# Photo‐Accelerated Synthesis of Oligo(triazole amide)s

## TL;DR

This paper introduces a faster method for making oligo(triazole amide)s using light to speed up a key chemical reaction.

## Contribution

A photo-assisted CuAAC method is introduced to significantly reduce reaction times in solid-phase synthesis.

## Key findings

- 30 mol% photoinitiator enabled quantitative reactions in 8 minutes in model experiments.
- Solid-phase synthesis achieved quantitative CuAAC in one hour, twice as fast as previous methods.
- Oligo(triazole amide)s of varying lengths were successfully synthesized using optimized conditions.

## Abstract

A photo‐assisted process is explored for improving the synthesis of oligo(triazole amide)s, which are prepared by solid phase synthesis using a repeated cycle of two reactions: amine‐carboxylic acid coupling and copper‐catalyzed azide‐alkyne cycloaddition (CuAAC). The improvement of the second reaction is investigated herein. A catalytic system involving Cu(II)Cl2, N,N,N’,N″,N″‐pentamethyldiethylenetriamine (PMDETA) and a titanocene photoinitiator is explored for reducing the reaction time of CuAAC. This catalyst is first tested on a model reaction involving phenylacetylene and ethyl azidoacetate in DMSO. The kinetics of these model experiments are monitored by 1H NMR in the presence of different concentrations of the photoinitiator. It is found that 30 mol% of photoinitiator leads to quantitative reactions in only 8 min. These conditions are then applied to the solid phase synthesis of oligo(triazole amide)s, performed on a glycine‐loaded Wang resin. The backbone of the oligomers is constructed using 6‐heptynoic acid and 1‐amino‐11‐azido‐3,6,9‐trioxaundecane as submonomers. Due to slow reagent diffusion, the CuAAC step required more time in the solid phase than in solution. Yet, one hour only is necessary to achieve quantitative CuAAC on the resin, which is twice as fast as previously‐reported conditions. Using these optimized conditions, oligo(triazole amide)s of different length are prepared.

A photo‐assisted process is explored to improve the time‐consuming copper‐catalyzed azide‐alkyne cycloaddition step used in the solid‐phase synthesis of oligo(triazole amide)s. Employing a Cu(II)Cl2/PMDETA complex and a titanocene photoinitiator, reaction times are significantly reduced. Model reaction and solid‐phase synthesis experiments evidence that the use of 30 mol% of photoinitiator as compared to Cu(II) led to fast and efficient oligo(triazole amide) synthesis.