1,2-Benzoquinones, Diels-Alder reactions

The Diels-Alder Reaction consists in the direct combination of a compound containing a conjugated diene system u ith a reagent which possesses a double or triple bond activated bj suitable adjacent groups. Examples of such reagents are maleic anhydride, p-benzoquinone, acraldehyde and acetylene dicarboxylic esters. Combination always occurs at the 1,4 positions of the diene system ... 

Most examples of Diels-Alder reactions reported for both 2-vinyl and 3-vinylindoles involve typical electrophilic dienophiles such as benzoquinone, A"-phenylmaleimide and dimethyl acetylenedicarboxylate (see Table 16.1). T hese symmetrical dienophiles raise no issues of rcgiosclectivity. While there arc fewer examples of use of mono-substituted dienophiles, they appear to react... 

Since the six carbons shown above have 10 additional bonds, the variety of substituents they carry or the structures they can be a part of is quite varied, making the Diels-Alder reaction a powerful synthetic tool in organic chemistry. A moment s reflection will convince us that a molecule like structure [XVI] is monofunctional from the point of view of the Diels-Alder condensation. If the Diels-Alder reaction is to be used for the preparation of polymers, the reactants must be bis-dienes and bis-dienophiles. If the diene, the dienophile, or both are part of a ring system to begin with, a polycyclic product results. One of the first high molecular weight polymers prepared by this synthetic route was the product resulting from the reaction of 2-vinyl butadiene [XIX] and benzoquinone [XX] ... 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

Benzoquinone is an excellent dienophile in the Diels-Alder reaction. What product would you expect from reaction of benzoquinone with 1 equivalent of 1,3-butadiene Prom reaction with 2 equivalents of 1,3-butadiene ... 

Ethyl H-, 2-diazepine-l-carboxylate functions as a 2 -component in the Diels-Alder reaction with tetrachloro-l,2-benzoquinone to give a mixture of the regioisomers 20 and 21.100... 

Since the reactivity depends on the lowest HOMO-LUMO energy separation that can be achieved by the reacting partners, all the factors, steric and electronic, that lower the HOMO-LUMO distance increase the reaction rate and, as a consequence, allow the reactions to be carried out under mild conditions. Thus the normal electron-demand Diels-Alder reaction between 1,4-benzoquinone and 1,3-butadiene (Equation 2.2) proceeds at 35 °C almost quantitatively. 

The Diels-Alder reactions of dienes 11 and 12 with many dienophiles allowed other fluorinated aromatics to be synthesized [12,13]. For example, diene 11 reacted with dimethylacetylenedicarboxylate and ethylpropiolate (Scheme 2.8) to give trifluoromethyl diethylphthalate and trifluoromethylethylbenzoate, and diene 12 with/ -benzoquinone affords 5-fluoronaphthoquinone (Equation 2.5). 

The discovery that Lewis acids can promote Diels-Alder reactions has become a powerful tool in synthetic organic chemistry. Yates and Eaton [4] first reported the remarkable acceleration of the reactions of anthracene with maleic anhydride, 1,4-benzoquinone and dimethyl fumarate catalyzed by aluminum chloride. The presence of the Lewis-acid catalyst allows the cycloadditions to be carried out under mild conditions, reactions with low reactive dienes and dienophiles are made possible, and the stereoselectivity, regioselectivity and site selectivity of the cycloaddition reaction can be modified [5]. Consequently, increasing attention has been given to these catalysts in order to develop new regio- and stereoselective synthetic routes based on the Diels-Alder reaction. 

Luche and coworkers [34] investigated the mechanistic aspects of Diels-Alder reactions of anthracene with either 1,4-benzoquinone or maleic anhydride. The cycloaddition of anthracene with maleic anhydride in DCM is slow under US irradiation in the presence or absence of 5% tris (p-bromophenyl) aminium hexachloroantimonate (the classical Bauld monoelectronic oxidant, TBPA), whereas the Diels Alder reaction of 1,4-benzoquinone with anthracene in DCM under US irradiation at 80 °C is slow in the absence of 5 % TBPA but proceeds very quickly and with high yield at 25 °C in the presence of TBPA. This last cycloaddition is also strongly accelerated when carried out under stirring solely at 0°C with 1% FeCh. The US-promoted Diels Alder reaction in the presence of TBPA has been justified by hypothesizing a mechanism via radical-cation of diene, which is operative if the electronic affinity of dienophile is not too weak. 

The photo-induced exo selectivity was observed in other classic Diels-Alder reactions. Data relating to some exo adducts obtained by reacting cyclopentadiene or cyclohexadiene with 2-methyl-1,4-benzoquinone, 5-hydroxynaphtho-quinone, 4-cyclopentene-l,3-dione and maleic anhydride are given in Scheme 4.13. The presence and amount of EtsN plays a decisive role in reversing the endo selectivity. The possibility that the prevalence of exo adduct is due to isomerization of endo adduct under photolytic conditions was rejected by control experiments, at least for less reactive dienophiles. 

Enantiomers (M)- and (P)-helicenebisquinones [32] 93 have been synthesized by high pressure Diels-Alder reaction of homochiral (+)-(2-p-tolylsulfo-nyl)-l,4-benzoquinone (94) in excess with dienes 95 and 96 prepared from the common precursor 97 (Scheme 5.9). The approach is based on the tandem [4 + 2] cycloaddition/pyrolitic sulfoxide elimination as a general one-pot strategy to enantiomerically enriched polycyclic dihydroquinones. Whereas the formation of (M)-helicene is explained by the endo approach of the arylethene toward the less encumbered face of the quinone, the formation of its enantiomeric (P)-form can be the result of an unfavourable interaction between the OMe group of approaching arylethene and the sulfinyl oxygen of 94. 

The rate of the Diels-Alder reaction betweenp-benzoquinone and cyclopenta-diene was measured in SC-CO2 and subcritical CO2 [85]. Relative reaction rates at different pressures are reported in Table 6.14. On going from CO2 in the liquid phase (below 31 °Q to SC-CO2, the reactivity increased significantly only when the reaction was carried out under high pressure. At 30 °C and 60 bar the reaction was 1.36 times faster than when it was performed in diethyl ether at 30 °C and 1 bar. 

Furukawa and coworkers reported preparation and isolation of thiophene 1-oxides 111-113. Diels-Alder reaction of 111 with maleic anhydride, benzoquinone, and cw-l,2-dibenzoylethylene gave the corresponding syn adducts exclusively [61] (Scheme 50). 

Synthetic Applications of the Diels-Alder Reaction. Diels-Alder reactions have long played an important role in synthetic organic chemistry.74 The reaction of a substituted benzoquinone and 1,3-butadiene, for example, was the first step in one of the early syntheses of steroids. The angular methyl group was introduced by the methyl group on the quinone and the other functional groups were used for further elaboration. 

The Diels-Alder reactions of alkyl-substituted benzoquinones with penta-1,3-diene and isoprene were also studied in aqueous cyclodextrin solutions. Highly enhanced ortho- and mefa-regioselectivities were observed (Eq. 12.11).48... 

Wassermann (6) has studied the Diels-Alder reaction of benzoquinone (B) and cyclopen-tadiene (C) at 25 °C. 

Consider the Diels-Alder reaction between benzoquinone (B) and cyclopentadiene (C), which was discussed in Illustration 8.1. 

The use of masked o-benzoquinones or o-benzoquinoid structures (MOB) as potential synthons for Diels-Alder reactions have furnished elegant and reliable approaches to a multitude of structurally diverse organic compounds [41, 42]. 

Another synthesis using in situ-prepared o-benzoquinones has been reported by Liao and coworkers [45]. These authors observed that oxidation of 2-methoxy-phenols 7-92 with DAIB in the presence of unsaturated alcohols 7-93 furnish transient o-benzoquinone monoacetal intermediates, which easily undergo an intramolecular Diels-Alder reaction to provide bicyclo[2.2.2]octenones 7-94 with high regio- and stereoselectivity, as well as in acceptable yields (Scheme 7.25). 

The oxidative formation of p-benzoquinones from anilides such as 7-108 was used for the synthesis of the core scaffold of the natural products elisabethin A (7-106) and pseudopterosin A aglycone (7-107) (Scheme 7.30). Exposure of anilide 7-108 to DMP [53] led to the formation of the o-imidoquinone 7-109, which underwent an intramolecular Diels-Alder reaction to give 7-110 in 28% yield after hydration. In a competitive pathway, the p-quinone 7-111 is also formed from 7-108, which on heating in toluene again underwent an intramolecular Diels-Alder reaction to give cycloadduct 7-112 in 25% overall yield. Hydrolysis of 7-112 furnished the carbocyclic skeleton 7-113 of elisabethin A (7-106). 

SCHEME 4. Diels-Alder reactions with 1,4-benzoquinones as dienophiles... 

In total syntheses where a homogeneously catalyzed transfer hydrogenation is applied, almost exclusively aluminum(III) isopropoxide is utilized as the catalyst. At an early stage in the total synthesis of (-)-reserpine (65) by Woodward [106], an intermediate with two ketone groups and two C-C double bonds is formed (66) by a Diels-Alder reaction of para-benzoquinone (67) and vinylacry-late (68). The two ketone groups were reduced with aluminum(III) isopropoxide... 

Indeed, it has been found that the Diels-Alder reaction of benzoquinone 47 and cyclohexadiene 48 is accelerated by encapsulation in the hydroxysoftball 7-7.[251 It is known that the capsule in its resting state is occupied with two benzoquinone molecules,... 

Figure 8. Catalytic cycles for the Diels-Alder reactions of benzoquinone 47 with cyclohexadiene 48 (top) and tetramethyl thiophene dioxide 51. While the reaction of 47 with 48 suffers from product inhibition, adduct 52 is easily replaced by new reactants inside the capsule.

Marchand and coworkers102 reported a difference in site selectivity between the thermodynamically and kinetically controlled Diels-Alder reactions of cyclopentadiene with 2,3-dicyano-p-benzoquinone (126) (equation 37). Under kinetic conditions, the more reactive double bond of 126 reacted with cyclopentadiene affording 127, whereas the less substituted double bond reacted under thermodynamic conditions affording 128. Both reactions proceeded with complete endo selectivity. These findings were in agreement with ab initio HF/3-21G calculations. 

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