Minimizing side reactions in chemoenzymatic dynamic kinetic resolution: organometallic and material strategies

Abstract

Chemoenzymatic dynamic kinetic resolution (DKR) of rac-1-phenyl ethanol into R-1-phenylethanol acetate was investigated with emphasis on the minimization of side reactions. The organometallic hydrogen transfer (racemization) catalyst was varied, and this was observed to alter the rate and extent of oxidation of the alcohol to form ketone side products. The performance of highly active catalyst [(pentamethylcyclopentadienyl)IrCl(2)(1-benzyl,3-methyl-imidazol-2-ylidene)] was found to depend on the batch of lipase B used. The interaction between the bio- and chemo-catalysts was reduced by employing physical entrapment of the enzyme in silica using a sol-gel process. The nature of the gelation method was found to be important, with an alkaline method preferred, as an acidic method was found to initiate a further side reaction, the acid catalyzed dehydration of the secondary alcohol. The acidic gel was found to be a heterogeneous solid acid.

Artificial Nanometalloenzymes for Cooperative Tandem Catalysis

“…A high local concentration of Shvo’s catalyst inside CALB-Shvo@MiMBN improved the racemization efficiency. In addition, the proximity of CALB and Shvo’s catalyst increased the transportation of reaction intermediate in the tandem catalysis. − …”

A Recyclable Acidic Ionic Liquid Gel Catalyst for Dehydration: Comparison with an Analogous SILP Catalyst

“…Dehydration of rac -1-phenyl ethanol is applied industrially to the synthesis of styrene. − In this way, 1-phenyl ethanol, a byproduct of the Oxirane process (propylene oxide synthesis), can be effectively utilized. Poisoning is a major problem for the most active heterogeneous systems, and research is ongoing to develop new liquid phase catalysts. − The serendipitous discovery of dehydration activity in toluene at low temperatures (100–120 °C) in the presence of acidic PEG gels led us to examine the dehydration activity and recycling of acidic ionic liquid gels and compare this with the reaction catalyzed by the parent liquid and related SILP system.…”

“…The activity reported here is significantly higher than that measured previously for PEG-based acid gels. 44 The high activity of the SILP compared to the ion-gel opened the possibility that extraction of the SILP could lead to a catalyst with performance similar to the ion-gel. The effect of extracting the SILP catalyst with ethanol, as required for the ion-gel synthesis, was investigated.…”

“…Poisoning is a major problem for the most active heterogeneous systems, and research is ongoing to develop new liquid phase catalysts. [33][34][35][36][37][38][39][40][41][42][43] The serendipitous discovery of dehydration activity in toluene at low temperatures (100-120 °C) in the presence of acidic PEG gels, 44 led us to examine the dehydration activity and recycling of acidic ionic liquid gels, and compare this with the reaction catalyzed by the parent liquid and related SILP system. Appending a sulfonyl group to the cation of an ionic liquid or solid is achieved relatively easy by nucleophilic attack on a sultone.…”

Lipases: Valuable catalysts for dynamic kinetic resolutions

“…It must be taken in account that mutual inactivation may occur and that some metal catalysts work only at high temperatures or require additives, such as strong bases, which may be detrimental to enzymatic performance. The use of bulky organometallics and physical entrapment of the metal or biocatalyst has been reported to minimize interaction between chemo and biocatalyst, though it can slow reaction rates due to diffusion limitations (Pollock et al, 2012). The efficiency of a lipase/metal-catalyzed DKR reaction can also be affected by parameters such as solvent, temperature and nature of the acyl donor.…”