Use of Heterodienophiles

Tetr 37 1825 (1981) (singlet oxygen review) 38 1299, 3087 (review) (1982) 42 5045, 6477 (1986) (both asymmetric aldehyde, high pressure) 

Weinreb, Hetero Diels-Alder Methodology in Organic Synthesis, Academic Press, New York (1987) (review) 

Houben-Weyl, Methods in Organic Chemistry, 4th ed, Vol E21c, G. Thieme, Stuttgart-New York (1995) (enantioselective review) 

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Examples of the use of heterodienophiles under the action of microwave irradiation are not common. Soufiaoui [84] and Garrigues [37] used carbonyl compounds as die-nophiles. The first example employed solvent-free conditions the second is an example of the use of graphite as a susceptor. Cycloaddition of a carbonyl compound provided a 5,6-dihydro-2H-pyran derivative. These types of reaction proceed poorly with aliphatic and aromatic aldehydes and ketones unless highly reactive dienes and/or Lewis acid catalysts are used. Reaction of 2,3-dimethyl-l,3-butadiene (31) with ethyl glyoxylate (112) occurred in 75% yield in 20 min under the action of microwave irradiation. When conventional heating is used it is necessary to heat the mixture at 150 °C for 4 h in a sealed tube to obtain a satisfactory yield (Scheme 9.33). 

Two reports of the use of heterodienophiles, amidines100 and aldehyde N,N-dimethylhydrazones,l00b in [4 + 2] cycloadditions with 1,2,4-triazines have been detailed (Table 10-IX). 

The method has then been efficiently used to remove selectively the exocycHc methylsulfanyl group from phosphorylated thiopyranyl derivatives 85 resulting from hetero Diels-Alder reaction of a phosphono-dithioformate or dithioacetate (see Sects. 2.1.2 and 2.2.3). FimctionaHzed thiopyrans 86 [17,18,27a] are thus obtained (Scheme 25). Owing to this selective desulfanylation, phospho-nodithioesters can be used as heterodienophiles in place of the corresponding phosphonothioaldehyde, not described so far and probably very unstable. 

J0rgensen and co-workers (229,230) examined the use of a-ketoesters and 1,2-diones as heterodienophiles in reactions with Danishefsky s diene. Catalyst 269c was found to exert the highest facial bias in these reactions, and is generally tolerant of substitution on the dione. These reactions may be conducted with as little as 0.05 mol% catalyst loadings. 

The versatility of these [4+2] heterocyclization reactions is a consequence of the wide range of ene and diene components which can be used. In addition to alkenes and alkynes functioning as ene components, a variety of heterodienophiles is available such as electron-deficient imines (e.g. equation 89), nitriles e.g. equation 90), electrophilic carbonyl compounds (e.g. equation 91), thiocarbonyl compounds (e.g. equation 92), singlet oxygen (e.g. equation 93), nitroso compounds (e.g. equation 94), sulfenylsulfonamides (e.g. equation 95) and azo compounds (e.g. equation 96). Many of these reactions proceed with excellent regioselectivity and stereoselectivity, probably because in many instances they involve... 

Clearly, an important feature will be the selectivity of these reactions. In this respect, the control of endo- and exo-selectivity using different Lewis acids, the induced diastereoselectivity with chiral heterobutadienes as well as chiral heterodienophiles and finally the use of chiral Lewis acids for the enantioselec-tive synthesis will be discussed. In recent time some attention has been paid to hetero Diels-Alder reactions in aqueous solutions and in the presence of inor-... 

The hetero-Diels-Alder reaction is amongst the most efficient processes for the synthesis of six-membered heterocyclic ring systems. Solvent-free conditions have been used to improve reactions of heterodienophiles and heterodynes with low reactivities. Cado et al. (1997) have described the hetero-Diels-Alder reaction of ethyl lH-perimidine-2-acetate as heterocyclic ketene aminal with ethyl propiolate nnder solvent-free conditions with focused microwave irradiation. The new fused perimi-dines (23) were obtained in good yields (67-98%). 

Thioaldehydes have been used as heterodienophiles in cycloadditions (Diels-Alder or 1,3-dipolar) mainly in connection with attempts to show the formation of the transient thioaldehydes by trapping in situ. During... 

Diels-Alder reactions of heterodienophiles have been known for decades, but only recently has this methodology become widely accepted by the synthetic community. There is enormous diversity in the structural types of compounds which can act as heterodienophiles, and a wide array of heterocyclic adducts can be prepared via these [4 + 2] cycloadditions. It seems clear that hetero Diels-Alder reactions span a range of mechanism from concerted to stepwise ionic processes. In many instances, mechanistic information is totally lacking. The discussion below therefore classifies heterodienophiles by structural rather than mechanistic class. Only the major types of synthetically useful heterodienophiles have been included. Moreover, the significant regio- and stereo-chemical features of the reactions have been exemplified as much as possible using recently reported cases. Other more comprehensive and more specialized reviews should be consulted for older material and more obscure hetero Diels-Alder cycloadditions. 

Since Danishefsky demonstrated that activated dienes, such as siloxydiene (commonly referred to as Danishefsky s diene) react with a wide spectrum of aldehydes to afford 5,6-dihydro-y-pyrones in 1982 [l],the hetero-Diels-Alder reaction has attracted a great deal of attention over the last two decades [2,3]. The use of asymmetric catalysis in these reactions is overwhelmingly associated with heterodienophiles. Especially, the cyclocondensations of activated dienes with aldehydes or their derivatives are of particular importance, providing a multitude of opportunities for the highly efficient regio- and stereoselective construe-... 

A useful group of heterodienophiles are imines, containing the group RCH=NR. These react with 1,3-dienes to form 1,2,3,6-tetrahydropyridines. Most reactive are imines bearing an electron-withdrawing substituent on one or both of the carbon... 

Nitroso compound 84, imine 85, azodicarboxylate 86, and carbonyl compound 87 are used as heterodienophiles in Diels-Alder reactions for the synthesis of heterocycles. 

These pentacyclic products arise from aniline-derived iminium ions functioning as dienes rather than heterodienophiles in two sequential [4+2] cycloaddition reactions with cyclopentadiene. It is noteworthy that use of the preformed Schiff base under non-aqueous conditions leads to the formation of tricyclic tetrahydroquinoline derivatives wherein one cyclopentene unit is incorporated [5]. 

Grieco et al. have also reported the use of C-acyl iminium ions as heterodienophiles in the aqueous Diels-Alder reaction with cyclopentadiene [8]. This work details the cyclocondensation of C-acyl A-alkyl iminium ions 18 and C-acyl A-unsubstituted iminium ions 19 with cyclopentadiene in water ... 

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