Self-selection in olefin cross-metathesis: the effect of remote functionality

Area of Science:

• Organic Chemistry
• Catalysis
• Polymer Science

Background:

• Dynamic combinatorial libraries (DCLs) are crucial for drug discovery and materials science.
• Olefin cross-metathesis (CM) offers a potential route to DCLs due to its ability to form new carbon-carbon bonds.
• The utility of CM for DCLs hinges on its insensitivity to remote functional groups.

Purpose of the Study:

• To investigate the influence of remote functionality on olefin cross-metathesis (CM) reactions.
• To assess the feasibility of using CM for generating dynamic combinatorial libraries (DCLs).
• To explore unusual reactivity patterns in CM, such as cis-selectivity.

Main Methods:

• Synthesis of a series of allyl- and homoallylamides with varying remote functionalities.
• Execution of olefin cross-metathesis (CM) reactions using these substrates.
• Analysis of reaction course and product distribution to determine the impact of remote functionality.

Main Results:

• CM reactions involving the studied amides were found to be strongly dependent on remote functionality.
• This dependence challenges the requirement for insensitivity in CM for DCL production.
• An unusual case of cis-selective CM was observed and reported.

Conclusions:

• The strong influence of remote functionality on CM reactions limits their direct application for creating robust DCLs.
• Further research is needed to develop CM methodologies that are less sensitive to structural variations.
• The discovery of cis-selective CM opens new avenues for stereoselective synthesis.