One-pot dynamic kinetic resolution (DKR) has garnered considerable attention for its potential to generate enantiomerically pure compounds in high yields and simplifying operation. However, the ...challenge lies in achieving compatibility between enzymes and metals due to their distinct operating conditions. In this study, we present a novel cascade catalytic platform for the DKR of amines to address this issue. Pd nanoparticles were immobilized on lysine-decorated lipase nanogels, forming isolated metal-enzyme catalysts. The microwave-assisted one-pot DKR of amines was carried out under non-pressurized conditions at 50 °C for 5 h. The metal-enzyme nanogel biochemical composite exhibited excellent performances, with a high conversion rate of 98% and enantiomeric excess values exceeding 99%. This innovative approach demonstrates the potential of constructing a multifunctional metalloenzyme catalytic platform with a distinctive three-dimensional structure, which offers promising prospects for DKR applications.
The metal-enzyme nanogel biochemical composite exhibits excellent catalytic performance in non-pressurized microwave conditions at 50 °C, achieving an outstanding 98% conversion rate and ee value＞99%. Display omitted
•A novel Pd@CALB-Lys-nanogels cascade catalytic platform was developed.•Lysine modification reduces the size of enzyme nanogels and can promotes the dispersion of metal.•The catalyst exhibited high activity and selectivity in microwave-assisted Dynamic Kinetic Resolution.•The catalyst can spontaneously catalyze reactions at mild temperatures without the need for hydrogen pressure.
We have discovered that the racemization of configurationally stable, axially chiral 2,2′‐dihydroxy‐1,1′‐biaryls proceeds with a catalytic amount of a cyclopentadienylruthenium(II) complex at 35–50 ...°C. Combining this racemization procedure with lipase‐catalyzed kinetic resolution led to the first lipase/metal‐integrated dynamic kinetic resolution of racemic axially chiral biaryl compounds. The method was applied to the synthesis of various enantio‐enriched C1‐ and C2‐symmetric biaryl diols in yields of up to 98 % and enantiomeric excesses of up to 98 %, which paves the way for new developments in the field of asymmetric synthesis.
Enantiopure compounds: The first lipase/metal‐integrated dynamic kinetic resolution of axially chiral racemic biaryl compounds has been established. A highly compatible combination of ruthenium‐catalyzed racemization and atropo‐enantioselective lipase‐catalyzed kinetic resolution provides access to valuable homochiral C1‐ and C2‐symmetric biaryl diols.
A method for enantiodivergent production of S and R propargylic alcohols from their racemates by using commercial lipase‐based dynamic kinetic resolution achieves quantitative conversion of the ...racemates into optically pure substances. The right and left hands, wearing jeweled rings indicating individual reaction steps, lead to opposite enantioselection, producing S and R alcohols, respectively. The order of the jewels is key to the enantioswitch. More information can be found in the Research Article by S. Akai and co‐workers (DOI: 10.1002/chem.202202437).
Mesoporous core–shell structured nanocatalysts with a PdPt bimetallic core and enzyme-immobilized polydopamine (PDA) shell were designed, in which the PDA shell worked as a barrier to position the ...bimetallic core and enzyme in separated locations. The accessible mesoporous structures of both the core and shell significantly facilitate mass transfer and catalyst utilization, improving the synergistic catalytic abilities in cascade reactions. The obtained bifunctional nanocatalysts enabled efficient two-step one-pot cascade reactions of different types: dynamic kinetic resolution of primary amines in organic solvent with high yield and enantioselectivity (up to 99% yield and 98% ee) and degradation of organophosphate nerve agent in aqueous solution with high rate constant and turnover frequency number values (0.8 min–1 and 20 min–1, respectively).
Display omitted The goal of this review is to collect the major developments in organocatalytic dynamic kinetic resolution reported since the beginning of 2011, well illustrating that the synthetic ...scope of these powerful processes allowing the resolution of racemic compounds with up to 100% yield has been widely expanded in the last five years. Indeed, an important number of chiral organocatalysts are now available that afford excellent levels of stereocontrol in a myriad of transformations evolving through dynamic kinetic resolution that could only previously be achieved by using biocatalysts. This review is divided into six sections, according to the different types of organocatalytic activation modes employed in these reactions, such as aminocatalysis, N-heterocyclic carbene catalysis, hydrogen-bonding catalysis, Brønsted acid catalysis, Brønsted base catalysis, and Lewis base catalysis.
An unprecedented example of a chiral phosphoric acid‐catalyzed atroposelective Pictet–Spengler reaction of N‐arylindoles is reported. Highly enantioenriched N‐aryl‐tetrahydro‐β‐carbolines with C−N ...bond axial chirality are obtained via dynamic kinetic resolution. The hydrogen bond donor introduced on the bottom aromatic ring, forming a secondary interaction with the phosphoryl oxygen, is essential to achieving high enantioselectivity. A wide variety of substituents are tolerable with this transformation to provide up to 98 % ee. The application of electron‐withdrawing group‐substituted benzaldehydes enables the control of both axial and point stereogenicity. Biological evaluation of this new and unique scaffold shows promising antiproliferative activity and emphasizes the significance of atroposelective synthesis.
Catalytic and enantioselective control of the C–N stereogenic axis of heterocyclic scaffolds is reported. The asymmetric Pictet–Spengler reaction is achieved by employing a chiral phosphoric acid via dynamic kinetic resolution. Application to substituted benzaldehyde enables control of both axial and point chirality.
Combining the advantages of homogeneous and heterogeneous catalysis is highly desired but remains a challenging goal. Herein, we fabricated a semiheterogeneous metal–enzyme-integrated catalyst using ...soluble porous imine molecule cages (IMCs), which could partially dissolve in organic solvents under heating conditions for catalytic tasks while precipitate completely at room temperature for catalyst recovery. The IMCs play three vital roles: (1) acting as a support and stabilizer for metal nanoparticles and enzymes, (2) partially solubilizing the heterogeneous catalyst in organic medium, and (3) creating hydrophobic and basic microenvironments for improved catalytic efficiency. The covalent immobilization of the enzyme by utilizing imine bonds via the Ugi-type reaction was disclosed, in which the effect of different parameters on enzyme immobilization and the structure–activity relationship were investigated. The semiheterogeneous catalyst exhibited high activity, selectivity, and reusability in chemoenzymatic dynamic kinetic resolution of amines at low temperature (50–60 °C) with high yields and enantioselectivities (up to 94% yield and 98% ee).
In a continuous effort to emulate the efficiency of biosynthetic pathways, considerable progress has been made in developing one-pot chemoenzymatic processes that take full advantage of the chemo-, ...regio-, and stereoselectivity of biocatalysts and the productivity of chemical catalysts. Over the last 20 years, research in this area has provided us with proof of concept examples in which chemical and biological transformations occur in one vessel, sequentially or concurrently. These transformations typically access products with high enantiopurity and chemical diversity. In this perspective, we present some of the most successful reports in this field.
A highly enantio- and diastereoselective dynamic kinetic resolution (DKR) of configurationally labile 3-aryl indole-2-carbaldehydes is described. The DKR proceeds via a Rh-catalyzed intermolecular ...asymmetric reductive aldol reaction with acrylate esters, with simultaneous generation of three stereogenic elements. The strategy relies on the labilization of the stereogenic axis that takes place thanks to a transient Lewis acid–base interaction (LABI) between the formyl group and a thioether moiety strategically located at the ortho′ position. The atropisomeric indole products present a high degree of functionalization and can be further converted to a series of axially chiral derivatives, thereby expanding their potential application in drug discovery and asymmetric catalysis.
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