(E)-2-butenyl(triphenyl)phosphonium bromide -Drug Synthesis Database

【结构式】

【分子编号】48753

【品名】(E)-2-butenyl(triphenyl)phosphonium bromide

【CA登记号】

【分子式】C₂₂H₂₂BrP

【分子量】397.294442

【元素组成】C 66.51% H 5.58% Br 20.11% P 7.8%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XVI)

The asymmetric reduction of the carbonyl group of tetracyclic compound (I) by means of BH3 and a chiral borane catalyst in THF gives the (R)-alcohol (II), which by a Sharpless epoxidation yields the chiral epoxide (III). The reaction of the (cis)-(III) with (-)-camphanic acid (IV), DAD and PPh3 under Mitsunobu conditions affords after chromatographic purification the (trans)-camphanate (V), which is submitted to a rearrangement reaction by means of BF3/Et2O in dichloromethane to provide the tetracyclic spiro compound (VI). The protection of the ketonic group of (VI) by means of silylated ethyleneglycol and Tms-OTf gives the cyclic ketal (VII), which is treated with NaOH in methanol and the resulting alcohol oxidized with DMP in dichloromethane to yield the monoprotected diketone (VIII). The disulfenylation of (VIII) affords the disulfide (IX), which by treatment with TFA and oxidation with MCPBA provides the unsaturated sulfinyl (X). The cyclization of (X) with the homophthalic anhydride (XI) (obtained from trimethoxybromobenzene (XII)), followed by methylation of the resulting free OH group with MeI and K2CO3 in DMF furnishes the spiro-hexacyclic compound (XIII). The selective demethylation of (XIII) with Tms-I in dichloromethane gives the pyridinone derivative (XIV), which is oxidized at the methyl group with SeO2 to yield the carbaldehyde (XV). The condensation of (XV) with the phosphonium bromide (XVI) by means of BuLi in THF affords the precursor (XVII), which is finally demethylated with BBr3 and submitted to oxidation by air to provide the target compound.

参考文献中间体

合成目标

【1】 Kitagaki, S.; Kita, Y.; Fujioka, H.; Iio, K.; Yoshida, Y.; Higuchi, K.; Akai, S.; Asymmetric total synthesis of fredericamycin A. Angew Chem. Int Ed Engl 1999, 38, 5, 683.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	48738	10,11-dimethoxy-8-methyl-2,3,4,5-tetrahydro-1H-indeno[5,4-g]isoquinolin-1-one	C₁₉H₁₉NO₃	详情	详情
(II)	48739	(1R)-10,11-dimethoxy-8-methyl-2,3,4,5-tetrahydro-1H-indeno[5,4-g]isoquinolin-1-ol	C₁₉H₂₁NO₃	详情	详情
(III)	48740		C₁₉H₂₁NO₄	详情	详情
(IV)	48741	4,7,7-trimethylbicyclo[2.2.1]heptane-2-carboxylic acid	C₁₁H₁₈O₂	详情	详情
(V)	48742		C₃₀H₃₇NO₅	详情	详情
(VI)	48743		C₃₀H₃₇NO₅	详情	详情
(VII)	48744		C₃₂H₄₁NO₆	详情	详情
(VIII)	48745		C₂₁H₂₃NO₅	详情	详情
(IX)	48746		C₃₃H₃₁NO₅S₂	详情	详情
(X)	48747		C₂₅H₂₁NO₅S	详情	详情
(XI)	48748	4,5,7,8-tetramethoxy-1H-isochromene-1,3(4H)-dione	C₁₃H₁₄O₇	详情	详情
(XII)	48749	1-Bromo-2,4,5-trimethoxybenzene	C₉H₁₁BrO₃	详情	详情
(XIII)	48750		C₃₂H₃₁NO₉	详情	详情
(XIV)	48751		C₃₁H₂₉NO₉	详情	详情
(XV)	48752		C₃₁H₂₇NO₁₀	详情	详情
(XVI)	48753	(E)-2-butenyl(triphenyl)phosphonium bromide	C₂₂H₂₂BrP	详情	详情
(XVII)	48754		C₃₅H₃₃NO₉	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXVIII)

The reaction of carbaldehyde (VII) with phenylsulfanylacetylene (XVII) by means of LiHMDS in toluene gives the intermediate lithium alcoxide (XVIII), which is condensed with benzoyl chloride (XIX) to yield the ester (XX). The migration of the aroyl group of (XX) to the methyl ketone group under basic medium (LiHMDS) affords diketone (XXI), which is oxidized with DMP, complexed with Co2(CO)8 and debenzylated, providing the cobalt complex (XXII). The cycloaddition of (XXII) by means of Me2SiCl2, chloranil in refluxing toluene, followed by protection of the peri-OH groups with tBu2Si(OTf)2 and oxidation of the sulfanyl group with MCPBA, gives the polycyclic spiro compound (XXIII). The reaction of (XXIII) with chloroacetate (XXIV) by means of Ts-OH yields the chloroacetoxy compound (XXV). Selective demethylation of (XXV) with trimethylsilyl iodide affords the pyridinone (XXVI), which is oxidized with SeO2 in dioxane to provide the carbaldehyde (XXVII). The condensation of (XXVII) with phosphonium bromide (XXVIII) by means of BuLi in THF furnishes the alkylated precursor (XXIX), which is finally deprotected by means of BBr3 in dichloromethane and oxidized by air to afford the target compound.

参考文献中间体

合成目标

【1】 Kita, Y.; et al.; Total synthesis of the antitumor antribiotic (±)-fredericamycin A by a linear approach. Chemistry (Weinheim) 2000, 6, 21, 3897.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VII)	48761	8-acetyl-1,9-dimethoxy-3-methyl-7,8-dihydro-6H-cyclopenta[g]isoquinoline-8-carbaldehyde	C₁₈H₁₉NO₄	详情	详情
(XVII)	48768	ethynyl phenyl sulfide; 1-(ethynylsulfanyl)benzene	C₈H₆S	详情	详情
(XVIII)	48769		C₂₆H₂₄LiNO₄S	详情	详情
(XIX)	48770	2-(benzyloxy)-4,5-dimethoxybenzoyl chloride	C₁₆H₁₅ClO₄	详情	详情
(XX)	48771	1-(8-acetyl-1,9-dimethoxy-3-methyl-7,8-dihydro-6H-cyclopenta[g]isoquinolin-8-yl)-3-(phenylsulfanyl)-2-propynyl 2-(benzyloxy)-4,5-dimethoxybenzoate	C₄₂H₃₉NO₈S	详情	详情
(XXI)	48772	1-[2-(benzyloxy)-4,5-dimethoxyphenyl]-3-[8-[1-hydroxy-3-(phenylsulfanyl)-2-propynyl]-1,9-dimethoxy-3-methyl-7,8-dihydro-6H-cyclopenta[g]isoquinolin-8-yl]-1,3-propanedione	C₄₂H₃₉NO₈S	详情	详情
(XXII)	48773	1-[1,9-dimethoxy-3-methyl-8-[3-(phenylsulfanyl)-2-propynoyl]-7,8-dihydro-6H-cyclopenta[g]isoquinolin-8-yl]-3-(2-hydroxy-4,5-dimethoxyphenyl)-1,3-propanedione	C₃₅H₃₁NO₈S	详情	详情
(XXIII)	48774		C₄₄H₄₅NO₉S	详情	详情
(XXIV)	48775	1-ethoxyvinyl 2-chloroacetate	C₆H₉ClO₃	详情	详情
(XXV)	48776		C₄₀H₄₂ClNO₁₀	详情	详情
(XXVI)	48777		C₃₉H₄₀ClNO₁₀	详情	详情
(XXVII)	48778		C₃₉H₃₈ClNO₁₁	详情	详情
(XXVIII)	48753	(E)-2-butenyl(triphenyl)phosphonium bromide	C₂₂H₂₂BrP	详情	详情
(XXIX)	48779		C₄₃H₄₄ClNO₁₀	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XXIX)

The condensation of the carbaldehyde (XXVIII) with the phosphonium bromide (XXIX) by means of BuLi gives the precursor (XXX), which is finally demethylated with BBr3 and submitted to oxidation by air to yield the target compound.

参考文献中间体

合成目标

【1】 Kita, Y.; et al.; Enantioselective total synthesis of a potent antitumor antibiotic, fredericamycin A. J Am Chem Soc 2001, 123, 14, 3214.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXVIII)	48752		C₃₁H₂₇NO₁₀	详情	详情
(XXIX)	48753	(E)-2-butenyl(triphenyl)phosphonium bromide	C₂₂H₂₂BrP	详情	详情
(XXX)	48754		C₃₅H₃₃NO₉	详情	详情

Extended Information