|
【结 构 式】 
|
【分子编号】61133 【品名】tert-butyl(dimethyl)(vinyloxy)silane; tert-butyl(dimethyl)silyl vinyl ether 【CA登记号】 |
【 分 子 式 】C8H18OSi 【 分 子 量 】158.31582 【元素组成】C 60.69% H 11.46% O 10.11% Si 17.74% |
合成路线1
该中间体在本合成路线中的序号：(X)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：(XXXVI)The reaction of the chiral diol (XXIV) first with MsCl and TEA, and then with NaCN gives the chiral butyronitrile (XXV), which is reduced with DIBAL in dichloromethane to yield the butyraldehyde (XXVI). The reaction of (XXVI) with allyl tributyl tin (XXVII), (S)-BINOL and Ti(OiPr)4 affords the secondary alcohol (XXVIII), which is condensed with acetal (XXIX) by means of PPTS to provide the diene (XXX). A ring closing metathesis reaction in (XXX) by means of a Ru catalyst gives the dihydropyran derivative (XXXI). Alternatively, the reaction of (XXVIII) with propenoyl chloride (XXXII) by means of TEA gives the diene (XXXIII), which is submitted to a ring closing metathesis reaction as before to yield the dihydropyranone (XXXIV). The reduction of (XXXIV) with DIBAL, followed by treatment with CSA and ethanol affords the dihydropyran derivative (XXXV). The reaction of both acetals (XXXI) or (XXXV) with CH2=CH-O-Tbdms (XXXVI) in the presence of Montmorillonite as Lewis acid, followed by a treatment with NaBH4 provides the dihydropyran (XXXVII) as a single isomer.
| 【1】 Ghosh, A.K.; Wang, Y.; Kim, J.T.; Total synthesis of microtubule-stabilizing agent (-)-laulimalide. J Org Chem 2001, 66, 26, 8973. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIV) | 63122 | (2R)-3-(benzyloxy)-2-methyl-1-propanol | C11H16O2 | 详情 | 详情 | |
| (XXV) | 63123 | (3R)-4-(benzyloxy)-3-methylbutanenitrile | C12H15NO | 详情 | 详情 | |
| (XXVI) | 63124 | (3R)-4-(benzyloxy)-3-methylbutanal | C12H16O2 | 详情 | 详情 | |
| (XXVII) | 61128 | C4H8 | 详情 | 详情 | ||
| (XXVIII) | 63125 | (4S,6R)-7-(benzyloxy)-6-methyl-1-hepten-4-ol | C15H22O2 | 详情 | 详情 | |
| (XXIX) | 63126 | 3,3-diethoxy-1-propene; 1-ethoxy-2-propenyl ethyl ether | C7H14O2 | 详情 | 详情 | |
| (XXX) | 63127 | 1-[({(2R,4S)-4-[(1-ethoxy-2-propenyl)oxy]-2-methyl-6-heptenyl}oxy)methyl]benzene; benzyl (2R,4S)-4-[(1-ethoxy-2-propenyl)oxy]-2-methyl-6-heptenyl ether | C20H30O3 | 详情 | 详情 | |
| (XXXI) | 63128 | (2S,6R)-2-[(2R)-3-(benzyloxy)-2-methylpropyl]-6-ethoxy-3,6-dihydro-2H-pyran; benzyl (2R)-3-[(2S,6R)-6-ethoxy-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl ether | C18H26O3 | 详情 | 详情 | |
| (XXXII) | 11577 | Acryloyl chloride; Acrylyl chloride;2-Propenoyl chloride | 814-68-6 | C3H3ClO | 详情 | 详情 |
| (XXXIII) | 63130 | (1S)-1-[(2R)-3-(benzyloxy)-2-methylpropyl]-3-butenyl acrylate | C18H24O3 | 详情 | 详情 | |
| (XXXIV) | 63131 | (6S)-6-[(2R)-3-(benzyloxy)-2-methylpropyl]-5,6-dihydro-2H-pyran-2-one | C16H20O3 | 详情 | 详情 | |
| (XXXV) | 63132 | (2S,6S)-2-[(2R)-3-(benzyloxy)-2-methylpropyl]-6-ethoxy-3,6-dihydro-2H-pyran; benzyl (2R)-3-[(2S,6S)-6-ethoxy-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl ether | C18H26O3 | 详情 | 详情 | |
| (XXXVI) | 61133 | tert-butyl(dimethyl)(vinyloxy)silane; tert-butyl(dimethyl)silyl vinyl ether | C8H18OSi | 详情 | 详情 | |
| (XXXVII) | 63129 | benzyl (2R)-3-[(2S,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl ether; (2-{(2R,6S)-6-[(2R)-3-(benzyloxy)-2-methylpropyl]-5,6-dihydro-2H-pyran-2-yl}ethoxy)(tert-butyl)dimethylsilane | C24H40O3Si | 详情 | 详情 |