Gold(I)-Catalyzed Intramolecular Cyclization/Intermolecular Cycloaddition Cascade: Fast Track to Polycarbocycles and Mechanistic Insights

doi:10.21203/rs.3.rs-91303/v1

Download PDF

Article

Gold(I)-Catalyzed Intramolecular Cyclization/Intermolecular Cycloaddition Cascade: Fast Track to Polycarbocycles and Mechanistic Insights

https://doi.org/10.21203/rs.3.rs-91303/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 19 Feb, 2021

Read the published version in Nature Communications →

Version 1

posted

You are reading this latest preprint version

Herein we report a gold-catalyzed cascade protocol for the assembly of polycarbocyclic frameworks in high yields under mild reaction conditions. Mechanistic studies indicate that the unique β-aryl gold-carbene species, generated via gold-promoted 6-endo-dig diazo-yne cyclization, is the key intermediate in this reaction, followed by a [4 + 2]-cycloaddition with external alkenes. In comparison to the well-documented metal carbene cycloadditions, this is the first example of the carbene intermediate to serve as a 4-C synthon in a cycloaddition reaction. A variety of elusive π-conjugated polycyclic hydrocarbons (CPHs) with multiple substituents are readily accessible from the initially generated products by a mild oxidation procedure.

Organic Chemistry

Catalysis

Materials Chemistry

Optical Materials and Devices

gold-catalyzed cascade protocol

polycarbocyclic frameworks

cycloaddition reaction

Reactive metal carbene species participate in a broad range of applications for the effective formation of C-C and C–heteroatom bonds in synthetic organic chemistry^1-4. The versatile reactivity of this species is mainly dependent on the choice of catalysts and the substituent(s) proximal to the carbene center^5,6. The effect of these two variables can be quite pronounced, and novel synthetic transformations could be expected by switching either of these parameters. For example, concerted and stepwise reaction pathways have been disclosed in the cyclopropanation reaction, depending on the type of metal catalysts that were used in these transformations with corresponding carbene precursors (Fig. 1a, path a vs path b)^7-9. Moreover, various [4+1]-cycloaddition reactions of carbene species with α,β-unsaturated carbonyl compounds¹⁰, in situ generated o-QMs^11,12, 1,3-dienes¹³, or other functionalized alkenes¹⁴ have been realized through different reaction pathways in the presence of corresponding metal catalysts. On the other hand, the vinyl metal carbene, which possesses two electrophilic sites, could function as 1- or 3-carbon building blocks. Davies et al. have demonstrated that vinylogous addition¹⁵ or C-H insertion¹⁶ of this intermediate with enol ethers are the dominating transformations in the presence of dirhodium catalysts. But a [3+2]-cycloaddition could be enabled in the presence of gold-catalyst with identical starting materials¹⁷. Later, a variety of [3+n]-cycloadditions of vinyl/enol metal carbene species with corresponding dipolarophiles have been disclosed independently by Doyle^18,19, Davies^20,21, and Yoo²², assembling five- to eight-membered carbocyclic and heterocyclic frameworks (Fig. 1b). Despite these significant achievements, the carbene precursors in these cycloadditions have been severely limited to α-vinyl and α-silyl enol diazoacetates. Thus, the exploration of effective catalytic approaches for the access to a new type of carbene intermediate with readily available materials is highly desirable, which would substantially broaden the substrate scope for the diversity synthesis, and more importantly, enabling novel methods for the practical synthesis.

Recently, the gold(I) complexes, which are versatile and selective catalysts for alkyne activation due to their strong Lewis acidity and potential to stabilize cationic reaction intermediates, have been employed in a plethora of synthetic transformations, allowing rapid and efficient assembly of structurally complex molecules^23-28. In this regard, the three-center four-electron σ-bond model for the fundamental description of the gold carbene intermediate has been proposed by Toste and Goddard in 2009²⁹, however, the electronic nature of these gold intermediates is still under exploring^30-33. In 2015, Echavarren pointed out that according to IUPAC rules the in-demand term “gold carbene” describes the gold carbene species, regardless of whether the carbene or carbocation extreme resonance dominates³⁴. Beyond this terminological point, the catalytic cycloadditions of gold carbene with olefins have attracted much attention. Cyclopropanation of olefins with a variety of carbene precursors, including diazo compounds, 1,n-enynes, yne-enones, propargyl esters, cyclopropenes, 1,3,5-cycloheptatrienes, and alkynes via oxidation/nitrene transfer processes, is the main focus in this area³⁵. Gold-catalyzed [4+1]-³⁶ and [3+2]-cycloadditions^37,38 have been disclosed by Echavarren with 1,3,5-cycloheptatriene as the carbene precursor. Meanwhile, the gold-catalyzed formal [4+2]-cyclization of enynes with tethered alkene via cyclopropyl metal carbene intermediate has been studied by the same group³⁹. Inspired by these advances and our recent study on gold-catalyzed diazo-yne carbocyclization^40-42, we envisioned that novel reactivity could be disclosed with these new types of in situ generated carbene intermediates, which could not be formed through other approaches or precursors. For example, if an asynchronous reaction pathway is dominating in the reaction of carbene intermediate with alkenes (Fig. 1a, path b), then, unprecedented transformations beyond the cyclopropanation might become possible by trapping the carbocation intermediate I (Fig. 1a, path c). However, the second C-C bond formation occurs through a rather low energy barrier in the stepwise cyclopropanation reaction, thus, the interception of the carbocation I with an external nucleophile (NuH) is still a challenge. Herein, we describe our recent results in this direaction, an unprecedented cycloaddition reaction of the cross-conjugated β-aryl gold-carbene II serving as a 4-C synthon, which generated in situ through a selective 6-endo-dig diazo-yne carbocyclization^43-46. This novel reaction features an asynchronous process⁴⁷: the gold carbene intermediate reacts with an olefin to form the carbocation species III, which could be successfully intercepted by the tethering aryl group rather than the cyclopropanation, leading to a general access for the assembly of polycarbocyclic frameworks in high to excellent yields (Fig. 1c). Moreover, these products could be readily transformed into p-conjugated polycyclic hydrocarbons (CPHs) under mild oxidation procedure. Owing to their various useful properties including their intriguing pharmacological activities⁴⁸, electrical and optical properties⁴⁹, the CPHs have attracted significant attention^50,51.

Reaction optimization. Initially, the alkyne-containing 1,3-dicarbonyl diazo compound 1a and styrene 2a were chosen as the model substrates to optimize the reaction conditions (Table 1). A variety of metal catalysts, such as Rh^I-, Rh^II-, Cu^II-, Pd⁰-, and Ag^I-complexes were examined in dichloroethane (DCE) at different temperatures, which all led to the tricyclic product 3’ in high to excellent yields rather than the desired tetracyclic product 3 (entries 1-5). Given the fact that the formation of 3’ with these catalysts should go through a carbene/alkyne metathesis process (CAM)^52-⁶¹, the gold-complexes, which have shown unique ability to selectively activate alkyne species with the pendant diazo group serves as a latent functionality^40-42,62, were then evaluated. Due to the competition between ligand and carbene for the contribution of electron density of gold center, the ligands of the gold catalysts have a significant influence on the bonding and reactivity of corresponding gold-complex intermediates^29-34, and we have observed these dramatic influences in the outcome of the following optimization. The gold catalysts with trialkylphosphines as the ligands could produce mainly the polycarbocyclic product 3 in moderate conversions (entries 6-8, 29%-36% yields), whereas, the triarylphosphines showed relative lower reactivity (27%-39% conversions), preferring to form the intramolecular cyclization product 3’ (entries 9-11). Further investigation of phosphine ligands with structural and electronic diversity implied that ligands bearing electron-donating substituents (entries 12 vs 13) and with appropriate steric hindrance (entry 14 vs entries 12, 16, and 17) gave better results, affording 3 in 90% NMR yield when JohnPhos (L3) was used as the ligand (entry 14, 84% isolated yield). A comparably good result was obtained by switching the counter anion of gold catalyst from SbF₆⁻ to NTf₂⁻ (entry 15). Based on these results, we set out to explore a statistical regression approach to interpretation and prediction of ligand effects. The calculated Au-Cl bond distance, which has been disclosed by Fey and co-workers⁶³, might provide such a platform to quantify the steric and electronic properties of these ligands^64,65. Our optimization results have shown good correlation with the calculated parameters of the Au-Cl bond distance of gold-complexes with corresponding ligands (see Supplementary Fig. 1 for detail). Moreover, these results bring us to predict that electron-donating substituents with moderate steric hindrance on the phosphine ligand might further improve the yield. Thus, the ligand (Me₂N)₃P, which is similar to triisopropylphosphine (entry 8), but is much more flexible due to the additional freedom of nitrogen inversion and the three amino groups offer complementary donor functions^66,67, was introduced. Gratifyingly, this ligand proved to the most effective one, delivering the desired product 3 in 89% isolated yield (entry 18).

Substrate scope. Under the optimized reaction conditions, the scope of this gold-catalyzed [4+2]-cycloaddition with respect to the 1,3-dicarbonyl diazo compound 1 in combination with styrene 2a was examined (Fig. 2). The substitutions on the aryl linkage (Ar¹), including fluoro on the different positions (4-7), methyl (8), and methoxy (9) groups did not obviously affect the reactivity, and 82%-93% isolated yield was obtained in these cases. The diazo compound with naphthyl group as the linkage provided the pentacyclic product 10 in 53% yield. Then, the nature of the alkyne terminus was investigated (Ar²). The steric hindrance resulting from the ortho- and meta-methyl substituents on the phenyl ring did not impact the reactivity a lot, delivering corresponding products 11 and 12 in 75% and 95% yield, respectively. Other diazo derivatives, containing different substituents on the para-position of the aryl ring, performed well under these conditions (13-16), although low yields were obtained in the halogen-substituted cases. This may due to the lower nucleophilicity of these aromatic rings. Naphthyl- and thienyl-alkynes reacted effectively under gold-catalysis, offering the corresponding polycyclic products all in high yields (17-20). The installation of cyclohexenyl group proximal to the alkyne motif instead of aryl led to the product 21 as two isomers in 33% and 50% yields, respectively, and with 21b in 1.7:1 dr.

To further explore the substrate scope of this gold-catalyzed [4+2]-cycloaddition, we next examined a variety of olefins 2 (Fig. 3). The electronic effects and the position of the substituent groups on the phenyl ring of the styrene had little influence; substrates containing bromo, chloro, fluoro, trifluoromethyl, methyl, tert-butyl, and methoxy groups effectively reacted with 1l to form the tetracyclic products 22-30 in synthetically useful to high yields. Relatively high yields were obtained when an electron-withdrawing substituent was incorporated in the arene. Olefins with bulky ortho-substituent also tolerated in this reaction, selectively affording the corresponding products 31-35 as signal diastereomer in 49%-94% yields. Even 1,2-divinylbenzene could be used, interestingly only the mono-cycloaddition product 36 was generated in 81% yield as a mixture of two diastereomers. The diastereomers resulted from the additionally formed axial chirality due to the hindered rotation of the ortho-substituted aryl group in these products. Despite the inefficiency of the reaction with internal and alkyl alkenes, which only generated the intramolecular cyclization byproducts from 1l, the disubstituted terminal alkene, 1-methyl-1-phenylethene, worked well, leading to the cycloadduct 35 in 76% yield. The structures of 23 and 34 were confirmed by single-crystal X-ray diffraction analysis.

Development of the oxidation procedure for polycyclic aromatic hydrocarbons (PAHs) With these polycarbocyclic products in hand, we then achieved their transformation to the corresponding CPHs. The aromatization occurred smoothly in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) under mild and neutral conditions (Fig. 4). Various functional groups, such as phenolic hydroxyl, ester, methoxy, halogen, alkyl, and aryl were well tolerated, assembling multiple substituted CPHs 38-53 in high to excellent yields. In addition to the chrysene derivatives, a few of elusive CPHs, including picene (46, 86%), benzo[c]chrysene (47, 98%), and phenanthro[2,1-b]thiophene (48, 84%) were also readily prepared in high yields. It could be envisioned that additional different types of polyaromatic hydrocarbons with structural diversity would become accessible with this method by the manipulation of the structure of the substrates or via further synthetic transformations.

Optical properties. After the construction of these elusive p-conjugated polycyclic hydrocarbons (CPHs), we then investigated the optical properties of representative analogous in DMSO (Fig. 5). The absorption spectra of tested PAHs displayed the λ_max in the range of 402-421 nm. For the fluorescence spectra, compounds 43, 45, 50, and 51 exhibited sky-blue lights with similar peaks at around 490 nm; whereas, the five-fused aromatic product 46 showed green light with a maximum emission of 550 nm due to the extension of the p-conjugated system.

Mechanistic studies. Mechanistic experiments were performed to gain insights into the reaction pathway of this transformation (Fig. 6). To verify the existence of the on-ring β-aryl gold-carbene intermediate, the interception reaction with 1l in the presence of diphenyl sulfoxide (1.5 equiv), instead of styrene, was carried out under standard conditions, and the corresponding cyclic ketone product 54 was isolated in 84% yield (Fig. 6a). These results are also consistent with a direct 6-endo-dig diazo-yne carbocyclization process for the generation of this on-ring carbene intermediate, otherwise, the linear ketone product that furnished via direct carbonylation of the diazo group might be observed⁴³. Evidence for the carbocation-like reactivity of this generated gold-complex was verified by the reactions of 1l with two disubstituted terminal alkenes, 1,1-diphenylethylene and 1-phenyl-1-trimethylsiloxyethylene, delivering the coupling-type and addition-type products 55 and 56 in 71% and 80% yields, respectively (Fig. 6b and 6c). Moreover, a non-concerted, step-wise mechanism of the cyclization process was well supported by the interception reaction with external alcohol. The identifiable three-component product 57 was isolated in 79% yield when the reaction was carried out in the presence of o-bromobenzyl alcohol (Fig. 6d). The comparison reaction with 1,3-dicarbonyl diazo compound 1aa without the alkyne species turned out that only very slowly decomposition of the diazo compound was observed under the current conditions (Fig. 6e). The ³¹P NMR analysis results by mixing the gold catalyst (5.0 mol%) with 1l (0.02 mmol) in CDCl₃ at 20 °C suggested that, rather than direct decomposition of the diazo species^59-61, the formation of a relative stable Au-alkyne complex is favorable under these conditions (Fig. 6f, and see Supplementary Fig. 2 for detail). In addition, this protocol could also be applied for the preparation of benzo[c]phenanthridine 58 and 6H-dibenzo[c,h]chromene 59 from corresponding materials in 91% and 94% yields, respectively (Fig. 7a and 7b). All these results well rationalized the reaction mechanism, and also underlined the synthetic potential of this method in diversity-oriented synthesis.

Based on the above studies and the reported literature^40-47, a possible reaction mechanism is depicted in Fig. 8. Initially, the gold-promoted 6-endo-dig carbocyclization of 1 formed intermediate B via A, which further led to the key intermediate vinyl gold carbene C after the extrusion of N₂. The resonance phenomenon of this gold-complex between carbene (C) and carbocation (C’) forms, which mainly depends on the ligands of the gold catalyst, might be existing. In this case, carbocation-like intermediate C’ has been suggested based on the observations of the control experiments (Fig. 6). Subsequently, this gold intermediate reacted with an external alkene to form the carbocation intermediate D, followed by a Friedel-Crafts-type cyclization, furnishing the corresponding polycyclic products, and regenerating the gold catalyst. It is worth noting that this is the first example of an in situ-generated β-aryl gold carbene serving as a 4-C synthon in a cycloaddition reaction.

Applications. To demonstrate the utility of the current method, we performed the reaction on a gram scale (Fig. 9, 4.0 mmol), providing 1.48 g of 14 in 87% yield. Then, the cycloadduct 14 was subjected to further transformations. Sulfonylation of the phenolic hydroxyl group with trifluoromethanesulfonic anhydride (Tf₂O) led to the coupling precursor 60 in quantitative yield. The following Sonogashira and Suzuki coupling reactions with terminal alkyne and naphthylboronic acid gave 61 and 62 in 93% and 98% yields, respectively. Oxidation of 62 with DDQ followed by an acid-promoted Friedel-Crafts-type intramolecular cyclization delivered the polycyclic hydrocarbon 63 in a total 82% yield for the two steps.

We have developed an unprecedented gold-catalyzed diazo-yne cyclization/intermolecular [4+2]-cycloaddition reaction of alkyne-containing diazo compounds with alkenes. Mechanistic studies indicate that the β-aryl gold-carbene is the key intermediate in this cascade transformation, which is generated via gold-promoted 6-endo-dig diazo-yne cyclization and served as a 4-C synthon in following stepwise [4+2]-cycloaddition. A variety of polycarbocyclic frameworks are synthesized in good to high yields, and these generated products could be readily converted to elusive p-conjugated polycyclic hydrocarbons (CPHs) with multiple substituents under a mild oxidation procedure. Preliminary photophysical studies have been conducted with representative CPHs, which emit sky-blue and green fluorescence. This new protocol complements the common carbene/alkyne metathesis strategies in terms of chemoselectivity and reactivity patterns. Novel cascade transformations and synthetic applications could be envisioned in due course with the unique carbene species in situ generated under gold catalysis.

General methods. See Supplementary Methods for further details.

Typical procedure for the gold-catalyzed formal [4+2] cycloaddition. To a 10-mL oven-dried vial containing a magnetic stirring bar, (Me₂N)₃PAuCl (3.95 mg, 0.01 mmol), AgSbF₆ (3.43 mg, 0.01 mmol), and DCE (0.5 mL) were added in sequence in a nitrogen-filled glove-box. The reaction mixture was stirred at 25 ˚C for 2.0 hours. The solvent was removed and the residue was dissolved in DCE (0.5 mL). Then the mixture was filtered through a pad of Celite. The filtrate was added into a solution of 1 (0.2 mmol) and 2 (olefin, 0.3 mmol) in DCE (0.5 mL) at 60 ˚C, and the resulting reaction mixture was stirred under these conditions for 6.0 hours. Then, the solvent was removed under reduced pressure and the crude product was purified by column chromatography on silica gel (eluent: Ethyl acetate/light petroleum ether =1/30~1/10) to afford the polycyclic compounds 3 – 37 in good to high yields.

Typical procedure for the oxidative aromatization. To a 10-mL oven-dried flask equipped with a magnetic stirring bar, the above prepared polycyclic products (0.10 mmol), 2,3-Dicyano-5,6-dichlorobenzoquinone (DDQ, 25.0 mg, 0.11 mmol), and 1,4-dioxane (6.0 mL) were added in sequence. The reaction mixture was stirred at 25 ˚C for 12.0 hours. Then, the solvent was removed under reduced pressure and the crude product was purified by column chromatography on silica gel (eluent: petroleum ether/ethyl acetate = 20:1) to give the polycyclic aromatic hydrocarbons 38-53 in high to excellent yields.

Additional data supporting the findings described in this manuscript are available in the Supplementary Information. For full characterization data of new compounds and experimental details, see Supplementary Methods and Figures in Supplementary Information file. The X-ray crystallographic coordinates for structures 23 and 34 reported in this study have been deposited at the Cambridge Crystallographic Data Centre (CCDC), under deposition number 1828268 (23) and 1849634 (34). These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc. cam.ac.uk/data_request/cif. All other data are available from the authors upon reasonable request.

Acknowledgements

Support for this research from the National Natural Science Foundation of China (21971262), Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery (2019B030301005), and The Program for Guangdong Introducing Innovative and Entrepreneurial Teams (No. 2016ZT06Y337) is greatly acknowledged. C.Z. is grateful to the CSC (China Scholarship Council) for the PhD fellowship.

Author contributions

X.X. and A.S.K.H. conceived and designed the study; C.Z., K.H. and C.P. performed the experiments; C.Z. analyzed the experimental data; S.Z. checked the experimental data; All the authors contributed to scientific discussion. X.X., A.S.K.H. and C.Z. wrote the paper.

Competing interests

The authors declare no competing interests.

Additional information

Supplementary information is available for this paper at http://www.nature. com/naturecommunications.

Davies, H. M. L. & Manning, J. R. Catalytic C-H functionalization by metal carbenoid and nitrenoid insertion. Nature 451, 417−424 (2008).
Zhu, S. & Zhou, Q. Transition-metal-catalyzed enantioselective heteroatom–hydrogen bond insertion reactions. Chem. Res. 45, 1365−1377 (2012).
Doyle, M. P. et al. Catalytic carbene insertion into C−H bonds. Rev. 110, 704−724 (2010).
Xia, Y., Qiu, D. & Wang, J. Transition-metal-catalyzed cross-couplings through carbene migratory insertion. Rev. 117, 13810−13889 (2017).
Ford, A. et al. Modern organic synthesis with α−diazocarbonyl compounds. Rev. 115, 9981−10080 (2015).
Marinozzi, M., Pertusati, F. & Serpi, M. λ5-Phosphorus-containing α-diazo compounds: a valuable tool for accessing phosphorus-functionalized molecules. Rev. 116, 13991−14055 (2016).
Wang, H. et al. Rhodium-catalyzed enantioselective cyclopropanation of electron-deficient alkenes. Sci. 4, 2844–2850 (2013).
Pérez-Galán, P. et al. Mechanism of the gold-catalyzed cyclopropanation of alkenes with 1,6-enynes. Sci. 2, 141–149 (2011).
Ringger, D. H. & Chen, P. Rational design of a gold carbene precursor complex for a catalytic cyclopropanation reaction. Chem. Int. Ed. 52, 4686–4689 (2013).
Zhou, J.-L. et al. Tunable carbonyl ylide reactions: selective synthesis of dihydrofurans and dihydrobenzoxepines. Chem. Int. Ed. 50, 7874–7878 (2011).
Suneja, A. & Schneider, C. Phosphoric acid catalyzed [4 + 1]-cycloannulation reaction of ortho-quinone methides and diazoketones: catalytic, enantioselective access toward cis-2,3-dihydrobenzofurans. Lett. 20, 7576–7580 (2018).
Pandit, R. P., Kim, S. T. & Ryu, D. H. Asymmetric synthesis of enantioenriched 2-aryl-2,3-dihydrobenzofurans by a Lewis acid catalyzed cyclopropanation/intramolecular rearrangement sequence. Chem. Int. Ed. 58, 13427–13432 (2019).
Rodriguez, K. X., Pilato, T. C. & Ashfeld, B. L. An unusual stereoretentive 1,3-quaternary carbon shift resulting in an enantioselective RhII-catalyzed formal [4+1]-cycloaddition between diazo compounds and vinyl ketenes. Sci. 9, 3221–3226 (2018).
Meloche, J. L. & Ashfeld, B. L. A. A rhodium(II)-catalyzed formal [4+1]-cycloaddition toward spirooxindole pyrrolone construction employing vinyl isocyanates as 1,4-dipoles. Chem. Int. Ed. 56, 6604–6608 (2017).
Smith, A. G. & Davies, H. M. L. Rhodium-catalyzed enantioselective vinylogous addition of enol ethers to vinyldiazoacetates. Am. Chem. Soc. 134, 18241−18244 (2012).
Fu, L., Guptill, D. M. & Davies, H. M. L. Rhodium(II)-catalyzed C–H functionalization of electron-deficient methyl groups. Am. Chem. Soc. 138, 5761−5764 (2016).
Briones, J. F. & Davies, H. M. L. Enantioselective gold(I)-catalyzed vinylogous [3 + 2] cycloaddition between vinyldiazoacetates and enol ethers. Am. Chem. Soc. 135, 13314−13317 (2013).
Xu, X. & Doyle, M. P. The [3 + 3]-cycloaddition alternative for heterocycle syntheses: catalytically generated metalloenolcarbenes as dipolar adducts. Chem. Res. 47, 1396−1405 (2014).
Cheng, Q.-Q. et al. Cycloaddition reactions of enoldiazo compounds. Cycloaddition reactions of enoldiazo compounds. Soc. Rev. 46, 5425-5443 (2017).
Qin, C. & Davies, H. M. L. Rh₂(R-TPCP)₄-Catalyzed enantioselective [3+2]-cycloaddition between nitrones and vinyldiazoacetates. Am. Chem. Soc. 135, 14516−14519 (2013).
Parr, B. T. & Davies, H. M. L. Highly stereoselective synthesis of cyclopentanes bearing four stereocentres by a rhodium carbene-initiated domino sequence. Commun. 5, 4455 (2014).
Lee, D. J. et al. Multicomponent [5+2] cycloaddition reaction for the synthesis of 1, 4-diazepines: Isolation and reactivity of azomethine ylides. Am. Chem. Soc. 136, 11606–11609 (2014).
Echavarren, A. M. Carbene or cation? Chem. 1, 431–433 (2009).
Hashmi, A. S. K. Homogeneous gold catalysis beyond assumptions and proposals-characterized intermediates. Chem. Int. Ed. 49, 5232–5241 (2010).
Fürstner, A. & Morency, L. On the nature of the reactive intermediates in gold-catalyzed cycloisomerization reactions. Chem. Int. Ed. 47, 5030–5033 (2008).
Zheng, Z. et al. Au-Catalysed oxidative cyclisation. Soc. Rev. 45, 4448–4458 (2016).
Yeom, H. & Shin, S. Catalytic access to α-oxo gold carbenes by N-O bond oxidants. Chem. Res. 47, 966–977 (2014);
Harris, R. J. & Widenhoefer, R. A. Gold carbenes, gold-stabilized carbocations, and cationic intermediates relevant to gold-catalysed enyne cycloaddition. Soc. Rev. 45, 4533–4551 (2016).
Benitez, D. et al. A bonding model for gold(I) carbene complexes. Chem. 1, 482−486 (2009).
Harris, R. J. & Widenhoefer, R. A. Synthesis, structure, and reactivity of a gold carbenoid complex that lacks heteroatom stabilization. Chem. Int. Ed. 53, 9369–9371 (2014).
Hussong, M. W. et al. Isolation of a non-heteroatom-stabilized gold-carbene complex. Chem. Int. Ed. 53, 9372–9375 (2014).
Joost, M. et al. Enhanced π-backdonation from gold(I): isolation of original carbonyl and carbene complexes. Chem. Int. Ed. 53, 14512–14516 (2014).
Nunes dos Santos Comprido, L. et al. The stabilizing effects in gold carbene complexes. Chem. Int. Ed. 54, 10336–10340 (2015).
Wang, Y., Muratore, M. E. & Echavarren, A. M. Gold carbene or carbenoid: is there a difference? Eur. J. 21, 7332−7339 (2015).
Qian, D. & Zhang, J. Gold-catalyzed cyclopropanation reactions using a carbenoid precursor toolbox. Soc. Rev. 44, 677–698 (2015).
Wang, Y. et al. Formal (4+1) cycloaddition of methylenecyclopropanes with 7-aryl-1,3,5-cycloheptatrienes by triple gold(I) catalysis. Chem. Int. Ed. 53, 14022–14026 (2014).
Wang, Y. et al. Gold(I) carbenes by retro-Buchner reaction: generation and fate. Am. Chem. Soc. 136, 801−809 (2014).
Yin, X., Mato, M. & Echavarren, A. M. Gold(I)-catalyzed synthesis of indenes and cyclopentadienes: access to (±)-Laurokamurene B and the skeletons of the cycloaurenones and dysiherbols. Chem. Int. Ed. 56, 14591–14595 (2017).
Nieto-Oberhuber, C. et al. Gold(I)-catalyzed intramolecular [4+2] cycloadditions of arylalkynes or 1,3-enynes with alkenes: scope and mechanism. Am. Chem. Soc. 130, 269–279 (2008).
Zhang, C. et al. Selective vinylogous reactivity of carbene intermediate in gold-catalyzed alkyne carbocyclization: synthesis of indenols. ACS Catal. 9, 2440–2447 (2019).
Bao, M. et al. Gold(I)-catalyzed and H₂O-mediated carbene cascade reaction of propargyl diazoacetates: furan synthesis and Mechanistic Insights. Lett. 20, 5332–5335 (2018).
Zhang, C. et al. Gold(I)-Catalyzed aromatization: expeditious synthesis of polyfunctionalized naphthalenes. iScience 21, 499–508 (2019).
Witham, C. A. et al. Gold(I)-catalyzed oxidative rearrangements. Am. Chem. Soc. 129, 5838–5839 (2007).
Nösel, P. et al. 1,6-Carbene transfer: gold-catalyzed oxidative diyne cyclizations. Am. Chem. Soc. 135, 15662−15666 (2013).
Mézailles, N., Rocard, L. & Gagosz, F. Phosphine gold(I) bis-(trifluoromethanesulfonyl)imidate complexes as new highly efficient and air-stable catalysts for the cycloisomerization of enynes. Lett. 7, 4133–4136 (2005).
Dateer, R. B., Shaibu, B. S. & Liu, R.-S. Gold-catalyzed intermolecular [4+2] and [2+2+2] cycloadditions of ynamides with alkenes. Chem. Int. Ed. 51, 113–117 (2012).
Wessig, P. & Müller, G. The dehydro-Diels−Alder reaction. Rev. 108, 2051–2063 (2008).
Azam, S. S. et al. Identification of unique binding site and molecular docking studies for structurally diverse Bcl-xL inhibitors. Chem. Res. 23, 3765–3783 (2014).
Ponomarev, O. A. et al. Electronic absorption spectra and fluorescent properties of non-associated 16,17-bis(alkoxy)violanthrone dyes and their dependence on the nature of substituent and solvent's parameters. Dyes Pigm. 156, 45–52 (2018).
Gandeepan, P. & Cheng, C.-H. Cobalt catalysis involving π components in organic synthesis. Chem. Res. 48, 1194−1206 (2015).
Hoye, T. R. et al. The hexadehydro-Diels–Alder reaction. Nature 490, 208–212 (2012).
Pei, C. et al. Catalytic carbene/alkyne metathesis (CAM): a versatile strategy for alkyne bifunctionalization. Biomol. Chem. 16, 8677–8685 (2018).
Padwa, A. et al. Rearrangement of alkynyl and vinyl carbenoids via the rhodium(II)-catalyzed cyclization reaction of .alpha.-diazo ketones. Am. Chem. Soc. 115, 2637–2647 (1993).
Hoye, T. R. & Dinsmore, C. J. Rhodium(II) acetate catalyzed alkyne insertion reactions of .alpha.-diazo ketones: mechanistic inferences. Am. Chem. Soc. 113, 4343–4345 (1991).
Le, P. Q. & May, J. A. Hydrazone-initiated carbene/alkyne cascades to form polycyclic products: ring-fused cyclopropenes as mechanistic intermediates. Am. Chem. Soc. 137, 12219–12222 (2015).
González-Rodríguez, C. et al. Nucleophilic addition of amines to ruthenium carbenes: ortho-(alkynyloxy)benzylamine cyclizations towards 1,3-benzoxazines. Chem. Int. Ed. 54, 2724–2728 (2015).
Qian, Y., Shanahan, C. S. & Doyle, M. P. Templated carbene metathesis reactions from the modular assembly of enol-diazo compounds and propargyl acetates. J. Org. Chem. 2013, 6032–6037 (2013).
Torres, Ò. et al. Enantioselective rhodium(I) donor carbenoid-mediated cascade triggered by a base-free decomposition of arylsulfonyl hydrazones. Eur. J. 21, 16240–16245 (2015).
Zhang, C. et al. Chemodivergent synthesis of multi-substituted/fused pyrroles via copper-catalyzed carbene cascade reaction of propargyl α-iminodiazoacetates. Commun. 52, 12470–12473 (2016).
Dong, K. et al. Selective C(sp³)–H bond insertion in carbene/alkyne metathesis reactions. enantioselective construction of dihydroindoles. ACS Catal. 8, 9543–9549 (2018).
Dong, K. et al. Transient-axial-chirality controlled asymmetric rhodium-carbene C(sp2)-H functionalization for the synthesis of chiral fluorenes. Commun. 11, 2363 (2020).
Qiu, H. et al. Unprecedented intramolecular [4 + 2]-cycloaddition between a 1,3-diene and a diazo ester. Am. Chem. Soc. 138, 1808−1811 (2016).
Jover, J. et al. Expansion of the ligand knowledge base for monodentate P-donor ligands (LKB-P). Organometallics 29, 6245−6258 (2010).
Christian, A. H. et al. Uncovering subtle ligand effects of phosphines using gold(I) catalysis. ACS Catal. 7, 3973–3978 (2017).
Wang, W., Hammond, G. B. & Xu, B. Ligand effects and ligand design in homogeneous gold(I) catalysis. Am. Chem. Soc. 134, 5697–5705 (2012).
Carden, W. G. et al. Halide effects on the sublimation temperature of X–Au–L complexes: implications for their use as precursors in vapor phase deposition methods. ACS Appl. Mater. Interfaces 9, 40998−41005 (2017).
Bauer, A. et al. Tris(dimethylamino)phosphane as a new ligand in gold(I) chemistry: synthesis and crystal structures of [(Me₂N)₃P]AuCl, {[(Me₂N)₃PAu]₃O}⁺BF₄⁻, {[Me₂N)₃PAu]₃NP(NMe₂)₃}²⁺ {BF₄⁻}₂ and the precursor molecule (Me₂N)₃PNSiMe₃. Ber. 130, 323−328 (1997).

Due to technical limitations, table 1 is only available as a download in the supplemental files section.

There is NO Competing Interest.

Table1.docx
SupplementaryInformation.pdf
Supplementary Information
23.cif
23.cif
32.cif
32.cif
checkcif23.pdf
checkcif_23
checkcif32.pdf
checkcif_32
TOC.Png

Download PDF

Journal Publication

published 19 Feb, 2021

Read the published version in Nature Communications →

Version 1

posted

You are reading this latest preprint version

Gold(I)-Catalyzed Intramolecular Cyclization/Intermolecular Cycloaddition Cascade: Fast Track to Polycarbocycles and Mechanistic Insights

Status:

Journal Publication

Version 1

Abstract

Figures

Background

Results

Discussion

Methods

Data Availability

Declarations

References

Table

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1