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

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

Synthesis of spiroannulated and 3-arylated 1,2,4-trioxanes from mesitylol and methyl 4-hydroxytiglate by photooxygenation and peroxyacetalization

• Axel G. Griesbeck,
• Lars-Oliver Höinck and
• Jörg M. Neudörfl

Beilstein J. Org. Chem. 2010, 6, No. 61, doi:10.3762/bjoc.6.61

• discovered such as activities against several cancer cell lines, schistosomiasis and antiviral properties [6][7]. The introduction of substituents into the central peroxide ring system as well as further ring annulation are straightforward approaches for the preparation of other active derivatives which

One-pot three-component synthesis of quinoxaline and phenazine ring systems using Fischer carbene complexes

• Priyabrata Roy and
• Binay Krishna Ghorai

Beilstein J. Org. Chem. 2010, 6, No. 52, doi:10.3762/bjoc.6.52

• biological activity including antiviral and antibacterial properties and also act as kinase inhibitors [9][10][11]. These heterocyclic ring systems are most commonly assembled by the annulation of a heterocyclic ring onto a pre-existing benzene ring [12][13][14][15][16][17][18][19][20][21]. A less common

• approach to these ring systems is the annulation of benzene rings onto pre-existing heterocyclic rings [22]. This manuscript focuses on the successful execution of the latter transformation through a multicomponent reaction process to access these ring systems (Scheme 1). The synthetic approach involves a

A short synthesis of (±)-cherylline dimethyl ether

• Bhima Y. Kale,
• Ananta D. Shinde,
• Swapnil S. Sonar,
• Bapurao B. Shingate,
• Sanjeev Kumar,
• Samir Ghosh,
• Soodamani Venugopal and
• Murlidhar S. Shingare

Beilstein J. Org. Chem. 2009, 5, No. 80, doi:10.3762/bjoc.5.80

• anticipated that 5 could be constructed via a Pictet–Spengler ring annulation from amine 6 which, in turn, could be obtained by reduction of the corresponding isocyanate. The required isocyanate would arise from the aldehyde 7 via radical azidonation followed by Curtius reaction. Lastly, aldehyde 7 could be

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• was the trans-annulation using tetrafluoroboric acid as catalyst. It was expected that the product of this reaction would be fairly stable because of the decreased nucleophilicity of the pyrrole nitrogen in conjugation with the quinone ring. Mitomycin C itself is indeed only moderately reactive with

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• data (1H and 13C NMR) of synthetic asimicin was identical to those of naturally occurring compounds. In 2005, Roush’s group synthesized the bis-THF core of asimicin [98] from two sequential chelate-controlled [3+2] annulation reactions of allylsilanes and appropriately substituted aldehydes (Scheme 38

• ). Subjecting the protected allylsilane 281 to the [3+2] annulation reaction with α-benzyloxyacetaldehyde (282) afforded the 2,5-trans-THF 283. Conversion of 283 to aldehyde 284 was achieved by reductive removal of the benzyl group and subsequent oxidation of the alcohol. Treatment of aldehyde 284 with

• group reported the total synthesis of (+)-bullatacin (311) via a diastereoselective [3+2] annulation reaction (Scheme 43) [104]. Racemic aldehyde 314, which was prepared from allylsilane (±)-312 and α-benzyloxy acetaldehyde (313), was treated with the highly enantiomerically enriched allylsilane 315 in

Sordarin, an antifungal agent with a unique mode of action

• Huan Liang

Beilstein J. Org. Chem. 2008, 4, No. 31, doi:10.3762/bjoc.4.31

• reaction leading to a series of tricyclic analogs 85 displaying various functional groups. The C-10 ketone in this material would enable annulation sequences leading to tetracyclic compounds 84. The precursor to 85, intermediate 86, would arise from a Baylis-Hillman reaction [48] between aldehyde 87 and

Synthesis of 2-substituted 9-oxa-guanines {5-aminooxazolo[5,4-d]pyrimidin- 7(6H)-ones} and 9-oxa-2-thio- xanthines {5-mercaptooxazolo[5,4-d]pyrimidin- 7(6H)-ones}

• Subrata Mandal,
• Wen Tai Li,
• Yan Bai,
• Jon D. Robertus and
• Sean M. Kerwin

Beilstein J. Org. Chem. 2008, 4, No. 26, doi:10.3762/bjoc.4.26

• prepared were found to inhibit ricin with IC50 ca. 1–3 mM. Keywords: Annulation; Click Chemistry; Cyclization; Purine Analogs; Ricin; Introduction Oxazolo[5,4-d]pyrimidines have been reported to possess a variety of biological activities including kinase inhibition [1][2], adenosine receptor antagonism

• unsuccessful. An alternative route was sought in which the oxazole ring was formed first, followed by elaboration of the pyrimidine ring. Our previous work had demonstrated that in the case of ethyl 5-amino-2-methyloxazole-4-carboxylate 3a [20], direct annulation with chloroformamidine in DMSO at 120 °C or

• with 2-methylisothiourea sulfate neat or in ethylene glycol at 170 °C did not afford the oxazolo[5,4-d]pyrimidine 2 (Figure 2). Thus, a stepwise annulation [15] strategy was explored for the preparation of analogs of 2 bearing different 2-positions substituents. The required 5-aminooxazoles 3b,c were