Transition Metal Catalyzed Radical Cyclizations

Synthesis of trichlorinated γ-lactones or γ-lactams from allyl trichloroacetates or N-allyl trichloroacetamides was achieved by transition metal-catalyzed radical cyclizations. Treatment of these trichlorinated starting materials with a catalytic amount of cuprous salts or a ruthenium-phosphine complex resulted in cleavage of a carbon-chlorine bond and subsequent intramolecular addition of the carbon moiety and the chlorine atom to the carbon- carbon double bond. Stereochemistry of the product was similar to that observed in free radical cyclizations ; e.g. stereochemistry of β- and γ-substituents generated by the cyclization of 1-methyl-2-propenyl trichloroacetate was predominantly trans, whereas a cis-fuzed bicyclic lactone was formed by the reaction of 2-cyclohexenyl trichloroacetate. The cyclization of N-allyl trichloroacetamides offers a facile preparative method for pyrrolidinone derivatives from easily available allylic alcohols by the combination with the [3.3] -sigmatropic rearrangement of allyl trichloroimidates. It also provides an interesting entry to alkaloid skeletons. In the cyclization of N-substituted N-allyl trichloroacetamides, judicious choice of the N-substituent and the catalyst dramatically lowered the reaction temperature, and enabled very efficient stereocontrol.