Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• -acetylhydroxyamino acids. They were in fact the first researchers to at all investigate compounds belonging to this class of amino acid derivatives. Under the mantra «acidity favors O-acylation, while alkalinity favors N-acylation», they accomplished this feat by treatment of hydroxy-L-proline, DL-serine, DL

• products is too voluminous to justify any exhaustive listing in this work, thus for the purposes herein, it will suffice to point out that the outcome of acetylation reactions on such amino alcohols varied greatly depending on the acidity or alkalinity of the reaction medium. In a previous section, we were

Highly selective electrochemical fluorination of dithioacetal derivatives bearing electron-withdrawing substituents at the position α to the sulfur atom using poly(HF) salts

• Bin Yin,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2015, 11, 85–91, doi:10.3762/bjoc.11.12

• aromatic dithioacetal is more acidic compared to that of an aliphatic dithioacetal, the deprotonation of the former is faster than it is for the latter. Therefore, it can be stated that the product selectivity is controlled by the kinetic acidity of the cationic intermediate A [26][27]. With these facts in

• substrates. It is known that the acidity of the α-proton of N,N-diethylacetoamide is 4 to 5 times lower than that of acetone and ethyl acetate [35]. Therefore, the acidity of the α-proton of 1f having an amide group would be much lower compared to that of 1b and 1d having an ester and acetyl group

• fluorination of 1b and 1d (Figure 1a and Table 3, entries 2 and 4). Thus, it was found that due to the low acidity of the α-proton of 1f, fluorodesulfurization took place prior to α-fluorination even in the presence of Et3N·3HF containing the free base Et3N. In sharp contrast to these cases, α,α-bis(phenylthio

Anion effect controlling the selectivity in the zinc-catalysed copolymerisation of CO₂ and cyclohexene oxide

• Sait Elmas,
• Muhammad Afzal Subhani,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 42–49, doi:10.3762/bjoc.11.7

• amounts of CO2. Non-coordinating anions lead to a more electrophilic zinc centre with a stronger Lewis acidity, thereby triggering the homopolymerization in case of the CF3SO3− anion. In this context, it is known that the rate of the CO2 insertion into metal–oxygen bonds depends critically on the

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• ∙H2O, Cu(OAc)2∙H2O and Cu(NO3)2∙3H2O instead of CuSO4∙5H2O (Table 1, entries 2–4b). Among the Cu2+ salts tested, Cu(OAc)2∙H2O was found to be better than others and yielded 10% of 4a (Table 1, entries 3–4b). In the literature, we found that additives, such as Brønsted acids, enhance the acidity of the

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• presence of an equimolar amount of phenol (as a source of phenolic acidity) led to the formation of dihydroisoxazolopyridines 5a,c rather than benzoxazocines 6a,c thus supporting the assumptions. A plausible mechanistic rationale is outlined in Scheme 4. It should be firstly noted that the formation of any

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

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

• , bromopropargyloxy ester 12 was converted using [Ni(tmc)]Br2 (tmc = 1,4,8,11-tetramethylcyclam) as catalyst, leading to cyclization products 13 and 14 (Scheme 5). When 12 was electrolyzed in absence of mediator, significantly lower yields were obtained [42]. The acidity of the reaction medium strongly influences the

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• energy is the less reactive and fails to participate in the photo-Favorskii rearrangement. Wan’s work clearly demonstrates, however, that the excited state acidity of 1-naphthols is much greater than 2-naphthols and that excited-state intramolecular proton transfer (ESIPT) for 1-naphthols occurs at both

• ][45][46][48]. In non-hydroxylic solvents, the (n,π*)3 dominates which leads to the classical α- and β-homolytic cleavage and H-abstraction reactions. For 2,6-HNA and 5,8-BQA, the reduction product, a methyl ketone, probably results from homolysis. The lower excited state acidity and the poor

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• by the formation of 4-nitrobenzaldehyde. This can potentially occur by benzylic deprotonation, due to the enhanced acidity of these protons in 1o or a reactive intermediate. Such a problem was not encountered in the reactions of other benzylic alcohols. Use of K2CO3 in place of DBU did not ameliorate

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• into 22 long reaction times were required and the high acidity led to the formation of side products. Nevertheless, the target compound 22 was isolated in a moderate yield of 59%. As a milder alternative, samarium diiodide was examined for the N–O bond cleavage [40][41][42][43][44][45]. With this

A promising cellulose-based polyzwitterion with pH-sensitive charges

• Thomas Elschner and
• Thomas Heinze

Beilstein J. Org. Chem. 2014, 10, 1549–1556, doi:10.3762/bjoc.10.159

• ). Moreover, the question arises how the pKa value is influenced by further substituents. Therefore, the acidity of the ammonium groups of ω-aminoethylcellulose carbamate [23], (3-ethoxy-3-oxopropyl)(2-aminoethyl)cellulose carbamate 6 and the polyzwitterion 7a were compared. Polycation 6 was titrated forth

A complete series of 6-deoxy-monosubstituted tetraalkylammonium derivatives of α-, β-, and γ-cyclodextrin with 1, 2, and 3 permanent positive charges

• Martin Popr,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2014, 10, 1390–1396, doi:10.3762/bjoc.10.142

• of derivatizing agent along with an excess of base lead to the 6I-O-substituted products, while the preparation of 2I-O-substituted derivatives [15] takes advantage of the highest acidity of 2-OH hydroxy groups. A widely used methodology that leads to a variety of 6I-O-substituted analogues is the

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• formanilide (R = H) or chloroacetanilide (R = CH2Cl) as a substrate (Scheme 10) produced the expected phosphoramidate by a mechanism which simultaneously involved deacetylation. The higher reactivity of formanilide and chloroacetanilide, when compared to aniline, was explained by the higher acidity of the

• must be activated as a sulfonamide (or acetamide) to produce the expected phosphoramidate [42]. The authors, who used a phase-transfer agent, postulated that this activation resulted from the increase of the acidity of the N–H bond despite the evident reduction of the nucleophilic character (Scheme 14

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• cheaply available, making them seemingly ideal building blocks for the synthesis of such complex pyrone-containing molecules. As heterocyclic aromatic enols, they have a high acidity and dense functionality which leads to a diverse reactivity profile. This means that 4-hydroxy-2-pyrones are also useful

• high acidity of hydroxypyrones such as 3 (Scheme 1; R1 = H, pKa = 4.94 [13]), they would appear to be ideal coupling partners in the Mitsunobu reaction. We recently published an example of the Mitsunobu reaction using the compound 4-hydroxy-6-methyl-2-pyrone (3a) [14]. To the best of our ability, we

On the mechanism of photocatalytic reactions with eosin Y

• Michal Majek,
• Fabiana Filace and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2014, 10, 981–989, doi:10.3762/bjoc.10.97

• acidity of most Brønsted acids in DMSO [28]. These observations lead to the conclusion that photoredox reactions catalyzed by eosin Y (or similar organic dyes) cannot be discussed without strict specification of the employed form of the dye and the reaction conditions. Conclusive mechanistic proposals of

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• removed during the reaction due to the high acidity of the CF3 phosphinic acid group. The variability of Schiff bases ensures access to a range of structurally diverse phosphinic acid analogues of amino acids in the relatively simple way. Thus, we investigated the hydrophosphinylation of some Shiff bases

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• deprotected and cyclized the linear products towards the oxazole derivatives 146 in yields up to 73%. Tetrazoles In medicinal chemistry, tetrazoles are often used as carboxylic acid bio-isosteres due to their comparable acidity [114]. However, studies towards 1,5-disubstituted tetrazoles have shown that these

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

• synthesis of the imidazole core structure via a Mannich-type condensation of imines. An alternative method to activate the α-carbon atom of an isocyanide group as a nucleophile is the coordination of a metal at the terminal carbon in the isocyanide group resulting in an increase in the acidity of the α

• substituents by using methanol as a solvent. Further improvements can be achieved in the presence of a catalytic amount of AgOAc acting as a Lewis acid to improve the α-acidity of the isocyanide component. However, the presence of an electron withdrawing group in α-position of 61 is essential in any case

• one hand, as an electron withdrawing group, it decreases the nucleophilicity of the amine, thus avoiding the formation of detrimental Michael-type adducts with the alkene. On the other hand, it increases the α-acidity of the imine intermediate, thus favoring the azomethine ylide formation. Moreover

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

• 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

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• incorporation of a chiral amido-scaffold into bis(amido)cyclodiphosphazanes (cis-[R'NHP(S)(μ-NR)]2), bulky and conformationally constrained bidentate HB catalysts with an improved H-acidity should be accessible. HB interaction with donor substrates of the different structural motifs I–IV is expected to be

• dependent on the H-acidity, and on spacing and angle of the H-bond. The H-bond spacings for N,N'-dimethylthiourea and N,N'-dimethylsquaramide have been computed by the Takemoto and Rawal groups and were given to be 2.1 Å [9] and 2.7 Å [11], respectively. Computations of the H-bonding properties of both P

• –Onitrobenzene (2.19 Å). This is in accordance with the experimentally observed higher acidity [27] of thiourea over urea. Squaramide complex II forms the strongest hydrogen bonds of all computed motifs. The bond lengths NHsquaramide–Onitrobenzene are shortest with 2.11 Å while the bonding energy is highest (8.3

Four-component reaction of cyclic amines, 2-aminobenzothiazole, aromatic aldehydes and acetylenedicarboxylate

• Hong Gao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 2934–2939, doi:10.3762/bjoc.9.330

• (D) and piperidine. Then 2,3-pyrrolidinedione D transforms to the more stable enol-form through the keto–enol tautomerism. Because the enol connects to both ester and amide groups, it has much stronger acidity and is deprotonated by piperidine in the solution to give the piperidinium 2-pyrrolidinon-3

Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde

• Haijun Qu,
• Xuejian Li,
• Fan Mo and
• Xufeng Lin

Beilstein J. Org. Chem. 2013, 9, 2846–2851, doi:10.3762/bjoc.9.320

• as an inexpensive, low-toxic catalyst with moderate Lewis acidity and water-tolerance in organic chemistry [16]. Previously, we have developed some molecular iodine-catalyzed organic transformations [17][18][19][20][21], herein we describe the first molecular iodine-catalyzed one-pot three-component

• iodine is a mild catalyst with moderate Lewis acidity. Thus, a possible mechanism was proposed in Scheme 1. The first step is the condensation via the primary nitrogen of mono-substituted urea 1 with the aromatic aldehyde 3 to give the intermediate 5. Then, the enamide 6 is generated through the

3-Pyridinols and 5-pyrimidinols: Tailor-made for use in synergistic radical-trapping co-antioxidant systems

• Luca Valgimigli,
• Daniele Bartolomei,
• Riccardo Amorati,
• Evan Haidasz,
• Jason J. Hanthorn,
• Susheel J. Nara,
• Johan Brinkhorst and
• Derek A. Pratt

Beilstein J. Org. Chem. 2013, 9, 2781–2792, doi:10.3762/bjoc.9.313

• ][10][27][28]. Since the formation of the H-bonded complex is driven by both the HBA ability of the solvent and the hydrogen-bond donating (HBD) ability of the H-atom donor, the KSEs evident in the data above reflect the H-bond acidity of the various radical-trapping antioxidants we have studied. On

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• , are especially valuable as starting materials [17][18][19][20][21][22]. In these compounds the profound steric influence of the SF5 group [14][15] is accompanied by a dramatic increase in the acidity of the adjacent α-proton, a phenomenon underlying the abstraction of protons by methyllithium and a

• mentioned above, the preparation of N-ethyl 3,3,3-trifluoropropanaldimine, the Schiff base of 3,3,3-trifluoropropanal, was accompanied by enamine formation, likely as a consequence of the acidity of the proton α to the trifluoromethyl group [45][47]. Not surprisingly, 5 was relatively reactive. After

• increases the acidity of the α-proton of the imine 5 and of the iminium ion intermediate B formed on the initial nucleophilic attack of the imine on the ketene as illustrated in Scheme 4. The ring closure step requires bond formation between the iminium ion carbon and the enolate carbon B to be particularly

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• formed via a standard hydroamination reaction (Scheme 14, path a), compound 55 was formed via Brønsted acid catalysis because of the enhancement of alcohol acidity due to gold coordination (Scheme 14, path b). Under these conditions various pyrrolidines and piperidines were obtained in excellent yields

• -/hetero-nucleophilic manipulations, mono-/difunctionalizations, intra-/intermolecular transformations and regio-/stereoselective methodologies. In this chemistry, it should be mentioned that concomitant catalytic activity exerted by Brønsted acidity can not be ruled out a priori and it should not be