Alkenes, cycloaddition reactions with benzoquinones

As part of an extensive study of the 1,3-dipolar cycloadditions of cyclic nitrones, Ali et al. (392-397) found that the reaction of the 1,4-oxazine 349 with various dipolarophiles afforded the expected isoxazolidinyloxazine adducts (Scheme 1.78) (398). In line with earlier results (399,400), oxidation of styrene-derived adduct 350 with m-CPBA facilitated N—O cleavage and further oxidation as above to afford a mixture of three compounds, an inseparable mixture of ketonitrone 351 and bicyclic hydroxylamine 352, along with aldonitrone 353 with a solvent-dependent ratio (401). These workers have prepared the analogous nitrones based on the 1,3-oxazine ring by oxidative cleavage of isoxazolidines to afford the hydroxylamine followed by a second oxidation with benzoquinone or Hg(ll) oxide (402-404). These dipoles, along with a more recently reported pyrazine nitrone (405), were aU used in successful cycloaddition reactions with alkenes. Elsewhere, the synthesis and cycloaddition reactions of related pyrazine-3-one nitrone 354 (406,407) or a benzoxazine-3-one dipolarophile 355 (408) have been reported. These workers have also reported the use of isoxazoles with an exocychc alkene in the preparation of spiro[isoxazolidine-5,4 -isoxazolines] (409). 

Olefinic double bonds substituted with one or more electron-withdrawing groups show significant dipolarophilic activity in cycloaddition reactions with organic azides,43,276-278 similar to the electron-rich double bonds of enamines and enol ethers the reactivity is less pronounced in azide additions compared to that observed in diazomethane reactions.7 The first triazolines reported resulted by the action of aryl azides on benzoquinones.1,279-281 As a rule, stereospecific cis additions occur,32 which are usually unidirectional except in the case of methacrylic derivatives67 and certain alkenes bearing... 

Hong and coworkers have investigated the cycloaddition chemistry of fulvenes with a wide variety of alkenes and alkynes in great detail [191]. As one example, the reaction of 6,6-dimethylfulvene with benzoquinone is shown in Scheme 6.92. Under microwave conditions in dimethyl sulfoxide (DMSO) at 120 °C, an unusual hetero-[2+3] adduct was formed in 60% yield, the structure of which was determined by X-ray crystallography. The adduct is a structural analogue of the natural products aplysin and pannellin and differs completely from the reported thermal (benzene, 80 °C) Diels-Alder cycloaddition product of the fulvene and benzoquinone (Scheme 6.92) [191]. 

The carbonyl ir-bond has been found to add chemo- and regio-selectively across the alkenic ir-bond of ketenes. Thus diphenylketene readily reacts with benzoquinone to yield a stable [2 + 2] adduct (equation 1). With an excess of diphenylketene the bis-adduct is formed, which decomposes into tetraphe-nylquinodimethane and carbon dioxide (equation 2). With the less stable ketene, thermal [2 + 2] cycloadditions are observed with highly electrophilic carbonyl compounds (equation 3). With unactivated aldehydes and ketones, yields are much lower due to a faster oligomerization of the ketene reagent. However, in the presence of a Lewis acid catalyst, most aldehydes or ketones form P-lactones with ketene (equation 4). Cycloadditions with ketones usually require more active catalysts than with aldehydes. The catalyzed reaction of ketene with methyl vinyl ketone is chemoselective, yielding a 10 1 ratio of [2 + 2] versus [4 + 2] adducts (equation 5). In the absence of catalyst, methyl vinyl ketone reacts with ketene to give exclusively the [4 + 2] adduct. 

Cycloaddition reactions of triplet excited 1,4-quinones to ground-state alkenes occur either via a triplet exciplex intermediate, which collapses to a triplet biradical,1000 or via separated radical ion intermediacy.990 The existence of biradical intermediates has been proven by measurements of chemically induced dynamic nuclear polarization (CIDNP) (Special Topic 5.3), for example in the reaction of 1,4-benzoquinone (313) with norbomadiene (314) yielding two products, the spiro-oxetane 315 and the spiro-oxolane 316 (Scheme 6.139).1001 Interestingly, quadricyclane (317) provides the same reaction as norbomadiene. 

Cycloadditions. Methylenecyclopentanes are formed in the catalyzed reaction of 2-trimethylsilylmethyl-3-benzoyloxypropene derivatives with electron-rich alkenes. The condensation of benzoquinone bisimines and styrenes furnishes... 

Other cycloadditions. A [3+2]-cycloaddition involving a benzoquinone and an alkene to give 2,3-dihydrobenzofuran derivatives, and an intramolecular [4+3]-cycloaddition to provide functionalized polycyclic compounds, are further demonstrations of the utility of LiClQj-OEtj. The reaction of aromatic or a,p-unsaturated aldehydes with acid chlorides proceeds via ketenes and then 2-oxetanones. ... 

Hong [70] described the cycloaddition reactions of fulvenes 87 with quinones 88 and several activated alkenes and alkynes in an attempt to provide new examples of the microwave effect. Two examples warrant particular attention. Reaction of 6,6-dimethylfulvene (87) with p-benzoquinone (88) produced the [4+2] cycloaddition when the reaction was performed with conventional heating. Use of microwave heating, however, gave rise to the [6+4] cycloaddition product (Scheme 5.26). 

In 2006, Lu and coworkers [53] described a method for the synthesis of carbazoles using the palladium(ll)-catalysed oxidative Heck reaction (Scheme 9.25). Indole 177 was subjected to catalytic Pd(OAc)2 and 2.1equiv of benzoquinone to afford carbazole 178 in 88% yield. Because the alkene is 1,1-disubstituted, a 5-exo cyclization mode (as seen in Ferreira and Stoltz s [48] indole annulation) is unproductive, and a 6-endo cyclization ultimately occurs. The putative intermediate is then believed to be oxidized to the aromatic carbazole by the excess benzoquinone. When indole 179, featuring a terminal alkene, was treated with these oxidative conditions, a mixture of products from 6-endo cyclization (180) and 5-exo cyclization (and subsequent isomerization and [3+2] cycloaddition, 181) was observed. A variety of substituted carbazoles were obtained by this palladium(n)-catalysed oxidative cyclization. 

The chemistry of o-benzoquinones, especially their involvement in cycloadditions, has been the subject of extensive investigations in recent years (Nair and Kumar 1994, 1996a, b). In contrast, their aza analogs, viz., o-quinonediimines, have received only scant attention (Friedrichsen and Bottcher 1981), the available information on their cycloadditions being mainly concerned with their participation in Diels-Alder reactions with alkenes (Friedrichsen and Schmidt 1978). 

Cycloadditions of alkenes and alkynes onto imine cation radicals have been reported, with the cation radicals generated by either PIET mediated by DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)180, or by TIET mediated by FeCb1066. The reaction is shown in Scheme 77. 

If D-A adduct 1 contains some 1 2 adducts as impurities, 1,4-benzoquinone is formed by a retro-Diels-Alder reaction during the pyrolytic distillations. In this case, a dark yellow solid of benzoquinone can be seen on the walls of the air condenser, and the distillate has a deeper yellow color. Contamination with a small amount of 1,4-benzoquinone apparently does not interfere with photochemical [2+2] cycloadditions of enedione 3 with alkenes and alkynes, an important application of 3. Fractional distillation of the benzoquinone-contaminated 3 as described for the second distillation of 3 can remove the benzoquinone with some loss of enedione 3. The benzoquinone deposits initially as a dark yellow solid on the walls of the distillation head and air condenser during early fractions. 

It has been demonstrated that N-hydroxytryptophan can be converted to /3-carbolines in two ways (Fig. 41). Pictet-Spengler reaction of 1 with acetals provided the N -hydroxytetrahydro-/8-carbolines (2) (287). A modified Bischler-Napieralski reaction of 1 with trimethylorthoformate gave N -0X0-3,4-dihydro-/3-carbolines (3), the nitrone function of which can undergo 1,3-dipolar cycloaddition with alkenes (288) and nitriles (289), providing isoxazolidine (4) and dehydro-1,2,4-oxadiazoline (5), annulated TBCs, respectively. Nitrone 3 also was obtained by oxidation of the N-hydroxy-j8-carboline 2 with 2,3-dichloro-5,6-dicyano-l, 4-benzoquinone (DDQ). N-Oxygenated TBCs showed no affinity for the benzodiazepine and tryptamine receptors (290). Unfortunately, no toxicity data were recorded for these substituted hydroxylamines. 

If the oxidation is performed in the presence of an external dienophile, the respective products of [4+2] cycloaddition are formed [351-356]. Typical examples are illustrated by a one-pot synthesis of several silyl bicyclic alkenes 283 by intermolecular Diels-Alder reactions of 4-trimethylsilyl substituted masked o-benzoquinones 282 generated by oxidation of the corresponding 2-methoxyphenols 281 [351] and by the hypervalent iodine-mediated oxidative dearomatization/Diels-Alder cascade reaction of phenols 284 with allyl alcohol affording polycyclic acetals 285 (Scheme 3.118) [352]. This hypervalent iodine-promoted tandem phenolic oxidation/Diels-Alder reaction has been utilized in the stereoselective synthesis of the bacchopetiolone carbocyclic core [353]. 

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