Cp₂TiCl/D₂O/Mn, a formidable reagent for the deuteration of organic compounds

• Antonio Rosales and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2016, 12, 1585–1589, doi:10.3762/bjoc.12.154

• develop efficient procedures for the preparation of deuterated compounds, several methodologies of deuteration have been reported [5]. One of the first procedures reported was the acid- or base-catalyzed exchange of enolizable protons for deuterium. However, in order to achieve high isotopic purities

• through this procedure, multiple treatments of the enolizable substrate with deuterium oxide are required. Also, this method is not suitable for the incorporation of deuterium at not enolizable positions [6]. Later, the reduction of functional groups using deuterated reagents emerged as a powerful tool

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• developed organocatalytic conjugate addition–enantioselective protonations of α,β-unsaturated imides using thiols. Thiols are attractive nucleophiles due to their acidity, which facilitates deprotonation by amine bases and also reduces undesired competitive deprotonation and epimerization of the enolizable

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

• spirooxindoles utilizing the hydroxy group and the unsaturated ketone moiety. Song and co-workers designed a novel [2.2]paracyclophane-based thiourea catalyst (cat. 25), which was successfully applied to the enantioselective aldol reaction of isatins with enolizable ketones using H2O as the additive. The desired

• was proposed to explain the high enantioselectivity, highlighting the pivotal role of the dual activation of the catalyst. In 2014, Zhao and co-workers designed a series of (thio)urea catalysts (cat. 29) bearing an axially unfixed biphenyl moiety for the aldol reactions between isatins and enolizable

• for the reactions, although the starting materials were poorly solubilized. However, ten equivalents of aldehyde were used in the reactions. Similarly, Gong and co-workers reported an organocatalytic α-alkylation of enolizable aldehydes with 3-indolyl-3-hydroxyoxindoles co-catalyzed by the cinchona

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• substrate; however, to date, the carbonyl components for these reactions are mostly restricted to 1,3-diones, β-ketoesters, malonates, α-cyanoacetates, 3-substitued oxindoles and related systems. Generally, enolizable esters or carboxylic acid derivatives have been challenging in this strategy, because

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

• over two steps. A conceptually similar enamine-NHC dual-catalytic Michael–benzoin cascade was also developed by Rovis. The reaction proceeds via the generation of an enamine from the enolizable aldehyde 62 in presence of the prolinol catalyst 60 and its subsequent addition to the Michael acceptor 63

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• ) and provide for the onward retro-Claisen reaction. Imines like 2 are less prone to hydration and, lacking an enolizable substituent, have no retro-Claisen pathway available. Conclusion Two new fates of imine intermediates formed on radical cyclizations of ene-sulfonamides have been identified. Tin

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• : an aldehyde, a primary (or a secondary) amine, and an enolizable aldehyde (or ketone) (Scheme 1a) [47][48]. The use of a hydrogen active component other than an enolizable aldehyde or ketone leads to a variety of structurally diverse products (Scheme 1b). The Mannich reaction products (commonly named

A convenient enantioselective decarboxylative aldol reaction to access chiral α-hydroxy esters using β-keto acids

• Zhiqiang Duan,
• Jianlin Han,
• Ping Qian,
• Zirui Zhang,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 969–974, doi:10.3762/bjoc.10.95

• one point-binding aldehydes and two-point binding β-keto acids under mild reaction conditions. The lack of strong Lewis acids or very basic intermediates enabled it to tolerate functionalities that would normally be incompatible with ester enolates, for instance, hydroxy groups, phenols, enolizable

A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

• Antoine Pignon,
• Erwan Le Gall and
• Thierry Martens

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• ][37][38]. Although the scope of the reaction was demonstrated to be quite broad, some limitations were noticed, especially in reactions involving aryl halides. For instance, primary amines and enolizable aldehydes were unusable in this process. As a part of our ongoing efforts to improve reliability

• imine remains partly unconsumed at the end of the process. Nevertheless, we were pleased to observe that the reaction works with enolizable aldehydes (Table 2, entries 4 and 5), a notable result considering the acidity of the protons α to the carbonyl. Logically, Ms-containing sulfonamides (Table 2

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

• Fei Wang,
• Lingchun Li,
• Chuanfa Ni and
• Jinbo Hu

Beilstein J. Org. Chem. 2014, 10, 344–351, doi:10.3762/bjoc.10.32

• yields. It should be mentioned that the aromatic aldehydes with substituents such as t-butylthio, methoxy, and bromo groups on the phenyl ring showed similar reactivity. Moreover, this approach is also amenable to enolizable aldehydes, for example, gem-difluoroolefin 2h could be obtained in 47% yield

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

• (Scheme 26) [93]. Functionalization of the sp3 C–H bond α to the nitrogen atom in tetrahydroquinolines and indolines via iminium ions is challenging because the corresponding iminium ions are enolizable and thus tend to tautomerize to enamines [94][95] and/or aromatize [96][97]. The authors adopted a

Gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones

• Marie Hoffmann,
• Solène Miaskiewicz,
• Jean-Marc Weibel,
• Patrick Pale and
• Aurélien Blanc

Beilstein J. Org. Chem. 2013, 9, 1774–1780, doi:10.3762/bjoc.9.206

• attention to the problematic R3 position in which only phenyl and tert-butyl substituents adjacent to the ketone, i.e. without enolizable position, were tolerated under copper(I)-catalyzed reaction conditions. We were pleased to observe that various other substituents, such as methyl, propyl, 2-phenylethyl

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• addition of enolizable aldehydes to maleimides in the original method suggested the possibility of producing chiral γ-lactams through the use of a chiral proline-like organocatalysts. In fact, Córdova and co-workers have previously established a protocol for such a process [13]. Based on this initial

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

• electrophilicity relative to aromatic aldehydes [40][46][47][50]. To our delight, this methodology was found to be also suitable for the enolizable aliphatic aldehydes. Under the optimal reaction conditions (Table 1, entry 5), acetaldehyde and other primary alkyl aldehydes bearing functional groups such as ether

Highly selective synthesis of (E)-alkenyl-(pentafluorosulfanyl)benzenes through Horner–Wadsworth–Emmons reaction

• George Iakobson and
• Petr Beier

Beilstein J. Org. Chem. 2012, 8, 1185–1190, doi:10.3762/bjoc.8.131

• -enolizable ones such as 4,4'-dichlorobenzophenone or 2,2,2-trifluoroacetophenone, did not provide the expected alkene products. Next, we investigated analogous HWE reactions of isomeric phosphonate 4 with various aldehydes. Good yields of products 6 were obtained with both aromatic and aliphatic aldehydes

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• . This was due in part to undesired base-promoted reactions of the enolizable ketone segments, but also to the slow rate of interconversion of 47 and 48 (only the former can produce the desired pyridone). Experiment revealed that it was best to carry out the Michael step with DBU in pyridine, followed by

Development of the titanium–TADDOLate-catalyzed asymmetric fluorination of β-ketoesters

• Lukas Hintermann,
• Mauro Perseghini and
• Antonio Togni

Beilstein J. Org. Chem. 2011, 7, 1421–1435, doi:10.3762/bjoc.7.166

• presence of Lewis acids As a starting point for our investigation, we chose to study the fluorinations of the readily enolizable β-ketoesters 1 and 2 and of α-cyanoester 3 as model compounds with the reagent F–TEDA under either “neutral” conditions [66][67][68][69][70][71] or in the presence of Lewis acids

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• , thioether and ester groups, although enolizable alkylimines were not suitable under these conditions (Scheme 1). Replacement of the acid chloride with a chloroformate under 1 atmosphere of carbon monoxide as a fourth component led to ketocarbamates 3 in a single operation through a carbonylative coupling [3

• precatalysts and ligands, the palladacycle 10 in combination with the di-tert-butyl-2-biphenylphosphine (11) furnished the best results in terms of reaction time and yield. A large variety of imines and acid chlorides can be used in this reaction, with only enolizable imines and those bearing bulky nitrogen

Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols

• Michel Chiarucci,
• Mirko Locritani,
• Gianpiero Cera and
• Marco Bandini

Beilstein J. Org. Chem. 2011, 7, 1198–1204, doi:10.3762/bjoc.7.139

• outset of our investigation, we focused our attention on the non-enolizable allyl alcohol (Z)-1a, as a model candidate for the intramolecular oxaallyl alkylation. Our choice was dictated by the well-known reluctance of disubstituted malonyl derivatives to provide vinylbutyrolactones. This aspect was

• allylic SN1 mechanism is involved in the present methodology, due to the similar optical outcomes obtained in the presence of BA metal-free catalysts (entry 15, Table 1). Then, enolizable substrates carrying different malonyl residues (1b–e) were taken into account. In all cases the cyclization occurred

• intermediates) [53][54][55] in the nucleophilic attack was excluded; non-enolizable compounds being suitable candidates for the cyclization reaction. Conclusions In conclusion, we have documented an unprecedented example of gold-catalyzed lactonization with primary allylic alcohols. Cationic NHCAu carbene gold