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

• product hamamelitannin and several of its analogues have been identified as quorum sensing inhibitors. In this paper the synthesis of pyrrolidine-based analogues of a more lead-like hamamelitannin analogue is reported. A convergent synthetic route based on a key ring-closing metathesis reaction was

• ’-homoazanucleosides. This possible precursor was synthesized convergently in 12 steps [20]. The pyrrolidine ring was constructed via alkylation of 6 and 7, followed by ring-closing metathesis. Stereoselective dihydroxylation of the resulting alkene then furnished the protected iminosugar 5. However, using

• subsequently the secondary amine converted to the pyrrolidine ring via a ring-closing metathesis reaction [21]. Results and Discussion Chemistry The synthesis of fragment 9 is depicted in Scheme 2 and proved to be challenging. It was essential to introduce the nosyl group only in the last step, since several

Design and synthesis of C₃-symmetric molecules bearing propellane moieties via cyclotrimerization and a ring-closing metathesis sequence

• Sambasivarao Kotha,
• Saidulu Todeti and
• Vikas R. Aswar

Beilstein J. Org. Chem. 2018, 14, 2537–2544, doi:10.3762/bjoc.14.230

• groups and a benzene ring as a central core. The synthesis of these C3-symmetric molecules involves simple starting materials. Our approach to C3-symmetric compounds relies on a Diels–Alder reaction, cyclotrimerization and ring-closing metathesis as key steps. Keywords: cyclotrimerization; Diels–Alder

• ; propellane; ring-closing metathesis; Introduction In 1966 Ginsburg coined the word “propellane” [1][2] and Wiberg reviewed various aspects of medium and small ring propellanes [3][4]. Propellanes consist of tricyclic compounds where three rings are conjoined by a common C–C bond [1][5][6]. Heterocyclic

• developed simple synthetic approaches to propellanes via ring-closing metathesis (RCM) as a key step [17][18]. The development of new synthetic strategies to C3-symmetric molecules bearing propellane moieties from commercially available starting materials is worthy of systematic investigation. To this end

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

• reaction occurs under mild reaction conditions. Among different metathetic processes, ring-closing metathesis (RCM) [1][2][3][4][5][6] is of a greater interest than cross-metathesis (CM). It is a widely used protocol for the synthesis of unsaturated cyclic systems [7]. Palladium-catalyzed Suzuki–Miyaura

Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis

• Tobias Fiedler,
• Michał Barbasiewicz,
• Michael Stollenz and
• John A. Gladysz

Beilstein J. Org. Chem. 2018, 14, 2354–2365, doi:10.3762/bjoc.14.211

• intramolecular ring closing metathesis (giving VI). In contrast, with the analogous intermediate derived from 11·2BH3 (V), there is only one P(CH2)6CH=CH2 moiety that can give non-productive chemistry. It is also worth noting that high dilution provides less of an advantage in Scheme 2, as one wants to favor

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

• and Brückner reported the synthesis of 7-hydroxy-2,3-benzotropones by ring-closing metathesis (Scheme 48) [173]. 7-Hydroxy-2,3-benzotropone (241) was synthesized in four steps starting from a Br/Li exchange reaction of o-bromostyrene (283) followed by the addition of aldehyde 284 to give the benzylic

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• -O-benzylsucrose with different unsaturated monosaccharide units is presented. Such a highly functionalized intermediate was cyclized under RCM conditions to afford a macrocyclic derivative containing a 31-membered ring in 26% yield. Keywords: chiral macrocycles; ring-closing metathesis; sucrose

• positions in 6,6’-diamino-1’,2,3,3’,4,4’-hexa-O-benzyl-6,6’-dideoxysucrose (2) were elongated with the same polyhydroxylated unit 1 providing diamide 3, which subsequently underwent cyclization under the chosen ring-closing metathesis (RCM) conditions [29][30] to give the 21-membered macrocycle 4 (Scheme 1

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• . The latter could be constructed through ring-closing metathesis of the corresponding precursor, e.g., 4,4,5,5-tetrafluoroocta-1,7-diene 5, using a Grubbs' catalyst. The octa-1,7-diene 5 could be obtained through a nucleophilic addition of a vinylic Grignard reagent to the γ-keto ester 6. Lastly, the γ

• . However, performing the reaction in the presence of 10 mol % of the catalyst for 40 h drove the reaction to completion. Intriguingly, the ring-closing metathesis proceeded in a highly diastereoselective manner and produced the corresponding cyclized adduct 4a as a single isomer [26]. Finally, with

• to the LC display industry. The stereochemistry in the ring-closing metathesis step 5→4 was determined as follows. As depicted in Table 2, it has been generally recognized that the melting points of trans-1,4-disubstituted cyclohexane-1,4-diols are much higher than those of the corresponding cis

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• compound 9. This compound was synthesised by esterification of pent-4-en-2-ol (31) with acryloyl chloride (32) to 33, followed by ring-closing metathesis using the Hoveyda–Grubbs catalyst of the second generation (Scheme 8). The synthetic material proved to be identical to the volatile of D. clavata

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• proposed strategy of bicyclo[3.2.1]octanone 14 assembly is based on a combination of ring closing metathesis reaction and intramolecular addition of the malonate anion to a nitrosoalkene unit (Scheme 6). On the first stage, readily available chlorodiene 9 was subjected to a metathesis reaction with the

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• ] and oxasilacycloalkenes (cyclic siloxanes, cf. Figure 1) [6][7][8] is an excellent method to prepare stereodefined alkenes. The cyclic siloxanes can be prepared in a number of ways: hydrosilylation of alkynes [11][12][13], semihydrogenation of silyl alkynes [14], ring-closing metathesis (RCM) [15][16

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• . Importantly catalytic application of these mechano-synthesized complexes are also explored. Friščić and co-workers recently reported an efficient mechanochemical approach towards Ru-based Hoveyda–Grubbs catalyzed olefin metathesis, cross-metathesis and ring-closing metathesis reactions (Scheme 49) [181

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• potential of the new eco-compatible approach for the macrocyclic library generation. Keywords: carbohydrate; click chemistry; diversity-oriented synthesis; macrocycles; ring-closing metathesis; Introduction Macrocycles offer very complex molecular architectures with a diverse range of ring sizes decorated

• transition-metal-catalyzed coupling reactions [19]. Recently, ring-closing alkyne metathesis (RCAM) [20][21] and ring closing metathesis (RCM) [22][23][24][25][26][27][28][29][30][31] have emerged as very powerful tools for macrocyclization including for the preparation of peptidomimetic [17][18][32

• carbohydrate conjugates in which the heterocyclic triazolyl ring serves as a shackle for joining the carbohydrate building blocks. Further, these carbohydrate conjugates decorated with appropriate coupling partner can be paired through ring closing metathesis (RCM) reaction. Carrying out the metathesis

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• could successfully couple the three main fragments 39, 40 and 6 by first a Stille reaction, followed by a Kita esterification. Notably, this esterification was critical to avoid unfavorable isomerizations. For closing of the macrolide core they planned a challenging Hoye relay ring closing metathesis

• , 56 and 57 as shown in Scheme 12 [45][46][48]. The challenging ring-closing metathesis between C13 and C14 could not be established mainly due a competing backbiting process of the corresponding western fragment [46]. O'Neil’s syntheses of advanced dihydroarchazolid B fragments Synthesis of the

• and the subsequent HWE macrocyclization are remarkable. The Trauner group in turn effectively employed various ruthenium-catalyzed reactions, including a relay ring-closing metathesis, which demonstrates the powerfulness of such a tactic even for highly elaborate substrates with several initiation

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• . Rojas et al. proposed a convenient two-step pathway for the preparation of alkyl α,ω-dienes 3. These dienes are well-known precursors in ring-closing metathesis (RCM) and acyclic diene metathesis (ADMET) chemistry [32]. They first reported the quantitative α-alkylation of primary nitriles 1 [33]. In a

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• , the structure of another major component was suggested to be a tetradecen-13-olide. The synthesis of the two candidate compounds (Z)-5- and (Z)-9-tetradecen-13-olide revealed the former to be the naturally occurring compound. The synthesis used ring-closing metathesis as key step. While the Hoveyda

• in femoral glands of male mantellid frogs such as Spinomantis aglavei. The mass spectra of the synthesized macrolides as well as their rearranged isomers obtained during ring-closing metathesis showed that it is possible to assign the location of the double bond in an unsaturated macrolide on the

• , is usually not possible from an EI mass spectrum. In the article, we present the synthesis and for the first time elucidate the structure of macrolides from the frog family Hyperoliidae. Keywords: chemical communication; chiral gas chromatography; macrocyclic lactones; ring-closing metathesis

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

• Michał Malik and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255

• 1,4-addition of vinylmagnesium bromide to sugar-derived cyclohexenone, followed by an aldol reaction with a derivative of but-3-enal. The obtained diene is then subjected to an assisted tandem catalytic sequence: ring-closing metathesis with the subsequent reuse of the Ru-catalyst in the syn

• -dihydroxylation. The stereochemical outcome of these reactions is discussed. Keywords: carbasugars; one-pot reactions; ring-closing metathesis; syn-dihydroxylation; Introduction Derivatives of carbohydrates, in which the endocyclic oxygen atom is replaced with a methylene group are known as carbasugars [1]. Due

• Snapper [41][42]. Both groups described a methodology, in which the ring-closing metathesis (RCM) reaction is followed by the reuse of the Ru catalyst in the syn-dihydroxylation step. In our recent papers [43][44], we extended this concise and effective approach to the synthesis of bicyclic iminosugars

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• ) and then successfully connected in a silicon-tethered ring closing metathesis (RCM) [98] to provide the main backbone of cis-sylvaticin (40). Moreover, in 2009, Brown and co-workers reported on a short synthesis of the non-adjacent bis-THF core of cis-sylvaticin (40) making use of a permanganate

Bridgehead vicinal diallylation of norbornene derivatives and extension to propellane derivatives via ring-closing metathesis

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2016, 12, 1877–1883, doi:10.3762/bjoc.12.177

• propellanes via ring-closing metathesis. Single-crystal X-ray diffraction analysis of four compounds led to the realization of configurational correction of earlier reported molecules. Keywords: norbornene; propellane derivatives; ring-closing metathesis; single-crystal X-ray diffraction; vicinal

• ring-closing metathesis (RCM) [24][25][26][27][28][29][30][31][32]. Whereas, the diallyl derivative 2 can be derived from a readily available Diels–Alder (DA) adduct 3 through an allylation sequence. Results and Discussion Installation of two C–C bonds to generate quaternary centers in a

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• corresponding 1,4-DHQ of scaffold 1 has not been synthesised to our knowledge. Similar DHQs are typically prepared by methods such as ring-closing metathesis, or by controlled Birch-type reductions of the corresponding quinoline [10][11][12]. Very few instances of iodine-containing THQs or DHQs exist in the

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• ], multicomponent reactions [8], ring-closing metathesis approaches [9][10], tandem reactions of 1,3-dicarbonyl compounds [11][12] and cyclocondenzation reactions of salicylic aldehydes with α,β-unsaturated carbonyl compounds [13][14][15]. The utility of some of these methods are limited by drawbacks such as

Effective immobilisation of a metathesis catalyst bearing an ammonium-tagged NHC ligand on various solid supports

• Krzysztof Skowerski,
• Jacek Białecki,
• Stefan J. Czarnocki,
• Karolina Żukowska and
• Karol Grela

Beilstein J. Org. Chem. 2016, 12, 5–15, doi:10.3762/bjoc.12.2

• on activated carbon (8-C*) we were eager to test its catalytic properties. A model ring-closing metathesis (RCM) reaction leading to product 10 (Scheme 2) was used to check the influence of temperature and concentration on the activity of 8 on the solid support. We observed that the use of higher

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

• . Different strategies for the construction of E- or Z-cyclononenes have been reported to date and common reactions are summarized in Scheme 3. Transition metal-catalyzed ([M] = Ru, Mo, W) ring-closing metathesis (RCM) reactions of 1,10-dienes A can be employed for the synthesis of cyclononenes. The E/Z

• ring segment. The application of this useful intermediate was elegantly demonstrated in the synthesis of coraxeniolide A proceeding in 14% yield over five steps. Altmann and co-workers disclosed the total synthesis of blumiolide C (11) [20] employing a Z-selective ring-closing metathesis reaction for

• with acryloyl chloride gave ester 87 and a ring-closing metathesis reaction using Grubbs second generation catalyst [50] furnished an α,β-unsaturated lactone. Subsequent 1,4-addition of the cuprate derived from alkylmagnesium chloride 88 provided the trans-product with excellent diastereoselectivity

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• ring closing metathesis to afford the bicyclic product 53. Finally, the RCM of the 1,4-adduct resulting from the addition of 3-butenylmagnesium bromide yielded the spiro compound 54. Interestingly, the conversion of bicyclic compound 40 catalyzed by the same system also occurred selectively in the 4

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• delineate some guidelines for the use of these challenging substrates in metathesis reactions. Keywords: catalyst deactivation; cross-metathesis; N-heteroaromatic; pyridine; ring-closing metathesis; Introduction Over the past decades, metathesis has become a key reaction within the organic chemist’s

• allow the use of primary and secondary amines in ring-closing metathesis (RCM) and cross-metathesis (CM), and one of them is the transformation of amines into carbamates, amides or sulfonamides [27][28][29]. As an alternative, metathesis reactions can be performed with olefins possessing ammonium salts

• temperature (Scheme 11) [48]. This method was used to prepare polycyclic scaffolds that can be encountered in diverse alkaloid natural products such as coralyne and berberine (Scheme 12) [49]. Similarly, enyne ring-closing metathesis reactions were performed to access a variety of vinyl-3,4

Ru complexes of Hoveyda–Grubbs type immobilized on lamellar zeolites: activity in olefin metathesis reactions

• Hynek Balcar,
• Naděžda Žilková,
• Martin Kubů,
• Michal Mazur,
• Zdeněk Bastl and
• Jiří Čejka

Beilstein J. Org. Chem. 2015, 11, 2087–2096, doi:10.3762/bjoc.11.225

• cationic tags on NHC ligands were linker-free immobilized on the surface of lamellar zeolitic supports (MCM-22, MCM-56, MCM-36) and on mesoporous molecular sieves SBA-15. The activity of prepared hybrid catalysts was tested in olefin metathesis reactions: the activity in ring-closing metathesis of

• in ring-closing metathesis Hybrid catalysts were tested in ring-closing metathesis (RCM) of (−)-β-citronellene and N,N-diallyl-2,2,2-trifluoroacetamide (DAF) (Scheme 1). Figure 2 shows conversion curves of RCM of (−)-β-citronellene over HGIIN+Cl−/MCM-22, HGIIN+Cl−/MCM-56, HGIIN+Cl−/MCM-36, HGIIN+PF6