【结 构 式】 |
【分子编号】36883 【品名】1-[1-[(1R,2R)-2-[[tert-butyl(dimethyl)silyl]oxy]-1-hydroxy-1-methyl-4-(trimethylsilyl)-3-butynyl]cyclopropyl]-1-methyl-2-propynyl acetate 【CA登记号】 |
【 分 子 式 】C23H40O4Si2 【 分 子 量 】436.7392 【元素组成】C 63.25% H 9.23% O 14.65% Si 12.86% |
合成路线1
该中间体在本合成路线中的序号:(IX)The chiral 6(R) isomer of 213351 has been obtained as follows: The condensation of 1,1-diacetylcyclopropane monoethylene ketal (I) with acetylenic phosphonate (II) by means of NaHMDS in THF gives the silylated pentenyne (III), which is treated with TsOH in acetone/water yielding the acetylcyclopropane (IV). The Sharpless asymetric dihydroxylation of the double bond of (IV) by means of chiral auxiliary (DHQD)2PYR, K2OsO2(OH)4, K3Fe(CN)6 and K2CO3 in tert-butanol/water affords the chiral diol (V), which is monosilylated with TBDMS-OTf providing the silyl ether (VI). The condensation of (VI) with ethynylmagnesium bromide (VII) and CeCl3 gives the diacetylenic diol (VIII), which is regioselectively acetylated with Ac2O, TEA and DMAP yielding the monoacetate (IX). The treatment of the propargylic acetate (IX) with [(PPh3)CuH]6 in methanol affords the allene (X), which is regioselectively desilylated at the terminal acetylenic group furnishing the cyclization precursor (XI). The Mo(CO)6 promoted cyclization of (XI) in refluxing toluene/DMSO gives the chiral tricyclic ketone (XII). The methylation of (XII) with MeLi yields the monosilylated diol (XIII), which is desilylated with TBAF to the chiral diol (XIV). The oxidation of (XIV) with Dess Martin periodinane (DMP) affords the chiral hydroyketone (XV), which is finally hydroxymethylated with formaldehyde and H2SO4 to furnish the target compound.
【1】 Brummond, K.M.; et al.; A rapid synthesis of hydroxymethylacylfulvene (HMAF) using the allenic Pauson - Khand reaction. A synthetic approach to either enantiomer of this illudane structure. J Am Chem Soc 2000, 122, 20, 4915. |
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) | 36876 | 1-[1-(2-methyl-1,3-dioxolan-2-yl)cyclopropyl]-1-ethanone | C9H14O3 | 详情 | 详情 | |
(II) | 36877 | diethyl 3-(trimethylsilyl)-2-propynylphosphonate | C10H21O3PSi | 详情 | 详情 | |
(III) | 36878 | trimethyl[(Z)-4-[1-(2-methyl-1,3-dioxolan-2-yl)cyclopropyl]-3-penten-1-ynyl]silane | C15H24O2Si | 详情 | 详情 | |
(IV) | 36879 | 1-[1-[(Z)-1-methyl-4-(trimethylsilyl)-1-buten-3-ynyl]cyclopropyl]-1-ethanone | C13H20OSi | 详情 | 详情 | |
(V) | 36880 | 1-[1-[(1R,2R)-1,2-dihydroxy-1-methyl-4-(trimethylsilyl)-3-butynyl]cyclopropyl]-1-ethanone | C13H22O3Si | 详情 | 详情 | |
(VI) | 36881 | 1-[1-[(1R,2R)-2-[[tert-butyl(dimethyl)silyl]oxy]-1-hydroxy-1-methyl-4-(trimethylsilyl)-3-butynyl]cyclopropyl]-1-ethanone | C19H36O3Si2 | 详情 | 详情 | |
(VII) | 17778 | ETHYNYLMAGNESIUM BROMIDE; bromo(ethynyl)magnesium | 4301-14-8 | C2HBrMg | 详情 | 详情 |
(VIII) | 36882 | (2R,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-[1-(1-hydroxy-1-methyl-2-propynyl)cyclopropyl]-5-(trimethylsilyl)-4-pentyn-2-ol | C21H38O3Si2 | 详情 | 详情 | |
(IX) | 36883 | 1-[1-[(1R,2R)-2-[[tert-butyl(dimethyl)silyl]oxy]-1-hydroxy-1-methyl-4-(trimethylsilyl)-3-butynyl]cyclopropyl]-1-methyl-2-propynyl acetate | C23H40O4Si2 | 详情 | 详情 | |
(X) | 36884 | (2R,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-[1-(1-methyl-1,2-propadienyl)cyclopropyl]-5-(trimethylsilyl)-4-pentyn-2-ol | C21H38O2Si2 | 详情 | 详情 | |
(XI) | 36888 | (2R,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-[1-(1-methyl-1,2-propadienyl)cyclopropyl]-4-pentyn-2-ol | C18H30O2Si | 详情 | 详情 | |
(XII) | 36885 | C19H30O3Si | 详情 | 详情 | ||
(XIII) | 36886 | C20H32O2Si | 详情 | 详情 | ||
(XIV) | 36887 | C14H18O2 | 详情 | 详情 | ||
(XV) | 26689 | 6(R)-6-Hydroxy-2,4,6-trimethyl-6,7-dihydro-5H-spiro[indene-5,1'-cyclopropan]-7-one; 6(R)-6-Hydroxy-2,4,6-trimethyl-6,7-dihydro-5H-spiro[indene-5,1'-cyclopropan]-7-one | C14H16O2 | 详情 | 详情 |