1,2-trans-Diaminocyclohexane (DACH) in Asymmetric Catalysis: Nearing Fifty Years of Faithful Service and Counting

Abstract

This review highlights the use of DACH as a versatile ligand in catalytic asymmetric transformations providing mechanistic rationales and relevant comments presented in chronological order for each of the 21 reaction types with references up to December 25, 2023. Intended to be as practically comprehensive as possible, this review assembles useful examples of using DACH as a ligand in organocatalytic or as metal complexes in asymmetric transformations. The resulting enantiomerically enriched, if not pure, chiral non-racemic small molecules are of great utility as value added intermediates in the total synthesis of natural products, in the design and synthesis of medicinally important compounds, and in other areas in organic and bioorganic chemistry where chirality plays a role. The graphic image depicts Spartacus with his arms folded in the same sense of chirality as (R,R)-DACH.1 Introduction2 DACH: A Brief Historical Narrative3 Catalytic Asymmetric Hydrogenation of Alkenes4 Catalytic Asymmetric Dihydroxylation of Alkenes5 Catalytic Asymmetric Sulfoxidation and Sulfimidation6 Catalytic Asymmetric 1,4-Conjugate Addition6.1 Using Jacobsen’s DACH Metal–salen Complexes as Catalysts6.2 Using Takemoto’s Bifunctional H-Bonding DACH Thiourea Organocatalyst6.3 Using DACH Ni(II) Complexes as Catalysts6.4 Using DACH H-Bonding Catalysis7 Catalytic Asymmetric Epoxidation of Alkenes8 Catalytic Asymmetric Claisen Rearrangement9 Catalytic Asymmetric 1,2-Nucleophilic Addition to Carbonyl Compounds9.1 Catalytic Asymmetric Addition of Dialkylzinc to Aldehydes and Ketones9.2 Catalytic Asymmetric Alkynylation of Aldehydes and Ketones9.3 Catalytic Asymmetric Addition of Cyanide to Aldehydes and Ketones10 Catalytic Asymmetric Allylic Alkylation11 Catalytic Asymmetric Cyclopropanation of Alkenes12 Catalytic Asymmetric Cycloaddition Reactions13 Catalytic Asymmetric Aziridination of Alkenes14 Catalytic Asymmetric Hydrogenation of Prochiral Ketones and Imines15 Catalytic Asymmetric Aldol Reactions16 Catalytic Asymmetric Opening of Small Ring Systems16.1 Desymmetrization of meso-Epoxides and meso-Aziridines16.2 Kinetic Resolution of Racemic Epoxides16.3 Enantioselective Addition of CO2 to Epoxides16.4 Enantioselective Ring Opening of Oxetanes17 Catalytic Asymmetric Strecker Reactions18 Catalytic Asymmetric Mannich Reactions19 Catalytic Asymmetric Henry and Aza-Henry Reactions20 Catalytic Asymmetric Morita–Baylis–Hillman and Rauhut–Currier Reactions21 Catalytic Asymmetric Petasis Reactions22 Organocatalytic Asymmetric Cascade Reactions23 Miscellaneous Catalytic Reactions24 Conclusion and Outlook25 DACH Catalysts and Ligands List