Synthesis of Unsymmetrically Tetrasubstituted Pyrroles and Studies of AIEE in Pyrrolo[1,2-]pyrimidine Derivatives

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2022 Jun 13

PMID 35694357

Authors

Taian Li

Mong-Feng Chiou

YaJun Li

Changqing Ye

Min Su

Mengyu Xue

Xiaobin Yuan

Chuanchuan Wang

Wen-Ming Wan

Daliang Li

Hongli Bao

Affiliations

Soon will be listed here.

Abstract

Pyrroles are among the most important heterocycles in pharmaceuticals and agrochemicals. Construction of pyrrole scaffolds with different substituents and a free NH group, however, is challenging. Herein, a metal-free method for the synthesis of unsymmetrically tetrasubstituted NH-pyrroles using a consecutive chemoselective double cyanation is reported. The desired pyrroles were obtained with yields up to 99% and good functional group tolerance. Mechanistic studies identified a reaction mechanism that features a subtle sequence of first cyano-addition and migration, followed by cyano-addition and aromatization to afford the pyrrole skeleton. Pyrrolo[1,2-]pyrimidines are synthesized as the synthetic applications of NH-pyrroles, and these pyrrolo[1,2-]pyrimidines exhibit unpredicted time-dependent aggregation-induced emission enhancement (AIEE) properties.

Citing Articles

Metal-Free Catalyzed Oxidation/Decarboxylative [3+2] Cycloaddition Sequences of 3-Formylchromones to Access Pyrroles with Anti-Cancer Activity.

Li X, Chen X, Fan B, Yu Q, Lei J, Xu Z Molecules. 2023; 28(22).

PMID: 38005323 PMC: 10673291. DOI: 10.3390/molecules28227602.

Recent Advances in Synthetic Routes to Azacycles.

Nguyen A, Kim H Molecules. 2023; 28(6).

PMID: 36985708 PMC: 10054516. DOI: 10.3390/molecules28062737.

References

Xuan J, Xia X, Zeng T, Feng Z, Chen J, Lu L . Visible-light-induced formal [3+2] cycloaddition for pyrrole synthesis under metal-free conditions. Angew Chem Int Ed Engl. 2014; 53(22):5653-6. DOI: 10.1002/anie.201400602. View

Ye C, Jiao Y, Chiou M, Li Y, Bao H . Direct synthesis of pentasubstituted pyrroles and hexasubstituted pyrrolines from propargyl sulfonylamides and allenamides. Chem Sci. 2021; 12(26):9162-9167. PMC: 8261710. DOI: 10.1039/d1sc02090k. View

Zhang J, He B, Hu Y, Alam P, Zhang H, Lam J . Stimuli-Responsive AIEgens. Adv Mater. 2021; 33(32):e2008071. DOI: 10.1002/adma.202008071. View

Torres G, Quesnel J, Bijou D, Arndtsen B . From Aryl Iodides to 1,3-Dipoles: Design and Mechanism of a Palladium Catalyzed Multicomponent Synthesis of Pyrroles. J Am Chem Soc. 2016; 138(23):7315-24. DOI: 10.1021/jacs.6b02314. View

Bauer I, Knolker H . Synthesis of pyrrole and carbazole alkaloids. Top Curr Chem. 2011; 309:203-53. DOI: 10.1007/128_2011_192. View

Li J, Zhou B, Tian Y, Jia C, Xue X, Zhang F . Potassium Acetate-Catalyzed Double Decarboxylative Transannulation To Access Highly Functionalized Pyrroles. Org Lett. 2020; 22(24):9585-9590. DOI: 10.1021/acs.orglett.0c03621. View

Jiang Y, Chan W, Park C . Expedient synthesis of highly substituted pyrroles via tandem rearrangement of α-diazo oxime ethers. J Am Chem Soc. 2012; 134(9):4104-7. DOI: 10.1021/ja300552c. View

Li B, Wang N, Liang Y, Xu S, Wang B . Ruthenium-catalyzed pyrrole synthesis via oxidative annulation of enamides and alkynes. Org Lett. 2012; 15(1):136-9. DOI: 10.1021/ol303159h. View

Zhuang C, Zhang W, Sheng C, Zhang W, Xing C, Miao Z . Chalcone: A Privileged Structure in Medicinal Chemistry. Chem Rev. 2017; 117(12):7762-7810. PMC: 6131713. DOI: 10.1021/acs.chemrev.7b00020. View

10.

Kilani J, Fillinger S . Phenylpyrroles: 30 Years, Two Molecules and (Nearly) No Resistance. Front Microbiol. 2016; 7:2014. PMC: 5159414. DOI: 10.3389/fmicb.2016.02014. View

11.

Huffman J, Padgett L . Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes. Curr Med Chem. 2005; 12(12):1395-411. DOI: 10.2174/0929867054020864. View

12.

Young I, Thornton P, Thompson A . Synthesis of natural products containing the pyrrolic ring. Nat Prod Rep. 2010; 27(12):1801-39. DOI: 10.1039/c0np00014k. View

13.

Wang L, Ackermann L . Versatile pyrrole synthesis through ruthenium(II)-catalyzed alkene C-H bond functionalization on enamines. Org Lett. 2012; 15(1):176-9. DOI: 10.1021/ol303224e. View

14.

Zheng X, Liu W, Zhang D . Recent Advances in the Synthesis of Oxazole-Based Molecules via van Leusen Oxazole Synthesis. Molecules. 2020; 25(7). PMC: 7180750. DOI: 10.3390/molecules25071594. View

15.

Chen M, Li L, Nie H, Tong J, Yan L, Xu B . Tetraphenylpyrazine-based AIEgens: facile preparation and tunable light emission. Chem Sci. 2017; 6(3):1932-1937. PMC: 5501095. DOI: 10.1039/c4sc03365e. View

16.

Gholap S . Pyrrole: An emerging scaffold for construction of valuable therapeutic agents. Eur J Med Chem. 2016; 110:13-31. DOI: 10.1016/j.ejmech.2015.12.017. View

17.

Rostami Osanloo M, Saadat A, Van de Put M, Laturia A, Vandenberghe W . Transition-metal nitride halide dielectrics for transition-metal dichalcogenide transistors. Nanoscale. 2021; 14(1):157-165. DOI: 10.1039/d1nr05250k. View

18.

Tan W, Ong Y, Yoshikai N . Synthesis of Highly Substituted Pyridines through Copper-Catalyzed Condensation of Oximes and α,β-Unsaturated Imines. Angew Chem Int Ed Engl. 2017; 56(28):8240-8244. DOI: 10.1002/anie.201704378. View

19.

Chand K, Rajeshwari , Hiremathad A, Singh M, Santos M, Keri R . A review on antioxidant potential of bioactive heterocycle benzofuran: Natural and synthetic derivatives. Pharmacol Rep. 2017; 69(2):281-295. DOI: 10.1016/j.pharep.2016.11.007. View

20.

Gomes M, Muratov E, Pereira M, Peixoto J, Rosseto L, Cravo P . Chalcone Derivatives: Promising Starting Points for Drug Design. Molecules. 2017; 22(8). PMC: 6152227. DOI: 10.3390/molecules22081210. View