Newly developed Pd/ZU-Phos/DBN cooperative catalysis enables enantioselective [4+2] annulations for efficient synthesis of diverse spirocyclic scaffolds

新开发的Pd/ZU-Phos/DBN协同催化可实现对映选择性[4+2]环加成反应,从而高效合成多种螺环骨架。

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Abstract

Chiral ligands are essential for asymmetric catalysis, as they greatly improve the chemical selectivity of the catalytic process. The cooperative action of multiple ligands may enhance catalytic efficiency and selectivity by optimizing individual steps within the catalytic cycle. Here, we synthesized a series of novel P-chiral ligands (ZU-Phos) that enabled highly efficient asymmetric [4+2] annulations of 1,2-disubstituted allylic carbonates with activated olefins, yielding a variety of optically active and medicinally relevant spirocyclic scaffolds in yields of ≤96% and with ≤98% ee through a novel dual coordination mechanism. Mechanistic investigations disclosed that 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) served a dual function as a Brønsted base and formed a unique mixed ligated Pd/ZU-Phos/DBN complex. This study highlights the distinctive benefits of Pd/ZU-Phos ligand catalysis and underscores the efficacy of the dual-ligand system in broadening the scope of palladium-catalysed reactions. Density functional theory calculations showcase that DBN modulated the catalytic activity of the palladium catalysts via weak coordination and enhanced product enantioselectivity by stabilizing the chiral environment through weak interactions with phosphorus ligands.

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