Hydroxysulfonylation of alkenes: an update

Abstract

The direct difunctionalization of inexpensive and widely available alkenes has been recognized as a strong and straightforward tool for the rapid fabrication of complex molecules and pharmaceutical targets by introducing two different functional groups on adjacent carbon atoms of common alkene moieties in a single operation. This synthetic strategy avoids the purification and isolation of the intermediates and thus makes synthetic schemes shorter, simpler and cleaner. In this family of reactions, the hydroxysulfonylation of alkenes has emerged as an increasingly promising strategy for the synthesis of β-hydroxysulfones, which are found in many biologically important molecules and widespread applications in organic synthesis. The objective of this review is to illustrate the advancements in the field of hydroxysulfonylation of alkenes with special emphasis on the mechanistic details of the reaction pathways.

Scheme 1. Selected examples of bioactive compounds possessing a β-hydroxysulfone unit.

Fig. 1. Direct hydroxysulfonylation of alkenes.

Scheme 2. Acid-promoted of hydroxysulfonylation of alkenes 1 with sulfonyl chlorides 2, and water.

Scheme 3. Possible mechanism for the reaction in Scheme 2.

Scheme 4. Visible light mediated synthesis of β-hydroxysulfones 6 through the reaction of styrenes 4 and sulfonyl chlorides 5 in the presence of water.

Scheme 5. Mechanistic explanation for the formation of β-hydroxysulfones 6.

Scheme 6. Synthesis of cyclopropane-containing β-hydroxysulfones 9 developed by Li and Wang.

Scheme 7. Base-mediated hydroxysulfonylation of alkenes 10 with sulfinic acids 11 and O₂.

Scheme 8. Possible reaction pathway for the formation of β-hydroxysulfone derivatives 12.

Scheme 9. Regio- and stereoselective hydroxysulfonylation allenes 13 with arenesulfinic acids 14 reported by Lei.

Scheme 10. Electrochemical synthesis of β-hydroxysulfones 18 developed by Sun.

Scheme 11. Mechanism that accounts for the formation of β-hydroxysulfones 18.

Scheme 12. Fe-catalyzed direct synthesis of β-hydroxysulfones 21 from alkenes 19 and sulfonylhydazides 20.

Scheme 13. A plausible reaction mechanism for the formation of β-hydroxysulfones 21.

Scheme 14. Cu-mediated synthesis of β-hydroxysulfones 24 from styrenes 22 and sulfonylhydrazides 23 in the presence of O₂.

Scheme 15. I₂-catalyzed aerobic hydroxysulfonylation of styrenes 25 with sulfonylhydazides 26.

Scheme 16. Cu-catalyzed synthesis of β-hydroxysulfones 30 through the aerobic oxidative reaction of alkenes 28, arylhydrazines 29, and DABCO·(SO₂)₂.

Scheme 17. Itoh's synthesis of β-hydroxysulfones 33.

Scheme 18. Nickel-catalyzed aerobic hydroxysulfonylation of alkenes 34 with sodium sulfinates 35.

Scheme 19. Possible pathway of β-hydroxysulfones 36 formation.

Scheme 20. Synthesis of chiral β-hydroxysulfones 40 from terminal alkynes 37 and sodium sulfinates 38via Fe-catalyzed aerobic oxysulfonylation and consecutive Ru-catalyzed asymmetric transfer hydrogenation.

Scheme 21. Jang's synthesis of β-hydroxysulfones 43.

Scheme 22. Mechanism that accounts for the formation of β-hydroxysulfones 43.

Scheme 23. Synthesis of 2-(tert-butylsulfonyl)-1-arylylethanols 46 from styrenes 44 and t-butylsulfinamide 45 under aerobic Cu-catalyzed conditions.

Scheme 24. A plausible reaction mechanism for the formation of 2-(tert-butylsulfonyl)-1-arylylethanols 46.

Scheme 25. (a) Huo's synthesis of β-hydroxysulfones 49; (b) mechanistic explanation for the formation of β-hydroxysulfones 49.

Zinatossadat Hossaini

Evan Abdulkareem Mahmood

Mohammad Reza Poor Heravi

Abdolghaffar Ebadi

Esmail Vessally