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【结 构 式】 
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【分子编号】42368 【品名】vinyllithium 【CA登记号】917-57-7 |
【 分 子 式 】C2H3Li 【 分 子 量 】33.98682 【元素组成】C 70.68% H 8.9% Li 20.42% |
合成路线1
该中间体在本合成路线中的序号：(VII)The reaction of 1(R)-phenylethane-1,2-diol (I) with N-hydroxyphthalimide (II) by means of DEAD and PPh3 gives the N-alcoxyphthalimide (III) with(S)-configuration. The hydrazinolysis of (III) with hydrazine hydrate affords the O-alkylhydroxylamine (IV), which is condensed with benzaldehyde (V) to provide the alkylated benzaldoxime (VI). The alkylation of the oxime (VI) with vinyl lithium (VII) in toluene gives the N, O dialkylated hydroxylamine (VIII), which is treated with Zn and AcOH to yield 1(R)-phenylallylamine (IX). The protection of the amine (IX) with Boc2O and NaOH affords the carbamate (X), which is oxidized at the vinyl double bond by means of OsO4 and NaIO4 to provide the acetaldehyde (XI). The reaction of aldehyde (XI) with allylmagnesium bromide (XII) in ethyl ether gives the aminoalcohol (XIII), which is protected with Tbdms-Cl and imidazole to yield the silyl ether (XIV).
| 【1】 Yamazaki, N.; et al.; Nucleophilic addition of methyllithium to chiral oxime ethers: Asymmetric preparation of 1-(aryl)ethylamines and application to a synthesis of calcimimetics (+)-NPS R-568 and its thio analogue. Tetrahedron Lett 2001, 42, 30, 5029. |
| 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) | 56141 | (R)-(-)-1-Phenyl-1,2-ethanediol; (R)-(-)-alpha,beta-Dihydroxyethylbenzene; (R)-(-)-Phenyl-1,2-ethanediol; (R)-(-)-Styrene glycol; (-)-Styrene glycol | 16355-00-3 | C8H10O2 | 详情 | 详情 |
| (II) | 13505 | N-Hydroxyphthalimide; 2-Hydroxy-1H-isoindole-1,3(2H)-dione | 524-38-9 | C8H5NO3 | 详情 | 详情 |
| (III) | 56142 | 2-{[(1S)-2-hydroxy-1-phenylethyl]oxy}-1H-isoindole-1,3(2H)-dione | C16H13NO4 | 详情 | 详情 | |
| (IV) | 56143 | (2S)-2-(aminooxy)-2-phenyl-1-ethanol | C8H11NO2 | 详情 | 详情 | |
| (V) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (VI) | 62256 | benzaldehyde O-[(1S)-2-hydroxy-1-phenylethyl]oxime | C15H15NO2 | 详情 | 详情 | |
| (VII) | 42368 | vinyllithium | 917-57-7 | C2H3Li | 详情 | 详情 |
| (VIII) | 62257 | (2S)-2-phenyl-2-({[(1R)-1-phenyl-2-propenyl]amino}oxy)-1-ethanol | C17H19NO2 | 详情 | 详情 | |
| (IX) | 62258 | (1R)-1-phenyl-2-propenylamine; (1R)-1-phenyl-2-propen-1-amine | C9H11N | 详情 | 详情 | |
| (X) | 62259 | tert-butyl (1R)-1-phenyl-2-propenylcarbamate | C14H19NO2 | 详情 | 详情 | |
| (XI) | 45428 | tert-butyl (1S)-2-oxo-1-phenylethylcarbamate | C13H17NO3 | 详情 | 详情 | |
| (XII) | 61128 | C4H8 | 详情 | 详情 | ||
| (XIII) | 62260 | tert-butyl (1S)-2-hydroxy-1-phenyl-4-pentenylcarbamate | C16H23NO3 | 详情 | 详情 | |
| (XIV) | 62261 | tert-butyl (1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenyl-4-pentenylcarbamate | C22H37NO3Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Synthesis of intermediate (VII): The condensation of epoxide (I) with vinyl lithium (II) by means of CuCN gives the allylic alcohol (III), which is epoxidated to epoxide (IV). The silylation of (IV) with TBDPSCl and imidazole yields the silyl ether (V), which is condensed with 1,3-dithiane (VI) by means of n-BuLi and protected with TBDPSCl as before to afford the desired intermediate (VII).
| 【1】 Guo, J.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 1. Angew Chem. Int Ed Engl 1998, 37, 1-2, 187. |
| 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) | 42367 | benzyl 2-[(2S)oxiranyl]ethyl ether; (2S)-2-[2-(benzyloxy)ethyl]oxirane | C11H14O2 | 详情 | 详情 | |
| (II) | 42368 | vinyllithium | 917-57-7 | C2H3Li | 详情 | 详情 |
| (III) | 42369 | (3R)-1-(benzyloxy)-5-hexen-3-ol | C13H18O2 | 详情 | 详情 | |
| (IV) | 42370 | (2S)-4-(benzyloxy)-1-[(2S)oxiranyl]-2-butanol | C13H18O3 | 详情 | 详情 | |
| (V) | 42371 | benzyl (3S)-3-[[tert-butyl(diphenyl)silyl]oxy]-4-[(2S)oxiranyl]butyl ether; ([(1S)-3-(benzyloxy)-1-[(2S)oxiranylmethyl]propyl]oxy)(tert-butyl)diphenylsilane | C29H36O3Si | 详情 | 详情 | |
| (VI) | 42372 | 1,3-dithiane | 505-23-7 | C4H8S2 | 详情 | 详情 |
| (VII) | 42373 | benzyl (3S,5S)-3,5-bis[[tert-butyl(diphenyl)silyl]oxy]-6-(1,3-dithian-2-yl)hexyl ether; (5S,7S)-5-[2-(benzyloxy)ethyl]-7-(1,3-dithian-2-ylmethyl)-2,2,10,10-tetramethyl-3,3,9,9-tetraphenyl-4,8-dioxa-3,9-disilaundecane | C49H62O3S2Si2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)Synthesis of intermediate (XXXIII): The silylation of epoxide (XXI) with TBDMSCl gives the silyl ether (XXII), which is condensed with 1,3-dithiane (VI) by means of n-BuLi to yield the alcohol (XXIII). Epoxidation of (XXIII) with TBAF and NaH affords the epoxide (XXIV), which is condensed with vinyl lithium and CuCN to provide the allyl alcohol (XXV). The methylation of (XXV) with MeI and NaH in THF gives the methyl ether (XXVI). The silylation of epoxide (XXI) with TBDPSCl gives the silyl ether (XXVII), which is condensed with vinyl lithium (II) by means of CuCN in THF, yielding the allyl alcohol (XXVIII). The reaction of (XXVIII) with Boc-ON, n-BuLi and IBr affords the cyclic carbonate (XXIX), which is treated with K2CO3 in MeOH and silylated with TBDPSCl to provide the protected epoxide (XXX). The condensation of epoxide (XXX) with allyl ether (XXVI) by means of NaOtBu and n-BuLi in THF furnished the adduct (XXXI), which is cyclized by means of TBAF and converted into the acetylenic tetrahydropyran (XXXII). Finally, the iodination and reprotection of (XXXII) with Bu3SnH, AIBN, NIS, Mpm-OCH2Cl and DIEA gives the desired intermediate (XXXIII).
| 【1】 Guo, J.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 1. Angew Chem. Int Ed Engl 1998, 37, 1-2, 187. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 42368 | vinyllithium | 917-57-7 | C2H3Li | 详情 | 详情 |
| (VI) | 42372 | 1,3-dithiane | 505-23-7 | C4H8S2 | 详情 | 详情 |
| (XXI) | 19241 | (2S)oxiranylmethanol | 60456-23-7 | C3H6O2 | 详情 | 详情 |
| (XXII) | 42374 | tert-butyl(dimethyl)[(2R)oxiranylmethoxy]silane; tert-butyl(dimethyl)silyl (2R)oxiranylmethyl ether | C9H20O2Si | 详情 | 详情 | |
| (XXIII) | 42387 | (2R)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-(1,3-dithian-2-yl)-2-propanol | C13H28O2S2Si | 详情 | 详情 | |
| (XXIV) | 42388 | (2R)-2-(1,3-dithian-2-ylmethyl)oxirane | C7H12OS2 | 详情 | 详情 | |
| (XXV) | 42389 | (2S)-1-(1,3-dithian-2-yl)-4-penten-2-ol | C9H16OS2 | 详情 | 详情 | |
| (XXVI) | 42390 | (1S)-1-(1,3-dithian-2-ylmethyl)-3-butenyl methyl ether; 2-[(2S)-2-methoxy-4-pentenyl]-1,3-dithiane | C10H18OS2 | 详情 | 详情 | |
| (XXVII) | 26421 | tert-butyl[(2R)oxiranylmethoxy]diphenylsilane; tert-butyl(diphenyl)silyl (2R)oxiranylmethyl ether | C19H24O2Si | 详情 | 详情 | |
| (XXVIII) | 26422 | (2R)-1-[[tert-butyl(diphenyl)silyl]oxy]-4-penten-2-ol | C21H28O2Si | 详情 | 详情 | |
| (XXIX) | 42391 | (4R,6S)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-6-(iodomethyl)-1,3-dioxan-2-one | C22H27IO4Si | 详情 | 详情 | |
| (XXX) | 42392 | tert-butyl(diphenyl)silyl (1R)-2-[[tert-butyl(diphenyl)silyl]oxy]-1-[(2S)oxiranylmethyl]ethyl ether; (5R)-2,2,9,9-tetramethyl-5-[(2S)oxiranylmethyl]-3,3,8,8-tetraphenyl-4,7-dioxa-3,8-disiladecane | C37H46O3Si2 | 详情 | 详情 | |
| (XXXI) | 42393 | (2S,4R)-4,5-bis[[tert-butyl(diphenyl)silyl]oxy]-1-[2-[(2S)-2-methoxy-4-pentenyl]-1,3-dithian-2-yl]-2-pentanol | C47H64O4S2Si2 | 详情 | 详情 | |
| (XXXII) | 42394 | tert-butyl(diphenyl)silyl [(2R,4S,6R)-4-[[tert-butyl(diphenyl)silyl]oxy]-6-methoxy-6-[(2S)-2-methoxy-4-pentynyl]tetrahydro-2H-pyran-2-yl]methyl ether; tert-butyl([(2R,4S,6R)-4-[[tert-butyl(diphenyl)silyl]oxy]-6-methoxy-6-[(2S)-2-methoxy-4-pentynyl]tetrahydro-2H-pyran-2-yl]methoxy)diphenylsilane | C45H58O5Si2 | 详情 | 详情 | |
| (XXXIII) | 42395 | tert-butyl(dimethyl)silyl (2R,4S,6R)-2-[(2S,4E)-5-iodo-2-methoxy-4-pentenyl]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-4-yl ether; tert-butyl[[(2R,4S,6R)-2-[(2S,4E)-5-iodo-2-methoxy-4-pentenyl]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-4-yl]oxy]dimethylsilane | C28H47IO7Si | 详情 | 详情 |