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【结 构 式】

【分子编号】40293

【品名】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

【CA登记号】

【 分 子 式 】C20H44O2Si3

【 分 子 量 】400.82466

【元素组成】C 59.93% H 11.06% O 7.98% Si 21.02%
与该中间体有关的原料药合成路线共 2 条
合成路线1合成路线2

合成路线1

该中间体在本合成路线中的序号：(XVIII)

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).

参考文献 中间体
合成目标
【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2

该中间体在本合成路线中的序号：(XVIII)

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).

参考文献 中间体
合成目标
【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
Extended Information