Cyclopropyl Gold Carbene Research Articles

Gold-Catalyzed Addition of β-Oxo Enols at Tethered Alkynes via a Non-Conia-ene Pathway: Observation of a Formal 1,3-Hydroxymethylidene Migration.

With the relay process of Ag(I)/Au(I) catalysts, a one-pot synthesis of skeletally rearranged (1-hydroxymethylidene)indene derivatives from 2-alkynylbenzaldehydes and α-diazo esters is described. This cascade sequence involves Au(I)-catalyzed 5-endo-dig attack of highly enolizable aldehydes at the tethered alkynes, leading to carbocyclizations with a formal 1,3-hydroxymethylidene transfer. On the basis of density functional theory calculations, the mechanism likely involves formation of cyclopropylgold carbenes, followed by an appealing 1,2-cyclopropane migration.

Dodging the Conventional Reactivity of o-Alkynylanilines under Gold Catalysis for Distal 7-endo-dig Cyclization

A direct ring-closing strategy involving a less facile 7-endo-dig carbacyclization of o-alkynylaniline derivatives for the synthesis of benzo[b]azepines has been presented. The trivial well-documented 5-endo-dig cyclization in o-alkynylaniline derivatives due to high nucleophilicity of nitrogen has been overcome by using their vinylogous amides under gold catalysis to access a wide array of benzo[b]azepines in an atom economical way with excellent functional group compatibility. Deuterium scrambling experiments and DFT studies favor a mechanism involving stabilizing conformational change of the initially formed seven-membered vinyl gold intermediate through a key cyclopropyl gold carbene intermediate and its subsequent protodeauration mediated by the counter anion.

Atom-economical synthesis of bicyclo[3.1.0]hexane silanes by gold-catalyzed Si–H bond insertion reaction of 1,6-enynes with hydrosilanes

A gold-catalyzed Si–H bond insertion reaction of 1,6-enynes with hydrosilanes via cyclopropyl gold carbene intermediates is herein reported, and a gold-catalyzed carbene insertion into Ge–H bonds is reported for the first time.

Unlocking the 5-exo Pathway with the AuI -Catalyzed Alkoxycyclization of 1,3-Dien-5-ynes.

The first general regio- and stereoselective 5-exo gold(I)-catalyzed alkoxycyclization of a specific class of 1,5-enynes such as 1,3-dien-5-ynes has been described, despite 1,5-enynes being known to almost invariably proceed via endo cyclizations under gold-catalysis. The configuration of the terminal alkene in the starting 1,3-dien-5-yne plays a crucial role on the regiochemical outcome of the reaction. A wide variety of interesting alkoxy-functionalized alkylidenecyclopentenes have been synthesized from 1-monosubstituted (E)-1,3-dien-5-ynes. On the contrary, the corresponding Z isomers evolve affording formal 6-endo cyclization products. In addition, mechanistic exploration supports a highly stabilized carbocation as a key intermediate instead of a highly constrained cyclopropyl gold carbene from E isomers, and also accounts for the well differentiated reactivity observed between both E/Z geometrical isomers as well as for the stereochemical outcome of the reaction.

Gold-Catalyzed Diastereoselective Formal Intermolecular [4 + 2 + 1] Cycloaddition of 1,3-Dien-8-yne with Diazo Ester.

The first example of gold-catalyzed formal intermolecular [4 + 2 + 1] cycloaddition was developed using 1,3-dien-8-yne as C4 and C2 units and diazo ester as the C1 unit, which provides expedient access to a series of structurally complicated [5.3.0] bicyclic adducts in moderate yields with moderate to high diastereoselectivities. The key route involved a cascade process of dienyne cycloisomerization, cyclopropyl gold carbene's trapping, and subsequent divinyl cyclopropane (DVCP) Cope rearrangement.

Gold(i)-catalyzed nucleophilic cyclization of β-monosubstituted o-(alkynyl)styrenes: a combined experimental and computational study.

The stereospecific gold(i)-catalyzed nucleophilic cyclization of β-monosubstituted o-(alkynyl)styrenes to produce C-1 functionalized 1H-indenes including challenging substrates and nucleophiles, such as β-(cyclo)alkyl-substituted o-(alkynyl)styrenes and a variety of alcohols as well as selected electron-rich aromatics, is reported. DFT calculations support the stereochemical outcome of the process that involves the formation of a key cyclopropyl gold carbene intermediate through a regiospecific 5-endo cyclization.

Asymmetric Synthesis of Dihydropyranones via Gold(I)-Catalyzed Intermolecular [4+2] Annulation of Propiolates and Alkenes.

Intermolecular asymmetric gold catalysis involving alkyne activation presents a significant challenge due to its distinct mechanistic mode from other metals. Herein, we report a highly enantioselective synthesis of α,β-unsaturated δ-lactones from [4+2] annulation of propiolates and alkenes in upto 95 % ee. Notably, for the desired chiral recognition, the choice of 1,1,2,2-tetrachloroethane as solvent was found to be crucial. Furthermore, an anionic surfactant (sodium dodecyl sulfate) improved the product selectivity in the divergence of the cyclopropyl gold carbene intermediate.

Asymmetric Synthesis of Dihydropyranones via Gold(I)‐Catalyzed Intermolecular [4+2] Annulation of Propiolates and Alkenes

AbstractIntermolecular asymmetric gold catalysis involving alkyne activation presents a significant challenge due to its distinct mechanistic mode from other metals. Herein, we report a highly enantioselective synthesis of α,β‐unsaturated δ‐lactones from [4+2] annulation of propiolates and alkenes in upto 95 % ee. Notably, for the desired chiral recognition, the choice of 1,1,2,2‐tetrachloroethane as solvent was found to be crucial. Furthermore, an anionic surfactant (sodium dodecyl sulfate) improved the product selectivity in the divergence of the cyclopropyl gold carbene intermediate.

Intermolecular Gold(I)‐Catalyzed Cyclization of Furans with Alkynes: Formation of Phenols and Indenes

A heart of gold: Phenols can be obtained by the intermolecular reaction of furans with alkynes by using [AuIPr](+)A(-) catalysts (see scheme). 1,3-Diphenylisobenzofuran also reacts via a cyclopropyl gold carbene to selectively form 2,3-disubstituted indenes. (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene; A = anion.).

ChemInform Abstract: Complexity via Gold‐Catalyzed Molecular Gymnastics

AbstractReview: 97 refs.

Carbocations or Cyclopropyl Gold Carbenes in Cyclizations of Enynes

Theoretical and experimental studies on the gold(I)-catalyzed formal [4+2] cycloaddition of dienynes are consistent with a mechanism that proceeds by means of cyclopropyl gold(I) carbenes instead of simple carbocations. This work shows that homoallylic stabilization is significant even for systems in which the tertiary carbocation is stabilized by two methyl groups.

Complexity via Gold-Catalyzed Molecular Gymnastics

Reactions of 1,6-enynes catalyzed by gold(I) complexes usually proceed stereospecifically through highly distorted cyclopropyl gold carbenes. Substrates with an alkoxy substituent at the propargylic position undergo stereoselective transformations through intermediates in which the OR group and the gold carbene are anti-oriented. Intramolecular attack of carbonyl groups to the cyclopropyl gold carbene is faster than the 1,5-migration of the OR groups, which itself is faster than the intramolecular cyclopropanation by a pendant alkenyl group. The intramolecular attack of carbonyl groups is the key transformation in the [2+2+2] gold-catalyzed cycloaddition, which has been applied in the total synthesis of (+)-orientalol F.

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.

On the Mechanism of the Puzzling “Endocyclic” Skeletal Rearrangement of 1,6‐Enynes

AbstractSkeletal rearrangements of simple 1,6‐enynes have been studied in order to determine the factors that control the formation of five‐ or six‐membered rings. Simple 1,6‐enynes substituted only at C‐4 preferentially give six‐membered rings on skeletal rearrangement in the presence of gold(I) catalysts, whereas increasing electron‐withdrawing character of substituents at C‐4 leads to five‐membered rings. Reactions of these simple enynes in the presence of PtCl4 as catalyst give exclusively exo‐double skeletal rearrangements. Enynes substituted at the alkyne also react with AuI catalysts to give exclusively products of exo‐double rearrangement. The different mechanisms have been analyzed by DFT calculations. Although a pathway for the formation of six‐membered rings involving two steps in a ring‐expansion/ring‐contraction process was found, the activation energy of the first step is too high. Instead, this skeletal rearrangement appears to follow an exo‐single skeletal rearrangement in which the initial cyclopropyl gold carbene opens to form a six‐membered ring. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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)‐Catalyzed Intramolecular Cyclopropanation of Dienynes.

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Gold(I)‐Catalyzed Intramolecular Cyclopropanation of Dienynes

Gold(I) complexes are the most active catalysts for the biscyclopropanation of dienynes to form tetracyclic compounds. PtII and ZnII are also able to promote the biscyclopropanation, although less efficiently. The configurations obtained in all cases with the use of gold(I) catalysts can be explained by the pathway proceeding through anti cyclopropyl gold carbenes. Similar intermediates are most probably involved in reactions catalyzed by RuII and PtII. Two different cyclopropanation pathways have been found; they depend on the structures of the cyclopropyl gold carbenes (anti or syn) and the relative arrangements of the metal carbenes and the alkenes.