Sulfur-directed palladium-catalyzed C(sp³)–H α-arylation of 3-pyrrolines: easy access to diverse polysubstituted pyrrolidines

Abstract

A sulfur-directed palladium-catalyzed C(sp3)–H α-arylation of 3-pyrrolines with arylboronic acids has been disclosed, providing a range of 2-aryl-3-pyrolines, which could be readily converted to various polysubstituted pyrrolidines.

Installing the “magic methyl” – C–H methylation in synthesis

“…Despite this, in 2020, Wang & Yang reported the use of a thioamide directing group to enable the C-H arylation of 3-pyrroline derivatives using boronic acid nucleophiles (Scheme 67). 174 One example of methylation was exemplified, occurring in moderate yield. Following, downstream post-synthetic modifications, the protocol provided access to a-arylated or methylated pyrrolidines, a motif that appears in a variety of bioactive molecules.…”

Cp*Rh(III)-Catalyzed Regioselective C(sp2)–H Mono- and Dialkynylation of Thioamides by Sulfur Coordination

“…The development of Pd-catalyzed C­(sp 3 )–H arylation of azacycles using thioamide as a directing group by the Yu group and related discoveries are noteworthy . The Pd-catalyzed direct C–H arylation of thiophene directed by thioamides was reported by Murai. , Miura and Satoh disclosed Rh­(III)-catalyzed C–H olefination of benzothioamides. Nevertheless, under similar conditions the benzothioamides react with alkynes accompanied by desulfurization and C–N bond cleavage to afford indenone derivatives (Scheme a). , …”

Copper-Catalyzed C(sp3)–H Methylation via Radical Relay

“…C–H functionalization has enabled the installation of the methyl groups in a wide variety of settings via directed C­(sp 2 )–H activation , or radical-generating mechanisms. , Oxidative C­(sp 3 )-H methylation, however, has been far less explored and typically requires directing groups. − Recently undirected C­(sp 3 )–H methylation has been reported employing activated C–H bonds α to heteroatoms (Figure a). , In these protocols, C­(sp 3 )–H bonds are selectively oxidized to C–OH or C–OR moieties that serve as synthetic handles for subsequent methylation to provide products with C–Me bonds. Since these methods typically target activated, weaker C–H bonds, methylation of nonactivated C­(sp 3 )–H bonds poses a considerable challenge.…”