Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• to quinoline can be considered as an umpolung of the Skraup quinoline synthesis since it uses reversed polarity of reagents, where the C=C–NO2 fragment of the nitroarene is the electrophile reacting with an arylmethyl carbanion, the nucleophile (Scheme 2). Recently, we used the reactions of

A novel application of 2-silylated 1,3-dithiolanes for the synthesis of aryl/hetaryl-substituted ethenes and dibenzofulvenes

• Grzegorz Mlostoń,
• Paulina Pipiak,
• Róża Hamera-Fałdyga and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 1900–1906, doi:10.3762/bjoc.13.185

• -dithiolanes, as well as the generation of the corresponding carbanions are widely applied in the umpolung chemistry [27][28] and in the chemistry of protective groups [29][30], but tetrasubstituted ethenes have never been prepared by using this approach. Conclusion The presented study showed that 2

NHC-catalyzed cleavage of vicinal diketones and triketones followed by insertion of enones and ynones

• Ken Takaki,
• Makoto Hino,
• Akira Ohno,
• Kimihiro Komeyama,
• Hiroto Yoshida and
• Hiroshi Fukuoka

Beilstein J. Org. Chem. 2017, 13, 1816–1822, doi:10.3762/bjoc.13.176

• ; N-heterocyclic carbene; ring enlargement; Stetter reaction; vicinal polyketone; Introduction N-Heterocyclic carbenes (NHCs) have been indispensable catalysts for organic synthesis, particularly for umpolung of various functional groups [1][2][3][4][5][6][7][8][9]. In the Stetter reaction, NHCs

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• selective deprotonation of this hydroxy group over the others. This selective creation of a better nucleophile in the presence of the other protonated hydroxy groups can be regarded as an umpolung process. Despite this seeming difficulty, some protecting-group-free strategies to synthesize glycosides and

Electron-transfer-initiated benzoin- and Stetter-like reactions in packed-bed reactors for process intensification

• Anna Zaghi,
• Daniele Ragno,
• Graziano Di Carmine,
• Carmela De Risi,
• Olga Bortolini,
• Pier Paolo Giovannini,
• Giancarlo Fantin and
• Alessandro Massi

Beilstein J. Org. Chem. 2016, 12, 2719–2730, doi:10.3762/bjoc.12.268

• ). Keywords: C–C coupling; continuos-flow; diketone; electron-transfer; umpolung; Introduction The polarity reversal (umpolung) of carbonyl compounds by N-heterocyclic carbene (NHC) or cyanide catalysis represents a straightforward strategy for the synthesis of valuable molecules such as, among the many

• examples, α-hydroxy ketones (benzoin reaction) and 1,4-diketones (Stetter reaction) [1][2][3][4]. The synthetic utility of the umpolung methodology has therefore spurred intensive research on process intensification through the heterogeneization of NHC catalysts [5][6][7][8][9] for facilitating the post

• described by Lupton and co-workers [15]. Our group also contributed to this area of research fabricating polystyrene monolithic columns functionalized with thiazolium salt pre-catalysts to perform umpolung racemic processes (benzoin, acyloin, and Stetter reactions) with a good level of efficiency [16]. The

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• greenness. In research practice, synthetic organic chemists rely on a combination of retrosynthetic analysis [91][92][93][94][95][96][97], similarity and analogy patterning to known reactions, bond dissociation energy and bond polarity analysis (forward and umpolung), chemical intuition, and random

Correction: 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, 2124–2124, doi:10.3762/bjoc.12.201

• Interdisciplinary Science and Technology,Trivandrum 695 019, India.; Fax: +91 471 2491712; Tel: +91 471 2490406 10.3762/bjoc.12.201 Keywords: acyloin reaction; benzoin reaction; N-heterocyclic carbenes; organocatalysis; umpolung; On page 446, column 2, the sentence “Inoue and co-workers found that it promotes

Experimental and theoretical investigations on the high-electron donor character of pyrido-annelated N-heterocyclic carbenes

• Michael Nonnenmacher,
• Dominik M. Buck and
• Doris Kunz

Beilstein J. Org. Chem. 2016, 12, 1884–1896, doi:10.3762/bjoc.12.178

• heptafulvalene) as well as the very low N–C–N angle by X-ray structure analysis [41]. Weiss proposed this carbene to have a “built-in umpolung” [39] ability which means that there could be a participation of the dicationic bisylidene resonance form as it is usually described for carbodiphosphoranes [49] and

• low, net π-acceptor character of the dipyridocarbene. We are convinced that less electron-rich metal fragments could induce an overall π-donor character in dipyridocarbenes and could thus proof the “built-in umpolung” [39] ability proposed by Weiss and co-workers. This property might be advantageous

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• -unsaturated compounds Fernández, Lassaleta and co-workers provided an elegant, versatile and mild umpolung strategy, which leads to key synthetic precursors using the thiourea ent-4. In this study, an organocatalytic enantioselective addition of nucleophilic N,N-dialkylhydrazones to electron-deficient β,γ

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

• ; benzoin reaction; N-heterocyclic carbenes; organocatalysis; umpolung; Introduction The benzoin reaction (or condensation) is named after the product it furnishes via a catalytic assembly of two molecules of aromatic aldehydes. One molecule of the aldehyde functions as an acyl anion and the other as a

• as homo-benzoin reaction and that of two different aldehydes is known as crossed benzoin reaction. Mechanistically the reaction involves polarity reversal (umpolung) of one aldehyde to generate an acyl anion equivalent and this event is mediated by the catalyst. Alkali metal cyanides and N

Efficient synthetic protocols for the preparation of common N-heterocyclic carbene precursors

• Morgan Hans,
• Jan Lorkowski,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2015, 11, 2318–2325, doi:10.3762/bjoc.11.252

• ][23] and organic synthesis [24][25][26]. In particular, they were successfully employed for the umpolung of carbonyl compounds, sometimes in an asymmetric fashion [27][28][29]. Currently, the NHCs most frequently encountered are based on the imidazol-2-ylidene and imidazolin-2-ylidene scaffolds, which

Reaction of allene esters with Selectfluor/TMSX (X = I, Br, Cl) and Selectfluor/NH₄SCN: Competing oxidative/electrophilic dihalogenation and nucleophilic/conjugate addition

• A. Srinivas Reddy and
• Kenneth K. Laali

Beilstein J. Org. Chem. 2015, 11, 1641–1648, doi:10.3762/bjoc.11.180

• presence of phosphane catalysts an umpolung addition takes place, whereby the nucleophilic addition occurs inversely at the beta-gamma double bond [22][23]. Vinyl azides have been prepared by hydroazidation of allenyl esters through a Michael-type addition with high regio- and stereoselectivity [24

An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

• Roberto Blanco Trillo,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2015, 11, 313–322, doi:10.3762/bjoc.11.36

• ) were employed in enantioselective organozinc catalysis reactions [23][24][25][26], umpolung catalysis [27] and in organoaluminum [17] and chiral n-butyllithium aggregates [28][29][30][31][32][33]. The chlorophosphite BIFOP-Cl (1) is air-stable and very resistant to hydrolysis (Scheme 2) [13][15]. The

Photovoltaic-driven organic electrosynthesis and efforts toward more sustainable oxidation reactions

• Bichlien H. Nguyen,
• Robert J. Perkins,
• Jake A. Smith and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2015, 11, 280–287, doi:10.3762/bjoc.11.32

• efforts began by examining reactions where the substrate to be oxidized underwent the electron-transfer reaction directly at the electrode surface. We have employed reactions of this nature to functionalize amides [13][14] and to conduct umpolung reactions [15][16] that originate from electron-rich

A facile synthesis of functionalized 7,8-diaza[5]helicenes through an oxidative ring-closure of 1,1’-binaphthalene-2,2’-diamines (BINAMs)

• Youhei Takeda,
• Masato Okazaki,
• Yoshiaki Maruoka and
• Satoshi Minakata

Beilstein J. Org. Chem. 2015, 11, 9–15, doi:10.3762/bjoc.11.2

• group of 1a with t-BuOCl would generate N-monochlorinated BINAM (Int-A) and release t-BuOH. The N-chlorination would induce umpolung reactivity of the amino moiety because of the attachment of electronegative halogen species on the N atom [27][28][29][30], and thereby an intramolecular nucleophilic unit

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• electrochemical reaction leads to an Umpolung of the functional group with the lower redox potential, triggering the ring-closure reaction between a nucleophilic and an electrophilic site. Another possibility for an intramolecular ring closure is represented by electrochemically induced radical cyclization

• , electrochemistry represents a complementary method to conventional synthesis, due to unique selectivity and the possibility for electrochemical Umpolung. However, considering the fact that heterocycle-containing compounds represent the major part of active ingredients in pharmaceutics and crop protection, a lack

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• carbonates, Michael additions, γ-umpolung additions, and acylations of alcohols. Keywords: asymmetric catalysis; chiral phosphine; nucleophilic; organocatalysis; organophosphorus; synthesis; Introduction During the past two decades, tertiary phosphine catalysts have been applied extensively in a wide range

• developments in nucleophilic chiral phosphine-catalyzed asymmetric reactions, including annulations of allenes, ketenes, alkynes, and Morita–Baylis–Hillman (MBH) carbonates with activated alkenes and imines, allylic substitution of MBH acetates and carbonates, Michael additions, γ-umpolung additions, and

• bond between the amide NH proton and the enolate oxygen atom assisted the Michael addition from the si-face of the enolate. The alternative re-face attack was blocked by the 3,5-bistrifluoromethylphenyl group (Scheme 55). 2.17 γ-Umpolung additions of allenes or alkynes In the phosphine-catalyzed

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

• conducted under degassing conditions. This is in contrast to the chemistries involving iminium ions, which are often performed with exposure to air or oxygen. The reactivity umpolung at the carbon α to the nitrogen atom has expanded the repertoire of amine radical cations’ modes of reactivity. Compared to

Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

• Julien Lefranc,
• Alberto Minassi and
• Jonathan Clayden

Beilstein J. Org. Chem. 2013, 9, 628–632, doi:10.3762/bjoc.9.70

• primary, secondary and tertiary organolithium reagents. N-tert-butoxycarbonyl vinylcarbamates may be carbolithiated, protonated and deprotected in a one-pot synthesis of amines employing this unusual umpolung nucleophilic β-alkylation. With β-substituted vinylureas, the carbolithiation is

• structure of carbamate E-10. Carbolithiation of ureas 1. Diastereospecific carbolithiation of ureas 3. Diastereospecific carbolithiation of ureas 5. Synthesis of N-alkenyl carbamates 9–11. Umpolung carbolithiation of carbamates 9 and 10. Organolithium addition to ureas 1. Organolithium additions to ureas 3

NHC-catalysed highly selective aerobic oxidation of nonactivated aldehydes

• Lennart Möhlmann,
• Stefan Ludwig and
• Siegfried Blechert

Beilstein J. Org. Chem. 2013, 9, 602–607, doi:10.3762/bjoc.9.65

• led to a higher total conversion. We suppose that this is caused by the oxidation of the NHC, i.e., the consumption of the umpolung catalyst [23]. With this result in hand we focused on the aerobic autoxidation using only D as a precatalyst. An interesting conversion of aromatic aldehydes to acids

N-Heterocyclic carbene-catalyzed direct cross-aza-benzoin reaction: Efficient synthesis of α-amino-β-keto esters

• Takuya Uno,
• Yusuke Kobayashi and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2012, 8, 1499–1504, doi:10.3762/bjoc.8.169

• -amino-β-keto esters; cross-aza-benzoin; α-imino ester; N-heterocyclic carbenes; organocatalysis; umpolung reactions; Introduction α-Amino-β-keto ester derivatives are one of the fundamental structural subunits in natural products such as miuraenamides [1], and important building blocks for the

• of PhI=O is needed as the oxidant (Figure 1, (e)) [23]. Therefore, mild, efficient and environmentally friendly strategies for the synthesis of these esters are still needed. We envisioned that highly atom-efficient synthesis of α-amino-β-keto esters could be achieved by a novel umpolung approach

• including C–C bond construction, that is, formal addition of acyl anion equivalents generated from aldehydes 1 with NHCs, to α-imino esters 2 (Figure 1, (f)). Although a large number of NHC-catalyzed umpolung reactions, such as the benzoin reaction and Stetter reaction, have been developed [24][25][26][27

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• enantiomer. From the synthetic point of view, the conjugate addition of the nucleophile is, at the same time, a formal umpolung reaction with respect to the other carbonyl group (Figure 1). Results and Discussion Catalyst screening As a part of our ongoing studies in organocatalysis [16][17][18][19] we

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

• Sosale Chandrasekhar and
• V. Mohana Rao

Beilstein J. Org. Chem. 2012, 8, 1393–1399, doi:10.3762/bjoc.8.161

• transformation of 1 to 5 indicates that 1 functions as a glycine enolate equivalent with the benzoylamino group in 5 being introduced in umpolung fashion (reaction involves the migration to an electrophilic nitrogen center). Hofmann rearrangement approach Our strategy was based on the known ethyl

• amino group is being introduced in umpolung fashion in the strategy described above. Generally, the amino group is introduced nucleophilically, e.g., in the Gabriel method. The trioxaadamantylmethylamine carbamates 10 also represent α-amino acids with both carboxyl and amino group protection. The methyl

N-Heterocyclic carbene/Brønsted acid cooperative catalysis as a powerful tool in organic synthesis

• Rob De Vreese and
• Matthias D’hooghe

Beilstein J. Org. Chem. 2012, 8, 398–402, doi:10.3762/bjoc.8.43

• encouraged many chemists to search intensively for new NHC ligands, and this has led to the establishment of a very fruitful research area in organic chemistry [4][5][6][7][8][9][10]. A particularly interesting application comprises the use of “umpolung” reactions [11] (inversion of polarity) catalyzed by N

• -heterocyclic carbenes, such as the benzoin condensation and the Stetter reaction. In these reactions, the NHC effects an “umpolung” of the normal carbonyl reactivity, and the electrophilic aldehyde carbon atom thus becomes nucleophilic and can attack a variety of electrophiles. The story of “umpolung

• ” reactions of aldehydes started as long ago as 1832, and the preparation of sterically hindered triazolium salts in 1996 provided a solid basis for highly stereoselective “umpolung” reactions utilizing NHCs [12]. In addition, conjugate “umpolung” relates to a process in which α,β-unsaturated aldehydes 3 are

Lithium phosphonate umpolung catalysts: Do fluoro substituents increase the catalytic activity?

• Anca Gliga,
• Bernd Goldfuss and
• Jörg M. Neudörfl

Beilstein J. Org. Chem. 2011, 7, 1189–1197, doi:10.3762/bjoc.7.138

• ; lithium phosphonates; umpolung; Introduction Since the discovery of the cyanide catalyzed benzoin reaction by Liebig and Wöhler in 1832 [1], acyloin-type reactions evolved as powerful tools for couplings of acylanion equivalents with carbon electrophiles. In addition to cyanide [2][3][4][5] and