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Published on: May 21, 2019
Metal-Free Directed C-H Borylation of Pyrroles
Zheng-Jun Wang1, Xiangyang Chen2, Lei Wu1
1State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, China.
Abstract:
Robust strategies to enable the rapid construction of complex organoboronates in selective, practical, low-cost, and environmentally friendly modes remain conspicuously underdeveloped. Here, we develop a general strategy for the site-selective C-H borylation of pyrroles by using only BBr3 directed by pivaloyl groups, avoiding the use of any metal. The site-selectivity is generally dominated by chelation and electronic effects, thus forming diverse C2-borylated pyrroles against the steric effect. The formed products can readily engage in downstream transformations, enabling a step-economic process to access drugs such as Lipitor. DFT calculations (wB97X-D) demonstrate the preferred positional selectivity of this reaction.
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Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
Regioselectivity and Stereochemistry of Hydroboration
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration-Oxidation of Alkenes
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
Nucleophilic Aromatic Substitution: Elimination–Addition
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene

