Dienes, cycloaddition reactions benzoquinones

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. 

The Diels Alder reaction, involving the [4 + 2]-cycloaddition of an unsaturated group (di-enophile) to a 1,3-diene, has been studied for the synthesis of ladder polymers, such as the reaction of 2-vinyl-l,3-butadiene with benzoquinone [Bailey, 1972] (Eq. 2-247). Related polymerizations are those utilizing the [2 + 2]-cycloaddition reaction [Dilling, 1983]. While [4 + 2]-cycloaddition reactions are thermally induced, [2 + 2]-cycloaddition reactions are... 

Molecular electrostatic potentials have been used to explain the regioselectivity exhibited in the Diels-Alder cycloaddition reactions between 1-trimethylsilyloxy-butadiene and the quinones 5-formyl-8-methyl-1,4-naphthoquinone, 5-methoxy-7-methyl-1,4-phenanthrenequinone, and 5,6,7-trimethyl-1,4-phenanthrenequinone.128 The intramolecular Diels-Alder reaction of masked o-benzoquinones (123) with a variety of dienes provides adducts (124) which rearrange to functionalized ris-decal ins (125) with complete stereocontrol of up to five stereocentres. This methodology ... 

Recently, the reaction of masked ortho-benzoquinone [92] with C60 was tested [93]. The [4+2] cycloaddition reaction of such electron-deficient dienes with fullerenes resulted in the formation of highly functionalized bicyclo [2.2.2] octenone-fused fullerenes. The reactants were generated in situ by the oxidation of the readily available 2-methoxy phenols with hypervalent iodine agents. For the several different masked ortho-benzoquinones that were tested, it was found that the yield of the cycloadducts depends on the nature of the starting materials and the reaction conditions. Other Diels-Alder reactions of such electron-deficient dienes with electron-poor fullerenes involved tropones [94], 1,3-butadienes substituted with electron-withdrawing groups [95], and 2-pyrone [96]. 

Diels-Alder reactions. The laboratories of Breslow and of Grieco have reported that water can enhance the rate of Diels-Alder reactions of dienes that possess carboxylic acid or similar hydrophilic groups (12, 314). Liotta et al. have examined solvent effects on cycloaddition reactions of benzoquinones with dienes substituted with a relatively hydrophobic group, and report significant rate enhancement in ethylene glycol relative to benzene (26 1) or even to reactions in the absence of a solvent. They attribute the solvent effect to aggregation of the diene and the quinone. 

Vinyl- and 3-vinyl-thiophenes behave as a diene on reaction with dienophiles to give six-membered ring-fused thiophenes. Cycloaddition of the cyclobutene 842 with 841 or with 844 followed by aromatization gives benzo[/ ]thio-phene-fused benzocyclobutenedione 843 or 845, respectively (Scheme 129) <1996J(P1)497>. Heterohelicene 847 is synthesized by the reaction of 846 with 1,4-benzoquinone <2001JA11899>. 

The Diels-Alder cycloaddition reaction of 2,6-dimethyl-1,4-benzoquinone with methyl (ii)-3,5-hexadienoate, carried out in toluene as solvent, gives only traces of the cycloadduct shown in Eq. (5-160), even after seven days. However, when the solvent is changed to water and sodium ( )-3,5-hexadienoate is used as the diene, 77 cmol/mol of the desired cycloadduct is obtained after one hour and esterification with diazomethane [714] f Again, hydrophobic interactions between diene and dienophile in the aqueous medium seem to be responsible for this remarkable and synthetically useful rate acceleration. 

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 Diels-Alder cycloaddition reaction between the transient diene 208 and /i-quinonic dienophiles such as /i-benzoquinone or 1,4-naphthoquinone, followed by further aromatization with DDQ, afforded cycloadducts 216 and 217, which were used for the preparation of TTF derivatives (Scheme 26) <1998CC2197, 2000TL2091>. 

Titanium alcoholates of diols 2.50 generated by exchange with (/-PrO TiC are also potent catalysts, and the most efficient catalyst is derived from 2.50 (R = Me, R = Ar=Ph). These catalysts promote the diastereo- and enantioselective cycloaddition of cyclopentadiene or acyclic dienes with some a,P-unsaturated imides 7.68 (R = H, Rg=Me, MeOOC) [45, 778] or of acyclic dienes with substituted benzoquinones at -78°C [1572, 1573] (Figure 9.20). Reactions occur at 0°C in the presence of molecular sieves, and only catalytic amounts of these alcoholates are used. Intramolecular cycloadditions also give useful sdectivities under these conditions [1574]. However, the process for preparation of the catalyst varies according to the reaction [778, 1573], and this is veiy important to the observation of high selectivities. 

Saracoglu and Cavdar investigated the Diels-Alder cycloadditions of 2-vinylindoles with various substituted quinone compounds [66] (Scheme 40). Thus, the cycloaddition reaction between 2-vinylindole 163 and naphthoquinone (166), followed by a [l,3]-hydrogen shift, provided compound 167. Similar to what was seen previously, the secondary orbital interactions between the diene and the dienophile lead to the formation of the endo product. Other quinone dienophUes, such as p-benzoquinone (164) and DDQ (168), also participated in similar cycloaddition reactions to produce quinolinocarbazole derivatives. In the case of DDQ, overoxidation by elimination of 2 moles of HCl from the cycloaddition product led to the formation of compound 169. 

The adducts obtained from acyclic dienes and cyclic dienophiles are frequently formed in accordance with the endo rule. A classic example is found in the Woodward synthesis of reserpine, which started with the Diels-Alder reaction of i -pentadienoic acid and benzoquinone (3.67). In this cycloaddition reaction, the endo adduct 78, in which the carboxylic acid and the benzoquinone carbonyl groups become cLs to one another, is obtained as the exclusive product. 

Various approaches to the assembly of the 1,3-dienes that engage in the Diels-Alder cycloaddition reactions leading to substrates for DPM and ODPM processes have been reported. Thus, for example. Yen and Liao demonstrated, during the course of a total synthesis of the Lycopodium alkaloid magellanine, that oxidation of acetovanillone (109) rScheme 9.151 with diacetoxyiodobenzene (DAIB) in the presence of methanol afforded the o-benzoquinone monoketal 110. The latter conpound engaged in an in situ Diels-Alder reaction with added cyclopentadiene (111) and the resulting adduct 112 proved to be an excellent substrate for the ODPM rearrangement reaction. Thus, photolysis of 112 as a solution in acetone afforded the pivotal tetracyclic diketone 113 in 92% yield. 

A review of the cycloaddition reactions of o-benzoquinones as carbodiene, heterodiene, dienophile, or heterodienophile has been published. In the Diels-Alder reaction of furans with masked o-benzoquinones (145), the furans unexpectedly behaved as dienophiles to yield cycloadducts (146) (Scheme 56). Masked benzoquinones behave as dienes which undergo Diels-Alder reactions with electron-rich dienophiles such as enol ethers and thienol ethers.The asymmetric Diels-Alder reactions of 5-substituted and 5,6-disubstituted (S)-2-(p-tolylsulflnyl)-l,4-benzoquinones with cyclopentadiene and fran -piperylene show complete regio- and jr-facial selectivities. The hetero-Diels-Alder reactions of o-benzoquinones with tetracyclone produce cyclopenta[I ][l,4]benzodioxinone derivatives in high yield. 

The use of Cr(0)-promoted 6 r - - 2 r-cycloaddition in the synthesis of pharmacologically active natural products has been reviewed. The 6 -I- 3-cycloaddition of dimethylaminofulvene (194) with benzoquinones provides an efficient route to the 3-oxabicyclo[4.3.0]nonane system (195) (Scheme 76). Density-functional theory calculations provide evidence for a feasible concerted antara-antara cycloaddition for the 6-I-4-reaction of c -hexa-l,3,5-triene with buta-1,3-diene. Azulene-1,5-quinones (196) and azulene-l,7-quinones undergo a variety of 6-1-4- and 2-1-4-cycloaddition reactions with cyclic dienes and cycloheptatrienes to produce cycloadducts, e.g. (197) and (198) (Scheme 77) ... 

Nair V, Kumar S (1996a) Diels-Alder reactions of o-benzoquinones with acyclic dienes. J Chem Soc, Perkin Trans 1(5) 443 47. doi 10.1039/P19960000443 Nair V, Kumar S (1996b) Recent developments in the cycloaddition reactions of o-benzoquinones. Synlett 12 1143-1147. doi 10.1055/s-1996-5699... 

Tetraene 141 has been converted into various complex polycondensed adducts by reacting with a variety of dienophiles such as maleic anhydride, N-phenylmaleimide, N-phenyltriazolinedione,p-benzoquinone and tetracyano-ethylene carried out under thermal conditions. All cycloadditions occurred facial-diastereoselectively from an outside attack and provided monocycloadducts which had an exceptionally close relationship between diene and dieno-phile and then underwent intramolecular cycloaddition [125]. The reaction between 141 and p-benzoquinone is illustrated in Scheme 2.53. 

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. 

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. 

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