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

Abstract

Free-radical addition of acyl radicalst o chiral aza-Baylis-Hillman adductsw as shown to affordt he corresponding 1,4-amino ketones in good yields and good 1,2-stereocontrol. These ketones were then elaborated further using conditions varying as af unction of the nature of the N-protecting group.R obust N-Ts protection thus allowed the formation, under acidic conditions,o facyclic iminium which was reduced using bulky (Me 3 Si) 3 SiH into the corresponding 2,3,5-pyrrolidine exhibiting a transtrans 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 PtO 2 ,l eading to 2,3,5-pyrrolidines having a trans-cis relativec onfiguration. When additional ketone or ester groups were presento nt he pyrrolidine skeleton, further cyclization led to indolizidinones and pyrrolizidines in good overally ield in 4steps and two-pot operations.

Thirty Years of (TMS)3SiH: A Milestone in Radical-Based Synthetic Chemistry

“…2106 A ( 242 ), a marine fungus secondary metabolite in 20% overall yield and 8 steps from commercially available D-xylose acetonide . An extension of this chemistry was finally performed to access 2,3,5-trisubstituted pyrrolidines and indolizidines starting from aza-Baylis-Hillman adducts 244 . TTMSS-mediated acyl radical addition to 244 starting from acylselenide 243 led to the desired addition product 245 in good yield and moderate diastereocontrol.…”

“…180 TTMSS-mediated acyl radical addition to 244 starting from acylselenide 243 led to the desired addition product 245 in good yield and moderate diastereocontrol. Addition of BF 3 •Et 2 O triggered the cyclization of 245 into a hemiaminal, followed by ionic hydrogen atom transfer from TTMSS, which eventually led to pyrrolidine 246 with high diastereocontrol (Scheme 71).…”

One-Pot Synthesis of Aza-Morita-Baylis-Hillman Adducts via Zinc-Mediated Allylation of 4-Bromocrotonates and Imines

“…Aza -Morita–Baylis–Hillman (MBH) type products are tremendously useful molecules in organic synthesis. They have several adjacent functional groups which play specific roles in further transformations . The traditional methods for the synthesis of these interesting compounds mainly involve the coupling of activated alkenes with imines mediated by a tertiary amine or a tertiary phosphine, commonly known as the aza -MBH reaction …”