SYNTHETIC STUDIES OF THE TANDEM ENEDIYNE-MONO-RADICAL AND BIS-RADICAL CYCLIZATIONS

The readily synthesized enediynes 12a-j possessing a tethered olefin radical acceptor can participate in a tandem enediyne-radical cyclization to yield dibydrobenzindene derivatives 14a-j. In the present study, the scope of this reaction was expanded to include a wide variety of olefin acceptors. Substitution at both ends of olefin leads to the formation of two diastereomers 14b and 14c in a 3.5:1 ratio when R3 is Me and R2 is CO2Me. The structures of the dihydrobenzindene products 14b and 14c were confirmed by generating a radical from 25 by a tributyltin hydride reaction which undergoes radical cyclization; this radical is similar to the enediyne-generated radical, which also cyclizes. It was shown that, in 14i and 14j, a substituent at R1 slowed the reaction but still resulted in a good to excellent yield of product. A tandem enediyne-6-exo-radical cyclization of 16 was also carried out but did not work as well as its 5-exo counterpart 12a. Finally, an enediyne 33 containing two olefinic tethers was cyclized in a process to form tetracycle 34 where three rings were formed in one synthetic operation.