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

作者：Grelaud Simon; Lusseau Jonathan; Massip Stephane; Landais Yannick^*

来源：Advanced Synthesis & Catalysis, 2017, 359(14): 2434-2441.

DOI：10.1002/adsc.201700362

• acyl addition
• aza-Baylis-Hillman reaction
• indolizidines
• pyrrolizidines
• radicals

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)(3)SiH 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.

• 出版日期2017-7-17