Fumaronitrile synthesis

Recently, dipolarophile 1)13 (fumaronitrile) (777) has been used in the synthesis of indolizine lactone (677). Both, intermolecular and intramolecular cycloadditions were studied. Intermolecular 1,3-cycloaddition of nitrone (671) to D13 led to the formation of isoxazolidine (672). Subsequent deprotection and esterification of the obtained alcohol (673) with (674) gave isoxazolidine (675) in 65% yield. Ester (675), when refluxed in xylene for 10 min, after elimination of fumaronitrile by cyclo-reversion, underwent spontaneously intramolecular cycloaddition to give the tricyclic cycloadduct (676) in 84% yield (Scheme 2.291). 

The conventional and efficient method for the synthesis of dithienyl-maleimide 185, according Scheme 56, was described by Chinese researchers (06TL9227). 2,3-Bis(5-bromo-2-methylthiophen-3-yl)fumaronitrile 184 was hydrolyzed with sodium methoxide-methanol followed by N-meth-ylation with potassium ferf-butoxide and iodomethane to give the target compound 2,3-bis(5-bromo-2-methylthiophen-3-yl)-N-methylmaleimide. Subsequent modification of the latter afforded 186 containing two ferrocene fragments. 

Nan ya et al. (97) also reported the synthesis of isoindolediones by the reaction of miinchnones with 1,4-benzoquinones. Reactions with an unsymmetrical mtinchnone were not regioselective. Several groups have examined the reactions of miinchnones with unsaturated nitriles, including 2-chloroacrylonitrile (98), cinna-monitrile (78,99) and fumaronitrile (78) to give unexpected products in several cases. Eguchi and co-workers (100) smdied the cycloaddition of several mtinch-nones with electron-deficient trifluoromethylated olehns. Thus, miinchnones 176... 

The Paterno-Biichi reaction has been employed in the synthesis, often in high yield, of a large variety of substituted oxetanes. In addition to simple aliphatic and aromatic alkenes, cycloaddition of ketones to, for example, fumaronitrile,284 l,3-diacetylimidazolin-2-one288 [Eq. (73)], and allenes286 has been reported. Allenes yield both 1,5- and l,6-dioxaspiro[3.3]heptanes as well as the 2-alkylidene-oxetane this is illustrated for benzophenone and tetramethylallene in Eq. (74). Cycloaddition of ketones to ketenimines to form 2- and... 

Styrene, ethyl acrylate and fumaronitrile have been used to mask (3S)-pentacyclic nitrone 77. After a suitable elaboration of isoxazolidines 78 affording 79, the nitrone moiety was restored by thermally induced cycloreversion (145-180 °C), and the tricyclic intermediate 80 was obtained directly through intramolecular 1,3-DC (31-84% yield). This approach was applied to the synthesis of stereodifferentiated polyhydroxyindolizidines such as 81 <02EJO1941>. 

An important new development is the demonstration that Diels-Alder reactions with phospholes and fumaronitriles are greatly accelerated under pressure, and this has led to the synthesis of a number of new 7-phosphanorbornene derivatives. Thus, 3,4-dimethyl-1-phenylphosphole reacted with fumaronitrile at 30 C under 9 kbar for 24 h to give an adduct in 67% yield (Equation (8)) <89T7083>. The stereochemistry at phosphorus was confirmed by x-ray analysis. 

Starting material for the synthesis of 2,3-naphthalocyaninatometal complexes (2,3-NcM) (Fig. 1) is 2,3-dicyanonaphthalene, which in turn is prepared in a one step reaction from ot,(x,a, a -tetrabromoorthoxylene and fumaronitrile in presence of sodium iodide [10]. The iron compound 2,3-NcFe for example is obtained when Fe(CO)5 is reacted with 2,3-dicyanonaphthalene in 1-chloro-naphthalene at 2S0°C in the absence of air (see Scheme 3) [10]. 

In the literature, several methods have been reported for the synthesis of 5-amino p5rrazole derivatives. Hasseneen and coworkers [18] have prepared pyrazole derivatives by the reaction of nitrile imine with fumaronitrile. Jachak and co-workers [19] also reported the synthesis of 4-cyano pyrazole derivatives by starting with cyanoacetaldehyde, DMF-DMA (N,N-Dime-thylformamide dimethyl aceta) and hydrazines. 

The synthesis of non-peripherally substituted octa(alkoxymethyl)phthalocyanines is outlined in Seheme 57 [213, 214]. 2,5-fcij(Alkoxymethyl)furan can be prepared by lithiation of furan followed by quenching the anion with (bromomethyl)alkyl ether to give the mono-substituted furan, and repetition of the procedure to give the required product [213]. A more simple synthesis involves chlorination of 2,5-furan dimethanol with thionyl chloride, followed by nucleophilic displacement of chloride with sodium alkoxide [214]. The furan is equilibrated with fumaronitrile for about a week and the Diels-Alder adduct aromatized by treatment with lithium fcwftrimethylsilyl)-amide (a non-nucleophilic base), followed by an acidic work-up. The 3,6-/7i5(alkoxy-methyl)phthalonitrile is cyclized under standard conditions (lithium/pentanol). 

Scheme 56. The synthesis of 1,4-disubstituted phtha-lonilriles via a Diels-Alder reaction between a furan or thiophene-1,1-dioxide (diene) and fumaronitrile (dienophile).

Scheme 57. Synthesis of non-peripherally substituted octa(alkoxymethyl)phthalocyanines [214]. Reagents (a) SOCI2, (b) RONa/ROH, 36-78% over two steps (c) BuLi (d) ROCHjBr, 20% overall (Cg) (e) fumaronitrile (f) LiN(SiMe3)2/THF (g) H, 4-23% (h) ROLi/ROH, A (i) H 7-34% (j) M acetate, 72-87%.

Arnold first discovered that PET reactions of cis- and rrans-2,3-diphenyloxiranes (1 and 2) with electron-accepting sensitizers such as DCN, 1,4-dicyanobenzene, dimethyl terephthalate, and methyl 4-cyanoben-zoate produce the isomeric tetrahydrofuran derivatives 7 and 8 (Scheme 2). The proposed mechanism involves the CC bond cleavage of the oxirane radical cations to give ylide radical cations 3 and 4, followed by back electron transfer (BET) to generate carbonyl ylides 5 and 6. The resulting carbonyl ylides are trapped with dipolarophiles, such as acrylonitrile, maleonitrile, and fumaronitrile, to produce the observed products. In the absence of dipolarophiles, C)S-/ir s-isomerization (1/2 = 0.19-0.28) was observed, which is consistent with the formation of carbonyl ylides 5 and 6, as well as their radical cations 3 and 4. This method was successfully apphed to the synthesis of various tetrahydrofurans (Scheme 3) and dihydrofurans (Scheme 4). ... 

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