Formal Aerobic Oxidative Cross-Coupling of Benzofuranones with Azo Compounds Using Pd-μ-hydroxo Complex

Abstract

We have developed a catalytic aerobic oxidative dimerization reaction of benzofuranones using a Pd(II)-µ-hydroxo complex. Radical-radical cross-coupling of the resulting dimers with azo compounds enabled the one-pot synthesis of structurally congested benzofuranones having two distinct vicinal all-carbon quaternary centers.

Pd‐catalyzed Aerobic Cross‐Dehydrogenative Coupling of Catechols with 2‐Oxindoles and Benzofuranones: Reactivity Difference Between Monomer and Dimer

“…We should also note that the oxidative dimerization of 1 does not always yield the desired dimers 2 . For example, we encountered a low yield (2%) when we prepared benzofuranone dimer 2 c (Ar=4‐MeO‐C 6 H 4 ) from 1 c with K 3 [Fe(CN) 6 ], [21b,c] a widely‐used oxidant for the oxidative dimerization of 1 [40] . Furthermore, the application of another protocol using a Pd(II) catalyst for the aerobic oxidative dimerization of 1 c resulted in only a slight increase in the yield of 2 c (28%) [21c] …”

“… [40] Furthermore, the application of another protocol using a Pd(II) catalyst for the aerobic oxidative dimerization of 1 c resulted in only a slight increase in the yield of 2 c (28%). [21c] …”

“…The yield of 4 bb was reduced to 7%, with the 42% recovery of 1 b . However, from the mechanistic viewpoint, we should note that the dimer 2 b (9%)[ 21c , 42 ] was formed with concomitant generation of tert ‐alcohol 5 b (8%). These results suggest that the addition of catechol ( 3 b ) assisted in the generation of 1 b ⋅ even in the absence of Pd(II) catalyst I .…”

“…The observed robustness with various radical precursors 1 further prompted us to apply the developed conditions with the Pd catalyst I to benzofuranone 1 c (Ar=4‐MeO‐C 6 H 4 ), which has been difficult to control in the radical‐based oxidative transformations (Scheme 3 ). [ 21b , 21c ] Based on our preliminary DFT calculations for the model reaction of 1 a⋅ and 3 a , we hypothesized that a catalytic amount of the Pd−catecholate/ 1 c ⋅ should be transiently generated when the benzofuranone 1 c is mixed with catechol ( 3 b ) under the developed aerobic conditions. If so, 1 c⋅ should be preferentially trapped with the proximal Pd−catecholate, to promote the sequential HAS and oxidative aromatization.…”

Recent Advances in Palladium-Catalyzed Oxidative Couplings in the Synthesis/Functionalization of Cyclic Scaffolds Using Molecular Oxygen as the Sole Oxidant

“…In 2020, Sohtome and Sodeoka reported a formal aerobic oxidative cross-coupling of benzofuranones with subsequent functionalization with azo compounds promoted by Pd--hydroxo complexes in a radical-radical coupling fashion (Scheme 39). 65 Using a persistent transient radical strategy, the dimerization of benzofuranones was achieved in high yields by using a highly bulky palladium-based dimer as a co-catalyst and molecular oxygen (1 atm). The dimeric species were used as intermediates in the synthesis of azo compounds in a single-flask operation, providing nitrogenated benzofuranones in moderate to high yields (Scheme 39).…”