Addition of CF3 across unsaturated moieties: a powerful functionalization tool

Abstract

In the last few years, the efficient introduction of trifluoromethyl groups in organic molecules has become a major research focus. This review highlights the recent developments enabling the incorporation of CF3 groups across unsaturated moieties, preferentially alkenes, and the mechanistic scenarios governing these transformations. We have specially focused on methods involving the simultaneous formation of C-CF3 and C-C or C-heteroatom bonds by formal addition reactions across π-systems, as such difunctionalization processes hold valuable synthetic potential.

Scheme 1. Hydrotrifluoromethylation of fumaronitrile 1.

Scheme 2. Trifluoromethylation of acyl-oxazolidinones.

Scheme 3. Silver-catalyzed hydrotrifluoromethylation of unactivated alkenes.

Scheme 4. Hydrotrifluoromethylation of unactivated alkenes and the proposed reaction mechanism.

Scheme 5. Hydrotrifluoromethylation of alkynes.

Scheme 6. Metal-free hydrotrifluoromethylation of aliphatic mono-, di-, and trisubstituted alkenes.

Scheme 7. Allyl trifluoromethylation of unactivated alkenes.

Scheme 8. Trifluoromethylation of 2-substituted allylsilanes.

Scheme 9. Copper-catalyzed synthesis of trifluoromethylated vinylsilanes.

Scheme 10. Synthesis of oxindoles by Pd-catalyzed aryltrifluoromethylation of alkenes.

Scheme 11. Synthesis of carbocycles by trifluoromethylation of alkenes.

Scheme 12. Copper-catalyzed carbotrifluoromethylation of N-protected allyl- and homoallylaniline derivatives.

Scheme 13. Trifluoromethylation–cyclization on N-allyl-N-sulfonylamines.

Scheme 14. Trifluoromethylation–cyclization of enynes.

Scheme 15. Copper-catalyzed aryltrifluoromethylation–desulfonylation cascade on acrylamides 18.

Scheme 16. Mechanism of the copper-catalyzed aryltrifluoromethylation–desulfonylation cascade.

Scheme 17. Metal-free trifluoromethylation reaction of methacryloyl benzamides and α,β-unsaturated amides.

Scheme 18. Metal-free synthesis of 6-trifluoromethyl-phenanthridines.

Scheme 19. Copper-catalyzed trifluoromethylation and radical 1,2-aryl migration in α,α-diaryl allylic alcohols.

Scheme 20. Trifluoromethylation–cyanation of styrene derivatives.

Scheme 21. Electrooxidative alkene oxotrifluoromethylation.

Scheme 22. Copper-catalyzed enantioselective oxotrifluoromethylation of unactivated olefins.

Scheme 23. Oxytrifluoromethylation of 2,3-allenoic acids.

Scheme 24. Oxotrifluoromethylation of styrene and aryl alkyne derivatives.

Scheme 25. Synthesis of panomifene.

Scheme 26. Oxytrifluoromethylation of alkenes using Langlois'reagent.

Scheme 27. Synthesis of α-trifluoromethyl ketones 41.

Scheme 28. Metal-free trifluoromethylaminoxylation of terminal alkenes.

Scheme 29. Diastereoselective trifluoromethylation of internal alkenes.

Scheme 30. Aminotrifluoromethylation of allylamines.

Scheme 31. Aminotrifluoromethylation of terminal alkenes.

Scheme 32. Products of aminotrifluoromethylation of internal alkenes.

Scheme 33. Photolysis of trifluoromethanethiosulfonate and trifluorothioacetate in the presence of alkenes.

Scheme 34. Reaction of polyfluoroalkyl halides with alkenes and alkynes.

Scheme 35. Reaction of perfluoroalkanesulphonyl chlorides with alkenes.

Scheme 36. Sodium dithionite initiated addition of CF₂Br₂, CF₃I and (CF₃)₂CFI to allylbenzenes.

Scheme 37. Iodotrifluoromethylation of alkynes.

Scheme 38. Iodotrifluoromethylation of arynes.

E. Merino

C. Nevado