Diastereoselective synthesis of 3,4-dihydro-2H-pyran-4-carboxamides through an unusual regiospecific quasi-hydrolysis of a cyano group

• Mikhail Yu. Ievlev,
• Oleg V. Ershov,
• Mikhail Yu. Belikov,
• Angelina G. Milovidova,
• Viktor A. Tafeenko and
• Oleg E. Nasakin

Beilstein J. Org. Chem. 2016, 12, 2093–2098, doi:10.3762/bjoc.12.198

• diastereoselective cascade reaction [23]. The crucial stage of the described transformation is the formation of a pyran-4-carboxamide intermediate. A trace amount of it was isolated accidentally and we could not repeat this procedure and characterize the compound by spectra. Results and Discussion In continuation of

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• turn be synthesised by an aminolysis/oxidation/olefination sequence of the terminal alcohol 6, following traceless nitro group removal. 5-Nitropiperidin-2-one 6 in turn could be accessed by a nitro-Mannich lactamisation cascade reaction between Michael adduct 7, formaldehyde and a suitable primary

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• . Differently, treatment of 3-indolylmethanols with Nazarov reagents with TfOH in MeCN led to the generation of indoles through a cascade reaction in an (E/Z)-selective mode. These unusual reactions may serve as stereoselective and chemodivergent methods for accessing indole-containing scaffolds. Shi and co

• diastereoselectivities (all >95:5 dr) and enantioselectivities (up to >99% ee, Scheme 58) [75]. Mechanistic studies showed that this cascade reaction proceeded via a vinylogous Michael addition/Friedel–Crafts process involving a dual H-bonding activation of substrates. In 2015, Wang and co-workers reported Lewis acid

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• systems rapidly and efficiently, though additional catalyst development is needed. Keywords: bridged rings; carbene; cascade reaction; C–H bond insertion; nitrene; Introduction Bridged polycyclic natural products are an inviting challenge to the synthetic chemist for their rich display of functional

• , without having to preinstall functional groups at those positions (Figure 2). Ideally, the choice of catalyst or reagent would control the product formed. The transformation of 5 to 1 or 3 could occur in a single-bond-forming event, or multiple rings could be synthesized in a cascade reaction (i.e., 6 to

• synthesis of phomoidride B (Scheme 16) [76]. While this strategy was ultimately not productive for the total synthesis of the natural product, it did synthesize the key synthetic intermediate 62 very rapidly by taking advantage of insertion into the ether-activated C–H bond of 61. A carbene cascade reaction

Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter

• Sara Meninno,
• Chiara Volpe,
• Giorgio Della Sala,
• Amedeo Capobianco and
• Alessandra Lattanzi

Beilstein J. Org. Chem. 2016, 12, 643–647, doi:10.3762/bjoc.12.63

• affording the heterocyclic products in good yields and moderate stereoselectivities. Keywords: cascade reaction; tetrahydrothiophenes; aymmetric synthesis; amine thioureas; organocatalysis; Introduction The interest toward the development of stereoselective methodologies to prepare tetrahydrothiophenes

• /nitroaldol reaction and herein we report our preliminary results. Results and Discussion According to the literature data, low control of the diastereoselectivity was observed in the cascade reaction of 1,4-dithiane-2,5-diol with trans-β-nitrostyrenes, and in the case of (E)-1-aryl-2-nitropropene all four

• predicted relative free energies for 10, 11 and 12 fall within a range of 0.1 kcal/mol. Pleasingly, a solvent screening for the cascade reaction carried out on compound 2a with catalyst VII enabled to improve the diastereoselectivity as only 7a/8a were detected in 75:25 ratio and the enantiocontrol

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• the electrophilic component in a few reactions of NHC-bound aldehydes. The addition of acyl anions occur at the nitrogen atom of the nitroso compound. A NHC-catalysed cascade reaction of o-vinylarylaldehydes with nitrosoarenes afforded functionalised 2,3-benzoxazin-4-ones 45 [44]. The initial

• intermolecular aza-benzoin reaction is followed by an intramolecular oxa-Michael reaction to form the observed product (Scheme 28). Enders reported a cascade reaction which is initiated by an NHC-catalysed aza-benzoin condensation between various aldehydes and nitrosobenzenes to generate the hydroxamic acids 47

• catalyst rapidly shuttles the intermediate δ-keto aldehyde 61 to the final product preventing the erosion of enantioselectivity [54]. This cascade reaction constitutes a fine example of symbiotic dual-catalysis wherein both catalysts perform better together in a one-pot reaction than they do independently

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• -forming carbocation cascade reaction, thereby increasing the likelihood of direct formation of epi-isozizaene over byproducts. Outlook Clearly, non-statistical dynamic effects play important roles in carbocation rearrangement reactions. Neglecting such dynamic effects may lead to incorrect conclusions

A quadruple cascade protocol for the one-pot synthesis of fully-substituted hexahydroisoindolinones from simple substrates

• Hong-Bo Zhang,
• Yong-Chun Luo,
• Xiu-Qin Hu,
• Yong-Min Liang and
• Peng-Fei Xu

Beilstein J. Org. Chem. 2016, 12, 253–259, doi:10.3762/bjoc.12.27

• [65]. However, substrates with aliphatic R1, R2 or R3 did not produce the desired products (Table 2, entries 21–26). This bifunctional catalysis cascade reaction was also amenable to scale-up. When the reaction was carried out on a 3 mmol scale, the desired product was obtained in 84% yield. Therefore

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• [24][25][26]. In this context, our group recently introduced an interesting asymmetric organo-cascade reaction of 2-cyanobenzaldehyde (5) with malonate 6. This resulted in enantioenriched 2-(1-oxoisoindolin-3-yl)malonate 7 which is supposed to serve as a potentially useful building block for further

• cascade reaction, investigating novel trans-1,2-cyclohexane diamine-based bifunctional ammonium salts 8. These catalysts were recently introduced by our groups in a variety of different reactions [27][28][29], as exemplified by a related aldol-initiated cascade reaction of glycine Schiff base with 2

• -cyanobenzaldehydes [29]. Then we decided to address the asymmetric synthesis of bioactive isoindolinones, identifying the chiral isoindolinone 9 as a very useful, key building block, as shown in Scheme 1. Results and Discussion Asymmetric cascade reaction of 2-cyanobenzaldehyde under phase-transfer conditions As

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• ][25][26]. In this context, we have recently reported a catalytic and enantioselective Michael/Michael cascade reaction in which α-nitro-δ-ketoesters react with nitroalkenes to provide densely functionalized cyclohexanes in excellent yield and stereoselectivity (Scheme 1) [27]. This reaction made use

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• ester 75. Finally, an elegant cascade reaction involving an aldol condensation, followed by a hetereo Diels–Alder reaction closed the last three rings and antheliolide A (18) was obtained in 74% yield. In summary, the successful total synthesis of antheliolide A proceeded in 25 linear steps with an

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• of the cascade reactions was proposed as shown in Scheme 23 wherein the intermediate 89 generated by Ullmann C–N coupling reaction, the bidentate copper complex 90 and 91 were assumed as the key stages of the cascade reaction. Recently, cascade reactions using analogous o-halobenzenesulfonamide 92

• the absence of a ligand, but with evidently lower yield than the equivalent reaction with ligand (Scheme 23). Based on a novel cascade reaction, the synthesis of quinazolinones was realized by employing o-aminobenzamides and methylated electron-deficient heterocycles. As reported by Han et al, the

• related ring-fused products, the formation of other ring sized scaffolds such as five-membered structure were much less. An interesting cascade reaction between DG-functionalized benzamides 99 and malonates 100, which enabled the synthesis of indolinones 101 via selective C–C and C–N bond construction

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• selectivity by heating at 100 °C and air atmosphere in water. Simple arenes, including toluene, anisole and cresole were all well tolerated in this transforamtion (Scheme 14). Besides the direct halogenation, a cascade reaction involving a C–H halogenation represents another important approach in preparing C

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