One-Pot Synthesis of Diverse γ-Lactam Scaffolds Facilitated by a Nebulizer-Based Continuous Flow Photoreactor

Abstract

The use of a modified prototype continuous flow reactor (CFR) as a pivotal part of a number of versatile singlet oxygen-mediated reaction sequences is presented herein. These sequences target rapid access to structural complexity and diversity. The prototype reactor achieves high conversions and productivities by attaining large specific surface areas for these biphasic reactions. In the reactor, the reaction solution is nebulized (using either oxygen or air) and the resulting aerosol is irradiated by an LED jacket that surrounds the Pyrex reaction chamber. The one pot procedures developed herein are, according to many different criteria, both highly efficient and green. The key common intermediates and the source of both the complexity and variety of the final products are N-acyl imminium ions (NAI; protonated N-acyl enamines). The initial substrates are simple and readily accessible furans and the diverse array of products is composed of different complex γ-lactams. Many of the products are of particular interest due to their close relationships to known biologically active molecules.

Keywords: Aerosol; N-acyl imminium; continuous flow reactor; nebulizer; singlet oxygen.

Scheme 1

Rapid and scalable access to a diverse array of γ‐lactams.

Figure 1

Schematic representation of the NebPhotOX continuous flow reactor set‐up.