Pyridine‐Hydrazone Ligands in Asymmetric Palladium‐Catalyzed 1,4‐ and 1,6‐Additions of Arylboronic Acids to Cyclic (Di)enones

Abstract

Catalysts generated by combinations of Pd(TFA) 2 and enantiomerically pure pyridine-hydrazone ligands have been applied to the 1,4-addition of arylboronic acids to b-substituted cyclic enones, building allcarbon quaternary stereocenters in high yields and enantioselectivities (up to 93% ee). The developed methodology allows the efficient introduction of ortho-substituted aryl groups in b-position of cyclopentanone cores, giving scaffolds present in a broad range of biologically active natural products. These Pd(II)complexes served also as catalysts in the 1,6-addition of arylboronic acids to cyclic dienones, affording complete regioselectivities, moderate yields and good enantioselectivities (up to 80% ee).

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

“…For the whole series of different substrates and boronic acids, there were enantioselectivities of about 90% ee and average to excellent yields of 43-97% (Table 36) [62]. This catalytic system worked for 3-unsubstituted enones but was much more powerful in the case of addition reactions to 3-substituted enones that lead to all-carbon quaternary stereogenic centres [62].…”

“…Optically pure pyridine-hydrazones were successfully used for a number of various enantioselective transformations [62]. In 2019, Retamosa et al used them for 1,4-and 1,6-addition reactions of boronic acids to cyclic (di)enones.…”

“…In 2019, Retamosa et al used them for 1,4-and 1,6-addition reactions of boronic acids to cyclic (di)enones. Initial studies showed the best yields when DCE was used as a solvent upon the addition of 0.2 equiv of water [62]. Without the addition of water, no reproducible results were obtained.…”

“…This led to the conclusion that the ligand is not chemically stable in the reaction medium and undergoes decomposition over time. Only low to average conversions (up to 81%) and only average enantioselectivities (up to 80% ee; Table 37) were achieved for the studied substrates [62].…”

“…Addition reactions of arylboronic acids to five and six-membered enones catalysed by L16/Pd(TFA) 2[62].…”