Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2024; 35(14): 1725-1727
DOI: 10.1055/s-0042-1751548
DOI: 10.1055/s-0042-1751548
letter
Regioselective Formation of Pyridines by Cycloaddition/Cycloreversion of 1,4-Oxazinone Precursors with Bisalkyne Substrates
This work was supported by the National Institutes of Health, General Medical Sciences (NIH R15GM107702 to J.R.S.).
Abstract
This study explores the merged cycloaddition/cycloreversion of a 1,4-oxazinone substrate and conjugated bisalkyne precursors. Good regioselectivity in the Diels–Alder operation is observed and pyridines bearing 3-alkynyl functionality are afforded following cycloreversion and extrusion of CO2. Examples with both symmetric and nonsymmetric bisalkyne substrates are included.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0042-1751548.
- Supporting Information
Publication History
Received: 21 November 2023
Accepted after revision: 13 December 2023
Article published online:
18 January 2024
© 2024. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References and Notes
- 1a Foster RA. A, Willis MC. Chem. Soc. Rev. 2013; 42: 63
- 1b Meerpoel L, Deroover G, Van Aken K, Lux G, Hoornaert G. Synthesis 1991; 765
- 1c Meerpoel L, Hoornaert G. Tetrahedron Lett. 1989; 30: 3183
- 2 Rooshenas P, Hof K, Schreiner PR, Williams CM. Eur. J Org. Chem. 2011; 983
- 3 Carrillo Vallejo NA, Scheerer JR. J Org. Chem. 2021; 86: 5863
- 4 Angello NH, Wiley RE, Abelt CJ, Scheerer JR. Molecules 2020; 25: 3358
- 5 Scheerer JR, Leeth EB, Sprow JA. Synthesis 2023; 55: 2319
- 6a Thirumurugan P, Matosiuk D, Jozwiak K. Chem. Rev. 2013; 113: 4905
- 6b Binder WH, Kluger C. Curr. Org. Chem. 2006; 10: 1791
- 7 General Experimental Conditions for Cycloaddition/Cycloreversion for all New Compounds An oven-dried vial was charged with oxazinone (1 equiv), a magnetic stir bar, and dissolved in PhMe (1 M). The alkyne substrate (1.0–2.0 equiv) was added, the vial was sealed with a Teflon cap and placed in a warm aluminum block set to 110 °C. The reaction was stirred with heating overnight (12–18 h), cooled to rt, and concentrated. The ratio of pyridine products was estimated based on 1H NMR analysis of the unpurified reaction mixture. The resulting residue was purified by flash column chromatography on silica gel.
- 8 Experimental Conditions and Data for Compound 11a Oxazinone 6 (269 mg, 1.47 mmol) and bisalkyne 10a (428 mg, 2.20 mmol) were reacted following the general experimental conditions. 1H NMR analysis of the unpurified mixture revealed a single pyridine isomer (>19:1). Purification by flash column chromatography on silica gel (gradient elution: 5% EtOAc to 30% EtOAc in hexanes) gave 11a (599 mg, 1.41 mmol, 96% yield) as a colorless amorphous solid. TLC (10% EtOAc in hexanes), Rf = 0.21 (UV, KMnO4). IR (film): 2963, 1739, 1112 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.12 (s, 1 H), 4.03 (s, 2 H), 3.71 (s, 3 H), 2.53 (s, 3 H), 0.37–0.36 (m, 9 H), 0.25–0.23 (m, 9 H). 13C NMR (100 MHz, CDCl3): δ = 170.9, 156.0, 155.6, 152.5, 126.5, 121.3, 103.9, 102.9, 51.9, 42.9, 24.5, –0.4, –1.7. HRMS: m/z calcd for C17H27NO2Si2Na+: 356.1473; found: 356.1472.
- 9 Deng J.-C, Chuang S.-C. Org. Lett. 2014; 16: 5792
- 10 Rama Rao AV, Reddy SP, Reddy ER. J. Org. Chem. 1986; 51: 4158
- 11 Park H, Edgar LJ, Lumba MA, Willis LM, Nitz M. Org. Biomol. Chem. 2015; 13: 7027
- 12 Hale EA, Ryan HM, McOsker AM, Funk CM, Green LC, Mazur LE, Uthappa DM, Flood BM, Young DD, Hinkle RJ. ChemMedChem 2022; 17: e20220045