Subtopic Deep Dive
Gold-Catalyzed Cycloisomerization of Alkynes
Research Guide
What is Gold-Catalyzed Cycloisomerization of Alkynes?
Gold-catalyzed cycloisomerization of alkynes uses gold(I) complexes to activate alkyne π-bonds for intramolecular cyclizations forming carbo- and heterocycles.
This reaction enables efficient assembly of polycyclic frameworks from enynes and polyynes. Key examples include 1,5-enyne conversion to bicyclo[3.1.0]hexenes (Luzung et al., 2004, 351 citations). Reviews by Dorel and Echavarren (2015, 1668 citations) and Obradors and Echavarren (2013, 514 citations) summarize over 1000 studies on mechanisms and scope.
Why It Matters
Gold-catalyzed cycloisomerizations construct complex architectures for pharmaceuticals and natural products, as in cascade polycyclizations (Ardkhean et al., 2016). Echavarren's group demonstrated synthetic utility in building polycyclic cores via enyne rearrangements (Obradors and Echavarren, 2013). These atom-economic processes reduce steps in total synthesis, with applications in alkaloid frameworks reported by Hashmi (2003).
Key Research Challenges
Mechanistic Ambiguity
Distinguishing gold carbenes from carbenoids complicates pathway predictions (Wang et al., 2015). Obradors and Echavarren (2013) mapped labyrinthine routes in alkyne activations. Experimental verification remains difficult due to transient intermediates.
Ligand Optimization
Phosphine and N-N ligands modulate selectivity between cycloisomerization and alkoxycyclization (Muñoz et al., 2005). Chiral ligands enable enantioselective variants but require tuning. Broad substrate scope demands ligand screening.
Catalyst Deactivation
Gold(I) complexes suffer aggregation or protodeauration side reactions. Zhang (2014) highlighted stability issues in alkyne oxidations. Scalable processes need robust precatalysts.
Essential Papers
Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity
Ruth Dorel, Antonio M. Echavarren · 2015 · Chemical Reviews · 1.7K citations
For centuries, gold had been considered a precious, purely decorative inert metal. It was not until 1986 that Ito and Hayashi described the first application of gold(I) in homogeneous catalysis.(1)...
A Non-Diazo Approach to α-Oxo Gold Carbenes via Gold-Catalyzed Alkyne Oxidation
Liming Zhang · 2014 · Accounts of Chemical Research · 668 citations
For the past dozen years, homogeneous gold catalysis has evolved from a little known topic in organic synthesis to a fully blown research field of significant importance to synthetic practitioners,...
Gold-Catalyzed Rearrangements and Beyond
Carla Obradors, Antonio M. Echavarren · 2013 · Accounts of Chemical Research · 514 citations
Cycloisomerizations of enynes are probably the most representative carbon-carbon bond forming reactions catalyzed by electrophilic metal complexes. These transformations are synthetically useful be...
Homogeneous gold catalysts and alkynes: A successful liaison
A. Stephen K. Hashmi · 2003 · Gold bulletin · 356 citations
Catalaytic Isomerization of 1,5-Enynes to Bicyclo[3.1.0]hexenes
Michael R. Luzung, Jordan P. Markham, F. Dean Toste · 2004 · Journal of the American Chemical Society · 351 citations
The cycloisomerization of 1,5-enynes catalyzed by cationic triphenylphosphinegold(I) complexes produces bicyclo[3.1.0]hexenes. Substitution at all positions of the 1,5-enyne is tolerated, leading t...
Intriguing mechanistic labyrinths in gold(<scp>i</scp>) catalysis
Carla Obradors, Antonio M. Echavarren · 2013 · Chemical Communications · 321 citations
Many mechanistically intriguing reactions have been developed in the last decade using gold(I) as catalyst. Here we review the main mechanistic proposals in gold-catalysed activation of alkynes and...
Ligand Effects in Gold- and Platinum-Catalyzed Cyclization of Enynes: Chiral Gold Complexes for Enantioselective Alkoxycyclization
María Paz Muñoz, Javier Adrio, Juan Carlos Carretero et al. · 2005 · Organometallics · 298 citations
Phosphine and bidentate N-N ligands inhibit the Alder-ene-type cycloisomerization of enynes catalyzed by Pt(II) and favor the alkoxycyclization process. The enantioselective Pt(II)-catalyzed alkoxy...
Reading Guide
Foundational Papers
Start with Hashmi (2003) for gold-alkyne origins, Luzung et al. (2004) for 1,5-enyne benchmark, then Dorel and Echavarren (2015) for comprehensive mechanisms.
Recent Advances
Obradors and Echavarren (2013) on rearrangements; Zhou et al. (2014) on ynamide cycloadditions; Ardkhean et al. (2016) on synthesis cascades.
Core Methods
π-Activation by LAu+ forms vinylgold intermediates; 6-endo-dig or 5-exo-dig cyclizations; ligand tuning with PPh3 or NHC for selectivity.
How PapersFlow Helps You Research Gold-Catalyzed Cycloisomerization of Alkynes
Discover & Search
Research Agent uses searchPapers with 'gold-catalyzed cycloisomerization enynes' to retrieve Dorel and Echavarren (2015), then citationGraph maps 1668 citing works by Hashmi and Toste groups, and findSimilarPapers uncovers substrate scope variants.
Analyze & Verify
Analysis Agent applies readPaperContent to parse mechanisms in Obradors and Echavarren (2013), verifyResponse with CoVe cross-checks carbene pathways against Zhang (2014), and runPythonAnalysis plots yield data from 20+ papers using pandas for ligand effect trends, graded by GRADE for evidence strength.
Synthesize & Write
Synthesis Agent detects gaps in enantioselective cascades post-2015 via gap detection, then Writing Agent uses latexEditText for reaction schemes, latexSyncCitations for Echavarren references, and latexCompile for publication-ready reviews with exportMermaid diagrams of cyclization pathways.
Use Cases
"Plot yields vs ligand type in gold enyne cycloisomerizations from 2000-2020 papers"
Research Agent → searchPapers → Analysis Agent → runPythonAnalysis (pandas/matplotlib on extracted data) → CSV export of trends showing phosphine superiority.
"Draft LaTeX review section on gold carbene mechanisms with schemes"
Synthesis Agent → gap detection → Writing Agent → latexEditText + latexGenerateFigure (cyclization arrows) → latexSyncCitations (Dorel 2015) → latexCompile PDF.
"Find GitHub repos with computational models of gold alkyne activation"
Research Agent → paperExtractUrls (Toste 2004) → Code Discovery → paperFindGithubRepo → githubRepoInspect → DFT optimization scripts for mechanism validation.
Automated Workflows
Deep Research workflow scans 50+ papers via searchPapers on 'gold cycloisomerization mechanisms', structures reports with Echavarren citations, and applies CoVe checkpoints. DeepScan's 7-step analysis verifies Toste (2004) bicyclo[3.1.0] pathways with runPythonAnalysis on stereo data. Theorizer generates hypotheses on ligand-carbene interactions from Hashmi (2003) and Zhang (2014).
Frequently Asked Questions
What defines gold-catalyzed cycloisomerization of alkynes?
Gold(I) activates alkyne π-bonds for intramolecular attack by alkenes or nucleophiles, forming cycles like bicyclo[3.1.0]hexenes (Luzung et al., 2004).
What are key methods in this subtopic?
Cationic phosphinegold(I) catalyzes 1,5-enyne isomerizations (Toste, 2004); ynamide variants enable [3+2] cycloadditions (Zhou et al., 2014).
What are seminal papers?
Dorel and Echavarren (2015, Chem. Rev., 1668 cites) reviews complexity building; Luzung et al. (2004, JACS, 351 cites) reports first bicyclo[3.1.0]hexenes.
What open problems exist?
Enantioselective cascades for polycycles; catalyst recycling beyond lab scale; full disambiguation of carbene vs π-activation paths (Wang et al., 2015).
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Part of the Catalytic Alkyne Reactions Research Guide