Fluoroalkylation–Borylation of Alkynes: An Efficient Method To Obtain (Z)-Tri- and Tetrasubstituted Fluoroalkylated Alkenylboronates

Abstract

Efficient methods for the synthesis of fluoroalkylated alkenylboronates are very limited, despite their importance in modern organic synthesis. Herein, we report a palladium-catalyzed trans-fluoroalkylation–borylation of alkynes with fluoroalkyl iodides and B2pin2. The reaction tolerates a series of difluoroalkyl iodides and perfluoroalkyl iodides and can enable coupling with a variety of alkynes, including internal and terminal alkynes, with high efficiency, high functional group compatibility, and high regio- and stereoselectivities. Preliminary mechanistic studies reveal that a trans-fluoroalkylated alkenyl iodide is the key intermediate, which subsequently undergoes borylation to produce the trans-fluoroalkylated alkenylboronate.

Copper‐Catalyzed Three‐Component Reactions of 2‐Iodo‐2,2‐difluoroacetophenones, Alkynes, and Trimethylsilyl Cyanide

“…and Zhang et al. independently reported the palladium‐catalyzed difunctionalization of alkynes with ethyl difluoroiodoacetate and B 2 pin 2 [6c,d] . A Pd (0)‐catalyzed three‐component reactions of 2‐iodo‐2,2‐difluoroacetophenones, alkynes, and arylboronic acids was also reported by our group.…”

Integrated redox-active reagents for photoinduced regio- and stereoselective fluorocarboborylation

“…Synthetic applications. The synthetic utility of the method was demonstrated in a number of transformations of the highly functionalized alkylboronates and alkenylboronates 20,52,53 (Fig. 4).…”

“…Studer and co-workers 19 have reported a radical 1,2-trifluoromethylboration of unactivated alkenes using gaseous CF 3 I. Meanwhile, the direct 1,2-fluoroalkylboration of alkynes has also been explored [20][21][22] . The consequential vicinial vinylboronates, which can be readily transformed to a myriad of fluorine-containing building blocks, have been seldom realized.…”

“…Through the cleavage of the stabilized N-S bond (BDE ≈ 70 kcal mol −1 ) 46 , this cationic complex undergoes SET process to generate CF 3 SO 2 radical. Meanwhile, as a Lewis base, the imidazole residue can further activate the diboron reagents towards homolytic cleavage of the diboron reagent 20,[34][35][36][37][38][39] . Herein, we have synthesized a dual functional reagent IMDN-SO 2 CF 3 1a-1g, a scalable and airstable crystalline salt for a sequential radical fluoroalkylationborylation of unsaturated hydrocarbons (Fig.…”

Recent advances in Cu-catalyzed C(sp3)–Si and C(sp3)–B bond formation

“…Straightforward methods for their synthesis involve the copper-catalyzed addition of organoboron compounds to alkynes, alkenes, and unsaturated carbonyl compounds, as well as the nucleophilic borylation of alkyl or aryl halides. While there are reports on the formation of C-B bonds in the presence of NHC complexes [87] with Au [88], Pd [89], Pt [90], and Ir [91] catalysts, the focus here is on Cu-catalyzed reactions. Enantioselective processes have also been studied due to applications of medicinal interest involving optically active organoboron derivatives and their intermediacy as precursors to other functional groups, such as nonracemic alcohols.…”