Steric tuning of C2-symmetric chiral N-heterocyclic carbene in gold-catalyzed asymmetric cyclization of 1,6-enynes

Steric tuning of C₂-symmetric chiral N-heterocyclic carbene (NHC) was performed in Au(I)-catalyzed asymmetric cyclization of 1,6-enyne. Higher enantioselectivity was realized when chiral NHC–AuCl/AgSbF₆ catalysts whose N-substituent on the NHC overlays the Au–Cl bond was utilized.     

Rhodium-catalyzed asymmetric cyclization/hydroboration of 1,6-enynes

[reaction: see text] Reaction of enyne 1 with catecholborane catalyzed by a 1:1 mixture of [Rh(COD)(2)](+)SbF(6)(-) and (S)-BINAP (5 mol %) followed by Pd-catalyzed arylation with p-IC(6)H(4)CF(3) gave benzylidenecyclopentane 5 in 65% yield with 88% ee. Rhodium-catalyzed asymmetric cyclization/hydroboration followed either by Pd-catalyzed arylation or by oxidation was applied to the synthesis of a number of chiral, nonracemic carbocycles and heterocycles.     

Copper-catalyzed asymmetric silylative cyclization of cyclohexadienone-containing 1,6-enynes

The first copper-catalyzed asymmetric silylative cyclization of cyclohexadienone-containing 1,6-enynes has been accomplished through a tandem process: regioselective silylcupration of terminal unactivated alkynes and subsequently enantioselective conjugate addition to cyclohexadienones. This reaction proceeded smoothly to afford the cis-hydrobenzofuran and cis-hydroindole frameworks bearing two consecutive chiral carbon centers in high to excellent yields and moderate enantioselectivities. Additionally, the cyclization products could be readily subjected to several transformations for elaborating synthetic utilities.     

Chiral diene-phosphine tridentate ligands for rhodium-catalyzed asymmetric cycloisomerization of 1,6-enynes

Asymmetric cycloisomerization of nitrogen-bridged 1,6-enynes proceeded in the presence of a cationic rhodium complex coordinated with a chiral diene/phosphine tridentate ligand to give high yields of chiral 3-azabicyclo[4.1.0]heptenes with high enantioselectivity.     

Nickel-catalyzed hydrosilylation/cyclization of difluoro-substituted 1,6-enynes

Ni-catalyzed hydrosilylative cyclization of difluoro-substituted 1,6-enynes can be carried out. The presence of a geminal-difluoromethylene group at an alkene terminus in enynes is essential for the reaction to proceed.     

Palladium-catalyzed tandem cyclization/Suzuki coupling of 1,6-enynes

[reaction: see text] A Pd(0)-catalyzed 1,6-enyne cyclization-arylation cascade reaction was effected via pi-allylpalladium intermediate formation and subsequent Suzuki coupling to give cyclic products with stereodefined exocyclic double bonds.     

Enantioselective reductive cyclization of 1,6-enynes via rhodium-catalyzed asymmetric hydrogenation: C-C bond formation precedes hydrogen activation

Asymmetric hydrogenation of 1,6-enynes using chirally modified cationic rhodium precatalysts enables enantioselective reductive cyclization to afford alkylidene-substituted carbocycles and heterocycles in a completely atom economical fashion. Good to excellent yields and exceptional levels of asymmetric induction are observed across a structurally diverse set of substrates. Mechanistic studies involving hydrogen-deuterium crossover experiments, along with the observance of nonconjugated cycloisomerization products 14c and 15c, suggest rhodium(III) metallocyclopentene formation occurs in advance of hydrogen activation. This oxidative coupling-hydrogenolytic cleavage motif should play a key role in the design of related hydrogen-mediated couplings.     

Towards asymmetric Au-catalyzed hydroxy- and alkoxycyclization of 1,6-enynes

The efficiency of a Au(III)/chiral ligand system has been studied. The association of several chiral mono- and bidentate phosphanes with gold has been tested in the formal addition of an oxygen nucleophile to an alkene followed by a cyclization process, namely the hydroxycyclization reaction of 1,6-enynes. The use of (R)-4-MeO-3,5-(t-Bu)₂-MeOBIPHEP ligand led to clean cycloisomerizations and afforded the highest enantiomeric excesses. The enantiomeric excesses were highly dependant on the substrate/nucleophile combination. A ³¹P NMR study of the catalytic species tends to prove that Au(III) catalyst may be reduced to Au(I) intermediate in the presence of phosphanes.     

Rhodium-catalyzed cyclization of 1,6-enynes triggered by addition of arylboronic acids

1,6-Enynes reacted with arylboronic acids in the presence of a catalytic amount of a rhodium(I) complex under mild conditions to give (Z)-1-(1-arylethylidene)-2-vinylcyclopentanes. The regioselective addition of an arylrhodium(I) species across the carbon-carbon triple bond triggered the cyclization process. Intramolecular carborhodation onto the pendent alkene in a 5-exo mode furnished a five-membered ring. Finally, the rhodium(I) methoxide generated by beta-methoxy elimination reacted with the arylboronic acid to promote the next catalytic cycle.     

A diversity-oriented approach to spiroindolines: post-ugi gold-catalyzed diastereoselective domino cyclization

Caught "Spiro" handed: A diversity-oriented approach comprised of an Ugi four-component reaction and a diastereoselective gold(I)-catalyzed domino cyclization for the generation of complex spiroindolines under mild conditions has been developed. Variously substituted spiroindolines were synthesized in good to excellent yields and with complete diastereoselectivity.     

Metal-free visible-light-induced oxidative cyclization reaction of 1,6-enynes and arylsulfinic acids leading to sulfonylated benzofurans

A new and convenient visible-light-induced method has been developed for the synthesis of sulfonylated benzofurans via oxidative cyclization reaction of 1,6-enynes and arylsulfinic acids.This reaction was carried out under metal-free and mild conditions,in which the C-S,C-C and C=O bonds could be sequentially formed in one pot operation.     

Functionalized carbo- and heterocycles via Pt-catalyzed asymmetric alkoxycyclization of 1,6-enynes

This paper describes the asymmetric version of highly atom-economical alkoxycyclization of 1,6-enynes, using a combination of silver salts with the Pt(II)/(R)-Ph-BINEPINE system.     

Pd catalyzed oxidative cyclization of 1,6-enynes derived by Ugi-4-component reaction

A variety of 1,6-enynes were synthesized by an Ugi-reaction and further elaborated by a Pd^II/IV catalyzed oxidative cyclization to produce N-substituted 3-aza-bicyclo[3.1.0]hexan-2-ones. Different substitution patterns were tested to examine the scope and limitations of the amide tethered substrates.     

cis-chloropalladation of 1,6-enynes

A PdCl(2)-catalyzed cis-chloropalladation-cyclization reaction of various 1,6-enyne substrates was developed. This Pd-catalyzed enyne cyclization reaction represents a new route for the synthesis of stereodefined alpha-halomethylene-gamma-butyrolactones, lactams, tetrahydrofurans, and cyclopentanes. A mechanism involving a neighboring coordination group is proposed to explain the experiment results.     

Cationic Pd(II)-catalyzed arylative cyclization of 1,6-enynes with arylboronic acids

A cationic Pd(II)-catalyzed redox neutral arylative cyclization of enynes by using β-acetoxy elimination as the quenching step has been developed. The reaction offers an efficient method to access a variety of carbocycles and N-heterocycles bearing an exocyclic double bond.