[3+3]-ANNULATION BASED ON 6-ENDO-TRIG RADICAL CYCLIZATION - REGIOSELECTIVITY AND DIASTEREOSELECTIVITY

The development of a [3 + 3] annulation strategy based on sequential ''two-electron'' and ''one-electron'' allylation of beta-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 PhSO(2) 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 (R(3)Sn, PhSO(2), and to a lesser extent PhS) are shown to be sufficiently activating to achieve 6-endo regioselectivity.