Title

Ni(II) Catalyzed Bromination of Unactivated Biphenyl C-H Bonds

Document Type

Presentation

Publication Date

4-10-2014

Faculty Mentor

Siddhartha Das

Abstract

Efficient conversions of aromatic C-H to C-halogen provide access to organic halides, which can, next, be utilized for several C-C coupling reactions. Halogenations of organic molecules are carried out using the following methods: using (a) X2/light, (b) Lewis acids (FeCl2)/X2, (c) peroxides/MX (M: Na, K), (d) hypervalent iodine reagent/MX (M: Na/K), (e) X2/M (M: Fe). Achieving this halogenation on aromatic rings, bearing electron withdrawing groups (EWG) like CF3, is especially important; incorporation of a CF3 group in an aromatic ring is widely used in drugs (e.g. in kinase inhibitors) to make them (a) more permeable through cell membrane, as well as to (b) increase their target-specificity through directed electrostatic interactions and (c) decrease their chance of oxidative/metabolic damage. Selective halogenation of aromatic systems bearing EWG, like CFÎÎ3 or NO2, would provide a facile step for follow-up C-C couplings and, therefore, alternative routes for drug synthesis. Among first row transition metals, Ni(II) has become appealing for C-C cross coupling. Several groups have extensively explored the application of Ni(II) complexes for C-C cross coupling utilizing aryl systems bearing various functional groups and ArB(OH)2/ArZnX/ArMgX (X: halide). There has been a rare report of Suzuki cross coupling between Ar-X and ArâB(OH)2, with Ni(II)CNC (1) as the catalyst. This inspired us to investigate the potency of this Ni(II)CNC complex in selective bromination of aryl rings and its functional group toleration. While our major goal is to incorporate the halogenation and Suzuki or Heck coupling in one-pot (if they require the same catalyst), this report is exploration of Ni(II)CNC and several commercially available Ni(II) salts for selective aryl halogenation. In this work, we report the bromination of C(sp2)-H bonds in biphenyl systems having electron donating group (EDG) and EWG. We have used an air stable Ni(II) N-heterocyclic complex and some commercially available Ni(II) salts. We found that PhI(OAc)2 is effective as the oxidizing agent in presence of an electron withdrawing functional group, whereas C6F5I(OCOCF3)2 is effective in presence of an electron donating group (otherwise the phenyl group of the oxidant was found to be halogenated). N-bromosuccinimide (NBS) is used as the source of bromine.

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