Ligand-Enabled Gold-Catalyzed C(sp²)–S Cross-Coupling Reactions

Abstract

Herein we report C­(sp2)–S cross-coupling reactions of aryl iodides and arylsulfonyl hydrazides under ligand-enabled, Au­(I)/Au­(III) redox catalysis. This strategy operates under mild reaction conditions, requires no prefunctionalized aryl coupling partner, and works across several aryl iodides. The utility of this protocol is highlighted through the synthesis of various medicinally relevant biaryl sulfones. The reaction mechanism is supported with control experiments, mass spectrometry, and NMR studies.

Benzylic C(sp3)–H Bonds Play the Dual Role of Starting Material and Oxidation Inhibitor for Hydrazides in the Electrochemical Synthesis of Hydrazones

“…Colorless solid, 1 H NMR (500 MHz, CDCl 3 ) δ 7.85 (d, J = 8.9 Hz, 2H), 7.02 (d, J = 9.0 Hz, 2H), 5.69 (s, 1H), 3.89 (s, 3H), 3.35 (s, 2H). Known compound …”

“…Known compound. 72 4-Methoxybenzenesulfonohydrazide (2i). Colorless solid, 1 H NMR (500 MHz, CDCl 3 ) δ 7.85 (d, J = 8.9 Hz, 2H), 7.02 (d, J = 9.0 Hz, 2H), 5.69 (s, 1H), 3.89 (s, 3H), 3.35 (s, 2H).…”

“…Known compound. 72 Benzohydrazide (2p). Colorless solid, 1H NMR (500 MHz, CDCl 3 ) δ 7.76 (dd, J = 7.2, 1.9 Hz, 2H), 7.50 (t, J = 7.3 Hz, 1H), 7.41 (t, J = 7.7 Hz, 2H), 4.26 (s, 2H).…”

Heart of gold: enabling ligands for oxidative addition of haloorganics in Au(i)/Au(iii) catalysed cross-coupling reactions

“…16A. 28 Functionally, the methodology is similar between the two protocols, featuring the catalytic use of 1a, stoichiometric use of AgY activation reagents, and the application of heat to promote the desired reactivity for the coupling of iodoarenes ( 8) and a variety of amines (40), yielding the desired aryl-functionalized amines (41). The authors of these studies note that the use of electron-deficient amines work best as they are more readily deprotonated, even in absence of base.…”

“…19A. 40 In this methodology, iodoarenes (8) and arylsulfonyl hydrazides (46) were coupled in the presence of catalyst 1a and AgSbF 6 under basic conditions to give the biaryl sulfones (47). Apart from the usual scope featuring electron-rich and 51) yielding 52.…”