Diels-Alder reaction diene reactivity

In stereoselective reactions, Zn11 Lewis acids work well to achieve high selectivities (Scheme 54). Chiral complexes of Zn11 with chiral bis(oxazoline) ligands act as effective catalysts in Diels-Alder reactions of reactive dienes with dienophiles having bidentate chelating moieties such as... 

Currently available chiral Diels-Alder catalysts have major limitations with regard to the range of dienes to which they can be applied successfully. Indeed, most of the reported catalytic enantioselective Diels-Alder reactions involve reactive dienes such as cyclopentadiene, but 1,3-butadiene and 1,3-cyclohexadiene have not been successfully utilized without reactive 2-bromoacrolein. To solve this problem, a new class of super-reactive chiral Lewis acid catalysts has been developed from chiral tertiary amino alcohols and BBr3 [24] (Eq. 8A.13). This type of chiral super Lewis acid works well for a,fj-acetylenic aldehydes [25],... 

An extremely useful enantioselective Diels-Alder reaction which uses a super-reactive cationic oxazaborinane catalyst was recently reported by Corey and co-workers (Eq. 25) [25]. This strong chiral Lewis acid promotes the Diels-Alder reaction between reactive and unreactive dienes and dienophiles. With tetrabromoborate as a counter-ion, good enantioselectivities were achieved in the reaction of cyclopenta-diene with several a,/3-enals. With tetrakis[3,5-bis(trifluoromethyl)phenyl]borate as a counter-ion, the reaction of isoprene and a-bromoacrolein at -94 °C gave the desired cycloadduct in 90 % yield and 96 % ee. 

In electron-demand Diels-Alder reactions, dienes are activated by electron-donating substituents, such as alkyl, -NR2, and -OR. Electron-rich dienes accelerate the reaction with electron-deficient dienophiles, as illustrated by the relative reactivity trend shown below. 

In order to achieve the necessary geometry in the Diels-Alder transition state, the diene must be able to adopt the 5-cis conformation. In Section 10.10, we saw that the s-cis conformation of 1,3-butadiene is 12 kJ/mol (2.8 kcal/mol) less stable than the 5-trans form. This is a relatively small energy difference, so 1,3-butadiene is reactive in the Diels-Alder reaction. Dienes that cannot readily adopt the s-cis conformation are less reactive. For example, 4-methyl-1,3-pentadiene is a thousand times less reactive in the Diels-Alder reaction than ra/25-1,3-pentadiene because its 5-cis conformation is destabilized by the steric effect imposed by the additional methyl group. 

Different kinds of diene and dienophile are used in the Diels-Alder reactions. Dienes and dienophiles with a heteroatom such as N, O, or S in their Jt systems are known as heterodienes and heterodienophiles, and their cycloaddition reactions are called the hetero-Diels-Alder reactions. Some highly reactive dienes and dienophiles used in Diels-Alder reactions are listed in Table 3.4. 

Silyl-substituted alkenes or dienes can undergo the Diels-Alder reaction . The reactivity of these alkenes, however, is generally lower than those without silyl substituent. In addition, the degree of regioselectivity of the silyl group is evidently small. Only when... 

Rank the following dienes in order of increasing reactivity in a Diels-Alder reaction (1 reactive). Briefly explain your ranking. 

For some early reviews that the author (DJH) has found useful when teaching the fundamentals of the Diels-Alder reaction see Sauer, J. Diels-Alder Reactions. II. Reaction Mechanism Anpfcwandte Chem. Int. Ed. Enp[. 1967, 6, 16-33. Sauer, J. Lang, D. Wiest, H. Diels-Alder Reaction. II. The Addition Capacity of Cis-Trans Isomeric Dienophiles in Diene Additions Chem. Ber. 1964, 97, 3208-3218. Sauer, J. Wiest, H. Mielert, A. Diels-Alder Reaction. I. Reactivity of Dienophiles Towards Cyclopentadiene and 9,10-Dimethylanthracene Chem. Ber. 1964, 97, 3183-3207. 

A few years after the first articles of Breslow had appeared, Grieco elegantly demonstrated that the astonishing rate and selectivity enhancements of Diels-Alder reactions in water can be exploited sirccessfully in organic synthesis. He extensively studied the reactivity of dienes containing... 

In summary, we have demonstrated that it is possible to extend the scope of Lewis-acid catalysis of Diels-Alder reactions in water, by employing a chelating auxiliary. We envisage that analogues of 4.39 capable of undergoing a Mamrich reaction with 4.50 can be treated with reactive dienes in the presence of a Lewis-acid catalyst in water. 

Simple cyclobutanes do not readily undergo such reactions, but cyclobutenes do. Ben-zocyclobutene derivatives tend to open to give extremely reactive dienes, namely ortho-c]uin(xlimethanes (examples of syntheses see on p. 280, 281, and 297). Benzocyclobutenes and related compounds are obtained by high-temperature elimination reactions of bicyclic benzene derivatives such as 3-isochromanone (C.W. Spangler, 1973, 1976, 1977), or more conveniently in the laboratory, by Diels-Alder reactions (R.P. Thummel, 1974) or by cycliza-tions of silylated acetylenes with 1,5-hexadiynes in the presence of (cyclopentadienyl)dicarbo-nylcobalt (W.G, Aalbersberg, 1975 R.P. Thummel, 1980). 

The allenyl moiety (2,3-aikadienyl system) in the carbonylation products is a reactive system and further reactions such as intramolecular Diels-Alder and ene reactions are possible by introducing another double bond at suitable positions of the starting 2-alkynyl carbonates. For example, the propargylic carbonate 33 which has l,8(or 1.9)-diene-3-yne system undergoes tandem carbonylation and intramolecular Diels-Alder reaction to afford the polycyclic compound 34 under mild conditions (60 C, 1 atm). The use of dppp as ligand is important. One of the double bonds of the allenyl ester behaves as part of the dieneflSj. 

The balance between aromatic and aUphatic reactivity is affected by the type of substituents on the ring. Furan functions as a diene in the Diels-Alder reaction. With maleic anhydride, furan readily forms 7-oxabicyclo [2.2.1]hept-5-ene-2,3-dicarboxyhc anhydride in excellent yield [5426-09-5] (4). 

Vinylboranes are interesting dienophiles in the Diels-Alder reaction. Alkenylboronic esters show moderate reactivity and give mixtures of exo and endo adducts with cyclopentadiene and 1,3-cyclohexadiene (441). Dichloroalkenylboranes are more reactive and dialkylalkenylboranes react even at room temperature (442—444). Dialkylalkenylboranes are omniphilic dienophiles insensitive to diene substitution (444). In situ formation of vinyl-boranes by transmetaHation of bromodialkylboranes with vinyl tri alkyl tin compounds makes possible a one-pot reaction, avoiding isolation of the intermediate vinylboranes (443). Other cycloadditions of alkenyl- and alkynylboranes are known (445). 

Isoprene is highly reactive both as a diene and through its allyhc hydrogens, and its reactions are similar to those of butadiene (qv) (8). Apart from polymerisation, the most widely investigated isoprene reactions are the formation of six-membered rings by the Diels-Alder reaction ... 

Maleic anhydride has been used in many Diels-Alder reactions (29), and the kinetics of its reaction with isoprene have been taken as proof of the essentially transoid stmcture of isoprene monomer (30). The Diels-Alder reaction of isoprene with chloromaleic anhydride has been analy2ed using gas chromatography (31). Reactions with other reactive hydrocarbons have been studied, eg, the reaction with cyclopentadiene yields 2-isopropenylbicyclo[2.2.1]hept-5-ene (32). Isoprene may function both as diene and dienophile in Diels-Alder reactions to form dimers. 

Benzo[Z)]furans and indoles do not take part in Diels-Alder reactions but 2-vinyl-benzo[Z)]furan and 2- and 3-vinylindoles give adducts involving the exocyclic double bond. In contrast, the benzo[c]-fused heterocycles function as highly reactive dienes in [4 + 2] cycloaddition reactions. Thus benzo[c]furan, isoindole (benzo[c]pyrrole) and benzo[c]thiophene all yield Diels-Alder adducts (137) with maleic anhydride. Adducts of this type are used to characterize these unstable molecules and in a similar way benzo[c]selenophene, which polymerizes on attempted isolation, was characterized by formation of an adduct with tetracyanoethylene (76JA867). 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

It has long been known that the Diels-Alder reaction is particularly efficient and rapid when the dienophile contains one or more electron-attracting groups. These substituent effects are illustrated by the data in Table 11.3. In the case of the diene, reactivity is increased by electron-releasing substituents. Some illustrative data are given in Table 11.4. 

Bis(trifluoromethyl)-l,l-dicyanoethylene is a very reactive dienophile. It undergoes facile and high-yield [2+4] cycloadditions with 1,3-dienes, cyclopen-tadiene, and anthracene [707] (equation 86). It is reactive enough in a Diels-Alder reaction with styrene [702] (equation 86). 

The mechanism for the hetero-Diels-Alder reaction of benzaldehyde 9 with the very reactive diene, Danishefsky s diene 10, catalyzed by aluminum complexes has been investigated from a theoretical point of view using semi-empirical calculations [27]. The focus in this investigation was to address the question if the reaction proceeds directly to the hetero-Diels-Alder adduct 11, or if 11 is formed via a Mukaiyama aldol intermediate (Scheme 8.4) (see the chapter dealing with hetero-Diels-Alder reactions of carbonyl compounds). 

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