Browsing by Author "Entz, Emily D."

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Chemodivergence between Electrophiles in Cross‐Coupling Reactions
(Wiley, 2021-04) Reeves, Emily K.; Entz, Emily D.; Neufeldt, Sharon R.
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.
Nickel-Catalyzed Stille Cross Coupling of C-O Electrophiles
(2019-04) Russell, John E.; Entz, Emily D.; Joyce, Ian M.; Neufeldt, Sharon R.
Aryl sulfamates, tosylates, and mesylates undergo efficient Ni-catalyzed cross coupling with diverse organostannanes in the presence of relatively unhindered alkylphosphine ligands and KF. The coupling is valuable for difficult bond constructions, such as aryl-heteroaryl, aryl-alkenyl, and aryl-alkynyl, using nontriflate phenol derivatives. A combination of experimental and computational studies implicates an unusual mechanism for transmetalation involving an 8-centered cyclic transition state. This reaction is inhibited by chloride sources due to slow transmetalation of organostannanes at a Ni(II)-chloride intermediate. These studies help to explain why prior efforts to achieve Ni-catalyzed Stille coupling of phenol derivatives were unsuccessful.
Small Phosphine Ligands Enable Selective Oxidative Addition of Ar–O over Ar–Cl Bonds at Nickel(0)
(2020-08) Entz, Emily D.; Russell, John E. A.; Hooker, Leidy V.; Neufeldt, Sharon R.
Current methods for Suzuki-Miyaura couplings of nontriflate phenol derivatives are limited by their intolerance of halides including aryl chlorides. This is because Ni(0) and Pd(0) often undergo oxidative addition of organohalides at a similar or faster rate than most Ar–O bonds. DFT and stoichiometric oxidative addition studies demonstrate that small phosphines, in particular PMe3, are unique in promoting preferential reaction of Ni(0) with aryl tosylates and other C–O bonds in the presence of aryl chlorides. This selectivity was exploited in the first Ni-catalyzed C–O-selective Suzuki-Miyaura coupling of chlorinated phenol derivatives where the oxygen-containing leaving group is not a fluorinated sulfonate such as triflate. Computational studies suggest that the origin of divergent selectivity between PMe3 and other phosphines differs from prior examples of ligand-controlled chemodivergent cross-couplings. PMe3 effects selective reaction at tosylate due to both electronic and steric factors. A close interaction between nickel and a sulfonyl oxygen of tosylate during oxidative addition is critical to the observed selectivity.