Palladium-Catalyzed Sonogashira Coupling of a Heterocyclic Phosphonium Salt with a Terminal Alkyne

Abstract

An efficient Sonogashira coupling of a heterocyclic phosphonium salt with a terminal alkyne via C–P bond cleavage was developed. The reactions proceeded smoothly in the presence of palladium catalyst, copper­(I) iodide, and N,N-diisopropylethylamine (DIPEA) in N-methyl-2-pyrrolidone (NMP) at 100 °C for 12 h, producing the corresponding alkynyl-substituted pyridine, quinoline, pyrazine, and quinoxaline in moderate to good yields with wide substrate scope and broad functional group tolerance. In addition, gram-scale synthesis could also be achieved, and the reaction could be applied to the functionalization of alkyne-containing complex molecules derived from sugars and pharmaceutical and naturally occurring products (e.g., estrone, d-galactopyranose, menthol, and ibuprofen).

Copper‐Catalyzed C4‐selective Carboxylation of Pyridines with CO2 via Pyridylphosphonium Salts

“…These transformations showed robust functional group tolerance and compatible with multiple pyridine drug frameworks. However, there are only a few reports on transition‐metal (palladium, nickel, or cobalt) catalyzed functionalization (arylation, [8f,9] alkylation, [8g–h] alkynylation, [10] and allylation [11] ) of pyridylphosphonium salts. Due to the lack of efficient catalytic reduction system, carboxylation of these pyridylphosphonium salts remains untapped.…”

Recent Expedition inPd‐CatalyzedSonogashira Coupling and Related Processes†

“…[ 26 ] Apart from heteroaryl halides, heterocyclic phosphonium salts were also feasible substrates for Sonogashira coupling using 10 mol% Pd(PPh 3 ) 2 Cl 2 and 10 mol% CuI catalyst system. [ 27 ]…”

Diversity-oriented synthesis of P-stereogenic and axially chiral monodentate biaryl phosphines enabled by C-P bond cleavage

“…Alkynes are among the most important class of compounds in all aspects of chemistry and are readily available starting materials for versatile transformations via the functionalization of the triple bond 35,36 . Though the achiral alkynylation of C-P bond has been achieved 32,33 , no examples of C(sp 2 )-C(sp) cross-coupling via asymmetric C-P bond cleavage have been reported. Thus we set our sights on developing the enantioselective alkynylation of t-butyl methyl biaryl phosphonium salt 1a with terminal alkyne 2a, leading to the alkynylated MOPs 3a with an alkynyl group as a versatile handle for further synthetic elaborations to construct structurally diverse MOPs containing both Pand axial chirality.…”