Palladium 2.2 Paracyclophanes

Less than two years after Chan and I disclosed the synthesis of 72 and 73, a more practical synthesis of 72 based on palladium-mediated reactions was reported by Armin de Meijere. I was deeply impressed by the highly efficient way Armin and his co-worker, Oliver Reiser, were preparing 72 as well as its derivatives. Immediately, I realized that it was impractical to compete with them. I therefore quit the dibenzo[2.2]paracyclophane field, with the strong conviction that many other unknown theoretically interesting molecules were still waiting for our pursuit. 

Palladium acetate, 61, 82 Paracyclophanes, table, 60, 47 Paraformaldehyde [30525-89-4], 61, 65 Paraformaldehyde (polyoxymethylene), 60, 88 Pentadecanoic acid, 60, 13 PENTAN01C-2-13C ACID, 3-HYDROXY-3-METHYL-5-(PHENYLMETHOXY)-[57830-65-6], 60, 94... 

Dibenzo[2.2]paracyclophane-1,9-diene (2), a unique molecule with two parallel sets of mutually orthogonal aromatic rings, was first synthesized in 1985 by Wong et al. [18]. The reported five-step synthesis gave the strained hydrocarbon in only 0.5% yield. Later a more versatile and economic approach to dibenzoannelated [2.2]paracyclophanedienes 11 including the parent compound 2 was developed by de Meijere et al. [19]. The dibromo[2.2]paracyclo-phane-l-ene (6) and the tetrabromo[2.2]paracyclophane-1,9-diene (7) were obtained from commercially available [2.2]paracyclophane (1) in a bromination-dehydrobromination reaction sequence. With compounds 6 and 7 available in large quantities, the palladium catalyzed coupling with alkenes (Heck reaction)... 

Scheme 10. Palladium-catalyzed assembly of [2.2]paracyclophane-l-ene and its 1-bromo derivative attempted synthesis of dihydrotrifoliaphane (a) Pd(OAc)2, K2C03, Bu4NBr, DMF, 85°C,4h [30]...

In view of the successful palladium-catalyzed [2 + 2 + 2] assembly of a cyclo-hexa-1,3-diene derivative from one molecule of norbornene and two molecules of /i-bromostyrene [30 a], a rationally designed synthesis of dihydrotrifoliaphane 33 as a precursor to 29 appeared to be plausible. However, when a 1 2 mixture of [2.2]paracyclophane-l-ene (32) and its 1-bromo derivative 4 was subjected to the reported conditions, the novel hydrocarbon 34 with a different array of three [2.2]paracyclophane units was obtained in 62% yield [30b]. Trifoliaphane 29, arising from oxidation of the primarily formed dihydro derivative 33, was obtained as a minor by-product (2 % yield) in this coupling. The constitution of 34 was established by an X-ray crystal structure analysis. 

Both decks of the [2.2]paracyclophane derivatives 160 and 161 could be transformed into 1,4-distyrylbenzene chromophores via the palladium-catalyzed coupling (Heck reaction) with styrene and substituted styrenes adopting the protocol of Jeffery [106]. The fourfold coupling products 162 and 163 were thus obtained with yields up to 70% [107a]. As four new carbon-carbon bonds are formed in this transformation, each single coupling step must proceed with excellent yield. All these reactions lead stereoselectively to products with (E)-configurated double bonds. 

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