【结 构 式】 |
【分子编号】63875 【品名】(2R)-2-((2R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-2-methylpentyl)-2,3-dihydro-4H-pyran-4-one 【CA登记号】 |
【 分 子 式 】C27H36O3Si 【 分 子 量 】436.66654 【元素组成】C 74.27% H 8.31% O 10.99% Si 6.43% |
合成路线1
该中间体在本合成路线中的序号:(XII)The acetylenic ester intermediate (XVI) has been obtained as follows. The reaction of acetaldehyde (I) with acetyl bromide (II) by means of a chiral Al catalyst gives lactone (III), which is condensed with N,O-dimethylhydroxylamine (IV) to yield the Weinreb amide (V). The reduction of (V) with iBu2AlH affords the chiral butyraldehyde (VI), which is condensed with acetyl bromide (II) and DIEA to provide the lactone (VII). The reaction of (VII) with methylmagnesium bromide gives the chiral pentanoic acid (VIII), which is reduced with BH3/Me2S and reoxidated with PCC to yield the aldehyde (IX). The condensation of (IX) with acetyl bromide (II) and DIEA affords the lactone (X), which is treated with the lithium salt (XI) to provide the dihydropyranone (XII). The reduction of (XII) with NaBH4 and CeCl3, followed by reaction with Ac2O and TEA gives the acetoxy derivative (XIII), which is desilylated with TBAF and oxidized with PDC to yield the methyl ketone (XIV). Finally, the condensation of (XIV) with the allenic tributyl tin derivative (XV) by means of Bu3Sn-OTf in dichloromethane affords the target acetylenic ester intermediate (XVI).
【1】 Nelson, S.G.; Cheung, W.S.; Kassick, A.J.; Hilfiker, M.A.; A de novo enantioselective total synthesis of (-)-laulimalide. J Am Chem Soc 2002, 124, 46, 13654. |
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) | 11974 | Acetaldehyde | 75-07-0 | C2H4O | 详情 | 详情 |
(II) | 63866 | acetyl bromide | C2H3BrO | 详情 | 详情 | |
(III) | 63867 | (4R)-4-methyl-2-oxetanone | C4H6O2 | 详情 | 详情 | |
(IV) | 13361 | (Methoxyamino)methane; N,O-Dimethylhydroxylamine | 1117-97-1 | C2H7NO | 详情 | 详情 |
(V) | 63868 | (3R)-3-{[tert-butyl(diphenyl)silyl]oxy}-N-methoxy-N-methylbutanamide | C22H31NO3Si | 详情 | 详情 | |
(VI) | 63871 | (3R)-3-{[tert-butyl(diphenyl)silyl]oxy}butanal | C20H26O2Si | 详情 | 详情 | |
(VII) | 63870 | (4R)-4-((2R)-2-{[tert-butyl(diphenyl)silyl]oxy}propyl)-2-oxetanone | C22H28O3Si | 详情 | 详情 | |
(VIII) | 63869 | (3S,5R)-5-{[tert-butyl(diphenyl)silyl]oxy}-3-methylhexanoic acid | C23H32O3Si | 详情 | 详情 | |
(IX) | 63872 | (3S,5R)-5-{[tert-butyl(diphenyl)silyl]oxy}-3-methylhexanal | C23H32O2Si | 详情 | 详情 | |
(X) | 63873 | (4S)-4-((2R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-2-methylpentyl)-2-oxetanone | C25H34O3Si | 详情 | 详情 | |
(XI) | 63874 | C7H13LiN2 | 详情 | 详情 | ||
(XII) | 63875 | (2R)-2-((2R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-2-methylpentyl)-2,3-dihydro-4H-pyran-4-one | C27H36O3Si | 详情 | 详情 | |
(XIII) | 63879 | C27H37AcO3Si | 详情 | 详情 | ||
(XIV) | 63878 | (2R,4S)-2-[(2R)-2-methyl-4-oxopentyl]-3,4-dihydro-2H-pyran-4-yl acetate | C13H20O4 | 详情 | 详情 | |
(XV) | 63877 | tert-butyl 2-(tributylstannyl)-2,3-butadienoate | C20H38O2Sn | 详情 | 详情 | |
(XVI) | 63876 | tert-butyl 4-{(2R,6R)-6-[(2R)-2-methyl-4-oxopentyl]-5,6-dihydro-2H-pyran-2-yl}-2-butynoate | C19H28O4 | 详情 | 详情 |