Mechanistic and stereochemical aspects of the asymmetric cyclocarbonylation of 1,6-enynes with rhodium catalysts

NMR and kinetic investigations of the cyclocarbonylation of 1,6-enynes with cationic rhodium(i) catalysts, modified with atropisomeric diphosphines, disprove the involvement of carbonyl species for 1,6-enyne activation; low-temperature catalysis, with molecular sieves as the carbon monoxide reservoir, is highly enantioselective (ee up to 97%).     

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.     

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.     

Cycloisomerization of 1,6-enynes using acetate as a nucleophile under palladium(II) catalysis

[reaction: see text] An efficient method for the synthesis of five-membered carbo- and heterocyclic compounds, including fused rings, was reported using acetate as a nucleophile in the cyclization of 1,6-enynes under palladium(II) catalysis. The reaction is initiated by trans-acetoxypalladation of the alkynes and quenched by either trans- or cis-deacetoxypalladation in the presence of 2,2'-bipyridine as the ligand. An example of the catalytic asymmetric cyclization is presented with moderate enantioselectivity using chiral bisoxazoline ligand.     

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.     

Chiral carbene approach to gold-catalyzed asymmetric cyclization of 1,6-enynes

Chiral C₂-symmetric N-heterocyclic carbenes (NHCs) were tested for their stereocontrolling abilities in gold(I)-catalyzed asymmetric cyclization of 1,6-enynes giving the corresponding cyclopentane derivatives with moderate enantioselectivity of up to 59%.     

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.     

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.     

A highly reusable rhodium catalyst-organic framework for the intramolecular cycloisomerization of 1,6-enynes

The intramolecular cycloisomerization of 1,6-enynes in 95-99% ee is reported using an immobilized Rh catalyst-organic framework synthesized from alternating ring-opening metathesis polymerization (altROMP) assembly. The framework was reused up to seven times, and it was used in high turnover number (TON) batch reactions. The catalyst provided the highest TONs to date (up to 890) for the cycloisomerizations, with catalyst loadings ranging from 0.2 to 0.06 mol %.     

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.     

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.     

Gold(I) complexes with hydrogen-bond supported heterocyclic carbenes as active catalysts in reactions of 1,6-enynes

Complexes [AuCl{C(NHR)(NHPy-2)}] (Py-2 ) 2-pyridyl; R ) Me, tBu, nBu, iPr, nheptyl) have been prepared in amodular way from [AuCl(CNPy-2)]. The carbene moiety has a hydrogen-bond supported heterocyclic structure similar to the nitrogen heterocyclic carbenes in the solid state, and in CH2Cl2 or acetone solution, which is open in the presence of MeOH. The compounds are good catalysts for the skeletal rearrangement of enynes, and for the methoxycyclization of enynes. In contrast, the complexes [AuCl{C(NHR)(NHPy-4)}] are scarcely active due to the blocking effect of the coordination position required for the catalysis by the nitrogen of the NHPy-4 group.     

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.     

Iridium complex-catalyzed reaction of 1,6-enynes: cycloaddition and cycloisomerization

[reaction: see text] 1,6-Enynes reacted with monoynes to give cyclohexadiene derivatives in the presence of a catalytic amount of [Ir(cod)Cl](2)/ligand. DPPE was most suitable for cycloaddition. Diastereoselective cycloaddition was also possible. In the absence of monoynes, 1,6-enynes cycloisomerized to (Z)-1-alkylidene-2-methylenecyclopentane derivatives. DPPF was most suitable for cycloisomerization. These results are the first examples of highly Z-selective cycloisomerization.     

Novel rhodium-catalyzed cycloisomerization of 1,6-enynes with an intramolecular halogen shift

A new Rh-catalyzed 1,6-enyne cycloisomerization process with a pi-allyl rhodium species as the key intermediate is investigated. A halogen shift happened in this novel process. The synthesis of stereodefined alpha-halomethylene gamma-butyrolactones has been achieved using the readily accessible Rh catalysts.     

Rhodium-catalyzed cycloisomerization of 1,6-enynes with an intramolecular halogen shift: reaction scope and mechanism

The rhodium(I)-species-catalyzed cycloisomerization reaction of a wide spectrum of 1,6-enynes with an unusual intramolecular halogen shift was investigated. This Rh-catalyzed enyne cyclization reaction represents a new process for the synthesis of stereodefined alpha-halomethylene-gamma-butyrolactones, lactams, tetrahydrofurans, pyrrolidines, and cyclopentanes. Coordinatively unsaturated rhodium species ([Rh(COD)Cl](2) + dppb + AgSbF(6)) only catalyzes the reaction with enyne substrates bearing a Z-form double bond, while neutral rhodium species (RhCl(PPh(3))(3)) could catalyze enyne substrates bearing a Z- or E-form double bond to form the desired products and has a wider substrate scopes. The mechanism of the reaction was studied by the employment of control experiments with different enyne isomers, and a pi-allyl rhodium intermediate was suggested to explain the formation of the cyclic products with an intramolecular halogen shift.     

Palladium-catalyzed cascade cyclization-coupling reactions of 2-bromo-1,6-enynes with organoboronic acids

2-Bromo-1,6-enynes 5 with a palladium catalyst would form the alkenylpalladium intermediates via an intramolecular Heck reaction, which were cross-coupled with various organoboronic acids 8 to give the cyclization-coupling products 6 in synthetically valuable yields.