Gold-catalyzed Cycloisomerization Research Articles

Synthesis of Spiroaminals and Spiroketals with Bimetallic Relay Catalysis

A novel tandem metal relay catalytic system was developed by combining gold-catalyzed cycloisomerization with an early transition-metal-catalyzed inverse-electron-demand hetero-Diels-Alder (IED-HDA) reaction. Various biologically important spiroaminals and spiroketals were obtained with very high efficiency under mild conditions.

Gold-catalyzed cycloisomerizations of 1,6-enynes. A computational study

The catalytic activity of gold phosphines for enyne cycloisomerizations is related to the very special bonding between the metal center and its substrate. We have computed mechanistic energy profiles for the formation of key 5- or 6-membered ring intermediates, by varying the nature of the enynes. We have found that equilibria between those two intermediates are possible. However, in several cases, our results suggest that the regioselectivity is already decided in the ring closure step, as the following attack of a nucleophile (ethanol) takes place readily, once the ring is formed. A correlation between the initial coordination of the alkyne moiety onto the metal and the further evolution of the complex could be found and discussed in terms of back-bonding. Thus, the electronic molecular structure of the initial gold–enyne complex allows us to predict to some extent the further reactivity of the substrate, regarding the regioselectivity between the 5- and 6-membered ring intermediates.

Access to the Protoilludane Core by Gold-Catalyzed Allene-vinylcyclopropane Cycloisomerization

Access to the Protoilludane Core by Gold-Catalyzed Allene-vinylcyclopropane Cycloisomerization

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

The synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine (22, normethylazafuranomycin) by the gold-catalyzed cycloisomerization of α-aminoallene 17 is described. The target molecule was synthesized in 13 linear steps from Cbz-protected Garner aldehyde (R)-2 in an overall yield of 2.4%. The approach was first examined in model studies, which afforded the alkylated azafuranomycin derivative 13a in 2.9% yield over 12 steps.

Regioselective Synthesis of Elusive 4,9-Dihydro-1H-Carbazoles by Gold-Catalyzed Cycloisomerization of 3-Allenylmethylindoles

A general and efficient synthesis of 4,9-dihydro-1H-carbazoles from 3-allenylmethylindoles is reported. The process, catalyzed by a cationic gold(I) complex, involves a formal C2-H bond activation of the indole unit by reaction with the allene. The nature of the substituents at the allylic and terminal positions of the allene moiety has a crucial effect on the regioselectivity of the cyclization, which is also influenced by the catalyst and the solvent employed. Moreover, some evidence of the contribution of different reaction routes is provided, which led us to propose a plausible multipathway mechanism consistent with all of the results described.

Access to the Protoilludane Core by Gold-Catalyzed Allene-vinylcyclopropane Cycloisomerization

Gold(I)-catalyzed allene-vinylcyclopropane cycloisomerization leads to the tricyclic framework of the protoilludanes in a single step by a reaction that involves a cyclopropane ring expansion and a Prins cyclization.

Gold-Catalyzed Cycloisomerization of 1,6-Diyne Carbonates and Esters to 2,4a-Dihydro-1H-fluorenes

A synthetic method to prepare 2,4a-dihydro-1H-fluorenes efficiently from gold(I)-catalyzed 1,2-acyloxy migration/cyclopropenation/Nazarov cyclization of 1,6-diyne carbonates and esters is described. The suggested reaction pathway provides rare examples of [2,3]-sigmatropic rearrangement in this class of compounds as well as the involvement of an in situ formed cyclopropene intermediate in gold catalysis. Experimental and ONIOM(QM:QM') [our own n-layered integrated molecular orbital and molecular mechanics(quantum mechanics:quantum mechanics')] computational studies based on the proposed Au carbenoid species provide insight into this unique selectivity.

Gold‐Catalyzed Intramolecular Regio‐ and Enantioselective Cycloisomerization of 1,1‐Bis(indolyl)‐5‐alkynes

Bis(indole) alkaloids analogues were prepared under mild conditions and in high yields through a gold-catalyzed cycloisomerization of 1,1-bis(indolyl)-5-alkynes (see scheme). The enantioselective version of this reaction gave the corresponding products in moderate to excellent yields (55–90 %), moderate to good ee values (48–96 %), and satisfactory regioselectivities (3.5:1→20:1).

ChemInform Abstract: A Perspective on the Stereodefined N,O‐Acetals: Synthesis and Potential Applications

AbstractReview: ca. 50 refs.

Gold-catalyzed cascade cycloisomerization of 1,7-diyn-3,6-bis(propargyl carbonate)s: stereoselective synthesis of naphtho[b]cyclobutenes

Gold-catalyzed cycloisomerization of 1,7-diyn-3,6-bis(propargyl carbonate)s leads to a highly efficient and diastereoselective synthesis of functionalized naphtho[b]cyclobutenes. A cascade sequence involving gold-catalyzed double 3,3-rearrangement, 6π-electrocyclic reaction and a decarbonylative cyclization was proposed for this reaction.

Regioselective synthesis of oxepinones and azepinones by gold-catalyzed cycloisomerization of functionalyzed cyclopropyl alkynes

A regioselective synthesis of oxepinones and azepinones in good to excellent yields from alkynylcyclopropanecarboxylic acid derivatives is described. This novel cycloisomerization cascade process consists of a nucleophilic addition followed by a cyclopropane ring-opening, where both donor and acceptor groups are required as substituents of the cyclopropane ring.

Gold for the Generation and Control of Fluxional Barbaralyl Cations

The frog prince with his two identities pales in comparison with the shape-shifting barbaralyl cation, which exists as a mixture of 181,400 degenerate forms. Gold-catalyzed cycloisomerizations of 7-alkynyl cyclohepta-1,3,5-trienes were found to proceed via fluxional barbaralyl intermediates. The evolution of the intermediates into 1- or 2-substituted indenes could be controlled by the choice of gold complex.

Ring Expansions Within the Gold‐Catalyzed Cycloisomerization of O‐Tethered 1,6‐Enynes. Application to the Synthesis of Natural‐Product‐like Macrocycles

The gold-catalyzed cycloisomerization of O-tethered 1,6-enynes proceeds via a small-sized ring expansion leading to the tricyclic compounds that contain a substituted dihydropyran moiety.

A Perspective on the Stereodefined N,O-Acetals: Synthesis and Potential Applications

Developing chemical reactions that rapidly introduce molecular diversity in a controlled manner represents a prime goal in synthetic organic chemistry. In this regard, our recent studies on the asymmetric synthesis and utilization of stereodefined N,O-acetal opens up a conceptually new methodology. The synthesis of labile N,O-acetals was accomplished by highly efficient and chemoselective Pd-catalyzed asymmetric hydroamination of alkoxyallenes. Furthermore, the utility of the stereodefined N,O-acetals as a stereodiversity-generating element was established by the gold-catalyzed cycloisomerization. In addition to these results, new aspects of the N,O-acetals as diversity-generating elements are also discussed.

Selective Monoterpene-like Cyclization Reactions Achieved by Water Exclusion from Reactive Intermediates in a Supramolecular Catalyst

A polyanionic supramolecular assembly (1) is shown to catalytically cyclize the monoterpene citronellal and two homologues. In contrast to cyclization in acidic aqueous solution, the hydrophobic interior of 1 prevents the capture of reactive intermediates by water. This effect was also observed in the gold-catalyzed cycloisomerization of an enyne. Due to the steric confinement of the catalyst's interior, Prins cyclizations in 1 proceed cleanly both for substrates containing and lacking gem-dimethyl substitution. Encapsulation in 1 consequently imposes a degree of mechanistic control that, similar to enzyme catalysis, is not observed in bulk aqueous solution.

ChemInform Abstract: Gold‐Catalyzed Cascade Cyclizations of 1,6‐Diynyl Carbonates to Benzo[b]fluorenes Involving Arylation of Oxocarbenium Ion Intermediates and Decarboxylative Etherification.

Rearranged: The described gold-catalyzed cycloisomerizations give access to highly substituted benzo[b]fluorenes under mild reaction conditions (see scheme). Experimental results indicate that the in situ formed oxocarbenium ion intermediates, derived from gold-catalyzed 3,3-rearrangement and 6-endo-dig cyclization, undergo intramolecular arylation and subsequent decarboxylative etherification to furnish the final ether products.

A DFT-Based Analysis of the Gold-Catalyzed Cycloisomerization of 1-Siloxy 1,5-Enynes to Cyclohexadienes

In this work, we present a deep theoretical study on the intriguing and unexpected gold-catalyzed cycloisomerization of siloxy enynes to cyclohexadienes. To this end, we have evaluated the electronic and steric properties for three types of alkynyl substituents along the reaction paths and the implications on the evolution through divergent, competitive pathways. For an alkynyl -OR substituent, the results strongly suggest a polarization of the π electrons along the delocalized C2-C1-O system in the key cyclopropyl-carbene intermediate, which is enhanced by the bulkiness of the R group. The results reproduce the experimental observations in excellent agreement and provide interesting and useful clues for predicting the effects of the alkynyl substituent on the nature of the key intermediate and, hence, on the reactivity mode and selectivity.

DFT Studies on Gold-Catalyzed Cycloisomerization of 1,5-Enynes

Gold-catalyzed cycloisomerization of 1,5-enynes has been investigated with the aid of density functional theory calculations at the B3LYP level of theory. We have examined how substituents influence the reaction paths in the cycloisomerization of 1,5-enynes catalyzed by both AuCl and [AuL]+ (L = phosphine).

Gold‐Catalyzed Cascade Cyclizations of 1,6‐Diynyl Carbonates to Benzo[b]fluorenes Involving Arylation of Oxocarbenium Ion Intermediates and Decarboxylative Etherification

Rearranged: The described gold-catalyzed cycloisomerizations give access to highly substituted benzo[b]fluorenes under mild reaction conditions (see scheme). Experimental results indicate that the in situ formed oxocarbenium ion intermediates, derived from gold-catalyzed 3,3-rearrangement and 6-endo-dig cyclization, undergo intramolecular arylation and subsequent decarboxylative etherification to furnish the final ether products.

Gold-Catalyzed Cycloisomerization of Functionalized 1,5-Enynes - An Entry to Polycyclic Framework

Gold-Catalyzed Cycloisomerization of Functionalized 1,5-Enynes - An Entry to Polycyclic Framework