0-Quinodimethane, thermolysis

Mandelate and lactate esters have been found to generate diastereoselectivity in reactions of hydroxy-substituted quinodimethanes generated by thermolysis of benzo-cyclobutenols.88 The reactions are thought to proceed by an exo TS with a crucial hydrogen bond between the hydroxy group and a dienophile carbonyl. The phenyl (or methyl in the case of lactate) group promotes facial selectivity. 

Sulfolene dioxide thermolysis has also been applied to formation of o-quinodimethanes. 

The thiophene ring system can be utilized as a synthetic scaffold for the preparation of nonthiophene materials as the sulfur moiety can be removed by reduction (desulfurization) or extrusion (loss of SO2). The extrusion of sulfur dioxide from 3-sulfolenes (2,5-dihydrothiophene 1,1-dioxides) give dienes (butadienes or o-quinodimethanes) that can be utilized to prepare six-membered rings by cycloaddition chemistry. For example, thermolysis of 3-sulfolene 120 provided tricyclic pyrazole 122 via an intramolecular cycloaddition of the o-quinodimethane 121 that results by extrusion of sulfur dioxide <00JOC5760>. Syntheses of 3-sulfolenes 123 and 124 <00S507> have recently been reported. 

The Parylene family has very attractive properties for use as dielectric materials as was noted above, but their thermal stability at the temperatures used in the fabrication of electronic devices is less than optimum. When considering alternatives as possible precursors for VDP, the isomeric ortho-xylylene (o-quinodimethane) is a likely candidate (Scheme 4). This approach involves the thermolysis ofbenzocyclobutene derivatives to generate a reactive dieneoid intermediate (o-quinodimethane),... 

These cycloadditions with o-quinodimethanes provide a broad variety of useful fullerene functionalizations, since o-quinodimethanes can be prepared using several routes and the resulting cycloadducts are thermally stable [42], There exist several alternatives to the iodide-induced bromine 1,4-elimination of 1,2-bis (bromomethyl)-benzenes [44-47]. o-Quinodimethanes have been prepared by thermolysis of 3-isochromanone (42) [43], benzocyclobutenes (43) [48-50], isobenzothiophene 2,2-dioxides (44) [42] and sultines [51,52] or by photolysis of o-alkylphenones such as 45 [53-55] and could be added to Cjq in good yields (Scheme 4.7). Indene, thermally rearranged to isoindene, also adds to Cjq in similar fashion to quinodimethanes [56]. 

The thermolysis of benzocyclobutene either in the condensed or vapor phase has been shown by a variety of techniques to initially yield an o-quinodimethane (Fig. 9). The fate of the o-quinodimethane in the absence of other coreactive species appears to depend to a large extent upon the conditions under which it is generated. Thus for example, the thermolysis of benzocyclobutene hydrocarbon itself in a sealed flask at 200 °C gave a 24% yield of 1,2,5,6-dibenzocycloocta-diene 20 along with a mixture of unidentified oligomeric materials (Fig. 12) [70]. 

Fig. 15. Proposed mechanism for the formation of poly(o-xy]ylene) from the thermolysis of o-quinodimethane spirodimer 24...

Intramolecular [4 + 2] cycloaddition reactions are illustrated by thermolysis of the benzocyclo-butene (144) to the tetracyclic system (145), via trapping of a quinodimethane by the nitrile group. 

An enantioselective synthesis of (+)-estradiol has been accomplished from 1,3-dihy-drobenzo[c]thiophene 2,2-dioxide (306) by successive thermal S02-extrusion and cycloaddition (80HCA1703). Treatment of the optically active iodide (307) with two mole equivalents of the masked quinodimethane (306) in the presence of two mole equivalents of sodium hydride gave (308) as a 1 1 mixture of diastereoisomers. Thermolysis of this alkenic sulfone in 1,2,4-trichlorobenzene furnished the trans-anti-trans steroid (309) in 80% yield. Treatment of (309) with methyllithium gave the methyl ketone, which was subjected to a Baeyer-Villiger oxidation and then silyl ether-acetate cleavage to afford (-l-)-estradiol (310 Scheme 66). 

Polystyrene-bound o-quinodimethanes, which are formed upon thermolysis of ben-zocyclobutanes, can be converted into 1,2,3,4-tetrahydroisoquinoline derivatives by reaction with /V-sulfonylimines. Reaction of o-quinodimethanes with electron-poor nitriles leads to the formation of 1,4-dihydroisoquinolines, which undergo elimination with simultaneous release of isoquinolines into solution (Entry 7, Table 15.25). 

The synthetic strategies used for the preparation of pyrans on insoluble supports have mainly been hetero-Diels-Alder reactions of enones with enol ethers and ringclosing olefin metathesis (Table 15.33). Benzopyrans have been prepared by hetero-Diels-Alder reactions of polystyrene-bound o-quinodimethanes with aldehydes. The required quinodimethanes were generated by thermolysis of benzocyclobutanes, which were prepared in solution [308]. Other solid-phase procedures for the preparation of benzopyrans are the palladium-mediated reaction of support-bound 2-iodo-phenols with 1,4-dienes (Entry 5, Table 15.33) and the intramolecular Knoevenagel... 

Cyclization of side chain nitriles has found extensive use in the synthesis of benzocyclobutenes (70 n = 2),104 the versatile synthons which open on mild thermolysis to give o-quinodimethanes for inter- and intra-molecular [4 + 2] trapping.108 The nitrile group in (70) can be manipulated into a variety of functionalities for appending the dienophile portion. For example, in the synthesis of chelidonine, the nitrile (71) was converted, by hydrolysis followed by Curtius degradation and reaction of the formed isocyanate with benzyl alcohol, to a urethane (72). The latter was then condensed with a benzyl bromide to get the compound (73), which was elaborated further as shown in Scheme 14.109... 

In a recent re-examination of the thermolysis of benzocyclobutenes for the in situ generation of o-quinodimethanes, the resultant IMDA diastereoselectivity was highly dependent on the nature of the hydroxyl protective group.90 The intramolecular 4 + 2-cycloaddition of o-quinodimethanes (83), derived from ene-bis(sulfinylallenes) (82), with electron-deficient and electron-rich alkenes produced the corresponding polycyclic aromatic compounds (84) (Scheme 22).91 The enantioselective Diels-Alder... 

The second category of [4+2] cycloadditions has been applied in order to construct novel organofullerene materials possessing fused furan and thiophene rings [87,88], suitable for nanoelectronics and photovoltaics applications. Other examples of such cycloadditions involve reactive quinodimethane species created in situ by thermolysis of cyclic sulfones [89], substituted cyclo- [89,90] or ben-zocyclobutanes [91], and 1,4-elimination of dibromides [91]. 

The thermolysis of isothiazolo-3-sulfolenes 265 (see Section 4.05.9.2.1) allows the generation of o-quinodimethane analogues 266 which can be trapped with dienophiles affording 267 or 268 <1996TL4189>. 

As to the underlying reaction mechanism, it appears that vacuum thermolysis of (545), (554) and (561) generates in each case, initially, a transient o-quinodimethane which cyclizes in the highly dilute gas phase. o-Quinoid vinylketene intermediate (562) could be regenerated in solution from the isolated benzocyclobutenone (563) on heating or irradiation and trapped by electron-poor dienophiles, e.g. (632) (Scheme 141). = Alternatively, benzocyclobutenones can be easily functionalized at the carbonyl group or at Ca, affording further o-quinodimethane precursors. 

A synthetic route to asymmetric tetralins applies the cyclization of chiral acrylates 28 or fumarates 38 to 2-quinodimethanes, which must be generated in situ. Different procedures lead to a-hydroxy 2-quinodimethanes 49 and 56, for instance the irradiation of 2-methylbenzalde-hyde (48)10 or thermolysis of the benzocyclobutene 53 or the cyclic sulfone 541... 

Heterocycles have been synthesized using o-quinodimethane chemistry. Thermolysis of l,2-dihydro-jY-(2-propenyl)-1-benzocyclobutadicnecarboxamide gave exclusively the m-fuscd hexahydrobenz[e]isoindol-l -one 31. 

Treatment of 194 with n-BuLi afforded the benzocyclobutenol 195 in 71% yield. Thermolysis of 195 in refluxing toluene and treatment with methyl (S)-mandelate (196) gave a mixture of cycloadducts via the a-hydroxy-a-aryl-o-quinodimethane 197 intermediate. The major... 

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