Towards the activity of twisted acyclic amides

Area of Science:

• Organic Chemistry
• Computational Chemistry

Background:

• N,N-Boc2 amides are prevalent acyclic twisted amides utilized in C-N bond activation and cross-coupling reactions.
• Their synthesis involves site-selective tert-butoxycarbonylation of primary amides.
• The steric bulk of di-tert-butoxy groups induces significant C=N bond twisting, promoting N-C bond cleavage.

Purpose of the Study:

• To computationally investigate the C=N bond rotation mechanism in N,N-Boc2 amides.
• To understand how substituent effects influence rotational barriers and twist angles.
• To explore the relationship between electronic properties and amide bond distortion.

Main Methods:

• Computational modeling to analyze C=N bond rotation.
• Calculation of rotational barriers and twist angles (τ).
• Analysis of substituent effects and accompanying phenyl ring rotations.

Main Results:

• The rotational barrier and twist angle are dependent on the substituents at the sp2 carbon.
• Sterically hindered substituents lead to greater distortions and lower rotation barriers.
• Phenyl ring rotation occurs concurrently to minimize steric hindrance.
• A significant correlation exists between rotational barriers and Highest Occupied Molecular Orbital (HOMO) energies.

Conclusions:

• Amide bond distortion is crucial for C-N activation processes.
• Computational insights reveal the factors governing C=N bond rotation in N,N-Boc2 amides.
• Understanding these factors can guide the design of more efficient catalysts and reactions.