Department of Chemistry Seminar - Sustained Electrophilic Catalysis for Cross-Coupling Chemistry and Beyond

Speaker: Prof. Takashi Niwa

Institution: Graduate School of Pharmaceutical Sciences, Kyushu University, Japan

Hosted by: Prof. Hugh NAKAMURA

Abstract

The transition-metal-catalyzed cross-coupling reaction is one of the most reliable methods for forming carbon–carbon bonds and has been driven by advances in controlling nucleophile reactivity. A key step in these reactions is the transmetalation of organometallic intermediates with nucleophiles, which typically requires the addition of a base to enhance nucleophilicity. An alternative strategy is the electrophilic activation of the organometallic intermediate, which should also facilitate transmetalation while eliminating the need for an external base, thereby enabling the use of substrates bearing basesensitive functional groups. The challenge is to sustain catalytically active electrophilic organometallic intermediates under practical reaction conditions.

In this context, we found that a Lewis acidic zinc complex enables sustained access to a cationic arylpalladium(II) intermediate through controlled release, allowing external base-free Suzuki– Miyaura cross-coupling. We subsequently extended this concept by achieving sustained electrophilic palladium catalysis through ligand design, enabling the catalytic capture of thermodynamically disfavored, low-population enamines generated from secondary amines and acyclic ketones—species that have rarely been exploited in conventional enamine catalysis.3 Although distinct molecular strategies were employed, both studies demonstrate that sustaining catalytically active electrophilic palladium species provides a general platform for expanding the scope of transition-metal-catalyzed transformations.