O-quinodimethane intermediate

Several ingenious syntheses of natural products have been developed by exploiting benzcyclobutene ring opening to o-quinodimethane. Particularly, the intramolecular Diels-Alder strategy employing o-quinodimethane intermediates has been very effective for the construction of polycyclic structures. Selected examples are gathered in Table 12. 

Photochemical hydrogen abstraction reaction for the silylimine 161 give an o-quinodimethane intermediate 162 which could be trapped with dimethyl fumarate, dimethyl maleate, trans-methyl cinnamate, methyl acrylate, acrylonitrile (equation 94)... 

An alternative polymerization mechanism and polymer architecture has been proposed by Kirchhoff [1, 2, 3], Tan and Arnold [77], By this mechanism, polybenzocyclobutenes which do not contain reactive sites of unsaturation are proposed to polymerize by the 1,4 addition of the o-quinodimethane intermediates to give a substantially linear poly(o-xylylene) structure. Since the monomers all contain at least two benzocyclobutene units the net result of this reaction will to a first approximation be a ladder type polymer as shown in Fig. 17. The formation of a true ladder polymer however would require that all... 

Formation of ring c ( disconnection b) was readily accomplished by addition of o-quinodimethane intermediates, e.g. (562) or 7,8-dibromo-o-quinodimefliane, to tetrahydronqihthoquinones such as racemic or enantiomerically pure (632) (Scheme 141). 

Imidazole o-quinodimethane intermediate 8, synthesized from 2-bromo-... 

Interestingly, the putative o-quinodimethane intermediate in this case undergoes cyclization with regiochemistry opposite to Oppolzer s system. Whether this result is due to the nature of the bridge between diene and dienophile or to some sort of polar interaction is not clear. From the product stereochemistry it is evident that cyclizations must have occurred via an endo-phenyl transition state. 

Pyrazine derivatives have also served as precursors for quinoxalines in acceptable yields under MWI in solvent-free conditions through the reaction of pyrazine o-quinodimethane intermediates with electron-rich dienophiles. Thus, 2,3-bis... 

Kametani et al. [10] and Oppolzer et aL [11] reported the Diels-Alder reaction of benzocyclobutane by heating. In this reaction, the benzocy-clobutanes produced o-quinodimethane intermediates, which readily reacted with acetylenic compounds to afford cycloadduct aromatic compoimds. Furthermore, Noland et aL reported the Diels-Alder reaction of the o-quino-dimethane intermediate obtained by heating indene [12]. 

Scheme 2 Diels-Alder reaction via o-quinodimethane intermediate...

One of the key features in Scheme 27 is the intramolecular cycloaddition of an o-quinodimethane intermediate, and this reaction has featured in several other new approaches to steroidal and related polycyclic carbon skeletons (Scheme 28). The last example in Scheme 28 also illustrates a new route to the cyclization precursor (119) via a nucleophilic induced elimination-addition of an a-halogeno-... 

The Chi group further developed a highly enantioselective formal [4 + 2] cycloaddition of a-branched indole 3-carboxaldehydes with trifluoromethyl ketones or isatins to give polyeyelic and spiro lactones, respectively. The reaction is postulated to undergo a catalytic cycle of NHC-eatalyzed aetiva-tion of the C(sp )—H bond of 2-methyl indole 3-carboxaldehydes to produee ort/ o-quinodimethane intermediates. Notably, 2-methyl benzofuran and ben-zothiophene aldehydes are also suitable substrates for this reaction, while 2-methylbenzaldehyde gives the partially oxidized carboxylic acid under these conditions without the observation of the desired lactone product (Scheme 7.115). 

Sol 3. (i) A stereoselective total synthesis of estrone proceeds via thermal 47T-conrotatory ring opening reaction of benzocyclobutane derivative to generate reactive o-quinodimethane intermediate followed by an intramolecular Diels—Alder reaction. 

D-A-substituted a-quinquethiophene 2.110 capped by an anthracene and Ceo unit has been synthesized via a [4-1-2] cycloaddition reaction of Ceo with anthrylquinquethieno-o-quinodimethane intermediate, which was generated in situ by cheletropic extrusion of SO2 from the precursor cyclic sulfone 2.109 (Scheme 1.19) [212]. Energy transfer from the anthracene donor to the fullerene acceptor has been observed for the triad. Photoinduced electron transfer processes in the triad were observed in low-temperature ESR measurements [213]. 

Contemporaneous with the work of Ito was a synthesis of 11-a-hydroxyestrone methyl ether (148) by Magnus and coworkers (Scheme 54)in which the requisite o-quinodimethane intermediate was generated by the fragmentation of the o-[(trimethylsilyl)methyl]aryl oxirane derivative (147) using CsF. 

The idea of generating an o-quinodimethane intermediate from a benzyl silane was first published by Saegusa. The method was first applied to steroid synthesis by others, but Saegusa and his co-workers have now published their studies in this area. They include the treatment of the benzyl silane (43) with fluoride ion in the presence of dimethyl fumarate to give the diester (44) as a single stereoisomer (Scheme 35). 

Transformation of Benzocyclobutenones into 2,3-Benzodiazepines. Benzocyclobutenones react with TMSC(Li)N2 to give 2,3-benzodiazepines via 2-diazo-2-(trimethylsilyl)ethoxide anions and o-quinodimethane intermediates (eq 34). ... 

Several additional illustrations of the use of intramolecular cycloadditions of o-quinodimethane intermediates in the synthesis of steroidal molecules have been published by Kametani and co-workers. ... 

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