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【结 构 式】 
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【分子编号】35693 【品名】[2-[(E)-3-pentenyl]-1,3-dithian-2-yl]lithium 【CA登记号】 |
【 分 子 式 】C9H15LiS2 【 分 子 量 】194.2911 【元素组成】C 55.64% H 7.78% Li 3.57% S 33.01% |
合成路线1
该中间体在本合成路线中的序号：(XXI)The cyclization of (XVII) by means of Me2AlCl in dichloromethane gives the tricyclic ketone (XVIII), which is desilylated with TBAF in THF yielding the ethanol (XIX). The oxidation of (XIX) with Dess Martin periodinane (DMP) in dichloromethane affords the corresponding aldehyde (XX), which is condensed with the lithium 1,3-dithiane (XXI) in THF to give the secondary alcohol (XXII). The silylation of this alcohol with Tes-OTf and NaH in THF yields the silyl ether (XXIII), which is treated with Ph-NTf2 and KHMDS in THF to afford the enol ether (XXIV). The reaction of (XXIV) with Pdo and CO in methanol gives the methyl ester (XXV), which is treated with PhI(OCOCF3)2 and methanol to afford the gem-dimethoxy compound (XXVI).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-263,114 and CP-225,917 - Part 1: Synthesis of key intermediates and intelligence gathering. Angew Chem. Int Ed Engl 1999, 38, 11, 1669. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVII) | 35689 | (E)-1-(5-[(2E,9E)-1-[(E)-2-(4-methoxyphenyl)ethylidene]-2,9-undecadienyl]-2,2-dimethyl-1,3-dioxan-5-yl)-7-[(triisopropylsilyl)oxy]-4-hepten-3-one | C42H68O5Si | 详情 | 详情 | |
| (XVIII) | 35690 | C42H68O5Si | 详情 | 详情 | ||
| (XIX) | 35691 | C33H48O5 | 详情 | 详情 | ||
| (XX) | 35692 | C33H46O5 | 详情 | 详情 | ||
| (XXI) | 35693 | [2-[(E)-3-pentenyl]-1,3-dithian-2-yl]lithium | C9H15LiS2 | 详情 | 详情 | |
| (XXII) | 35694 | C42H62O5S2 | 详情 | 详情 | ||
| (XXIII) | 35695 | C48H76O5S2Si | 详情 | 详情 | ||
| (XXIV) | 35696 | C49H75F3O7S3Si | 详情 | 详情 | ||
| (XXV) | 35697 | C50H78O6S2Si | 详情 | 详情 | ||
| (XXVI) | 35698 | C49H78O8Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXV)The condensation of (S)-glycidol (XVI) with trimethylsilylacetylene (XVII) by means of tert-butyllithium in THF, followed by quenching with TBDMS triflate gives the protected acetylenic diol (XVIII), which is iodinated with K2CO3, Cp2ZnCl and I2 yielding the vinyl iodide (XIX). The condensation of (XIX) with the intermediate aldehyde (XV) in THF, followed by oxidation with DMP affords the chiral ketone (XX), which is submitted to a diastereoselective cyclization catalyzed by dichloroaluminum phenoxide (XXI) in toluene to furnish the polycyclic ketone (XXII) as a 5.7:1 diastereomeric mixture. The desilylation of this mixture with TBAF in THF allowed the separation of the mayor diastereomeric diol (XXIII) by flash chromatography. The oxidation of (XXIII) with NaIO4 affords the corresponding aldehyde (XXIV), which is condensed with the lithium 1,3-dithiane (XXV) in THF to give the secondary alcohol (XXVI). The silylation of this alcohol with TES-OTf and NaH in THF yields the silyl ether (XXVII), which is treated with Ph-NTf2 and KHMDS in THF to afford the enol ether (XXVIII).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-263,114 and CP-225,917 - Part 1: Synthesis of key intermediates and intelligence gathering. Angew Chem. Int Ed Engl 1999, 38, 11, 1669. |
| 【2】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 35687 | 3-(5-[(2E,9E)-1-[(E)-2-(4-methoxyphenyl)ethylidene]-2,9-undecadienyl]-2,2-dimethyl-1,3-dioxan-5-yl)propanal | C29H42O4 | 详情 | 详情 | |
| (XVI) | 19241 | (2S)oxiranylmethanol | 60456-23-7 | C3H6O2 | 详情 | 详情 |
| (XVII) | 23897 | ethynyl(trimethyl)silane；trimethylsilyl acetylene | 1066-54-2 | C5H10Si | 详情 | 详情 |
| (XVIII) | 40293 | tert-butyl(dimethyl)silyl (1R)-1-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-(trimethylsilyl)-3-butynyl ether; (5R)-2,2,3,3,8,8,9,9-octamethyl-5-[3-(trimethylsilyl)-2-propynyl]-4,7-dioxa-3,8-disiladecane | C20H44O2Si3 | 详情 | 详情 | |
| (XIX) | 40294 | tert-butyl(dimethyl)silyl (2R,4E)-2-[[tert-butyl(dimethyl)silyl]oxy]-5-iodo-4-pentenyl ether; (5R)-5-[(E)-3-iodo-2-propenyl]-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane | C17H37IO2Si2 | 详情 | 详情 | |
| (XX) | 40295 | (E,7R)-7,8-bis[[tert-butyl(dimethyl)silyl]oxy]-1-(5-[(2E,9E)-1-[(E)-2-(4-methoxyphenyl)ethylidene]-2,9-undecadienyl]-2,2-dimethyl-1,3-dioxan-5-yl)-4-octen-3-one | C46H78O6Si2 | 详情 | 详情 | |
| (XXI) | 40296 | C15H23AlCl2O | 详情 | 详情 | ||
| (XXII) | 40297 | C46H78O6Si2 | 详情 | 详情 | ||
| (XXIII) | 40298 | C34H50O6 | 详情 | 详情 | ||
| (XXIV) | 35692 | C33H46O5 | 详情 | 详情 | ||
| (XXV) | 35693 | [2-[(E)-3-pentenyl]-1,3-dithian-2-yl]lithium | C9H15LiS2 | 详情 | 详情 | |
| (XXVI) | 35694 | C42H62O5S2 | 详情 | 详情 | ||
| (XXVII) | 35695 | C48H76O5S2Si | 详情 | 详情 | ||
| (XXVIII) | 35696 | C49H75F3O7S3Si | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XXI)The cyclization of (XVII) by means of Me2AlCl in dichloromethane gives the tricyclic ketone (XVIII), which is desilylated with TBAF in THF yielding the ethanol (XIX). The oxidation of (XIX) with Dess Martin periodinane (DMP) in dichloromethane affords the corresponding aldehyde (XX), which is condensed with the lithium 1,3-dithiane (XXI) in THF to give the secondary alcohol (XXII). The silylation of this alcohol with Tes-OTf and NaH in THF yields the silyl ether (XXIII), which is treated with Ph-NTf2 and KHMDS in THF to afford the enol ether (XXIV). The reaction of (XXIV) with Pdo and CO in methanol gives the methyl ester (XXV), which is treated with PhI(OCOCF3)2 and methanol to afford the gem-dimethoxy compound (XXVI).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-263,114 and CP-225,917 - Part 1: Synthesis of key intermediates and intelligence gathering. Angew Chem. Int Ed Engl 1999, 38, 11, 1669. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVII) | 35689 | (E)-1-(5-[(2E,9E)-1-[(E)-2-(4-methoxyphenyl)ethylidene]-2,9-undecadienyl]-2,2-dimethyl-1,3-dioxan-5-yl)-7-[(triisopropylsilyl)oxy]-4-hepten-3-one | C42H68O5Si | 详情 | 详情 | |
| (XVIII) | 35690 | C42H68O5Si | 详情 | 详情 | ||
| (XIX) | 35691 | C33H48O5 | 详情 | 详情 | ||
| (XX) | 35692 | C33H46O5 | 详情 | 详情 | ||
| (XXI) | 35693 | [2-[(E)-3-pentenyl]-1,3-dithian-2-yl]lithium | C9H15LiS2 | 详情 | 详情 | |
| (XXII) | 35694 | C42H62O5S2 | 详情 | 详情 | ||
| (XXIII) | 35695 | C48H76O5S2Si | 详情 | 详情 | ||
| (XXIV) | 35696 | C49H75F3O7S3Si | 详情 | 详情 | ||
| (XXV) | 35697 | C50H78O6S2Si | 详情 | 详情 | ||
| (XXVI) | 35698 | C49H78O8Si | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XXV)The condensation of (S)-glycidol (XVI) with trimethylsilylacetylene (XVII) by means of tert-butyllithium in THF, followed by quenching with TBDMS triflate gives the protected acetylenic diol (XVIII), which is iodinated with K2CO3, Cp2ZnCl and I2 yielding the vinyl iodide (XIX). The condensation of (XIX) with the intermediate aldehyde (XV) in THF, followed by oxidation with DMP affords the chiral ketone (XX), which is submitted to a diastereoselective cyclization catalyzed by dichloroaluminum phenoxide (XXI) in toluene to furnish the polycyclic ketone (XXII) as a 5.7:1 diastereomeric mixture. The desilylation of this mixture with TBAF in THF allowed the separation of the mayor diastereomeric diol (XXIII) by flash chromatography. The oxidation of (XXIII) with NaIO4 affords the corresponding aldehyde (XXIV), which is condensed with the lithium 1,3-dithiane (XXV) in THF to give the secondary alcohol (XXVI). The silylation of this alcohol with TES-OTf and NaH in THF yields the silyl ether (XXVII), which is treated with Ph-NTf2 and KHMDS in THF to afford the enol ether (XXVIII).
| 【1】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 【2】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-263,114 and CP-225,917 - Part 1: Synthesis of key intermediates and intelligence gathering. Angew Chem. Int Ed Engl 1999, 38, 11, 1669. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 35687 | 3-(5-[(2E,9E)-1-[(E)-2-(4-methoxyphenyl)ethylidene]-2,9-undecadienyl]-2,2-dimethyl-1,3-dioxan-5-yl)propanal | C29H42O4 | 详情 | 详情 | |
| (XVI) | 19241 | (2S)oxiranylmethanol | 60456-23-7 | C3H6O2 | 详情 | 详情 |
| (XVII) | 23897 | ethynyl(trimethyl)silane；trimethylsilyl acetylene | 1066-54-2 | C5H10Si | 详情 | 详情 |
| (XVIII) | 40293 | tert-butyl(dimethyl)silyl (1R)-1-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-(trimethylsilyl)-3-butynyl ether; (5R)-2,2,3,3,8,8,9,9-octamethyl-5-[3-(trimethylsilyl)-2-propynyl]-4,7-dioxa-3,8-disiladecane | C20H44O2Si3 | 详情 | 详情 | |
| (XIX) | 40294 | tert-butyl(dimethyl)silyl (2R,4E)-2-[[tert-butyl(dimethyl)silyl]oxy]-5-iodo-4-pentenyl ether; (5R)-5-[(E)-3-iodo-2-propenyl]-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane | C17H37IO2Si2 | 详情 | 详情 | |
| (XX) | 40295 | (E,7R)-7,8-bis[[tert-butyl(dimethyl)silyl]oxy]-1-(5-[(2E,9E)-1-[(E)-2-(4-methoxyphenyl)ethylidene]-2,9-undecadienyl]-2,2-dimethyl-1,3-dioxan-5-yl)-4-octen-3-one | C46H78O6Si2 | 详情 | 详情 | |
| (XXI) | 40296 | C15H23AlCl2O | 详情 | 详情 | ||
| (XXII) | 40297 | C46H78O6Si2 | 详情 | 详情 | ||
| (XXIII) | 40298 | C34H50O6 | 详情 | 详情 | ||
| (XXIV) | 35692 | C33H46O5 | 详情 | 详情 | ||
| (XXV) | 35693 | [2-[(E)-3-pentenyl]-1,3-dithian-2-yl]lithium | C9H15LiS2 | 详情 | 详情 | |
| (XXVI) | 35694 | C42H62O5S2 | 详情 | 详情 | ||
| (XXVII) | 35695 | C48H76O5S2Si | 详情 | 详情 | ||
| (XXVIII) | 35696 | C49H75F3O7S3Si | 详情 | 详情 |