Cycloaddition reactions condensation protocols

By combining the catalytic and template effect of copper(I), Leigh et al. have developed a new powerful tool, which permits to use only catalytic amounts of the template agents for the synthesis of mechanically interlocked architectures. In theory, this concept can be applied to many other metal-mediated reactions, such as cross-couplings, condensations or other cycloaddition reactions.This new development may be the seminal idea that could lead to a whole new range of catenane- and rotaxane-forming protocols. 

Scheme 6.186) [347]. The condensation of O-allylic and O-propargylic salicylalde-hydes with a-amino esters was carried out either in the absence of a solvent or - if both components were solids - in a minimal volume of xylene. All reactions performed under microwave conditions rapidly proceeded to completion within a few minutes and typically provided higher yields compared to the corresponding thermal protocols. In the case of intramolecular alkene cycloadditions, mixtures of hexa-hydrochromeno[4,3-b]pyrrole diastereoisomers were obtained, whereas transformations involving alkyne tethers provided chromeno[4,3-b]pyrroles directly after in situ oxidation with elemental sulfur (Scheme 6.186). Independent work by Pospisil and Potacek involved very similar transformations under strictly solvent-free conditions [348]. 

Confalone et al. (85) also made use of an intramolecular cycloaddition step in the construction of a range of tri- and tetracyclic products. Phenyl allyl ethers, of the type shown in Scheme 3.94, underwent dehydrative condensation with the requisite amine to furnish the intermediate ylides, which suffered cycloaddition resulting in 285 and 286 in essentially quantitative yield. The ratio of cis/trans fused products was in the range of 10 1. Such a process has been developed to construct the alkaloid (+ / ) sceletium A4 by reaction of the intermediate 287 with amine 288 via the cycloaddition protocol already developed, followed by further chemical manipulation, in an efficient five step synthesis (Scheme 3.94). 

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