Organocatalysts for enantioselective synthesis of fine chemicals: definitions, trends and developments

Chiara Palumbo,Matteo Guidotti

doi:10.14293/s2199-1006.1.sor-chem.agziib.v1

Abstract

Abstract Organocatalysis, that is the use of small organic molecules to catalyse organic transformations, has been included among the most successful concepts in asymmetric catalysis and it has been used for the enantioselective construction of C-C, C-N, C-O, C-S, C-P and C-halide bonds. Since the seminal works in early 2000, the scientific community has been paying an ever-growing attention to the use of organocatalysts for the synthesis, with high yields and remarkable stereoselectivities, of optically active fine chemicals of interest for the pharmaceutical industry. A brief overview is here presented about the two main classes of substrate activation by the catalyst: covalent organocatalysis and non-covalent organocatalysis, with a more stringent focus on some recent outcomes in the field of the latter and of hydrogen-bond-based catalysis. Finally, some successful examples of heterogenisation of organocatalysts are also discussed, in the view of a potential industrial exploitation.

Highlights

ASYMMETRIC SYNTHESIS: THE QUERY AND THE OFFER The observation of symmetry and asymmetry in bodies and, in general, in the whole universe is an ancient matter [1]
Among the well-known methods for asymmetric synthesis, catalysis gained an ever-growing success since it presents many advantages with respect to the traditional wasteful stoichiometric methods: the catalyst is used at low or very low loading, the starting material does not need to come from the chiral pool, and the synthesis does not require extra steps for the installation and removal of a chiral auxiliary
Many patents have already been disclosed on enantioselective organocatalytic transformations and this is a clear clue of the relevant potential of the technique [96,97,98,99]

Summary

INTRODUCTION

ASYMMETRIC SYNTHESIS: THE QUERY AND THE OFFER The observation of symmetry and asymmetry in bodies and, in general, in the whole universe is an ancient matter [1]. Guidotti: Organocatalysts for enantioselective synthesis of fine chemicals identified on the mechanistic basis: (i) covalent organocatalysis and (ii) non-covalent organocatalysis [26] In the former case, within the catalytic cycle, the catalyst covalently binds the substrate, in the latter case only noncovalent interactions, such as hydrogen bonding (H-bonding) or the formation of ion pairs, activate the molecule towards the asymmetric transformation (Figure 4) [27]. With this brief review contribution, we would like to give a sketchy overview on both types of activation modes, subsequently focusing on some recent outcomes in the field of noncovalent organocatalysis

Covalent organocatalysis

Findings

Brønsted acid catalysis