Gold(I)-catalysed arylation of 1,6-enynes: different site reactivity of cyclopropyl gold carbenes

Gold(I)-catalysed addition of electron-rich arenes and heteroarenes to 1,6-enynes gives two different types of products by reaction of the intermediate cyclopropyl gold carbenes at the cyclopropane or at the carbene.     

Gold(I)-catalysed cycloisomerisation of 1,6-cyclopropene-enes

The gold(I)-catalysed cycloisomerisation of appropriately substituted 1,6-cyclopropene-enes proceeds through regioselective electrophilic ring opening of the three-membered ring to generate an alkenyl gold carbenoid that achieves the intramolecular cyclopropanation of the remote olefin. This strategy allows straightforward, highly efficient and diastereoselective access to a variety of substituted 3-oxa- and 3-azabicyclo[4.1.0]heptanes, as well as to bicyclo[4.1.0]heptan-3-ol derivatives. Since the isopropylidene group in the resulting cycloisomerisation products can be subjected to ozonolysis, 3,3-dimethylcyclopropenes behave as interesting surrogates for α-diazoketones.     

Computational studies on the mechanism of the gold(I)-catalysed rearrangement of cyclopropenes

Density functional theory calculations have been employed to investigate the mechanism of gold(I)-catalysed rearrangements of cyclopropenes. Product formation is controlled by the initial ring-opening step which results in the formation of a gold-stabilised carbocation/gold carbene intermediate. With 3-phenylcyclopropene-3-methylcarboxylate, the preferred intermediate allows cyclisation via nucleophilic attack of the carbonyl group and hence butenolide formation. Further calculations on simple model systems show that substituent effects can be rationalised by the charge distribution in the ring-opening transition state and, in particular, a loss of negative charge at what becomes the β-position of the intermediate. With 1-C(3)H(3)R cyclopropenes (R = Me, vinyl, Ph), ring-opening therefore places the substituent at the β-position.     

Gold(I)-catalyzed cyclizations of 1,6-enynes: alkoxycyclizations and exo/endo skeletal rearrangements

Gold(I) complexes are the most active catalysts for alkoxy- or hydroxycyclization and for skeletal rearrangement reactions of 1,6-enynes. Intramolecular alkoxycyclizations also proceed efficiently in the presence of gold(I) catalysts. The first examples of the skeletal rearrangement of enynes by the endocyclic cyclization pathway are also documented. Iron(III) is also able to catalyze exo and endo skeletal rearrangements of 1,6-enynes, although the scope of this transformation is more limited. The gold(I)-catalyzed endocyclic cyclization proceeds by a mechanism different from those followed in the presence of PdII, HgII, or RhI catalysts.     

Missing cyclization pathways and new rearrangements unveiled in the gold(I) and platinum(II)-catalyzed cyclization of 1,6-enynes

Cyclopropyl metal carbenes formed in the 6-endo-dig cyclization may evolve to form seven-membered ring intermediates. This has been achieved for the first time by using highly electrophilic platinum(II) and gold(I) complexes. Gold(I) also triggers a remarkable rearrangement of certain enynes leading to complex cyclic systems. A new cationic platinacycle is described, which catalyzes skeletal rearrangements and other reactions of enynes at room temperature.     

Phosphate ligands in the gold(I)-catalysed activation of enynes

Gold(I) forms neutral complexes with binol phosphates that are unreactive in the catalytic cyclisation of enynes. Reaction in protic solvents or activation by silver(I) restores the catalytic activity.     

Dialkylaluminum hydride-promoted cyclodimerization of silylated 1,3-enynes via skeletal rearrangement

The dialkylaluminum hydride-promoted reaction of 1-silylalk-3-en-1-ynes gave symmetrical 1,2,3,5-tetrasubstituted benzenes as single regioisomers. The novel cyclodimerization via skeletal rearrangement can be rationalized by an unprecedented mechanism involving sequential hydroalumination, alkene isomerization, carboalumination, carbon-carbon bond cleavage, and retro-hydroalumination.     

Nature of the intermediates in gold(I)-catalyzed cyclizations of 1,5-enynes

The carbene or carbocationic nature of the intermediates in the gold-catalyzed cycloisomerization of 1,5-enynes can be revealed, depending on the ligands on the gold catalysts. Gold complexes with highly electron-donating ligands promote reactions that proceed via intermediates with carbene-like character, leading to products with a bicyclo[3.1.0]hexene skeleton. The intermediate cyclopropyl endo-gold carbenes formed in this cyclization have been trapped, for the first time, to give biscyclopropane derivatives in a reaction that proceeds in a concerted fashion, according to DFT calculations.     

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.     

A gold(I)-catalyzed intramolecular oxidation-cyclopropanation sequence of 1,6-enynes: a convenient access to [n.1.0]bicycloalkanes

A gold(I)-catalyzed tandem oxidation/cyclopropanation reaction of 1,6-enynes with an external oxidant has been developed. This quite simple and rapid strategy will provide a safe, mild and versatile avenue to numerous carbo- and hetero [n.1.0]bicyclic frameworks.     

Gold(I)-catalyzed intermolecular addition of carbon nucleophiles to 1,5- and 1,6-enynes

Gold(I)-catalyzed addition of carbon nucleophiles to 1,6-enynes gives two different type of products by reaction at the cyclopropane or at the carbene carbons of the intermediate cyclopropyl gold carbenes. The 5-exo-dig cyclization is followed by most 1,6-enynes, although those bearing internal alkynes and alkenes react by the 6-endo-dig pathway. The cyclopropane versus carbene site-selectivity can be controlled in some cases by the ligand on the gold catalyst. In addition to electron-rich arenes and heteroarenes, allylsilanes and 1,3-dicarbonyl compounds can be used as the nucleophiles. In the reaction of 1,5-enynes with carbon nucleophiles, the 5-endo-dig pathway is preferred.     

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.     

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 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.     

A synthesis of 2-epi-fagomine using gold(I)-catalysed allene cyclisation

A synthesis of 2-epi-fagomine via a highly stereoselective gold(I)-catalysed allene cyclisation is described. The stereochemical outcome of the cyclisation is opposite to that observed in previous studies. In contrast, gold(III)-catalysed cyclisation is inefficient and gives rise to double cyclisation by-products.     

Gold(I)-catalysed iodoalkoxylation of allenes

Gold(I)-catalysed intermolecular iodoalkoxylation of allenes occurs in a regioselective and stereoselective manner to produce versatile iodo-tert-allyllic ether products. The products can be further elaborated through cross-couplings to yield highly substituted tert-allylic ethers.