Oxacycles, tandem synthesis

Tandem 5-exo-oxacyclizations of polyepoxides to form polycyclic ethers are well known. In Evans s synthesis of lonomycin A, diepoxide 66 underwent the desired... 

Sibi et al. reported an elegant new tandem radical addition-cyclization process for the synthesis of oxacycles [122]. The method relies on the inter-molecular addition of alkyl radical to a doubly activated Michael acceptor moiety, followed by a cyclization step (Scheme 39). The outcome of the re-... 

Alkenyl and aryl radicals are also useful for expedient synthesis of oxacyclic natural products. For example, the hexahydrobenzofuran subunit 12 for avermectin synthesis was obtained from the bromopropenyl ether 11 [13] (Scheme 6). A formal synthesis of morphine (15) was reported by Parker utilizing tandem radical cyclizations initiated by the aryl radical from the bromoaryl ether 13 [14] (Scheme 7). A closely related example for the morphine skeleton synthesis also employed aryl radical cyclization [15]. 

The oxacycles have remained a more challenging synthetic task as compared to the N- and S-containing medium sized rings. The medium sized lactones have also attracted significant attention as these are considered to be a rare class of organic compounds, which are even difficult to produce in natural biosynthetic pathways (Shiina, 2007). Bagley et al. (2009) reported microwave-assisted synthesis of seven membered lactones through a tandem oxidation- cyclocondensation of 1,6-hexane-diol. 

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