Generalizing Vinyl Halide Cross-Coupling Reactions with Photoredox and Photoredox/Nickel Dual Catalysis

Area of Science:

• Organic Chemistry
• Photocatalysis
• Synthetic Methodology

Background:

• Efficient cross-coupling reactions are crucial for pharmaceutical research, particularly for lead discovery and late-stage diversification.
• Existing methods for vinyl halide cross-coupling often lack broad applicability and require extensive optimization.
• A general strategy for diverse vinyl halide cross-coupling reactions is needed to streamline synthetic efforts.

Purpose of the Study:

• To report a general, predictable, and broadly applicable method for vinyl halide cross-coupling under photoredox conditions.
• To develop complementary catalytic systems for diverse nucleophile coupling.
• To demonstrate the utility of the developed method in complex molecule synthesis and late-stage functionalization.

Main Methods:

• Utilized two complementary photoredox catalytic systems for vinyl halide cross-coupling.
• Employed the organic photocatalyst 4CzIPN for coupling with various nucleophiles (thiols, selenols, sulfinates, alkenes, P(III), B compounds).
• Developed a dual nickel-photoredox catalytic system for coupling with less reactive nucleophiles (P(V), N, O).

Main Results:

• Achieved efficient C(sp2)─S, ─Se, ─C, ─P, and ─B bond formation using the 4CzIPN system.
• Enabled seven distinct bond-forming reactions, including C(sp2)─P(V), ─N, and ─O bonds with the dual catalytic system.
• Demonstrated broad electrophile and nucleophile scope, high functional group tolerance, and applicability to late-stage functionalization of complex biomolecules.

Conclusions:

• The developed photoredox method offers a general and predictable strategy for vinyl halide cross-coupling.
• The complementary catalytic systems expand the scope of accessible bond formations.
• The method's efficiency and versatility facilitate rapid drug discovery and development through streamlined synthesis.