Annulation Based on 6-Endo-Trig Radical Cyclization: Regioselectivity and Diastereoselectivity

Article abstract of DOI:10.1021/jo00129a024

The development of a <3+3> annulation strategy based on sequential "two-electron" and "one-electron" allylation of β-substituted aldehydes and derivatives with the bifunctional isobutene conjunctive reagent 1 is described.The key step involves an unusual 6-endo-trig radical cyclization.Yields of 6-endo products are improved if the PhS group is oxidized to a PhSO2 group prior to cyclization.The structural factors affecting the regioselectivity and stereoselectivity of the cyclization are examined.In general, the stereoselectivity of 6-endo-trig cyclization of 5-hexenyl radicals can be rationalized by conformational analysis of chairlike transition states and can be calculated effectively with an MM2 force field model.High 6-endo regioselectivity requires a strong driving force.Fragmentable allylic groups (R3Sn, PhSO2, and to a lesser extent PhS) are shown to be sufficiently activating to achieve 6-endo regioselectivity.