A Diastereoselective Catalytic Approach to Pentasubstituted Pyrrolidines by Tandem Anionic-Radical Cross-Over Reactions

0552859 - ÚOCHB 2023 RIV DE eng J - Journal Article
Hidasová, Denisa - Pohl, Radek - Císařová, I. - Jahn, Ullrich
A Diastereoselective Catalytic Approach to Pentasubstituted Pyrrolidines by Tandem Anionic-Radical Cross-Over Reactions.
Advanced Synthesis & Catalysis. Roč. 364, č. 3 (2022), s. 671-678. ISSN 1615-4150. E-ISSN 1615-4169
R&D Projects: GA ČR GA13-40188S; GA MŠMT(CZ) EF16_019/0000729
Institutional support: RVO:61388963
Keywords : pyrrolidines * asymmetric synthesis * single-electron transfer * Aza-Michael addition * radical reactions
OECD category: Organic chemistry
Impact factor: 5.4, year: 2022
Method of publishing: Open access
https://doi.org/10.1002/adsc.202101172

Pentasubstituted pyrrolidines are ubiquitous constituents of natural products and drugs, however the access options to them especially with respect to absolute and relative stereochemistry are not well developed. We report an asymmetric synthesis of N,2,3,4,5-pentasubstituted pyrrolidines by oxidative single-electron transfer-catalyzed tandem aza-Michael addition/radical 5-exo cyclization/oxygenation reactions. The absolute stereochemistry is set by applying readily accessible chiral allylamines in asymmetric conjugate additions to various β-substituted-α,β-unsaturated esters, which dependent on the substituent R2 sets the configuration of the two stereocenters next to the amine function, whereas two more are diastereoselectively generated by the radical 5-exo cyclization step. This allows the diastereodivergent single-step synthesis of pyrrolidines with four contiguous stereogenic centers. The stereoselectivity is rationalized by a predictive model.
Permanent Link: http://hdl.handle.net/11104/0327955


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