Organic Chemistry Seminar: SELECTIVE OXIDATIVE CROSS-COUPLING REACTIONS OF PHENOLS BY IRON CATALYSIS

Abstract:

Biomimetic oxidative coupling reactions of phenols provide an environmentally friendly strategy to form new CC bonds directly from two CH bonds. For many years this radical chemistry suffered from a lack of selectivity, making the cross-coupling of two non-identical coupling partners at specific sites with control over the stereoselectivity, difficult to obtain. 

To address the selectivity problem in this chemistry, a set of highly selective catalytic systems based on redox iron catalysts suitable for oxidative phenol-phenol and phenol-arene cross-coupling were developed. With the aid of DFT calculations, electrochemical techniques and EPR spectroscopy a prediction model to anticipate the feasibility of phenol pairs to favor cross-coupling over homocoupling has been developed, thereby enabling direct entry to specific phenolic architectures in high efficiency. To address the stereoselectivity issue in this chemistry, novel chiral iron phosphate complexes were prepared and applied as catalysts for the synthesis of enantio-enriched C1- and C2-symmetric BINOLs. A destructive BINOL racemization process that competes with the enantioselective oxidative coupling of 2-naphthols was revealed, thereby offering new insights into this highly important reaction.

Selected References: 

Stereoselectivity [  Fe[phosphate]3  ]: 

[1] Narute, S. ; Pappo, D. Org. Lett. 2017, 19 (11), 2917.

[2] Narute, S.; Parnes, R.; Toste, F. D.; Pappo, D. J. Am. Chem. Soc. 2016,  138 (50), 16553.

Chemoselectivity [  FeCl3 and Fe[TPP]Cl  ]:

[3] Shalit, H.; Libman, A.; Pappo, D. 2017, submitted.

[4]  Libman, A.; Shalit, H.; Vainer, Y.; Narute, S.; Kozuch, S.; Pappo, D. J. Am. Chem. Soc. 2015, 137, 11453.

[5]  Gaster, E.; Vainer, Y.; Regev, A.; Narute, S.; Sudheendran, K.; Werbeloff, A.; Shalit, H.; Pappo, D. Angew. Chem. Int. Ed. 2015, 54 (14), 4198.

Regioselectivity [  FeCl3  ]: 

[6] Vershinin, V.; Dyadyuk, A.; Pappo, D. Tetrahedron 2017, Early View. [invited paper]

[7] Dyadyuk, A.; Sudheendran, K.; Vainer, Y.; Vershinin, V.; Shames, A. I.; Pappo, D. Org. Lett. 2016, 18 (17), 4324.

Seminar Organizer: Dr. Roman Dobrovetsky