Asymmetric Dearomative Dual-Functionalization via Rearomatization-Blocked Sulfonium Claisen Rearrangement.

Area of Science:

• Organic Chemistry
• Asymmetric Synthesis
• Reaction Mechanism

Background:

• Aromatic Claisen rearrangement typically generates unstable dearomatized intermediates that rapidly rearomatize.
• Intercepting these transient intermediates is crucial for developing novel synthetic pathways.
• Existing methods lack efficient strategies to suppress rearomatization and achieve asymmetric functionalization.

Purpose of the Study:

• To develop a method for suppressing the rearomatization of dearomatized intermediates in aromatic Claisen rearrangements.
• To enable asymmetric dearomative dual functionalization of aromatic compounds.
• To synthesize complex chiral molecules with multiple stereocenters.

Main Methods:

• Developed an asymmetric dehydrative rearrangement of chiral aryl sulfimides.
• Conducted reactions at exceptionally low temperatures (-95 °C) to stabilize reactive intermediates.
• Employed a variety of nucleophiles (enol silyl ethers, organozinc reagents, heteroatom nucleophiles) for intermediate trapping.

Main Results:

• Successfully suppressed the inevitable rearomatization of dearomatized intermediates.
• Achieved asymmetric dearomative dual functionalization, yielding products with up to four contiguous stereocenters.
• Demonstrated three distinct desulfurization pathways leading to structurally diverse chiral products with axial and point chirality.

Conclusions:

• The developed method provides a unique strategy for controlling the reactivity of dearomatized intermediates.
• Enables the synthesis of complex chiral molecules through a novel dearomatization manifold.
• Computational studies elucidated the mechanism and confirmed high fidelity in chirality transfer.