Tunable catalyst-controlled syntheses of β- and γ-amino alcohols enabled by silver-catalysed nitrene transfer

TLDR: Two complementary silver catalysts are reported that are capable of selecting between β- or γ-C–H bonds that reside in similar steric/electronic environments, overriding a reaction at a weaker C–H bond in favour of a stronger one and activating primary C-H bonds.

Abstract: Carbon–hydrogen bond functionalization methods are important tools for efficiently upgrading simple precursors to more valuable compounds. The ubiquity of amines in pharmaceuticals and natural products has led to considerable interest in strategies for the selective amidation of C–H bonds in a tunable manner. An ongoing challenge involves achieving control in situations where targeted bonds have varying bond strengths or similar steric/electronic environments. Herein, we report two complementary silver catalysts that are capable of selecting between β- or γ-C–H bonds that reside in similar steric/electronic environments, overriding a reaction at a weaker C–H bond in favour of a stronger one and activating primary C–H bonds. The mild conditions, low cost of silver, good yields and easy purification make this approach ideal for late-stage functionalizations to furnish valuable 1,2- and 1,3-aminoalcohols from easily prepared carbamate esters. One of the major challenges in C–H functionalization is to achieve selectivity when multiple bonds of similar reactivity are present. Now, a method to selectively amidate sterically and electronically similar β- or γ-C–H bonds that utilize different silver catalysts is reported, giving access to valuable 1,2- and 1,3-aminoalcohols.