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【结 构 式】 
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【分子编号】41537 【品名】tert-butyl(dimethyl)[2-[(2R,3S)-3-methyl-6-methylenetetrahydro-2H-pyran-2-yl]ethoxy]silane; tert-butyl(dimethyl)silyl 2-[(2R,3S)-3-methyl-6-methylenetetrahydro-2H-pyran-2-yl]ethyl ether 【CA登记号】 |
【 分 子 式 】C15H30O2Si 【 分 子 量 】270.4875 【元素组成】C 66.61% H 11.18% O 11.83% Si 10.38% |
合成路线1
该中间体在本合成路线中的序号：(I)The cyclization of tetrahydropyran (I) with 2-butylacrolein (II) by means of K2CO3 at 110 C gives the spirodipyran (III), which is epoxidated with dimethyldioxirane in dichloromethane yielding the epoxide (IV). The rearrangement of (IV) by means of camphorsulfonic acid (CSA) affording the carbaldehyde (V), which is condensed with lithium trimethylsilylacetylene (VI) affording carbinol (VII) with incorrect stereochemistry. The oxidation of (VII) with DMP in dichloromethane providing the ketone (VIII), which is reduced with L-Selectride to the carbinol (IX) with the correct stereochemistry. The treatment of (IX) with K2CO3 in MeOH eliminates the trimethylsilyl group giving the acetylene (X), which is silylated at the OH group with TBDMS-OTf and lutidine in dichloromethane yielding (XI). The selective desilylation of (XI) with HF·pyr in THF affords the primary alcohol (XII), which is oxidated with DMP in dichloromethane affording the aldehyde (VIII). The Wittig condensation of (XIII) with phosphorane (XIV) in hot chlorobenzene furnishes the aldehyde (XV).
| 【1】 Guzzupe, A.N.; et al.; Total synthesis of the epidermal growth factor inhibitor (-)-reveromycin B. J Org Chem 2001, 66, 7, 2382. |
| 【2】 Cuzzupe, A.N.; et al.; Total synthesis of (-)-reveromycin B. Org Lett 2000, 2, 2, 191. |
| 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) | 41537 | tert-butyl(dimethyl)[2-[(2R,3S)-3-methyl-6-methylenetetrahydro-2H-pyran-2-yl]ethoxy]silane; tert-butyl(dimethyl)silyl 2-[(2R,3S)-3-methyl-6-methylenetetrahydro-2H-pyran-2-yl]ethyl ether | C15H30O2Si | 详情 | 详情 | |
| (II) | 41538 | (Z)-2-butyl-2-butenal | C8H14O | 详情 | 详情 | |
| (III) | 41539 | tert-butyl(dimethyl)silyl 2-[(2R,3S,6S)-9-butyl-3-methyl-1,7-dioxaspiro[5.5]undec-8-en-2-yl]ethyl ether; tert-butyl[2-[(2R,3S,6S)-9-butyl-3-methyl-1,7-dioxaspiro[5.5]undec-8-en-2-yl]ethoxy]dimethylsilane | C22H42O3Si | 详情 | 详情 | |
| (IV) | 41540 | C22H42O4Si | 详情 | 详情 | ||
| (V) | 41541 | (2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]decane-2-carbaldehyde | n/a | C22H42O4Si | 详情 | 详情 |
| (VI) | 16299 | Lithium (trimethylsilyl)acetylide; [2-(Trimethylsilyl)ethynyl]lithium | 54655-07-1 | C5H9LiSi | 详情 | 详情 |
| (VII) | 41542 | (1R)-1-[(2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-3-(trimethylsilyl)-2-propyn-1-ol | n/a | C27H52O4Si2 | 详情 | 详情 |
| (VIII) | 41543 | 1-[(2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-3-(trimethylsilyl)-2-propyn-1-one | n/a | C27H50O4Si2 | 详情 | 详情 |
| (IX) | 41544 | (1S)-1-[(2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-3-(trimethylsilyl)-2-propyn-1-ol | n/a | C27H52O4Si2 | 详情 | 详情 |
| (X) | 41545 | (1S)-1-[(2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-2-propyn-1-ol | n/a | C24H44O4Si | 详情 | 详情 |
| (XI) | 41546 | (1S)-1-[(2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-2-propynyl tert-butyl(dimethyl)silyl ether; tert-butyl([(1S)-1-[(2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-2-propynyl]oxy)dimethylsilane | n/a | C30H58O4Si2 | 详情 | 详情 |
| (XII) | 41547 | 2-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-1-ethanol | n/a | C24H44O4Si | 详情 | 详情 |
| (XIII) | 41548 | 2-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]acetaldehyde | n/a | C24H42O4Si | 详情 | 详情 |
| (XIV) | 39940 | 2-(triphenylphosphoranylidene)propanal | C21H19OP | 详情 | 详情 | |
| (XV) | 41549 | (E)-4-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-2-methyl-2-butenal | n/a | C27H46O4Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The condensation of 3-(tert-butyldimethylsilyloxy)propanal (XXXIII) with the chiral borane (XXXIV) by means of H2O2 and NaHCO3 gives the chiral alcohol (XXXV), which is oxidized with OsO4 and NaIO4 to yield the aldehyde (XXXVI). The Wittig condensation of (XXXVI) with phosphorane (XVI) affords the heptenoic ester (XXXVII), which is reduced with H2 over Pd/C to provide the saturated hydroxy ester (XXXVIII). The cyclization of (XXXVIII) by means of PPTS in refluxing dichloromethane gives the lactone (XXXIX), which by reaction with Cp2TiMe2 yields the methylene derivative (I).
| 【1】 Guzzupe, A.N.; et al.; Total synthesis of the epidermal growth factor inhibitor (-)-reveromycin B. J Org Chem 2001, 66, 7, 2382. |
| 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) | 41537 | tert-butyl(dimethyl)[2-[(2R,3S)-3-methyl-6-methylenetetrahydro-2H-pyran-2-yl]ethoxy]silane; tert-butyl(dimethyl)silyl 2-[(2R,3S)-3-methyl-6-methylenetetrahydro-2H-pyran-2-yl]ethyl ether | C15H30O2Si | 详情 | 详情 | |
| (XVI) | 14689 | Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate | 2605-67-6 | C21H19O2P | 详情 | 详情 |
| (XXXIII) | 45546 | 3-[[tert-butyl(dimethyl)silyl]oxy]propanal | 570-24-1 | C9H20O2Si | 详情 | 详情 |
| (XXXIV) | 50353 | (E)-2-butenyl[bis[(1R,2R,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane | C24H41B | 详情 | 详情 | |
| (XXXV) | 50354 | (3R,4S)-1-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-hexen-3-ol | C13H28O2Si | 详情 | 详情 | |
| (XXXVI) | 50355 | (2R,3R)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxy-2-methylpentanal | C12H26O3Si | 详情 | 详情 | |
| (XXXVII) | 50356 | methyl (E,4S,5R)-7-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4-methyl-2-heptenoate | C15H30O4Si | 详情 | 详情 | |
| (XXXVIII) | 50357 | methyl (4S,5R)-7-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4-methylheptanoate | C15H32O4Si | 详情 | 详情 | |
| (XXXIX) | 50358 | (5S,6R)-6-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-5-methyltetrahydro-2H-pyran-2-one | C14H28O3Si | 详情 | 详情 |