Epoxides: Small Rings to Play with under Asymmetric Organocatalysis

Abstract

Optically pure epoxides are recognized as highly valuable products and key intermediates, useful in different areas from pharmaceutical and agrochemical industries to natural product synthesis and materials science. The predictable fate of the ring-opening process, in terms of stereoselectivity and often of regioselectivity, enables useful functional groups to be installed at vicinal carbon atoms in a desired manner. In this way, products of widespread utility either for synthetic applications or as final products can be obtained. The advent of asymmetric organocatalysis provided a new convenient tool, not only for their preparation but also for the elaboration of this class of heterocycles. In this review, we focus on recent developments of stereoselective organocatalytic ring-opening reactions of meso-epoxides, kinetic resolution of racemic epoxides, and Meinwald-type rearrangement. Examples of asymmetric organocatalytic processes toward specific synthetic targets, which include ring opening of an epoxide intermediate, are also illustrated.

Figure 1

Ring-opening reactions to functionalized optically active molecules and heterocycles via meso- and racemic epoxides under asymmetric organocatalysis (1), via an asymmetric organocatalytic route involving a key epoxide intermediate (2).

Scheme 1. ARO of a meso-Diol Epoxide with 2-Mercaptobenzothiazole Catalyzed by BINOL-Derived Phosphoric Acid 3a

Scheme 2. ARO of meso-Epoxides with 2-Mercaptobenzothiazoles Catalyzed by PCCP-Based Chiral Acid 6

Scheme 3. ARO of Cyclohexene Oxide with Benzoic Acid Catalyzed by Chiral Calixarene-Based Phosphonic Acid 9

Scheme 4. Asymmetric Amination of Cyclohexene Oxide with Cyclopropyl Amine Catalyzed by Soy Polysaccharide

Scheme 5. VAPOL-Based Phosphoric-Acid-Catalyzed Desymmetrization of 1-Aminocyclohept-4-ene-Derived Epoxides to Tropanols

Scheme 6. BINOL-Derived Bis(sulfuryl)imide-Catalyzed Desymmetrization of Epoxytropinone

Scheme 7. TRIP-Catalyzed Kinetic Resolution of Terminal Epoxides to Thiiranes

Scheme 8. H₈-BINOL-Derived Phoshoric-Acid-Catalyzed Kinetic Resolution of Racemic Terminal Epoxides with Carboxylic Acids

Scheme 9. H₈-BINOL-Derived Phoshoric-Acid-Catalyzed Kinetic Resolution of Racemic α-Chiral Carboxylic Acids with a Model Racemic Epoxide

Scheme 10. SPINOL-Derived Phoshoric-Acid-Catalyzed Kinetic Resolution of Racemic Terminal Spiro-Epoxyindoles in Friedel–Crafts Alkylation with Indoles

Scheme 11. H-Bond-Catalyzed Kinetic Resolution of Racemic Disubstituted trans-Epoxides with CO₂

Scheme 12. H₈-Binaphthyl-Linked Hemisquaramide-Catalyzed Kinetic Resolution of Racemic Styrene Epoxide with CO₂

Scheme 13. Mechanism of the Catalytic Enantioselective Meinwald Rearrangement

Scheme 14. Catalytic Enantioselective Meinwald Rearrangement of Racemic Epoxides for the Synthesis of Ketones Bearing a Quaternary Stereocenter

Scheme 15. Proposed Mechanism of the Catalytic Enantioselective Meinwald Rearrangement of Racemic Epoxides

Scheme 16. Catalytic Enantioselective Meinwald Rearrangement of Tetrasubstituted Racemic Epoxides and Desymmetrized Meinwald Rearrangement

Scheme 17. Synthesis of Optically Active Building Block (2S,3S)-epi-Oxetin via Enantioselective Epoxidation Promoted by Jørgensen Catalyst as the Key Step

Scheme 18. Three-Step Synthesis of Enantioenriched γ-Butenolides Exploiting Asymmetric Organocatalytic Epoxidation of Chalcones as the Key Step (MK-10: montmorillonite K10)

Scheme 19. NHC-Catalyzed Regio- and Stereoselective Ring Opening of Epoxy Enals to Access 1,2-Amino Alcohols and 1,4-Fluoro Alcohols (NFSI: N-Fluorobenzenesulfonimide)

Scheme 20. Hypothetical Transition States and Mechanism Involved in the Amination and Fluorination Reaction of Chiral Epoxy Enals

Scheme 21. Asymmetric Synthesis and Manipulation of Chiral Synthons Bearing Three Consecutive Functional Groups, Including Aziridine, Epoxide, and Aldehyde

Scheme 22. Enantioselective Formal [3 + 2] Cycloaddition of β,γ-Epoxysulfones with Imines Catalyzed by a Chiral Organosuperbase

Scheme 23. Synthesis of Enantioenriched Hydroxy Fatty Acids, Fatty Acid Esters of Hydroxy Fatty Acids, and Fatty γ-Lactones via Asymmetric Organocatalytic Synthesis of Terminal Epoxides

Scheme 24. Asymmetric Synthesis of Oxazolines and Dihydrooxazines through an Epoxidation/Regioselective Cyclization Sequence

Scheme 25. Regiodivergent Chiral Phosphoric-Acid-Catalyzed Intramolecular Ring-Opening Reaction of Antibiotic Mupirocin Methyl Ester

Scheme 26. Asymmetric Synthesis of Dihydroquinoxalinones and Dihydroquinoxalinyl Spiro-Oxindole via Enantioenriched gem-Dicyanoepoxides

Scheme 27. Enantioselective Synthesis of 2-Oxopiperazines from Aldehydes via Transient Epoxy Lactone Intermediate

Scheme 28. Enantioselective One-Pot Catalytic Strategy to Dihydroquinoxalinones via Novel 1-Phenylsulfonyl-1-cyano-Enantioenriched Epoxides Catalyzed by Quinine-Derived Urea