转自：康龙化成

Photochemical Permutation of Thiazoles,Isothiazoles and Other Azoles

BaptisteRoure1,2, Maialen Alonso2,7, Giovanni Lonardi2,7, Dilara Berna Yildiz2,3, Cornelia S. Buettner2, Thiago dos Santos2, Yan Xu2,4, Martin Bossart5, Volker Derdau5, María Méndez5, Josep Llaveria6, Alessandro Ruffoni2* & DanieleLeonori2*

1 Department of Chemistry, Universityof Manchester, Manchester, UK. 

2 Instituteof Organic Chemistry, RWTH Aachen University, Aachen, Germany. 

3 Department of Chemistry, Faculty ofScience, Gazi University, Teknikokullar, Turkey. 4 College of Chemistry andEnvironmental Engineering, Shenzen University, Shenzhen, China. 

5 Integrated Drug Discovery, R&D,Sanofi Germany, Frankfurt am Main, Germany. 

6 Global Discovery Chemistry,Therapeutics Discovery, Janssen-Cilag, Johnson & Johnson InnovativeMedicine, Toledo, Spain. 

7 Theseauthors contributed equally: Maialen Alonso, Giovanni Lonardi.

—Nature, 2025, 10.1038/s41586-024-08342-8

Recommended by Rui Jin _ MC5 

\KEYWORDS: photochemistry,skeletal editing, chemical permutation (反应类型), C(sp2)-S, C(sp2)-N, S-N（成键类型）, thiazoles, isothiazoles (原料), benzo[d]isothiazole, indazole, pyrazole, isoxazole (产物)

ABSTRACT: Alessandro Ruffon i& Daniele Leonori et al. report a conceptually different approach in which photochemical irradiation can be used to alter the structure of thiazoles and isothiazoles in a selective and predictable manner. On photoexcitation, these derivatives populate their π,π* singlet excited states that undergo a series of structural rearrangements, leading to an overall permutation of the cyclic system and its substituents. Preliminary findings also show the potential for extending this method to other azole systems, including benzo[d]isothiazole, indazole, pyrazole and isoxazole. This strategy establishes photochemical permutation as a powerful and convenient method for the preparation of complex and difficult-to-access derivatives from more available structural isomers.

Background and this work: Syntheticstrategies for thiazole and isothiazole preparation versus a permutation concept

Permutation of Ph-substituted thiazolesand isothiazoles

Permutation of disubstituted thiazolesand isothiazoles:  (a) Ph- and Me-disubstituted thiazoles and isothiazoles, (b)disubstituted thiazoles

Permutation chemistry of (a)trisubstituted thiazoles, (b) bicylic thiazoles and (c) other azoles

Permutation chemistry of bioactive molecules

Proposed mechanism

Alessandro Ruffoni & Daniele Leonori et al. reporta conceptually different approach in which photochemical irradiation can beused to alter the structure of thiazoles and isothiazoles in aselective and predictable manner. On photoexcitation, these derivativespopulate their π,π* singlet excited states that undergo aseries of structural rearrangements, leading to an overall permutation of thecyclic system and its substituents. Preliminary findings also show thepotential for extending this method to other azole systems, including benzo[d]isothiazole,indazole, pyrazole and isoxazole. This strategy establishes photochemicalpermutation as a powerful and convenient method for the preparation of complexand difficult-to-access derivatives from more available structural isomers.

亚琛工业大学有机化学研究所Alessandro Ruffoni& Daniele Leonori课题组报道了一类光化学噻唑和异噻唑骨架编辑方法，利用光激发使底物分子轨道跃迁到π,π*单线态激发态后，可以使它们的骨架发生选择性重排得到苯并异噻唑、吲唑、吡唑和异噁唑等化合物。该反应条件温和，底物适用范围广，可用于生物活性分子的后期修饰，是制备杂环衍生物的一种强大而便捷的方法。

（转自：康龙化成）