Carbene-controlled regioselectivity in photochemical cascades

Area of Science:

• Organic Chemistry
• Photochemistry
• Synthetic Chemistry

Background:

• Carbocyclic scaffolds are crucial building blocks in medicinal chemistry and materials science.
• Developing regioselective synthetic routes remains a key challenge in organic synthesis.
• Photochemical methods offer unique pathways for molecular construction but often lack predictable selectivity.

Purpose of the Study:

• To report a novel, highly regioselective continuous photochemical process for synthesizing complex carbocyclic scaffolds.
• To elucidate the mechanism governing the observed exclusive regioselectivity.
• To explore the influence of electronic substituents on product distribution and uncover new photochemical transformations.

Main Methods:

• A continuous flow photochemical reactor was employed for the synthesis.
• Varied non-symmetrically substituted aryl moieties were used to probe substituent effects.
• Spectroscopic and analytical techniques were used to characterize products and intermediates.

Main Results:

• Achieved a highly regioselective synthesis of carbocyclic scaffolds via a continuous photochemical process.
• Identified that ortho-substituents direct away from a transient carbene, ensuring exclusive regioselectivity.
• Demonstrated control over product outcome (cyclobutenes vs. cycloheptatrienes) by tuning electronic properties of aryl substituents.
• Discovered a novel photochemically induced rearrangement yielding complex hydroperoxides for electron-rich substrates.

Conclusions:

• The reported one-step photochemical process is fast, high-yielding, and provides exclusive regioselectivity.
• This method offers a powerful platform for exploring new chemical space and accessing complex carbocyclic structures.
• The findings highlight the potential of continuous flow photochemistry in modern synthetic strategies.