Cycloaddition reactions paracyclophanes

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. 

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... 

Cyclophanes prepared by cycloaddition reactions include the tetra-substituted [2.2]paracyclophanes (435) and the [4.2]paracyclophanes (436), these being obtained by cycloaddition of dispiro[2.2.2.2]deca-4,9-diene (437) with styrene derivatives (438), with homolytic cleavage of the cyclopropane rings. 

Cycloadditions of [2.2]Paracyclophane and its Analogs 3.3.1. Diels—Alder Reactions... 

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]. 

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. ... 

Intramolecular Cycloadditions. - Intramolecular (2 + 2)-photocycloaddi-tion has been reported within diene 1,1-dicarbonitriles. Both direct and sensitized irradiation is effective. Unlike the singlet process, where an exciplex is involved, the sensitized process proceeds via 1,4-biradicals. The singlet and triplet reactivity has been investigated for a series of 1-alkene-1,1-dicarbonitriles with additional unsaturation at the 5, 6 or 7 positions. The cyclophane moiety shown in the derivative (23) has been suggested as a useful reaction control system. The irradiation of this cinnamate derivative affords the (3-truxinic acid derivative (24), which can be uncoupled from the paracyclophane. ... 

Most of the synthetic approaches towards benzoannelated [2.2]paracyclo-phanes use the Diels-Alder reaction to build up the annelated rings [18,22,29]. [2.2]Paracyclophane-l-ene (32) and [2.2]paracyclophane-1,9-diene (42) can be considered as the simplest dienophiles for this purpose. Since the first syntheses of these compounds in 1958 by Cram et al. [32], various attempts have been made to get them to react with dienes in terms of Diels-Alder reactions. However, [2 + 4] cycloadditions were never observed [33], and could not be facilitated either by the application of high pressure, or the presence of Lewis acid catalysts Diels-Alder adducts were not even obtained with dienes such as tetrachloro-thiophene dioxide, known for its high reactivity in [2 + 4] cycloadditions with an inverse electron demand. All the more surprising was the observation that monoene 32 reacts smoothly with dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate at room temperature leading to a dihydropyridazine-annelated paracyclophane 39 in high yield [34a]. As reported for other tetrazine Diels-Alder reactions... 

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. 

A new cage molecule [263(1,4)3(1,3,5)2-bicyclophanehexaene (446) has result-ed from a multi-stage reaction sequence, and the [10]paracyclophanes (447) from a mixture of two inside-inside [10.2.2]hexadecadienes (448) and (449) obtained by cycloaddition of methyl propiolate with cyclodecene. 

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