Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• Diels–Alder reaction, Claisen rearrangement, cross-metathesis, and cross-enyne metathesis are used. The synergistic combination of these powerful reactions is found to be useful for the construction of complex targets and fulfill synthetic brevity. Keywords: Claisen rearrangement; Diels–Alder reaction

Studies towards the synthesis of hyperireflexolide A

• G. Hari Mangeswara Rao

Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185

• reported from our laboratory the synthesis of γ-lactone-fused cyclopentane derivative 5 from the respective Diels–Alder adduct in 5 steps with an overall yield of 29% [32]. Hydrolysis of dimethyl ketal 5 with MeSO3H in 1,2-DCE furnished γ-lactone-fused cyclopentanone 6 in 97% yield. Cyclopentanone 6 exists

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• synthesis, otherwise subsequent steps are complicated. Synthetic chemists, armed with various elegant artificial orthogonal bond formations, including alkyne–azide cycloaddition [27][28][29][30][31][32][33][34], thiol–ene ligation [35][36][37][38], Staudinger ligation [39][40], inverse-electron-demand Diels

• –Alder reaction [41][42][43][44], and hydrazone/oxime formation [45][46][47][48], have developed selective conjugation reactions under mild conditions. Although these bond-forming reactions have proven to be truly powerful approaches and will remain as first options to create novel bioconjugates

First thia-Diels–Alder reactions of thiochalcones with 1,4-quinones

• Grzegorz Mlostoń,
• Katarzyna Urbaniak,
• Paweł Urbaniak,
• Anna Marko,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2018, 14, 1834–1839, doi:10.3762/bjoc.14.156

• initially formed [4 + 2] cycloadducts. In general, the yields of the isolated products were high. With 5-chloro-10-hydroxy-1,4-anthraquinone, the thia-Diels–Alder reaction occurred with complete regioselectivity. In the case of the reaction of vitamin K3 (menadione) with diphenylthiochalcone, the initial

• cycloadduct was isolated in 37% yield. Keywords: hetero-Diels–Alder reactions; quinone dyes; quinones; sulfur heterocycles; thiochalcones; Introduction Hetero-Diels–Alder reactions are considered to be a powerful methodology widely explored for the synthesis of six-membered heterocycles [1][2] with numerous

• applications for the construction of complex molecules including naturally occurring products [3][4], drugs [5][6], agrochemicals [7], etc. In addition, asymmetric hetero-Diels–Alder reactions are of current interest [8][9][10]. Whereas aza- and oxa-Diels–Alder reactions are frequently applied, thia-Diels

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• target, cyclohexenylcytosine 99 was designed and was planned to synthesize using the oxidative coupling reaction. To prepare the substrate of the coupling reaction, cyclohexenylsilane 96 was synthesized using the Diels–Alder reaction of trimethylsilylbutadiene 92 and dimethyl fumarate (93), which gave

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• reaction in the following order: phase-transfer catalysis, Henry reaction, Suzuki–Miyaura cross-coupling and Tsuji–Trost allylic substitution, hydrogenation, Michael addition, aldol and multicomponent Biginelli reactions, epoxidation, Meerwein−Ponndorf−Verley reduction, aza-Diels−Alder and epoxide ring

• exhibited the best result. Aza-Diels–Alder and epoxide ring-opening reaction Manoury et al. have very recently reported facile synthesis of an enantiomerically pure inherently chiral calix[4]arene phosphonic acid (cR,pR)-121 from the readily available (cS)-enantiomer of calix[4]arene acetic acid 119 or its

• methyl ester 120 in four steps (Scheme 39) [73]. The organocatalytic properties of this inherently chiral calixarene Brønsted acid was firstly examined in the aza-Diels–Alder reaction of imines bearing electron-withdrawing or electron-donating substituents 122 with Danishefsky’s diene (123, Scheme 40

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• bicyclic intermediate via a concerted [3 + 2]-cycloaddition followed by its very fast decomposition (extrusion of CO2) via a retro-Diels–Alder [4 + 2]-cycloaddition. The almost spontaneous extrusion of CO2 is caused by an energetically favorable aromatization occurring in this step leading to the formation

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• spirocyclization of naphthol carboxylic acid [34]. Later Birman et al. reported a new variation of a chiral I(V) reagent, namely 2-(o-iodoxyphenyl)oxazoline derivative 28 [35]. The reagent was applied to an asymmetric [4 + 2] Diels–Alder dimerization of phenolic derivatives 29 to construct tricyclic derivatives 30

• different dienophiles furnished Diels–Alder adducts 35 with excellent enantioselectivity. Intramolecular H-bonding and the presence of an achiral alcohol as additive helped them to achieve outstanding enantioselectivity (up to 99%) even when using very low catalyst loadings (1–10 mol %, Scheme 6) Ciufolini

• . Asymmetric oxidation of sulfides by chiral hypervalent iodine reagents. Oxidative dearomatization of naphthol derivatives by Kita et al. [4 + 2] Diels–Alder dimerization reported by Birman et al. m-CPBA guided catalytic oxidative naphthol dearomatization. Oxidative dearomatization of phenolic derivatives by

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• Diels–Alder reaction. Ghosh’s group reported an exclusive peri-, regio-, and stereoselective cycloaddition reaction of 5H-benzo[7]annulen-5-one (Scheme 35) [137]. The intermolecular [4 + 2] cycloaddition of 2,3-benzotropone (12) with cyclopentadiene (202) in the presence of boron trifluoride occurred

• totally periselectively, regioselectively, and exo-diaselectively to afford the adduct 203 in 75% yield. The Diels–Alder reaction of 2,3-benzotropone (12) with various dienophiles has also been reported. In the first example, Rennhard’s group realized the cycloaddition of benzotropone 12 with maleic

Stepwise radical cation Diels–Alder reaction via multiple pathways

• Ryo Shimizu,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 704–708, doi:10.3762/bjoc.14.59

• -8588, Japan 10.3762/bjoc.14.59 Abstract Herein we disclose the radical cation Diels–Alder reaction of aryl vinyl ethers by electrocatalysis, which is triggered by an oxidative SET process. The reaction clearly proceeds in a stepwise fashion, which is a rare mechanism in this class. We also found that

• two distinctive pathways, including “direct” and “indirect”, are possible to construct the Diels–Alder adduct. Keywords: Diels–Alder reaction; radical cation; rearrangement; single electron transfer; stepwise; Introduction Umpolung, also known as polarity inversion, is a powerful approach in

• produces a radical cation species, which offers electrophilic reactivity for subsequent transformations. Enol ether radical cations are among the simplest members of this class and thus have been widely used in synthetic organic chemistry [13][14][15]. The Diels–Alder reaction is a classic reaction, and

Investigating radical cation chain processes in the electrocatalytic Diels–Alder reaction

• Yasushi Imada,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 642–647, doi:10.3762/bjoc.14.51

• , the turnover number, also referred to as catalytic efficiency, remains unclear in most cases. Herein, we disclose our investigations of radical cation chain processes in the electrocatalytic Diels–Alder reaction, leading to a scalable synthesis. A gram-scale synthesis was achieved with high current

• efficiency of up to 8000%. The reaction monitoring profiles showed sigmoidal curves with induction periods, suggesting the involvement of intermediate(s) in the rate determining step. Keywords: chain process; Diels–Alder reaction; electrocatalytic; radical cation; single electron transfer; Introduction

• amount of electricity passed can be precisely controlled in a switchable manner. Described herein is a demonstration of excellent current efficiency and high productivity for the electrocatalytic Diels–Alder reaction. Results and Discussion The present work began by optimizing the SET-triggered Diels

An air-stable bisboron complex: a practical bidentate Lewis acid catalyst

• Longcheng Hong,
• Sebastian Ahles,
• Andreas H. Heindl,
• Gastelle Tiétcha,
• Andrey Petrov,
• Zhenpin Lu,
• Christian Logemann and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 618–625, doi:10.3762/bjoc.14.48

• Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom Institute of Inorganic Chemistry, University of Cologne, Greinstr. 4, 50939 Cologne, Germany 10.3762/bjoc.14.48 Abstract We report an air-stable bisboron complex as an efficient catalyst for the inverse electron-demand Diels–Alder (IEDDA

• enhancing its practicality. Comparative reactions were carried out to evaluate its catalytic activity in IEDDA reactions of diazine including phthalazine as well as 1,2,4,5-tetrazine. Keywords: air-stable catalyst; bidentate; bisboron; diazine; Diels–Alder; Lewis acid; Introduction The development of

• efficient and practical methods for synthesis is one of the prime objectives in chemistry. Especially transformations relying on new catalytic activation principles are of importance. In the past years, the inverse electron-demand Diels–Alder (IEDDA) reaction has been well established for the construction

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• ]. These o-QM precursors by a thermal elimination of dimethylamine were then reacted with different cyclic dienophiles to give various inverse electron-demand Diels–Alder adducts 35–37. In case of 36, the cis-fused ring system found to be similar to bioactive xyloketals isolated from fungi (Scheme 4) o-QMs

• are also known to undergo oligomerization in the absence of dienophiles and nucleophiles via an oxo-Diels–Alder protocol (Table 4). During the syntheses of 1,4,9,10-anthradiquinones with potential antitumor activity, Kucklaender et al. isolated new spiro derivatives 38 [77]. These latter spirocyclic

• dimers formed in a Diels–Alder dimerization process by heating the corresponding Mannich bases under reflux in dichloromethane for 2 hours. In the synthesis of 3,4-dihydro-2-aryl-2H-benzo[f]chromenes and 2-aryl-6,7-dimethylchromans starting from substituted styrenes and 1-dimethylaminomethyl-2-naphthol

Oxidative cycloaddition of hydroxamic acids with dienes or guaiacols mediated by iodine(III) reagents

• Hisato Shimizu,
• Akira Yoshimura,
• Keiichi Noguchi,
• Victor N. Nemykin,
• Viktor V. Zhdankin and
• Akio Saito

Beilstein J. Org. Chem. 2018, 14, 531–536, doi:10.3762/bjoc.14.39

• , Winnipeg, MB R3T 2N2, Canada 10.3762/bjoc.14.39 Abstract [Bis(trifluoroacetoxy)iodo]benzene (BTI) and (diacetoxyiodo)benzene (DIB) efficiently promote the formation of acylnitroso species from hydroxamic acids in the presence of various dienes to give the corresponding hetero-Diels–Alder (HDA) adducts in

• moderate to high yields. The present method could be applied to the HDA reactions of acylnitroso species with o-benzoquinones generated by the oxidative dearomatization of guaiacols. Keywords: acylnitroso; benzoquinone; cycloaddition; dearomatization; iodine(III); Introduction The hetero-Diels–Alder (HDA

• -Diels–Alder (HDA) reactions of N-acylnitroso species. DIB-mediated oxidative HDA reactions of 1a–c with various guaiacols. Screening of I(III) reagents and solvents for HDA reaction of 1a with 2a. BTI or DIB-mediated oxidative HAD reactions of 1a–c with various dienes. Supporting Information Supporting

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• -dithioacetals [4] are of particular interest as attractive nucleophiles for the addition to halonium ions [5][6], acyl chlorides [7] and other electrophiles [8][9][10] and are broadly used as precursors for [2 + 2]-cycloaddition [11][12], (aza)-Diels–Alder reaction [13][14], and [3 + 2]-cycloaddition reactions

Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu₄NI

• Mi-Hai Luo,
• Yang-Ye Jiang,
• Kun Xu,
• Yong-Guo Liu,
• Bao-Guo Sun and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35

• in 64% and 58% yield, respectively. Substituted styrenes and 1-ethynylbenzene were also tolerated well, giving corresponding products 3ai–3aj in 45–50% yields. The formations of 3ah–3aj likely derives from an azo-Diels–Alder reaction of styrene or ethynylbenzene with an imine intermediate, in situ

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• [22]. There are not many transformations of aliphatic SF5 compounds described in the literature. Among them are the preparation and derivatization of SF5-aldehydes [23], Diels–Alder reactions [24][25][26], the “click reaction” of SF5-acetylenes with azides to form triazoles [27], and 1,3-dipolar

Diels–Alder cycloadditions of N-arylpyrroles via aryne intermediates using diaryliodonium salts

• Huangguan Chen,
• Jianwei Han and
• Limin Wang

Beilstein J. Org. Chem. 2018, 14, 354–363, doi:10.3762/bjoc.14.23

• extensive attention [14][15][16]. Also as a five-membered heterocyclic ring, the cycloaddition reaction of N-substituted pyrroles is much less than that of furan [17][18][19][20][21]. As a matter of fact, the Diels–Alder adduct formation of pyrroles with benzyne has been postulated in 1965 as transient

• products under thermal conditions to afford arylamines [22]. Inspired by the pioneering work of Stuart and Wang [12][13], herein we reported the usage of diaryliodonium salts as aryne precursor for Diels–Alder cycloadditions of N-arylpyrroles (Scheme 1d). Results and Discussion We initially started the

• cycloaddition reaction of 1-phenylpyrrole (1a) using phenyl(mesityl)iodonium tosylate (2a) as benzyne precursor. To our delight, with LiHMDS as the base in toluene, the Diels–Alder adduct 3aa was obtained in 23% yield at room temperature (Table 1, entry 1). However, when the reaction temperature was increased

Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives

• Imane Nekkaa,
• Márta Palkó,
• István M. Mándity and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2018, 14, 318–324, doi:10.3762/bjoc.14.20

• syntheses of various pyrimidinones as potentially bioactive products by means of the highly controlled continuous-flow retro-Diels–Alder reaction of condensed pyrimidinone derivatives are presented. Noteworthy, the use of this approach allowed us to rapidly screen a selection of conditions and quickly

• confirm the viability of preparing the desired pyrimidinones in short reaction times. Yields typically higher than those published earlier using conventional batch or microwave processes were achieved. Keywords: continuous-flow; desulfurisation; norbornene-fused heterocycles; pyrimidinones; retro-Diels

• –Alder reaction; Introduction The continuous-flow (CF) technology has gained significant importance in modern synthetic chemistry [1][2][3] and becomes a core technology in the pharmaceutical, agrochemical, and fine chemical industries [4][5]. The use of this technology opens a new door to a quick

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• CaCO-2. Lin et al. [52] developed the synthesis of pyrazolo[3,4-b]pyridine derivatives 45 via aza-Diels–Alder reaction of pyrazolylimines 43 with maleimides 44 (Scheme 8). Pyrazolylimines 43 were in turn obtained from the reaction of 5-aminopyrazole 16 with diisopropylformamide dimethyl acetal (R

• -arylmaleimides 44 in a solvent-free methodology based on microwave-assisted (80 W, 80 °C, 1.5 h) hetero-Diels–Alder reaction for the synthesis of pyrazolo[3,4-b]pyridine derivatives 45 (Scheme 8). Jiang et al. [54] described the synthesis of macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives 49 by the

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• base to give the σ-adducts. Earlier it was found that an aza analog of DNBF – 4-aza-6-nitrobenzofuroxan (1, ANBF) ranks among the most electrophilic heteroaromatics known to date [17][18]. Compound 1 gives a remarkably stable hydrate in aqueous solution and forms Diels–Alder cycloadduts 2 with dienes

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• structure of Ecm1 which forms a substrate binding cleft rather than a pocket [94]. Vinylbenzyl-modified cap analogues (bearing the modification at either the N7 or N2-position) provided a platform for inverse electron-demand Diels–Alder reactions with tetrazine conjugates and for photo-click reactions using

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• -Diels–Alder reaction [87]. Coupling between alkynoic acid and 2-aminobenzothiazole and the use of ionic liquids have also been developed [88]. Heterogeneous catalysts such as kaolin and hydrotalcites have been employed in the synthesis of benzo[4,5]thiazolo[3,2-a]pyrimidin-4-ones [89][90

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• vinylphosphonium salts can be used in the Diels–Alder reaction with dienes such as isoprene, 1,3-butadiene, 2,3-dimethyl-1,3-butadiene, cyclopentadiene, and 1,3-cyclohexadiene, resulting in cyclic phosphonium salts 115 in yields of 90–96% (Scheme 66) [78]. Gelmi et al. showed that vinylphosphonium bromide 8 in

• )vinylphosphonium salt. Synthesis of 7-oxo-7H-pyrido[1,2,3-cd]perimidine derivative via nucleophilic displacement of the triphenylphosphonium group in intermediate α,β-di(methoxycarbonyl)vinylphosphonium salt. Application of vinylphosphonium salts in the Diels–Alder reaction with dienes. Synthesis of pyrroline