Organic Stress: A Tool for Chemical Synthesis

Ring-strain in organic molecules is a powerful driving force that promotes reactivity through strain-release, allowing the facile construction of a myriad of useful scaffolds via ring-opening or ring-expansion reactions.

Carbene chemistry has been widely studied and found numerous applications in organic synthesis such as X–H (X = C, Si, N, O, etc.) insertions, cyclopropanations, ylide formations, and 1,2-migrations. Due to their high reactivity, carbenes are also ideal for initiating a cascade sequence, leading to rapid generation of structural complexity. In this talk, I will first discuss strain-enabled radical cascades for synthesizing functionalized spirocyclobutyl lactones, – lactams, and -oxindoles. To introduce a more diverse set of functional groups, we have developed a dual photoredox/nickel system capable of mediating the carbosulfonylation of BCB allyl amides.

In the second part, I will talk about how we merged strain-release and metal-carbene chemistry to unlock new strategies for organic synthesis. A copper-catalyzed highly diastereoselective strain-release [2,3]-sigmatropic rearrangement will be discussed first. Then, I will show how we utilized the ring strain in [1.1.1]propellane to access copper-carbenes for [2,3]-sigmatropic rearrangement.

In the end, I will focus on rhodium-catalyzed strain-enabled stereoselective synthesis of skipped dienes.

Key takeaways for the attendees:

• Strain-Enabled Radical Spirocyclization Cascades
• Merging Ring-Strain and Carbene Chemistry
• Diastereoselective Doyle-Kirmse reaction
• Harnessing Carbene Reactivity of BCB and [1.1.1]Propellane
• New strategies for Methylenecyclopropanes and Methylenecyclobutanes