Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• has been reported that nitration and bromination of 2 take place at the 1-position (however, the bromine atom in 1-bromopyrene can migrate into the 4-position in the presence of AlCl3) [8][9], whereas Friedel–Crafts acylation and Vilsmeier formylation take place at the 4-position [10]. We recently

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• of aroyl building block 9 (Scheme 1). Vilsmeier formylation of 1,3-dihydroxy-5-methylbenzene (5) gave 2,4-dihydroxy-6-methylbenzaldehyde (6) in 75% yield [25][26]. Then compound 6 could react with methyl iodine in acetone by using K2CO3 as base. The obtained 2,4-dimethoxy-6-methylbenzaldehyde (7) was

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

Reactions of N,3-diarylpropiolamides with arenes under superelectrophilic activation: synthesis of 4,4-diaryl-3,4-dihydroquinolin-2(1H)-ones and their derivatives

• Larisa Yu. Gurskaya,
• Diana S. Belyanskaya,
• Dmitry S. Ryabukhin,
• Denis I. Nilov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 950–956, doi:10.3762/bjoc.12.93

• intermediate cationic species A and B (Scheme 1), that complicated this reaction. Thus, reaction of amides 1 with benzene and some other arenes in TfOH is an effective way to 4,4-diaryl-3,4-dihydroquinolin-2(1H)-ones 2. To show the synthetic potential of dihydroquinolinones 2 their N-formylation and N

• , B under the superelectrophilic activation. N-Formylation and N-acylation of dihydroquinolinones 2. Superelectrophilic activation of the N-formyl group of compounds 5 and their reaction with benzene. Reactions of amides 1a–u with benzene (and other arenes) under superelectrophilic activation, leading

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

• trifluoroacetic acid (TFA) or 6 M HCl in dioxane [10] gave the corresponding benzoic acids 11, 12, and 13 as illustrated in Scheme 1. Direct palladium catalysed formylation of aryl iodides 6/7 as a mixture was explored using Pd(PPh3)4, Bu4SnH and CO [11]. This generated benzaldehyde derivatives 14 and 15 in a 1:3

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

• needed for the radical precursors was made in high yield as shown in Scheme 3. Vilsmeier–Haack formylation [25] of ene-sulfonamide 20 was followed by sodium chlorite oxidation [26] of the resulting aldehyde (90% yield over two steps). The radical precursors 22–24 were readily made in 54–69% yield by

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• corresponding dibromide followed by formylation (Scheme 13). In 2006, Rajkumar and co-workers [103] have published the synthesis of stilbenophane 85 via McMurry coupling as a key step (Scheme 14). Terphenyl derivative 82 was subjected to benzylic bromination in the presence of NBS to generate compound 83. Later

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

• approach in which Auto-MATE equipment combined with reaction simulation software was used to predict heat flow data for making and using Vilsmeier reagent at scale [73]. Using this information the formylation of 3,5-dimethoxyphenol was then performed at multi-kilo scale showing good agreement of the

Solution processable diketopyrrolopyrrole (DPP) cored small molecules with BODIPY end groups as novel donors for organic solar cells

• Diego Cortizo-Lacalle,
• Calvyn T. Howells,
• Upendra K. Pandey,
• Joseph Cameron,
• Neil J. Findlay,
• Anto Regis Inigo,
• Tell Tuttle,
• Peter J. Skabara and
• Ifor D. W. Samuel

Beilstein J. Org. Chem. 2014, 10, 2683–2695, doi:10.3762/bjoc.10.283

• was synthesised (compound 7). The synthesis of 7 was achieved from the α-brominated derivative of bithiophene carbaldehyde 4. This synthetic route to prepare 7 has been described previously in the literature [47]. Formylation of the bithiophene was carried out using Vilsmeier–Haack conditions by

• treatment with phosphoryl chloride and N,N-dimethylformamide to give 3, which in turn was brominated with NBS (1.05 equiv) to yield compound 4. Both reactions proceeded in high yields: 90% for the formylation step and 88% for bromination. Compound 7 was prepared following the same procedure used to

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• ]. For the synthesis of the title compounds a similar approach was envisaged. As starting material the commercially available 1-phenyl-3-trifluoromethyl-1H-pyrazol-5-ol (1) was employed which, after Vilsmaier formylation [18] and concomitant transformation of the hydroxy function into a chloro

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

• decomposition of DMF or by the formylation side reactions. The authors recovered pure 4 after lengthy chromatographic separation on a carboxymethylcellulose column, involving the collection of 150 fractions. We decided to optimize the reaction conditions with the goal of improving the yield and avoiding the

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• formylation of chloroacetonitrile with methyl formate. The resulting volatile and unstable chloroaldehyde 6 was used without further purification. Cyclocondensation of 6 with 2,4-diamino-4-hydroxypyrimidine afforded 1 regiospecifically with no detectable formation of the undesired 6-substituted-furo[2,3-d

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

• library of acyclic products (Scheme 11), in which the isocyanide input 30 was derived from the corresponding amine via an N-formylation/dehydration sequence [52]. An additional palladium-catalyzed cyclization gave the pyrrolidine mimics 32 in excellent yields and modest to good selectivities (de 8–78

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• Buchwald’s procedure for the catalytic asymmetric vinylation of enones [51]. However, the desired vinylated product could not be obtained under the described conditions. An alternative α-formylation/Wittig olefination sequence gave only low yields. O’Brien et al. [41] described the failure of a direct

One-pot synthesis of cyanohydrin derivatives from alkyl bromides via incorporation of two one-carbon components by consecutive radical/ionic reactions

• Shuhei Sumino,
• Akira Fusano,
• Hiroyuki Okai,
• Takahide Fukuyama and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2014, 10, 150–154, doi:10.3762/bjoc.10.12

• Shuhei Sumino Akira Fusano Hiroyuki Okai Takahide Fukuyama Ilhyong Ryu Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan 10.3762/bjoc.10.12 Abstract The consecutive radical/ionic reaction consisting of radical formylation of alkyl

• work in collaboration with Dennis Curran has revealed that, with the use of NHC-borane [18], hydroxymethylation of aromatic iodides can be attained [19]. All these reactions consist of the combination of radical formylation with CO and ionic hydride reduction by hydride reagents (Scheme 1, reaction 1

• formylation. Thus, we thought that the two step radical/ionic reactions can be extended to the consecutive C–C bond forming reactions. Cyanohydrins are important subunits frequently found in biologically active compounds and are also versatile building blocks for further synthetic transformations [20][21

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• asymmetric formylation reaction from Funk’s achiral alkene (Scheme 5) [34]. The formylation reaction provided (R)-1 and (S)-1 in acceptable yields (71% and 70%, respectively) and excellent enantioselectivities (94% ee and 97% ee, respectively). However, this synthesis suffers from many drawbacks. Firstly

• , the synthesis of the Funk’s alkene commences from DL-serine and is a multistep sequence requiring Pb(OAc)4. DL-Serine costs 524 €/kg (Aldrich, June 2013 price) compared to L-serine’s 818 €/kg (Aldrich, June 2013). Secondly, both the formylation catalyst and bis(diazaphospholane) ligand are expensive

• and have to be used in large amounts. Thirdly, the formylation reaction was performed only in a 5 mmol scale and was not optimized for large scale synthesis. Asymmetric induction with Garner’s aldehyde Nucleophilic addition to Garner’s aldehyde gives an easy access to 2-amino-1,3-dihydroxypropyl

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 chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

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

• for a more labile methoxymethyl ether at the benzophenone stage. The following prenylation and formylation proceeded smoothly under the same conditions to give 191b (Scheme 24). Cleavage of the MOM ethers afforded pestalone (192), which could be converted into 193 in a single step by treatment of 192

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• /ethyl acetate (3:2), N-methylation and N-formylation were observed (Supporting Information File 1). Considering prior evidence that methanol can generate formaldehyde in the presence of Pd(0) by an oxidative addition mechanism [43][44] and the observation that apolar solvents cause N-formylation during

Dipyrazolo[1,5-a:4',3'-c]pyridines – a new heterocyclic system accessed via multicomponent reaction

• Wolfgang Holzer,
• Gytė Vilkauskaitė,
• Eglė Arbačiauskienė and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2012, 8, 2223–2229, doi:10.3762/bjoc.8.251

• formylation (with concomitant transformation of the oxygen into a chlorine substituent), followed by Sonogashira cross-coupling reaction of the obtained 5-chloropyrazole-4-carbaldehydes with appropriate alkynes, has been described by us in a former publication [21]. Compounds 1 containing an alkyne function

Synthesis of szentiamide, a depsipeptide from entomopathogenic Xenorhabdus szentirmaii with activity against Plasmodium falciparum

• Friederike I. Nollmann,
• Andrea Dowling,
• Marcel Kaiser,
• Klaus Deckmann,
• Sabine Grösch,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 528–533, doi:10.3762/bjoc.8.60

• , Germany) in N-methylpyrrolidone (NMP; VWR, Germany; c = 2 mol/L). Fmoc protecting groups were cleaved with 20% piperidine in DMF by using microwave irradiation as well. Formylation. The free N-terminus was formylated with 5 equiv para-nitrophenyl formate (pNPF; Sigma Aldrich, Germany) and 3 equiv N

Multicomponent synthesis of artificial nucleases and their RNase and DNase activity

• Anton V. Gulevich,
• Lyudmila S. Koroleva,
• Olga V. Morozova,
• Valentina N. Bakhvalova,
• Vladimir N. Silnikov and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2011, 7, 1135–1140, doi:10.3762/bjoc.7.131

• or 12 carbon atoms by the standard formylation–dehydration protocol (Scheme 2). We found that these diisocyanides 3 participate successfully in the catalytic three-component reaction via a modified List procedure [25]. Diamides 4 with benzyl protective groups were synthesized in moderate to good

High chemoselectivity in the phenol synthesis

• Matthias Rudolph,
• Melissa Q. McCreery,
• Wolfgang Frey and
• A. Stephen K. Hashmi

Beilstein J. Org. Chem. 2011, 7, 794–801, doi:10.3762/bjoc.7.90

• vinylcarbenoid F, the two competing reactions would be the formation of the phenol 10 and cyclopropanation to form 11. The synthesis of 8 was possible by a short route (Scheme 5). Starting from the commercially available 2-bromostyrene (12), a halogen–metal exchange and subsequent formylation according to a

Synthesis of 5-(6-hydroxy-7H-purine-8-ylthio)- 2-(N-hydroxyformamido)pentanoic acid

• Yanmei Zhang,
• Greg Elliot,
• Adrian Saldanha,
• Igor Tsigelny,
• Dennis Carson and
• Wolf Wrasidlo

Beilstein J. Org. Chem. 2010, 6, 742–747, doi:10.3762/bjoc.6.93

• -formylation produced 12. Finally, debenzylation with boron tribromide afforded the hybrid molecule 13 as a slightly tan powder [9][10][11][12]. All compounds were fully characterized and their structures confirmed by 1H NMR and mass spectroscopy. The purity of the final product was determined by HPLC and

The efficient synthesis of dibenzo[d,d′]benzo[1,2-b:4,3-b′]dithiophene and cyclopenta[1,2-b:4,3-b′]bis(benzo[d]thiophen)-6-one

• Zhihua Wang,
• Sheng Zhu,
• Jianwu Shi and
• Hua Wang

Beilstein J. Org. Chem. 2009, 5, No. 55, doi:10.3762/bjoc.5.55

• ] as starting material, dibenzo[d,d′]benzo[1,2-b:4,3-b′]dithiophene, a [5]heterohelicene, was synthesized efficiently in 60% yield via formylation and McMurry reaction. Cyclopenta[1,2-b:4,3-b′]bis(benzo[d]thiophen)-6-one, another interesting helical ketone, was also prepared in 79% yield via

• photolysis of RCH(SPh)2 (R = benzo[b]thiophene). However, a non-photochemical method for preparing 1 has, to the best of our knowledge, not been reported. In our work, with 3,3′-bis[benzo[b]thiophenyl] (3) [18] as starting material, 1 (see Figure 1) was synthesized efficiently via formylation and McMurry

• starting material, formylation and McMurry reaction were employed for preparing 1. The formylation step involves sequential deprotonation of 3 and treatment of the intermediate dilithiated species with N,N-dimethylformamide (DMF). Attempted generation of dilithiated 3 with either lithium diisopropylamide