Work

Effective and Practical Stereoselective Synthesis of Nutlins Precursors by Immobilization of Privileged Chiral Mono‐Amidine Catalyst

Year: 2025

Type: article

Abstract: A strategy for the immobilization of Johnston's Mono(AMidine) catalyst ( MAM ) onto polystyrene, silica and hybrid silica‐polystyrene nanoparticles is presented. The catalyst activity was evaluated in the stereoselective aza‐Henry reaction leading to the pivotal β‐amino nitroalkane precursors of the anti‐cancer agents Nutlins (with Nutlin‐3a as the most active drug). The effect of the support and the linker on the catalytic performance was investigated, observing an interesting match/mismatch effect when using a chiral linker. The polystyrene‐supported 3‐pyrrolidinol‐linked PS‐( S )‐Pyr‐MAM organocatalyst showed the best activity among the tested catalysts, behaving very similarly to the homogeneous counterpart in the synthesis of a library of Nutlins precursors: yield up to 95%, ee up to 99%, and dr up to >99:1. The catalyst recyclability was also assessed through simple filtration, yielding a satisfactory 93% ee after 5 cycles, showing only a moderate decrease in conversion efficiency (ca. 5% after each cycle), which resulted in an accumulated turnover number (TON) of 69.7.

Source: Advanced Synthesis & Catalysis

DOI: 10.1002/adsc.202500058