Modular Dearomative 1,4-Addition to Simple Arenes with Dual Nucleophiles: Overriding the Inherent 1,2-Selectivity via...

Area of Science:

• Organic Chemistry
• Organometallic Chemistry
• Synthetic Methodology

Background:

• Functionalized 1,4-cyclohexadienes are crucial synthetic intermediates.
• Direct assembly from arenes via dearomative 1,4-addition is challenging.
• Existing η⁶-coordination chemistry typically yields undesired 1,2-adducts due to regiochemical bias.

Purpose of the Study:

• To report the first intermolecular dearomative 1,4-addition to simple, unactivated arenes.
• To develop a method utilizing dual nucleophiles via η⁶-coordination to chromium/molybdenum.
• To overcome the inherent 1,2-selectivity in arene dearomatization.

Main Methods:

• Employed η⁶-coordination of arenes to chromium/molybdenum catalysts.
• Utilized a labile iodine placeholder to block inner-sphere reductive elimination.
• Investigated dual nucleophile additions, including dialkylation and hydroalkylation.

Main Results:

• Achieved the first intermolecular dearomative 1,4-addition to simple arenes.
• Enabled both dearomative 1,4-dialkylation and 1,4-hydroalkylation reactions.
• Demonstrated broad arene scope, excellent functional group tolerance, and predictable regioselectivity.

Conclusions:

• The developed method effectively overrides the innate 1,2-selectivity in arene dearomatization.
• An outer-sphere pathway is supported by mechanistic studies, including isolation of a key Mo(II)-I intermediate.
• The methodology shows significant synthetic utility in polyaromatics, drug modification, and alkaloid synthesis.