Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• the stereochemistry of the less common extender units, labeling studies indicate that the (2S) isomer of ethylmalonyl-CoA is also used [39], which correlates with it originating predominantly from the reductive carboxylation of crotonyl-CoA [40]. Several extender units including aminomalonyl-ACP [41

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

• Maurizio Selva,
• Alvise Perosa,
• Sandro Guidi and
• Lisa Cattelan

Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181

• should therefore implement greener reactions, such as the direct carboxylation of diols by CO2, for which however, effective catalysts are currently not available. The Asahi Kasei process also highlights that the synthesis of DMC by transesterification of ethylene carbonate with methanol does not

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• previously reported [8]. Palladium catalysed carboxylation [9] was explored with aryl iodides 5 or 6/7 as a mixture, and these gave the corresponding ethyl esters 8 and 9/10, respectively. The meta and para esters 9 and 10 were easily separated by chromatography. Hydrolysis of esters 8–10 using

• -tetrafluorocyclohexane motif has been incorporated in a range of products prepared from aryl iodides 5–7. These derivatives derive from aryl carboxylation or carbonylation, and complement those that can be prepared directly by electrophilic aromatic substitution of phenyl derivative 4. This chemistry should more readily

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• oxolane bridge between C1 and C7. Hajos–Parrish diketone (107) [39] served as the starting material for the preparation of key intermediate 112. Selective reduction of the ketone and silylation of the resulting alcohol furnished enone 108. α-Carboxylation of the enone with magnesium methyl carbonate and a

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• generated through oxidation of inorganic chemicals (chemoautotrophs) [47]. As detailed in Scheme 1, the carbon fixation step entails the carboxylation of ribulose-1,5-bisphosphate (1), generating two equivalents of 3-phosphoglycerate (2) and is catalysed by ribulose-1,5-bisphosphate carboxylase oxygenase

• decarboxylation. In some autotrophs this pathway is known to operate in the reverse (reductive) direction resulting in CO2 fixation through carboxylation [52]. Autotrophic fixation through the reductive TCA cycle was first described by Arnon and Buchanan [53], and hence is also referred to as the Arnon–Buchanan

• two steps catalysed by NAD(P)H dependent dehydrogenases. Later in the pathway, propionyl-CoA (17) is the substrate for a second carboxylation with HCO3− to methylmalonyl-CoA (18), performed by the same ATP-dependent bifunctional carboxylase that carries out the first step [71][72]. Succinyl-CoA (5) is

Surprisingly facile CO₂ insertion into cobalt alkoxide bonds: A theoretical investigation

• Willem K. Offermans,
• Claudia Bizzarri,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 1340–1351, doi:10.3762/bjoc.11.144

• calculations to elucidate the reaction step of CO2 insertion into cobalt(III)–alkoxide bonds, which is also the central step of metal catalysed carboxylation reactions. It was found that CO2 insertion into the cobalt(III)–alkoxide bond of [(2-hydroxyethoxy)CoIII(salen)(L)] complexes (salen = N,N”-bis

• cycloaddition. Direct catalytic carboxylation of aliphatic compounds and arenes by rhodium(I)– and ruthenium(II)–pincer complexes, respectively. Insertion of carbon dioxide into a metal–oxygen bond via a cyclic four-membered transition state. R is either an aliphatic or aromatic group. Facile CO2 uptake by zinc

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• important pharmaceutical. The Kirschning group (2013) also demonstrated a multi-step flow synthesis of the antidepressant amitriptyline (127) [105]. They developed a sequence harnessing reactions at several different temperature regimes allowing processing of low temperature lithiation and carboxylation

• intermediate passes into a tube-in-tube reactor, where carboxylation takes place furnishing the lithium carboxylate 129. Excess carbon dioxide is subsequently removed using a degassing tube before reacting species 129 with a further stream of n-BuLi to induce cyclisation to dibenzosuberone (130) in a short

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

• -diazabicycloundec-7-ene (DBU) is reported. This reaction provides convenient access to the biologically important compounds 4-hydroxy-2H-chromen-2-one and 4-hydroxy-2(1H)-quinolinone in moderate to good yields using carbon dioxide as the carboxylation reagent. An acyl migration from nitrogen to carbon is observed

• in the reaction of o-acetamidoacetophenone. Keywords: acyl migration; carbon dioxide; carboxylation; cyclization; condensation; Introduction 4-Hydroxy-2H-chromen-2-ones and 4-hydroxy-2(1H)-quinolinones are key structural subunits found in many natural products [1], commercial drugs [2][3] and

• availability and toxicity of the starting materials, environmental benignity and economical concerns, the development of an alternative method for the synthesis of these compounds using carbon dioxide as the carboxylation reagent [9][10][11][12][13][14][15][16] is highly desirable. It was previously reported

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

Microsolvation and sp²-stereoinversion of monomeric α-(2,6-di-tert-butylphenyl)vinyllithium as measured by NMR

• Rudolf Knorr,
• Monika Knittl and
• Eva C. Rossmann

Beilstein J. Org. Chem. 2014, 10, 2521–2530, doi:10.3762/bjoc.10.263

• generated arylalkyne [14] with formation of 6 and 8a. After carboxylation and aqueous work-up, the acidic product fraction contained only the arylpropiolic acid (δH = 1.56 and 7.33 ppm in CDCl3) derived from 6 but not the α-arylacrylic acid to be expected from 4. In t-BuOMe as the solvent, bromoalkene 3 was

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• % H2SO4 in water, no C6 product is formed (Table 1, entry 1). Only in an anhydrous catholyte and anolyte, applying MgO in the anolyte as reducing agent, the carboxylation becomes more selective for C6, reaching appreciable current efficiencies (Table 1, entry 2). Furthermore, the presence of water in the

• generated at the anode, cathodes with high hydrogen overpotential, like mercury and lead, are necessary to minimize current loss through hydrogen gas formation [41][42]. The counter ion seems to have a significant influence on the fate of the cathodically formed CO2•− radical anion. For carboxylation of a

• system appear to be less reactive towards CO2 fixation, due to steric hindrance and the presence of electron donating substituents [49][51]. However, working at atmospheric CO2 pressures and at lower current densities allows effectively performing the double carboxylation of internal conjugated double

Synthesis, characterization and DNA interaction studies of new triptycene derivatives

• Sourav Chakraborty,
• Snehasish Mondal,
• Rina Kumari,
• Sourav Bhowmick,
• Prolay Das and
• Neeladri Das

Beilstein J. Org. Chem. 2014, 10, 1290–1298, doi:10.3762/bjoc.10.130

• frameworks (MOFs) with applications including but not limited to catalysis and gas uptake/storage [37][38][39][40][41][42]. It is well known that terminal alkynes can be conveniently subjected to carboxylation using CO2 to yield the corresponding alkynyl carboxylic acids. As shown in Scheme 2, 2,6,14

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

• review on organosilver compounds by Pouwer and Williams exhaustively highlights all these aspects of silver chemistry [100]. For example, functionalized propiolic acids can be selectively prepared by an AgI catalyzed carboxylation of terminal alkynes with CO2 under ligand free conditions with the

• intermediacy of an organosilver compound, namely silver acetilide (Csp–Ag) [101]. The direct carboxylation of active C–H bonds of (hetero)arenes [102] and terminal alkynes [103] with CO2 in the presence of copper or gold-based catalysts has also been reported. However, these latter transformations require

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

• . The latter side-products (ca. 10%) were formed against a substantially increasing repulsive resistance, as testified through the diminished rotational mobility of their aryl groups. As a less troublesome further side-product, the dianion of the above key acid was recognized through carboxylation which

• , we applied nonaqueous quenching of residual 34, using either carboxylation by solid CO2 or the commended treatments with aniline [41] as the proton donor or with Me3SiCl [40] prior to the aqueous work-up. However, none of these three precautionary measures improved the 38/39 ratios (ca. 9:1 after ca

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

• carbon dioxide transfer in the formation of ketoacetates [46][47] and carboxylation of epoxides [48]. Some of us have recently reported a green application of BMIM-2-CO2, highlighting its efficiency for the conversion of raw glycerol to glycerol carbonate by transesterification [49]. More recently, this

NHC-catalysed highly selective aerobic oxidation of nonactivated aldehydes

• Lennart Möhlmann,
• Stefan Ludwig and
• Siegfried Blechert

Beilstein J. Org. Chem. 2013, 9, 602–607, doi:10.3762/bjoc.9.65

• with 15 mol % of an NHC-salt, DBU and CO2 has been reported by Nair et al. [24]. However Bode et al. recently concluded that oxygen is the oxidant in these reactions [25]. An oxidative carboxylation of activated arylaldehydes with 10% water in DMF by 5 mol % of a sulfoxylalkyl-substituted NHC has been

Polar reactions of acyclic conjugated bisallenes

• Reiner Stamm and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 36–48, doi:10.3762/bjoc.9.5

• spectrum the acetylenic (δ 74.2 and 83.8 ppm) and tertiary carbon atoms (δ 41.4 and 66.7 ppm) are clearly visible as singlets. All other spectroscopic details agree with the proposed structure (Supporting Information File 1). Miscellaneous reactions of 2 and 4 with electrophiles The carboxylation of simple

Stereoselective synthesis of tetrasubstituted alkenes via a sequential carbocupration and a new sulfur–lithium exchange

• Andreas Unsinn,
• Cora Dunst and
• Paul Knochel

Beilstein J. Org. Chem. 2012, 8, 2202–2206, doi:10.3762/bjoc.8.248

• was quenched with typical electrophiles with a high retention of the double-bond geometry. Thus, the treatment of 7a with EtI (2 equiv, −78 °C, 15 min) provides the tetrasubstituted alkene 5a in 75% yield and an E/Z ratio of 1:99. Direct carboxylation by the reaction with ethyl chloroformate (1.1

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• cyclization of alkenylindoles by Pd(II) catalysis under carbonylative conditions [81][82]. This approach, based on the use of copper(II) chloride as oxidant, has been applied to 2- and 3-alkenylindoles, resulting in a domino process that involves an alkenylation/carboxylation sequence (Scheme 23). Thus

• alkenylation/carboxylation sequence was successfully performed by reaction of styrene compounds with 2-substituted indoles to give 3-benzylindoles bearing an ester group (Scheme 24). It should be pointed out that the presence of a functional group at the C-2 indolyl position is essential to obtain a

• . The subsequent transfer of carbon monoxide with stereochemical retention determines the generation of the σ-acyl-palladium complex XVIII, which in turn is converted in the final cis-substituted tetrahydrocarbazole by methanolysis giving the carboxylation step. Again, the released Pd(0) species

Novel fatty acid methyl esters from the actinomycete Micromonospora aurantiaca

• Jeroen S. Dickschat,
• Hilke Bruns and
• Ramona Riclea

Beilstein J. Org. Chem. 2011, 7, 1697–1712, doi:10.3762/bjoc.7.200

• from [2H5]sodium propionate is in agreement with the biosynthesis of FAs (Scheme 1): One deuterium is lost during carboxylation of propionyl-CoA to yield methylmalonyl-CoA, the second is possibly exchanged with water due to the C,H-acidity of malonyl-CoA derivatives, but it is lost, at the latest, in

Structural conditions required for the bridge lithiation and substitution of a basic calix[4]arene

• Conrad Fischer,
• Wilhelm Seichter and
• Edwin Weber

Beilstein J. Org. Chem. 2011, 7, 1602–1608, doi:10.3762/bjoc.7.188

• the lower-rim site as well as tert-butylated or non-tert-butylated upper-rim positions. Whereas this reaction fails for symmetric calix[4]arene ethers with alkoxy residues greater than methoxy, the carboxylation of mixed methoxy-propoxy calixarene ethers is possible. In connection with this, several

• undergo lithiation and subsequent carboxylation to yield the carboxylic acid 6 [4], we became interested in the question of whether the upper-rim unsubstituted calix[4]arene 1, as well as higher ether homologues, such as 3 and 4, can also be used for this reaction (Scheme 1). While the upper-rim site

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• regioselective functionalization. Ortho-lithiation by means of alkyllithium and lithium amides bases has been extensively developed as lithiated species display a high reactivity towards many electrophiles, leading to various substitutions (e.g., halogenation, carboxylation, acylation, hydroxymethylation

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

• methodology. Thus, ortho-deprotonation of diethylamide 16 (Scheme 3) and carboxylation afforded anhydride 17 directly after workup with 12 N aqueous HCl. Fischer esterification and condensation of the resultant 18 with diethyl succinate, according to Kelly [6][7], afforded 19, which was then elaborated to a 1

Scalable synthesis of (1-cyclopropyl)cyclopropylamine hydrochloride

• Sergei I. Kozhushkov,
• Alexander F. Khlebnikov,
• Rafael R. Kostikov,
• Dmitrii S. Yufit and
• Armin de Meijere

Beilstein J. Org. Chem. 2011, 7, 1003–1006, doi:10.3762/bjoc.7.113

• degradation [19][20]. Results and Discussion Preparation of the acid 2 from the known 1-bromo-1-cyclopropylcyclopropane (1) [21][22] according to the published procedure [17] was accomplished on a 100 g scale (Scheme 1). However, the yield of the carboxylation on a scale of 12.4 mmol, 900 mmol and 1400 mmol

The role of silver additives in gold-mediated C–H functionalisation

• Scott R. Patrick,
• Ine I. F. Boogaerts,
• Sylvain Gaillard,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2011, 7, 892–896, doi:10.3762/bjoc.7.102

• a carboxylation reaction [12] with substrate 2 using catalyst 1 under optimised carboxylation conditions (Scheme 3). The general procedure employed 2, 1 (3 mol %), Ag2O (3 mol %) and three equivalents of potassium hydroxide. Gratifyingly, whereas a reaction in the absence of silver leads to no

• carboxylation product, the addition of silver leads to formation of 2,4,6-trifluorobenzoic acid (5). The use of a stoichiometric amount of Ag2O results in aggregation of the reagents that seemingly affects mass transport of CO2 and halts the reaction. However, the catalytic use of Ag2O gave a 22% isolated yield

• of 5. This observation clearly shows that silver can have a positive role in the carboxylation of C–H bonds. Conclusion The C–H functionalisation of arenes using (NHC)gold(I) complexes has been shown to be significantly affected by the leaving group on the gold. The gold(I) chloride may only react by