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 Introduction

2 DACH: A Brief Historical Narrative

3 Catalytic Asymmetric Hydrogenation of Alkenes

4 Catalytic Asymmetric Dihydroxylation of Alkenes

5 Catalytic Asymmetric Sulfoxidation and Sulfimidation

6 Catalytic Asymmetric 1,4-Conjugate Addition

6.1 Using Jacobsen’s DACH Metal–salen Complexes as Catalysts

6.2 Using Takemoto’s Bifunctional H-Bonding DACH Thiourea Organocatalyst

6.3 Using DACH Ni(II) Complexes as Catalysts

6.4 Using DACH H-Bonding Catalysis

7 Catalytic Asymmetric Epoxidation of Alkenes

8 Catalytic Asymmetric Claisen Rearrangement

9 Catalytic Asymmetric 1,2-Nucleophilic Addition to Carbonyl Compounds

9.1 Catalytic Asymmetric Addition of Dialkylzinc to Aldehydes and Ketones

9.2 Catalytic Asymmetric Alkynylation of Aldehydes and Ketones

9.3 Catalytic Asymmetric Addition of Cyanide to Aldehydes and Ketones

10 Catalytic Asymmetric Allylic Alkylation

11 Catalytic Asymmetric Cyclopropanation of Alkenes

12 Catalytic Asymmetric Cycloaddition Reactions

13 Catalytic Asymmetric Aziridination of Alkenes

14 Catalytic Asymmetric Hydrogenation of Prochiral Ketones and Imines

15 Catalytic Asymmetric Aldol Reactions

16 Catalytic Asymmetric Opening of Small Ring Systems

16.1 Desymmetrization of meso-Epoxides and meso-Aziridines

16.2 Kinetic Resolution of Racemic Epoxides

16.3 Enantioselective Addition of CO₂ to Epoxides

16.4 Enantioselective Ring Opening of Oxetanes

17 Catalytic Asymmetric Strecker Reactions

18 Catalytic Asymmetric Mannich Reactions

19 Catalytic Asymmetric Henry and Aza-Henry Reactions

20 Catalytic Asymmetric Morita–Baylis–Hillman and Rauhut–Currier Reactions

21 Catalytic Asymmetric Petasis Reactions

22 Organocatalytic Asymmetric Cascade Reactions

23 Miscellaneous Catalytic Reactions

24 Conclusion and Outlook

25 DACH Catalysts and Ligands List