Highly Selective Rhodium-Catalyzed C-H Borylations in Preparation of Substrates for Suzuki-Miyaura Cross-Couplings: Mono- and Chemoselective Formation of Aromatic Compounds

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Date
2015-03-27
Authors
Moore, Brandon
Keyword
Cross-Coupling , Suzuki , Borylation , Heck , Transition Metal , C-H Activation , Palladium , Boronic Ester , Catalysis , Carbenes , Chemoselective , Regioselective , NHC , Arylation , Boron , Rhodium
Abstract
The advent of the Suzuki–Miyaura cross–coupling reaction and its significance to the synthesis of new carbon–carbon bonds has increased the demand for efficient routes to organoboron starting materials. C–H borylation (activation) has provided an interesting approach to alleviate the requirement for prefunctionalized molecules such as aryl halides to obtain these desired organoboron substrates. We report the first use of a rhodium N–heterocyclic carbene (NHC) complex for the catalytic C–H borylation. The reaction is found to proceed under very mild conditions (room temperature, short reaction times) and is applicable to a variety of 2–phenylpyridine (2–Ph–pyr) derivatives. Additionally, exclusive selectivity for the monoborylated product is observed with no bisborylation occurring in the reaction, which was found to be attributable to the key nitrogen–boron coordination. The selective monoborylation was further united with a Suzuki–Miyaura cross–coupling in a one–pot reaction to produce monoarylated phenylpyridines in good overall yields with no formation of the bisarylated compounds. Commonly, metal–catalyzed direct arylations require the use of steric blocking groups in order to obtain the desired monoselectivity and prevent bisarylation from occurring. However, these sterically biased substrates are avoided with the system described herein. Further, the chemoselectivity of the Suzuki–Miyaura cross–coupling of secondary boronic esters was investigated in intermolecular competition reactions with Mizoroki–Heck acceptors. Interestingly, the conditions of the reaction could be easily tuned to chemoselectively produce either the Suzuki–Miyaura or the Mizoroki–Heck cross–coupled product in good yields. This knowledge was then applied to an intramolecular competition reaction on a substrate containing both Suzuki–Miyaura and Mizoroki–Heck acceptor sites. Excitingly, the Suzuki–Miyaura cross–coupled product was obtained in good yield leaving the alkene substituent unreacted in the reaction. This chemoselectivity pathway opens the door for the preparation of polysubstituted aromatic compounds without the additional need for protection and deprotection steps which could result in a reduced overall yield of the desired product.
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