Micelle-Mediated Chemistry in Water for the Synthesis of Drug Candidates

Abstract

Micellar reaction conditions, in a predominantly aqueous medium, have been developed for transformations commonly used by synthetic chemists working in the pharmaceutical industry to discover and develop drug candidates. The reactions covered in this review are the Suzuki–Miyaura, Miyaura borylation, Sonogashira coupling, transition-metal-catalysed C_Ar–N coupling, S_NAr, amidation, and nitro reduction. Pharmaceutically relevant examples of these applications will be used to show how micellar conditions can offer advantages in yield, operational ease, amount of waste generated, transition-metal catalyst loading, and safety over the use of organic solvents, irrespective of the setting in which they are used.

1 Introduction

2 Micelles as Solubilising Agents

3 Micelles as Nanoreactors

4 Designer Surfactants

5 A Critical Evaluation of the Case for Chemistry in Micelles

6 Scope of Review

7 Suzuki–Miyaura Coupling

8 Miyaura Borylation

9 Sonogashira Coupling

10 Transition-Metal-Catalysed C_Ar–N Couplings

11 S_NAr

12 Amidation

13 Nitro Reduction

14 Micellar Sequences

15 Summary and Outlook

Key words

amphiphile - micelle - pharmaceutical - surfactant - Suzuki–Miyaura - TPGS-750-M

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