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Acyl Radical Addition onto Aza‐Baylis–Hillman Adducts: A Stereocontrolled Access to 2,3,5‐Trisubstituted Pyrrolidines
Author(s) -
Grélaud Simon,
Lusseau Jonathan,
Massip Stéphane,
Landais Yannick
Publication year - 2017
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201700362
Subject(s) - chemistry , pyrrolidine , adduct , yield (engineering) , radical , iminium , ketone , protecting group , stereoselectivity , medicinal chemistry , stereochemistry , organic chemistry , catalysis , materials science , metallurgy , alkyl
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 (Me 3 Si) 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 PtO 2 , 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.