Radical cyclization proved to be synthetically useful for the construction of 5- and 6-membered rings, and mostly utilized carbon–carbon multiple bonds as radical acceptors. However, the carbonyl group, one of the most important functional groups, has not been widely used as a radical acceptor because the addition of an alkyl radical to the carbonyl group is energetically unfavorable and reversible due to the strong π-bond strength of the carbonyl group. On the other hand, we found that alkenylacylphosphonate 1 would be applicable for the radical cyclization under Co-catalysis (Scheme 1). The cyclization reaction proceeded smoothly to give various 5- or 6-membered cycloadduct 3a-l in good yield. Furthermore, our protocol does not require higher temperature and light irradiation as observed in previous radical cyclizations. Having established a new hydroacylation of alkenylacylphosphonate 1, we next examined tandem cyclization using 4 as a starting material (Scheme 2). The initial C-H bond fortunately formed at terminal sp2 carbon of disubstituted alkene, and the bicyclic adducts 6 and 7 were given in 44% yield. In conclusion, the free radical acylation approach will find useful applications for the synthesis of a variety of carbonyl compounds and have great synthetic potential because these methods proceed under mild reaction conditions.

Cyclization using alkene and acylphosphonate under Co catalysis

255th National Meeting (2018)

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