Functionalization of α-C(sp3 )-H Bonds in Amides Using Radical Translocating Arylating Groups

Abstract

α-C-H arylation of N-alkylamides using 2-iodoarylsulfonyl radical translocating arylating (RTA) groups is reported. The method allows the construction of α-quaternary carbon centers in amides. Various mono- and disubstituted RTA-groups are applied to the arylation of primary, secondary, and tertiary α-C(sp³ )-H-bonds. These radical transformations proceed in good to excellent yields and the cascades comprise a 1,6-hydrogen atom transfer, followed by a 1,4-aryl migration with subsequent SO₂ extrusion.

Keywords: aryl migration; hydrogen atom transfer; radical; visible light catalysis.

Scheme 1

C‐arylation using radical and ionic chemistry. a) Remote C−H arylation of unactivated C(sp³)−H bonds using RTA groups. ^[9] b) Radical α‐arylation of prefunctionalized amides.[ ^11a , ^11b , ^11c , ¹² ] c) Stereoselective anionic remote α‐C(sp³)−H arylation of amino acids. ^[13] d) This work: remote radical C(sp³)−H arylation of amides under construction of an all‐carbon quaternary center.

Scheme 2

Substrate scope—variation of the N substituent R. Reaction scale between 0.1 and 0.25 m. Yields of isolated product. [a] Reaction time: 72 h.

Scheme 3

Substrate scope—variation of the radical translocating arylating group. Reaction scale: 0.1 ‐ 0.25 mmol. Yields of isolated product.

Scheme 4

Substrate scope—primary, secondary, and tertiary α‐amide radicals. Reaction scale: 0.1–0.15 mmol. Yields of isolated product.

Scheme 5

Suggested mechanism for the remote arylation of α‐C(sp³)−H amide bonds via a 1,6‐HAT/1,4‐aryl migration/desulfonylation cascade.