Radical Reactions with Double Memory of Chirality (²MOC) for the Enantiospecific Synthesis of Adjacent Stereogenic Quaternary Centers in Solution: Cleavage and Bonding Faster than Radical Rotation

The solution photochemistry of bis(phenylpyrrolidinonyl)ketones (R,R)-1b and (S,S)-1b exhibited a remarkably high memory of chirality. Stereospecific decarbonylation to products (R,R)-3b and (S,S)-3b, respectively, occurred with an ee of ca. 80%. The reaction is thought to occur along the single state manifold by sequential Norrish type-I α-cleavage, decarbonylation, and radical−radical combination in a time scale that is comparable to that required for the radical intermediate to expose its other enantiotopic face by rotation about an axis perpendicular to that of the p orbital (ca. 3−7 ps). The absolute configuration of a key intermediate and that of ketone (R,R)-1b were determined by single-crystal X-ray diffraction and the ee values of the photochemical products with the help of chiral shift reagent (+)-Eu(tfc)3 and chiral LC-MS/MS. On the basis of the ee and de values at 25 °C, it could be determined that ca. 70% of the bond forming events occur with double memory of chirality, ca. 21% occur after rotation of one radical to form the meso product (R,S)-3b, and only 9% occur after double rotation to form the opposite enantiomer. This report represents the first example of a doubly enantiospecific Norrish type-I and decarbonylation reaction in solution and illustrates potentially efficient ways to obtain compounds with adjacent stereogenic quaternary centers.