Interception of Transient Allyl Radicals with Low-Valent Allylpalladium Chemistry: Tandem Pd(0/II/I)–Pd(0/II/I/II) Cycles in Photoredox/Pd Dual-Catalytic Enantioselective C(sp³)–C(sp³) Homocoupling

Creators: Li, Bo; Zhang, Hong-Hao; Luo, Yongrui; Yu, Shouyun; Goddard, William A., III¹; Dang, Yanfeng

1. California Institute of Technology

Abstract

We present comprehensive computational and experimental studies on the mechanism of an asymmetric photoredox/Pd dual-catalytic reductive C(sp³)–C(sp³) homocoupling of allylic electrophiles. In stark contrast to the canonical assumption that photoredox promotes bond formation via facile reductive elimination from high-valent metal–organic species, our computational analysis revealed an intriguing low-valent allylpalladium pathway that features tandem operation of Pd(0/II/I)–Pd(0/II/I/II) cycles. Specifically, we propose that (i) the photoredox/Pd system enables the in situ generation of allyl radicals from low-valent Pd(I)-allyl species, and (ii) effective interception of the fleeting allyl radical by the chiral Pd(I)-allyl species results in the formation of an enantioenriched product. Notably, the cooperation of the two pathways highlights the bifunctional role of Pd(I)-allyl species in the generation and interception of transient allyl radicals. Moreover, the mechanism implies divergent substrate-activation modes in this homocoupling reaction, suggesting a theoretical possibility for cross-coupling. Combined, the current study offers a novel mechanistic hypothesis for photoredox/Pd dual catalysis and highlights the use of low-valent allylpalladium as a means to efficiently intercept radicals for selective asymmetric bond constructions.

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Acknowledgement

Financial support from the National Natural Science Foundation of China (Nos. 22073067, 21971110, and 22001120), the Natural Science Foundation of Jiangsu Province (No. BK20200297), and the Haihe Laboratory in Tianjin (No. 22HHXCJC00007) is acknowledged. The authors also acknowledge National Supercomputer Center in Tianjin, where the calculations were performed on Tianhe 3F. W.A.G. thanks the US National Science Foundation for support (CBET 2311117, Robert McCabe, prog. Mgr.).

Contributions

B.L. and H.-H.Z. contributed equally to this work.

Data Availability

Computational and experimental results; general procedure for the synthesis of products 2 and characterization; energies and Cartesian coordinates of optimized structures; NMR spectra of synthesized compounds; photoexcitation of Ir^III species (Figure S1); Ir^III/Pd^II-allyl quenching pathways (Figure S2); Ir^III*/DIPEA ligand reduction pathways (Figure S3); reduction of allylpalladium Pd^IIA by I• and IrII (Figure S4); transition-state bonding interactions in reductive elimination (Figure S5); calculations for outer-sphere bond-formation pathway (Figure S6), direct Pd(0/II/IV) coupling pathway (Figure S7), radical generation pathway (Figure S8), C(sp³)–C(sp³) coupling pathway (Figure S9); screening of the chiral ligands and the reductant (Tables S1 and S2) (PDF)

Conflict of Interest

The authors declare no competing financial interest.

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