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

Abstract

AbstractThis paper reports the synthesis of enantiopure aryl alkyl ethers via the Pd(II)‐catalyzed picolinamide‐aided γ‐C(sp2)−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(sp2)−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.