Modern Stereoselective Synthesis of Chiral Sulfinyl Compounds

Abstract

Chiral sulfinyl compounds, sulfoxides, sulfoximines, sulfinamides, and other derivatives, play an important role in asymmetric synthesis as versatile auxiliaries, ligands, and catalysts. They are also recognized as pharmacophores found in already marketed and well-sold drugs (e.g., esomeprazole) and used in drug design. This review is devoted to the modern methods of preparation of sulfinyl derivatives in enantiopure or enantiomerically enriched form. Selected new approaches leading to racemic products for which the asymmetric variant can be developed in the future are mentioned as well.

Figure 1

General formula of sulfinyl compounds showing resonance structures of sulfinyl group.

Figure 2

Examples of enantiomerically pure sulfinyl compounds exhibiting biological activity: leinamycin (1), esomeprazole (2), modafinil (3), roniciclib (4).

Figure 3

Main classes of chiral sulfinyl compounds. R,R′, R′′,R′′′ = alkyl or aryl, but when attached to N then also H; X = F, Cl, Br, I.

Scheme 1. Possible Interconversions of Sulfinyl Derivatives

Scheme 2. Enantioselective Oxidation of Sulfides Catalyzed by Ti(IV) Complex with Chiral Tetraol 5(41)

Scheme 3. Enantioselective Oxidation Catalyzed by Titanium/(S,S)-Hydrobenzoin

Scheme 4. Oxidation of Hydroxypropyl Sulfides with a Catalytic System Based on Dinuclear Titanium Complex with Chiral Ligand 7 Described by Bhadra et al.

Scheme 5. Oxidation of Sulfides Catalyzed by Manganese Complex

Scheme 6. Synthesis of Esomeprazole 2 Catalyzed by Fe(III)-Chiral Schiff Base Complex

Scheme 7. Chiral Anion as the Source of Asymmetric Induction in Sulfoxidation Catalyzed by Achiral Cationic Fe(III) Complex

Scheme 8. One-Pot Photooxidation of Sulfide 14 Catalyzed by Iridium Complex 15 Coupled with Resolution of Sulfoxide 16 by Chiral-at-Metal complex Δ-17 Described by Li and Ye

Scheme 9. Enantioselective Preparation of R-Sulindac with a Chiral Confined Brønsted Acid

Scheme 10. Stereoselective Preparation of Sulfoxides via Palladium-Catalyzed Arylation of Sulfenate Anion with Josiphos-Type Ligand

Scheme 11. Chiral Phase-Transfer Catalyst 22 in Synthesis of Aryl Methyl Sulfoxides

Scheme 12. Use of Iodinated Pentanidium Salt 23 as Phase-Transfer Agent for Preparation of Optically Active Benzyl Heteroaryl Sulfoxides

Scheme 13. Enantioselective Reaction of Sulfenate Anions with Aryl and Alkenyl Bromides

Scheme 14. Palladium-Catalyzed Preparation of Sulfoxides Reported by Zhang and Co-workers

Scheme 15. Sulfoxidation of Thiochromanone Derivatives by Cytochrome P450-BM3 Variants Obtained through Directed Evolution

Scheme 16. Reductive Resolution of Alkyl Aryl Sulfoxides by Methionine Reductase paMsrA

Scheme 17. Diastereoselective Oxidation of Sulfenates Bearing a Phosphonate Group

Scheme 18. Enantioselective Preparation of Sulfinates from Racemic Sulfinyl Chlorides in the Presence of Quinidine

Scheme 19. Preparation of Optically Active Sulfinates from Dialkyl Sulfites in the Presence of Quinine

Scheme 20. Stereospecific Radical Cyclization of Enantiopure Sulfinamide

Scheme 21. Preparation of tert-Butane tert-Butyl Thiosulfinate Developed by Ellman and Co-workers^,−

Scheme 22. Oxidation of tert-Butyl Disulfide by Cyclohexanone Monooxygenase

Scheme 23. Oxidation of Cyclic Disulfides by Chloroperoxidase

Scheme 24. Preparation of Optically Active Thiosulfinate by Decomposition of Corresponding Sulfoxide

Scheme 25. Synthesis of Enantioenriched Thiosulfinates from Sulfinyl Chlorides and Thiols

Scheme 26. Preparation of Optically Active Sulfinamides by Oxidation of Sulfenamides Catalyzed by Chiral Phosphoric Acid Derivative

Scheme 27. Enantioselective Oxidation of Sulfinylimines with Oxaziridines

Scheme 28. Use of Menthyl Sulfinate in Stereoselective Preparation of Sulfinamides and Sulfinylimines

Scheme 29. Senanayake’s Approach to Chiral Sulfinamides

Scheme 30. Preparation of Enantiomerically Pure tert-Butanesulfinamide and Its Transformations^,,

Scheme 31. Preparation of Perfuorobutanesulfinamide

Scheme 32. Preparation of Sulfinamide 58 by Li and Co-workers

Scheme 33. Preparation of Chiral Epimeric Secondary Sulfinamides from Sulfonyl Chlorides and Enantiopure Amines

Scheme 34. Biocatalytic Deracemization of N-Acyl Sulfinamides

Scheme 35. Possible Pathways for Preparation of Sulfoximines from Sulfides

Scheme 36. Enantioselective Imination of Sulfides and Enantiospecific Oxidation of Sulfilimines

Scheme 37. Preparation of Optically Active Sulfoximines through Kinetic Resolution of Racemic Sulfoxides

Scheme 38. Stereospecific Formation of N-Cyanosulfoximine from Sulfoxide

Scheme 39. Stereospecific Formation of Sulfoximine from Sulfoxide-Direct NH Transfer and Rh-Catalyzed Carbamate Transfer^,

Scheme 40. Sulfoximines Obtained from Epimeric Sulfonimidamidates

Scheme 41. Preparation of 2,1-Benzothiazines from Compound 73 and Alkynes or Alkenes^,

Scheme 42. [3+2]-Cycloaddition Leading to Cyclic Sulfoximines

Scheme 43. Alkylation of Pivaloyl-Protected Sulfinamides

Scheme 44. Preparation of Sulfoximine from Sulfides^,,

Scheme 45. Desymmetrization of Sulfoximine 75 Yielding Myristic Acid Derivative

Scheme 46. Reaction between (S)-Aryl Bromide and (R)-Sulfoximine

Scheme 47. Synthesis of 2,1-Benzothiazines from Enantiopure Sulfoximine (R)-66 Described by Harmata and Pavri

Scheme 48. Preparation of Sulfonimidoyl Chlorides from Sulfinyl Chlorides or Sulfinamides⁻

Scheme 49. Synthesis of Sulfonimidoyl Fluorides from SOF₄ Reported by Sharpless and Co-workers

Scheme 50. Transformations of Sulfinamide (S)-84 through Chloride (R)-85 to Sulfonimidamide (R)-86, Sulfonimidate (S)-87, and Sulfoximine (S)-88

Scheme 51. Preparation of Sulfonimidamidates from Sulfinamides by Malacria and Co-workers^,

Scheme 52. Preparation of Sulfonimidates from Thiols

Scheme 53. Preparation of Enantiopure Sulfonimidamides from Sodium Sulfinate

Scheme 54. Synthesis of Sulfonimidamides from Tertiary Sulfinamides

Scheme 55. Preparation of Sulfonimidamides from Sulfonamides

Scheme 56. Formation of Sulfonimidamidates from N-Tritylsulfinylamine

Scheme 57. One-Pot Preparation of Sulfonimidamides from Sulfenamides