Chemoselective synthesis of highly substituted 1,2-allenyl ketones, furans, and 2-alkynyl ketones from reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and electrophiles

A homo-Michael addition reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and the subsequent reaction with electrophiles such as PhSeBr, NFSI and NCS is reported. Based on the nature of electrophiles, this reaction may afford highly substituted 1,2-allenyl ketones or furans (E(+) = PhSe(+)) and 2-alkynyl ketones (E(+) = F(+), Cl(+), active halides) as the final products, respectively.     

Library construction of 1-(1H-imidazol-1-yl)-1,2-dihydroisoquinolines via three-component reaction of 2-alkynylbenzaldehyde, amine, and imidazole

Parallel diversity-oriented synthesis of diverse 1-(1H-imidazol-1-yl)-1,2-dihydroisoquinolines via AgOTf-catalyzed three-component reaction of 2-alkynylbenzaldehyde, amine, and imidazole is described. This reaction works efficiently under mild conditions to generate a small library of imidazole-incorporated 1,2-dihydroisoquinolines.     

Regioselective synthesis of cytotoxic 4-(1-alkynyl)-substituted 2-(5H)-furanones

4-(1-Alkynyl)-3-bromo- and 4-(1-alkynyl)-3-chloro-2(5H)-furanones have been regioselectively synthesized in moderate to good yields by a new version of the Pd/Cu-catalyzed Sonogashira reaction involving treatment of 1-alkynes with 3,4-dibromo- and 3,4-dichloro-2(5H)-furanone, respectively, in the presence of KF as a base. 4-(1-Alkynyl)-3-bromo-2(5H)-furanones have been found to be able to undergo Stille-type and Suzuki-type reactions with aryl(tributyl)tins and arylboronic acids, respectively, to give 4-(1-alkynyl)-3-aryl-2(5H)-furanones in modest to satisfactory yields. Some 4-(1-alkynyl)-substituted 2(5H)-furanones so prepared have been found to exhibit significant cytotoxic activities, especially against human leukemia cell lines.     

Synthesis of highly substituted furans by the electrophile-induced coupling of 2-(1-alkynyl)-2-alken-1-ones and nucleophiles

[reaction: see text] The coupling of 2-(1-alkynyl)-2-alken-1-ones with nucleophiles, either catalyzed by AuCl3 or induced by an electrophile, provides highly substituted furans in good to excellent yields under very mild reaction conditions. Various nucleophiles, including functionally substituted alcohols, H2O, carboxylic acids, 1,3-diketones, and electron-rich arenes, and a range of cyclic and acyclic 2-(1-alkynyl)-2-alken-1-ones readily participate in these cyclizations. Iodine, NIS, and PhSeCl have proven successful as electrophiles in this process. The resulting iodine-containing furans can be readily elaborated to more complex products using known organopalladium chemistry.     

Synthesis, structure, and reaction of 1-alkynyl(aryl)-lambda3-bromanes

Reported here for the first time are the synthesis, structure, and reaction of hypervalent 1-alkynyl(aryl)-lambda3-bromanes. BF3-catalyzed ligand exchange on bromine(III) of p-trifluoromethylphenyl(difluoro)-lambda3-bromane with 1-alkynyl(trimethyl)stannanes in dichloromethane at -78 degrees C afforded 1-alkynyl(aryl)-lambda3-bromanes in good yields. Trimethyl(trimethylsilylethynyl)stannane gave silylethynyl-lambda3-bromane selectively. 13C NMR chemical shifts of acetylenic carbon atoms of alkynylbromanes are compared with those of alkynyl-lambda3-iodanes and explained in terms of the spin-orbit-induced heavy atom effects. The structure of tert-butylethynylbromane was established by a single-crystal X-ray analysis of its crown ether complex. The 1-alkynyl(aryl)-lambda3-bromanes serve as highly electron-deficient Michael acceptors and undergo tandem Michael-carbene rearrangements by the reaction with sulfonate anions, yielding 1-alkynyl sulfonates.     

Palladium-catalyzed carbonylative annulation reaction of 2-(1-alkynyl)benzenamines: selective synthesis of 3-(halomethylene)indolin-2-ones

A novel and selective palladium-catalyzed carbonylative annulation process for the synthesis of 3-(halomethylene)indolin-2-ones was demonstrated. In the presence of PdX2 and CuX2, 3-(halomethylene)indolin-2-ones were selectively obtained from the carbonylative annulations of 2-(1-alkynyl)benzenamines with CO in moderate to good yields.     

DBU-promoted cyclization of ortho-(3-hydroxy-1-alkynyl)benzamide: synthesis of trans-3,4-dihydroisoquinolin-1(2H)-ones and (E)-4-(1-alkenyl)isoquinolin-1(2H)-ones

DBU-promoted cyclization of ortho-(3-hydroxy-1-alkynyl)benzamide is presented, providing an efficient method for the synthesis of trans-3,4-dihydroisoquinolin-1(2H)-ones and (E)-4-(1-alkenyl)isoquinolin-1(2H)-ones under mild conditions.     

Tandem Michael addition-carbene insertion reaction of 1-alkynyl(aryl)(tetrafluoroborato)-lambda3-bromanes: 1-(phenylsulfonyl)- and 1-(trifluoromethylsulfonyl)cyclopentene annulation

Exposure of 1-alkynyl[p-(trifluoromethyl)phenyl](tetrafluoroborato)-lambda(3)-bromanes to sodium benzenesulfinate or sodium trifluoromethanesulfinate in dichloromethane at 0 degree C under argon resulted in tandem Michael-carbene insertion reactions to produce 1-sulfonylcyclopentenes selectively, with concomitant formation of a small amount of rearranged 1-alkynyl sulfones.     

Facile synthesis of sulfenyl-substituted isocoumarins,heterocycle-fused pyrones and 3-(inden-1-ylidene)isobenzofuranones by FeCl3-promoted regioselective annulation of o-(1-alkynyl)benzoates and o-(1-alkynyl)heterocyclic carboxylates with disulfides

Reported herein is the FeCl₃-promoted intermolecular sulfoesterification of o-(1-alkynyl)benzoates with disulfides, which provides a convenient and efficient method for synthesis of 4-sulfenylisocoumarins. Various functional groups such as methoxy, halides, ester, cyano and silicon groups in the substrates are tolerated, and heterocycle-fused chalcogenylpyrones are also successfully achieved directly from the corresponding heterocyclic precursors under the same reaction conditions. In addition, starting from diynylbenzoate, this reaction sequence can be combined with a bicyclization step leading to the tetracyclic (E)-3-(2-phenyl-3-phenylchalcogenylinden-1-ylidene)isobenzofuranone frameworks with high regiospecificity and exclusive trans stereoselectivity.     

Synthesis of 4-halophosphaisocoumarins via halocyclization of 2-(1-alkynyl)phenylphosphonates

A series of 4-halophosphaisocoumarins were prepared with high regioselectivity in good to excellent yields under mild conditions by the reaction of 2-(1-alkynyl)phenylphosphonic acid diesters with I₂ in CHCl₃ or ICl in CH₂Cl₂, or by the reaction of 2-(1-alkynyl)phenylphosphonic acid monoesters with NBS or NCS in DMF. Whether the alkynylphosphonates could cyclize or not was affected by the substituents, reaction solvents and electrophiles. A rationale for this reaction is discussed.     

Synthesis of 1-alkynyl(diphenyl)onium salts of group 16 elements via heteroatom transfer reaction of 1-alkynyl(phenyl)-lambda 3-iodanes

1-Alkynyl(phenyl)-lambda 3-iodanes undergo selective transfer of the alkynyl groups over the phenyl group onto diphenyl chalcogens. Exposure of 1-alkynyl(phenyl)-lambda 3-iodanes to diphenyl chalcogens (S, Se, and Te) in dichloromethane or 1,2-dichloroethane affords 1-alkynyl(diphenyl)sulfonium, -selenonium, and -telluronium salts in high yields.     

Synthesis of 2-substituted 3-aroylindenes via palladium-catalyzed carbonylative cyclization of diethyl 2-(2-(1-alkynyl)phenyl)malonates with aryl halides

[reaction: see text] The palladium-catalyzed reaction of readily accessible diethyl 2-(2-(1-alkynyl)phenyl)malonates with aryl halides under a balloon pressure of CO produced 2-substitued 3-aroylindenes in good yields. The reaction is believed to proceed via cyclization of the alkyne containing a proximate nucleophilic center promoted by an acylpalladium complex.     

Palladium/copper-catalyzed tandem Sonogashira coupling/lactonization of methyl 2-(2′,2′-dibromovinyl)benzoate with terminal alkynes: Facile access to 3-alkynyl isocoumarins

An efficient palladium/copper-catalyzed tandem Sonogashira reaction/lactonization of methyl 2-(2′,2′-dibromovinyl)benzoate with terminal alkynes has been developed. This facile and direct approach furnishes a variety of 3-alkynyl isocoumarins in moderate to good yields under mild reaction conditions. Furthermore, this method enables concise total synthesis of natural products 3′-hydroxycorfin and gymnopalynes A.     

Exo/endo selectivity-control in Lewis-acid catalyzed tandem heterocyclization/formal [4+3] cycloaddition: synthesis of polyheterocycles from 2-(1-alkynyl)-2-alken-1-ones and 1,3-diphenylisobenzofuran

A novel catalytic exo/endo selectivity-controllable tandem heterocyclization/formal [4+3] cycloaddition was developed, which provides rapid, efficient and stereoselective access to highly fused polyheterocycles from readily available 2-(1-alkynyl)-2-alken-1-ones and 1,3-diphenylisobenzofuran under mild conditions.     

Tetrasubstituted furans by Pd(II)/Cu(I)-cocatalyzed three-component domino reactions of 2-(1-alkynyl)-2-alken-1-ones, nucleophiles and diaryliodonium salts

A novel Pd(OAc)(2)/CuI-cocatalyzed three-component reaction of 2-(1-alkynyl)-2-alken-1-ones, nucleophiles and diaryliodonium salts has been developed. The procedure allows the synthesis of tetrasubstituted furans in good to high yields under mild conditions.     

Synthesis of 2-alkylidenecyclopentanones via palladium-catalyzed carbopalladation/ring expansion of 1-(1-alkynyl)cyclobutanols

The palladium-catalyzed cross-coupling of aryl halides or vinylic halides or triflates and 1-(1-alkynyl)cyclobutanols affords good yields of stereoisomerically pure 2-arylidene- or 2-(2-alkenylidene)cyclopentanones, respectively. The process involves (1) oxidative addition of the organic halide or triflate to Pd(0), (2) regioselective, intermolecular carbopalladation of the carbon-carbon triple bond of the 1-(1-alkynyl)cyclobutanol to produce a vinylic palladium intermediate, (3) regioselective ring expansion to a palladacycle, and (4) reductive elimination of the 2-alkylidenecyclopentanone with simultaneous regeneration of the Pd(0) catalyst. Generally, the best results are obtained by employing 10 mol % of Pd(OAc)(2), 20 mol % of PPh(3), 2 equiv of the aryl or vinylic iodide or vinylic triflate, 2 equiv of diisopropylethylamine, and n-Bu(4)NCl in DMF as the solvent.     

Syntheses of 4-(1-alkynyl)-2(5H)-furanones and coumarins via the palladium catalyzed cross-coupling reactions of potassium alkynyltrifluoroborates

An efficient synthesis of 4-(1-alkynyl)-2(5H)-furanones has been developed utilizing a palladium catalyzed coupling reaction of β-tetronic acid bromide with potassium alkynyltrifluoroborates in the absence of base. 4-Alkynylcoumarins were also synthesized using this method. The reactions are straightforward and the yields are excellent.     

AuCl(3)-catalyzed synthesis of highly substituted furans from 2-(1-alkynyl)-2-alken-1-ones

Highly substituted furans have been synthesized by the reaction of 2-(1-alkynyl)-2-alken-1-ones and various nucleophiles under very mild reaction conditions in good to excellent yields. Gold and some other transition metals are efficient catalysts for this reaction.     

Unexpected C-C bond cleavage of epoxide motif: rhodium(I)-catalyzed tandem heterocyclization/[4+1] cycloaddition of 1-(1-alkynyl)oxiranyl ketones

A rhodium(I)-catalyzed tandem heterocyclization and formal [4+1] cycloaddition of 1-(1-alkynyl)oxiranyl ketones was developed, which provides a general, efficient and practical route to highly substituted furo[3,4-b]furan-3(2H)-ones, wherein the epoxide motif undergo unexpected C-C bond cleavage rather than the classical C-O bond cleavage.     

Hydrosilylation of 2-(2-Propynyl)-2,3-dihydro-1,2-benzothiazol-3-one 1,1-Dioxide with 1-Alkynyl(dimethyl)- and Bis(1-alkynyl)methylsilanes

Hydrosilylation of 2-(2-propynyl)-2,3-dihydro-1,2-benzothiazol-3-one 1,1-dioxide with 1-alkynyldimethyl- and bis(1-alkynyl)methylsilanes of the general formula Me _n HSi(C=-CR)₃-n (n = 1, 2) in the presence of H₂PtCl₆ (Speier's catalyst) occurs in a nonregioselective but stereoselective fashion, yielding mixtures of the corresponding trans-- and -adducts. The fraction of the latter ranges from 50 to 70%, depending mainly on the substrate nature rather than on the nature of substituent at the triple bond of the reagent.