Expeditious synthesis of 1,1-diarylethylenes related to isocombretastatin A-4 (isoCA-4) via palladium-catalyzed arylation of N-tosylhydrazones with aryl triflates

International audienceA quick and efficient entry to 1,1-diarylethylenes via the reaction of poly-oxygenated aryl N-tosylhydrazones with aryl triflates is described. The reaction employs the catalytic system Pd(OAc)2/XPhos, tBuOLi as the base and dioxane as the solvent. A variety of substituents on both coupling partner's hydrazones and triflates are tolerated. This procedure provides a complementary route to the existing methods for the access to 1,1-diarylethylenes of biological interest

One-pot hydrosilylation–protodesilylation of functionalized diarylalkynes: a highly selective access to Z-stilbenes. Application to the synthesis of combretastatin A-4

International audienceAn efficient stereoselective synthesis of Z-stilbenes has been developed from diarylalkynes via a new hydrosilylation-protodesilylation process. Scope and limitation of this method to prepare stereoselectively a wide range of (Z)-stilbenes in a one-pot way is presented. A concise application to the preparation of combretastatin A-4 (CA-4), a vascular targeting agent inhibitor of tubulin polymerisation is described

Disproportionation reaction of diarylcarbinols: a versatile access to diarylmethanes speeded up using microwave irradiation

International audienceAn efficient synthesis of diarylmethanes under classical thermal conditions and under microwave heating has been established from diarylcarbinols via a new disproportionation reaction. The key step involve a selective hydride transfert of iso-propylic ethers intermediates. Soft experimental procedure using catalytic CBr4 or TfOH in i-PrOH and good yields render this method useful and competitive to the conventional approaches relying on application of external reducing agents

p-Toluenesulfonic acid-promoted selective functionalization of unsymmetrical arylalkynes: a regioselective access to various arylketones and heterocycles

International audienceRegioselective hydration of a wide range of internal alkynes has been afforded in high to good yields by using PTSA in EtOH. The scope of the reaction of alkynes has been delineated. Arylaliphatic alkynes and diarylalkynes were regioselectively hydrated in good to excellent yields and short reaction times when the reaction was achieved under microwave irradiation. Moreover, diarylalkynes, arylenynes as well as diaryldiynes bearing a methoxy-or a thiomethyl substituent on the ortho position underwent a regioselective 5-endo-dig-cyclization to give a variety of 2-aryl-and 2-styrylbenzofuran or benzothiphene derivatives. We believe that, this new environmentally metal-free procedure combined to microwave irradiation would be in importance in the search of green laboratory-scale synthesis

Tributyltin Hydride in NMP-Promoted Reduction of Acid Chlorides to Aldehydes under Transition-Metal-Free Conditions

International audienceTributyltin hydride in NMP was used for the partial reduction of various functionalized acid chlorides at room temperature. This metal-free procedure allowed the synthesis of a range of (hetero)aromatic-and aliphatic aldehydes in good to excellent yields

α-Iodination of Ketones with MnO 2 /I 2 Reagent Combination: A New Environmentally Friendly Procedure

International audienceIn alcoholic media, α-iodination of ketones was accomplished using MnO2/I2 reagent combination in a new environmentally friendly procedure. The reactions carried out under thermal conditions or microwave irradiation afforded α-iodoketones in reasonable to good yields

MPHT-Promoted Bromocyclization of ortho-Substituted Arylalkynes: Application to the Synthesis of 2-Substituted 3-Bromobenzofurans and -Benzo[b]thiophenes

International audienceA convenient and general approach to the synthesis of 2‐substituted 3‐bromobenzofurans and ‐benzothiophenes was developed. The procedure is based on the cyclization of ortho‐substituted arylalkynes in the presence of N‐methylpyrrolidin‐2‐one hydrotribromide (MPHT) as a soft and easy‐to‐handle electrophilic brominating reagent. Under mild reaction conditions, MPHT promoted the bromocyclization of various enynes and diynes as well as arylalkynes to give 2‐substituted 3‐bromobenzofurans and ‐benzothiophenes in high to excellent yields. Subsequent functionalization by palladium‐catalyzed coupling reactions at the C–Br bond afforded general access to 2,3‐disubstituted benzofurans and benzothiophenes of biological interest

Gold versus Palladium: A Regioselective Cycloisomerization of Aromatic Enynes

International audienceAromatic enynes can be transformed into arylnaphthalenes or benzofulvenes depending on the reaction conditions. Under gold(I) catalysis, exclusive or major 6-endo-dig cyclization took place leading to arylnaphthalenes. However, a catalytic system based on palladium iodide/1,3-Bis(diphenylphosphino)propane, in the presence of cesium carbonate as a base was necessary to furnish exclusively 5-exo-dig cyclization pattern, regardless to the electronic effects of the substituents. In the latter transformation, a mechanistic study (Kinetic Isotopic Effect, Density Functional Theory) involving a C-H activation is suggested for the exclusive benzofulvenes formation

Palladium-Catalyzed Coupling of 3-Halo-Substituted Coumarins, Chromenes, and Quinolones with Various Nitrogen-Containing Nucleophiles

International audienceAn efficient and general palladium‐catalyzed coupling reaction between 3‐bromocoumarins, 3‐bromoquinolin‐2(1H)‐ones, and 3‐iodo‐2H‐chromenes with a variety of nitrogen‐containing nucleophiles (azole, amide, lactam, sulfonamide, aniline, amine, and urea) is described. The reaction proceeded rapidly and cleanly in dioxane providing the coupling products in good to excellent yields. The chemoselectivity of this reaction was also studied with polyhalocoumarins. Under optimized conditions, these underwent a site‐selective amination at the C‐3–Br bond, regardless of the nature of the nitrogen‐containing nucleophile used

Palladium-catalyzed coupling of N-tosylhydrazones with ortho substituted aryl halides: synthesis of 4-arylchromenes and related heterocycles

International audienceA convenient and efficient procedure for the synthesis of 4-arylchromenes, thiochromenes, and related heterocycles via a four step-sequence has been developed. The first three steps, which involve hydration of alkynes, hydrazones formation, and their Pd-coupling with ortho substituted aryl halides, furnished stereoselectively Z-trisubstituted olefins without any purification of the intermediates generated in each stage. These latter proved to be suitable precursors, in the last step, for the synthesis of the desired heterocycles of biological interest.