# Cobalt-catalyzed alkyne silylamidation unlocks Z-selective unnatural dehydropeptides synthesis

## TL;DR

A new cobalt-catalyzed method enables the efficient and selective synthesis of diverse unnatural dehydropeptides with potential applications in medicinal chemistry.

## Contribution

A modular cobalt-catalyzed silylamidation method for Z-selective synthesis of non-canonical sila-dehydropeptides with high regio- and stereoselectivity.

## Key findings

- The method allows for efficient peptide ligation with Z/E-stereoselectivity and diastereoretentive control.
- It exhibits broad substrate scope and excellent functional group compatibility.
- The approach enables late-stage diversification of pharmaceutical molecules.

## Abstract

Due to their unique conformational properties and activities, dehydropeptides play a pivotal role in the fields of biological and medicinal chemistry. Yet, the synthesis of unnatural dehydropeptides still suffers from cumbersome steps and less generality, in particular, with rather limited structural diversity. Herein, a modular cobalt-catalyzed 1,2-silylamidation of non-conjugated alkynes with dioxazolones and silylzinc pivalates is disclosed, thus affording structurally diverse non-canonical sila-dehydropeptides with complete control of regio- and stereoselectivity. Notably, the reaction enables efficient peptide ligation between peptide-containing dioxazolones and peptide-containing alkynes in a Z/E-stereoselective and diastereoretentive manner. Moreover, broad substrate scope, outstanding functional group compatibility, as well as facile late-stage diversifications of pharmaceutically active molecules substantiate the synthetic value of this method.

Regio- and stereoselective cobalt-catalyzed silylative peptide-ligation of non-conjugated alkynes with dioxazolones and silylzinc pivalates unlocks Z-selective unnatural sila-dehydropeptides synthesis.