Tandem RCM-isomerization-cyclopropanation reactions

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Developing efficient synthetic routes for complex organic molecules is crucial.
• Bicyclic compounds and nitric oxide synthase (iNOS) inhibitors have significant therapeutic potential.
• Existing methods may require multiple steps or harsh conditions.

Purpose of the Study:

• To introduce a novel triple tandem reaction for synthesizing bicyclic compounds.
• To demonstrate a one-pot synthesis of iNOS inhibitor precursors.
• To showcase the utility of second-generation Grubb's catalyst in this transformation.

Main Methods:

• A triple tandem process involving Ring-Closing Metathesis (RCM), double bond isomerization, and cyclopropanation.
• Catalysis using second-generation Grubb's catalyst.
• A one-pot RCM-isomerization followed by cyclopropanation using chloroform and sodium hydroxide.

Main Results:

• Successful transformation of simple acyclic substrates into bicyclic compounds.
• The process is catalyzed efficiently by second-generation Grubb's catalyst without additives.
• Synthesis of iNOS inhibitor-related compounds was achieved in a one-pot procedure.

Conclusions:

• A new, efficient triple tandem reaction has been established for bicyclic compound synthesis.
• This methodology offers a streamlined approach to potential iNOS inhibitors.
• The discovered process highlights the versatility of Grubb's catalyst in complex transformations.