Enantioselective Pallada-Electrocatalyzed C-H Activation by Transient Directing Groups: Expedient Access to Helicenes

Abstract

Asymmetric pallada-electrocatalyzed C-H olefinations were achieved through the synergistic cooperation with transient directing groups. The electrochemical, atroposelective C-H activations were realized with high position-, diastereo-, and enantio-control under mild reaction conditions to obtain highly enantiomerically-enriched biaryls and fluorinated N-C axially chiral scaffolds. Our strategy provided expedient access to, among others, novel chiral BINOLs, dicarboxylic acids and helicenes of value to asymmetric catalysis. Mechanistic studies by experiments and computation provided key insights into the catalyst's mode of action.

Keywords: asymmetric C−H activation; biaryls; helicene; palladium; transient directing group.

Figure 1

Enantioselective electrocatalytic C−H activation enabled by TDG.

Scheme 1

Atroposelective electrocatalyzed C−H olefination of biaryls 1.25

Scheme 2

Atroposelective pallada‐electrocatalysis with alkenes 2.25

Scheme 3

Atroposelective pallada‐electrocatalyzed C−H olefination of N‐aryl pyrroles.25

Scheme 4

Summary of key mechanistic findings.

Figure 2

Computed relative Gibbs free energies (ΔG _333.15) in kcal mol⁻¹ for the key C−H activation and migratory insertion elementary steps at the PW6B95‐D4/def2‐TZVP+SMD(AcOH)//PBE0‐D3BJ/def2‐SVP level of theory. Superscripts 5 and 7 relate to structures, which lead to the formation of the 7‐membered versus the 5‐membered cyclometallated intermediates. B and L correspond to the branched and linear products.

Figure 3

Visualization of the non‐covalent interactions calculated with the help of the NCIPLOT program, for the intermediates I‐1⁷ and I‐1⁵. In the plotted surfaces, red correspond to strong repulsive interactions, while green and blue correspond to weak and strong attractive interactions, respectively.

Scheme 5

Electrochemical access to chiral helicenes. (a) K₂OsO₄⋅2 H₂O (15 mol %), NaIO₄ (10 equiv), THF/H₂O (2/1), 50 °C, 24 h; (b) MePPh₃Br (4 equiv), nBuLi (3.8 equiv), THF, −78 °C to rt, 1 h; (c) Grubbs II (10 mol %), CH₂Cl₂, MW, 95 °C.