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

• ) followed by oxidative coupling of the formed alkylgold moiety with the ortho C–H bond of the tethered phenyl group. Compound 137 was finally obtained via reductive elimination of intermediate 141 (Scheme 34). The formal [3 + 2] annulation between the aniline moiety and the C–C double bond constitutes the

Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

• -catalyzed oxidative lactonization or an intramolecular cyclization reaction of δ-ketoaldehydes [12], a ruthenium-catalyzed aerobic oxidative cyclization of aromatic acids with alkynes [13], an FeCl3-promoted regioselective annulation of o-(1-alkynyl)benzoates with disulfides [14], a Heck–Matsuda cyclization

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

• be formally considered as a [4 + 3] annulation. A possible mechanism would involve a gold-mediated 1,2-acyloxy migration of the propargyl ester to generate a gold–carbene species III which cyclopropanates a C–C double bond of the diene to form a cis-cyclopropane intermediate IV. A subsequent gold

• gold-activated allene complexes have been shown to participate in a great variety of intra- and intermolecular cycloaddition reactions, including [4 + 3], [4 + 2], [3 + 3], [3 + 2] or [2 + 2] annulation processes [1][2][3][4][5][6][7][8][9][10][24][25][26]. Particular attention has been paid during the

• intramolecular cyclopropanation. Gold-catalyzed cyclohepta-annulation cascade. Application to the formal synthesis of frondosin A. Gold(I)-catalyzed enantioselective cyclopropenation of alkynes. Enantioselective cyclopropanation of diazooxindoles. Gold-catalyzed enantioselective [2 + 2] cycloadditions of

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• (distonic ion) [106]. We have applied Ru(bpz)3(PF6)2-catalyzed photooxidation of N-cyclopropylanilines to induce this rearrangement reaction. The resulting distonic ion was then intercepted by alkenes to produce [3 + 2] annulation products (Scheme 32) [107]. An aryl group on the amine was required for the

• reaction. Both mono- and bicyclic cyclopropylanilines were viable substrates to provide the annulation products in good to excellent yields. The former gave little to poor diastereoselectivity whereas the later produced modest diastereoselectivity. The reaction has 100% atom economy. It is also overall

• redox-neutral and thus does not require an external oxidant. We believe that the annulation reaction proceeds first via reductive quenching of the photoexcited state of Ru(II) by cyclopropylaniline 147 to generate amine radical cation 148 and Ru(I) (Scheme 33). Amine radical cation 148 then triggers the

Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed annulation with diarylethynes

• Yan-Chao Shi,
• Rong-Fei Yang,
• De-Wei Gao and
• Shu-Li You

Beilstein J. Org. Chem. 2013, 9, 1891–1896, doi:10.3762/bjoc.9.222

• Road, BDA, Beijing, 100176, China 10.3762/bjoc.9.222 Abstract When Boc-L-Val-OH was used as a ligand for the enantioselective Pd(II)-catalyzed annulation of N,N-substituted aminomethyl ferrocene derivatives with diarylethynes, ferrocenes with planar chirality could be achieved with excellent

• enantioselectivity (up to 99% ee). Keywords: annulation; asymmetric catalysis; C–H activation; ferrocene; palladium; planar chirality; Introduction Chiral ferrocene derivatives have been widely applied to asymmetric catalysis, materials science, biomedical research, etc. [1][2][3][4]. Particularly, ferrocenes with

• enhance the enantiocontrol of the planar chiral P,N-ligand (Scheme 1). Cui, Wu and their co-workers recently reported a Pd-catalyzed dehydrogenative annulation of N,N-dimethylaminomethylferrocene in a racemic form [58][59][60][61][62][63][64][65][66]. To test our hypothesis, we decided to turn such a Pd

A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

• Mitsuhiro Ueda,
• Yoshitaka Uenoyama,
• Nozomi Terasoma,
• Shoko Doi,
• Shoji Kobayashi,
• Ilhyong Ryu and
• John A. Murphy

Beilstein J. Org. Chem. 2013, 9, 1340–1345, doi:10.3762/bjoc.9.151

• tandem reaction of iodoaryl alkenyl azides under radical conditions (Scheme 1) [13][14]. Curran et al. reported the synthesis of spirocyclic pyrrolidinyl dihydroquinolinones by tandem radical cyclization [15][16]. In this study we report a radical cyclization/annulation approach to 4.4-spirocyclic γ

• -lactams (Scheme 2). Results and Discussion For the first model reaction in our investigation of the development of a novel tandem radical cyclization/annulation strategy, we prepared N-(2-(azidomethyl)allyl)-N-(2-iodophenyl)-4-methylbenzenesulfonamide (1a) according to the methods shown in Scheme 3. The

• construction of spirocyclic pyrrolidinyl oxindole by tandem radical cyclization with azide [14]. A tandem radical cyclization/annulation strategy for the synthesis of 4,4-spirocyclic γ-lactams with the incorporation of CO. The synthetic methods of 1a. The tandem radical spirocyclization reaction of N-(2

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• ]undecanes fused to aromatic rings [11]. Then, we devised an annulation protocol inspired by the work of Donohoe and co-workers [12][13] that provided access to substituted pyridones of the type found in 1 from thioester precursors [14]. Based on these encouraging results, we decided to target lyconadin A

• for synthesis. Herein, we provide an account of our studies directed toward the construction of this alkaloid. Specifically, we describe our efforts to prepare advanced intermediates that could be employed in the aforementioned pyridone annulation and tandem radical cyclization processes. In the

• functional-group manipulations. Based on the aforementioned model study [11], 7-exo–6-exo tandem radical cyclization of phenyl selenoester 4 was expected to produce ketone 3. Disassembly of the pyridone moiety of 4 according to our annulation protocol [14] revealed thioester 5 as a suitable precursor. We

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• ] annulation reaction is described here. Use of piperidinium trifluoroacetate salt as the catalyst and toluene as the solvent appears to be critical for a successful annulation. We also demonstrated for the first time that microwave irradiation can accelerate aza-[3 + 3] annulation reactions. An attempt to

• expand the scope of the enone aza-[3 + 3] annulation was made in the form of propyleine synthesis as a proof of concept. While synthesis of the enone annulation precursor was successfully accomplished, the annulation proved to be challenging and was only modestly successful. Keywords: alkaloids

• synthesis; catalysis; enones; intramolecular aza-[3 + 3] annulation; N-heterocycles; natural product; vinylogous amides; Introduction Throughout the past decade, we have been developing an aza-[3 + 3] annulation reaction as a general and unified strategy in alkaloid synthesis [1][2][3][4][5][6][7][8][9][10

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• majucin-type sesquiterpenes is described here. This strategy is based on an organocatalyzed asymmetric Robinson annulation and provides an efficient approach for a diversity-oriented synthesis of Illicium natural products that holds remarkable therapeutic potential for neurodegenerative diseases

• represents an efficient route toward a diversity-oriented synthesis of several Illicium sesquiterpenes. The enantioselective entry to these molecules is based on an organocatalyzed asymmetric Robinson annulation that allows access to the enantiomerically enriched bicyclic motif 8 from achiral diketone 11

• ][38][39][40][41][42][43][44][45][46][47][48][49][50]. Organocatalyzed asymmetric Robinson annulation has long been proven to be one of the most powerful strategies to construct bicyclic systems with a chiral quaternary center [51][52][53][54][55][56][57][58]. Among them, the Hajos–Wiechert and Wieland

Direct alkenylation of indolin-2-ones by 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles: a novel approach

• Sandeep Kumar,
• Ramendra Pratap,
• Abhinav Kumar,
• Brijesh Kumar,
• Vishnu K. Tandon and
• Vishnu Ji Ram

Beilstein J. Org. Chem. 2013, 9, 809–817, doi:10.3762/bjoc.9.92

• group as well as by Wittig reaction [23][24]. The growing importance of 3-alkenylindolin-2-ones has resulted in the design of numerous new synthetic routes. Recently, metal-catalyzed carbonylative annulation of alkynyl-arylamines has been employed for the synthesis of this class of compounds [25][26][27

Synthesis of SF₅-containing benzisoxazoles, quinolines, and quinazolines by the Davis reaction of nitro-(pentafluorosulfanyl)benzenes

• Petr Beier and
• Tereza Pastýříková

Beilstein J. Org. Chem. 2013, 9, 411–416, doi:10.3762/bjoc.9.43

• observed compared to unsubstituted ortho-aminoacetophenone, but it could be overcome by using an excess of the condensation reagent and longer reaction times. Quinoline 12 was prepared in high yield by the Friedländer annulation reaction of 10a with excess ethyl acetoacetate in the presence of catalytic

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles

• Rajesh K. Arigela,
• Sudhir K. Sharma,
• Brijesh Kumar and
• Bijoy Kundu

Beilstein J. Org. Chem. 2013, 9, 401–405, doi:10.3762/bjoc.9.41

• functionalized with epoxide by reacting 2-alkynylindole with epichlorohydrin. This can then be followed by ring opening of the oxirane by azide to furnish a bis-functionalized indole intermediate having azide and alkyne groups in close proximity. Such an intermediate may then undergo annulation following an

• significant increase in the yield of the title compound 6a was observed by prolonging the reaction. Carrying out the reaction in DMF at rt also failed to promote annulation even after 15 h of prolonged stirring (Table 1, entry 5). Increasing the temperature to 120 °C furnished the intermediate 4a as a single

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• catalytic carbomagnesiation of dialkylacetylenes. Note that Ilies and Nakamura reported iron-catalyzed annulation reactions of various alkynes, including dialkylacetylenes with 2-biphenylylmagnesium reagents to form phenanthrene structures [113]. In 2007, Yorimitsu and Oshima reported that chromium chloride

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• -annulation cascade reaction with N,N-(dialkylamino)benzaldehydes, a process in which a 1,5-hydride shift occurs followed by larger ring formation [16]. After the evaluation of different Brønsted acid catalysts, diphenylphosphate (20 mol %) was identified as a suitable catalyst for the reaction. Toluene again

• more organocatalytic non-asymmetric and asymmetric sp3 C–H activation processes are expected [37]. Triflic acid-catalysed synthesis of cyclic aminals. PTSA-catalysed synthesis of cyclic aminals. Plausible mechanism for cyclic aminal synthesis. Annulation cascade reaction with double nucleophiles

• . Mechanism for the indole-annulation cascade reaction. Synthesis of N-alkylpyrroles and δ-hydroxypyrroles. Synthesis of N-alkylindoles 9 and N-alkylindolines 10. Mechanistic study for the N-alkylpyrrole formation. Benzoic acid catalysed decarboxylative redox amination. Organocatalytic redox reaction of ortho

Chiral multifunctional thiourea-phosphine catalyzed asymmetric [3 + 2] annulation of Morita–Baylis–Hillman carbonates with maleimides

• Hong-Ping Deng,
• De Wang,
• Yin Wei and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 1098–1104, doi:10.3762/bjoc.8.121

• of Chemistry & Molecular Engineering, East China University of Science and Technology, and 130 MeiLong Road, Shanghai 200237, People’s Republic of China 10.3762/bjoc.8.121 Abstract We have developed a multifunctional thiourea-phosphine catalyzed asymmetric [3 + 2] annulation of Morita–Baylis–Hillman

• previous literature. Keywords: asymmetric [3 + 2] annulation; maleimides; Morita–Baylis–Hillman carbonates; multifunctional thiourea-phosphine; organocatalysis; Introduction Highly functionalized cyclopentene derivatives are important subunits in a variety of biologically active molecules and have

• attracted the broad attention of synthetic and pharmaceutical chemists [1][2]. Among numerous synthetic approaches, phosphine-mediated [3 + 2] annulation of electron-deficient olefins is an efficient method to construct this interesting structural motif [3][4][5][6][7][8][9][10]. According to the pioneering

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

• 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

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• a long time [16][17]. This prominent appearance results from the electronic transition between the S0 and S1 state [18], as a consequence of low energy frontier molecular orbital transitions [19]. The bicyclic structure of this nonbenzoid hydrocarbon results from a five–seven ring annulation with a

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• Friedel–Crafts-type cyclization, which completes the catalytic cycle and regenerates the gold catalyst [39][60]. Interestingly, small changes in the substitution of the alkene, or the use of other catalysts, such as PtCl2 (under a CO atmosphere), affect the result of the annulation, such that it is now

• possible to induce (2 + 2) instead of (4 + 2) cycloadditions [61]. Very recently, Echavarren and coworkers reported an intermolecular variant of this type of (2 + 2) alkyne–alkene cycloaddition reaction (Scheme 14) [62][63]. A less common annulation is the intramolecular (6 + 2) cycloaddition between non

• ) catalyst is able to activate these allenic intermediates in situ, triggering a stepwise intramolecular (3 + 2) annulation reaction with the pendant alkene. This cycloaddition provides a cyclic gold carbene species XXV, which is eventually transformed into the final bicyclic adduct by a 1,2-hydrogen shift

Cationic gold(I) axially chiral biaryl bisphosphine complex-catalyzed atropselective synthesis of heterobiaryls

• Tetsuro Shibuya,
• Kyosuke Nakamura and
• Ken Tanaka

Beilstein J. Org. Chem. 2011, 7, 944–950, doi:10.3762/bjoc.7.105

• biaryls [5][6][7]. These reports clearly demonstrated the utility of the asymmetric annulation strategy for the atropselective biaryl synthesis [8]. As an alternative asymmetric annulation method for the atropselective biaryl synthesis, we turned our attention to transition-metal catalyzed

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• -enaminone derivatives 161 and the cyclization of α-allenyl-β-enaminone intermediates has been developed by Saito and co-workers (Scheme 29) [75]. Toste’s group has reported a novel gold(III)-catalyzed [3 + 3]-annulation of azomethine imines 165 with propargyl esters 164. Substitution of the β-position of

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• activation of the cyclopropene, cation 55 is formed. C–C bond cleavage of the cyclopropyl ring followed by a Friedel–Crafts reaction affords, after recovery of aromaticity, the observed products [47]. 4 Ring expansions involving annulation reactions Diels–Alder, [1,3]-dipolar-, [2 + 2]- and [4 + 3

• -membered-rings in a stereocontrolled manner [48][49], the use of the analogous gold-catalyzed transformations has remained, until recently, largely unexplored. Usually, 1,n-dipoles are elusive intermediate species, which can undergo many side reactions preceding the desired annulation/cyclization processes

• . Zhang envisioned that if the negative terminus of the dipole could be stabilized in the presence of gold, a better handling of these species could be achieved to trigger [n + m] annulation processes. In fact, the cationic end of the dipole was proposed to react in a bimolecular process in the presence

One-pot gold-catalyzed synthesis of 3-silylethynyl indoles from unprotected o-alkynylanilines

• Jonathan P. Brand,
• Clara Chevalley and
• Jérôme Waser

Beilstein J. Org. Chem. 2011, 7, 565–569, doi:10.3762/bjoc.7.65

• attempt a one-pot 3-steps synthesis of alkynyl indoles starting directly from iodoaniline. In conclusion, an efficient access to 2-substituted 3-silylalkynyl indoles is reported. 2-Alkynylanilines underwent a sequential one-pot Au(III)-catalyzed annulation and Au(I)-mediated direct alkynylation

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• A-366833, a selective α4β2 neural nicotinic receptor agonist. A new route to oxcarbazepine. Synthesis of key intermediates for norepinephrine transporter (NET) inhibitors. N-Annulation yielding substituted indole for the synthesis of demethylasterriquinone A1. Palladium-catalysed double N-arylation

A new and facile synthetic approach to substituted 2-thioxoquinazolin-4-ones by the annulation of a pyrimidine derivative

• Nimalini D. Moirangthem and
• Warjeet S. Laitonjam

Beilstein J. Org. Chem. 2010, 6, 1056–1060, doi:10.3762/bjoc.6.120

• yield of 2a was obtained when 5 equiv of ZnCl2 was used (Table 2, entry 13). The excessive amount of ZnCl2 for the annulation is probably due to the chelating effect of zinc ion. Thus, the NH4OAc/AcOH combination in ZnCl2 was found to be the best and gave the highest yield of 2b (85%) after refluxing

Recent advances in carbocupration of α-heterosubstituted alkynes

• Ahmad Basheer and
• Ilan Marek

Beilstein J. Org. Chem. 2010, 6, No. 77, doi:10.3762/bjoc.6.77

• Me2Zn (5:1) [26][27]. The rhodium-catalyzed annulation of ynamides with arylboron compounds containing an aldehyde or a ketone moiety have also been developed and lead to functionalized 2-amidoindenes with good levels of regioselectivity [28]. P-substituted alkynes Stereo- and regioselective