Diels-Alder reaction heterodienes

Hetero-Intramolecular Diels- Alder Reactions Heterodiene-Homodienophile Reactions... 

Pyrazolin-5-ones with an exocyclic double bond at the 4-position (369 X = CMe2> react as heterodienes towards alkyl vinyl ethers (77G91). The kinetics of this Diels-Alder reaction giving pyrazolopyrans (370) have been studied. 

Fluorinated heterodienophiles and heterodienes Diels-Alder reactions in which the dienophiles have perfluoroalkyl-substituted multiple bonds between carbon and a heteroatom are quite common Reported earlier were reactions of perfluoroketones, thiones, ketimines, thioesters, nitroso compounds, and nitriles [9] Examples of a-fluoroimines [107], co-hydroperfluorothioaldehydes [108], perfluorosulfines [109, IIO], and selenocarbonyidifluoride [III] (equations 89-92) have been reported recently... 

Fluorine-substituted heterodienes are particularly prone to inverse electron demand Diels-Alder reactions with electron-rich dienophiles, as can be seen from the examples in equations 94-97 [113, 114, 115, 116, 117]... 

Bis(trifluoromethyl)-substituted heterodienes are electron-deficient species They therefore react preferentially with electron-rich multiple bond systems to give [4+2] cycloadducts (Diels-Alder reaction with inverse electron demand) [238]... 

Nitro compounds have been converted into various cyclic compounds via cycloaddidon reactions. In particular, nitroalkenes have proved to be nsefid in Diels-Alder reactions. Under thermal conditions, they behave as electron-deficient alkenes ind react v/ith dienes to yield 3-nitrocy-clohexenes. Nitroalkenes c in also act as heterodienes ind react v/ith olefins in the presence of Lewis acids to yield cyclic alkyl nkronates, which undergo [3- 2 cycloaddidon. Nitro compounds are precursors for nitnie oxides, alkyl nitronates, and trialkylsilyl nitronates, which undergo [3- 2 cycloaddldon reacdons. Thus, nitro compounds play important roles in the chemistry of cycloaddidon reacdons. In this chapter, recent developments of cycloaddinon chemistry of nitro compotmds and their derivadves are summarized. 

The /zetero-Diels-Alder reaction permits heterocyclic-six- membered rings to be constructed by the interaction of heterodienes and/or heterodienophiles. Both the intermolecular and intramolecular versions of the /zctcro-Diels Alder reaction are, therefore, very important methods for synthesizing heterocyclic compounds. 

Inverse electron-demand Diels-Alder reaction of (E)-2-oxo-l-phenylsulfo-nyl-3-alkenes 81 with enolethers, catalyzed by a chiral titanium-based catalyst, afforded substituted dihydro pyranes (Equation 3.27) in excellent yields and with moderate to high levels of enantioselection [81]. The enantioselectivity is dependent on the bulkiness of the Ri group of the dienophile, and the best result was obtained when Ri was an isopropyl group. Better reaction yields and enantioselectivity [82, 83] were attained in the synthesis of substituted chiral pyranes by cycloaddition of heterodienes 82 with cyclic and acyclic enolethers, catalyzed by C2-symmetric chiral Cu(II) complexes 83 (Scheme 3.16). 

Keywords 1,2-azapyrylium as heterodiene components and aikynes as dienophiles in a Diels-Alder reaction with inverse eiectron demand as cruciai step... 

Although disilenes do not undergo Diels-Alder reaction with 1,3-dienes,68 they react with heterodienes like benzil,67-89 acylimines,90 and 1,4-diazabutadienes91 to give [4 + 2] cycloadducts (Eqs. 26-28). 

Diels-Alder reactions are one of the most fundamental and useful reactions in synthetic organic chemistry. Various dienes and dienophiles have been employed for this useful reaction.1 Nitroalkenes take part in a host of Diels-Alder reactions in various ways, as outlined in Scheme 8.1. Various substituted nitroalkenes and dienes have been employed for this reaction without any substantial improvement in the original discovery of Alder and coworkers.2 Nitrodienes can also serve as 4ti-components for reverse electron demand in Diels-Alder reactions. Because the nitro group is converted into various functional groups, as discussed in Chapters 6 and 7, the Diels-Alder reaction of nitroalkenes has been frequently used in synthesis of complex natural products. Recently, Denmark and coworkers have developed [4+2] cycloaddition using nitroalkenes as heterodienes it provides an excellent method for the preparation of heterocyclic compounds, including pyrrolizidine alkaloids. This is discussed in Section 8.3. 

Denmark and coworkers have developed an elegant method for generating cyclic nitronates using nitroalkenes as heterodienes in the Diels-Alder reaction (Eq. 8.78). The synthetic utility of this reaction is discussed in Section 8.3. 

While disilene 5 does not undergo Diels-Alder reactions with 1,3-dienes, the [4+2]-cycloaddition products are formed with heterodienes, e.g. 1,4-diazabutadienes [17] or a-ketoimines [19]. It can be deduced that the electron deficient properties of such dienes cause them to readily take part in hetero-Diels-Alder reactions, which have inverse electron demands. This is corroborated by theoretical calculations which predict an inverse electron demand of the Si-Si double bond it is strongly electron donating rather than electron accepting towards butadienes and other compounds [24,25]. 

The doubly protected indolinethiol 275 undergoes deprotection by treatment with silica gel at low pressure the intermediate heterodiene then reacts with the protected glucal 276 in an inverse electron demand Diels-Alder reaction to give the fused tetracyclic product 277 (Equation 96) <2003JOC7907>. 

The hetero-Diels-Alder reaction is one of the most important methods of synthesis of heterocycles, yet as a potentially powerful synthetic tool it has found relatively little general use. Microwave irradiation has been used to improve reactions involving heterodienophiles and heterodienes of low reactivity. 

Jimenez et al. studied the asymmetric Diels-Alder reactions of 1-aryl-1,2-diaza-l,3-butadienes 114, heterodienes derived from sugars, with diethyl azodicarboxylate (115), a heterodienophile [85]. The reactions were performed without solvent in a focused microwave reactor for periods of a few hours. The reaction is stereoselective... 

The heterodiene and dienophile behaviours of thioketones have been investigated by Saito in diene-trasmissive112 and transannular113 Diels Alder reactions. 

SCHEME 14. Diels-Alder reaction with acyclic heterodienophiles and heterodienes... 

In Scheme 14 the effect of pressure on Diels-Alder reactions with acyclic heterodienophiles or heterodienes is presented. The application of high pressure leads also in these reactions to an enhancement of rates and improvement of yields. The hetero-Diels-Alder reaction (entry 3) is a good example of the interplay between pressure and temperature. At high pressure the rate of reaction as well as the diastereoselectivity are increased. The pressure-induced acceleration allows the temperature of reaction to be lowered, which leads to a further increase of diastereoselectivity. 

On the basis of available experimental data, it is impossible to choose a definite pathway of elimination of silanol. However, study of silylation of methyl P -nitropropionate (411) with BSA in the presence of trapping agents rigorously proved that silyl nitronate D is initially formed. This compound can be detected in the [3 + 2]-cycloaddition reaction with methyl acrylate product (413). If silylation of AN (411) is performed in the presence of ethyl vinyl ether, a-nitrosoalkene E can be successfully trapped in as heterodiene a Diels-Alder reaction. Dihydroox-azine (414) is formed, and its silylation affords isolable product (415). 

Cycloadditions and cyclization reactions are among the most important synthetic applications of donor-substituted allenes, since they result in the formation of a variety of carbocyclic and heterocyclic compounds. Early investigations of Diels-Alder reactions with alkoxyallenes demonstrated that harsh reaction conditions, e.g. high pressure, high temperature or Lewis acid promotion, are often required to afford the corresponding heterocycles in only poor to moderate yield [12b, 92-94]. Although a,/3-unsaturated carbonyl compounds have not been used extensively as heterodienes, considerable success has been achieved with activated enone 146 (Eq. 8.27) or with the electron-deficient tosylimine 148 (Eq. 8.28). Both dienes reacted under... 

In the [4 + 2] cycloadditions discussed so far, the enol ether double bond of alkoxyallenes is exclusively attacked by the heterodienes, resulting in products bearing the alkoxy group at C-6of the heterocycles. This regioselective behavior is expected for [4+2] cycloadditions with inverse electron demand considering the HOMO coefficients of methoxyallene 145 [100]. In contrast, all known intramolecular Diels-Alder reactions of allenyl ether intermediates occur at the terminal C=C bond [101], most probably because of geometric restrictions. 

Aiming at the pyranose form of sugars, normal type hetero-Diels-Alder reactions were extensively used for the synthesis of functionally substituted dihydropyran and tetrahydropyran systems (5-10) (see routes A - D in the general Scheme 1) which are also important targets in the "Chiron approach" to natural product syntheses (2.) Hetero-Diels-Alder reactions with inverse electron demand such as a, p-unsaturated carbonyl compounds (l-oxa-1,3-dienes) as heterodienes and enol ethers as hetero-dienophiles, are an attractive route for the synthesis of 3,4-dihydro-2H-pyrans (11). 

Conjugated oximes were converted to pyrazoles in a one-pot reaction by refluxing with hydrazine and iodine in ethanol. The process proceeds via an inverse electron-demand Diels-Alder reaction involving electron-deficient heterodienes and diimide species as dipolarophiles . ... 

As another application, treatment of bromotrifluoroacetone oxime with a base yields an interesting heterodiene. This molecule can be involved in hetero-Diels-Alder reactions with electron-rich olefins (Figure 2.56). In the presence of indole, it allows the introduction of the 2-aminotrifluoropropane motif (Figure 2.56). ... 

Novel 2-amino-substituted- 3-methylenedihydropyrans 2 have been obtained from inverse electron demand Diels-Alder reactions of allenamides with heterodienes <99TL6903> and the reaction of styrenes with a,p-unsaturated 2-oxonitriles yields predominantly the cis-2-aryldihydropyran-6-carbonitriles 3 <99HCA1122>. 

The other dihydropyridines containing electron-deficient 7r-systems should also be capable of undergoing cycloaddition reactions. However, the instability of these compounds and lack of general methods for their preparation have precluded their study. In principle both the 2,3- and 3,4-dihydropyridines could behave as heterodienes in the Diels-Alder reaction. Although these reactions are known for the 2-azadienes, lack of information in the literature on 1-azadienes suggests that they will be reluctant to participate in cycloadditions double bonds present in the 2,5-dihydropyridine are isolated and would only be expected to behave as two-electron partners in cycloaddition reactions. 

Only two examples of the synthesis of pyrrolo[3,4-r-]pyridazines that begin with a pyridazine have been reported. The first involves a Diels-Alder reaction. Thus pyridazine 88 under thermal conditions provides the heterodiene 89 intermediate with loss of CO2, which is trapped / situ with A -phenyldiazamaleimide to form 90 in the yields shown (Scheme 8) <20010L3647>. Alternatively, the thiadiazole 1,1-dioxide 91 can produce 89 by loss of SO2. 

Diels-Alder reactions have featured heavily during the period of review. Ar-Vinyl-2-oxazolidinone has been reported as a dienophile for the first time, including the preparation of various tetrahydro-277,77/-pyrano[4,3-. ]pyrans <2002SL952>. The heterodiene cycloaddition reaction of 3-formylchromone with a series of ketene acetals formed from C2-symmetric l,2-diarylethane-l,2-diols is completely diastereoselective (Scheme 40) <1995J(P1)2293>. 

In the presence of aluminum chloride, which presumably lowers the energy of the LUMO of the heterodiene by Lewis acid complexation, electron-rich alkenes give dihydropyrans on reaction with acyl cyanides at room temperature (82AG(E)859). Unsaturated esters further extend the range of diene components of value in these Diels-Alder reactions with inverse electron demand (82TL603). 

Hetero-Diels—Alder reactions, via cobalt(III) complexes, 7,44 Heterodienes, with iron, 6, 145 if- Heterodienes, with tantalum, 5, 176 Heterodinuclear iridium complexes, synthesis, 7, 371 Heterodinuclear iridium—platinum complexes, synthesis and characterization, 7, 380... 

Selenophene and selenium-nitrogen five-membered heterocycles serve as heterodienes in Diels-Alder reactions. [l,4]Cycloaddition at the W/Z positions in 75a (four atom fragment) is equivalent to [l,3]dipolar cycloaddition in 75b or 75c, both providing the 47i-electron component of the cycloaddition (Fig. 7)... 

Selenazole and the 1,2,4- and 1,2,5-selenadiazoles serve as heterodienes in the Diels-Alder reaction. [l,4]Cycloaddition of the active dienophiles to these selenaheterocyclic compounds, followed by deselenation, is a convenient means of synthesis of a nonselenium azaaromatic ring. Cycloaddition of 2,4-disubstituted 1,3-selenazole (131) with DMAD forms a bicyclo intermediate (132) that undergo extrusion of elemental selenium liberating the pyridine product (133) (Scheme 42) [110]. 

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