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Synlett 2021; 32(02): 211-214
DOI: 10.1055/a-1315-1014
DOI: 10.1055/a-1315-1014
cluster
Modern Heterocycle Synthesis and Functionalization
Synthesis of Spirocyclic Piperidines by Radical Hydroarylation
This work was funded by the National Institutes of Health (NIH, GM129495). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS.
Abstract
Reported here are conditions for the construction of spirocyclic piperidines from linear aryl halide precursors. These conditions employ a strongly reducing organic photoredox catalyst in combination with a trialkylamine reductant to achieve formation of aryl radical species. Regioselective cyclization followed by hydrogen-atom transfer affords a range of complex spiropiperidines. This system operates efficiently under mild conditions without the need for toxic reagents or precious metals.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1315-1014. Included are experimental procedures and characterization data for new compounds.
- Supporting Information
Publication History
Received: 25 October 2020
Accepted after revision: 19 November 2020
Accepted Manuscript online:
19 November 2020
Article published online:
18 December 2020
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Spiropiperidines 1–12; General Procedure
A 16 mL screw-top test tube was charged with the appropriate aryl halide precursor (0.3 mmol, 1.0 equiv) and photocatalyst P1 (3DPAFIPN; 0.015 mmol, 5 mol%). The tube was then equipped with a stirrer bar and sealed with a PTFE/silicone septum. The atmosphere in the tube was exchanged by applying vacuum and backfilling with N2, and solvent was added along with DIPEA (1.5 mmol, 5.0 equiv). The resulting mixture was stirred at 800 rpm for 16 h with irradiation by commercial blue LEDs. The reaction mixture was then diluted with H2O and extracted with EtOAc (3 × 20 mL). The combined organic layer was dried (Na2SO4), filtered, and concentrated by rotary evaporation, and the residue was purified by chromatography (silica gel).