Supramolecular Approaches To Control Activity and Selectivity in Hydroformylation Catalysis

Abstract

The hydroformylation reaction is one of the most intensively explored reactions in the field of homogeneous transition metal catalysis, and many industrial applications are known. However, this atom economical reaction has not been used to its full potential, as many selectivity issues have not been solved. Traditionally, the selectivity is controlled by the ligand that is coordinated to the active metal center. Recently, supramolecular strategies have been demonstrated to provide powerful complementary tools to control activity and selectivity in hydroformylation reactions. In this review, we will highlight these supramolecular strategies. We have organized this paper in sections in which we describe the use of supramolecular bidentate ligands, substrate preorganization by interactions between the substrate and functional groups of the ligands, and hydroformylation catalysis in molecular cages.

Scheme 1. General Reaction Scheme of the Hydroformylation Reaction, Converting Alkenes into Aldehydes, and Potential Side Products

Scheme 2. Mechanism of Rhodium-Catalyzed Hydroformylation

Figure 1

Some typical ligands that have been used in the rhodium-catalyzed hydroformylation.

Figure 2

Some typical ligands that have successfully been used in asymmetric hydroformylation, typically of styrene derivatives.

Figure 3

Schematic representation of supramolecular bidentates formed via a template (I) or via direct interactions between functionalized ligand building blocks (II). M = metal center. FG = functional group. Do = donor center.

Scheme 3. Bis-Zinc(II) and Bis-Tin(IV) Porphyrin Templates (top) and Phosphorus Monodentate Ligands (middle) Used for Supramolecular Assemblies

Synthesis of the rhodium hydroformylation catalyst based on the self-assembly of template 13 and ligand a.

Figure 4

Bis-zinc(II) salphen templated heterobidentate complex 16.

Scheme 4. Synthesis of a Multicomponent Assembly from Ligand 17 and DABCO (as templates) and the Rhodium(I) Complex

Figure 5

Building blocks used to generate bidentate SUPRAPhos ligands via self-assembly.

Scheme 5. Self-Assembly of the 2-Pyridone/2-Hydroxypyridine System via Hydrogen Bonding

Scheme 6. Room-Temperature, Ambient-Pressure Hydroformylation of Functionalized Terminal Alkenes with the Rhodium/6-DPPon Catalyst (FG = functional group)

Scheme 7. Application of Rhodium/6-DPPon and Rhodium/29 Catalysts in Tandem Hydroformylation Reactions and Hydroformylation of Allenes and Alkynes

Scheme 8. Self-Assembly of the Aminopyridine/Isoquinolone System To Generate Heterodimeric Bidentate Ligands (Do = donor center)

Figure 6

Self-assembly of heterocyclic systems to generate methanol-stable heterodimeric bidentate ligands. D = hydrogen-bond donor. A = hydrogen-bond acceptor. Do = donor center.

Figure 7

Metal-templated self-assembly of peptide-based P-ligands.

Scheme 9. Phosphinourea Ligands and Synthesis of Supramolecular Rhodium Complexes Thereof

The Rh complex is also suggested as one of the intermediates of the hydroformylation cycle.

Figure 8

Schematic representation of substrate preorganization via traditional approaches (I) or via supramolecular strategies (II). M = metal center. DG = directing group. RG = reactive group. RS = recognition site. Do = donor center.

Figure 9

Guanidinium-functionalized phosphine ligands.

Scheme 10. Regioselective Hydroformylation of Unsaturated Carboxylic Acids (o = outermost; i = innermost)

Scheme 11. Hydroformylation of a Substrate Containing Multiple Olefinic Sites

Figure 10

Substrate orientation in the selectivity-determining hydride migration step (DFT study).

Scheme 12. Decarboxylative Hydroformylation of α,β-Unsaturated Carboxylic Acids

Scheme 13. Tandem Processes Using Supramolecular Substrate Preorganization Ligands

Figure 11

Anion receptor-functionalized bisphosphines (DIMPhos).

Scheme 14. Regioselective Hydroformylation of ω-Unsaturated Carboxylic Acids (DIPEA = N,N-diisopropylethylamine)

Figure 12

Substrate preorganization in the selectivity-determining hydride migration step (DFT study).

Scheme 15. Regioselective Hydroformylation of Internal Unsaturated Carboxylic Acids

Scheme 16. Regioselective Hydroformylation of 2-Carboxyvinylarenes and Cyclic Analogues

Figure 13

Catalytic scaffolding ligands (reversible bond colored red).

Scheme 17. Regioselective Hydroformylation Employing Catalytic Scaffolding Ligands (PCC = pyridinium chlorochromate)

Scheme 18. Regioselective Hydroformylation of Homoallylic and Bishomoallylic Alcohols Employing Catalytic Scaffolding Catalysts

Scheme 19. Hydroformylation of α,α-Disubstituted Alcohols To Form Quaternary Carbon Centers

Scheme 20. Enantioselective Hydroformylation of Amine-Based Substrates

Scheme 21. Directed Hydroformylation of 2,5-Cyclohexadienyl-1-carbinols

Scheme 22. Divergent Selectivity upon Variation of the Scaffolding Ligand

Figure 14

Schematic representation of the α-, β-, and γ-cyclodextrins that have a hydrophobic cavity that can host organic guest molecules.

Scheme 23. Phase-Transfer Catalysis Mediated by Cyclodextrins

Scheme 24. Representation of the Effect of the Depth of Inclusion of the Substrate in the Cyclodextrin Cavity on the Observed Aldehyde Product Selectivity

Figure 15

Structures of the water-soluble ligands 70, 71, and 72a–72c.

Scheme 25. Proposed Mode of Action of the β-Cyclodextrin-Modified Diphosphine-Based Catalytic System

Scheme 26. Formation of the Active Species 73b from the Monophosphine Rhodium Complex 73a

Figure 16

Structure of HRh(CO)₃ coordinated to the central phosphine of the first-generation assembly. Molecular structure (top) and modeled structure (bottom) of the encapsulated catalyst.

Figure 17

Highly unusual supramolecular structure containing a mixture of penta- and hexacoordinate zinc porphyrins.

Figure 18

Molecular structures of the smaller building blocks 75a–75d and 76.

Figure 19

Energy profile for the hydride migration step leading to the two possible intermediates b and c. Reprinted with permission from ref (84).

Figure 20

Comparison of the crystal structures of assemblies 74 and 77, formed by the self-assembly of 3 equiv of Zn(II) meso-tetraphenylporpholactone and tris(m-pyridyl)phosphine in toluene (letop) and a molecular structure of assembly 77 (bottom). Reprinted with permission from ref (86). Copyright 2017 Creative Commons.

Figure 21

Bis-zinc(II) salphen-templated supramolecular “box” 78.