Base‐Activated Latent Heteroaromatic Sulfinates as Nucleophilic Coupling Partners in Palladium‐Catalyzed Cross‐Coupling Reactions

Abstract

Heteroaromatic sulfinates are effective nucleophilic reagents in Pd0‐catalyzed cross‐coupling reactions with aryl halides. However, metal sulfinate salts can be challenging to purify, solubilize in reaction media, and are not tolerant to multi‐step transformations. Here we introduce base‐activated, latent sulfinate reagents: β‐nitrile and β‐ester sulfones. We show that under the cross‐coupling conditions, these species generate the sulfinate salt in situ, which then undergo efficient palladium‐catalyzed desulfinative cross‐coupling with (hetero)aryl bromides to deliver a broad range of biaryls. These latent sulfinate reagents have proven to be stable through multi‐step substrate elaboration, and amenable to scale‐up.

Visible Light-Driven, Gold(I)-Catalyzed Preparation of Symmetrical (Hetero)biaryls by Homocoupling of Arylazo Sulfones

“…Spectroscopic data were in accordance with the literature data. 59 1 H NMR (300 MHz, CDCl 3 ) δ 8.69–8.65 (m, 2H), 8.40 (dd, J = 8.0, 1.2 Hz, 2H), 7.81 (td, J = 7.8, 1.8 Hz, 2H), 7.29 (ddd, J = 7.5, 4.8, 1.2 Hz, 2H). 13 C{ 1 H} NMR (75 MHz, CDCl 3 ) δ 156.0, 149.2, 137.1, 123.9, 121.3.…”

Photocatalytic Late-Stage Functionalization of Sulfonamides via Sulfonyl Radical Intermediates

“…The 2-pyridine substrate showed no SO 2 extrusion and delivered the expected β-ketone; analogous motifs have successfully been used in palladium-catalyzed cross-coupling reactions. 33 Sulfamides are a further important aza-sulfur pharmacophore 34 and have been incorporated into a variety of pharmaceuticals. Using a sulfamide substrate under our standard reaction conditions delivered sulfonamide 2w in 32% yield, thus establishing applicability to nonsulfonamide substrates.…”

Synthesis of Bis-heteroaryls Using Grignard Reagents and Pyridylsulfonium Salts

“…Ligand-coupling reactions have recently experienced a resurgence in organic chemistry. − They have been shown to be a powerful strategy for forming C­(sp 2 )–C­(sp 2 ) bonds, most notably through phosphorane and sulfurane intermediates, obviating the need for costly transition metals. − These hypervalent species can be used to synthesize a wide range of bis-aromatics, but perhaps most notably, access to bis-heterocycles such as bipyridines is enabled. − Bis-heterocycles are privileged pharmacophores found in many natural products and therapeutics. − Currently, the state-of-the-art for accessing bis-aromatics relies heavily on transition-metal-catalyzed cross-coupling methods. However, although aryl–aryl couplings with transition-metal-catalyzed cross couplings are remarkably efficient, the analogous heteroaryl–heteroaryl couplings are considerably more restricted. − Willis and co-workers have addressed some of these issues through the use of pyridyl sulfinates; however, they have also noted that the incorporation of 2-pyridyl groups into compounds still requires much attention. − …”

“… 14 − 16 Willis and co-workers have addressed some of these issues through the use of pyridyl sulfinates; however, they have also noted that the incorporation of 2-pyridyl groups into compounds still requires much attention. 14 − 17 …”