Intramolecular Cycloadditions Under Dilution Conditions

Pericyclic reactions were used successfully, too, to build up macrocycHc ring systems as found, for example, in natural peptides and peptide alkaloids. These reactions are carried out in general at moderate dilution conditions (10 -10 M). An example of a Diels-Alder reaction is the cyclization of 106 to 107, where the basic framework of cytochalasane B (108), a substance found in fungi, is built up in yet 27% yield [79]. 

The bridged paracyclophanes 111 and 112 could be obtained from the aziridines 109 by 1,3-dipolar cycloaddition with remarkable diastereoselectivity [80] First 

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Intramolecular 1,3-dipolar cycloadditions represent a powerful synthetic tool. Kato and co-workers were apparently the first to report an intramolecular munchnone-alkyne cycloaddition. Thus munchnones 184, as generated from iV-acylamino acids 183, yield the corresponding benzopyrano[4,3-f ]pyrroles 186 after extrusion of carbon dioxide from adduct 185 (Fig. 4.65). The yields shown are for high-dilution reaction conditions. Under normal conditions of concentration, the yields are stiU about 60%. Interestingly, attempts to divert the intramolecular cycloaddition by the addition of A -phenylmaleimide had no effect on the reaction pathway. 

Weinreb reported the intramolecular Diels-Alder reaction of oximino malonates tethered to a diene 268 under high dilution conditions. The cycloaddition adduct 269 underwent double eliminations with cesium carbonate to afford the pyridine 270. 

The Wulff-Ddtz reaction is another approach to the synthesis of the cyclophane system by formal [2 + 2 + 2] cycloaddition. The intramolecular benzannulation of the Fischer carbene complex, which has an alkyne tethered to the a-position of the alkenyl substituent, gave a para-cyclophane in moderate yield under highly diluted conditions (Scheme 8.6) [6]. 

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