Fumaroylation

The Diels-Alder reaction catalyzed by this chiral titanium catalyst 31 has wide generality (Scheme 1.53, 1.54, Table 1.22, 1.23). Acryloyl- and fumaroyl-oxazolidinones react with isoprene giving cycloadducts in high optical purity. 2-Ethylthio-l,3-buta-diene can also be successfully employed as the diene [42]. 

The double-bond isomerization of maleoylacetoacetate to fumaroyl acetoacetate is catalyzed by practically any nucleophile, Nu-. Propose a mechanism. 

Whereas for the hexamethyl compound 150 only products formed by the linear route have been detected with a sizeable number of dienophiles (X=X inter alia TCNE, maleic anhydride, benzoquinone, 1,4-naphthoquinone, acrolein, methyl acrylate102), the parent system 4 undergoes threefold Diels-Alder addition in a star-shaped manner leading to 164 with dimethyl acetylenedicarboxylate and to 165 with fumaroyl chloride followed by methanolysis (equation 20)92. 

Dihydroxy benzoyl, see Protocatechuoyl 2.3- Dihydroxybutanedioyl, see Tartaroyl Dihydroxyiodo 2.3- Dihydroxy propanoyl, see Glyceroyl 3.4- Dimethoxybenzoyl, (Hoy— Formyl not methanoyl) Formylamino Formylimino Formyloxy Fumaroyl or trans-hutewe-dioyl) Furancarbonyl, see Furoyl Furfuryl (2- only pre- OCH— or —C(0)H H—CO—NH— H—CO—N= H—CO—0— —CO—CH=CH—CO— trans) OH=C—CH2— H< ... 

Obtained by ozonolysis of N-crotonoyl- or /4-fumaroyl-(2/7)-bomane-10,2-sultam [50]. Prepa ration of (2/f)-bomane-10,2-sultam W. Oppolzer, C. Chapuis, and G. Bemardinelli, Helv. Chim Acta 67 1397 (1984). 

Further reaction of the bromide 33 with acrylonitrile in the presence of PI13P affords the disubstituted product 34 [21]. Selection of amines used in the reaction is critical. Fumaroyl dichloride (35) undergoes oxidative addition, decarbonylation and insertion of acrylate to produce octatrienedioate (36) [22]. 

FNA was synthesized by reaction of /(-naltrexamine (48) with the monomethyl ester of fumaroyl chloride [79], Amine (48) was prepared first from naltrexone by reductive amination with sodium cyanoborohydride in the presence of ammonium acetate to give 6a- and 6/i-epimers (ratio ca. 2 1). Separation was achieved by fractional crystallization [83], An improved synthesis of (48) was reported via the dibenzyliminium salt of naltrexone (46 easily accessible from naltrexone and dibenzylamine) which was reduced with sodium cyanoborohydride to give exclusively the 6/i-epi-mer (47). Catalytic hydrogenolysis afforded /i-naltrexamine (Scheme 3.6) [84]. 

Propose a chemiudly reasonable mecttaniKm for the biological conversion of fumaroyl-aceiooceiate to- fumarate plus acetoacetate tProblem. 4l)k. 

Z)-(l,4-Dioxo-2-butene-l,4-diyl) -COCH=CHCO- the E-form is fumaroyl (Z)-(3-Carboxy-l-oxo-2-propenyl) HOOCCH=CHCO-(l,3-Dioxo-l,3-propanediyl) -COCH2CO-(2-Hydroxy-l,4-dioxo-l,4-butanediyl)-COCH2CH(OH)CO-(Hydroxyphenylacetyl) PhCH(OH)CO--SH... 

Since the [6]radialenes are triple-diene systems, it comes as no surprise that they have been used in multiple Diels-Alder reactions. In fact, after a first 1 1 addition with 150, leading to 161, has taken place, the reaction could proceed in two fashions—a linear course of addition leading to a ara-xylylene 162, and an angular route which produces an crf/ic-xylylene intermediate 163 (equation 19)102-103 Whereas for the hexamethyl compound 150 only products formed by the linear route have been detected with a sizeable number of dienophiles (X=X inter alia TCNE, maleic anhydride, benzoquinone, 1,4-naphthoquinone, acrolein, methyl acrylate ), the parent system 4 undergoes threefold Diels-Alder addition in a star-shaped manner leading to 164 with dimethyl acetylenedicarboxylate and to 165 with fumaroyl chloride followed by methanolysis (equation 20). ... 

Propose a chemically reasonable mechanism for the biological conversion of fumaroyl-acetoacetate to fumarate plus acetoacetate (Problem 29.43). 

The first 5-fluorouracil containing polymer had the 5-FU units in the polymer backbone and this structure is shown below as (XVI). This was claimed to be biologically active (47). More recently, monomer (XVII) was prepared by the reaction of 5-FU with methyl fumaroyl chloride. The polymers and copolymers of (XVII) do show antitumor activity but this may be due to the hydrolysis of this unit to release 5-FU (48). 

The titanium-TADDOL system is notable for its breadth of reacting partners. Fumaroyl [104b] andacryloyl [107] imidedienophiles maybe employed with substituted and unsubstituted butadienes to afford cyclohexenes in high enantiomeric excess (Scheme 37). In the case of 2-thioethylbutadiene, the lower yield is accounted for by the intervention of a competing [2-1-2] cycloaddition pathway. 

This method can be extended to less reactive dienes, as well as to fumaroyl derivatives69. 

Fumaroyl chloride 1115 Maleic anhydride (98 g), ca. 94% phthaloyl chloride (230 g), and anhydrous ZnCl2 (2 g) are placed in a flask fitted with a thermometer reaching almost to the bottom and with a 30-cm column which has a heating mantle and is attached to a descending condenser. The mixture is heated for 2 h in an oil-bath so that the internal temperature of the mixture is 130-135° (not higher ) and then allowed to cool to 90-95°, whereafter the crude fumaroyl dichloride is distilled off as fast as possible (b.p. 60-85°/14 mm). Slow fractionation of the distillate gives a 82-95% yield of chloride, b.p. 62-64°/13 mm. This is best stored in a sealed vessel. 

HOOCCH=CHCOOH I cis-Maleic I frarcs-Fumaric Maleoyl I Fumaroyl I OCCH=GHCO-... 

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