Chemodivergent cross‐couplings are those in which either one of two (or more) potentially reactive functional groups can be made to react based on choice of conditions. In particular, this review focuses on cross‐couplings involving two different (pseudo)halides that can compete for the role of the electrophilic coupling partner. The discussion is primarily organized by pairs of electrophiles including chloride vs. triflate, bromide vs. triflate, chloride vs. tosylate, and halide vs. halide. Some common themes emerge regarding the origin of selectivity control. These include catalyst ligation state and solvent polarity or coordinating ability. However, in many cases, further systematic studies will be necessary to deconvolute the influences of metal identity, ligand, solvent, additives, nucleophilic coupling partner, and other factors on chemoselectivity.

Two N-heterocyclic carbene (NHC) ligands provide orthogonal chemoselectivity during the Pd-catalyzed Suzuki-Miyaura (SM) cross coupling of chloroaryl triflates. The use of SIPr [SIPr = 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene] leads to selective cross coupling at chloride, while the use of SIMes [SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene] provides selective coupling at triflate. With most chloroaryl triflates and arylboronic acids, ligand-controlled selectivity is high (≥10:1). The scope of this methodology is significantly more general than previously reported methods for selective SM coupling of chloroaryl triflates using phosphine ligands. Density functional theory (DFT) studies suggest that palladium's ligation state during oxidative addition is different with SIMes compared to SIPr. Ar OTf [Pd] SIPr [Pd] SIMes ArB(OH) 2 KF, r.t. ArB(OH) 2 KF, r.t. OTf Cl Ar Cl Ar OTf [Pd] SIPr [Pd] SIMes ArB(OH) 2 KF, r.t. ArB(OH) 2 KF, r.t.OTf Cl Ar Cl SIPr SIMes IPr IMes N Cl Pd Cl Cl SIPr 7 Cl NHC Pd tBu 3, NHC = SIPr 4, NHC = IPr 5, NHC = SIMes 6, NHC = IMes Me PMP OTf Cl

The use of polar solvents MeCN or dimethylformamide (DMF) was previously shown to induce a selectivity switch in the Pd/P t Bu 3 -catalyzed Suzuki-Miyaura coupling of chloroaryl triflates. This phenomenon was attributed to the ability of polar solvents to stabilize anionic transition states for oxidative addition. However, we demonstrate that selectivity in this reaction does not trend with solvent dielectic constant. Unlike MeCN and DMF, water, alcohols, and several polar aprotic solvents such as MeNO 2 , acetone, and propylene carbonate provide the same selectivity as nonpolar solvents. These results indicate that the role of solvent on the selectivity of Suzuki-Miyaura couplings may be more complex than previously envisioned. Furthermore, this observation has the potential for synthetic value as it greatly broadens the scope of solvents that can be used for chloride-selective cross coupling of chloroaryl triflates.

This manuscript describes a Ni-catalyzed method for the direct arylation of azoles using benzoates. Perfluorophenyl and 2-nitrobenzoates participate in these reactions to afford the corresponding products in modest to good yields. The efficiency of the arylations with perfluorobenzoates is highly dependent on both the degree and position of fluorine atoms in the benzoates.

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