Oxyfunctionalization of the Remote C−H Bonds of Aliphatic Amines by Decatungstate Photocatalysis

Abstract

Aliphatic amines, oxygenated at remote positions within the molecule, represent an important class of synthetic building blocks to which there are currently no direct means of access. Reported herein is an efficient and scalable solution that relies upon decatungstate photocatalysis under acidic conditions using either H O or O as the terminal oxidant. By using these reaction conditions a series of simple and unbiased aliphatic amine starting materials can be oxidized to value-added ketone products. Lastly, NMR spectroscopy using in situ LED-irradiated samples was utilized to monitor the kinetics of the reaction, thus enabling direct translation of the reaction into flow.

Activation and Deactivation Strategies Promoted by Medium Effects for Selective Aliphatic C−H Bond Functionalization

“…Evidence for the stereospecificity of the reaction was also provided by the oxidation of an optically pure ester substrate,w hich was hydroxylated with complete stereoretention (Scheme 50). [70] Pyrrolidine was selected as the model substrate and reaction optimization was carried out by high-throughput experimentation, whereby tetrabutylammonium decatungstate (TBADT) was screened with different oxidants,a cids,a nd solvents for ap hotochemical reaction. [70] Pyrrolidine was selected as the model substrate and reaction optimization was carried out by high-throughput experimentation, whereby tetrabutylammonium decatungstate (TBADT) was screened with different oxidants,a cids,a nd solvents for ap hotochemical reaction.…”

“…7 to oxidize remote aliphatic C À Hbonds of protonated amines. [70] Pyrrolidine was selected as the model substrate and reaction optimization was carried out by high-throughput experimentation, whereby tetrabutylammonium decatungstate (TBADT) was screened with different oxidants,a cids,a nd solvents for ap hotochemical reaction. Theoptimal conditions involved the use of light with l = 365 nm, H 2 SO 4 /H 2 O 2 in aqueous acetonitrile,a nd NaDT in place of TBADT for solubility reasons.Under these conditions,e xclusive formation of the product derived from C-3 oxidation was observed in 65 %y ield.…”

Anwendung von Mediumeffekten in Aktivierungs‐ und Deaktivierungsstrategien zur selektiven Funktionalisierung aliphatischer C‐H‐Bindungen

“…Schultz nutzte die HAT‐Eigenschaften des Decawolframatanions (DT, [W 10 O 32 ] 4− ) für die Oxygenierung entfernt liegender aliphatischer C‐H‐Bindungen protonierter Amine . Als Modellsubstrat wurde Pyrrolidin ausgewählt und die Reaktionsoptimierung erfolgte durch Hochdurchsatz‐Screening von Tetrabutylammoniumdecawolframat (TBADT) mit verschiedenen Oxidationsmitteln, Säuren und Lösungsmitteln in einer photochemischen Reaktion.…”

Second-Generation Palladium Catalyst System for Transannular C–H Functionalization of Azabicycloalkanes

“…5 In contrast, selective C–H functionalization of alicyclic amines at unactivated C–H sites that are remote from nitrogen remains much more challenging. 6,7,8,9,10 …”