ADC-Based Palladium Catalysts for Aqueous Suzuki–Miyaura Cross-Coupling Exhibit Greater Activity than the Most Advantageous Catalytic Systems

The reaction between the equimolar amounts of cis-[PdCl2(CNR1)2] (R1 = cyclohexyl (Cy) (1), tBu (2)) and the carbohydrazides R2CONHNH2 (R2 = Ph (5), 4-ClC6H4 (6), 3-NO2C6H4 (7), 4-NO2C6H4 (8), 4-CH3C6H4 (9), 3,4-(MeO)2C6H3 (10), naphth-1-yl (11), fur-2-yl (12), 4-NO2C6H4CH2 (13), Cy (14), 1-(4-fluorophenyl)-5-oxopyrrolidin-3-yl (15), (pyrrolidin-1-yl)­C­(O) (16)) proceeds in refluxing CHCl3 for ca. 4 h. A subsequent workup provided the aminocarbene species cis-[PdCl2{C(NHNHC­(O)­R2)N­(H)­R1}­(CNR1)] (18–33) in good to excellent (80–95%) isolated yields. The coupling of equimolar amounts of cis-[PdCl2(CNR1)2] (R1 = Cy (1), tBu (2), 2,6-Me2C6H3 (Xyl) (3), 2-Cl-6-MeC6H3 (4)) and PhSO2NHNH2 (17) occurs similarly and affords the aminocarbenes cis-[PdCl2{C(NHNHS­(O)2Ph)N­(H)­R1}­(CNR1)] (34–37; 60–90%). Complexes 18–37 were characterized by elemental analyses (C, H, N), ESI+-MS, IR, and 1D (1H, 13C­{1H}) and 2D (1H,1H-COSY, 1H,13C-HMQC/1H,13C-HSQC, 1H,13C-HMBC) NMR spectroscopy, as well as by X-ray diffraction for three species (34, 37, and 38).The catalytic properties of 18–37 in Suzuki–Miyaura cross-coupling in aqueous medium were evaluated, and 18–37 showed remarkable activity (0.001–0.01 mol % catalyst loading). The scope of the catalytic process covers sterically unhindered and sterically demanding aryl bromides and aryl iodides bearing donor and/or acceptor substituents and activated aryl chlorides. All organohalides reacted with a range of arylboronic acids at 80 °C within 2 h (100 °C and 3 h for the chlorides), providing target diaryls in yields up to 99% and with maximum TONs of 9.9 × 103 (for aryl iodides), 4.7 × 104 (for aryl bromides), and 9.2 × 103 (for aryl chlorides).