Acyl Radical Addition onto Aza‐Baylis–Hillman Adducts: A Stereocontrolled Access to 2,3,5‐Trisubstituted Pyrrolidines

Free-radical addition of acyl radicals to chiral aza-Baylis–Hillman adducts was shown to afford the corresponding 1,4-amino ketones in good yields and good 1,2-stereocontrol. These ketones were then elaborated further using conditions varying as a function of the nature of the N-protecting group. Robust N–Ts protection thus allowed the formation, under acidic conditions, of a cyclic iminium which was reduced using bulky (Me3Si)3SiH into the corresponding 2,3,5-pyrrolidine exhibiting a trans-trans relative configuration. In contrast, under these conditions, the N-Boc protecting group was removed, leading to the formation of stable dihydropyrroles, which were then hydrogenated with PtO2, leading to 2,3,5-pyrrolidines having a trans-cis relative configuration. When additional ketone or ester groups were present on the pyrrolidine skeleton, further cyclization led to indolizidinones and pyrrolizidines in good overall yield in 4 steps and two-pot operations.