Dearomatization of aromatic asmic isocyanides to complex cyclohexadienes

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Aromatic isocyanides are versatile building blocks in organic synthesis.
• Developing efficient methods for dearomatization of aromatic compounds is crucial for accessing complex molecular architectures.

Purpose of the Study:

• To develop a novel, rapid cascade reaction for the synthesis of highly functionalized cyclohexadienes from aromatic isocyanides.
• To investigate the mechanism of this transformation and explore its synthetic utility.

Main Methods:

• A dearomatization-dislocation-coupling cascade reaction.
• Experimental studies including reaction optimization and substrate scope.
• Computational analyses to elucidate the reaction mechanism.

Main Results:

• The cascade reaction efficiently transforms aromatic isocyanides into functionalized cyclohexadienes.
• The method installs three carbon-carbon bonds, two quaternary stereocenters, and three orthogonal functionalities.
• The reaction proceeds under mild conditions (minutes at -78°C) with broad substrate tolerance.
• An electron transfer-initiated mechanism involving isocyanide rearrangement and radical-radical anion coupling was proposed.

Conclusions:

• A novel and efficient cascade reaction for cyclohexadiene synthesis from aromatic isocyanides has been established.
• The method offers a mild and rapid route to complex molecular structures with significant synthetic value.
• The mechanistic insights provide a deeper understanding of isocyanide chemistry and dearomatization processes.