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Synlett 2022; 33(19): 1902-1906
DOI: 10.1055/a-1916-5335
DOI: 10.1055/a-1916-5335
letter
Direct Methenylation of 4-Alkylpyridines Using Eschenmoser’s Salt
Financial support for G.N.S. was received from the Center for Biocatalysis and Bioprocessing, University of Iowa (NIH Predoctoral Training Program in Biotechnology, T32-GM008365). Funds for the purchase of a Bruker Avance Neo 400 NMR spectrometer were provided by the NSF-MRI Program (NSF-CHE-2017828).
Abstract
4-Alkylpyridines are converted into conjugated 1,1-disubstituted alkenyl pyridines (vinyl pyridines) upon treatment with excess ethyl chloroformate, triethylamine, and Eschenmoser’s salt. The reaction proceeds under mild conditions via alkylidene dihydropyridine intermediates.
Key words
pyridine - alkylidene dihydropyridine - anhydrobase - alkylation - Eschenmoser’s salt - dearomatizationSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1916-5335.
- Supporting Information
Publication History
Received: 07 July 2022
Accepted after revision: 02 August 2022
Accepted Manuscript online:
02 August 2022
Article published online:
02 September 2022
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- 13 Representative Procedure Reactions were performed in a 20 mL scintillation vial. To a solution of 1a (50.0 mg, 0.28 mmol, 1 equiv) and Et3N (3 equiv) in THF (2.8 mL) were added ClCO2Et (3.5 equiv) and Eschenmoser’s salt (1.5 equiv). The vial was capped and placed in a J-KEM Lab benchtop shaker heating block set to 66 °C and agitated until the reaction was complete as indicated by TLC (ca. 16 h). After cooling to rt, the solvent was evaporated, and the residue purified by flash column chromatography using 25–100% EtOAc in hexanes as the eluent to afford 2a as an orange oil (47. 4 mg, 89%).
- 14 Characterization Data for 2a 1H NMR (400 MHz, CDCl3): δ = 8.65 (d, J = 5.9 Hz, 2 H), 7.31 (d, J = 5.9 Hz, 2 H), 6.00 (s, 1 H), 5.42 (s, 1 H), 3.52 (q, J = 7.1 Hz, 2 H), 2.01 (s, 3 H), 1.14 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 170.3, 150.9, 145.2, 143.4, 120.0, 117.4, 41.6, 22.2, 13.1. HRMS (ESI+): m/z calcd for C11H15N2O [M + H]+: 191.1179; found: 191.1177.