Rhodium(III)-Catalyzed Remote Hydroamidation of Internal Alkenes Via Chain Walking

Hydroamination of terminal alkenes represents a powerful and well-established way to introduce nitrogenous functionality to feedstock chemicals. Remote hydroamination reactions are far less known, and represent a way to functionalize unactivated C(sp³) centers distal to the site of the alkene. These transformations commonly take place via metal hydride-mediated chain walking, and as such, regioselectivity can be challenging. The remote introduction of amides is of particular interest due to their prevalence in pharmaceuticals. Herein we report a Rh(III)-catalyzed hydroamidation procedure to functionalize the terminal position of internal alkenes, using dioxazolones as amidation reagents and i-PrOH as a hydride source. The reaction proceeds with high yield and regioselectivity, and tolerates a variety of functionality. Regioconvergent synthesis of a single linear amide from a mixture of isomeric alkenes is demonstrated. Key to the development of this reaction was determining that inorganic bases poison the catalyst, and identifying a suitable trialkylamine replacement.