Cyclization reactions Diels-Alder

Scheme 3.83. First domino radical cyclization/intramolecular Diels-Alder reaction process.

Hetero substituted 2-cyclopropylideneacetates are ring-strain activated acrylates, highly reactive dienophiles in Diels-Alder reactions, but also powerful Michael acceptors. The reactivity of these compounds is enhanced by the same strain release in the Diels-Alder cycloadditions as well as in the 1,4-additions, and indeed the borderline between tandem Michael-cyclization and Diels-Alder-type cycloaddition is not well defined in many cases. 

Gorman and Gassman905 have shown that undecatetraenes undergo cyclization (intramolecular Diels-Alder reaction) in the presence of triflic acid to provide bicyclo[4.3.0]nonyl [Eq. (5.332)], bicyclo[4.4.0]decyl, and bicyclo[5.4.0]undecyl [Eq. (5.333)] ring systems, depending on the methyl-substitution pattern. On the basis of a comparative study with varied tetraenes, they concluded that product formation, at least in some cases, could be best interpreted by a stepwise... 

Scheme 2 Diversity-oriented synthesis of highly complex scaffolds via Ugi-5C CR followed by ROM/RCM cyclizations and Diels-Alder reactions...

Cyclohexane derivatives, 569 aldol cyclization, 575, 586 alkenylsilanes, 575 C-1 carbanions, 580 cycloaddition processes, 582 cycloaddition reactions, 582 2-deoxystrq)tamine, 571 Dieckmann cyclization, 574 Diels-Alder cyclizations, 571, 582,584, 585, 589... 

Synthesis of carbocyclic systems intramolecular free-radical cyclization, the Diels-Alder reaction, and ring-closing metathesis... 

Support-bound C-C-C-C fragments serve as components for cyclization in Diels-Alder and hetero-Diels-Alder reactions (HD). In normal Diels-Alder reactions these dienes should preferably be electron rich. The simplest way to introduce the diene is to couple a commercial diene or a diene synthesized by solution phase methodology to a support-bound group. This method, though efficient, restricts the user to a rather limited set of support-bound dienes. In several examples, 2,4-pentadiene-l-carboxylic acid and some of its derivatives were coupled to support-bound amines to give the support-bound diene, which is not particularly reactive in [2 -I- 4]-cycloadditions [301, 302]. 

N,N-Dicyclohexyl-4-morpholinocarboxa-mjdine, 126 Dicyclohexylurea, 162 ( )-Didesoxyzearalone, 329 Dieckmann cyclization, 158 Diels-Alder catalyst, 21 Diels-Alder reactions, 94, 95, 206, 282, 324, 325, 332, 392, 396, 399 Diels-Alder solvents, 126... 

The fact that no cyclohexene was detected in the present experiments suggests that the rate of cyclization through Diels-Alder reaction between formed butadiene and olefins is smaller than the rate of cyclization caused by the reaction of ally radical with olefins at these temperatures. 

Reaction of (903) with trifluoroacetic acid in boiling benzene effected stereospecific rearrangement into the bisnordiamantane (904) in essentially quantitative yield. This result is rationalized in terms of the stability differences between the various possible cations on the reaction profile. Compounds related to (903) have been prepared by intramolecular photochemical cyclization of Diels-Alder dimers of cyclo-hexadienones. ... 

Palladium catalyzed cycloisomerizations of 6-cn-l-ynes lead most readily to five-membered rings. Palladium binds exclusively to terminal C = C triple bonds in the presence of internal ones and induces cyclizations with high chemoselectivity. Synthetically useful bis-exocyclic 1,3-dienes have been obtained in high yields, which can, for example, be applied in Diels-Alder reactions (B.M. Trost, 1989). 

Two approaches to convergent steroid syntheses are based on the thermal opening of benzocyclobutenes to the o-quinodimethane derivatives (see p. 80 W. Oppolzer, 1978 A) and their stereoselective intramolecular Diels-Alder cyclizations. T, Kametani (1977 B, 1978) obtained (+ )-estradiol in a six-step synthesis. The final Diels-Alder reaction occurred regio- and stereoselectively in almost quantitative yield, presumably because the exo transition state given below is highly favored over the endo state in which rings A and D would stcrically inter-... 

Barrelene was obtained via a double Diels-Alder reaction from a-pyrone with methyl acrylate (H.E. Zimmerman, I969A). The primarily forming bicyclic lactone decarboxylates in the heat, and the resulting cyclohexadiene rapidly undergoes another Diels-Alder cyclization. Standard reactions have then been used to eliminate the methoxycarbonyl groups and to introduce C—C double bonds. Irradiation of barrelene produces semibullvalene and cyclooctatetraene (H.E. Zimmerman. 1969B). 

Indoles are usually constructed from aromatic nitrogen compounds by formation of the pyrrole ring as has been the case for all of the synthetic methods discussed in the preceding chapters. Recently, methods for construction of the carbocyclic ring from pyrrole derivatives have received more attention. Scheme 8.1 illustrates some of the potential disconnections. In paths a and b, the syntheses involve construction of a mono-substituted pyrrole with a substituent at C2 or C3 which is capable of cyclization, usually by electrophilic substitution. Paths c and d involve Diels-Alder reactions of 2- or 3-vinyl-pyrroles. While such reactions lead to tetrahydro or dihydroindoles (the latter from acetylenic dienophiles) the adducts can be readily aromatized. Path e represents a category Iley cyclization based on 2 -I- 4 cycloadditions of pyrrole-2,3-quinodimcthane intermediates. 

CATEGORY lldf AND CATEGORY Wfh CYCLIZATIONS - DIELS-ALDER REACTIONS OF VINYLPYRROLES... 

Vinyl ethers and a,P unsaturated carbonyl compounds cyclize in a hetero-Diels-Alder reaction when heated together in an autoclave with small amounts of hydroquinone added to inhibit polymerisation. Acrolein gives 3,4-dihydro-2-methoxy-2JT-pyran (234,235), which can easily be hydrolysed to glutaraldehyde (236) or hydrogenated to 1,5-pentanediol (237). With 2-meth5lene-l,3-dicarbonyl compounds the reaction is nearly quantitative (238). 

Myrcene with its conjugated diene system readily undergoes Diels-Alder reactions with a number of dienophiles. For example, reaction with 3-meth.5i-3-pentene-2-one with a catalytic amount of AlCl gives an intermediate monocyclic ketone, which when cyclized with 85% phosphoric acid produces the bicycHc ketone known as Iso E Super [54464-57-2] (49). The product is useful in providing sandalwood-like and cedarwood-like fragrance ingredients (91). 

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