Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• 26, which was subsequently converted to the cyclophane 28 by a Mannich-type condensation reaction (40%) (Scheme 1). Michael addition: In 1999, Reißig and co-workers [85] have synthesized a functionalized cyclophane by a cascade reaction, which proceeds with desilylation, ring opening, proton transfer

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

• all this information obtained, we propose the following gold-catalyzed cascade reaction mechanism. The proposed catalytic cycle was initiated with π-activation of the triple bond by the carbene-based cationic gold species to form the intermediate 51, which triggers a gold-promoted intramolecular

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• evidence that compounds 7–11 (26 when Z = allyl) and analogues could also be intermediates in the synthesis of the azepinodiindolones as proposed in Scheme 6 (Path C). Additionally, in support of the pathways proposed, the reaction of N-allylindigo 2 under the typical cascade reaction conditions for these

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• Zhengning Li Chongnian Wang Zengchang Li College of Environmental and Chemical Engineering, Dalian University, Dalian 116622, China 10.3762/bjoc.11.23 Abstract A copper-catalyzed cascade reaction of α,β-unsaturated esters with keto esters is reported. It features a copper-catalyzed reductive

• aldolization followed by a lactonization. This method provides a facile approach to prepare γ-carboxymethyl-γ-lactones and δ-carboxymethyl-δ-lactones under mild reaction conditions. Keywords: aldol addition; cascade reaction; catalysis; conjugate reduction; copper; lactonization; Introduction Paraconic acid

• –lactonization cascade reaction using diethylzinc as a reductant [9]. Floch et al. have reported a catalytic synthesis of the γ-lactones from aryl bromides, zinc, dimethyl itaconate and aldehydes/ketones [10][11], which is characteristic in its simplicity, conciseness and high yielding, however with low

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• (+)-vincadifformine (Scheme 14) [106]. The key step in the synthesis was an iminium ion cascade reaction that formed the fused ring systems by coupling 3,3-disubstituted tetrahydropyridine 57 with indole derivative 58. The former coupling partner was derived from chiral α-quaternary lactam 60, which was constructed

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

• °C, but also the cheaper Ph3PAuCl/AgOTf gave respectable results. Surprisingly, AuBr3 was not able to promote this cascade reaction. A special feature of this approach is that when R4 is a o-alkynylbenzene a further Au-catalyzed cascade process involving C–H activation can occur to give 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

• access to 3,3-difluoro-2-aryl-3H-indoles and 3-fluoro-2-arylindoles are described. An unprecedented aminoauration/oxidation/fluorination cascade reaction of 2-alkynylanilines bearing a linear alkyl group on the terminal triple bond is reported. Keywords: 2-alkynylanilines; fluorination; gold catalysis

• substrate- and solvent-dependent as different outcomes occur in ethanol or acetonitrile/DMSO mixture. The functionalized fluorinated indoles were isolated in moderate to very good yields. An unusual aminoauration/oxidation/fluorination cascade reaction was observed with 2-alkynylanilines bearing a linear

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

• (126) featuring an impressive gold-catalzed cascade reaction and a DVCPR. Davies early example of a formal [4 + 3]-cycloaddition in alkaloids synthesis. Fukuyama’s total synthesis of gelsemine, part 1. Fukuyama’s total synthesis of gelsemine, featuring a divinylcyclopropane rearrangement, part 2

A combined continuous microflow photochemistry and asymmetric organocatalysis approach for the enantioselective synthesis of tetrahydroquinolines

• Erli Sugiono and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 2457–2462, doi:10.3762/bjoc.9.284

• Erli Sugiono Magnus Rueping Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.9.284 Abstract A continuous-flow asymmetric organocatalytic photocyclization–transfer hydrogenation cascade reaction has been developed. The new protocol allows

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• lateral metalation–cyclization sequence. Metalation of 130 with excess n-butyllithium followed by carbonation then yielded piperolactam C (131). In 2008, Heo and coworkers reported the synthesis of several aristolactams employing a one-pot cross-coupling/aldol condensation cascade reaction (Scheme 17) [91

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

• of (−)-epimyrtine have been described to date including the intramolecular allylsilane N-acyliminium ion cyclization [6], the organocatalytic aza-Michael reaction [7], the intramolecular Mannich reaction [8], and the iminium ion cascade reaction [9][10]. More efficient, convenient and highly

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

• loss of a proton. 1,3-Dipolar cycloaddition of 50 with a dipolarophile 46 furnishes fused pyrrolidine 51 that is further oxidized to pyrrole 52. The Zhu group discovered that the use of α-ketoester 53 as a pronucleophile to intercept the iminium ion of 13 triggered a new cascade reaction en route to

• . Plausible mechanism for photoredox 1,3-dipolar cycloaddition. Photoredox-catalyzed cascade reaction for the synthesis of fused isoxazolidines. Plausible mechanism for the photoredox-catalyzed cascade reaction. Photoredox-catalyzed α-arylation of glycine derivatives. Photoredox-catalyzed α-arylation of

AgOTf-catalyzed one-pot reactions of 2-alkynylbenzaldoximes with α,β-unsaturated carbonyl compounds

• Qiuping Ding,
• Dan Wang,
• Puying Luo,
• Meiling Liu,
• Shouzhi Pu and
• Liyun Zhou

Beilstein J. Org. Chem. 2013, 9, 1949–1956, doi:10.3762/bjoc.9.231

• single operation, play an important role in atom-economical organic chemistry. A cascade reaction is the most efficient way for targeting fine chemicals, agrochemicals, pharmaceutical drugs, drug intermediates and ingredients by a one-pot reaction in environmentally and economically friendly synthetic

[3 + 2]-Cycloadditions of nitrile ylides after photoactivation of vinyl azides under flow conditions

• Stephan Cludius-Brandt,
• Lukas Kupracz and
• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1745–1750, doi:10.3762/bjoc.9.201

• was examined. With the optimized flow-protocol in hand we were able to synthesize a variety of dihydropyrroles (5a–5i) (Scheme 4). The electronic properties of the aromatic ring, which depend on the substituents have no prinicipal influence on the outcome of this cascade reaction. Only the pyridyl

Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition

• Yongguang Wang,
• Ruiyang Bao,
• Shengdian Huang and
• Yefeng Tang

Beilstein J. Org. Chem. 2013, 9, 1601–1606, doi:10.3762/bjoc.9.182

• the way for their application in further biomedical investigations. Biosynthetically, katsumadain A is assumed to be derived from styryl-2-pyranone 3 and alnustone (4) [9] through a 1,6-conjugate addition/oxa-Michael addition cascade reaction (path a, Scheme 1). Indeed, both 3 and 4 are known natural

Preparation of optically active bicyclodihydrosiloles by a radical cascade reaction

• Koichiro Miyazaki,
• Yu Yamane,
• Ryuichiro Yo,
• Hidemitsu Uno and
• Akio Kamimura

Beilstein J. Org. Chem. 2013, 9, 1326–1332, doi:10.3762/bjoc.9.149

• 10.3762/bjoc.9.149 Abstract Bicyclodihydrosiloles were readily prepared from optically active enyne compounds by a radical cascade reaction triggered by tris(trimethylsilyl)silane ((Me3Si)3SiH). The reaction was initiated by the addition of a silyl radical to an α,β-unsaturated ester, forming an α

• : bicyclodihydrosilole; free radical; radical cascade reaction; SHi reaction; tris(trimethylsilyl)silane; Introduction Radical cyclization occupies a unique position in organic synthesis because it is a useful reaction for the construction of cyclic molecules [1][2][3][4][5][6][7][8][9][10]. The radical cascade

• cyclization process is also an interesting synthetic reaction that often provides an efficient method [11][12][13]. Recently, we reported a new type of higher-order radical cascade reaction between chiral enyne compounds and Bu3SnH, which is recognized as a useful reagent in radical reactions [14]. In this

Anionic cascade reactions. One-pot assembly of (Z)-chloro-exo-methylenetetrahydrofurans from β-hydroxyketones

• István E. Markó and
• Florian T. Schevenels

Beilstein J. Org. Chem. 2013, 9, 1319–1325, doi:10.3762/bjoc.9.148

• formed in only poor yields. The major product was isolated in 36% yield and its structure was unambiguously determined as the (Z)-chloro-exo-methylenetetrahydrofuran 6. The generation of 6 can be rationalized as depicted in Scheme 2. Under the basic conditions employed for the cascade reaction, 1,1

Palladium-catalyzed synthesis of N-arylated carbazoles using anilines and cyclic diaryliodonium salts

• Stefan Riedmüller and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2013, 9, 1202–1209, doi:10.3762/bjoc.9.136

• present an alternative Pd-catalyzed method for the construction of N-substituted carbazoles based on a stable, cyclic iodonium salt and electron-deficient anilines [24][25]. In the initial C–N bond-forming step of this cascade reaction, a ring opening of the cyclic iodonium salt through the amine is

Cascade radical reaction of substrates with a carbon–carbon triple bond as a radical acceptor

• Hideto Miyabe,
• Ryuta Asada and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2013, 9, 1148–1155, doi:10.3762/bjoc.9.128

• –carbon triple bond as a radical acceptor. When substrates with a methacryloyl moiety and a carbon–carbon triple bond as two polarity-different radical acceptors were employed, the cascade reaction proceeded effectively. A high level of enantioselectivity was also obtained by a proper combination of

• and limitation of the cascade transformation of hydroxamate esters with carbon–carbon triple bonds, the substrates of choice were 5, 6A–C, 7 and 8 having hydroxamate ester functionality (Figure 3). At first, we studied the cascade reaction of 5 with an acryloyl moiety and 6A–C with a methacryloyl

• 6A–C. Enantioselective cascade reaction of 6A–C. Reaction of propiolic acid derivatives 7 and 8. Opposite regiochemical cyclization using substrate 12. Cascade reaction of 14. Enantioselective cascade reaction of 14 and 16. Reaction of 6A–C in the presence of chiral ligand. Reaction of 14 and 16 in

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• metathesis substrate (such as 14 or 16). Finally, a metathesis cascade reaction would yield a product scaffold (such as 15 and 17). It was planned that many of the product scaffolds would bear an o-nitrophenylsulfonyl protecting group. The combinations of building blocks were carefully chosen to ensure that

• metathesis cascade reaction of 32 was remarkable [25]. Presumably, in this case, the metathesis cascade leads to the generation of the intermediate 59 (Scheme 5); the intermediate could then react to conclude the metathesis cascade (to give 45 after deprotection), or cyclopropanate [25] the terminal alkene

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• cascade reaction of salicylaldehyde (5) and malononitrile (20) involving an aldol reaction followed by intramolecular cyclization and finally a dehydration to give intermediate 21. A subsequent Michael addition of the indole (25) to intermediate 21 gives cation 26, which loses a proton to give the product

• reaction between salicylaldehyde (5) and acetonitrile (28) involving an aldol reaction, cyclization and dehydration. A subsequent Michael addition of nitromethane (30) to the product of the cascade reaction gave the desired product 32. Kovalenko and co-workers used a quantitative amount of piperidine in

• (5), acetonitrile (28) and nitromethane (30) to give 2-aminochromene 32 in 88% yield and 84% enatiomeric excess (Scheme 11) [24]. The reaction was found to be equally efficient when malononitrile (20) and cyanoacetate 29 were used instead of 28. The reaction is thought to proceed through a cascade

Copper-catalyzed CuAAC/intramolecular C–H arylation sequence: Synthesis of annulated 1,2,3-triazoles

• Rajkumar Jeyachandran,
• Harish Kumar Potukuchi and
• Lutz Ackermann

Beilstein J. Org. Chem. 2012, 8, 1771–1777, doi:10.3762/bjoc.8.202

• fully substituted 1,2,3-triazoles with excellent chemo- and regioselectivities. Likewise, the optimized catalytic system proved applicable to the direct preparation of 1,2-diarylated azoles through a one-pot C–H/N–H arylation reaction. Keywords: cascade reaction; C–H functionalization; copper

• chromatography on silica gel (n-hexane/EtOAc). Copper-catalyzed step-economical C–H arylation-based cascade reaction. Copper-catalyzed sequential catalysis with alkyne 1a. Copper-catalyzed reaction sequence using alkyl bromides 2. General reaction conditions: 1 (1.00 mmol), 2 (1.00 mmol), NaN3 (1.05 mmol), CuI

Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives

• Zhi-Cong Geng,
• Jian Chen,
• Ning Li,
• Xiao-Fei Huang,
• Yong Zhang,
• Ya-Wen Zhang and
• Xing-Wang Wang

Beilstein J. Org. Chem. 2012, 8, 1710–1720, doi:10.3762/bjoc.8.195

• stereoselective cascade reaction for the synthesis of the pyrazolidine compounds through organocatalysis. In this paper, we present a convenient access to racemic and enantioenriched 5-hydroxypyrazolidines through a domino aza-Michael/hemiacetal organocatalytic sequence of disubstituted hydrazines to α,β

• pyrazolidine derivatives through the cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes. The asymmetric version of this one-pot cascade reaction has also been realized with (S)-diphenylprolinol trimethylsilyl ether 1m as a secondary amine organocatalyst, and

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• acyclic α,β-unsaturated compounds In the previously reported organocatalytic tandem oxa-Michael–aldol reactions, the instantaneous dehydration of the β-hydroxyaldimine intermediates generates products with only one stereogenic center. Hong et al. [52] in 2009 reported a novel quadruple-cascade reaction

• cascade reaction starts in an analogous manner to that previously mentioned, although the first oxa-Michael step is followed by a second Michael addition to form the chroman unit. A series of α,β-unsaturated aldehydes were reacted with the o-hydroxy-β-nitrostyrene as shown in Scheme 11. Except for the

• quadruple-cascade reaction exemplifies an efficient three-component reaction. In 2010 Wang et al. [11] reported the highly enantioselective synthesis of trisubstituted chiral 4H-chromenes 20 through iminium-allenamide catalysis. The reaction consists of a Michael–Michael-cascade sequence between alkynals 5

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