Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• Since the seminal 1998 report by Teles et al. on the gold(I)-catalyzed addition of alcohols to alkynes [1], a multitude of gold-catalyzed reactions have been reported. Great successes in mechanistic analysis and synthetic methods have been achieved for allene and alkyne activation, while the activation

• tropos BIPHEP-gold(I)-catalyzed hydroamination of alkenylureas in 2012 [9]. Michon [5][6][7][8][10] and Widenhoefer continued to make advancements in asymmetric intra- and intermolecular variants, and unique solvent and anion dependencies continue to be examined from a theoretical standpoint. For example

• /mol and ΔS‡ −42.1 ± 3.9 cal/mol·K. Non-linear behavior in the presence of methanol indicated a more complex rate law (less than first order in methanol and catalyst), precluding determination of activation parameters under those conditions at this time. Discussion The first reports of gold(I

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• of dithiin-fused allyl alcohols and similar non-cyclic sulfur-substituted allyl alcohols. Applications of dihydrodithiins in the rapid assembly of polycyclic terpenoid scaffolds [108][109]. Dihydrodithiin-mediated allyl cation and vinyl carbene cycloadditions via a gold(I)-catalyzed 1,2-sulfur

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• building blocks 5 and 8 in hand, ketone 9 was prepared via a palladium-catalyzed Sonogashira coupling reaction in a yield of 95%. The precursor 10 for the gold(I)-catalyzed [19][20][21][22][23][24] cycloisomerization was then synthesized by treating ketone 9 with sodium bis(trimethylsilyl)amide (NaHMDS

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• -cd]indoles 21 from the intramolecular cyclization of Ugi adducts 20 in moderate to good yields and excellent chemo-, regio-, and diastereoselectivity (Scheme 7) [17]. Mechanistically, the reaction involves a tandem gold(I)-catalyzed dearomatization/ipso-cyclization/Michael addition sequence to

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• catalytic activity was demonstrated in promoting gold(I)-catalyzed cycloisomerization of 1,6-enynes, with ample scope and high regioselectivity. However, preliminary studies suggested that the catalytic event occurs outside the macrocyclic cavity. In order to get more insights on the role of the cavity to

• in controlling the reactivity of gold(I)-catalyzed transformations by means of supramolecular macrocycles, we choose a cycloisomerization of 1,6-enynes as a model reaction [36]. Substrate 1a was reacted in the presence of monomeric gold(I) catalyst A’(AuCl) (2 mol %), using AgSbF6 as the chloride

• parental macrocycles A,B(AuCl)2, that arise from the proximity of the two gold(I) nuclei to the calix[6]arene scaffold. Although just preliminary, these results indicate that the conformational properties of this class of macrocycles can influence the selectivity in gold(I)-catalyzed cycloisomerization of

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• catalytic active forms of gold, gold(I) has so far, received main attention, likely due to the higher stability, as demonstrated by the development of a high number of gold(I)-catalyzed transformations and ligated gold(I) complexes, along with improved mechanistic understanding [9][10][11][12][13][14][15

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• Studi di Firenze, Via della Lastruccia 13, 50019 Sesto Fiorentino, Florence, Italy 10.3762/bjoc.16.255 Abstract The tandem gold(I)-catalyzed rearrangement/Nazarov reaction of enynyl acetates in which the double bond is embedded in a piperidine ring was computationally and experimentally studied. The

• first step [1][9][10][11][12]. In the framework of our studies on gold(I)-catalyzed reactions of propargyl alcohol derivatives [13][14][15], we have recently reported that the pentannulation of N-heterocycles [16] can be efficiently achieved by a cascade gold-catalyzed [3,3]-rearrangement/Nazarov

• of the reaction. Thus, they will be discussed later separately. Confirming our working hypothesis, this set of initial data contrasts with the computed gold(I)-catalyzed [3,3]-rearrangement/Nazarov reaction of 1. We had previously shown that for 2-substituted analogs of 1 (NCO2Me), the acetate

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• presumably renders an ionic [2 + 2] cycloaddition pathway competitive with the Diels–Alder reaction. The few reported examples of cyclobutene formation from alkynes and unactivated 1,3-dienes include the sensitized photocycloaddition of phenylacetylene and DMBD [30] and the gold(I)-catalyzed reaction of

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• , Japan 10.3762/bjoc.16.53 Abstract A series of α- and β-ethynyl-substituted BODIPY derivatives (3a, 4a, 5a, 5b, 6a, 6b) were synthesized by gold(I)-catalyzed direct C–H alkynylation reactions of dipyrromethane and BODIPY, respectively, with ethynylbenziodoxolone (EBX) in a regioselective manner

• BODIPY core has not yet been achieved. Inspired by the works of Waser and co-workers showing the gold(I)-catalyzed C–H electrophilic alkynylation of various heterocycles (e.g., pyrroles, indoles, etc.) with ethynylbenziodoxolone (EBX) as an activated ethynyl synthon [38][39][40][41][42], we investigated

• the synthesis of ethynyl-substituted BODIPY derivatives 3–6 by gold(I)-catalyzed direct C–H functionalization (Figure 1c). By taking advantage of the reactivity of β-(2 and 6)-positions of BODIPY (1), which are susceptible to electrophilic reactions, β,β'-diethynyl-substituted BODIPYs 5 and 6 were

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• reaction [20], tandem approach from (S)-Wynberg lactone [21], chiral ruthenium-catalyzed N-demethylative rearrangement of 1,2-isoxazolidines [22], gold(I)-catalyzed cyclization of a propargylic N-hydroxylamine [23], from β-sulfinamido ketones derived from chiral sulfinimines [24], and a Kornblum–DeLaMare

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• in Scheme 5, the oxazole-bearing α-amino ester 43 was prepared from the aspartic acid derivative 37 through the propargylamide 38 followed by a gold(I)-catalyzed cyclization to form the oxazoline derivative 40. Concerning the amidation step, propargylamide 38 was obtained in 78% yield provided that

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• molybdenum(VI)-catalyzed etherification of allylic alcohol with a gold(I)-catalyzed intramolecular cyclization process [5][6]. During the optimization process of this synthesis, we examined several catalysts to transform allylic alcohol 1 into ether 2, including Re2O7, which is described to efficiently

Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products

• Sultan Taskaya,
• Nurettin Menges and
• Metin Balci

Beilstein J. Org. Chem. 2015, 11, 897–905, doi:10.3762/bjoc.11.101

• acids has been reported in the literature to give the corresponding lactones [33][34][35][36][37][38][39][40]. For example, gold(I)-catalyzed reaction of 2-(phenylethynyl)benzoic acid (8) yielded the exo- and endo-dig cyclization products, lactones 9 and 10 in 62% yield in a ratio of 6:1 (Scheme 1) [41

• reactions. Structures of some marine natural products 1–4. Structures 5–7. Geometry optimized structures of 6, 7, 30 and 31. Intramolecular gold(I)-catalyzed cyclization reaction of 8 to give 9 and 10. Synthesis of 13 and its reaction with AuCl3. Synthesis of 6. Reaction of 15 with Au(I)/AgOTf in the

Aminofluorination of 2-alkynylanilines: a Au-catalyzed entry to fluorinated indoles

• Antonio Arcadi,
• Emanuela Pietropaolo,
• Antonello Alvino and
• Véronique Michelet

Beilstein J. Org. Chem. 2014, 10, 449–458, doi:10.3762/bjoc.10.42

• in 75% yield (Table 1, entry 9). The addition of NaHCO3 [20][33] as a base to the reaction mixture failed to give 2a, whereas it was successful for the preparation of fluorinated pyrazole, via the gold(I)-catalyzed tandem aminofluorination of 1-phenyl-2-(4-phenylbut-3-yn-2-ylidene)hydrazine. Other

Gold(I)-catalyzed domino cyclization for the synthesis of polyaromatic heterocycles

• Mathieu Morin,
• Patrick Levesque and
• Louis Barriault

Beilstein J. Org. Chem. 2013, 9, 2625–2628, doi:10.3762/bjoc.9.297

• ) complexes to C–C π-systems in the presence of other functional groups combined by its predictable reactivity pattern, the gold(I)-catalyzed reaction provides tremendous opportunities for the discovery of new and useful reactions [12]. Recently, we [13] and other groups [14][15][16][17] reported that

• represents an attractive and complementary approach for the synthesis of substituted aromatic rings. Taking advantage of the high regiospecificity of [L1AuNCMe][SbF6] associated with alkyne activation, we examined the scope of the reaction using various substituted alkynes (Scheme 3). Gold(I)-catalyzed

• = H) and furan 11g (R1 = Ph and R2 = H) were effectively transformed to the desired carbazole 12f and benzofuran 12g in 95% yields. It can be noticed that large substituents at R1 and R2 did not affect the efficiency of the reaction. The gold(I)-catalyzed cyclization of 11h (R1 = R2 = Ph) and 11i (R1

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• carbolactonization of terminal alkenes with arylboronic acids. Synthesis of tricyclic indolines via gold-catalyzed formal [3 + 2] cycloaddition. Gold(I) catalyzed aminoarylation of terminal alkenes in presence of Selectfluor [dppm = bis(diphenylphosphino)methane]. Mechanistic investigation on the aminoarylation of

Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis

• Yumeng Xi,
• Boliang Dong and
• Xiaodong Shi

Beilstein J. Org. Chem. 2013, 9, 2537–2543, doi:10.3762/bjoc.9.288

• vinyl ether synthesis using gold has been reported to date [17]. Nevertheless, there have been examples regarding the intermolecular addition of carboxylic acids [19][20], phenols [21][22] as well as phosphoric acids [23][24][25] to alkynes. In this context, we report a gold(I)-catalyzed O-vinylation of

• -cyclopentadione in DCM at room temperature. Finally and notably, all tested acyclic 1,3-diketones as well as 1,2-diketones gave no O-addition products under the current reaction conditions, likely caused by the intramolecular H-bonding. Conclusion In this letter, we report the first successful gold(I)-catalyzed

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• opposite regioselection. Besides, the resulting relative configuration of Δ1-pyrroline 11 is equivalent to the exo-approach of the dipolarophile when an endo-transition state was the most favourable in the gold(I)-catalyzed 1,3-DC with α-imino esters and alkenes [37]. To gain more insight into the

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• Investigación en Química Biolóxica e Materiais Moleculares (CIQUS). Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain 10.3762/bjoc.9.264 Abstract In recent years there have been extraordinary developments of gold(I)-catalyzed enantioselective processes. This includes progress in the

• processes. Keywords: alkyne; allene; asymmetric catalysis; cycloaddition; enantioselective; gold; gold catalysis; Introduction In the past decade, there have been extraordinary advances in the development of novel stereoselective gold(I)-catalyzed transformations [1][2][3][4][5][6][7][8][9][10]. In this

• the species that participates in the cycloaddition to the nitrone, probably in a concerted pathway, and thus providing the corresponding products with high levels of stereoselectivity [82][83]. Previously, in 2009, J. Zhang had reported a gold(I)-catalyzed 1,3-dipolar [3 + 3] cycloaddition between 2

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• compound [D]-7b in 75% yield (>90% deuterium incorporation at C4). The generation of that compound could be explained by deuterodemetallation of the vinylgold species B generated by an attack of the nucleophile on intermediate 4b or 4b’ (Scheme 8). Conclusion We described an efficient gold(I)-catalyzed 6

• -catalyzed cycloisomerization of these substrates. The new oxygen-functionalized dihydronaphthalene derivatives have been synthesized in high yields. Gold(I)-catalyzed reactions of 1,6-enynes. Cyclization of o-(alkynyl)-(3-methylbut-2-enyl)benzenes 1. Previous work and proposed pathways. Synthesis of o

• -(alkynyl)-(3-methylbut-2-enyl)benzenes 1. Gold(I)-catalyzed cycloisomerization of 1a. Initial experiments and proof of concept. Gold(I)-catalyzed hydroxycyclization of enynes 1m,n. Gold(I)-catalyzed methoxycyclization of selected 1,6-enynes 1 [45]. Labelling experiment and proposed mechanism. Effect of the

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

• Pablo Morán-Poladura,
• Eduardo Rubio and
• José M. González

Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249

• the proof of the configurational stability of a chiral center in the vicinity of the alkyne. For this purpose, optically active 1j was prepared. As next step, its reactivity in the gold(I)-catalyzed hydroarylation study was investigated (Scheme 3). Though the regioselectivity was lower and requires

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• renders gold catalysis a straightforward protocol in the realm of the synthesis of natural products [17][18]. Herein we report a short total synthesis of (−)-epimyrtine employing an alternative strategy by using a gold(I)-catalyzed hydroamination of a β-aminoynone as the key step. Actually, cyclization of

Gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones

• Marie Hoffmann,
• Solène Miaskiewicz,
• Jean-Marc Weibel,
• Patrick Pale and
• Aurélien Blanc

Beilstein J. Org. Chem. 2013, 9, 1774–1780, doi:10.3762/bjoc.9.206

• )-catalyzed rearrangement of γ-acyloxyalkynyl ketones under mild conditions. Further work is currently underway in our laboratory to fully understand this novel rearrangement. Experimental General procedure for gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones. In an oven-dried flask, γ

• the crude residue was purified by silica gel flash chromatography (pentane/Et2O). Gold(I) or gold(III)-catalyzed furan syntheses with or without nucleophiles. Copper(I)-catalyzed 1,2-migration/cycloisomerization of γ-acyloxyalkynyl ketones. Mechanistic hypothesis for gold(I)-catalyzed conversion of γ

• -acyloxyalkynyl ketones into furans. Screening of the catalysts and the conditions. Scope of the gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones. Supporting Information Supporting Information File 336: General procedures, characterization data and NMR spectra for compounds 1a–l, 2a–l and 3

Gold-catalyzed cyclization of allenyl acetal derivatives

• Dhananjayan Vasu,
• Samir Kundlik Pawar and
• Rai-Shung Liu

Beilstein J. Org. Chem. 2013, 9, 1751–1756, doi:10.3762/bjoc.9.202

• . Experimental General procedure for the gold-catalyzed carbocyclization General procedure for the the gold(I)-catalyzed carbocyclization of vinylallenyl acetal: A two-necked flask was charged with chloro(triphenylphosphine)gold(I) (11.1 mg, 0.022 mmol) and silver triflate (5.8 mg, 0.022 mmol), and to this

• silica bed. The solvent was evaporated under reduced pressure. The crude product was eluted through a short silica column (3% ethyl acetate in hexane) to afford the desired ketone 4a (70.6 mg, 0.40 mmol, 89%) as a pale yellow oil. General procedure for the gold(I)-catalyzed carbocyclization of

Synthesis of fluoranthenes by hydroarylation of alkynes catalyzed by gold(I) or gallium trichloride

• Sergio Pascual,
• Christophe Bour,
• Paula de Mendoza and
• Antonio M. Echavarren

Beilstein J. Org. Chem. 2011, 7, 1520–1525, doi:10.3762/bjoc.7.178

• demonstrated to be amongst the best catalysts in many gold(I)-catalyzed cyclizations [6][58]. No reaction was observed with complex 5 after heating for 5 min at 70 °C in CH2Cl2 under microwave irradiation (Table 1, entry 1), whereas the more electrophilic 6, bearing a less donating phosphite ligand, led almost

• pathway. The cyclization of 9-(3-phenylprop-2-ynyl)-9H-fluorene (7a) to form 3-phenylfluoranthene (8a) [59] was also examined by using catalysts 5, 6, and GaCl3 (Table 2). Since the initial gold(I)-catalyzed reaction provided a mixture of 3-phenyl-1,10b-dihydrofluoranthene, 3-phenyl-1,2,3,10b

• 6. Proposed metal catalyzed annulation for the synthesis of triaryldiacenaphtho[1,2-j:1',2'-l]fluoranthenes 2. Pd(OAc)2-catalyzed isomerization of 7a to form (E)-9-(3-phenylallylidene)-9H-fluorene (9). Gold(I)-catalyzed hydroarylation of 7k to give 1,10b-dihydrofluoranthene 9. Gold(I)-catalyzed