4-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-2-butenal -Drug Synthesis Database

【结构式】

【分子编号】60351

【品名】4-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-2-butenal

【CA登记号】

【分子式】C₂₀H₂₄O₂Si

【分子量】324.49486

【元素组成】C 74.03% H 7.45% O 9.86% Si 8.66%

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：(I)

Tetrahydropyran intermediate (X). The asymmetric addition of Ipc2B-crotyl to 4-(Tbdps-O)-2-butenal (I) gives the chiral secondary alcohol (II), which is protected with benzyl bromide and NaH to yield the benzyl ether (III). The desilylation of (III) by means of TBAF affords the primary alcohol (IV), which is submitted to a Sharpless asymmetric epoxidation to provide the epoxide (V). Ring opening of (V) by means of Ti(iPrO)4 and benzoic acid gives the benzoate ester (VI), which is cyclized by means of Hg(OAc)2 to yield the tetrahydropyran derivative (VII). Hydrolysis of the benzoate group of (VII) by means of MeONa affords the trihydroxy compound (VIII), which is treated with acetone and Ts-OH to provide the acetonide (IX). Finally, oxidation of the hydroxymethyl group of (IX) by means of Swern oxidant yields the target tetrahydropyran-2-carbaldehyde intermediate (X).

参考文献中间体

合成目标

【1】 Smith, A.B. III; Zhuang, L.; Brook, C.S.; Boldi, A.M.; McBriar, M.D.; Moser, W.H.; Murase, N.; Nakayama, K.; Verhoest, P.R.; Lin, Q.; Spongistatin synthetic studies. 1. Construction of a C(29-48) subtarget. Tetrahedron Lett 1997, 38, 50, 8667.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	60351	4-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-2-butenal	C₂₀H₂₄O₂Si	详情	详情
(II)	64595	(3S,4R,5E)-7-{[tert-butyl(diphenyl)silyl]oxy}-3-methyl-1,5-heptadien-4-ol	C₂₄H₃₂O₂Si	详情	详情
(III)	64596	benzyl (1R,2E)-4-{[tert-butyl(diphenyl)silyl]oxy}-1-[(1S)-1-methyl-2-propenyl]-2-butenyl ether; {[(2E,4R,5S)-4-(benzyloxy)-5-methyl-2,6-heptadienyl]oxy}(tert-butyl)diphenylsilane	C₃₁H₃₈O₂Si	详情	详情
(IV)	64597	(2E,4R,5S)-4-(benzyloxy)-5-methyl-2,6-heptadien-1-ol	C₁₅H₂₀O₂	详情	详情
(V)	54598	tert-butyl (1S,2R)-1-(sec-butyl)-2-methoxy-4-pentenyl(methyl)carbamate	C₁₆H₃₁NO₃	详情	详情
(VI)	64599	(1R,2R,3S)-2-(benzyloxy)-1-[(1R)-1,2-dihydroxyethyl]-3-methyl-4-pentenyl benzoate	C₂₂H₂₆O₅	详情	详情
(VII)	64600	(2R,3S,4R,5R)-2-[(acetyloxy)methyl]-4-(benzyloxy)-6-(hydroxymethyl)-5-methyltetrahydro-2H-pyran-3-yl benzoate	C₂₄H₂₈O₇	详情	详情
(VIII)	64601	(2R,3S,4R,5R)-4-(benzyloxy)-2,6-bis(hydroxymethyl)-5-methyltetrahydro-2H-pyran-3-ol	C₁₅H₂₂O₅	详情	详情
(IX)	64602	[(4aR,7R,8R,8aS)-8-(benzyloxy)-2,2,7-trimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]methanol	C₁₈H₂₆O₅	详情	详情
(X)	64603	(4aR,7R,8R,8aS)-8-(benzyloxy)-2,2,7-trimethylhexahydropyrano[3,2-d][1,3]dioxine-6-carbaldehyde	C₁₈H₂₄O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

The boron enolate aldol condensation between aldehyde (IX) and the chiral oxazolidinone (II) affords adduct (X). After conversion to the Weinreb amide (XI), addition of magnesium acetylide (XII) leads to alkynone (XIII). Diastereoselective reduction of (XIII) using DIBAL in THF furnishes diol (XIV) as the major isomer. After protection of diol (XIV) as the bis-silyl ether (XV), hydroboration of its triple bond with catecholborane, followed by alkaline work-up gives rise to the boronic acid fragment (XVI).

参考文献中间体

合成目标

【1】 Evans, D.A.; Starr, J.T.; A cascade cycloaddition strategy leading to the total synthesis of (-)-FR182877. Angew Chem. Int Ed 2002, 41, 10, 1787.

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)	25713	(4S)-4-benzyl-3-propionyl-1,3-oxazolidin-2-one		C₁₃H₁₅NO₃	详情	详情
(IX)	60351	4-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-2-butenal		C₂₀H₂₄O₂Si	详情	详情
(X)	60353	3-(6-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-3-hydroxy-2-methyl-4-hexenoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one		C₃₃H₃₉NO₅Si	详情	详情
(XI)	60354	6-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-3-hydroxy-N,2-dimethyl-N-(methyloxy)-4-hexenamide		C₂₅H₃₅NO₄Si	详情	详情
(XII)	17778	ETHYNYLMAGNESIUM BROMIDE; bromo(ethynyl)magnesium	4301-14-8	C₂HBrMg	详情	详情
(XIII)	60355	8-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-5-hydroxy-4-methyl-6-octen-1-yn-3-one		C₂₅H₃₀O₃Si	详情	详情
(XIV)	60356	8-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-4-methyl-6-octen-1-yne-3,5-diol		C₂₅H₃₂O₃Si	详情	详情
(XV)	60357	4,6-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-5-methyl-2-octen-7-ynyl (1,1-dimethylethyl)(diphenyl)silyl ether; 8-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-10-ethynyl-2,2,9,12,12,13,13-heptamethyl-3,3-diphenyl-4,11-dioxa-3,12-disila-6-tetradecene		C₃₇H₆₀O₃Si₃	详情	详情
(XVI)	60358	3,5-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-8-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-4-methyl-1,6-octadienylboronic acid		C₃₇H₆₃BO₅Si₃	详情	详情

Extended Information