A Metal‐Free Multicomponent Cascade Reaction for the Regiospecific Synthesis of 1,5‐Disubstituted 1,2,3‐Triazoles

Abstract

About specifics: A method for the regiospecific synthesis of the title compounds through an unprecedented Michael addition/deacylative diazo transfer/cyclization sequence has been established. The simple and practical method can be used for the modification of primary amines including chiral α‐amines. The process involves the formation three covalent bonds and the cleavage of two covalent bonds (see scheme, Ts=4‐toluenesulfonyl).

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

“…A multi-component cascade reaction to form the 1,5-regioisomer was also described. 26 This involved the use of primary amines, propynones and sulfonylazides.…”

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

“…20 Exploring this concept, an unprecedented methodology was developed comprising a Michael addition/deacylative diazotransfer/cyclization cascade utilizing primary amines, propynones, and sulfonyl azides in a single transformation (Scheme 9). This one-pot protocol afforded good yields for amines and alkynes functionalized with various functional groups (Scheme 9B).…”

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

“…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.…”

“…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] ).…”