Science of Synthesis

Murata, M., Science of Synthesis: Cross Coupling and Heck-Type Reactions, (2013) 2, 440.

Organoboronic acids and their esters can be synthesized from the corresponding C—X electrophiles by lithium–halogen exchange or Grignard reaction, followed by nucleophilic attack on an appropriate boron electrophile such as a trialkyl borate.[‌1‌,‌4‌] Although this traditional transmetalation protocol is still common for large-scale synthesis of simple boronic acids and esters, it is limited to substrates lacking base-sensitive functional groups. Since boronic acids and their esters play a crucial role in modern organic synthesis for the construction of complex molecules,[‌3‌] C—B bond-forming reactions have to tolerate the presence of a diverse and adequate number of functionalities. Although a palladium-catalyzed coupling reaction of C—X electrophiles should be an alternative route to functionalized boronates, the lack of boron nucleophiles has nevertheless limited the catalytic C—B bond-forming reaction. However, at the end of the 20th century, two reports on boron nucleophiles for palladium-catalyzed coupling opened the door to the catalytic borylation of C—X electrophiles. The metal-catalyzed cross-coupling reaction of bis(pinacolato)diboron [‌1‌, 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane)][‌9‌] or pinacolborane (‌2‌, 4,4,5,5-tetramethyl-1,3,2-dioxaborolane)[‌10‌] provides a simple, elegant, and direct method for the preparation of functionalized boronates from C—X electrophiles (‌Scheme 2‌).

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References