Styrenes, cycloaddition reactions 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). 

Cationic [5 + 2]cycloaddition involving a styrene and p-benzoquinone ketals in the presence of a Lewis acid is the key reaction to a number of neolignans fe nin [187]. The oxygen atoms of the dioxolane function in the cycloaddend rrinforce the a character of their neighboring carbons, and this character is transmitted to the termini which participate in the C-C bond formations. 

By using a stoichiometric amount of the chiral titanium reagent prepared by mixing chiral diol, Titanium IV) Chloride, and titanium tetraisopropoxide, the asymmetric [2 + 2] cycloaddition reaction of 1,4-benzoquinones and styrenes gives the corresponding cyclobutane derivatives with high optical purity. These rearrange to 2,3-dihydrobenzofuran derivatives on mild acid treatment (eq 13). ... 

The chiral titanium catalyst prepared by mixing the diol 1, TiCl4, and Ti(0-i-Pr)4 in a 1 1 1 ratio promotes the asymmetric [2+2] cycloaddition reaction between styrenes 16 and 1,4-benzoquinones 17 to afford cyclobutane derivatives in good optical purity (Scheme 10 and Table 5) [37]. This reaction is not a truly catalytic reaction because excess amounts of the catalyst (5 molar amounts) have to be employed in order to obtain a high enantiomeric excess. The catalyst in this reaction is thought to be different from the one prepared from the diol 1 and TiCl2(0-i-Pr)2 in a 1 1 ratio as described previously. 

Cycloadditions. The regioselectivity in the cycloaddition reactions of 2-alkoxy-5-allyl-l,4-benzoquinones with styrenes is controlled by the choice of Ti" or SnCU Lewis acids (eq 33). The use of an excess of TiCU or mixtures of TiCU and Ti(0-i-Pr)4 produces cyclobutane (13) as the major or exclusive product, while SnCU promotion with one equivalent of Lewis acid results in the formation of (14) only. These reactions represent a classic example of the mechanistic variability often associated with seemingly modest changes in Lewis acid. 

Cyclobutane formation via light-induced [2 + 2] cycloaddition is probably one of the best studied photochemical reactions and has been reviewed thoroughly up to 1972 (Houben-Weyl, Vols. 4/5 a and 4/5 b). The most important types of C —C double-bond chromophores undergoing such reactions arc alkenes, 1,3-dienes, styrenes, stilbenes, arenes, hetarenes, cycloalk-2-enones, cyclohexa-2,4(and 2,5)-dienones, 1,4-benzoquinones, and heteroanalogs of these cyclic unsaturated carbonyl compounds. For p notocyciodimerizations see Houben-Weyl, Vol. 4/5 a, p 278 and for mixed [2 + 2] photocycloadditions of these same chromophores to alkenes see Section 1.3.2.3. 

Certain olefinic substrates undergo thermally-forbidden [2 + 2] type cycloaddition in the presence of Lewis acid catalysts through coordination to the acceptor molecules. Scheme 111 illustrates the enantiose-lective version of this reaction (271). Some thio acetylenes can also be used. Substantial asymmetric induction has been observed in cycloadditions of styrenes and 1,4-benzoquinones using a stoichiometric amount of a chiral Ti(IV) complex (272). The [2 + 2] cycloadducts are readily rearranged to 2-ary 1-2,3-dihydrobenzofirrans. 

Engler reported [2 + 2] cycloaddition of 1,4-benzoquinones with styrenes using TAD-DOL-Ti complex. The [2 + 2] cycloaddition products can, upon warming the reaction mixture, be transformed to the formal [2 + 5] cycloaddition products, dihydrobenzofur-ans, although with reduced %ee. The dihydrobenzofurans thus obtained are useful intermediates in the synthesis of biologically interesting natural products (Sch. 59) [141]. 

Similar applications of chiral titanium Lewis acid catalysts to asymmetric [2 + 2] cycloadditions, with up to nearly quantitative asymmetric induction, have employed 4-benzoquinones as additions and substituted styrene-type substrates11. In all of these asymmetric [2 + 2]-cvcload-dition reactions, the Lewis acid catalyst presumably is attached to peripheral functional groups and thus, similar to Lewis acid catalyzed Diels Alder reactions (see Section 1.5.8.3.5.4.), is only indirectly involved in the reaction course7. 

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... 

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