Visible‐Light‐Mediated Click Chemistry for Highly Regioselective Azide–Alkyne Cycloaddition by a Photoredox Electron‐Transfer Strategy

Abstract

Click chemistry focuseso nt he development of highly selectiver eactionsu sing simple precursors for the exquisite synthesis of molecules. Undisputedly,t he Cu I -catalyzed azide-alkyne cycloaddition (CuAAC)i so ne of the most valuable examples of click chemistry, but it suffersf rom some limitations as it requires additional reducing agents and ligands as well as cytotoxic copper. Here, we demonstrate an ovel strategy for the azide-alkyne cycloaddition reaction that involves ap hotoredox electron-transfer radical mechanism insteado ft he traditional metal-catalyzed coordination process.T his newly developed photocatalyzeda zidealkyne cycloaddition reaction can be performed under mild conditions at room temperature in the presence of air and visiblel ight ands hows good functional group tolerance, excellenta tom economy, highy ields of up to 99 %, and absolute regioselectivity,a ffordingavariety of 1,4-disubstituted 1,2,3-triazole derivatives, including bioactive molecules and pharmaceuticals. The use of ar ecyclable photocatalyst,s olar energy, andw ater as solventm akes this photocatalytic systems ustainable and environmentally friendly.M oreover, the azide-alkyne cycloadditionr eaction could be photocatalyzed in the presenceo fametal-free catalyst with excellent regioselectivity,w hich represents an important development for click chemistry and should find versatile applicationsi n organic synthesis, chemical biology,and materials science.[a] Dr.Scheme1.Structures of 1,4-disubstituted 1,2,3-triazoles and strategies for their synthesis. (a) Bioactive molecules and pharmaceuticals based on the 1,4-disub-stituted1 ,2,3-triazole core. (b) The reported methodsf or the synthesis of 1,4-disubstituted 1,2,3-triazoles and the mechanism for the traditional metal-catalyzed AAC reaction. (c)Our designed strategy for the AAC reaction through photoredox electron-transfer cyclization and its features andadvantages, as well as the proposed mechanism.( Figure 1a). The recyclability of the photocatalystwas also evaluated and the resultsd emonstrate that the photocatalyst is air-and moisture-tolerant and can be readily recovered after use and reused severalt imes. Figure 1b shows that the photo-Scheme2.Scope of the PcAAC reaction.Standardreagents and conditions: Azide (0.2 mmol), alkyne (0.2 mmol), photocatalyst (5 mol %), DCM (2.0 mL), RT, air,6 -12 h, 26 Ww hite LED irradiation.

Plasmon-assisted click chemistry at low temperature: an inverse temperature effect on the reaction rate

“…In this case, a vibrational energy of 59 kJ mol À1 could lower the reaction barrier of the concerted process, but since it is much less than 124 kJ mol À1 required to reach TS, and this path cannot be responsible for the observed temperature dependence. We also briey considered the activation of the phenylacetylene substrate with hot holes, 19 analogous to the recently proposed photoredox AAC mechanism 50 (PW4 in Fig. 3A), and this pathway also did not lead to a substantial decrease of the reaction barrier and is thus likely not operative.…”

Role of Click Chemistry in Organic Synthesis

“…Recently, Wu et al [68] synthesized triazole analogs (36) through photo-redox electron-transfer mechanism. The authors inspected the reaction of benzyl azide with phenylacetylene using diverse photo-catalysts under ambient reaction conditions like room temperature (RT), air, and visible light irradiation.…”

An Overview on the Chemical N‐Functionalization of Sugars and Formation of N‐Glycosides

“…Recently Zheng and his co‐worker described an innovative strategy for the azide–alkyne cycloaddition reaction via a photoredox electron‐transfer radical mechanism in order to replace the traditional metal‐catalyzed coordination process as these process required additional reducing agents and ligands as well as cytotoxic copper (Scheme ) …”