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

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• the pyridine ring therefore yielding the corresponding piperidine 2.63. A base-mediated Dieckmann cyclisation and Krapcho decarboxylation [77] then furnishes 2.60. Traditionally, the reduction of 2.60 to prepare 2.59 can be carried out under fairly mild hydrogenation conditions that ultimately produce

• (Scheme 30) [82]. This compound was next treated with 3-oxoglutaric acid mono ethyl ester (2.78) in the presence of sodium acetate. Decarboxylation then yields the resulting aminoester 2.79 which was progressed through an intramolecular Mannich-type transformation using aqueous formaldehyde to allow

Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support

• Jagdish D. Tibhe,
• Hui Fu,
• Timothy Noël,
• Qi Wang,
• Jan Meuldijk and
• Volker Hessel

Beilstein J. Org. Chem. 2013, 9, 2168–2179, doi:10.3762/bjoc.9.254

• starting materials and products is the major factor of being restricted to a maximum of 40% yield. Here, removal of the product from the enzyme thereby readjusting the equilibrium is the method of choice. One opportunity to achieve this could be the decarboxylation of phenylserine as depicted in Scheme 2

• microreactor. Analysis of the four isomers of phenylserine on a chiral column. Phenylserine synthesis. Synthesis of chiral α-aminoalcohol by telescoping aldolase reaction with decarboxylation. Comparison of direct and indirect method. Comparison of productivity between the theoretical calculations and

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• molecules of imine 37 is catalyzed by the oxidase StaD and gives lycogalic acid A (38) [26][27][28]. StaP and StaC convert 38 into staurosporinone (30) via an intramolecular aryl–aryl coupling and an oxidative decarboxylation [29][30]. Formation of the N-glycosidic bonds is carried out by StaG/StaN and

• dioxolane formation gives stephanine (124). It is hypothesized that direct oxidation of 124 forms 4,5-dioxoaporphine 125, which upon benzilic acid rearrangement, N-methyl cleavage and decarboxylation provides aristolactam I (113) [96]. Additional oxidation of the amide function furnishes aristolochic acid I

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• ], glycosylglycerides [14][15], phosphoglycolipids [16], and various sphingolipids [17][18][19]. The terminal isopropyl group of the iso-fatty acids arises from valine and leucine, which through transamination and decarboxylation reactions yield isobutyryl-CoA and isovaleryl-CoA [20]. These starter units are elongated

• approaches have been used: (1) two-component cross-couplings that include α-ketoester alkylation/decarboxylation [32][33], aldehyde–olefin photoaddition [34], acetylide alkylation (sp3–sp) [35][36], Wittig coupling [3][21][37][38][39], Kolbe electrosynthesis [35][40][41][42], organocadmium (sp2–sp3) [43][44

Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones

• Robert J. Perkins,
• Hai-Chao Xu,
• John M. Campbell and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2013, 9, 1630–1636, doi:10.3762/bjoc.9.186

• Robert J. Perkins Hai-Chao Xu John M. Campbell Kevin D. Moeller Washington University in Saint Louis, Saint Louis, Missouri 63130, United States 10.3762/bjoc.9.186 Abstract Carboxylic acids have been electro-oxidatively coupled to electron-rich olefins to form lactones. Kolbe decarboxylation does

• taken because of the well-known Kolbe electrolysis reaction (Scheme 3) [10][11]. In the Kolbe electrolysis (Scheme 3, reaction 1), a carboxylic acid is oxidized. A decarboxylation reaction then leads to the formation of a radical that is subsequently trapped by a second radical formed in solution. The

• reaction has been used to form dimers [12], as well as in some cases cyclic products (Scheme 3, reaction 2) [13][14][15]. However, the chemistry highlighted in Scheme 2 suggests that a Kolbe-type decarboxylation reaction might not interfere at all with an oxidative coupling reaction between a carboxylic

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• decarboxylation enables construction of the C15−C16 bond by an aldol reaction. The product of this transformation is of the correct oxidation state and potentially three steps removed from the targeted epoxide fragment. Keywords: catalysis; natural product; nickel; reductive coupling; ripostatin A; synthesis

• recognized that reaction of the enolate of ester 45, a compound previously synthesized in just two steps, and subsequent oxidation could give the β-ketoester 61. Decarboxylation of this compound would provide rapid access to the key iodocyclization substrate 55. Aldehyde 62 was prepared by reduction of the

• . Initially, we attempted to induce decarboxylation of 61 by treatment with LiOH in a 1:1 water/THF mixture. No reaction was observed at room temperature, but heating to 70 °C resulted in elimination of the β-siloxy group. The Krapcho reaction offers an essentially neutral method for the decarboxylation of

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• . Retrosynthetically, we envisioned propyleine (12) to come from the decarboxylation reaction of vinylogous carbamic acid 15 [10][28], which could be derived from stereoselective hydrogenation of the endocyclic olefin in tricycle 16 (Scheme 4). Vinylogous urethane 16 should be accessible via our intramolecular aza-[3

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

• Stephan Klopries,
• Uschi Sundermann and
• Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75

• modular approach to our synthesis with an intrinsic transferability to variously substituted malonates. After optimization, mono-t-Bu-protected malonate provided the best starting point for the synthesis (Scheme 1) [34]. The sterically demanding protective group prevented decarboxylation during the

• of the desired product at low reaction rates with no detectable decarboxylation of the products. In contrast, TFA-promoted cleavage resulted in quantitative decarboxylation even at low temperatures, low acid concentrations and short reaction times. Subsequently, Lewis-acid-mediated reactions were

1-n-Butyl-3-methylimidazolium-2-carboxylate: a versatile precatalyst for the ring-opening polymerization of ε-caprolactone and rac-lactide under solvent-free conditions

• Astrid Hoppe,
• Faten Sadaka,
• Claire-Hélène Brachais,
• Gilles Boni,
• Jean-Pierre Couvercelle and
• Laurent Plasseraud

Beilstein J. Org. Chem. 2013, 9, 647–654, doi:10.3762/bjoc.9.73

• pentaerythritol as initiator alcohols, and the products were fully characterized by 1H and 13C{1H} NMR spectroscopy, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). BMIM-2-CO2 acts as an N-heterocyclic carbene precursor, resulting from in situ decarboxylation, either by heating

• decarboxylation, thus generating active carbene species, which occurs either by heating [51] or by the addition of Na+ or K+ (NaBPh4, KPF6) [47]. In this paper, we apply this dual approach to the solvent-free ROP of ε-caprolactone and rac-lactide using 1-n-butyl-3-methylimidazolium-2-carboxylate (BMIM-2-CO2) as a

• experimental and calculated Mn are low, and the PDIs measured by GPC indicate a poor control of molecular weight distribution. An alternate approach for the solvent-free ROP (method B, Scheme 1), based on the use of sodium cations as decarboxylation agent and circumventing vacuum conditions, was also tested

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• formation of the amidyl radical in this case calls for a different precursor and does not involve a stannane reagent. The sequence is triggered by the attack of undecyl radicals on thiosemicarbazone 12. Undecyl radicals arise from the thermal homolysis of lauroyl peroxide and decarboxylation. The lauroyl

• increases considerably the convergence of the synthetic scheme. One such instance is pictured in Scheme 4, whereby cyclobutyliminyl radical 17, generated from 16 by a modified Barton decarboxylation [16], undergoes a regioselective scission into secondary radical 18, followed by an initial intermolecular

• , exposure of bis-sulfone 25 to trimethylaluminium causes the regioselective replacement of the terminal sulfone with a methyl group to give compound 26 in good yield. The Barton decarboxylation reaction is an exceptionally powerful method that deserves without doubt a much greater attention from synthetic

N-Heterocyclic carbene–palladium catalysts for the direct arylation of pyrrole derivatives with aryl chlorides

• Ismail Özdemir,
• Nevin Gürbüz,
• Nazan Kaloğlu,
• Öznur Doğan,
• Murat Kaloğlu,
• Christian Bruneau and
• Henri Doucet

Beilstein J. Org. Chem. 2013, 9, 303–312, doi:10.3762/bjoc.9.35

• -methylpyrrole-2-carboxylate (25) also reacts with 4-chlorobenzonitrile (11) to give 26 in good yields with catalysts 2, 8 and 9 (Table 3). No significant decarboxylation of the pyrrole derivative was observed in the course of this reaction. Three aryl chlorides have also been coupled with 1-methylpyrrole (27

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• reported the K2CO3-mediated tandem reaction of salicylaldehyde derivatives of type 43 and α,β-unsaturated ester 44 in the synthesis of 2,2-dimethylchromene 45 in moderate yields (Scheme 17) [34]. The dehydration reaction in this case was accompanied by decarboxylation. The best yields were achieved when

Preparation of mixed trialkyl alkylcarbonate derivatives of etidronic acid via an unusual route

• Petri A. Turhanen,
• Janne Weisell and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2012, 8, 2019–2024, doi:10.3762/bjoc.8.228

• etidronate and alkyl chloroformate was developed by utilizing unexpected demethylation and decarboxylation reactions. The reaction with the sterically more hindered isobutyl chloroformate at a lower temperature (90 °C) produced the P,P'-diester (2) as a stable intermediate product. A possible reaction

• chloroformate, also the corresponding P,P'-diester 2 was isolated according to the 13C NMR spectrum and mass spectrometry. Most probably this rearrangement from carbonate 6 to ester 7 proceeds by decarboxylation in conjunction with the 1,5-migration of an alkyl group from the carbonate oxygen to the phosphorus

• likely that the observed rearrangement is based on a six-membered transition state, in which the anchimeric assistance of the P=O group permits 1,5-alkyl migration and irreversible decarboxylation, leading to intermediate 7. Similar pyrolytic elimination reactions were studied intensively ca. 60 years