Maleic anhydride, Diels-Alder cycloaddition

Heterocycles with a similar 1,4-dihydropyridine ring, such as TV-substituted 1,4-dihydroquinolines (39), have also been allowed to react with dimethyl acetylenedicarboxylate. Depending on the substituent at the ring, a (2 + 2)-cycloadduct (40)60 or a linear Michael adduct (41)59 was formed. The (2 + 2)-cycloadducts (43) of l,2-dihydropyridines(42) with dimethyl acetylenedicarboxylate are far less stable. Only NMR spectroscopy at —10° to 0° has provided evidence for the formation of 43. At room temperature the (2 + 2)-cycloaddition was followed by isomerization to the corresponding 1,2-dihydroazocine (44).15>6 The reaction took a different course when other dienophiles were employed for instance, with iV-phenylmaleimide or maleic anhydride, Diels-Alder-type adducts were formed. Reaction of a 1,2-dihydropyrazine (45) with dimethyl acetylenedicarboxylate yielded a bicyclic compound, which was shown to be not the expected (2 + 2)-cycloadduct 46, but the isomeric 2,7-diazabicyclo(4.2.0]octa-2,4-diene (47). This compound was claimed to result from initial (2 + 2)-cycloaddition, ring opening, and subsequent m/ramolecular (2 + 2) cycloaddition [Eq. (9)1.62... 

Syntheses have been reported of barrelene (505) and of Nenitzescu s hydrocarbon (503) on a reasonable scale and without some of the difficulties that attend the previously published routes." " The preparation of (503) is of central importance, it being obtained by the oxidative bisdecarboxylation of the cyclo-octatetraene-maleic anhydride Diels-Alder adduct (502) with dicarbonylbis(triphenylphosphine)-nickel in diglyme at reflux. Cycloaddition of (503) to 2,5-dimethyI-3,5-diphenyl-cyclopentadienone in hot benzene afforded (504) and its endo-isomer. Photolysis of (504) yielded (505) in 24% yield from cyclo-octatetraene. The thermally labile benzene-maleic anhydride [4 + 2] cycloadduct (506) was obtained in similar fashion from (502). A review of the mechanisms of pyrolysis of (503) and a number of isomers and benzo-fused (CH) derivatives (collectively termed Nenitzescu s hydrocarbons) has appeared." ... 

The product of a Diels-Alder cycloaddition always contains one more ring than was present m the reactants The dienophile maleic anhydride contains one ring so the product of Its addition to a diene contains two... 

Diels-Alder cycloadditions are sensitive to steric effects of two major types in the diene. Bulky substituents on the termini of the diene hinder approach of the two components to each other and decrease the rate of reaction. This effect can be seen in the relative reactivity of 1-substituted butadienes toward maleic anhydride.19... 

Dienes bonded to silicones to give products stable to hydrolysis are available in a wide variety of combinations, from the distillable l,3-bis(isoprenyl)-l,l,3,3-tetramethyldisiloxane to high polymers with dozens of diene groups attached [23], Diels-Alder cycloadditions may be performed with dieno-philes. Maleic anhydride adds almost quantitatively to the conjugated diene system, giving easy access to a siloxane species of considerable industrial importance [24]. 

Microwave heating has also been employed for performing retro-Diels-Alder cycloaddition reactions, as exemplified in Scheme 6.94. In the context of preparing optically pure cross-conjugated cydopentadienones as precursors to arachidonic acid derivatives, Evans, Eddolls, and coworkers performed microwave-mediated Lewis acid-catalyzed retro-Diels-Alder reactions of suitable exo-cyclic enone building blocks [193, 194], The microwave-mediated transformations were performed in dichloromethane at 60-100 °C with 0.5 equivalents of methylaluminum dichloride as catalyst and 5 equivalents of maleic anhydride as cyclopentadiene trap. In most cases, the reaction was stopped after 30 min since continued irradiation eroded the product yields. The use of short bursts of microwave irradiation minimized doublebond isomerization. 

For concerted Diels-Alder reactions, as discussed above, both AV and AF are negative and Owl. In some unhindered Diels-Alder reactions, such as those involving maleic anhydride, it was observed [275] that AV > AF. This means that the transition state has an additional volume contraction with respect to the products. Since Diels-Alder cycloadditions are essentially solvent-insensitive and thus have negligible or small environmental contribution to the activation volume, this contraction seems to be of intramolecular origin, and it was suggested [284] that it could be due to secondary orbital interactions in the transition state. This contribution to AjF has been indicated as A, V. ... 

Kochi and co-workers studied photoinduced Diels-Alder cycloadditions via direct photoexcitation of anthracene as a diene with maleic anhydride and various maleimides as dienophiles. Here, fluorescence-quenching experiments, time-resolved absorption measurements, and the effect of solvent polarity provide striking evidence for an ion-radical pair to be the decisive intermediate [83],... 

The pioneer work on this subject using simple 1-azadienes is due to Ghosez et al. (82TL3261 85JHC69) they succeeded in reacting 1-azadienes as 47r-electron components in Diels-Alder cycloadditions. Thus, l-dimethylamino-3-methyl-l-azabuta-l,3-diene (a,/3-unsaturated hydrazone) 54 did undergo [4 + 2] cycloaddition to typical electron-poor dienophiles, e.g., methyl acrylate, dimethyl fumarate, acrylonitrile, maleic anhydride, and naphthoquinone, producing pyridine derivatives 55-57 (Scheme 14). 

A number of reactions do not seem to belong to any of the above mechanistic types. Such processes are referred to as multicenter reactions. The Diels-Alder cycloaddition reaction of 1,3-butadiene with maleic anhydride is an example (Scheme 5). No charged or odd election intermediates seemingly are involved in this reaction. 

Attempts to isolate the silole monomer 2 or to trap it by reaction with maleic anhydride or perfluoro-2-butyne have failed. This is surprising given the successful trapping of 1-methylsilole5 and 1,1-dimethylsilole10. The authors conclude that silole 2 is not very reactive in Diels-Alder cycloadditions, except toward self-reaction19. 

While studies of reactions in supercritical fluids abound, only a few researchers have addressed the fundamental molecular effects that the supercritical fluid solvent has on the reactants and products that can enhance or depress reaction rates. A few measurements of reaction rate constants as a function of pressure do exist. For instance, Paulaitis and Alexander (1987) studied the Diels Alder cycloaddition reaction between maleic anhydride and isoprene in SCF CO2. They observed bimolecular rate constants that increased with increasing pressure above the critical point and finally at high pressures approached the rates observed in high pressure liquid solutions. Johnston and Haynes (1987) found the same trends in the... 

Solvent effect on rate constants. In this section, the rate constant will be predicted qualitatively in CO2 for the Diels-Alder cycloaddition of isoprene and maleic anhydride, a reaction which has been well-characterized in the liquid state (23,24). In a previous paper, we used E data for phenol blue in ethylene to predict the rate constant of the Menschutkin reaction of tripropylamine and methyliodide (19). The reaction mechanisms are quite different, yet the solvent effect on the rate constant of both reactions can be correlated with E of phenol blue in liquid solvents. The dipole moment increases in the Menschutkin reaction going from the reactant state to the transition state and in phenol blue during electronic excitation, so that the two phenomena are correlated. In the above Diels-Alder reaction, the reaction coordinate is isopolar with a negative activation volume (8,23),... 

The Diels-Alder cycloaddition reaction of maleic anhydride with isoprene has been studied in supercritical-fluid CO2 under conditions near the critical point of CO2 [759]. The rate constants obtained for supercritical-fluid CO2 as solvent at 35 °C and high pressures (>200 bar) are similar to those obtained using normal liquid ethyl acetate as the solvent. However, at 35 °C and pressures approaching the critical pressure of CO2 (7.4 MPa), the effect of pressure on the rate constant becomes substantial. Obviously, AV takes on large negative values at temperatures and pressures near the critical point of CO2. Thus, pressure can be used to manipulate reaction rates in supercritical solvents under near-critical conditions. This effect of pressure on reacting systems in sc-fluids appears to be unique. A discussion of fundamental aspects of reaction kinetics under near-critical reaction conditions within the framework of transition-state theory can be found in reference [759],... 

The Diels-Alder cycloaddition reaction occurs most rapidly if the alkene component, or dienophile ("diene lover"), has an electron-withdrawing substituent group. Thus, ethylene itself reacts sluggishly, but propenal, ethyl propenoate, maleic anhydride, benzoquinone, proiicnenitrile, and similar compounds are highly reactive. Note also that alkyncs, such as methyl propynoate, can act as Diels-Alder dienophiles. 

The total synthesis of complicated polycyclic closed-shell cage compounds represents one of the top achievements of modern synthesis. Progress in this area is mainly due to the ingenious use of the Diels-Alder cycloaddition, as is illustrated in the synthesis of basketene 357 (Scheme 2.123). " In this case the Diels-Alder reaction between diene 358 (the valent isomer form of cyclooctate-traene) and maleic anhydride leads in one step to the construction of the tricyclic structure 359 in quantitative yield. Subsequent [2 -I- 2] cycloaddition (see below) leads to product 360, which has the required structure but additional substituents. Saponification and oxidative decarboxylation of 360 gives basketene 357. 

The cyclopentadienyltin(IV) compounds undergo Diels-Alder cycloadditions with reactive dienophiles such as maleic anhydride, diethyl maleate, and diethyl acetylenedi-carboxylate," and an endoperoxide has been identified from the reaction with singlet oxygen.123... 

In a synthetic study of spinosyns A and D palladium-mediated couphng of a cy-clopentenyltriflate and a cyclopentenylstannane was followed by Diels-Alder cycloaddition of the resulting diene with maleic anhydride (Scheme 12.96) [198]. This sequence achieved the construction of the ABC-ring system of the target compounds with control of several stereocenters. 

S-Unsaturated hydrazones such as (12) have been shown to behave as 1 -aza-1, 3-dienes in Diels-Alder addition reactions with a range of dienophiles such as maleic anhydride (Scheme 2). The dimethylamino substituent in the cycloadducts (e.g. 13) may be cleaved by treatment with zinc and acetic acid, but no conditions have so far been found to cleave the N-N bond without reducing the C-C double bond 5-Nitropyrimidine undergoes inverse Diels-Alder cycloaddition with electron-rich dienophiles such as enamines and ketene N,N- and 0,0-acetals (Scheme 3). ... 

Another interesting development is the use of fluorous-based scavengers in conjunction with microwave synthesis and fluorous solid-phase extraction (F-SPE) for purification. This was recently illustrated by Werner and Curran [74] in their investigation of the Diels-Alder cycloaddition of maleic anhydride to diphenylbutadiene (Scheme 11.23). After performing microwave-assisted cycloaddition (160 °C, 10 min) with a 50% excess of the diene, the excess diene reagent was scavenged by a structurally related maleimide fluorous dienophile under the same reaction conditions. Elution of the product mixture from an F-SPE column with Me0H-H20 provided the desired cycloadduct 89 in 79% yield and 90% purity. Subsequent elution with diethyl ether furnished the fluorous Diels-Alder cycloadduct. 

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