 13170-43-9 | C4H11ClMgSi | 详情 | 详情 |
| (XX) | 61305 | tert-butyl(dimethyl)[2-((2R,6R)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)ethoxy]silane; tert-butyl(dimethyl)silyl 2-((2R,6R)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)ethyl ether | C23H46O2Si2 | 详情 | 详情 |