Free Amino Group-Directed γ-C(sp³)–H Arylation of α-Amino Esters with Diaryliodonium Triflates by Palladium Catalysis

Abstract

Free amino group-directed C­(sp3)–H functionalization of aliphatic amines is a fundamental challenge in synthetic organic chemistry. Also, the NH2-directed C­(sp3)–H functionalization of α-amino acids and their derivatives remains barely explored. With palladium as the catalyst and Ag2O as the additive, we developed the first NH2-directed γ-C­(sp3)–H arylation of α-amino esters with diaryliodonium triflates for the construction of synthetically useful γ-aryl-α-amino esters, and the result of the KIE study suggested that the catalytic reaction involved an irreversible C–H cleavage as the rate-determining step.

Transition-Metal-Catalyzed, Coordination-Assisted Functionalization of Nonactivated C(sp3)–H Bonds

“…Free primary aliphatic amine-directed arylation of unactivated C­(sp 3 )–H bonds with an acid additive has also been reported (Scheme ). , …”

General Access to Modified α‐Amino Acids by Bioinspired Stereoselective γ‐C−H Bond Lactonization

“…[7,8] In these reactions,p rimary C À Hb onds are preferentially functionalized driven by the kinetic advantage arising from the formation of af ivemembered ring metallacycle ( Figure 1B). [9][10][11][12][13][14][15] Procedures that can selectively target secondary CÀHb onds,a lthough less represented, have been also developed. [7,16] Forw hat concerns instead the issue of stereoselectivity, control over diastereoselectivity (when applicable) remains as tanding problem in aliphatic CÀHb ond functionalization of a-amino acid and oligopeptide scaffolds,with the available information being extremely limited.…”

Transient imine directing groups for the C–H functionalisation of aldehydes, ketones and amines: an update 2018–2020

“…Yao showed amine directed arylation of challenging amino ester substrates (Scheme 25a). 74 Aryliodonium salts were shown to be required as coupling partners for this transformation, enabling arylation in up to 72% yield using silver oxide as an additive. The reaction was effective fully α-substituted alkyl amines, but ceased to function when less substituted amines were used.…”