A Metal‐Free Three‐Component Reaction for the Regioselective Synthesis of 1,4,5‐Trisubstituted 1,2,3‐Triazoles

Abstract

A metal-free three-component reaction to synthesize 1,4,5-trisubstituted 1,2,3-triazoles from readily available building blocks, such as aldehydes, nitroalkanes, and organic azides, is described. The process is enabled by an organocatalyzed Knoevenagel condensation of the formyl group with the nitro compound, which is followed by the 1,3-dipolar cycloaddition of the azide to the activated alkene. The reaction features an excellent substrate scope, and the products are obtained with high yield and regioselectivity. This method can be utilized for the synthesis of fused triazole heterocycles and materials with several triazole moieties.

New click-chemistry methods for 1,2,3-triazoles synthesis: recent advances and applications

“…A three-component reaction between an aldehydes, a nitroalkane and an azides have also been reported. 25 The procedure shows good functional group tolerance leading to functionalized triazoles from inexpensive and commercially available starting materials. A multi-component cascade reaction to form the 1,5-regioisomer was also described.…”

Emerging approaches for the synthesis of triazoles: beyond metal-catalyzed and strain-promoted azide–alkyne cycloaddition

“…As was demonstrated by the Dehaen group, sequential nitroalkene formation and addition of organic azides in a single reaction vessel can generate 1,4,5-TTs. 34 Hence, the entire sequence can be carried out as a multicomponent type reaction (Scheme 17). As depicted in Scheme 17B, this protocol presents a broad substrate tolerability in terms of aldehydes, nitroalkanes and azides.…”

Azide–Enolate 1,3‐Dipolar Cycloaddition as an Efficient Approach for the Synthesis of 1,5‐Disubstituted 1,2,3‐Triazoles from Alkyl/Aryl Azides and β‐Ketophosphonates

“…Background and proposed approach to the synthesis of 1,5-disubstituted 1,2,3-triazoles involving the coupling of azide derivatives with certain substrates (ref. [7,[22][23][24][25][26] ) as well as synthesis by azide-free reactions (ref. [20,21] ).…”

“…From increasingly common reports on synthetic methods to obtain 1,5-disubstituted 1,2,3-triazole moieties, general methods can be sorted as (1) the cycloaddition of primary amines with α-chlorotosylhydrazones [Scheme 3, Equation (f )] [20] or with enaminones/tosylhydrazine [Scheme 3, Equation (g)] [21] and (2) the coupling of azide substrates with alkynes [Scheme 3, Equation (h)], [22] vinyl electronwithdrawing group substrates [Scheme 3, Equation (i)], [23] allenylmagnesium bromides [Scheme 3, Equation (j)], [24] amines/propynones [Scheme 3, Equation (k)], [25] and aldehydes/nitromethane [Scheme 3, Equation (l)]. [26] Thus, the development of an efficient synthesis of these nitrogen heterocycles is of increasing importance.…”