Pd(II)‐Catalyzed, γ‐C(sp2)−H Alkoxylation in α‐Methylbenzylamine, Phenylglycinol, 3‐Amino‐3‐Phenylpropanol Toward Enantiopure Aryl Alkyl Ethers

Abstract This paper reports the synthesis of enantiopure aryl alkyl ethers via the Pd(II)‐catalyzed picolinamide‐aided γ ‐C(sp 2 )−H alkoxylation of various enantiopure α ‐alkylbenzylamine derivatives using alcohols. Enantiopure α ‐methylbenzylamines and amino alcohol substrates such as 2‐amino‐2‐phenylethanol (phenylglycinol) and 3‐amino‐3‐phenylpropanol were subjected to the γ ‐C(sp 2 )−H alkoxylation (etherification) with alcohols using PIDA. α ‐Alkylbenzylamines and phenylglycinols are valuable building blocks in organic synthesis and medicinal chemistry research areas. Accordingly, this work has enabled the assembling of various enantiopure ortho ‐alkoxylated α ‐methylbenzylamine and 2‐amino‐2‐phenylethanol (phenylglycinol) and 3‐amino‐3‐phenylpropanol derivatives containing aryl alkyl ether functionality. We have shown the utility of ortho ‐alkoxylated α ‐methylbenzylamine derivatives for assembling enantiopure α ‐methylbenzylamine‐based sulfamoylcarbamates and carboxamides which are structurally related to the bio‐active compounds known in the literature. This work demonstrates the substrate scope elaboration in C−H functionalization and etherification through the C−O bond‐forming process and synthesis of aryl alkyl ether functionality containing enantiopure α ‐alkylbenzylamines.