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Electrochemically Driven Deoxygenative Borylation of Alcohols and Carbonyl Compounds

Weiyang Guan, Yejin Chang and Song Lin*

*Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14850, United States, Email: songlincornell.edu

W. Guan, Y. Chang, S. Lin, J. Am. Chem. Soc., 2023, 145, 16966-16972.

DOI: 10.1021/jacs.3c03418


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Abstract

Electroreductive conditions enable a transformation of benzylic and allylic alcohols, aldehydes, and ketones into boronic esters in the presence of readily available pinacolborane, which serves both as an activator and an electrophile. This strategy is applicable to a variety of substrates and can be employed for the late-stage functionalization of complex molecules.

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Safety when handling chemicals and reaction setup

H-Bpin: H-Bpin reacts violently with water or any proton source to release flammable hydrogen gas. It should be handled with care and kept under dry and inert atmosphere.

Reaction setup and workup: The reaction mixtures are prepared in a N2 glovebox before being transferred out to a bench top for electrolysis. THF was distilled over sodium/benzophenone or dried with 3~4 Ň molecular sieves before use. In the deoxygenative borylation reaction, the alcohol substrates react rapidly with H-Bpin to release H2 gas. Itís recommended to stir slowly at first to avoid spillover of the reaction solution. Usually, the reaction is very safe to work up, while Mg0 might precipitate on the cathode after 2 F/mol of charge or after alcohols or carbonyl substrates are fully consumed. Under these circumstances, the cathode (graphite or iron) could be combustible (because of the electrogenerated Mg0) when exposed to air and needs to be handled with care. In these cases, the reaction mixture can be quenched by slowly adding 1 mL of water to the vial before exposing the reaction mixture to air. After hydrogen evolution ceases, the reaction can be worked up as normal.

Suggestions on isolation of boronic esters

Benzylic and allylic boronic esters are known to decompose during silica gel column chromatography. Usually, the isolated yield is lower than the 1H NMR yield. To ensure successful isolation, it's recommended to run the column quickly, or use automated chromatography to minimize contact with silica gel. Alternatively, boric acid-treated silica gel can be used to reduce decomposition during chromatography.

Deoxygenative borylation of benzylic alcohols

Magnesium electrodes were polished with a razor and graphite electrodes were polished with 500 grit silicon carbide sandpaper until a shiny finish was obtained. Graphite electrodes were dried in oven for at least 10 min before use. In a glove box, TBABF4 (1 mmol, 2 equiv.) and alcohol substrate (0.5 mmol, 1 equiv.) were added into an oven dried ElectraSyn vial (5 mL) equipped with a magnetic stir bar. Dried THF (1 mL) was then added to the mixture. H-Bpin (1.25 mmol, 2.5 equiv) was slowly added to the solution. The reaction usually starts bubbling at this stage and the bubbling becomes more vigorous when stirring. The whole mixture was slowly stirred until the bubbling becomes less vigorous. Then, 3mL dried THF was added to the mixture. The vial was sealed with the ElectraSyn vial cap equipped with anode (Mg plate) and cathode (graphite plate), and then the assembly was brought out of the glove box. A nitrogen balloon was attached to the cap, and the reaction mixture was electrolyzed at a constant current of 10 mA until passing 2.5 F/mol of charge at room temperature. After electrolysis, the reaction mixture was added to diethyl ether (10 mL) to precipitate TBABF4. The resultant mixture was then filtered through a short silica plug (8 cm thick, ca. 10 g) and flushed with diethyl ether (100 mL). The crude mixture was concentrated under vacuum and purified with column chromatography. Notes: This reaction can also be carried out outside of a glovebox using the Schlenk technique.


Key Words

benzylboronates, electrochemistry


ID: J48-Y2023