# Computational Insights into the Mechanism of Lewis Acid‐Catalyzed Alkene‐Aldehyde Coupling

## TL;DR

This paper uses computational methods to understand how a Lewis acid catalyzes the coupling of alkenes and aldehydes, revealing key steps and factors affecting the reaction.

## Contribution

The study identifies a steric clash-driven enantioselective hydride shift and explains why longer alkyl chains hinder the reaction.

## Key findings

- An enantioselective transannular [1,5]-hydride shift occurs during the reaction.
- Steric clashes in the cyclization step determine the reaction's enantioselectivity.
- Longer alkyl chains hinder cyclization, preventing the reaction from proceeding.

## Abstract

The Lewis acid‐catalyzed coupling of alkenes and aldehydes presents a modern, versatile synthetic alternative to classical carbonyl addition chemistry, offering exceptional regio‐ and stereoselectivity. In this work, we present a comprehensive computational investigation into the reaction mechanism of this transformation. Our findings confirm the occurrence of an enantioselective transannular [1,5]‐hydride shift step and demonstrate that the enantioselectivity of the reaction arises predominantly from steric clashes between functional groups in the cyclization step. Combining computational and experimental results, we establish that the Lewis acid catalyst facilitates the initial C−O coupling step between the alkene and the activated aldehyde. Investigations into systems with longer alkyl chains reveal that while they follow a similar mechanistic pathway, cyclization becomes kinetically hindered, preventing the reaction from proceeding. These insights illuminate the factors governing reaction outcomes and limitations, paving the way for future developments in this area.

The reaction mechanism of an enantioselective Lewis acid‐catalyzed coupling of an alkene and an aldehyde was investigated using DFT methods. The study revealed two key steps in the transformation: cyclization and a hydride shift. Attempts with an alkene substrate bearing a longer alkyl chain failed to yield the expected product. Further computational analysis revealed that this experimental outcome is due to a hindered cyclization step