Ruthenium-catalyzed Asymmetric Addition Of Arylboronic Acids To Aromatic Aldehydes

Chiral diarylmethanol is an important precursor and intermediate for the synthesis of biological and pharmaceutical active compounds.The synthesis of chiral diarylmethanol can be achieved by two main strategies:1)asymmetric addition of aryl nucleophiles to aryl aldehydes;2)asymmetric reduction of diaryl ketones.For the first strategy,aryl zinc reagents are usually used in the initial research to perform asymmetric addition to aldehydes.Diphenyl zinc is a common aryl donor,which is expensive,relatively unstable,and limited to the transfer of phenyl groups;The operation steps of the arylation reaction involving diethylzinc are more complicated and require additional addition of DiMPEG.For the asymmetric reduction of chiral diarylketones,due to the stricter requirements on the substrate structure and the limited range of substrates,the applicability of this method is not much well.In 1998,Miyaura research group reported the first example of asymmetric nucleophilic addition to 1naphthylaldehyde with phenylboronic acid directly via a transition metal rhodium catalyst,afforded good yield(78%)and moderate enantioselectivity(41%).Due to the characteristics of cheap,non-toxic and stability of arylboronic acid,it is highly desirable to develope chiral transition metal catalysts on the asymmetric addition reaction to arylaldehyde with arylboronic acid.Based on a class of electron-rich dicyclohexylphosphine ligands derived from chiral amino alcohols developed by our group,the combination of transition metal ruthenium complex precursors[RuCl2(p-cymene)]2 and ligands enable the asymmetric addition reaction of arylboronic acid to aromatic aldehyde.The effects of the types of bases,solvents and their proportions,reactant equivalence ratio,ligand types,[RuCl2(pcymene)]2/L ratio,temperature,additive types,ruthenium source and reaction time on the reaction system were examined.Under the optimal conditions,aromatic aldehydes and arylboronic acids were screened respectively,the results show that this kind of catalyst can effectively catalyze the reactions and obtain higher reaction yields and upper-middle enantioselectivities.The development of this research is helpful to explore the relationship between catalyst structure and catalytic stereoselectivity,and provides new ideas for further improving the enantioselectivity of the reaction.