N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• N-(1-phenylethyl)aziridine-2-methanols 7 Aziridine alcohols 7 are usually prepared by LiAlH4 reduction of the corresponding esters 5 [22][35][36] although a milder method with a NaBH4 and LiCl mixture was also elaborated [37]. A multistep synthesis of (2S,1'R)-7 employing the aziridine ring closure

• lithium enolate of methyl 4-methoxyphenylacetate would give the β-hydroxyester 169 which when treated with Lewis acid experienced the aziridine ring cleavage with simultaneous dihydrofuran-2-one ring closure to produce 170 contaminated with small amounts of the corresponding furan-2(5H)-one 171

• with AD-mix-β provided an inseparable 82:18 mixture of diastereoisomers with the diol 196 as a major product. Silylation of the terminal hydroxy group was followed by mesylation of a secondary one to facilitate the piperidine ring closure triggered by hydrogenolytic removal of the chiral auxiliary to

A heteroditopic macrocycle as organocatalytic nanoreactor for pyrroloacridinone synthesis in water

• Piyali Sarkar,
• Sayan Sarkar and
• Pradyut Ghosh

Beilstein J. Org. Chem. 2019, 15, 1505–1514, doi:10.3762/bjoc.15.152

• nanoreactor which is a single molecule as catalyst in the earliest steps of the mechanistic pathway (Figure 6). This multicomponent reaction is expected to comprise a series of condensations and subsequent ring-closure cascade reactions (Scheme 3). To demonstrate the mechanistic pathway, dimedone (2), isatin

Selenophene-containing heterotriacenes by a C–Se coupling/cyclization reaction

• Pierre-Olivier Schwartz,
• Sebastian Förtsch,
• Astrid Vogt,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2019, 15, 1379–1393, doi:10.3762/bjoc.15.138

• the synthesis of dithienothiophene 1, which is mostly built up by oxidative dehydrocoupling of 3,3’-dithienyl sulfide or ring-closure reactions of brominated thiophenes with ethyl mercaptoacetate, are described in literature [24]. For comparability to the selenophene-containing triacenes 2–4, we

• reinvestigated the synthesis of DTT 1 by using a Cu-catalyzed C–S cross-coupling reaction with potassium sulfide (K2S) as sulfur source [29]. The best results for this C–S ring-closure reaction were achieved by reacting 3,3’-diiodo-2,2’-bithiophene (5) [30] with the system K2S and copper iodide (CuI) as catalyst

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• to the rigid nature of the steroidal and aryl components, a flexible diamine was required to facilitate the macrobicycle ring closure. As before, pseudo-dilution conditions were employed by the simultaneous slow addition of the three bifunctional components. Conclusion We have demonstrated that MCRs

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• , but also α-himachalene (2), γ-himachalene (3), longifolene (4), longicyclene (5), and α-longipinene (6) are traditionally considered to be derived from the himachalyl cation (B) [8][37] (Scheme 2). Whereas 1–3 are simple deprotonation products of B, 4 and 5 require a further 3,7-ring closure, leading

• to the non-classical cation C, which is a derivative of the 2-norbornyl cation [38]. This system either collapses by deprotonation at the methyl group to longifolene (4), or by deprotonation at C-4 with formation of a cyclopropane ring to longicyclene (5). Starting from B, a 2,7-ring closure and

• secondary cation D, which either stabilises by 2,10-ring closure to give the caryophyllenyl cation E that can be deprotonated at the methyl group to yield 9-epi-(E)-β-caryophyllene (7), or D undergoes a 1,3-hydride shift to the allylic cation F. Deprotonation leads to γ-humulene (8), but a 1,6-ring closure

An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS,7aR,E)-2-ethyl-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-1-ylidene)sulfamoyl chloride

• Aytekin Köse,
• Aslı Ünal,
• Ertan Şahin,
• Uğur Bozkaya and
• Yunus Kara

Beilstein J. Org. Chem. 2019, 15, 931–936, doi:10.3762/bjoc.15.89

• amides 4 are produced, they may be converted to other compounds. Graf [1] proposed that the reaction of CSI with unsaturated systems proceeds via the direct formation of dipolar intermediate 5 which may undergo a ring closure to form 3 or a hydrogen transfer to afford 4 (Figure 1). A wide variety of

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• ) [20][21][22][23]. This reaction proceeds through an intramolecular mechanism which leads to the formation of heterocyclic products as a result of a ring-closure process. In 1998, Ugi et al. reported the intramolecular Ugi-4C-3CR of ketoacids such as levulinic acid and phthalaldehydic acid with

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• resulting in (S)-A after ring closure (Scheme 1, path A) or via (S)-NPP, which would suggest involvement of (R)-A (Scheme 1, path B). This stereochemical link between NPP and A was also observed in a theoretical docking study with epi-isozizaene synthase suggesting (S)-NPP and (R)-A to be included in its

• of the C-2,C-3-double bond by the enzyme’s active site (e.g., on top of it, Figure 4A). This migration of OPP to C-3 results in a reorganisation of the resulting structure to a cisoid conformation for the follow up 1,6-ring closure. To explain the astonishing selectivity between the two NPP

• productive conformation that exhibits a close proximity between C-6 and C-1 for ring closure to (S)-A initiated by OPP abstraction, (S)-NPP cannot occupy this conformation for its different stereocentre. Instead, abstraction of the OPP moiety leads to an allylic cation with an unproductive conformation for

Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials

• Widukind Moormann,
• Daniel Langbehn and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 727–732, doi:10.3762/bjoc.15.68

• oxidative C–C coupling of 2-nitrotoluenes (75–82% yield) and a reductive ring closure to form the diazocines (56–60% yield). The cyclization of the dinitro compound to the azo compound was improved in yield and reproducibility, by over-reduction to the hydrazine and reoxidation to the azo unit. In contrast

• coupling of nitrotoluenes and the reductive ring closure of the dinitro compounds (Scheme 1). We recently improved the yield of the C–C coupling through addition of bromine as an oxidizing agent [27]. The reaction times thus are reduced to several minutes as compared to several hours in previous procedures

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• and efficient procedure to access the 2H-furo[2,3-c]pyrazole ring system was developed by employing the silver(I) ion-mediated ring-closure reaction of 4-alkynyl-3-hydroxy-1-phenyl-1H-pyrazoles as a key step. The required intermediate hydroxyalkynyl substrates for this reaction were prepared by a Pd

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• functionalized side chains are introduced prior to coupling and ring closure to afford 8. This new synthetic route would be more convergent and efficient for the preparation of 3. Retrosynthetic analysis led to 9 and 10 as two key synthons, which would be assembled via a Mitsunobu–Fukuyama reaction, and

Oxidative and reductive cyclization in stiff dithienylethenes

• Michael Kleinwächter,
• Ellen Teichmann,
• Lutz Grubert,
• Martin Herder and
• Stefan Hecht

Beilstein J. Org. Chem. 2018, 14, 2812–2821, doi:10.3762/bjoc.14.259

• double bond isomerization in addition to ring-closure, has been investigated. Electrochromism was observed in almost all cases, with the major pathway being the oxidatively induced cyclization of the open isomers. The influence of the ring size (to lock the reactive antiparallel conformation) as well as

• ), generated either in the irreversible oxidation process or photochemically. Both of these oxidation events occur at significantly lower potentials compared to the open isomers, reflecting the increased energy of the HOMO due to the extended π-system generated upon ring-closure. Irreversible oxidation of the

• the double bond geometry. Since ring-closure requires the two reactive α-thienyl carbon atoms to approach each other, presumably an additional electrochemically induced E → Z isomerization occurs prior to cyclization. Indeed, there are scattered reports about configurational isomerism in stilbene

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• process generally does not take place under such low molar concentration of the substrate [38][39][40][41][42][43]. We also did not isolate any copolymerization product. This may be attributed to the much faster rate of addition of the Ru-carbene 10 to the yne unit intramolecularly resulting in ring

• closure rather than intermolecular addition to an acetylenic unit of another molecule of 7b. It may be noted that changing the functional group from hydroxy to acetate the metathesis followed a different reaction course. In order to construct a polycyclic structure analogous to the B/C/D/E ring of

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• outlined in Figure 1, which for the sake of clarity omits the substituents not involved in the bond-forming step in the final ring closure. Almost all the strategies developed to date involve the formation of the C3–C3a bond in the ring-closing step leading to the hydrindane nucleus. The carbocyclization

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• with its β-ketoester moiety to give 17-exo-heterocycles, but also with its enone part to provide ring D-condensed pyrazolines [27]. Therefore, the ring-closure reactions of 4 with unsubstituted and monosubstituted hydrazines as binucleophilic reagents were investigated next. First, compound 4 was

• on the reaction rates. The ring-closure of 4 with 5d–g containing electron-donating groups (Table 1, entries 1–4) took place within shorter reaction times (5–10 min) compared to phenylhydrazine (5b). On the other hand the presence of electron-withdrawing halogens on the aromatic ring of 5 (Table 1

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• expensive diphenyl ether, which has a nauseating odor, at 0.01 molar dilution at reflux (259 °C) to effect the ring closure via electrophilic aromatic substitution; and (3) the aqueous work-up of this method which does not reliably produce a precipitate that can be filtered easily. Given the

• quinolines of type 10 via C→D, the ethyl acetopyruvate has two carbonyls a and b as depicted in 13 that result in regioisomeric products upon ring closure. The desired quinoline 11 requires ring closure onto carbonyl b. To that end, ethyl sodioacetopyruvate was prepared via Claisen condensation of acetone

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• by cyclodehydration allowed for a straightforward and efficient synthesis of 3,4-dihydroquinazolines with N-aryl substituents bearing electron-withdrawing groups. The sequence involves an initial SNAr displacement, N-acylation and MW-assisted ring closure. Remarkably, the uncatalyzed N-arylation of 2

• ]. An alternative method is the ring closure of N-acyl-2-ABAs, but this strategy generally requires high temperatures and/or long reaction times [5][37][38][39][40]. Recently, our group described efficient strategies to prepare 3,4- and 1,4-DHQs with different substitution patterns from 2-ABA [41

• condensation position [48][49][50]. An exception to this is the recently reported synthesis of 3-(m-nitrophenyl)-5-nitro-3,4-dihydroquinazoline from m-nitroaniline and 1,3-dioxolane in the presence of strong protic acids [51]. In a related methodology, the ring closure of N-aryl-2-ABA is promoted by formic

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• precursor 9 to [Ru-2] catalyst 5 gave the ring-closure product 10 in quantitative yield (Scheme 1). A sequential usage of SM cross coupling and RCM was responsible to construct various naphthalene derivatives such as 15 [31]. The SM coupling product 3,4-diallylbenzene derivative 13 (90%) was obtained from

• diiodobenzene 11 using allylboronate ester 12 via a SM-type allylation sequence [32]. Next, compound 13 was exposed to Grubbs 1st generation (G-I) catalyst 1 to effect the ring-closure to produce tetrahydronaphthalene derivative 14 (92%). Subsequently, aromatization of compound 14 was accomplished with 2,3

• the ring-closure product 25 (84%). Finally, CAN oxidation gave the desired tetracyclic compound 26 in 84% yield (Scheme 3). Spirocycles In another event, an efficient approach to spirocyclopentane derivatives has been described, where the combination of RCM and SM coupling was employed [34]. In this

A pyridinium/anilinium [2]catenane that operates as an acid–base driven optical switch

• Sarah J. Vella and
• Stephen J. Loeb

Beilstein J. Org. Chem. 2018, 14, 1908–1916, doi:10.3762/bjoc.14.165

• + was formed using [7][OTf]4 in the presence of DB24C8 followed by ring closure using the benzylaniline axle 4 to yield [8DB24C8][OTf]6. The reaction was performed under dilute conditions with 10 equivalents of crown ether to favor ring closure and kinetic trapping of the smaller ring. To isolate the

DFT calculations on the mechanism of copper-catalysed tandem arylation–cyclisation reactions of alkynes and diaryliodonium salts

• Tamás Károly Stenczel,
• Ádám Sinai,
• Zoltán Novák and
• András Stirling

Beilstein J. Org. Chem. 2018, 14, 1743–1749, doi:10.3762/bjoc.14.148

• copper(III)-catalysed carboarylation–ring closure reactions leading to the formation of functionalised heterocycles. We have performed DFT calculations along selected routes and compared their free energy profiles. The calculations considered two viable options for the underlying mechanism which differ

• the basis of the mechanism the origin of the stereoselectivity is ascribed to the interaction of the Cu ion with the oxazoline oxygen driving the ring-closure step selectively. Keywords: catalysis; DFT calculation; iodonium salts; reaction mechanism; tandem arylation–cyclisation; Introduction

• an aryl group transfer step affording a wide range of oxazoline derivatives [44]. An intriguing issue is the order of the arylation and ring-closure steps and whether this sequence can be affected by the electronic or steric properties of the ligands. Although these mechanistic variations have been

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• mechanism that first involves the formation of a 2’-iodobiphenyl-2-azide promoted by the copper complex. The latter then catalyzes an intermolecular [3 + 2] cycloaddition with the alkyne. Finally, the copper-triazole moiety inserts intramolecularly into the second Ar–I bond, allowing a ring closure after

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• of 3-phenylsydnone and proposed formation of N-phenylnitrilimine as the main reaction product via an internal ring closure, extrusion of CO2 and ring opening (Scheme 6). This very reactive 1,3-dipole was trapped by reaction with external (14C-labelled) CO2 to give 3-phenyl-1,3,4-oxadiazol-2(3H)-one

An unusual thionyl chloride-promoted C−C bond formation to obtain 4,4'-bipyrazolones

• Gernot A. Eller,
• Gytė Vilkauskaitė,
• Algirdas Šačkus,
• Vytas Martynaitis,
• Ashenafi Damtew Mamuye,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2018, 14, 1287–1292, doi:10.3762/bjoc.14.110

• -substituents at the pyrazole C4 position, like 5-chloropyrazole-4-carbaldehydes or 4-esters, turned out to be particularly useful due to the easy conversion of the chloro substituent into other functional groups or its nature as a good leaving group in ring-closure reactions. In this respect we were interested

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• compared by both experimental techniques and by means of MNDO calculations (Scheme 26) [131]. While the key steps for the thermal decomposition of tropones are electrocyclic ring closure and cheletropic CO extrusion to give an aromatic system, the cationic reactions occur with ring closure followed by the

Stepwise radical cation Diels–Alder reaction via multiple pathways

• Ryo Shimizu,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 704–708, doi:10.3762/bjoc.14.59

• rationalized that the six-membered ring closure of the acyclic radical cation intermediate (A·+) would be a stepwise process, leading to the Diels–Alder adduct 3 as an approximately cis/trans = 1:1 mixture. However, since the oxidative SET-triggered rearrangement of the vinylcyclobutane 4 gives the Diels–Alder

• adduct 3 as an approximately cis/trans = 1:4 mixture, this should proceed via a different intermediate from the acyclic radical cation intermediate (A·+). Here, we propose the cyclic radical cation intermediate B·+ for the rearrangement, imparting stereoselectivity for the six-membered ring closure. The