Enantioselective Ir(I)-catalyzed carbocyclization of 1,6-enynes by the chiral counterion strategy

Enantioenriched bicyclo[4.1.0]hept-2-enes were synthesized by Ir(I)-catalyzed carbocyclization of 1,6-enynes. No chiral ligands were used, CO and PPh(3) were the only ligands bound to iridium. Instead, the stereochemical information was localized on the counterion of the catalyst, generated in situ by reaction of Vaska's complex (trans-[IrCl(CO)(PPh(3))(2)]) with a chiral silver phosphate. Enantiomeric excesses up to 93% were obtained when this catalytic mixture was used. (31)P NMR and IR spectroscopy suggest that formation of the trans- [Ir(CO)(PPh(3))(2)](+) moiety occurs by chlorine abstraction. Moreover, density functional theory calculations support a 6-endo-dig cyclization promoted by this cationic moiety. The chiral phosphate anion (O-P*) controls the enantioselectivity through formation of a loose ion pair with the metal center and establishes a C-H···O-P* hydrogen bond with the substrate. This is a rare example of asymmetric counterion-directed transition-metal catalysis and represents the first application of such a strategy to a C-C bond-forming reaction.     

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.     

The carbocyclization of 1,6-anhydrogalactoses

Summary 2,3,4-Tri-O-methyl-1,6-anhydrogalactopyranose, like 2,3,4-Tri-O-methyl-1,6-anhydroglucopyranose forms phenol by the action of a solution of metallic sodium in liquid ammonia.     

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.     

Hydroxyl-directed cyclizations of 1,6-enynes

The palladium-catalyzed, hydroxyl-directed cyclization reactions of 1,6-enynes provide a highly diastereoselective process for the syntheses of stereochemically defined cyclopentanes. Consistently high levels of cis-selectivity are possible using homopropargyl alcohols in contrast to the corresponding propargyl alcohols. Hydroborylative enyne cyclizations coupled with this directing group effect provide a useful method for the syntheses of multifaceted compounds bearing all carbon quaternary centers.     

Intermolecular rhodium-catalyzed [2+2+2] carbocyclization reactions of 1,6-enynes with symmetrical and unsymmetrical alkynes

The crossed intermolecular rhodium-catalyzed [2+2+2] carbocyclization of carbon and heteroatom tethered 1,6-enynes can be accomplished with symmetrical and unsymmetrical alkynes, to afford the corresponding bicyclohexadienes in an efficient and highly selective manner.     

Regio- and enantioselective intermolecular rhodium-catalyzed [2+2+2] carbocyclization reactions of 1,6-enynes with methyl arylpropiolates

Transition metal-catalyzed [m+n+o] carbocyclization reactions provide powerful methods for the construction of complex polycyclic systems that are generally not accessible through classical pericyclic reactions. We have developed the first regio- and enantioselective crossed intermolecular rhodium-catalyzed [2+2+2] carbocyclization of carbon- and heteroatom-tethered 1,6-enynes with unsymmetrical 1,2-disubstituted alkynes. This study clearly delineates the ligand requirements for obtaining excellent regio- and enantioselectivity. Furthermore, the ability to utilize various electron-withdrawing groups, and to introduce quaternary carbon stereogenic centers, provides the level of versatility necessary for its application to target-directed synthesis. Additional studies on the development and application of this novel methodology to the total synthesis of natural products are currently underway.     

Iridium-catalyzed enantioselective Pauson-Khand-type reaction of 1,6-enynes

Iridium-chiral diphosphine complex catalyzes an enantioselective intramolecular Pauson-Khand-type reaction to give various chiral bicyclic cyclopentenones. The enantioselective reaction proceeds more smoothly and enantioselectively under a lower partial pressure of carbon monoxide. Moreover, aldehyde can be used as a CO source in the enantioselective carbonylative coupling.     

Highly enantioselective spiro cyclization of 1,6-enynes catalyzed by cationic skewphos rhodium(I) complex

A cationic rhodium(I) complex having a skewphos ligand is shown to be a highly enantioselective catalyst for asymmetric carbocyclization of 1,6-enynes with tri-substituted olefins to control quaternary stereogenic centers of spiro-rings.     

Enantioselective cyclization/hydrosilylation of 1,6-enynes catalyzed by a cationic rhodium bis(phosphine) complex

[reaction: see text] Reaction of 4,4-dicarbomethoxy-1-octene-6-yne (1) with triethylsilane and a catalytic 1:1 mixture of [Rh(COD)(2)](+) SbF(6)(-) and (R)-BIPHEMP (5 mol %) at 70 degrees C for 90 min gave (Z)-1,1-dicarbomethoxy-3-(1-triethylsilyl)ethylidene-4-methylcyclopentane (2) in 81% isolated yield with 98% de and 92% ee.     

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.     

Gold-catalyzed hydroamination/cycloisomerization reaction of 1,6-enynes

An efficient Au(I) catalytic system is described for the hydroamination/cycloisomerization reaction of functionalized 1,6-enynes. The reaction leads to carbo- and heterocyclic amino derivatives in good to excellent yields. The cyclizations were conducted in the presence of PPh(3)AuCl/AgSbF(6) catalyst in THF or dioxane at room temperature. The use of allyloxycarbonyl carbamate has allowed the formation of free amino derivatives via sequential Au- and Pd-catalyzed reactions.     

Enantioselective spiro ene-carbocyclization of 1,6-enynes catalyzed by tropos rhodium(I) complex with skewphos ligand

A tropos rhodium(I) complex having skewphos ligand is shown to be a highly enantioselective catalyst for asymmetric ene-type carbocyclization of 1,6-enynes with tri-substituted olefins to control quaternary stereogenic centers or spiro-rings.     

Co/C-catalyzed tandem carbocyclization reaction of 1,6-diynes

Cobalt on charcoal (Co/C) can be used as a catalyst in the tandem carbocycloaddition reaction of 1,6-diyne and carbon monoxide. The reaction product is dependent upon the reaction temperature, the position of the functional group, and the substrate itself.     

Cyclization of 1,6-enynes with allylic chromate species

[reaction: see text] Treatment of 1,6-enynes with tetramethallylchromate induces a cyclization reaction with concurrent introduction of a methallyl group. A catalytic amount of CrCl(3) combined with methallylmagnesium chloride also achieves this cyclization process. The resultant cyclic organometallic species undergo further functionalization upon reaction with electrophiles.     

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.