Synthesis and Facile Dearomatization of Highly Electrophilic Nitroisoxazolo[4,3-]pyridines

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2020 May 14

PMID 32397095

Authors

Maxim A Bastrakov

Alexey K Fedorenko

Alexey M Starosotnikov

Ivan V Fedyanin

Vladimir A Kokorekin

Affiliations

Soon will be listed here.

Abstract

A number of novel 6-R-isoxazolo[4,3-]pyridines were synthesized and their reactions with neutral C-nucleophiles (1,3-dicarbonyl compounds, π-excessive (het)arenes, dienes) were studied. The reaction rate was found to be dependent on the nature of the substituent 6-R. The most reactive 6-nitroisoxazolo[4,3-]pyridines are able to add C-nucleophiles in the absence of a base under mild conditions. In addition, these compounds readily undergo [4+2]-cycloaddition reactions on aromatic bonds C=C(NO) of the pyridine ring, thus indicating the superelectrophilic nature of 6-NO-isoxazolo[4,3-]pyridines.

References

Gryl M, Seidler T, Wojnarska J, Stadnicka K, Matulkova I, Nemec I . Co-Crystals of 2-Amino-5-Nitropyridine Barbital with Extreme Birefringence and Large Second Harmonic Generation Effect. Chemistry. 2018; 24(35):8727-8731. DOI: 10.1002/chem.201802057. View

Le S, Asahara H, Nishiwaki N . An Alternative Synthetic Approach to 3-Alkylated/Arylated 5-Nitropyridines. J Org Chem. 2015; 80(17):8856-8. DOI: 10.1021/acs.joc.5b01391. View

Makosza M . Nucleophilic substitution of hydrogen in electron-deficient arenes, a general process of great practical value. Chem Soc Rev. 2010; 39(8):2855-68. DOI: 10.1039/b822559c. View

Nepali K, Lee H, Liou J . Nitro-Group-Containing Drugs. J Med Chem. 2018; 62(6):2851-2893. DOI: 10.1021/acs.jmedchem.8b00147. View

Bruno I, Cole J, Kessler M, Luo J, Motherwell W, Purkis L . Retrieval of crystallographically-derived molecular geometry information. J Chem Inf Comput Sci. 2004; 44(6):2133-44. DOI: 10.1021/ci049780b. View

Sheldrick G . SHELXT - integrated space-group and crystal-structure determination. Acta Crystallogr A Found Adv. 2014; 71(Pt 1):3-8. PMC: 4283466. DOI: 10.1107/S2053273314026370. View

Sheldrick G . Crystal structure refinement with SHELXL. Acta Crystallogr C Struct Chem. 2015; 71(Pt 1):3-8. PMC: 4294323. DOI: 10.1107/S2053229614024218. View

Makosza M . Reactions of nucleophiles with nitroarenes: multifacial and versatile electrophiles. Chemistry. 2014; 20(19):5536-45. DOI: 10.1002/chem.201400097. View

Krause L, Herbst-Irmer R, Sheldrick G, Stalke D . Comparison of silver and molybdenum microfocus X-ray sources for single-crystal structure determination. J Appl Crystallogr. 2015; 48(Pt 1):3-10. PMC: 4453166. DOI: 10.1107/S1600576714022985. View

10.

Starosotnikov A, Shkaev D, Bastrakov M, Fedyanin I, Shevelev S, Dalinger I . Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds. Beilstein J Org Chem. 2018; 13:2854-2861. PMC: 5753140. DOI: 10.3762/bjoc.13.277. View

11.

Lopez Ortiz F, Iglesias M, Fernandez I, Sanchez C, Gomez G . Nucleophilic dearomatizing (DNAr) reactions of aromatic C,H-systems. A mature paradigm in organic synthesis. Chem Rev. 2007; 107(5):1580-691. DOI: 10.1021/cr030207l. View

12.

Lakhdar S, Goumont R, Boubaker T, Mokhtari M, Terrier F . Nitrobenzoxadiazoles and related heterocycles: a relationship between aromaticity, superelectrophilicity and pericyclic reactivity. Org Biomol Chem. 2006; 4(10):1910-9. DOI: 10.1039/b602002j. View

13.

Wertjes W, Southgate E, Sarlah D . Recent advances in chemical dearomatization of nonactivated arenes. Chem Soc Rev. 2018; 47(21):7996-8017. DOI: 10.1039/c8cs00389k. View

14.

Romero D, Morge R, Biles C, May P, Palmer J, Johnson P . Discovery, synthesis, and bioactivity of bis(heteroaryl)piperazines. 1. A novel class of non-nucleoside HIV-1 reverse transcriptase inhibitors. J Med Chem. 1994; 37(7):999-1014. DOI: 10.1021/jm00033a018. View

15.

Korolev S, Kondrashina O, Druzhilovsky D, Starosotnikov A, Dutov M, Bastrakov M . Structural-Functional Analysis of 2,1,3-Benzoxadiazoles and Their N-oxides As HIV-1 Integrase Inhibitors. Acta Naturae. 2013; 5(1):63-72. PMC: 3612826. View

16.

Gao H, Shreeve J . Azole-based energetic salts. Chem Rev. 2011; 111(11):7377-436. DOI: 10.1021/cr200039c. View

17.

Parry R, Nishino S, Spain J . Naturally-occurring nitro compounds. Nat Prod Rep. 2010; 28(1):152-67. DOI: 10.1039/c0np00024h. View

18.

TERRIER , Sebban , Goumont , Halle , Moutiers , Cangelosi I . Dual behavior of 4-aza-6-nitrobenzofuroxan. A powerful electrophile in hydration and sigma-complex formation and a potential dienophile or heterodiene in diels-alder type reactions. J Org Chem. 2000; 65(22):7391-8. DOI: 10.1021/jo0005114. View