Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• base [1][2][3]. The products of the Ireland–Claisen rearrangement, γ,δ-unsaturated acids, are useful precursors of biologically active compounds and natural products [4][5][6][7][8][9][10][11]. The ready availability of allylic esters, the ability to control the E/Z geometry of enolates as well as its

• stereospecificity make this transformation synthetically appealing [12][13]. Allyl esters of various carboxylic acids undergo rearrangement as their lithium enolates or silyl ketene acetals and the corresponding acids were isolated in 75–80% yields. Accordingly, the Ireland–Claisen rearrangement of lithium enolates

• generated from allyl fluoroacetates gave the corresponding α-fluoro-γ,δ-unsaturated acids [14]. The Ireland–Claisen rearrangement of Et3N-solvated enolates showed higher reactivity as well as diastereoselectivity when compared with analogous reactions in THF [15]. The required ester enolates are typically

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• also investigated this option for the first time in the synthesis of β-ketonitriles from esters, as described later (see Table 1). Finally, it is probable that the presence of protic IPA suppresses enolization as the reaction progresses, by quenching KOt-Bu generated enolates and similarly, reactive

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• over B after reaction of the enolates of 66 with chiral iodoarene 67. Steric factors restrict the formation of transition state B, and the reaction preferentially proceeds via transition state A to stereoselectively form the lactones [62]. Chiral catalysts Achieving enantiocontrol in electrochemical

• chiral enolates. Organocatalysts: From the outset of electroorganic chemistry, chemists have devoted substantial effort towards applying organocatalysts in electroorganic synthesis. Recent advances integrating organocatalysis and electroorganic synthesis were elegantly presented by Boydston and Ogawa in

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• allyldioxazaborolidine 11), respectively. The tetronate building blocks 4 and 5 were further converted to the corresponding enolates using lithium diisopropylamide and allowed to react with the common key intermediate 3 to afford the hydroxyalkylated products 18 and 19, in 78% and 59% yield, respectively (Scheme 4

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• asymmetric variant of our aldol route (α-diazoacetate ester anion addition to an α-ketoester) to the cycloaddition substrate 3 (X = H) did not appear promising [16]. An alternative and asymmetric route to such substrates, ultimately successful, built on stereoselective alkylation of enolates of tartrates

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• which are caused by the unsaturated character of the cyclopropyl ring. Although cyclopropanols are usually less reactive than enols and enolates, their chemical properties are somehow more diverse as they undergo useful transformations either with preservation or rupture of the cyclic structure [5

• cyclopropanol by Cottle [7], the most popular methods for the preparation of cyclopropanols rely on the transformation of enolates [8][9], silyl enol ether [10][11][12], vinyl borane [13][14][15][16][17], Fischer carbene addition [18], addition of nucleophiles to carbonyl groups [19][20][21][22][23][24][25

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• ketene acetals of (Z)-configuration 57a–l, arising from O-silylation of the corresponding chelated potassium enolates [60], underwent an efficient [3,3]-sigmatropic rearrangement upon warming to room temperature. After an acidic work-up and treatment of the crude carboxylic acids with

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• electrophilic hydroxylation at C4 When the lithium enolate of dimethyl N-Cbz-L-glutamate 63 was treated with Davis oxaziridine, an inseparable 9:1 mixture of diastereoisomers was formed with (2S,4S)-64 predominating (Scheme 16) [74]. For sodium and potassium enolates diastereoselectivity of the hydroxylation

• mentioning that hydroxylation of lithium enolates of pyroglutamate and glutamate results in the opposite stereochemical outcome at C4 (R vs S) and formation of a single diastereoisomer for the cyclic system and a 9:1 mixture for the linear one. 3,4-Dihydroxyglutamic acids Structures of enantiomers of 3,4

A convenient and practical synthesis of β-diketones bearing linear perfluorinated alkyl groups and a 2-thienyl moiety

• Ilya V. Taydakov,
• Yuliya M. Kreshchenova and
• Ekaterina P. Dolotova

Beilstein J. Org. Chem. 2018, 14, 3106–3111, doi:10.3762/bjoc.14.290

• solvent. Additional advantages of THF include its high miscibility with both 2-acetylthiophene and even long-chain perfluorinated esters, and the high solubility of sodium enolates in it. This fact makes it possible to obtain homogeneous reaction mixtures after completion of condensation. The optimum

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• derivatives, from the same source of chirality. Results and Discussion Synthesis of vancosamine and saccharosamine glycals. The chiral (−)-lactic methyl ester was identified as the privileged starting material considering that the Evans aldol reaction via boron enolates [26][27][28] with an appropriately O

Synthesis of functionalised β-keto amides by aminoacylation/domino fragmentation of β-enamino amides

• Pavel Yanev and
• Plamen Angelov

Beilstein J. Org. Chem. 2018, 14, 2602–2606, doi:10.3762/bjoc.14.238

• enolates is one of the main synthetic approaches towards β-keto amides and has found numerous applications [1][2][3][4][5][6][7][8][9]. However, while the generation of tertiary amide enolates is straightforward, this is not the case with secondary and primary amides. The NH acidity of the latter compounds

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• , we used an aprotic polar solvent like DMF, which weakly solvates the enolates. However, treatment of compound 10 with benzyl bromide and K2CO3 in DMF gave exclusively the C-3 alkylated derivative. Thus, we considered that a hard leaving group such as a sulfonate should play a key role in favouring O

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• cycloaddition of azides with activated dipolarophiles such as strained cyclic alkynes, enamines, enolates, electron-deficient olefins, ylides, iminium cations and alkyne anions, etc., have been identified as reliable approaches to access 1,2,3-triazole scaffolds with multiple substitution patterns [39][40][41

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• -arylation of carbonyl compounds In addition to their role as aryl donors in numerous metal-catalyzed couplings, diaryl-λ3-iodanes are also relevant reagents to perform the α-arylation of enolates. However, the reaction is again limited to the transfer of a single aryl group. As an alternative to address

• N-arylation/C(sp2)–H arylation with diaryl-λ3-iodanes. Catalytic intermolecular diarylation of anilines with diaryl-λ3-iodanes. Catalytic synthesis of diarylsulfides with diaryl-λ3-iodanes. α-Arylation of enolates using [bis(trifluoroacetoxy)iodo]arenes. Mechanism of the α-arylation using [bis

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• with good yields (62–83%) and uniformly excellent enantioselectivities (92–99% ee), as shown in Scheme 6. Along with enolates employed as nucleophilic partners in Mannich reactions, related reactions involving enamines have been developed. For example in 2018, Lu, Zhang and Shi reported the first

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• Keshaba N. Parida Gulab K. Pathe Shimon Maksymenko Alex M. Szpilman Department of Chemical Sciences, Ariel University, 4070000 Ariel, Israel 10.3762/bjoc.14.84 Abstract Due to their closely matched reactivity, the coupling of two dissimilar ketone enolates to form a 1,4-diketone remains a

• of enolates may be used to form the 1,4-diketone products in 38 to 74% yield. Due to the use of two TMS enol ethers as precursors, an optimization of the cross-coupling should include investigating the order of addition. Keywords: 1,4-diketones; enolates; enolonium species; hypervalent iodine

• . Recently, Loh reported the palladium-catalyzed coupling of an acid chloride with premade isolable indium homoenolates (In(CH2CHRC=OR')2), 1.2 equiv relative to the acid chloride) to give the corresponding 1,4-diketones [5]. Yet the direct coupling of two enolates is inarguably the shortest and most direct

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

• . The selectivity of these reactions depends on the geometry of the intermediate enolates. Here, we have reacted octyl pentafluoro-λ6-sulfanylacetate with substituted benzaldehydes and acetaldehyde under the conditions of the silicon-mediated Mukaiyama aldol reaction. The transformations proceeded with

• cycloadditions of azomethine ylides with pentafluoro-λ6-sulfanyl-substituted acrylic esters and amides [28]. A couple of years ago, we became interested in SF5-substituted ester enolates as reaction intermediates. Thus, in 2016 we reported a highly anti-selective aldol addition of SF5-substituted acetic ester

• -based boron enolates to aromatic and aliphatic aldehydes to form anti-2-pentafluoro-λ6-sulfanyl-3-hydroxyalkyl-carboxylic acid esters [29]. Quite similar results were published independently by Carreira et al. a couple of weeks before us [30]. Recently, we discovered that silylated enolates can be

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• constitute efficient alternatives to base-induced aldol condensations since the enolates are formed under neutral conditions, which allow an excellent functional group tolerance. However, the Reformatsky reaction generally provided lower yields and stereoselectivities along with narrower substrate scopes

• enolates can be considered as valuable alternatives to lithium enolates. Consequently, a number of samarium-mediated Reformatsky reactions have been developed. For example, SmI2 was found by Rinner et al. to mediate the diastereoselective Reformatsky reaction between chiral aldehyde 11 derived from D

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

• metal enolates [17]. The subsequent reactions occur so as to avoid unfavorable steric repulsive interaction with the oxazolidinone substituent, the iPr group in our case (Int-a). The selection of the two enantiotopic enolates should be explained on the basis of the Cieplak effect [18][19] for the

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• Stabilized enolates and their equivalents are the most studied C-nucleophiles in Michael addition reactions with nitrosoalkenes. A first systematic study in this area was done by Ohno and co-authors [13][23], who reported the addition of diethyl malonate and acetylacetone anions to cyclic nitrosoalkenes

• their reactions with enolates. Thus, our group has demonstrated that nitrosoacetals of nitrosoalkenes (N,N-bis(silyloxy)enamines 3) smoothly react with 1,3-dicarbonyl compounds in the presence of TBAF or DBU to give the corresponding oximes 6 in moderate to good yields (Scheme 3) [24]. The process is

• and ketones including cyclic ones were successfully used as nitrosoalkenes precursors to give oximes 8 in good to high yields. The same authors used the advantage of intramolecular Michael addition of enolates to nitrosoalkenes to construct bridged and fused carbocyclic systems [27]. For example, the

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• the spirocyclization reaction. Our multiple attempts to carry out this transformation with the participation of enolates generated from cyclohexane-1,3-diones 8 (vinylogous carboxylates) in the presence of bases were unsuccessful. This reaction did not proceed in the presence of weak bases (such as

• -membered ring of intermediate 11 (Scheme 3). Although the reasons for such divergence in the reactivity are not completely understood, one could argue that the lower nucleophilicity of enolates derived from 8 as compared to that of enamine 1a could be responsible for this effect. Indeed in this case, the

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• major advantages of all these chiral cation-based phase-transfer catalysts (Q+ X−) is their unique potential to control the reactivity of a broad variety of different prochiral nucleophiles (i.e., enolates) via formation of chiral ion pairs, which can then undergo stereoselective α-functionalization

• highly enantioselective approaches have been reported so far, which clearly proves the potential of this non-covalent activation principle. Besides versatile stereoselective C–C bond-forming reactions, the asymmetric α-heterofunctionalization of prochiral nucleophiles (i.e., enolates) became one of the

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• diastereoselective addition of a nucleophile on a carbonyl group. The latter can involve either the reduction of a ketone at C-5’ [12][33][34][35], or the addition on an aldehyde of various nucleophiles such as enolates [15][36][37][38], allylborane [39], dialkyl phosphites [40], TMSCN [41] or Grignard reagents [12

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• coupling in high yield with good stereocontrol [38][39][40]. With the auxiliary controlled alkylation of enolates products being analogous to radical hetero-coupling can be synthesized [41][42]. However, both methods require costlier reaction conditions as inert gas, dry solvents and LDA as reagent, and

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• provided crystallographic evidence that the alpha C–H bonds of tetraalkylammonium salts are highly polarized, and can form multiple hydrogen bonds with enolates in the solid state (Scheme 4) [40][41][42][43][44][45]. The existence of alpha C–H hydrogen bonds has also been invoked in the computational