Accessing the synthesis of natural products and their analogues enabled by the Barbier reaction: a review

Abstract

The Barbier reaction is significantly referred to as one of the efficient carbon-carbon bond forming reactions which involves the treatment of haloalkanes and carbonyl compounds by utilizing the catalytic role of a diverse range of metals and metalloids. The Barbier reaction is tolerant to a variety of functional groups, allowing a broad substrate scope with the employment of lanthanides, transition metals, amphoteric elements or alkaline earth metals. This reaction is also water-resistant, thereby overcoming the challenges posed by moisture sensitive organometallic species involving C-C bond formation reactions. The Barbier reaction has significantly found its applicability towards the synthesis of intricate and naturally occurring organic compounds. Our review provides an outlook on the synthetic applications of the Barbier reaction and its variants to accomplish the preparation of several natural products, reported since 2020.

Scheme 1. Synthesis of tertiary alcohol from Barbier and Grignard reaction.

Scheme 2. Layout for γ-regioselective and α-regioselective Ti & Zn-mediated Barbier allylation reaction.

Scheme 3. Layout for an enantioselective In-mediated Barbier allylation reaction.

Fig. 1. Synthesis of some naturally occurring organic compounds by employing Barbier allylation reaction as a key step.

Scheme 4. Synthesis of the alkaloid (–)-205B 27a.

Scheme 5. Synthesis of (−)-arborsidine (−)-36.

Scheme 6. Synthesis of casuarina 41 and 6-epi-casuarine 42.

Scheme 7. Synthesis of (±)-spirocollequins A 49a & B 49b.

Scheme 8. Synthesis of Cephalosporolide D 57.

Scheme 9. Synthesis of (R,R)-obolactone 63a, 6-epi-obolactone 63b, 7′,8′-dihydroobolactone 64a and 6-epi-7′,8′dihydroobolactone 64b.

Scheme 10. Synthesis of salinosporamide B 76, salinosporamide D 78 and salinosporamide I 79.

Scheme 11. Synthesis of (4S,5S)-4-hydroxy-γ-decalactone 85.

Scheme 12. Synthesis of cryptorigidifoliol I 93 and 2′-epi-cryptorigidifoliol I 94.

Scheme 13. Synthesis of thuggacin cmc-A 108.

Scheme 14. Synthesis of Paecilomycin F 115.

Scheme 15. Synthesis of (±)-methylenolactocin 120 and (+)-C75 123.

Scheme 16. Synthesis of 1,10-seco-guaianolides 128 and 129.

Scheme 17. Synthesis of 1,10-seco-guaianolides 138 and 140.

Scheme 18. Synthesis of naturally occurring sesquiterpene lactones 149–153.

Scheme 19. Synthesis of (1Z)-deacylcnicin 160.

Scheme 20. Synthesis of naturally occurring sesquiterpene lactone 164–167.

Scheme 21. Synthesis of (−)-toxicodenane A 179 and (−)-toxicodenane A ent-179.

Scheme 22. Synthesis of lanceolactone A 185a and 4-epi-lanceolactone 185b.

Scheme 23. Synthesis of aculene D 193 aculene B^.TFA 195.

Scheme 24. Synthesis of havellockate 207.

Scheme 25. Synthesis of makassaric acid's derivative 215 & fascioquinol derivative 216.

Scheme 26. Synthesis of C20 diterpenoids 224–229.

Scheme 27. Synthesis of C20 diterpenoids 231a, 231b and 232.

Scheme 28. Synthesis of phrymarolin II 240 and its various analogues.

Scheme 29. Synthesis of sacidmulignan 247.

Scheme 30. Synthesis of (±)-8-demethylnicotlactone 250a and its analogues.

Scheme 31. Synthesis of (−)-conduritol E 256, allo-inositol 257, (−)-palitantin 259 and (+)-talo-quercitol 258.

Scheme 32. Synthesis of (+)-azimic acid 265.

Scheme 33. Synthesis of (–)-cis-α-Ambrinol 269a.

Scheme 34. Synthesis of (–)-cis-α-ambrinol 269a.

Scheme 35. Synthesis of diospongin B analogue 277.