Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

• Dnyaneshwar N. Garad,
• Subhash D. Tanpure and
• Santosh B. Mhaske

Beilstein J. Org. Chem. 2015, 11, 1008–1016, doi:10.3762/bjoc.11.113

• synthesis of imides from the combination of aliphatic amines and unsaturated anhydrides. Plausibly, the intermediate amic acid in these cases may be prone to decarboxylation [57] and radical polymerization similar to the acrylamide polymerization using APS as a radical initiator [55]. Encouraged by this

DBU-promoted carboxylative cyclization of o-hydroxy- and o-acetamidoacetophenone

• Wen-Zhen Zhang,
• Si Liu and
• Xiao-Bing Lu

Beilstein J. Org. Chem. 2015, 11, 906–912, doi:10.3762/bjoc.11.102

• thermodynamically stable coumarins. Importantly, the use of an intramolecular in situ trap avoids the problem of decarboxylation during workup. In case of o-acetamidoacetophenones, an acyl migration from nitrogen to carbon was observed. The cross experiment showed that the N to C acyl shift occurred

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• Knoevenagel/reduction/hydrolysis/decarboxylation pathway (steps a–d in Scheme 4) to carboxylic acid 10 suffered from low yields of the last two steps (total yield 33%). The attempt to obtain 5a directly from 9 by means of Krapcho decarboxylation [33] failed, as the product was contaminated with inseparable

Trifluoromethyl-substituted tetrathiafulvalenes

• Olivier Jeannin,
• Frédéric Barrière and
• Marc Fourmigué

Beilstein J. Org. Chem. 2015, 11, 647–658, doi:10.3762/bjoc.11.73

• and Discussion Syntheses The reported preparation of 2bc is based on the coupling reaction of the trithiocarbonate 5 with the dithiocarbonate 6bc, affording also the symmetrical coupling product 4bc (Scheme 3) [31]. Further decarboxylation of 2bc with LiBr/DMF afforded 1c while reaction with NH3 in

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

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

• formation of 4 is described in Scheme 5. Initially alkynoic acid 2 undergoes decarboxylation to form the copper acetylide (A) in the presence of the Cu+ catalyst which is generated by the reduction of Cu2+ with sodium ascorbate. The obtained copper acetylide undergoes regioselective [3 + 2] cycloaddition

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• intermediate 2 undergoes decarboxylation to form 3 through Baeyer–Villiger oxidation to form the 7-membered lactone 4, then hydrolyzation, decarboxylation and lactonization to finally give aspergiloid I (1). Aspergiloid I (1) was evaluated for its cytotoxicity against eleven human cancer cell lines, K562

Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate

• Amjid Iqbal,
• El-Habib Sahraoui and
• Finian J. Leeper

Beilstein J. Org. Chem. 2014, 10, 2580–2585, doi:10.3762/bjoc.10.270

• ; pyruvate decarboxylase; thiamine diphosphate; Introduction The biologically active form of vitamin B1 is thiamine diphosphate (ThDP, 1, Figure 1), which is an essential cofactor and involved in a number of metabolic pathways, including oxidative and non-oxidative decarboxylation of α-keto acids (e.g

• Breslow [3][4], is given in Scheme 1. After formation of the ThDP ylid, the keto group of the substrate is attacked by the thiazolium C-2 carbanion to form the tetrahedral pre-decarboxylation intermediate 2-(2-lactyl)-ThDP, LThDP. It has been proposed that the covalent attachment of pyruvate to form LThDP

• introduces significant strain, the release of which is a driving force for the decarboxylation [5]. The effects of this type of strain on bond angles and lengths have recently been observed in a high resolution crystal structure of another ThDP-dependent enzyme, transketolase [6]. Another important factor of

(CF₃CO)₂O/CF₃SO₃H-mediated synthesis of 1,3-diketones from carboxylic acids and aromatic ketones

• JungKeun Kim,
• Elvira Shokova,
• Victor Tafeenko and
• Vladimir Kovalev

Beilstein J. Org. Chem. 2014, 10, 2270–2278, doi:10.3762/bjoc.10.236

• recently reported by us [27] and decarboxylation was subsequently carried out, 1,3-diphenylphosphorylated acetone 5 could be obtained (reaction 2 in Scheme 2). The two-stage one-pot reaction of γ-phenylbutanoic acid (1c) and 3-hydroxy-1-adamantylacetic acid (1k) gave as a result the trifluoroacetylated

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• palladium catalysis and subsequent decarboxylation yielded enone 118 as a single diastereomer. Addition of the Li anion of phosphonamide 24c to enone 118 afforded adduct 119 as a single isomer, with the attack occurring to the less hindered face of the enone. Further elaboration of the side chain was

An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• synthetic route to prepare 1 using cheap and commercially available diethyl 2-acetamidomalonate (4) and propargyl alcohol. The desired product 1 was obtained via alkylation of malonate 4 with propargyl tosylate followed by a one-pot four-step sequence of hydrolysis, decarboxylation, diazotization and

• economical and safe procedure using diethyl 2-acetamidomalonate (4) and propargyl alcohol as starting materials to synthesize 1. The synthesis was completed via alkylation of malonate 4 with propargyl tosylate followed by a one-pot four-step sequence of hydrolysis, decarboxylation, diazotization and

• sequential hydrolysis of amide and esters, and decarboxylation of the resulting malonic acid. The resulting intermediate 6 was not isolated and used directly for the subsequent reaction. Notably, basic treatment of 5 as discussed in literature [31][33] would not allow conversion of 5 to 6 in a convenient one

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• ester is utilised as a building block for the synthesis of 2-fluoro-2-arylacetic acid and fluorooxindole derivatives by a strategy involving nucleophilic aromatic substitution reactions with ortho-fluoronitrobenzene substrates followed by decarboxylation, esterification and reductive cyclisation

• structure of isolated diester 3 was confirmed by X-ray crystallography (Figure 1). In initial experiments, decarboxylation of 3 by reaction with potassium hydroxide gave good yields of the corresponding 2-fluoro-2-arylacetic acid 4a. However, in subsequent experiments, we found that further purification of

• the diester 3 after the initial SNAr step was not necessary and decarboxylation of crude diester 3 gave 4a very efficiently. Consequently, in all analogous experiments (Table 1), crude product diesters of type 3 were isolated and used without further purification, allowing the ready synthesis of a

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

• did not improve in the cases of methyl, isopropyl or benzyl esters (Table 2, entries 2–4). The mechanism of the reaction was proposed based on the kinetic studies of the malonic acid half thioester system by Shair [33]. Essentially β-keto acids can undergo decarboxylation or deprotonation to generate

• enolates. Though in the case of enzymatic reactions, decarboxylation occurs first to form the enolates, followed by condensation with esters; it is believed that in the scandium-catalysed aldol process of β-keto acid, similar to the case of malonic acid half thioesters, decarboxylation happens after the

• addition to the ester (Scheme 2). First, deprotonation and enolisation of 9 followed by addition of α-keto ester 2 gives intermediate 11. After decarboxylation to afford 12, a protonation step occurs late in the reaction pathway to form the aldol product 3 and completes the mechanistic cycle. Conclusion We

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• N-aryl-3-hydroxyisoindolinones with diethyl malonate and subsequent hydrolysis, decarboxylation and Friedel–Crafts acylation sequence also result in the formation of isoindolo[2,1-a]quinolones [16][17]. N-aryl-3-hydroxyisoindolinones with an aptly positioned alkene moiety at the ortho position of

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• indazole 3 has been generated by thermal decarboxylation of indazolium-3-carboxylates 1 [20] which belong to the class of pseudo-cross-conjugated heterocyclic mesomeric betaines (Scheme 1). Its properties have been calculated [20][21] and examined by means of vibrational spectroscopy [21]. It was shown

• that pseudo-cross-conjugated mesomeric betaines decarboxylate readily in the absence of stabilizing effects such as hydrogen bonds to protic solvents or water of crystallization [18][19]. Thus, the Gibbs free energy difference for the decarboxylation of 1,2-dimethylindazolium-3-carboxylate under

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

•  8. Insoluble in the reaction mixture phosphinic acid 37 was filtered off and characterized. 31P NMR analysis of filtrate showed the presence of adduct 35 and the decarboxylation product 36 in an approximate 1:10 ratio along with starting esters 3 and 4 and (trifluoromethyl)phosphonic acid (10) (<5

• to the activated C=C double bond of malonate 38 followed by hydrolysis and decarboxylation to generate adduct 39 in two steps (Scheme 10). Conclusion In conclusion, we have presented a variety of approaches to novel fluorinated (1-aminoalkyl)phosphinic acids starting from the appropriate fluorinated

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

Practical synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides via conventional and decarboxylative copper-free Sonogashira coupling reactions

• Andrea Caporale,
• Stefano Tartaggia,
• Andrea Castellin and
• Ottorino De Lucchi

Beilstein J. Org. Chem. 2014, 10, 384–393, doi:10.3762/bjoc.10.36

• ] or the Pd-catalyzed decarboxylation of allyl propiolates [69] have been reported, but these methods are limited to a narrow class of substrates and are not well suited for the preparation of aryl alkynes. More recently an optimized protocol for the synthesis of terminal arylalkynes from propiolic

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

• of aldehydes by using ClCF2CO2Na/PPh3 [19]. In 1967, Burton and Herkes suggested that the ylide intermediate involved in the olefination process was more likely to be formed by the decarboxylation of a difluorinated phosphonium salt rather than the combination of :CF2 and a phosphine (Scheme 1

Tuning the interactions between electron spins in fullerene-based triad systems

• Maria A. Lebedeva,
• Thomas W. Chamberlain,
• E. Stephen Davies,
• Bradley E. Thomas,
• Martin Schröder and
• Andrei N. Khlobystov

Beilstein J. Org. Chem. 2014, 10, 332–343, doi:10.3762/bjoc.10.31

• conditions and undergoes decarboxylation to form an insoluble amide compound 12. This reaction under acidic conditions is characteristic of carboxylic acids that contain an electron withdrawing substituent in the α-position [23]. To prevent decarboxylation processes we modified the linker to exclude the

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants^§

• Rudolf Knorr,
• Thomas Menke,
• Johannes Freudenreich and
• Claudio Pires

Beilstein J. Org. Chem. 2014, 10, 307–315, doi:10.3762/bjoc.10.28

• NMR signals). The constitution of 40 followed from its ready decarboxylation in CDCl3 solution at rt to regenerate acid 10 within four days. Conversion of the ketone 38a into bromoalkene 42a through brominative deoxygenation [42][43] with tribromide 41 was slow in hot chloroform but almost complete

• recrystallization from hot toluene afforded clean 40 (30 mg) but led to the decarboxylation of a portion that remained dissolved. The transparent needles of pure 40 had a mp of 195–197.5 °C (dec.), decomposed slowly on standing at rt in CDCl3 solution, and were weakly soluble in CCl4 only as long as they were a

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• . The resulting major alcohol was protected, followed by saponification of the ester with concomitant removal of the TBDPS-protecting group. The resulting free alcohol was then re-protected to give bicycle 40. Barton decarboxylation was then achieved using standard conditions, followed by trapping of

• , reduction of the remaining double bond and subsequent Krapcho decarboxylation [132] resulted in less functionalized ketone 150. Aldol condensation with furfural followed by O-allylation and Claisen rearrangement furnished enone 151. Standard functional group interconversiones were used to access TIPS

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• aroylacrylic acids as dipolarophiles has been realized through a one-pot 1,3-dipolar cycloaddition protocol. Decarboxylation of 2'-aroyl-2-oxo-1,1',2,2',5',6',7',7a'-octahydrospiro[indole-3,3'-pyrrolizine]-1'-carboxylic acids is accompanied by cyclative rearrangement with formation of dihydropyrrolizinyl

• undergoes decarboxylation via ring opening of the spiro cycle. The subsequent enolization of the intermediate leads to the formation of the dihydropyrrolizinyl oxindole system. Conclusion The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatins and sarcosine or cyclic amino acids to

Synthesis of novel derivatives of 5-hydroxymethylcytosine and 5-formylcytosine as tools for epigenetics

• Anna Chentsova,
• Era Kapourani and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 7–11, doi:10.3762/bjoc.10.2

• , decarboxylation of the 5caC by an unknown decarboxylase excluding action of BER should also be considered [15][23]. This variety of demethylation pathways might indicate that different tissues utilize different demethylation pathways [1][24]. While DNA methylation is usually associated with gene repression [8][25

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• aryldifluoroacetates and KF-promoted decarboxylation, a variety of difluoromethyl aromatics [57]. Unlike previous protocols where an excess of copper is required, this approach presents some advantages such as: (i) stability and availability of the required 2-silyl-2,2-difluoroacetates from trifluoroacetates or

• the double bond and the iodonium ion to provide intermediate C. The presence of HF in the reaction medium promotes the decarboxylation step in intermediate C, and subsequent reductive elimination leads to the formation of the thermodynamically stable E-alkene. Finally, protonation of intermediate E

• readily available nucleophilic trifluoromethyl source after decarboxylation at high temperature in the presence of stoichiometric amounts of copper salts [78][79]. In 2011, Y. M. Li et al. showed that the Cu-catalyzed C–CF3 bond formation of iodoarenes could be achieved by using a sodium salt of