March 3, 2026Open Access

Telescopic Synthesis of Triazol‐4‐yl Modified Phenylalanine Conjugates and Peptide Modification Using a Sonogashira Domino Strategy at Room Temperature

Key Points

The synthesis achieved excellent chiral integrity and 100% 1,4-regioselectivity, contributing to effective peptide modifications.
Using a telescopic approach, the method integrates Sonogashira coupling with click chemistry to improve efficiency.
A wide array of aromatic and heteroaromatic methyl bromides were successfully accommodated in the synthesis process.
The findings highlight the scalability of this synthesis method, which may enable broader applications in biochemistry.

Abstract

We report a telescopic two‐step synthetic strategy for efficiently constructing 1 H ‐1,2,3‐triazol‐4‐yl modified phenylalanine conjugates. The method combines Sonogashira coupling and a one‐pot domino reaction involving desilylation, azidation, and click chemistry. This protocol enhances the potential for peptide modification and facilitates the synthesis of polyazide derivatives that can be suitable for dendrimeric cores. This reaction yields good results and provides a scalable route, successfully accommodating a wide range of aromatic and heteroaromatic methyl bromides, while achieving excellent chiral integrity and 100% 1,4‐regioselectivity. We also explored the application of a 1,4‐disubstituted 1 H ‐1,2,3‐triazol‐4‐yl phenylalanine conjugate as a directing group for C(sp 2 )‐H di‐halogenation.

Telescopic Synthesis of Triazol‐4‐yl Modified Phenylalanine Conjugates and Peptide Modification Using a Sonogashira Domino Strategy at Room Temperature

Key Points

Abstract

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