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

## TL;DR

A new catalytic system efficiently creates diverse spirocyclic compounds with high purity and optical activity.

## Contribution

A novel Pd/ZU-Phos/DBN cooperative catalytic system enables efficient asymmetric [4+2] annulations.

## Key findings

- The Pd/ZU-Phos/DBN system achieves spirocyclic scaffolds with up to 96% yield and 98% ee.
- DBN acts as a Brønsted base and forms a mixed-ligated complex with Pd and ZU-Phos.
- DFT calculations show DBN enhances enantioselectivity via weak coordination and stabilization.

## 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.

New Pd/WQ-Phos/DBN complex enables asymmetric [4+2] annulations, yielding optically active and biologically relevant spiro scaffolds with up to 96% yield and 98% ee.