A Solid-Phase Assisted Flow Approach to In Situ Wittig-Type Olefination Coupling

Described herein is the development of a continuous flow, solid-phase triphenylphosphine (PS-PPh3) assisted protocol to facilitate the in situ coupling of reciprocal pairs of halogen and carbonyl functionalised molecular pairs by a Wittig olefination within 15 mins. The protocol entails injecting a single solution (1 : 1 CHCl3 : EtOH) containing the halogenated and carbonyl-based substrates into a continuously flowing stream of CHCl3 : EtOH (1 : 1), passed through a fixed bed of K2CO3 and PS-PPh3. With advancement to the previous PS-PPh3 coupling procedures, the method employs a traditional polystyrene-based immobilisation matrix, the substrate scope of the protocol extended to substituted ketones, secondary alkyl chlorides, and an unprotected maleimide scaffold.

Automated summary

The development of a continuous flow, solid-phase triphenylphosphine (PS-PPh3) assisted protocol for in situ coupling of halogen and carbonyl functionalised molecular pairs by Wittig olefination within 15 mins is described. This method uses a traditional polystyrene-based immobilisation matrix and expands the substrate scope to substituted ketones, secondary alkyl chlorides, and an unprotected maleimide scaffold.