Organocatalysis and Biocatalysis Hand in Hand: Combining Catalysts in One‐Pot Procedures

Abstract

Multi‐step processes catalysed by several catalysts working concurrently have been developed in nature, thus improving reaction efficiency. The quest for novel and improved catalytic systems has led to the development of biocatalytic and later to organocatalytic procedures as very valuable tools in asymmetric synthesis while using mild reaction conditions in the absence of metal catalysts. As a timeless challenge, chemists are facing the need for process designs in which different sorts of catalysts can operate successfully in a one‐pot concurrent fashion. Likewise, such designs bring about the best of each catalyst and, in certain cases, enable us to improve problematic issues, such as reactivity, selectivity, solubility, inhibition, etc. Specifically, to combine these two types of catalysts in one‐pot, achieving high yields and selectivity, is a fascinating aspect of catalysis. This review covers representative advances in this field, in particular those in which biocatalysts and organocatalysts are employed either in sequential reactions or in simultaneous processes.

Enantioenriched Methylene‐Bridged Benzazocanes Synthesis by Organocatalytic and Superacid Activations

“…This hypothesis was further reinforced by exploring the reactivity of 3a with Lewis acids. Using two equivalents of metal triflates or halides resulted in the recovery of the staring material or in ac omplex mixture ( Table 1, entries [13][14][15][16]. Any attempts with excess of Lewis acid (50 equivalents of FeCl 3 )d id not allow to convert the model substrate 3a into the desired compound ( Table 1, entries [17][18].…”

Deracemisation Processes Employing Organocatalysis and Enzyme Catalysis

“…[3] Apart from those in which metal catalysts are involved, with ab orderline exception, [4] we will be focusing in the latest advances performed for the development of deracemisation methodsu sing enzymes and/or organocatalysts.T he applicationo fb othb iological systems (free enzymes or wholec ells), [5] and( relatively) small organic molecules,r espectively,a sc atalysts in organic synthesis, [6] has gained an increasing interest in the recent years, since they are able to carry out the preparation of valuable compounds under mild ande nvironmentally benign conditions.B othm ethodologies have been successfully combinedi no rder to develop novels ynthetic routes. [7] Deracemisation protocols have been gathered into four groups,a ccording to the process taking place for the preparation of the chiral compound, i.e., (i)d eracemisation by stereoinversion (DbI), (ii)l ineard eracemisation (LD), (iii)c yclic deracemisation (CyD), and (iv) enantioconvergent process (EC), as shown in Figure 1.…”

“…The application of both biological systems (free enzymes or whole cells), and (relatively) small organic molecules, respectively, as catalysts in organic synthesis, has gained an increasing interest in the recent years, since they are able to carry out the preparation of valuable compounds under mild and environmentally benign conditions. Both methodologies have been successfully combined in order to develop novel synthetic routes …”

Enabling protein-hosted organocatalytic transformations

“…Provided its bio-orthogonality, organocatalysis can be used in biological contexts for valuable chemical and biological applications. [10][11][12][13][14][15][16][17] For instance, organocatalysts can serve to mediate labelling of biomolecules, 11,12 analogous to existing approaches that use metals for reactions. [18][19][20] Also, it is worth considering to merge organocatalysis and biocatalysis for the production of chiral synthons in a one-pot and atom economic fashion.…”

“…[18][19][20] Also, it is worth considering to merge organocatalysis and biocatalysis for the production of chiral synthons in a one-pot and atom economic fashion. [13][14][15][16][17] However, there are only a few examples where organocatalysts function along with biomolecules or under biological conditions. In fact, taking into account the aqueous reaction medium, physiological pH (near 7.4) and temperature (near 37 C), 20 many of the reported organocatalysts do not function under biocompatible conditions.…”