Pd(II)-catalyzed ortho- or meta-C-H olefination of phenol derivatives

Abstract

A combination of weakly coordinating auxiliaries and ligand acceleration allows for the development of both ortho- and meta-selective C-H olefination of phenol derivatives. These reactions demonstrate the feasibility of directing C-H functionalizations when functional groups are distal to target C-H bonds. The meta-C-H functionalization of electron-rich phenol derivatives is unprecedented and orthogonal to previous electrophilic substitution of phenols in terms of regioselectivity. These methods are also applied to functionalize α-phenoxyacetic acids, a fibrate class of drug scaffolds.

Figure 1

Previous ortho-C–H Functionalizations of Phenol

Figure 2

Remote ortho- and meta-C–H Functionalizations

Figure 3

Drug Molecules Based on α-Phenoxyacetic Acids

Figure 4

Catalytic Cycle of meta-C–H Olefination

Scheme 1

The removal of Directing Group^{a a} Reaction conditions: 3a (0.4 mmol), DPPA (0.4 mmol), Et₃N (0.4 mmol), toluene (5 mL), DMF (0.5 mL), refluxed 3h. DPPA: diphenylphosphoryl azide. Yield: 71%.