# Mannich reaction with organozinc reagents in continuous flow: experimental and computational studies

## TL;DR

The paper describes a continuous flow method for performing a Mannich reaction using organozinc reagents, which speeds up the reaction and improves efficiency.

## Contribution

A fully continuous flow system for the Mannich reaction using in-situ generated organozinc reagents is developed.

## Key findings

- Highly substituted amine products were obtained in moderate to good yields under mild conditions.
- Reaction times were significantly reduced to as little as 5 minutes.
- DFT studies suggest organometallic dimers act as nucleophiles via an SN1 pathway.

## Abstract

Herein, we report a fully continuous flow version of a Mannich reaction using organozinc reagents. These organometallics were generated in situ in a packed-bed reactor and subsequently introduced in a 1 mL chip to react with an array of substituted aldehydes and primary amines. The highly substituted amine products were obtained in moderate to good yields within 5 minutes and under mild conditions, thereby reducing reaction times. DFT studies suggest the participation of organometallic dimers as nucleophiles, responsible for C–C bond formation through an SN1 reaction pathway.

Fully continuous flow version of a Mannich reaction using organozinc reagents.