N-Vinylpyridinium and -ammonium Tetrafluoroborate Salts: New Electrophilic Coupling Partners for Pd(0)-Catalyzed Suzuki Cross-Coupling Reactions

Abstract

N-Vinylpyridinium and -trialkylammonium tetrafluoroborate salts represent a new class of electrophilic coupling partner for Pd(0)-catalyzed Suzuki cross-coupling reactions and give very good to excellent yields of products with a wide range of boronic acids. The salts are easily prepared from activated acetylenes and pyridinium or trialkylammonium tetrafluoroborates to form crystalline, air-stable, and nonhygroscopic crystals.The Suzuki reaction is a powerful member of the important and versatile suite of palladium catalyzed carbon-carbon bond-forming reactions. 1 The versatility is enhanced by the coupling of aryl, vinyl, and alkyl 1f-h halides or their corresponding triflates with literally hundreds of commercially available boronic acids and is thus ubiquitous in organic synthesis. Suzuki coupling additionally plays a major role in the production of diverse compound libraries in combinatorial chemistry employing either parallel or solid-phase methods. 2 Notwithstanding these advantages, the requisite vinyl halides and triflates can be unstable or rely on expensive or toxic reagents for their preparation. 3 As part of an ongoing program to build novel natural product-like libraries that rely on Suzuki cross-coupling protocols, we searched for a robust and reliable vinyl halide or triflate equivalent. We now report that the readily available Nvinylpyridinium and ammonium tetrafluoroborate salts 4 such as 1 and 2 (Figure 1) represent new and excellent electrophilic coupling partners for the Suzuki reaction.The synthesis of these salts was first reported by Jung and Buszek, 4 and they were employed as dienophiles by these workers in Diels-Alder cycloadditions. However, no other synthetic applications are found in the literature. This paper describes the first example of oxidative insertion of Pd (0) MacMillan shows that aryltrimethylammonium triflate salts undergo nickel-catalyzed Suzuki coupling, 5 it was noted that these same reactions fail with palladium catalysts. The MacMillan case more closely resembles the nickel-catalyzed Suzuki, Stille, and Kumada coupling of aryldiazonium salts, which have been known for some time. 6 There are no examples in the literature of any metal-mediated vinylpyridinium or vinyltrialkylammonium salt carboncarbon bond formation, 7 and furthermore, the corresponding vinyldiazonium salts are unknown. Accordingly, these salts represent a completely new and useful class of palladiumcatalyzed electrophilic coupling partner. The salts have the distinct advantage of being easily prepared almost quantitatively in one step from activated acetylenes and either pyridinium or trialkylammonium tetrafluoroborates. Additionally, they possess the highly desirable properties of being crystalline, nonhygroscopic, and indefinitely air-stable.We initially examined the coupling of the (E)-1-(3-oxobut-1-enyl)pyridinium tetrafluoroborate 1 with p-methoxyphenylboronic acid 3 (Scheme 1) and surveyed a range of parameters to optimize the reactions conditions for this class of substrate (Table 1)....

Chalcone: A Privileged Structure in Medicinal Chemistry

“…Buszek et al first reported an interesting example of Suzuki–Miyaura coupling for the synthesis of chalcones from N -vinylpyridinium tetrafluoroborate salt with yields of 60–81% (Scheme 4). 126 These salts represent a novel class of palladium-catalyzed electrophilic coupling partners reacting with a wide range of boronic acids. Additionally, the salts are air-stable and nonhygroscopic crystals that can be easily prepared quantitatively in one step from the activated acetylenes and either pyridinium or trialkylammonium tetrafluoroborates.…”

“…126 As shown in Scheme 8A, Al-Al-Masum and coworkers developed a direct cross-coupling reaction of benzoyl chlorides and potassium styryltrifluoroborates to obtain the corresponding chalcones in the presence of PdCl 2 (d t bpf) as the catalyst and K 2 CO 3 , taking advantage of microwave irradiation. Eight chalcones were synthesized using this condition, providing good to excellent yields (56–96%).…”

Pyridinium Salts as Redox‐Active Functional Group Transfer Reagents

“…[28] Forexample, N-vinylpyridinium salts have been successfully utilized as electrophilic coupling partner in the palladium-catalyzed Suzuki reaction but necessitate increased temperatures, most likely because of an energetically unfavorable oxidative addition. [29] Theu se of unactivated alkyl amines in crosscoupling reactions had not been realized until more recently.…”

Microwave‐Heated Transition Metal‐Catalyzed Coupling Reactions

“…Buszek and Brown described N-vinylpyridinium and ammonium tetrafluoroborate salts as a new class of electrophilic coupling partners for the Suzuki-Miyaura cross-coupling reaction (Scheme 15.16) [68]. Good to excellent yields of various 3-aryl-substituted enones were obtained by treating the salts with arylboronic acids, Pd 2 (dba) 3 (5 mol%), and PCy 3 (12 mol%) under microwave irradiation.…”