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

Radical carbonylations using a continuous microflow system

• Takahide Fukuyama,
• Md. Taifur Rahman,
• Naoya Kamata and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2009, 5, No. 34, doi:10.3762/bjoc.5.34

• pressurized carbon monoxide gas. Good to excellent yields of carbonylated products were obtained via radical formylation, carbonylative cyclization and three-component coupling reactions, using tributyltin hydride or TTMSS as a radical mediator. Keywords: continuous flow system; microreactor; radical

• CO and the liquid. Using the microflow system depicted by Figure 1, we carried out the radical formylation of 1-bromododecane (1) with CO in the presence of tributyltin hydride (bath temp. 80 °C) [21]. However, we encountered incomplete conversion of the starting bromide when we used AIBN (2,2

• carbonylation in a microflow system. The radical formylation of 1-bromododecane (1). 1-Bromododecane (1, 1 mmol, 249.5 mg), V-65 (0.1 mmol, 24.8 mg), Bu3SnH (1.2 mmol, 352.9 mg), and decane (59 mg) as an internal standard were dissolved in toluene (50 mL). The toluene solution was placed in a syringe (17 mL

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

A practical synthesis of the ¹³C/¹⁵N- labelled tripeptide N-formyl- Met-Leu-Phe, useful as a reference in solid- state NMR spectroscopy

• Sven T. Breitung,
• Jakob J. Lopez,
• Gerd Dürner,
• Clemens Glaubitz,
• Michael W. Göbel and
• Marcel Suhartono

Beilstein J. Org. Chem. 2008, 4, No. 35, doi:10.3762/bjoc.4.35

• Wolfgang Goethe University Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany 10.3762/bjoc.4.35 Abstract A mild synthetic method for N-formyl-Met-Leu-Phe-OH (1) is described. After Fmoc solid phase peptide synthesis, on-bead formylation and HPLC purification, more than 30 mg of the fully

• 13C/15N-labelled tripeptide 1 could be isolated in a typical batch. This peptide can be easily crystallised and is therefore well suited as a standard sample for setting up solid-state NMR experiments. Keywords: Fmoc solid phase peptide synthesis; formylation; f-MLF; magic-angle spinning; Wang resin

• , reflux, 24–65 h) were required to couple the first Boc-protected amino acid to the solid support (chloromethyl resin) and long reaction times (18 h) were necessary to attach further building blocks to the growing peptide chain. The formylation of the N-terminus with formic acid/acetic anhydride was

Synthesis of the Benzo- fused Indolizidine Alkaloid Mimics

• Daniel L. Comins and
• Kazuhiro Higuchi

Beilstein J. Org. Chem. 2007, 3, No. 42, doi:10.1186/1860-5397-3-42

• . Palladium-catalyzed carboalkoxylation reaction of 12 gave the α-methoxycarbonyl dihydropyridone 13 in 82% yield. The addition and modification of functional groups on 8a were investigated (Scheme 4). The protection of the C-4 carbonyl of 8a as a ketal followed by Vilsmeier-Haack formylation [25] furnished