Related Experiment Video
Updated: Sep 12, 2026

Synthesis of a Borylated Ibuprofen Derivative Through Suzuki Cross-Coupling and Alkene Boracarboxylation Reactions
Published on: November 30, 2022
Aromatization-Driven Borylene Generation from Borepin Precursors Enables Fused Borirane Synthesis and Selective
Jay Prakash Maurya1, Dmitrii Bushmin1, Jonathan R Church2
1Department of Molecular Chemistry and Materials Science, Weizmann Institute of Science, Rehovot7610001, Israel.
Abstract:
Borylenes are among the most intriguing low-valent species in main group chemistry, yet their broader use in synthetic organic chemistry has remained limited by the lack of mild and modular methods for their generation. Here, we report a new class of borepin precursors that undergo aromatization-driven, redox-neutral borylene formation under synthetically practical conditions. This platform enables efficient interception of the resulting borylene intermediates by tethered alkenes through formal intramolecular [1 + 2] cycloaddition, providing direct access to previously unreported fused borirane frameworks. These strained borirane intermediates serve as valuable synthetic linchpins, enabling divergent olefin functionalization through C-B, C-O, and C-C bond-forming processes with notable regioselectivity. The synthetic utility of this platform is further highlighted by the selective functionalization of substrates containing multiple alkene units, guided by a native alcohol directing group, as well as by its application to the formal synthesis of natural products. To the best of our knowledge, this work represents the first application of borylene chemistry for the preparation of valuable building blocks relevant to natural product synthesis, establishing low-valent boron intermediates as practical tools for complex-molecule construction. Mechanistic studies combining DFT calculations, NMR analysis, and X-ray crystallography support a sequence involving Lewis-base coordination, borepin rearrangement, and concerted borylene extrusion driven by naphthalene formation. Overall, this work marks an important milestone in borylene chemistry by demonstrating that these low-valent boron species can be generated and harnessed as practical intermediates in synthetic organic chemistry, thereby opening the door to new reactivity patterns and broader applications in molecular construction.
Related Concept Videos
Hydroboration-Oxidation of Alkenes
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.
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.
Preparation of Alcohols via Addition Reactions
The acid-catalyzed addition of water to the double bond of alkenes is a large-scale industrial method used to synthesize low-molecular-weight alcohols. An acidic atmosphere is required to allow the hydrogen in the water molecule to act as an electrophile and attack the double bond in an alkene. The addition of a proton to the double bond creates a carbocation intermediate. The proton preferentially bonds to the less substituted end of the double bond to create a more stable carbocation...
Radical Substitution: Allylic Bromination
Preparation of Alkynes: Alkylation Reaction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.

