SEBASTIAN BRAUCH*, ZHIPENG WANG, MATTHIJS C. M. VAN OERS, JAN C. M. VAN HEST* FLORIS P. J. T. RUTJES*
*Corresponding authors
Radboud University Nijmegen, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands

Abstract

Inspired by biosynthetic processes in nature, chemists increasingly design processes such that no longer single steps, but sequences of multiple steps are being conducted in a single reaction vessel. This does not only lead to lower costs (fewer workup steps are required), but additionally reactions with unfavourable equilibria, can be driven to full conversion if they are incorporated in a sequence of multiple steps. However, the multiple reagents and catalysts that are required in such multistep sequences often suffer from incompatibilities: they either interfere with each other, or may not be compatible with the solvent that is used. In this article we describe how supramolecular assemblies can be used to solve these issues. In particular the use of polymersomes, permeable nanoparticles that are composed of amphiphilic polymers, will be highlighted to physically separate different catalyst systems and to enhance phase separation, thereby enabling multiple reactions in one pot.

INTRODUCTION

In recent years, catalytic one-pot cascade reactions have attracted considerable attention in both academia and industry because of their great viability to access highly complex structures in a rapid and highly efficient manner. In general, such cascade reactions are composed of at least two successive catalytic transformations which proceed under the same reaction conditions, thus reducing the amount of intermediate steps, functional group (protective group) manipulations and purification steps required to obtain complex architectures otherwise produced in laborious multi-step procedures, generating significant higher amounts of waste (1−4). In order to create a well working cascade, several considerations regarding each individual transformation combined in a one-pot fashion have to be taken into account first:

1) Solvent incompatibilities – How does the solvent affect the stability and/or performance of the catalyst? Does the solvent have any influence on the stability of the formed reactive intermediates? Are the starting materials/products sufficiently soluble in the solvent?

2) Competing reactivities – Does deact ...