Chemoenzymatic dynamic kinetic resolution of α-trifluoromethylated amines: influence of substitutions on the reversed stereoselectivity

Abstract

Enzymatic resolution of a-trifluoromethylated amines via kinetic resolution (KR), dynamic kinetic resolution (DKR) employing CALB-Pd/Al 2 O 3 , and a one-pot sequential process of KR/DKR/KR was investigated comparatively for the first time. Although CALB-catalyzed KR of a-trifluoromethylated amines with substituents of methyl (1a), isopropyl (1c), phenyl (1d) and benzyl group (1e) can provide good stereoselectivity factors E from 31 to .200 respectively, DKR and sequential process of KR/DKR/KR possess better practical application potential because of the higher conversion (62%-84%) and the similar enantiomeric excesses (90%-99%). The enantiopreference and inversion for the a-trifluoromethylated amines displayed by CALB were observed and explained by docking modes. Namely, for 1,1,1-trifluoro-2propylamine (1a), the product amide with R-configuration was obtained, and the enantiopreference was converted to S for the amines (1b-1e) with substituents larger than methyl group. The catalysts recycle, and scale-up experiments were demonstrated successfully. All these results indicated the high efficiency and green feature of this enzymatic process, and its application significance.

Synergistic Effect of Pd/C and Novozyme 435 on the Dynamic Kinetic Resolution of 1,1,1-trifluoroisopropylamine

“…Materials Substrate 1,1,1-trifluoroisopropylamine was synthesized according to a previously published procedure (Cheng et al, 2013). 3 wt% of Pd on active carbon was purchased from Alfa Aesar.…”

Chemoenzymatic Dynamic Kinetic Resolution of Primary Benzylic Amines using Pd0‐CalB CLEA as a Biohybrid Catalyst

“…At the same time as Bäckvall's publication, the group of De Vos and Jacobs independently described the use of palladium nanoparticles immobilized on alkaline salts as racemization catalyst in the chemoenzymatic DKR of benzylic amines . In subsequent work several other similar heterogeneous systems were reported for DKR of amines including a nanohybrid catalyst …”

“…[14,15] At the same time as Bäckvall's publication, the group of De Vosa nd Jacobs independently described the use of palladium nanoparticles immobilized on alkaline salts as racemization catalyst in the chemoenzymatic DKR of benzylic amines. [16] In subsequent work several other similarh eterogeneouss ystemsw ere reportedf or DKR of amines [6,[17][18][19][20][21][22][23] including an anohybrid catalyst. [6] One intrinsic drawback with all these heterogeneous protocols is that the catalysts employed consist of an excess inert materiala ss upport.…”

Metal‐Free Decarboxylation of α,β‐Unsaturated Carboxylic Acids for Carbon–Carbon and Carbon–Heteroatom Coupling Reactions

“…The widespread popularity of multi‐halogenated compounds can be attributed to their applications in pharmaceuticals, agrochemicals and material science [38] . Conventional approaches for the synthesis of multi‐halogenated compounds usually require the assistance of oxidants, organometallic reagents or transition metal catalysts [39] . However, these methods have a few drawbacks such as high reaction temperature, the use of toxic metals and the lack of functional group tolerance.…”