o-Halogenation and -Alkoxylation of Phenylglycine Derivatives by Pd-Mediated C-H Functionalization: Scope and Limitations

Orthopalladated derivatives from substituted phenylglycines [Pd(μ-Cl)(C₆H₃R₁C(R₂)(R₃)N(R₄)₂]₂ (<b>1</b>) react with halogenating reagents (PhICl₂, Br₂, I₂) (<b>2</b>) to give the corresponding o-halogenated amino acids C₆H₃(X)R₁C(R₂)(R₃)N(R₄)₂ (<b>3</b>). The reaction is general and tolerates a variety of functional groups (R₁ to R₄) at the aryl ring, the Cα, and the N atom. On the other hand, the reaction of [Pd(μ-Cl)(C₆H₃R₁C(R₂)(R₃)N(R₄)₂]₂ (<b>1</b>) with PhI(OAc)₂ in the presence of a variety of alcohols R₅OH (<b>4</b>) gives the o-alkoxylated phenylglycines C₆H₃(OR₅)R₁C(R₂)(R₃)N(R₄)₂ (<b>5</b>), also as a general process. A partial loss of the enantiomeric excess is observed when the starting phenylglycine is enantiomerically pure, this arising from the formation of bridging azavinylidene (<b>6</b>) and imine intermediate species (<b>7</b>), which were characterized by X-ray diffraction methods.