Synthesis Diels-Alder

Cyclopentene-l-carboxaldehydes are obtained from cyclohexene precursors by the sequence cyclohexene - cyclohexane-1,2-diol -> open-chain dialdehyde - cyclopentane aldol. The main advantage of this ring contraction procedure is, that the regio-and stereoselectivity of the Diels-Alder synthesis of cyclohexene derivatives can be transferred to cyclopentane synthesis (G. Stork, 1953 G. BUchi, 1968). 

Bicyclic compounds of structure (4) are needed for the synthesis of the alkaloid dendrobine. What is the starting material for a Diels-Alder synthesis of (4) Stereochemistry is obviously vital here. 

Recently, Jankowski et al. [80] reported the application of MW to the Diels-Alder synthesis of N-methyloctahydroisoquinoline adducts, which are important intermediates in the synthesis of medicinally important compounds, such as HIV protease inhibitor isoquinoline carboxylate pharmaceuticals. The reaction of the arecoline 67 or its isomer 70 with Danishefsky s diene 68 in toluene (Scheme 4.32) was studied under both conventional and MW heating in sealed tubes, i. e. at elevated pressure. 

Scheme 4.32 Diels-Alder synthesis of isoquinoline carboxylates.

Generally, benzene and naphthalene derivatives show only little reactivity as dienes in Diels-Alder synthesis, contrary to anthracene and the higher acene derivatives which are frequently used as dienes. Exceptions are the reactions of benzene and naphthalene derivatives with highly reactive dienophiles such as dicyanoacetylene (DCA), which... 

Diels-Alder Synthesis. An additive combination of "dienes "(qv) with substances of the grouping >C=C-CO-R. For the description of this synthesis see Refs... 

Although the utilization of the Diels-Alder synthesis as a step-growth reaction for polymerization requires, in most cases, rather unusual monomers, an occasional lengthy and trying synthesis, torturous purifications, and, in certain cases, difficult reaction conditions, it does afford high... 

The usual reaction of alkenes with conjugated dienes is the Diels-Alder synthesis. This addition does not apply, with a few exceptions, to cycloaddition of fluorinated alkenes. The presence of fluorine atoms, especially if there are more of them around the double bond, retards the cycloadditions forming six-membered rings, and accelerates the (2 + 2) cycloaddition to form four-membered rings. 

A report of Backer and Blaas6 is responsible for evolution of the present procedure these workers were first to conduct a Diels-Alder synthesis utilizing a 3-sulfolene in place of the free diene (by heating the cyclic adduct of sulfur dioxide and 2-methyl-3-thiomethyl-1,3-butadiene with maleic anhydride). The generality of the method as a variant of the conventional diene synthesis is limited largely by the availability of the appropriate 3-sulfolene its greatest utility, perhaps, will be presently realized in those diene reactions normally requiring 1,3-butadiene, since 3-sulfolene itself is now the least expensive and most widely available diene cyclic sulfone. 

Staehle, W, Kunz, H, Carbohydrates as chiral templates stereoselective Diels-Alder synthesis with dienes of differing reactivity, Synlett, 260-262, 1991. 

Kresze, G., Albrecht, R. Heterocycles by diene synthesis. Dienophilic azomethines and their diene adducts. Ber. 1964, 97,490-493. Albrecht, R., Kresze, G. Heterocycles by diene synthesis. II. N-Carbobutyloxymethylene-p-toluenesulfonamide, a new dienophile for the preparation of pyridine, piperideine, and piperidine derivatives by the Diels-Alder synthesis. Chem. Ber. 1965, 98,1431-1434. 

Recently, Hashmi and coworkers reported a selective Diels-Alder synthesis of phenolic compounds catalysed by Au(III) (equation 130). The mechanism has proven to include an intramolecular migration of the oxygen atom of the furan ring. Several other transition metals with d configuration (Pd , Pt , Rh , Ir ) allow this conversion, but Au is shown to be the most active catalyst giving the cleanest conversion. 

This is followed by an example of a pyrrole synthesis DIMETHYL-3-PHENYLPYRROLE-2,5-DICARBOXYLATE is obtained via an inverse demand Diels-Alder synthesis using DIMETHYL-1,2,4,5-TETRAZINE-... 

X = S) reacts with diazonium salts to form 5-arylhydrazones, and is 5-aminomethylated under Mannich conditions. The dioxo analogue, however, does not take part in the second two reactions <87MI 302-01) (Scheme 71). 2-Alkylideneimidazolidines take part in inverse Diels-Alder synthesis <87TL2681, 87TL6027>, and they are C-alkylated by alkyl halides in neutral media <94H(37)1233>. 

In 1986, Keller-Schierlein, ZShner and their respective coworkers isolated ( )-differolide (135, Figure 5.14) from cultures of an actinomycete, Streptomyces aurantiogriseus Tii 3149. This compound ( )-135, whose structure was determined by X-ray diffraction studies, was reported to enhance the formation of aerial mycelium and spores of Streptomyces glaucescens. Especially noteworthy was the fact that the natural product was racemic. There are some examples of the occurrence of racemic and bioactive natural products such as magnosalicin (10) and olean (116), but they are rare. Although there was a straightforward Diels-Alder synthesis of ( )-135 by dimerization of 2-vinyl-2-buten-4-olide, this method would not afford the enantiomers of 135. 

The synthesis of captan starts from tetrahydrophthalic anhydride (10) obtained in the classical way from butadiene and maleic anhydride by Diels-Alder synthesis, according to the following reaction (Kohler and Jansen, 1938) ... 

Similar structures can be realised in low yield from the Friedel-Crafts reaction of 1,4-dimethoxybenzene with substituted phthalic anhydrides (R = Me, Et, i-Pr), which were obtained by the appropriate Diels-Alder synthesis. The acylations were effected in the presence of boron trifluoride etherate as catalyst, followed by demethylation of the product (ref.55). 

Clays [2] and zeolites [3] have been reported as good catalysts for Diels-Alder synthesis. Recently, we have studied the Diels-Alder cycloaddition between methyl acrylate (1) and cyclopentadiene (2) (Figure 1) and have shown that the solvent [4], the calcination of the solid [5] and the exchanged cation [6] play a decisive role. We now report the results obtained from the reactions of cyclopentadiene with methyl and (-)-menthyl acrylates, catalysed by K10 montmorillonites exchanged with different cations and dried at 120°C or calcined at 550°C. 

OTHER COMMENTS used as a dienophile in Diels-Alder synthesis used in the manu facture of dye intermediates, pharmaceuticals, and agricultural chemicals, used in the formatioi of fumaric and tartaric acid used in copolymerization reactions. 

The Diels-Alder reaction, a classic of synthetic organic chemistry, is theoretically a 4 + 2 cycloaddition in which a diene and a dienophile with very different electron abundances combine to form a new six-membered ring. Equation 7.1 is a typical Diels-Alder synthesis. The reaction has great synthetic usefulness and has attracted many researchers interested in its practical applications and mechanistic aspects. It is not at all certain whether any Diels-Alder reaction occurs under environmental... 

G, Kresze and E. Kysela, Polyhydroxyamines via Diels-Alder synthesis with nitroso compounds. 

G. Kresze, E. Kysela, and W. Dittel, Polyhydroxyamines via Diels-Alder synthesis with nitroso compounds. V. l,3-Cyclohexadiene-5,6-dicarboxylic acid derivatives as reactants, Liebigs Ann. Chem., 210 (1981). 

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