α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

0541690 - ÚOCHB 2022 RIV DE eng J - Článek v odborném periodiku
Klychnikov, Mikhail - Pohl, Radek - Císařová, I. - Jahn, Ullrich
α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams.
Beilstein Journal of Organic Chemistry. Roč. 17, Mar 9 (2021), s. 688-704. ISSN 1860-5397. E-ISSN 1860-5397
Grant CEP: GA ČR(CZ) GA16-18513S
Institucionální podpora: RVO:61388963
Klíčová slova: Brook rearrangement * cyclization * electron transfer * γ-lactams * tandem reactions
Obor OECD: Organic chemistry
Impakt faktor: 2.544, rok: 2021
Způsob publikování: Open access
https://doi.org/10.3762/bjoc.17.58

Pyrrolidones are common heterocyclic fragments in various biologically active compounds. Here, a two-step radical-based approach to γ-lactams bearing three to four stereocenters starting from epoxides, N-allylic silylacetamides and TEMPO is reported. The sequence starts with a new tandem nucleophilic substitution/Brook rearrangement/single electron transfer-induced radical oxygenation furnishing orthogonally protected α,γ-dioxygenated N-allylamides with wide scope, mostly good yields, and partly good diastereo- and enantioselectivity for defined combinations of chiral epoxides and chiral amides. This represents a very rare example of an oxidative geminal C–C/C–O difunctionalization next to carbonyl groups. The resulting dioxygenated allylic amides are subsequently subjected to persistent radical effect-based 5-exo-trig radical cyclization reactions providing functionalized pyrrolidones in high yields as diastereomeric mixtures. They converge to 3,4-trans-γ-lactams by base-mediated equilibration, which can be easily further diversified. Stereochemical models for both reaction types were developed.
Trvalý link: http://hdl.handle.net/11104/0319220