Dynamic Double Kinetic Resolution of Amines and Alcohols under the Cocatalysis of Raney Nickel/Candida antarctica Lipase B: From Concept to Application

Abstract

Herein, we have established a dynamic double kinetic resolution (DDKR) strategy under the co‐catalysis of Raney nickel and Candida antarctica lipase B (CAL‐B) for the one‐pot simultaneous resolution of primary amines and secondary alcohols (or esters). The DDKR strategy was successfully applied to the resolution of a series of racemic amines and secondary alcohols (or esters) as well as mexiletine, an important antiarrhythmic agent. The catalysts could be recycled and reused several times with the same high activity. Scale‐up experiments were also successful. As a more atom‐economical and efficient process than traditional simple kinetic resolutions, the DDKR strategy can be widely used to prepare optically pure amines and alcohols.

Fungal mediated kinetic resolution of racemic acetates to ( R )-alcohols using Fusarium proliferatum

“…Enzyme mediated kinetic resolution of such alcohols using lipases, esterases, and alcohol dehydrogenases have been reported in the literature. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] For example, resolution of (±)-lavandulol has been achieved previously with various lipases such as Candida antarctica lipase B (CAL B), 9 Hog pancreas lipase, 29 Porcine pancreas lipase, 26 and Yarrowia lipolytica lipases. 30 However, enzyme catalyzed resolution process is associated with several disadvantages such as higher cost, low substrate concentration, instability and cofactor dependency of the enzymes in several occasions.…”

Tandem Reactions Combining Biocatalysts and Chemical Catalysts for Asymmetric Synthesis

“…Liang and coworkers used a similar system to synthesize rasagiline [43]. Moreover, a modified solvent extraction system and a continuous flow reactor were developed to compartmentalize the Pd-based nanoparticles and lipases to overcome the incompatibility of reaction conditions required for the racemization and enzymatic steps [44][45][46]. However, Pd nanocatalysts did not work well for aliphatic amines.…”

“…Raney Ni and Co displayed preferences for aliphatic primary amine racemization (Scheme 3), but they have inhibitory effects on the enzyme, resulting in a slow DKR system [47]. lipases to overcome the incompatibility of reaction conditions required for the racemization and enzymatic steps [44][45][46]. However, Pd nanocatalysts did not work well for aliphatic amines.…”

“…In the second case, CALB catalysis was coupled with a dynamic dominonitrone addition-cyclization pathway to synthesize new, six-membered N,O,S-containing heterocycles (Scheme 4B). lipases to overcome the incompatibility of reaction conditions required for the racemization and enzymatic steps [44][45][46]. However, Pd nanocatalysts did not work well for aliphatic amines.…”

Lipases: Valuable catalysts for dynamic kinetic resolutions

“…Efficient DKR of benzylic amines with this catalyst, however, were not possible in one-pot reaction. Raney Nicatalyzed racemization was recently applied in the chemoenzymatic dynamic double kinetic resolution (DDKR) of the antiarrhythmic agent mexiletine (Xia et al, 2014) (Fig. 25).…”