Visible light-mediated metal-free alkyl Suzuki–Miyaura coupling of alkyl halides and alkenylboronic acids/esters: a green method for the synthesis of allyl difluoride derivatives

Abstract

Suzuki-Miyaura reaction has greatly facilitated the construction of C-C bonds and is well appreciated in medicinal chemistry, yet transition metal residues in this process are an unavoidable challenge. Herein, we...

A Chemoselective Polarity‐Mismatched Photocatalytic C(sp3)−C(sp2) Cross‐Coupling Enabled by Synergistic Boron Activation**

“…Finally, boron speciation was a key component -the boronic acid was the most effective, with Bpin and Bcat esters less effective (entries 5 and 6). Contrary to previous radical additions using vinyl organoboron reagents, [15][16][17] the BF 3 K and BMIDA were completely unreactive (entries 7 and 8). This, along with other evidence, revealed important information on the mechanism of the reaction (vide infra).…”

“…Importantly, in contrast to existing polarity-matched reactions, electrophilic radicals (e.g., α-carboxy) as well as benzylic radicals were unsuccessful (see ESI for a full description of limitations). [16][17][18] Allyl radicals were unsuccessful (41). Similarly, the styrene component was broadly tolerant of functional group electronic and regiochemical variation.…”

“…[12,13] Pertinent examples of these reactivity principles can be seen in radical additions to well-known electron-rich π-systems, such as vinyl boron compounds where ipso-substitution takes place using the electrophilic radicals generated from αhalocarbonyls, as developed by Leonori, [15] or the Togni reagent, as developed by Koike and Akita (Scheme 1b). [16,17] Examples of polarity-mismatched radical addition to alkenes are rare. This has inspired development of strategies for formal polarity-mismatched bond formations.…”

Recent Advances in the Synthesis of Fluoroalkylated Alkenes and Alkynes via Fluoroalkyl Radical Substitution Reactions

“…The metal-free photo-induced difluoroalkylation of alkenylboronic acids 96 with bromodifluoromethyl ketones 97 was accomplished by Tang, Liu, Song, et al (Figure 29). [38] In the presence of diisopropylethylamine (DIPEA, 2 equiv), 96 and 97 (3 equiv) were irradiated with blue LEDs in N,N-dimethylacetamide (DMA) at room temperature, affording difluoroalkylation products 98 in good yields. It was proposed that the photo-activation of halogen bonding complex 99 generates difluoroalkyl radical 100 and bromine-DIPEA complex 101.…”

“…Figure29. Deborylative difluoroalkylation of alkenylboronic acids using bromodifluoromethyl ketones under catalyst-free visible-light irradiation conditions (ref [38]…”