The Direct Amino Acid-Catalyzed Asymmetric Incorporation of Molecular Oxygen to Organic Compounds

Abstract

We have disclosed the direct catalytic incorporation of 1O2 to aldehydes. The unprecedented amino acid-catalyzed asymmetric alpha-oxidation of aldehydes with molecular oxygen or air proceeded with high chemoselectivity and was a direct entry for the synthesis of both enantiomers of terminal diols. The results demonstrated that simple amino acids accomplished catalytic asymmetric oxidations with molecular oxygen or air, which has previously been considered to be in the domain of enzymes and chiral transition-metal complexes. The efficiency of the catalytic process may warrant the existence of an ancient pathway for the synthesis of hydroxylated organic compounds.

Fortschritte bei katalytischen enantioselektiven α‐Aminierungen und α‐Oxygenierungen von Carbonylverbindungen

“…Kürzlich wurde auch photochemisch erzeugter Singulett-Sauerstoff als Elektrophil bei dieser Umwandlung verwendet, wobei allerdings nur mäßige Enantioselektivitäten erzielt wurden. [23] Ketone haben sich als schwierigere Substrate für diese Reaktion erwiesen. [24] Sie bilden einerseits weniger leicht mit Prolin reversibel Enamine, andererseits können zwei Kohlenstoffatome für die Enolisierung infrage kommen, was zu Problemen bei der Chemoselektivität der Oxygenierung führen kann.…”

Amine‐Catalyzed Asymmetric Epoxidation of α,β‐Unsaturated Aldehydes

“…[10] Organocatalysis has also been applied in the asymmetric a-oxidation of aldehydes and ketones with electrophilic oxidants such as nitrosobenzene, [11] iodosobenzene, [12] oxaziridines, [12] and singlet molecular oxygen. [13] More nucleophilic oxygen sources such as tert-butyl hydroperoxide, m-CPBA and hydrogen peroxide failed as oxidants for this transformation. [12] MacMillan and co-workers have demonstrated that chiral amines can catalytically activate a,b-unsaturated aldehydes and ketones towards nucleophilic attack by forming iminium ions.…”

“…[12] MacMillan and co-workers have demonstrated that chiral amines can catalytically activate a,b-unsaturated aldehydes and ketones towards nucleophilic attack by forming iminium ions. [14] Based on our research interest in organocatalysis [15] and the development of environmentally benign enantioselective oxidation processes, [12,13] we became intrigued in whether simple chiral amines would be able to catalyze asymmetric epoxidations of a,b-unsaturated aldehydes with nucleophilic oxidants by combination of an iminium and enamine activation mechanism (Scheme 1).…”

Singlet oxygen addition to cyclo-1,3-hexadienes from natural sources and from organocatalytic enal dimerization

“…We performed these experiments in the context of organocatalytic photooxygenation reactions following the α-hydroxylation route developed by Cordova et al from aliphatic ketones and aldehydes, respectively, with singlet oxygen and amino acids as chiral organocatalysts. 26,27 When these conditions were applied to α,ß-unsaturated aldehydes, complex mixtures of peroxides were observed that could not be separated. We expected the formation of dieneamines, as described in the work by Jørgensen et al 28,29 Obviously, we were not able to trap these dienes with singlet oxygen.…”