On the Hunt for Chiral Single-Atom Catalysts

Abstract

Enantioselective transformations are crucial in various fields, including chemistry, biology, and materials science. Today, the selective production of enantiopure compounds is achieved through asymmetric homogeneous catalysis. Single-atom catalysts (SACs) are emerging as a transformative approach in chemistry, enabling the heterogenization of organometallic complexes and effectively bridging the gap between homogeneous and heterogeneous catalysis. Despite their potential, the integration of SACs into enantioselective processes remains an underexplored area. This perspective offers a comprehensive analysis of possible strategies for the design of heterogeneous asymmetric catalysts, examining how chiral surfaces, chiral modifiers, grafted chiral complexes, and spatial confinement techniques can be effectively employed to enhance enantioselectivity. Each of these methods presents distinct advantages and challenges; for example, chiral surfaces and chiral modifiers offer potential for tailored reactivity but can suffer from limited stability and selectivity, while grafted chiral complexes provide robust platforms but may face issues related to scalability and synthesis complexity. Spatial confinement strategies show promise in enhancing catalyst efficiency but may be constrained by accessibility and reproducibility concerns. These strategies lay the groundwork for their adaptation to SACs, by providing innovative approaches to replicate the well-defined chiral environments of homogeneous catalysts while preserving the stability, reusability, and unique advantages of single-atom heterogeneous systems.

Figure 1

Key design strategies for introducing and controlling chirality in catalysts. These approaches are pivotal for precisely tailoring chiral environments at the atomic level, thereby also enhancing the selectivity and efficiency of SACs in asymmetric catalysis and enabling the production of optically pure compounds via single-atom catalysis.

Figure 2

Schematic representation of a metal nanoparticle on an intrinsically chiral surface. Only the atoms in contact with the asymmetric support (green) among the catalytically active sites (green and yellow) can convey chiral information. Internal atoms (red) are inactive both catalytically and chirally.

Figure 3

Cinchonidine-based chiral modifier structure–activity relationship (a); binding mode of cinchonidine on a generic supported metal nanoparticle (b). Adapted from ref (46, 47).

Figure 4

Photocatalytic α-alkylation of aldehydes using MacMillan’s organocatalyst as a chiral modifier, and PbBiO₂Br as the catalyst. For each substrate, the optimal light wavelength (λ), temperature (T), and reaction time (t) have been reported. Adapted from ref (44).

Figure 5

Diamine-modified Ni@SiO₂ for the batch and continuous-flow alkylation of diethylmalonate with nitroalkenes. Adapted from ref (43).

Figure 6

Cinchonidine-decorated Pt nanoparticles supported on Al₂O₃. Adapted from ref (86).

Figure 7

Schematic representation of the spatially controlled tethering of cinchona alkaloids next to Pt NPs dispersed on a high-surface-area silica support. Adapted from ref (90).

Figure 8

Immobilized Cu-bisoxazoline complex on SiO₂ for the asymmetric Friedel–Crafts hydroxyalkylation of 1,3-dimethoxybenzene. Adapted from ref (92).

Figure 9

Metolachlor synthesis as a case study: key synthetic step (top), active and inactive isomers (bottom right), homogeneous and heterogenized chiral modifiers (bottom left). Adapted from refs (−97).

Figure 10

Chiral Cu(I)-phosphoramidite complex tethered on a (poly)styrene-divinylbenzene resin for the alkylzinc-mediated alkylation of imines and ketones. Adapted from ref (98).

Figure 11

Confined Pd-DPPF complex in MCM-41 synthesis (a), and molecular view of the anchoring in the inner walls (b, left) and overall structure (b, right). Adapted from ref (102).

Figure 12

Ru-BINAP-DPEN confined in porous Zr phosphonate. Adapted from ref (103).

Figure 13

Mn-salen based MOF for the enantioselective epoxidation of alkenes. Adapted from ref (105).

Figure 14

Metallosalen-based COF for the asymmetric cascade epoxidation-nucleophilic ring opening of chromenones. Adapted from ref (106).

Figure 15

Cinchonidine-modified confined Pd NPs in carbon nanotubes for the hydrogenation of α-cinnamic acid and methyl benzoyl formate. Adapted from refs (107, 108).

Figure 16

Cu-based MOF for the asymmetric Friedel–Crafts alkylation of indole with benzylic imines. Adapted from ref (109).

Figure 17

Encapsulated Zn-salen@MWW zeolites for the one-pot three-component synthesis of β-amino carbonyl under ultrasonic irradiation. Adapted from ref (110).

Figure 18

Potential chiral SAC catalyst design strategies with their tuning features (left), advantages, and disadvantages (right).