Aerobic Oxidation Of Alcohols Catalyzed By Iron Combined With Amino Acids

Selective oxidation of primary and secondary alcohols to the corresponding carbonyl compounds using molecular oxygen as the oxidant is one of the most important transformations in organic synthesis.Inspired by various biomimetic complexes of heme and nonheme enzymes,an efficient biomimetic oxidation of alcohols that uses iron as catalyst in combination with amino acids as powerful N,O-bidentate ligand has been developed,in which dioxygen was utilized as an untimate oxidant.A wide range of primary/secondary benzyl,allylic,and heterocyclic alcohols have been efficiently converted into aldehydes and ketonesInitially,methionine,isoleucine,histidine,glycine,alanine,valine,phenylalanine,cysteine were used as starting material by acetylation,carbobenzyloxylation,fiuorenylmethoxy carbonylation,tert-butoxycarbonylation,and N-phenylation reactions afforded various mono N-Ac,N-Cbz,N-Fmoc,N-Boc protected amino acid and N-phenyl amino acid ligands.The structures of these ligands were characterized by ¹HNMR,¹³ CNMR.Then,a systematic screening of solvents,ligands,catalysts,and additives was carried out.Hence,the optimized reaction conditions were obtained: 1.0 mmol alcohol,5 mol% FeCl₃,10 mol% L-valine,10 mol% TEMPO,700 mg 4? MS in toluene under reflux and O₂ atmosphere.Various primary benzyl,allylic,and heterocyclic alcohols were efficiently transformed into corresponding aldehydes in this system.Meanwhile,the substrate was almost completely converted with excelent selectivity?>99%?.Secondly,based on the aforementioned oxidation conditions used for primary alcohols,the effects of iron salts,amino acids,TEMPO,additives and reaction time on the transformation were then examined for the secondary alcohols.To our delight,the optimal reaction conditions for the secondary alcohol oxidation was obtained: 1mmol alcohol,10 mol% FeCl₃,10 mol% L-valine,10 mol% TEMPO,700 mg 4? MS in toluene under reflux and O₂ atmosphere.Under this optimized reaction conditions,a range of secondary benzyl,allylic,and heterocyclic alcohols were efficiently converted to the desired carbonyl compounds with excellent functional-group compatibility and high isolated yields.