Dienophiles common

A carbonyl group is an effective electron-withdrawing group because the carbonyl carbon bears a partial positive charge (8 ), which withdraws electron density from the carbon-carbon double bond of the dienophile. Common dienophiles that contain a carbonyl group are shown in Figure 16.9. 

Reactions of simple fulvenes with dienophiles commonly take place at C(2) and C(5) and those with dienes at C(2) and C(3), i.e. the latter proceed by a [2 + 4] rather than a [6 + 4] cycloaddition. This, and other features of cycloaddition reactions involving fulvenes can be nicely explained in terms of frontier orbital theory [234,235]. In some reactions fulvenes may participate as 6ir rather than 27t components, for example with diazomethane ... 

In the Diels-Alder reaction (in older literature referred to as the diene synthesis ) a six-membered ring is fonned through fusion of a four-tt component, usually a diene and a two-7C component, which is commonly referred to as the dienophile (Scheme 1.1). 

In a Lewis-acid catalysed Diels-Alder reaction, the first step is coordination of the catalyst to a Lewis-basic site of the reactant. In a typical catalysed Diels-Alder reaction, the carbonyl oxygen of the dienophile coordinates to the Lewis acid. The most common solvents for these processes are inert apolar liquids such as dichloromethane or benzene. Protic solvents, and water in particular, are avoided because of their strong interactions wifti the catalyst and the reacting system. Interestingly, for other catalysed reactions such as hydroformylations the same solvents do not give problems. This paradox is a result of the difference in hardness of the reactants and the catalyst involved... 

Thiophene fails to undergo cycloaddition reactions with common dienophiles under normal conditions. However, when thiophene is heated under pressure with maleic anhydride, the exo adduct (136) is formed in moderate yield (78JOC1471). 

The same conclusions are drawn by analysis of the frontier orbitals involved in cycloadditions. For the most common case of the Diels-Alder reaction, which involves dienophiles with electron-attracting substituents, the frontier orbitals are l/2 of the diene (which is the HOMO) and n of the dienophile (which is the LUMO). Reaction occurs by interaction of the HOMO and LUMO, which can be seen from the illustration below to be allowed. 

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... 

Covalent fluondes of group 3 and group 5 elements (boron, tin, phosphorus, antimony, etc ) are widely used m organic synthesis as strong Lewis acids Boron trifluoride etherate is one of the most common reagents used to catalyze many organic reactions. A representative example is its recent application as a catalyst in the cycloadditions of 2-aza-l,3-dienes with different dienophiles [14] Boron trifluoride etherate and other fluonnated Lewis acids are effective activators of the... 

The most common and synthetically most useful Diels-Alder reactions involve the addition of an electron-rich diene and an electron-poor dienophile, e.g. 

In contrast, addition of dimethyl acetylenedicarboxylate to cyclopent[6]azepine (6) is slow and furnishes, in 53% yield, a mixture of the dimeric 1 2 adduct 7 (red crystals), the 1 3 adduct 8 (yellow oil), and an unidentified purple oil.2 Surprisingly, cyclopent[6]azcpine fails to react with other common dienophiles such as ethenetetracarbonitrile, diethyl maleate and chlorosulfonyl isocyanate. 

The Diels-Alder reaction is an organic chemical reaction (specifically, a cycloaddition) between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene system. The reaction can also proceed if the alkene is replaced by an alkyne moiety or even if some of the atoms... 

Recent study of silenes has clearly established their ability to act as dienophiles in [2 + 4] Diels-Alder-type reactions involving 1,3-dienes. However, it has also been clearly demonstrated that products of the ene reaction commonly accompany the [2 + 4] cycloadducts and may on occasion be the major products. In addition, unlike those in carbon chemistry, [2 + 2] cycloadditions are often observed to occur in competition with the above processes—not only from reactions of silenes with dienes... 

These reactions are found to be promoted by electron-donating substituents in the diene, and by electron-withdrawing substituents in the alkene, the dienophile. Reactions are normally poor with simple, unsubstituted alkenes thus butadiene (63) reacts with ethene only at 200° under pressure, and even then to the extent of but 18 %, compared with 100% yield with maleic anhydride (79) in benzene at 15°. Other common dienophiles include cyclohexadiene-l,4-dione (p-benzoquinone, 83), propenal (acrolein, 84), tetracyanoethene (85), benzyne (86, cf. p. 175), and also suitably substituted alkynes, e.g. diethyl butyne-l,4-dioate ( acetylenedicarboxylic ester , 87) ... 

Oxidative-pericydic processes, and in particular the oxidative/Diels-Alder reaction, are quite common in nature. The so-called Diels-Alderase is usually an oxidizing enzyme, which induces, for example, the formation of a suitable dienophile such as an enone from an allylic alcohol [49]. 

Cyclic ADC compounds are similarly prepared by oxidation of the corresponding cyclic hydrazine derivatives. The most commonly encountered compounds are the 3//-l,2,4-triazole-3,5(4//)-diones (5), and in particular the 4-phenyl derivative (5, R = Ph), usually abbreviated as PTAD. Similarly, the abbreviation MTAD is used for the 4-methyl derivative. First prepared by Thiele,18 PTAD remained unused in organic synthesis until Cookson reported its powerful dienophilic properties some 70 years later.19 PTAD is an isolable, red, crystalline compound, prepared by r-butyl hypochlorite oxidation of 4-phenylurazole.20 Other oxidants which have been successfully... 

As with five-membered ring formation, the reactions of ADC compounds which lead to six-membered ring heterocycles can be classified according to how the ADC compound reacts in the initial step. Most common is the Diels-Alder reaction, with the ADC compound acting as dienophile. Six-membered rings also result from the reaction of monoenes with ADC compounds acting as the 4n component, and by cyclization or other transformation of an initial adduct. 

Novel steroidal pyridazines are readily prepared from ADC compounds and steroidal A2,4-dienes,163 A14,1 -dienes,164 and A16,20-dienes.165 ADC compounds are also commonly used in the protection of the steroid 5,7-diene system (see Section V,A). These Diels-Alder adducts of steroidal dienes and azo dienophiles should not be confused with the so-called azasteroids, which are also prepared from ADC compounds. Cyclic ADC compounds such as the pyrazole-3,5-diones (7), and the diazaquinones 12 and 13 readily add to dienes to give bicyclic pyridazine derivatives,166168 and these reactions have been adapted to the synthesis of 5,10-diazasteroids (106).42 Similarly, the 13,14-diaza- (107) and 13,14,16-triazasteroid (108) ring systems have been prepared.169... 

For instance, cycloadditions of [60]fullerene (4) under the action of microwave irradiation usually require the use of this technique, because reactions are performed on a very small scale and C60. in common with many dienophiles, does not absorb microwaves efficiently [19]. 

A common method to synthesize pyridazines remains the inverse electron-demand Diels-Alder cycloaddition of 1,2,4,5-tetrazines with electron rich dienophiles. [4 + 2]-Cycloadditions of disubstituted 1,2,4,5-tetrazine 152 with butyl vinyl ether, acrylamide, phenylacetylene, and some enamines were performed to obtain fully substituted pyridazines 153 . This reaction was accelerated by electron withdrawing groups, and is slowed by electron donating groups, R1 and R2on the tetrazine. 

As in benzene, the substituents in ortho and para will be better conjugated than those in meta. These qualitative aspects of regioselectivity have been studied quantitatively by quantum mechanical studies. Further the molecular orbital considerations have shown that the favoured transition state will be that in which there is strongest interaction between the HOMO of the diene and LUMO of the dienophile. In the most common cases the dienophile bears an electron withdrawing substituent and the diene an electron releasing one. Here the interation is between the LUMO of the dienophile and the HOMO of diene. 

As a specific example of the vinylallenes, 294 demonstrates that not only can common dienophiles such as maleic anhydride (MA) be added (to furnish adduct 295 with a rich functionality) [122], but also carbonyl compounds such as propanal to afford 296 when the reaction is carried out in the presence of a Lewis acid catalyst [27]. 

In common with other azodicarboxylic acid derivatives, the uses of 4-phenyl-l,2,4-triazoline-3,5-dione are many. It undergoes a Diels-Alder reaction with most dienes11-14 and is, in fact, the most reactive dienophile so far reported.15 16 As with the formation of all Diels-Alder adducts the reaction is reversible, and in the case of the adduct with 3-j3-acetoxy-17-cyano-5,14,16-androstatriene, the reverse reaction can be made to proceed under especially mild conditions.14 An instance has also been reported of the dione photochemically catalyzing other retro Diels-Alder reactions.17 Along with the proven use of azodicarboxylic ester,18-18 the dione should be potentially important in the preparation of strained ring compounds. 

Metal complexes of bis(oxazoline) ligands are excellent catalysts for the enantioselective Diels-Alder reaction of cyclopentadiene and 3-acryloyl-l,3-oxa-zolidin-2-one. This reaction was most commonly utilized for initial investigation of the catalytic system. The selectivity in this reaction can be twofold. Approach of the dienophile (in this case, 3-acryloyl-l,3-oxazolidin-2-one) can be from the endo or exo face and the orientation of the oxazolidinone ring can lead to formation of either enantiomer R or S) on each face. The ideal catalyst would offer control over both of these factors leading to reaction at exclusively one face (endo or exo) and yielding exclusively one enantiomer. Corey and co-workers first experimented with the use of bis(oxazoline)-metal complexes as catalysts in the Diels-Alder reaction between cyclopentadiene 68 and 3-acryloyl-l,3-oxazolidin-2-one 69 the results are summarized in Table 9.7 (Fig. 9.20). For this reaction, 10 mol% of various iron(III)-phe-box 6 complexes were utilized at a reaction temperature of —50 °C for 2-15 h. The yields of cycloadducts were 85%. The best selectivities were observed when iron(III) chloride was used as the metal source and the reaction was stirred at —50 °C for 15 h. Under these conditions the facial selectivity was determined to be 99 1 (endo/exo) with an endo ee of 84%. 

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