A new route to hindered tertiary amines

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Sterically hindered amines are important building blocks in organic synthesis.
• Efficient methods for synthesizing hindered tertiary amines are valuable.
• Carbenoid insertion reactions offer a direct route to C-N bond formation.

Purpose of the Study:

• To investigate the insertion of a rhodium-stabilized carbenoid into the N-H bond of sterically hindered secondary aliphatic amines.
• To explore the scope and limitations of this reaction with various amine substrates.
• To evaluate the use of alternative diazo compounds in rhodium-catalyzed reactions.

Main Methods:

• Rhodium(II) acetate dimer catalyzed reaction of dimethyl diazomalonate with sterically hindered secondary aliphatic amines.
• Analysis of reaction products using standard organic chemistry techniques.
• Comparison of different diazo compounds and their reactivity.

Main Results:

• Successful synthesis of hindered tertiary aliphatic amines from sterically hindered secondary aliphatic amines with satisfactory yields.
• Dimethyl 2-(dicyclohexylamino)propanedioate obtained in 85% yield.
• Dimethyl 2-(2,2,6,6-tetramethyl-1-piperidinyl)propanedioate obtained in 38% yield.
• Reaction also effective for arylalkylamines and diarylamines, with minor C-H insertion products observed.
• Other diazo compounds showed varied reactivity depending on the amine substrate.

Conclusions:

• Rhodium(II) acetate dimer catalyzed carbenoid insertion is an effective method for synthesizing hindered tertiary amines.
• The reaction exhibits tolerance for sterically demanding substrates.
• C-H insertion can compete with N-H insertion in arylalkylamines and diarylamines, influenced by substrate substitution.
• The choice of diazo compound is crucial for achieving desired outcomes with different amine classes.