Stereoselective intermolecular radical additions to amide-substituted alkenes

Article abstract of DOI:10.1021/ja00005a051

The free-radical addition of carbon radicals to two alkenes substituted with chiral pyrrolidine amides has been studied. The two alkenes studied were both amides of 2,5-dimethylpyrrolidine, available as either the R,R or S,S enantiomer from D- or L-alanine. One alkene studied was the unsymmetrical monoamide derived from 4-oxo-2-pentenoic acid (1), while the other substrate examined was the diamide of fumaric acid, 2. Hexyl, cyclohexyl, and tert-butyl radical addition to the amide of 4-oxo-2-pentenoic acid (1) gave approximately equal amounts of addition at the carbonyl and amide ends of the alkene. The two stereoisomeric products formed from addition at the carbonyl end were formed in nearly 1:1 product ratio while the products formed by addition at the amide end were formed in ratios as high as 40:1 (tert-butyl addition at 0 °C). Addition of cyclohexyl or tert-butyl radical to the fumaric diamide gives essentially only one stereoisomer, (diastereomeric ratio 50:1 and 80:1 at room temperature). This approach provides the highest reported stereoselectivity for radical addition to an acyclic chiral alkene. Furthermore, a rationale for the diastereoselectivity is presented that suggests that the amide selectivity is steric in origin and will be general.