Cyclization of 7-octenoyl radicals

In contrast with the clean 1-exo cyclization of benzoyl radicals (e.g., selenoester 9, n = 3), no cyclization was observed from 2-indolylacyl radicals derived from selenoesters 33-35. Only the respective indole-2-carbaldehydes were isolated from the reaction mixtures, indicating that both exo and endo ring closures leading to 7- or 8-membered carbocycles fused to the indole ring are too slow for the radical chain to be productive 04OL759 07JOC4562 . 

On the other hand, 5-aza-7-octenoyl radicals derived from selenoester 39 behaved in a different way, leading to 1-exo and 8-endo cyclized products in ratios that were dependent on the hydride concentration. When working as above at 0.02 M, a 3 1 mixture of endo-exo products 40 and 41 was obtained, along with notable amounts of aldehyde 42. Interestingly, the use of more concentrated hydride solutions (0.14 M) not only resulted in a predictable 

The above results indicated that the equilibration of the initially formed exo-endo cyclized radicals E and F through an intramolecular rearrangement in favor of the thermodynamically more stable endo radical F was now included in the reaction pathway, playing a key role in the enhancement of the 8-endo regioselectivity at a low hydride concentration 87JA2565 93CRV2091 97CEJ376 . 

As the azocinoindole 40 constitutes the tricyclic substructure of the indole alkaloid apparicine B-83MI265 , we attempted to improve the cyclization yield. Satisfactorily, the regioselectivity was completely switched to the 8-endo mode when the alkene acceptor was substituted at the internal position by a bromine atom. Thus, cyclization of selenoester 43 led to the desired target 40 as the only reaction product in 75% yield. Clearly, the bromine atom not only sterically prevented the competitive 1-exo attack, but also benefited the cyclization by activation of the double bond. It should be noted that similar halogen-controlled 8-endo cyclizations are known in the literature, but involving amidyl-type radicals 06OL2647 . 

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