Intermolecular addition reactions of N-alkyl-N-chlorosulfonamides to unsaturated compounds

• Gerold Heuger and
• Richard Göttlich

Beilstein J. Org. Chem. 2015, 11, 1226–1234, doi:10.3762/bjoc.11.136

• cyclisation of various unsaturated N-hetero-substituted amines and amides via radicals [1][2][3] and other mechanistic pathways [4][5][6][7][8]. Although reported by other groups [9][10][11] in our hands an efficient intermolecular addition reaction of N-hetero substituted amines via radicals was not possible

• has been achieved by Zhang [22] using copper or palladium catalysts and proceeds via radicals and fluoropalladation, respectively. Cyclisation reactions of unsaturated sulfonamides which proceed via amidyl radicals have been described by Li [23] and by Oshima [24]. Chemler [25][26] discusses radical

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

• syntheses of two lead compounds reported earlier by AstraZeneca. The first one details the flow synthesis of a potent 5HT1B antagonist (28) that was assembled through a five step continuous synthesis including a SNAr reaction, heterogeneous hydrogenation, Michael addition–cyclisation and final amide

• 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

Hydrogenation of unactivated enamines to tertiary amines: rhodium complexes of fluorinated phosphines give marked improvements in catalytic activity

• Sergey Tin,
• Tamara Fanjul and
• Matthew L. Clarke

Beilstein J. Org. Chem. 2015, 11, 622–627, doi:10.3762/bjoc.11.70

• regioselectivity in enantioselective hydroformylation of alkyl- and arylalkenes [23][24], we reconsidered this cyclisation reaction using the new catalyst (Scheme 2). We were pleased to find that the selectivity is increased to 78%. Since the desired product is achiral, there is no need to use enantiopure BOBPHOS

Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole)

• Friederike Danneberg,
• Alice Ghidini,
• Plamena Dogandzhiyski,
• Elisabeth Kalden,
• Roger Strömberg and
• Michael W. Göbel

Beilstein J. Org. Chem. 2015, 11, 493–498, doi:10.3762/bjoc.11.55

• thiocarbonyldiimidazole and methyl 3,4-diaminobenzoate (Scheme 2). The cyclisation to form the first benzimidazole unit was then achieved by reacting thiourea 3 with Mukaiyama’s reagent in the presence of NEt3 at rt yielding 88% of 4. Although the yield is slightly lower compared to the cyclisation with HgO (97% yield

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• 9 and 10, while no such product was evident from the reaction with the larger cinnamyl bromide. Minor byproducts isolated were the corresponding N-monoallylated indigos (7–15%). These heterocycles arise from the cyclisation of one allyl unit onto a carbonyl, leading to the tertiary alcohol. They are

• derivatives of the azepino[1,2-a:3,4-b']diindolone skeleton have been reported previously, albeit in a different oxidation state and with notably different substitution patterns [5] (Figure 2), they were only obtained as very minor diastereomeric products (ca 1% yields) from acid-catalysed cyclisation studies

• and moisture. This is the first example of the synthesis of this bridged heterocyclic skeleton. The formation of 22 is an excellent example of the ‘gem-dimethyl effect’ [9] whereby the presence of that moiety enhances cyclisation [10]. This explains the formation of 22 and the lack analogous cyclised

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• -benzoyl-3-ethoxyprop-2-enoate reacted with 5-aminotetrazole by two reaction routes to form ethyl 2-benzoyl-3-(1H-tetrazol-5-ylamino)prop-2-enoate and ethyl 7-(1-ethoxy-1,3-dioxo-3-phenylpropan-2-yl)-5-phenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate. Keywords: 5-aminotetrazole; cyclisation

Anionic sigmatropic-electrocyclic-Chugaev cascades: accessing 12-aryl-5-(methylthiocarbonylthio)tetracenes and a related anthra[2,3-b]thiophene

• Laurence Burroughs,
• John Ritchie,
• Mkhethwa Ngwenya,
• Dilfaraz Khan,
• William Lewis and
• Simon Woodward

Beilstein J. Org. Chem. 2015, 11, 273–279, doi:10.3762/bjoc.11.31

• (47%), 7c (56%), 7f (44%) and 7g (38%). The decreasing yields suggest that meta substitution promotes the 6π cyclisation while para electronic affects are minor and unhelpful according to the observed trend. Increasing the reaction temperature, in attempts to facilitate E2 elimination, was generally

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• it to determine the complete relative stereochemistry of the natural products. Results and Discussion The proposed route to furo[2,3-b]chromene 7 was based around the preparation of benzylic ketone 8 which was hoped to under acidic conditions would undergo cyclisation to give 7 (Figure 2). We have

Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes

• Philipp Röse,
• Steffen Emge,
• Jun-ichi Yoshida and
• Gerhard Hilt

Beilstein J. Org. Chem. 2015, 11, 174–183, doi:10.3762/bjoc.11.18

• and pyran derivatives under indirect electrochemical conditions generating selenium or iodonium cations. The reactions proceed in good yields and regioselectivities for the formation of single diastereomers. Keywords: cyclic ethers; cyclisation; 1,4-dienes; electrochemistry; iodonium; selenium

• -dienols were transformed into cyclic phenylselenoethers by intramolecular cyclisation using selenium cations generated by indirect electrolysis. The reaction was carried out by electrolysing a mixture of the 1,4-dienol, diphenyl diselenide and tetraethylammonium bromide in CH3CN at room temperature in an

• undivided cell, using platinum foil electrodes (constant current 10 mA). In this investigation only diphenyl diselenide was used as selenium source. These reaction conditions led to the formation of products of type 3 as exclusive diastereomers (Scheme 2). The cyclisation of 2 could lead to a number of

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• are useful reactive synthetic intermediates in a variety of important carbon–carbon bond forming and cyclisation strategies in organic chemistry. The advent of an electrochemical anodic oxidation of unfunctionalised amides, more commonly known as the Shono oxidation, has provided a complementary route

• -acyliminium ion cyclisation strategy in the presence of a disubstituted acetylene nucleophile. Anodic oxidation proceeded in high yield and a smooth cyclisation of the pendant acetylene nucleophile was triggered by treatment with titanium tetrachloride. Ozonolysis of the chloromethyl alkene intermediate

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• from aminobiphenyl and arylaldehyde in dichloromethane in the presence of molecular sieves at room temperature. Radical cyclisation in the presence of (tert-butyl)peroxide in chlorobenzene at 140–150 °C for 48 h, yielded the corresponding phenanthridines in moderate yields. The t-BuO• radical

• second step under the catalysis of Pd(OAc)2 comprised both cyclisation and oxidation in a single step: a dehydrogenative C–H amination with PhI(OAc)2 as oxidant and removal of the picolinamide group followed by oxidation with Cu(OAc)2. This strategy afforded phenanthridines in moderate to good yields (up

• to 65% for the second step). Bowman et al. reported a palladium-mediated route using imidoyl-selenides as precursors besides the radical route. Comparison of the cyclisation yields for the same set of phenanthridine derivatives revealed an overall better efficiency of the t-BuO• radical-assisted

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

• , involving gold(I)-catalysed cyclisation of an alkynyl alcohol to form the furan ring. The furan analogue of thiamine diphosphate (ThDP) was also made and tested for binding to and inhibition of pyruvate decarboxylase (PDC) from Zymomonas mobilis (overexpressed in E. coli with a N-terminal His-tag). It is a

• very strong inhibitor, with a Ki value of 32.5 pM. It was also shown that the furan analogue of thiamine can be functionalised at the C-2 position, which will allow access to mimics of reaction intermediates of various ThDP-dependent enzymes. Keywords: furan synthesis; gold-catalysed cyclisation

• dehydrative cyclisation reaction of alkynyl alcohols catalysed by simple gold(I) salts [31]. The reaction proceeds rapidly under mild, open flask conditions to provide aromatic heterocycles such as furans, pyrroles and thiophenes in high yield with low catalyst loadings (Scheme 2). Following this synthetic

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• ., Koreničova 1, SK-811 03 Bratislava, Slovakia 10.3762/bjoc.10.216 Abstract The study of Pd-catalysed cyclisation reactions of alkenols using different catalytic systems is reported. These transformations affect the stereoselective construction of mono- and/or bicyclic oxaheterocyclic derivatives depending on

• a starting alkenol. The substrate scope and proposed mechanism of Pd-catalysed cyclisation reactions are also discussed. Moreover, the diastereoselective Pd-catalysed cyclisation of appropriate alkenols to tetrahydrofurans and subsequent cyclisation provided properly substituted 2,5-dioxabicyclo

• process, the terminal carbon–carbon double bond is bis-O-functionalised with two hydroxy groups by sequential intramolecular–intramolecular reaction. Based on our continuous interest in the palladium-catalysed cyclisation reactions and their applications in natural product syntheses [24][25], we have

Comparing kinetic profiles between bifunctional and binary type of Zn(salen)-based catalysts for organic carbonate formation

• Carmen Martín and
• Arjan W. Kleij

Beilstein J. Org. Chem. 2014, 10, 1817–1825, doi:10.3762/bjoc.10.191

• Scheme 2 first the epoxide coordinates to the Zn center allowing Lewis acid activation following the ring opening by nucleophilic attack of X. Then, carbon dioxide insertion into the metal–oxygen bond takes place and a consecutive cyclisation step (ring closure) occurs to give the cyclic carbonate and

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

• afforded the corresponding pyrazolo[4,3-c]pyridine 5-oxides 7a–c by a regioselective 6-endo-dig cyclisation [30] in high yields. Moreover, we tested an alternative approach to access compounds 7 through multicomponent reactions (MCR). Attempts to react chloroaldehyde 2 with hydroxylamine hydrochloride and

Multichromophoric sugar for fluorescence photoswitching

• Stéphane Maisonneuve,
• Rémi Métivier,
• Pei Yu,
• Keitaro Nakatani and
• Juan Xie

Beilstein J. Org. Chem. 2014, 10, 1471–1481, doi:10.3762/bjoc.10.151

• , 9-OF undergoes a cyclisation photoreaction yielding the molecule in its colored and non-fluorescent closed form (9-CF), as revealed by the appearance of a large absorption band peaking in the 500–700 nm range (Figure 3c, full blue line). The photostationary state (PSS) reached under 335 nm

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

• , presumably because of the high solubility of the amino acid intermediate in the aqueous reaction mixture and the well-established difficulty of direct amide bond formation processes. Consequently, before carrying out the nitro group reduction and amide forming cyclisation reactions, the acids 4a–e were

Rapid pseudo five-component synthesis of intensively blue luminescent 2,5-di(hetero)arylfurans via a Sonogashira–Glaser cyclization sequence

• Fabian Klukas,
• Alexander Grunwald,
• Franziska Menschel and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 672–679, doi:10.3762/bjoc.10.60

• solvent. Pseudo five-component Sonogashira–Glaser cyclisation synthesis of 2,5-di(hetero)arylfurans 2 (aobtained from the THP-protected precursor). Evaluation of different reaction conditions. Selected absorption and emission data (recorded in dichloromethane at T = 293 K). Selected cyclovoltammetrica

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

• combination of deprotection and activation is also possible and is found in the literature as an Ugi Deprotection/Activation–Cyclisation (UDAC). In addition, other MCR-post-condensation reactions, especially for macrocycles, include intramolecular aryl couplings, amidations, SnAr reactions, nucleophilic

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• , initial deprotection of D (to liberate the Lewis-basic –NHBn moiety) and subsequent reduction passing through a Cram-chelate transition state [54] should deliver the anti-amino alcohol C. After subsequent cyclisation trans-B would result. Noteworthy, this strategy would completely circumvent

• significant amounts in the cyclisation of amino diol 9c. This is explained by steric shielding of the amino function (→ decreased nucleophilicity) through the bulky phenyl group in α-position (compared to the less demanding Me and Bn side chains R of substrates 9a and 9c). As the R-substituent is in the β

• Et3N/CH2Cl2 can be attributed to the lower solubility of iodine in Et3N (which leads to a slower and thus more selective reaction) and general base catalysis: Simultaneous deprotonation (through Et3N) in the cyclisation step strongly favours the desired reaction pathway to piperidines 11. Due to this

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• initially-formed (E,E,E)-triene undergoes stereospecific epoxidation to a tri-epoxide and subsequent ring-opening and cyclisation to generate the polyether rings. This model has been confirmed and extended (Scheme 1) by the results of more recent work in which specific genes have been disrupted or deleted

• cyclisation is not initiated before the full-length chain is produced, and that the initial product of the PKS is a linear enzyme-bound (E,E,E)-triene, “premonensin” (2) [19]. The monensin PKS does not have a conventional C-terminal thioesterase domain that would catalyse polyketide chain release, and instead

• MonACPX, catalysed by the unusual thioesterase MonCII [20]. The evidently tight coupling between PKS-mediated chain assembly and oxidative cyclisation has hampered efforts to unravel the exact sequence and mechanism of events in the late stages of the biosynthesis. Indirect but suggestive evidence for the

Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde

• Haijun Qu,
• Xuejian Li,
• Fan Mo and
• Xufeng Lin

Beilstein J. Org. Chem. 2013, 9, 2846–2851, doi:10.3762/bjoc.9.320

• condensation of imine 5 with substituted acetaldehyde 2. This could then undergo an iodine-catalytic intramolecular cyclisation to afford the final dihydropyrimidinone 4. Based on the observations above, a preliminary investigation on the catalytic asymmetric version was performed. Recently, our group has

[²H₂₆]-1-epi-Cubenol, a completely deuterated natural product from Streptomyces griseus

• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2841–2845, doi:10.3762/bjoc.9.319

• the homomonoterpene 1 proceeds by S-adenosylmethionine-dependent methylation of GPP followed by a cyclisation reaction [3][4][5]. For biosynthetic studies on secondary metabolites isotopically labelled precursors are frequently used. Historically, the usage of radiolabelled compounds was most

Modulating NHC catalysis with fluorine

• Yannick P. Rey and
• Ryan Gilmour

Beilstein J. Org. Chem. 2013, 9, 2812–2820, doi:10.3762/bjoc.9.316

• the corresponding lactam 13 using a Ru(III)/NaIO4 system proceeded smoothly, followed by TFA-mediated Boc deprotection to yield 14 (75%, 2 steps). Reduction of the methyl ester to the primary alcohol (15, 18%), and subsequent protection as the TBDMS ether delivered the cyclisation substrate 16 in good

• yield (92%). A three step, one pot sequence consisting of methylation, treatment with phenylhydrazine and subsequent cyclisation furnished the triazolium salt 17 in 76% yield (3 steps). Finally, DAST-mediated TBDMS deprotection/deoxyfluorination completed the synthetic sequence to give 7 in 45% yield

• lactam 19 (21% over 2 steps) in preparation for the cyclisation sequence. As previously described, successive treatment with the Meerwein salt, phenylhydrazine and methyl orthoformate yielded the target triazolium salt 8 in 61% over 3 steps. The pre-catalysts 9 and 10 required for control experiments

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• the cyclisation event. 6.4 Enantioselective fluorocyclisation The lack of diastereoselectivity seen in Scheme 7 is attributable to the fluorination event preceding the cyclisation event, and this is a significant issue which inhibits the further development of diastereoselective processes. However

• synthesis this reagent fulfils both functions at different stages: thus, the target 78 is achieved from N-(tert-butylsulfinyl)imine 75 through a nucleophilic addition/radical cyclisation sequence. The selectivity during the radical cyclisation (77→78) can be explained by the Beckwith–Houk transition-state

• illustrates a strategy for achieving stereoselectivity in C–F bond formation. The racemic β-lactam 4b was synthesised as a single diastereoisomer from the Schiff base 79 (Scheme 11), by a Reformatsky addition followed by spontaneous cyclisation; removal of the amine protecting group under oxidative conditions