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Redox-neutral α-oxygenation of amines: reaction development and elucidation of the mechanism.

Richers MT, Breugst M, Platonova AY, Ullrich A, Dieckmann A, Houk KN, Seidel D - J. Am. Chem. Soc. (2014)

Bottom Line: Reactions performed under modified conditions lead to an apparent reductive amination and the formation of o-hydroxybenzylamines in a process that involves the oxidation of a second equivalent of amine.A detailed computational study employing density functional theory compares different mechanistic pathways and is used to explain the observed experimental findings.Furthermore, these results also reveal the origin of the catalytic efficiency of acetic acid in these transformations.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854, United States.

ABSTRACT
Cyclic secondary amines and 2-hydroxybenzaldehydes or related ketones react to furnish benzo[e][1,3]oxazine structures in generally good yields. This overall redox-neutral amine α-C-H functionalization features a combined reductive N-alkylation/oxidative α-functionalization and is catalyzed by acetic acid. In contrast to previous reports, no external oxidants or metal catalysts are required. Reactions performed under modified conditions lead to an apparent reductive amination and the formation of o-hydroxybenzylamines in a process that involves the oxidation of a second equivalent of amine. A detailed computational study employing density functional theory compares different mechanistic pathways and is used to explain the observed experimental findings. Furthermore, these results also reveal the origin of the catalytic efficiency of acetic acid in these transformations.

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Calculated structures [M06-2X-D3/def2-TZVPP/IEFPCM//TPSS-D2/6-31+G(d,p)/IEFPCM],relative free energies (in kcal·mol–1), selectedbond lengths (in Å), and selected NBO charges for transitionstate TS2.
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fig4: Calculated structures [M06-2X-D3/def2-TZVPP/IEFPCM//TPSS-D2/6-31+G(d,p)/IEFPCM],relative free energies (in kcal·mol–1), selectedbond lengths (in Å), and selected NBO charges for transitionstate TS2.

Mentions: A subsequent proton transfer via TS2 leads to theazomethine ylide 19f in another endergonic transformation(Figure 4). Theendergonicity of this step is also reflected in the short O–Hbond length of the late transition state TS2. This reactioncould proceed via either a 1,6-hydride shift or a 1,6-proton transfer,and our charge calculations (NBO or ChelpG) indicate that the latteris more likely due to a significant positive charge on the transferredhydrogen atom.


Redox-neutral α-oxygenation of amines: reaction development and elucidation of the mechanism.

Richers MT, Breugst M, Platonova AY, Ullrich A, Dieckmann A, Houk KN, Seidel D - J. Am. Chem. Soc. (2014)

Calculated structures [M06-2X-D3/def2-TZVPP/IEFPCM//TPSS-D2/6-31+G(d,p)/IEFPCM],relative free energies (in kcal·mol–1), selectedbond lengths (in Å), and selected NBO charges for transitionstate TS2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4333595&req=5

fig4: Calculated structures [M06-2X-D3/def2-TZVPP/IEFPCM//TPSS-D2/6-31+G(d,p)/IEFPCM],relative free energies (in kcal·mol–1), selectedbond lengths (in Å), and selected NBO charges for transitionstate TS2.
Mentions: A subsequent proton transfer via TS2 leads to theazomethine ylide 19f in another endergonic transformation(Figure 4). Theendergonicity of this step is also reflected in the short O–Hbond length of the late transition state TS2. This reactioncould proceed via either a 1,6-hydride shift or a 1,6-proton transfer,and our charge calculations (NBO or ChelpG) indicate that the latteris more likely due to a significant positive charge on the transferredhydrogen atom.

Bottom Line: Reactions performed under modified conditions lead to an apparent reductive amination and the formation of o-hydroxybenzylamines in a process that involves the oxidation of a second equivalent of amine.A detailed computational study employing density functional theory compares different mechanistic pathways and is used to explain the observed experimental findings.Furthermore, these results also reveal the origin of the catalytic efficiency of acetic acid in these transformations.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854, United States.

ABSTRACT
Cyclic secondary amines and 2-hydroxybenzaldehydes or related ketones react to furnish benzo[e][1,3]oxazine structures in generally good yields. This overall redox-neutral amine α-C-H functionalization features a combined reductive N-alkylation/oxidative α-functionalization and is catalyzed by acetic acid. In contrast to previous reports, no external oxidants or metal catalysts are required. Reactions performed under modified conditions lead to an apparent reductive amination and the formation of o-hydroxybenzylamines in a process that involves the oxidation of a second equivalent of amine. A detailed computational study employing density functional theory compares different mechanistic pathways and is used to explain the observed experimental findings. Furthermore, these results also reveal the origin of the catalytic efficiency of acetic acid in these transformations.

Show MeSH
Related in: MedlinePlus