Paracyclophanes 4+2 cycloaddition synthesis

MacGillivray s group has employed rigid bifunctional molecules [42], such as 1,3-dihydroxybenzene and 1,8-naphthalenedicarboxyHc acid [42a], as linear templates to organize reactants such as fra s-l,2-bis(4-pyridyl)ethylene via hydrogen bonds for single and multiple photoinduced [2+2] cycloadditions, for the template-controlled synthesis of a l,2,3,4-(4-pyridyl)cyclobutane] [42b] and also of paracyclophanes [42d]. Very recently, [ ]ladderanes ( =2,3) have been synthesized in the solid state by UV irradiation of 2(5-methoxyresorci-nol) 2(4-pyr-poly-m-ene) (m=2,3) [42e]. 

Twofold inter- and intramolecular PKRs have found interesting applications in synthesis of ansa-zirconocenes. An early example illustrated the use of this approach for the synthesis of cyclopentadiene anellated[2,2]para-cyclophanes 157-158. The reaction of several paracyclophanedienes (155) with alkynes gave the corresponding twofold cycloaddition products 156, which were transformed into cyclopentadienyl anions orthogonally attached to the bridges of the paracyclophane (Scheme 46) [158]. 

M. Shair and co-workers were the first to apply the enyne metathesis for macrocyclization during the biomimetic synthesis of (-)-longithorone A." The two 16-membered paracyclophane building blocks, one diene and one dienophile component, were prepared using 50 mol% Grubbs s first-generation catalyst under 1 atm ethylene gas pressure. These components, after several additional steps, underwent two facile Diels-Alder cycloaddition reactions to afford the natural product. 

Lewis acid catalyzed ene reactions with methyl propiolate have been used for the construction of steroid side chains,and for the synthesis of the A1 component of the female sex pheromone of the California red scale. AlCb catalyzed [2 + 2] cycloadditions of methyl propiolate have been used for the synthesis of inside-inside bicyclics and [10]paracyclophanes. An intramolecular version of this cycloaddition has been used in the construction of coronofacic acid. ... 

Although the [2 + 2] photocycloaddition is preferably prevented in the synthesis of PAHs, it has been proven to be a very feasible approach in the selective synthesis of syn-[2.2]cyclophanes [86,87]. Topological reaction control in solution has been achieved for a multistep intramolecular [2 + 2] cycloaddition reaction in the photochemical formation of [n]-ladderanes from pseudo-gem-bis(polyene) substituted [2.2]paracyclophanes [88]. The probably most well-known example of an intramolecular photocycloaddition process is one of the... 

If this evidence were not incriminating enough, additional substantiation for its likelihood was provided in 2002 by Professor Matthew Shair and two of his graduate students at Harvard University through the first chemical synthesis of longithorone A (1) predicated on these same Diels-Alder reactions. This accomplishment is the subject of this chapter, an achievement whose success ultimately relied not only on the power of [4- -2]-cycloadditions, but also on an inventive strategy to atropselectively construct both [12]-paracyclophanes at the heart of Schmitz biosynthetic hypothesis. 

The high-yielding and highly enantioselective synthesis of carba[10]paracyclophanes has been achieved by the cationic rhodium(I)/(S,S)-BDPP complex-catalyzed [2+2+2] cycloaddition of cyclic diynes with terminal monoynes (Scheme 21.22) [26]. 

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