Combining Pd nanoparticles on MOFs with cross-linked enzyme aggregates of lipase as powerful chemoenzymatic platform for one-pot dynamic kinetic resolution of amines Meng Wang, Xiaoxu Wang, Bo Feng, Yuanhua Li, Xinchen Han, Zijie Lan, Huajun Gu, Huamin Sun, Meng Shi, Hexing Li, Hui Li ⇑ Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, PR China article info Article history: Received 19 May 2019 Revised 20 August 2019 Accepted 22 August 2019 Keywords: Dynamic kinetic resolution Chiral amine Palladium CALB-CLEAs MOFs Microwave irradiation abstract Acquisition of chiral amines is a very important item in scientific research. Chemoenzymatic catalyst combination of Pd nanoparticles supported on the external surface of the ethylenediamine- functionalized MIL-101 (Pd@ED-MIL-101) with layered cross-linked enzyme aggregates of Candida antarctica lipase B (CALB-CLEAs) was established for the first time. This combination served as an ultra-efficient chemoenzymatic catalyst system for one-pot dynamic kinetic resolution (DKR) of rac-1- phenylethylamine leading to optically pure product (>99% ee value) with almost full conversion and excellent selectivity (>99%) without the aid of any additive. Significantly, aliphatic amines can be also efficiently converted to enantiomerically pure products, making this robust and heterogeneous combina- tion one of the most powerful chemoenzymatic platforms for microwave-assisted one-pot DKR of amines available up to now. Ó 2019 Elsevier Inc. All rights reserved. 1. Introduction In face of an ever-increasing demand for enantiomerically pure amines, constituting valuable synthetic targets and key building blocks in the manufacturing of many chemicals, such as fragrances, dyes, emulsifiers and pharmaceuticals [1], various synthesis meth- ods have been developed to the enantioselective achievement of amines [2–9]. Dynamic kinetic resolution (DKR) (Scheme 1), combo reaction of enzyme-aided KR of racemates and simultane- ous racemization of the remaining enantiomer, has proven a pow- erful tool to provide optically pure amines. Based on this process, one-pot DKR usually enhances the efficiency because of step- saving, high atom economy, as well as biomimetic nature [10,11]. In one-pot DKR process, the rate-determining step is generally the racemization of amines that requires harsh reaction conditions. Significant development of highly efficient racemization catalysts, including basic catalysts, enzymes, transition-metal complexes, and metal nanoparticles (NPs) [12–18], has made it possible to tackle the incompatibility between the enzymatic KR and the racemization reaction. Amongst them, metal (particularly Pd) NPs are the most widely used racemization catalysts owing to their superior activity, the easier work-up protocols, and heterogeneous property [19]. To date, extensive efforts have been devoted to enhance the Pd NPs dispersion via employing various carriers, and thus increasing their racemization rate [16,17,20–29]. Pre- sently, metal organic frameworks (MOFs) have attracted growing attention from both academia and industry owing to their outstanding features and thus specific applications in catalysis [30–32]. Pd NPs confined inside the cages of a MOFs material, MIL-101, has been developed by our group [33], and displayed great compatibility with commercial lipase for one-pot DKR of racemic benzylic amines [34]; nevertheless, the as-synthesized catalysts are usually formed at micrometer-scale, unfavorable to the reaction for the presence of mass transport. Obviously, design and synthesis of size-controllable Pd NPs [35] loaded on the exter- nal surface of MOFs [36] represent a promising approach to improving the accessibility. To establish an efficient one-pot DKR strategy for amines, another important aspect is to control the selectivity towards the target products. Ethylbenzene (EB) had proven the primary bypro- duct in (S)-1-phenylethylamine racemization [20,21], resulting from the hydrogenolysis of secondary amine formed via condensa- tion reactions (Fig. S1). A substantial deal of efforts has been devoted to suppress the side reaction. Incorporating alkalic salt to ±-a-phenylethylamine DKR system could efficiently inhibit the https://doi.org/10.1016/j.jcat.2019.08.033 0021-9517/Ó 2019 Elsevier Inc. All rights reserved. ⇑ Corresponding author. E-mail address: lihui@shnu.edu.cn (H. Li). Journal of Catalysis 378 (2019) 153–163 Contents lists available at ScienceDirect Journal of Catalysis journal homepage: www.elsevier.com/locate/jcat