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

• typical relatively dilute conditions in this study for 1a (0.05 M) and in the absence of added MeOH, the data is consistent with a second order rate law rate = k2[alkene][gold catalyst]. To determine activation parameters rates of urea 1a hydroamination were measured with 1 mol % [JPhosAu(NCCH3)]SbF6 (5

• have been masked by the high temperatures and long reaction times of early reports. For example, Widenhoefer engaged carbamates and amides in dioxane at temperatures >80 °C [12][13]. Later work showed that ureas could be engaged at room temperature when a NHC–gold catalyst system was used, outpacing

• , which boosts reaction rates, may be counterbalancing any expected slowdown. • Activation parameters suggest an ordered transition state. Reaction orders indicate an approach to zero-order dependence on gold catalyst when in the presence of MeOH, while first-order dependence on gold catalyst is

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

• ) itself failed to catalyze the cycloisomerization (Table 1, entry 1). Evaluation of a number of silver salts illustrated that silver hexafluoroantimonate (AgSbF6) was the optimal additive to activate the gold catalyst (Table 1, entries 2, 3, and 7). Screening of the other ligands of Au(I) catalysts

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

• calix[6]arene scaffold, we carried out the synthesis of three monomeric gold catalyst analogues A’,B’,C’(AuCl). The synthesis of these compounds was performed using the previously optimized protocol, starting from a 4-(octyloxy)aniline intermediate (Scheme 2). Subsequently, due to the general interest

• .), CH2Cl2, 0 °C to rt [A, 60%; B, 55%, C, 53%); iii) (Me2S)AuCl in CH2Cl2, 0 °C to rt (A(AuCl)2, 93%; B(AuCl)2, 74%; C(AuCl)2, 69%). Synthesis of the monomeric gold catalyst analogues A’,B’,C’(AuCl). Conditions: i) diphenylphosphinobenzoic acid, EDC∙HCl, DMAP (cat.), CH2Cl2, 0 °C to rt (A’, 71%; B’, 76%; C

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• derivative 28, which has a lower tendency for ring expansion. At room temperature, this substrate stopped at the hydrated intermediate 29, which could be isolated and remained intact when heated to 80 °C alone in 1,4-dioxane. Inclusion of the gold catalyst while heating, however, initiated the rearrangement

• to 30, confirming the importance of Au(I) in catalyzing both steps in the tandem reaction. Notably, this is the first time in the literature that α-ketol rearrangements have been initiated by a gold catalyst. Optimization revealed that the tandem reaction is best performed with Au(JohnPhos)SbF6 in

• . The catalyst is also capable of kinetic resolution of a mixture of enantiomeric substrates. Al* = 18. BF3-promoted diastereospecific rearrangement of α-ketol 21 to difluoroalkoxyborane 22. In the presence of a gold catalyst and water in 1,4-dioxane, 1-alkynylbutanol derivatives undergo tandem

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• changing the previously optimized mild reaction conditions (Scheme 6). Only traces of 10 were observed in the absence of one of the metal salts; this excluded the participation of the silver salt in the olefin activation but highlighted its usual role in the activation of the gold catalyst, namely halide

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

• trans product. Thus, the proper choice of the gold catalyst allows highly stereoselective formation of either cis or trans cyclopropanation products and facilitates the isolation of pure isomers. Despite the chiral nature of these ligands, no enantioselectivity was observed in the test reactions

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• -forming reaction under oxidant-free conditions, while the use of the gold catalyst gives promise of accessing highly site-selective transformations. Indeed, electrophilic Au(III) species were able to site-selectively activate C–H bonds of activated electron-rich arenes thus generating Au(III)–Ar species

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• which they detailed the Markovnikov hydrofluorination of alkynes using HF.DMPU coupled with a gold catalyst [60]. Accordingly, the appropriate propargylmalonate derivatives were fluorinated to give fluoroalkene intermediates, which were then converted into malonate-based enynes 37 (Z = CO2R) through a

Photoredox-catalyzed silyldifluoromethylation of silyl enol ethers

• Vyacheslav I. Supranovich,
• Vitalij V. Levin and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 1550–1553, doi:10.3762/bjoc.16.126

• analyzed by 19F NMR spectroscopy. A series of typical photocatalysts (for example, iridium catalysts) were ineffective in promoting the reaction. Rewardingly, a gold catalyst, [AuCl(μ-dppm)]2 [25][26][27], provided reasonable yields of 3a after one day of irradiation along with a full conversion of the

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• protocol using a gold catalyst and TIPS-EBX (1a) for the alkynylation of tryptophan-containing peptides and even proteins (Scheme 1C) [39]. This recent disclosure motivated us to report our own work on this transformation, resulting in an efficient direct alkynylation of tryptophan-containing peptides

Pyridylidene ligand facilitates gold-catalyzed oxidative C–H arylation of heterocycles

• Kazuhiro Hata,
• Hideto Ito,
• Yasutomo Segawa and
• Kenichiro Itami

Beilstein J. Org. Chem. 2015, 11, 2737–2746, doi:10.3762/bjoc.11.295

• numerous benefits such as high activity and stability of gold catalyst, thereby achieving otherwise-difficult oxidative transformations [37][38][39][40]. Recently, we have introduced highly electron-donating triaryl-2-pyridylidene (PyC: pyridine-based carbene) [82][83][84] as a new type of nonclassical N

Rapid pseudo five-component synthesis of intensively blue luminescent 2,5-di(hetero)arylfurans via a Sonogashira–Glaser cyclization sequence

• Fabian Klukas,
• Alexander Grunwald,
• Franziska Menschel and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 672–679, doi:10.3762/bjoc.10.60

• ]. However, the major drawback of this approach is the complex, time-consuming preparation of the complicated gold catalyst and the separate synthesis of the butadiyne substrates. In a similar study arylbutadiynes prepared by Glaser homocoupling were converted into symmetrical 2,5-di(hetero)arylfurans [32

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• reaction with the chloride ion released during the initial imine acylation. Finally, a combination between Brønsted acid and metal catalysis, promote the isomerization of V to oxazole 21. It is noteworthy, that the gold catalyst seemed to be essential only for the formation of the gold-acetylide

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

• competitive pathway in the presence of gold catalysts and Selectfluor [41][42][43] were observed. The yield of 2a was increased to 35% when the reaction was carried out in the presence of 10 mol % of the gold catalyst (Table 1, entry 3). Various other parameters were modified to increase the reaction

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• schisanwilsonene A (126, see Scheme 15), isolated from Schisandra wilsoniana [111], a plant used in traditional chinese medicine. Submission of 1,6-enyne 116 to cationic gold-catalyst 117 led to 5-exo-dig cyclization and intermediate formation of bridged bicycle 119. Subsequent 1,5-acyl-shift afforded

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

• moderate yields whereas monoalkyl olefins were completely unreactive under the optimized conditions. Although an activation of the acetals by the gold catalyst cannot be ruled out, a reaction pathway involving gold activation of the alkene, followed by addition of the alkyl gold intermediate 10 to the

• aldehydes was performed under synergistic activation of the substrate by gold catalyst 20c and organocatalyst 116 (Scheme 30). The 5-membered hetero- and carbocycles 115 were obtained in moderate to good yield and interesting level of diastereo- and enantioselectivity, supporting the perfect compatibility

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• cyclization of 7 gave a higher yield than the attempted gold(I) catalysis (39% overall yield), which might be due to the deactivation of the gold catalyst by impurities still present in the crude allenyl alcohol 7. Next, several methods for the introduction of the amino group were examined. We were very

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

• the reaction, likely caused by the low reactivity of the C–C triple bonds. Interestingly, the addition to the ethynylferrocene gave the corresponding vinyl ether in good yield, which highlighted the mild conditions of this catalytic system and potential applications of this gold catalyst in other

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

• , which was particularly successful in the abovementioned intermolecular cases, only provided good enantioselectivities in the case of systems affording products with seven-membered rings (3, n = 0, Scheme 2). For the eight-membered counterparts, the authors found that a related bisphosphine–gold catalyst

• -tuning of the catalyst and substrate is required to achieve excellent enantioselectivities. More recently, Nevado and co-workers have shown that propargyl acetates 4 react with 1,3-dienes in the presence of a gold catalyst to give good yields of cycloheptadiene products of type 5; thus the process could

• authors also demonstrated the feasibility of an enantioselective variant. Thus, treatment of pivaloate 4a with 6,6-dimethyl-1-vinylcyclohexene in the presence of the chiral gold catalyst (S)-MeO-DTBM-Biphep(AuCl)2/AgSbF6, followed by in situ hydrolysis, allowed the construction of the basic bicarbocyclic

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

• competition with a direct Friedel–Crafts-type cyclization reaction yielding 3. In previous work dealing with the cyclization of N-(3-iodoprop-2-ynyl)-N-tosylanilines to give related 1,2-dihydroquinolines (Scheme 4A, X = NTs) [43], we documented for a phosphite-based gold-catalyst, which render a more

• electrophilic metal center, an increase of the relative amount of the cyclization product 3 (4-iodo-substituted, X = NTs) at the expenses of the formation of the one with concomitant iodine shift, product 2 (3-iodo-substituted, X = NTs). On the contrary, under related conditions, a gold catalyst based on the

Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines

• Amit Kumar,
• Dipak D. Vachhani,
• Sachin G. Modha,
• Sunil K. Sharma,
• Virinder S. Parmar and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2013, 9, 2097–2102, doi:10.3762/bjoc.9.246

• hydroarylation [44]. Reaction of 5a with 5 mol % of Au(PPh3)SbF6 in chloroform at room temperature produced the desired spiroindoline 6a in a moderate yield of 55% along with some unidentified byproducts (Table 1, entry 1). The use of a protic acid with a gold catalyst is known in the literature [61][62][63][64

• starting material was recovered quantitatively (Table 1, entries 3 and 4). In absence of the gold catalyst no product could be observed (Table 1, entry 5). The application of p-toluenesulfonic acid (PTSA) instead of TFA did not improve the outcome (Table 1, entry 6). Having the optimized conditions in hand

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

• expected that the good side-chain functionality tolerance of the gold catalyst could easily provide chiral dihydropyridone from the corresponding β-aminoynone in a 6-endo-dig selective cyclization process. The β-aminoynone could be stereoselectively prepared in two steps from N-Boc-D-alanine. Preparation

Acid, silver, and solvent-free gold-catalyzed hydrophenoxylation of internal alkynes

• Marcia E. Richard,
• Daniel V. Fraccica,
• Kevin J. Garcia,
• Erica J. Miller,
• Rosa M. Ciccarelli,
• Erin C. Holahan,
• Victoria L. Resh,
• Aakash Shah,
• Peter M. Findeis and
• Robert A. Stockland Jr.

Beilstein J. Org. Chem. 2013, 9, 2002–2008, doi:10.3762/bjoc.9.235

• sustainable organic reactions. From the standpoint of the gold catalyst, there are several ways to generate an active species. One of the first reports on this type of catalysis entailed the use of strong acids to remove the methyl group from a methylgold compound and generate a (LAu+) species that promoted

• remain some of the most challenging substrates to functionalize through hydroelementation reactions. Initially, we selected compound 1 as the gold catalyst and used a focused microwave reactor to heat the reactions. After some experimentation, we discovered that heating the phenol and alkyne with gold

• gold catalyst in these reactions is proposed to occur through a protodeauration reaction between the arylgold compounds and the phenols. The observation of tert-butylbenzene in the reaction mixture supports this proposal. Furthermore, to probe whether or not simple chlorogold-coordination compounds

Gold-catalyzed reaction of oxabicyclic alkenes with electron-deficient terminal alkynes to produce acrylate derivatives

• Yin-wei Sun,
• Qin Xu and
• Min Shi

Beilstein J. Org. Chem. 2013, 9, 1969–1976, doi:10.3762/bjoc.9.233

• Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, People’s Republic of China 10.3762/bjoc.9.233 Abstract Oxabicyclic alkenes can react with electron-deficient terminal alkynes in the presence of a gold catalyst under mild conditions

• formed by a regioselective opening of the oxygen bridge in substrate 1a. Intermediate A releases a proton to afford intermediate B. Intermediate B attacks methyl propiolate, which is activated by the gold catalyst, to generate gold vinyl complex C. In intermediate C, the ester group and the naphthalene

• novel method to synthesize acrylate derivatives from oxabicyclic alkenes and electron-deficient terminal alkynes in toluene in moderate to good yields in the presence of the gold catalyst SPhosAu(MeCN)SbF6 under mild conditions. Efforts are in progress to elucidate the mechanistic details of this

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

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• the five-membered heterocycles 9/10 are summarized in Table 2. Treatment of the α-hydroxyallene 7a with 1 mol % AuCl3 in THF [21][22][23] afforded the desired 2,5-dihydrofuran 9a with 84% yield (Table 2, entry 1). The temperature was decreased to 5 °C to avoid acetal cleavage by the Lewis-acidic gold

• catalyst [19]. For the corresponding cyclization of the bromoallene 7b, the temperature had to be raised to 50°C in order to achieve complete conversion (Table 2, entry 2). Only traces of the acetal cleavage product were detected by TLC. However, the cycloisomerization was accompanied by partial