# Continuous flow unlocks modular ketones assembly enabled by dynamic orbital selection

## TL;DR

A new continuous-flow method enables efficient and scalable synthesis of diverse ketones using a dynamic orbital selection mechanism.

## Contribution

A scalable continuous-flow metallaphotoredox catalytic strategy for ketone synthesis with broad substrate scope and no need for oxidative addition.

## Key findings

- The method enables cross-coupling of aldehydes and carboxylic acids without stoichiometric redox reagents.
- It achieves excellent functional group tolerance and access to sterically hindered ketones.
- A 100 gram-scale synthesis in 24 hours demonstrates its scalability and practicality.

## Abstract

Cross-coupling based on diverse structural motifs offers a powerful strategy for ketone synthesis. However, existing methodologies are often hampered by a narrow substrate scope, non-neutral redox conditions, and poor scalability, particularly for sterically hindered ketones. Herein, we have developed a continuous-flow metallaphotoredox catalytic strategy driven by a dynamic orbital selection mechanism, leveraging the differential bond dissociation energies between various radicals and the metal. This approach enables efficient cross-coupling of aldehydes and carboxylic acids without the need for oxidative addition steps, thereby circumventing the reliance on stoichiometric redox reagents. It demonstrates broad substrate compatibility and excellent functional group tolerance, allowing access to a wide range of ketones, including highly sterically congested frameworks. Notably, the implementation of continuous-flow technology significantly enhances process efficiency and scalability. A successful 100 gram-scale conversion conducted in a flow microreactor within 24 h further underscores the potential of continuous-flow photocatalysis as a sustainable platform for organic synthesis.

A continuous-flow metallaphotoredox platform enables access to diverse aliphatic ketones via a dynamic orbital selection mechanism, with its practical applicability demonstrated by a successful 100 gram-scale synthesis.