Chemoenzymatic Cascades Combining Biocatalysis and Transition Metal Catalysis for Asymmetric Synthesis

Abstract

The combination of catalytic methods provides multiple advantages in organic synthesis, allowing access to diverse organic molecules in a straightforward manner. Merging metal and enzyme catalysis is currently receiving great attention due to the possibility to assemble metal catalysis in CÀ C coupling, olefin metathesis, hydration and other reactions with the exquisite stereospecificity displayed by enzymes. Thus, this minireview is organized based on the action of the metal species (Pd, Ru, Au, Ir, Fe…) in combination with different enzymes. Special attention will be paid to the design of sequential processes and concurrent cascades, presenting solutions such as the use of surfactants or compartmentalization strategies for those cases where incompatibilities could hamper the overall process.

Development of an amine transaminase-lipase cascade for chiral amide synthesis under flow conditions

“…These strategies could improve the bienzymatic approach outcome. 7,8,47,48 To achieve good results, the immobilised ArRmut11ATA and CALB were packed in separate PBR, compartmentalising and segregating them. The implementation of the flow setup resulted in a great improvement of the metrics (up to 3.4-fold for productivity) towards the enantiopure (R)-amide when compared to the equivalent batch cascade in a stepwise approach.…”

Status check: biocatalysis; its use with and without chemocatalysis. How does the fine chemicals industry view this area?

“…In terms of recognized potential for merging bio- and chemo-catalysis, concrete examples reported using physical or chemical compartmentalization were offered to the interviewees with some of the seminal work as already described in the literature. 8 The relatively recent literature on the topic 3,9 can make the field of chemoenzymatic catalysis difficult to grasp for non-experts and non-practitioners. Nonetheless, the perception was that it is no longer considered low hanging-fruit to just improve sustainability performance by recognizing an obvious need for improvement in this area, and then to rapidly design a suitable strategy to generate those improvements.…”

“…Several review articles point out that these two approaches to organic synthesis, while previously considered occupants of separate worlds, have actually been in hand for years. 3,9…”

“…Chemocatalysis and biocatalysis are no longer in “separate worlds”. 3,9,29 h They both rely on the secrets of Nature, and share the common denominator that has been with us since the beginning of time: water.…”

From oximes to tertiary alcohols in water, at room temperature and under air: a hybrid one-pot tandem assembly of enzymatic deoximation and RLi/RMgX reagents

“…2 Although these protocols have been successfully exploited to create a wide variety of natural products and other complex molecular architectures, there are currently relatively few examples of their hybrid versions 3 in which the combination of enzymatic, organocatalytic, and transition-metal or main-group-catalysed processes has been successfully assembled within the different reaction steps. 4 In this field, hybrid chemoenzymatic one-pot tandem protocols in which enzymes are successfully combined with transition-metal-based catalysts or organocatalysis are currently considered a hot topic of research. However, and to the best of our knowledge, the combination of enzymatic synthetic protocols (which intrinsically use water as the natural reaction medium, under aerobic conditions and at room temperature) 5 and the chemistry of highly reactive and polar organolithium (RLi) or Grignard (RMgX) reagents, 6,7 which usually requires the use of dry, often toxic and volatile organic solvents, under an inert atmosphere (N 2 or Ar) and at low temperature (ranging from 0 to −78 °C), is still in its infancy.…”