A Model Study of Intramolecular Asymmetric Radical Cyclizations of a-Ester and α-Amide Radicals

Article abstract of DOI:10.1002/jccs.199700039

Starting from malonate, a practical route was developed for the synthesis of α-phenylthio acid 3. Several chiral compounds including (-)-menthol, (-)-8-phenylmenthol and a camphor based oxazolidinone 8 reacted with 3 to give α-phenylthio esters or amide. These sulfides cyclized efficiently when reacted with tributyltin hydride. Among the chiral auxiliaries used, 8-phenylmenthyl group displayed moderate asymmetric induction (64% ee for cis-product and 40% ee for trans-product). Based on this results, a transition state model was proposed to explain the observed stereoselectivity. In this model, due to π,π-orbital overlap of the phenyl ring and the carbonyl, the si-face of the most stable conformer of the radical was shielded. This controlled the carbon-carbon bond formation to occur from the re-face.