We disclose that 1,3-bis(diphenylphosphino)methane]nickel(II) chloride NiCl(2)(dppp)] is a highly active, universally applicable, cheap, and stable catalyst for Suzuki-Miyaura cross-coupling reactions of aryl halides with a catalyst loading of lower than 1 mol%, and more notably, in the absence of extra supporting ligands. Under the optimized reaction conditions, a broad range of aryl bromides as well as the notoriously unreactive aryl chlorides, including activated, non-activated, deactivated, and heteroaromatic and sterically hindered substrates can be coupled smoothly with various boronic acids (47 examples, 48-98% yields). In addition, the transformation is tolerant of various functional groups such as ether, ester, ketone, aldehyde, cyano, and un-protected amino and hydroxy groups. Finally, the potential utilization of the methodology was further demonstrated by the gram-scale synthesis of several core structures of commercialized antihypertensive drugs and fungicides. Thus, the combination of high activity, broad applicability, cheapness, and high stability of NiCl(2)(dppp) presented in this work constitutes one of the few prominent catalysts which allow for practical and reliable construction of biaryls and heterobiaryls with structural diversity from readily available aryl halides and boronic acids.
We present a highly active, inexpensive, universally applicable, and markedly stable 1,3-bis(diphenylphosphino)propane]nickel(II) chloride Ni(dppp)Cl(2)] catalyst that is capable of effecting the Suzuki-Miyaura cross-coupling of the inherently less reactive but readily available aryl tosylates and mesylates with only 1 mol% loading and in the absence of extra supporting ligand. Under the optimized reaction conditions, cross-coupling of a wide range of activated, non-activated, and deactivated, as well as sterically hindered and heteroaromatic substrates (36 examples) could proceed efficiently to afford the coupled products in 53-99% yields. Consequently, the results presented in this work provide a significant advance in Suzuki-Miyaura cross-coupling in terms of generality, practicality, and cost which are key concerns in recent research regarding transition metal-catalyzed cross-couplings.
Enantioenriched potassiumβ-trifluoroboratoamides have been synthesizedviaan asymmetric, copper-catalyzed 1,4-addition of tetrahydroxydiboron (BBA) and tetrakis(dimethylamino)diboron toα,β-unsaturated amides. These dibora reagents provide access to the desired organotrifluoroborates using effective and atom economical sources of boron. The copper-catalyzedβ-boration is extended toα,β-unsaturated ketones and esters. Desired potassium organotrifluoroborates are synthesized with yields up to 92% and enantiomeric ratios up to 98:2. The enantioenriched potassiumβ-trifluoroboratoamides are successfully cross-coupled with an array of aryl and heteroaryl chlorides in high yield with complete stereochemical fidelity as the transmetalation proceeds through an SE2 mechanismviaan open transition state.
A Ritter-like coupling reaction of cyclic alcohols and both aryl and alkyl nitriles to form amides catalyzed by copper (II) triflate is described. These reactions proceed in good yields under mild and often solvent-free conditions. With 2- and 3-substituted cycloalkanols, amide products are formed with near complete retention of configuration. This is likely due to fast nucleophilic capture of a non-planar carbocations (hyperconjomers) stabilized by ring hyperconjugation. A critical aspect of this novel catalytic cycle is thein situactivation of the alcohol substrates by thionyl chloride to form chlorosulfites.
Herein, an efficient method for the Ullmann C?O coupling reaction between various kinds of phenols and aryl halides, including amino, ketone, cyano, methyl, methoxy, fluoro, chloro and bromo derivatives, is described. The catalyst used, copper ferrite (CuFe2O4) nanoparticles, are easily made, air-stable, and of low cost. The catalyst can be recycled easily just by using an external magnet. Even in the presence of sensitive substituents, the reaction proceeds successfully to provide the desired products in high yields without protection of other functional groups.
A one-pot cascade reaction for the synthesis of polysubstituted benzofurans and naphthopyrans from simple phenols and propargylic alcohols catalyzed by iron(III) is presented. The results demonstrate that the structural specificity for the formation of furan and pyran products is controlled by the structural nature of the propargylic alcohols. Namely, benzofurans could be synthesized efficiently from phenols and secondary propargylic alcohols in the presence of 5mol% of iron(III) chloride hexahydrate (FeCl36H2O) catalyst. On the other hand, pyran derivatives were obtained exclusively when tertiary propargylic alcohols were employed. Mechanistic studies revealed that presumably due to the discriminated steric effect of secondary and tertiary propargylic alcohols, the Fe-catalyzed FriedelCrafts (FC) reaction of phenols with the two types of alcohols proceeds via different models. Most importantly, we have demonstrated for the first time that fully 2,3,4-substituted naphthopyrans could be synthesized efficiently via the iron-catalyzed one-pot cascade reaction. Consequently, the results presented herein provide straightforward pathways for versatile syntheses of valuable benzofuran and pyran derivatives from simple phenolic compounds and propargylic alcohols.