Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• ]. Reaction of allyl iodide (17) with metalated 9d after addition of catalytic amounts of CuCN∙2LiCl led to the formation of the 5-allyl compound 18 in 37% yield. Metalation of 9d using TMPMgCl∙LiCl and subsequent transmetalation with ZnCl2 followed by Negishi cross-coupling reaction in the presence of Pd(dba

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• that the allylic fluorination was achieved by an SN2-type attack of fluoride on an electrophilic Pd(II)-allyl intermediate. One year later, the same author extended this method to a highly regio- and enantioselective fluorination of acyclic allylic chlorides. Compared to the previous process, this

• reaction used a different chiral bisphosphine ligand resulting in larger bite angles and afforded the products in good yields (Scheme 2b) [36]. A palladium-catalyzed method for the formation of allylic C–F bonds from allyl p-nitrobenzoate using TBAF(t-BuOH)4 as the fluoride source was explored by

• formation of fluorinated products with an overall retention of the stereochemical configuration suggests a mechanism wherein a palladium-π-allyl intermediate undergoes a rapid π-σ-π isomerization. In 2013, the first example of an allylic C–H fluorination reaction of simple alkenes with Et3N·3HF as a

Synthesis and anion binding properties of phthalimide-containing corona[6]arenes

• Meng-Di Gu,
• Yao Lu and
• Mei-Xiang Wang

Beilstein J. Org. Chem. 2019, 15, 1976–1983, doi:10.3762/bjoc.15.193

• -dichlorotetrazine [48] (2) under very mild conditions. The one-pot macrocyclic condensation reaction went to completion within 0.5 h to afford the corresponding O6-corona[3]arene[3]tetrazines 3a–c as the only macrocyclic ring products in yields of 38% to 63%. We then prepared N-allyl (1d), N-(2-(2-hydroxyethoxy

Halide metathesis in overdrive: mechanochemical synthesis of a heterometallic group 1 allyl complex

• Ross F. Koby,
• Nicholas R. Rightmire,
• Nathan D. Schley,
• Timothy P. Hanusa and
• William W. Brennessel

Beilstein J. Org. Chem. 2019, 15, 1856–1863, doi:10.3762/bjoc.15.181

• thermodynamic driving forces, intra-alkali metal exchange is one of the most challenging metathetical exchanges to attempt, especially when conducted without solvent. Nevertheless, grinding together the bulky potassium allyl [KA']∞ (A' = [1,3-(SiMe3)2C3H3]–) and CsI produces the heterometallic complex [CsKA'2

• between M'X and MX becomes particularly small? Here we describe the application of mechanochemistry in an organometallic context to examine alkali metal halide exchange unassisted by solvents. The organic group used is the bulky 1,3-bis(trimethylsilyl)allyl anion, [1,3-(SiMe3)2C3H3]− ([A']−) [13][14], for

• unreactive, even under mechanochemical conditions [20]. The iodides, in contrast, have the smallest lattice energies and thus should be the most easily disrupted and liable to exchange. Although several metal compounds of the allyl anion [A']– were potential candidates for the present study, the need for a

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

• allyl ether (2R,1'R,1''R)-135 which in the presence of Grubbs 1st generation catalyst produced (2R,1'R,1''R)-136. Transformation of the aziridine portion of 136 into an amino acid fragment of norfuranomycin (2S,2'R)-133 was accomplished starting from the hydrolytic opening of the aziridine ring and was

• )-135 instead of the allyl residue opened the way to synthesis of ʟ-(+)-furanomycin and its 5'-epimer. MeBmt (2S,3R,4R,6E)-139 is a nonproteinogenic amino acid found as a constituent of the naturally occurring cyclic peptide cyclosporine currently in medical use as immunosuppressant [89]. Syntheses of

• hydrolysis. Installation of the allyl group at the nitrogen atom required prior derivatization as an oxazolidin-2-one and Birch reduction to furnish 204. To construct a properly functionalized piperidine ring olefin metathesis was performed to supply the key intermediate 205. Taking advantage of the steric

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• calculations. Hydrolysis of these species resulted in the formation of phosphoryl-substituted allyl alcohols and 1,3-butadienes. A strong coordination of the oxygen of the P=O group with AlCl3 prevented the formation of cyclic 1,2-oxaphospholium ions and played a crucial role in the different reactivity of

• –H (Table 1). These species are formed by protonation of the central carbon atom of the allene system that gives the corresponding allyl cations, which undergo cyclization onto the oxygen of the P=O group. These ions have similar NMR data: the signal of the new proton H4 is located in the range 6.30

• oxaphospholium ion E1 (Table 1) through an intermediate formation of allyl cation E (Scheme 1). Ion E1 is transformed very fast into another species; after one minute new signals appear in the NMR spectra (see 31P NMR monitoring of this process in Figure 2), and after 12 hours it is completely converted to this

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• intermediates, building blocks 4 and 5 (4, R = Me and 5, R = CH2CH2Ph) were synthesized starting with allyldioxazaborolidine 11, an allyl-transfer reagent that was prepared as previously reported (Scheme 3) [27]. Allylation of methyl pyruvate (12) or 13 (synthesized from dimethyl oxalate and phenethylmagnesium

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• allyl groups could be transferred as well, although slightly lower yields were observed (Table 2, entries 8–11). Even an alkyl group could be transferred and interestingly, the best yields were achieved with this kind of group (Table 2, entries 12 and 13). It is worth noting that the same stereochemical

• corresponding carbenoid, especially with increasing temperature. Once the oxiranyllithium species is formed (A in Scheme 3), oxiranylborate complexes B are obtained by the addition of aryl-, benzyl-, allyl- or alkylboronic esters. This was clearly evidenced by the fast disappearance of the coloration linked to

• ][42]. From the results we so far gained, a migratory order could be assessed for the present reaction: Bu ≥ EDG-substitued Ar > EWG-substitued Ar ≥ Ar ≥ benzyl > allyl, and it appears that the larger the other substituents on the boron atom are, the easier the transfer is. A possible transition state

Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated O-, C-, N- and S-linked glycosides

• Madhu Babu Tatina,
• Xia Mengxin,
• Rao Peilin and
• Zaher M. A. Judeh

Beilstein J. Org. Chem. 2019, 15, 1275–1280, doi:10.3762/bjoc.15.125

• δ 6.01 (H2, H3) [19][21]. Using the optimized conditions in Table 1, entry 4, we then examined the substrate scope. Therefore, glucal 1a was reacted with various O-nucleophiles (using primary, secondary, tertiary, allyl, propargyl alcohols and sugars), C-nucleophiles (using trimethylsilyl cyanide

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• -dipropylated product 34a also being separately isolated, in 7% yield. Other primary ‘non-activated’ alkyl iodides also led to alkylated tartrates 33b,c and the corresponding dialkylated side-products 34b,c (Scheme 9). Under our modified alkylation conditions, ‘activated’ bromides (benzyl, allyl and prenyl

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• as linker to enable deprotection and cleavage under milder basic conditions [32]. The palladium-labile allyl groups were also used for amino protection [33][34]. The o-nitrobenzyl function was used as linker to enable photo cleavage [34]. However, these methods are still not ideal. The phenoxyacetyl

Switchable selectivity in Pd-catalyzed [3 + 2] annulations of γ-oxy-2-cycloalkenones with 3-oxoglutarates: C–C/C–C vs C–C/O–C bond formation

• Yang Liu,
• Julie Oble and
• Giovanni Poli

Beilstein J. Org. Chem. 2019, 15, 1107–1115, doi:10.3762/bjoc.15.107

• considerations in mind, a plausible mechanism for this annulation is proposed for the reaction between dimethyl 3-oxoglutarate (1a) and 2-cyclohexenone 4-benzoate (2a). The reaction starts with an oxidative addition of the bis-electrophile 2a onto the Pd(0) complex to generate η3-allyl complex B from the

• transient η2-alkene complex A (steps a and b). Deprotonation of the pro-nucleophile 1a by the counter-anion of the η3-allyl-Pd complex exchanges the benzoate for the enolate anion (step c) [50], and following C–C bond formation from the resulting anion-scrambled complex C leads to the Pd(0) complex D (step

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• excellent enantiomeric ratios could also be achieved (Scheme 7) [89]. However, the enantioselective and catalytic copper-catalyzed carbomagnesiation reaction gave poor enantiomeric ratios for the addition of vinyl, aryl and allyl groups and alternative strategies have been recently developed in our research

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• the solvent methanol to the double bond provided compound PO27 as major product (Scheme 17) [32]. It was not studied whether the use of other solvents can suppress this addition reaction. The allyl-substituted β-ketoenamide KE7 was converted under the standard conditions into condensation product PO28

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• -oxide using two different alkyl halides (R1X and R2X; R1, R2 = Me, Et, n-Bu, or allyl) as alkylating agents, leading to non-symmetric 1,3-dialkoxyimidazolium salts, was also reported [26]. In the present study, imidazole N-oxides 7 bearing either an adamantyloxy or adamantyl moiety at N(1) were smoothly

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• suitable molecule bearing the designated chiral segment (compound 2, vide infra). Results and Discussion For the synthesis, commercially available benzaldehyde (3) was allylated using Zn/allyl bromide in moist THF following Luche’s protocol to obtain the homoallylic alcohol (±)-4 (Scheme 1) [40]. We

• of most active HPA-12 isomers, originally proposed (1) and revised (2). Lipase-catalyzed trans-acylation of (±)-4 and subsequent Mitsunobu inversion. Conditions: (i) Zn/THF/allyl bromide/aqueous sat. NH4Cl/25 °C/3 h; (ii) vinyl acetate/lipase (Table 1); (iii) KOH/EtOH/25 °C/6 h; (iv) Ph3P/DIAD/p

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• -metathesis of allyl alcohol (59) and the cis–trans isomerization of cis-butenedienol (Z-58). Metathesis catalysts bearing quaternary ammonium groups provide an attractive alternative to classical ruthenium catalysts. Although they do not represent a great improvement in terms of catalytic activity, they

• allyl-sulfide on the surface of the protein. Cross metathesis of the modified protein 82 with allyl alcohol gave the CM product with over 90% conversion (Scheme 18). To achieve this challenging reaction, 200 equivalents (equiv) of HG-II catalyst were employed in a reaction mixture containing 0.01 mM 82

• . Remakably, no conversion was observed in the absence of MgCl2, which prevents the non-productive binding of the amino acid side chains to ruthenium. The authors suggested that the positive effect of allyl sulfides may be due to the coordination of the sulfur atom to the ruthenium center, favoring the

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• -azidoethyl 4,6-O-benzylidene-β-D-glucopyranoside (8) [18], prepared from D-glucose, was selectively O-allylated at the 3-hydroxy group by treatment with dibutyltin oxide followed by allyl bromide in the presence of cesium fluoride [19] via the formation of a stannylene acetal to give 2-azidoethyl 3-O-allyl

• experiment, allyl 2,3-di-O-benzyl-β-D-glucopyranoside (14) [25], prepared from D-glucose, was selectively 6-O-benzoylated by treatment with benzoyl chloride and pyridine at low temperature [26] to give allyl 6-O-benzoyl-2,3-di-O-benzyl-β-D-glucopyranoside (15) in 75% yield. The next step was to synthesize

• -benzylidene-2,3-di-O-benzyl-1-thio-α-D-mannopyranoside (5) [15] with compound 15 under a two-step activation using a combination of BSP and triflic anhydride in the presence TTBP as a base furnished allyl (4,6-O-benzylidene-2,3-di-O-benzyl-β-D-mannopyranosyl)-(1→4)-6-O-benzoyl-2,3-di-O-benzyl-β-D

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• ). Substitution on the sulfur atom was also screened, and small substituents [such as methyl- (1a), 2-hydroxyethyl- (1g), allyl- (1h)] rendered excellent conversions (98–99%, Table 2, entries 1, 7, and 8, respectively). For a bulkier linear S-substituent (butyl), 1k, the conversion dropped to 62% (Table 2, entry

• Scheme 3, α-chloroacetophenone (1.0 g, 6.47 mmol) was reacted with 1.1 equiv of potassium thioacetate, 1.1 equiv of allyl bromide and 2 equiv of K2CO3 in 5 mL of DMSO. After 24 h, 45 mL of buffer (Tris·HCl 50 mM pH 7.5) were added. Then, KH2PO4 was added in order to reach pH ≈7.5, followed by 200 mg of

• chromatography (petroleum ether/EtOAc 9:1) a 68% isolated yield was obtained for the S-allyl-β-ketosulfide 2h. The obtained β-ketosulfides can be chemoselectively converted into the corresponding sulfoxide/sulfone derivative [47][48]. It is well known that β-ketosulfoxides and β-ketosulfones are valuable

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• reagents [39][40] with various halo derivatives (e.g., aryl, vinyl, benzyl, or allyl) and has a broad scope to assemble diverse targets. This reaction was first reported in 1977, and it is an elegant and versatile method that allows the preparation of biaryls and olefins in good yields. To the best of our

Reusable and highly enantioselective water-soluble Ru(II)-Amm-Pheox catalyst for intramolecular cyclopropanation of diazo compounds

• Hamada S. A. Mandour,
• Yoko Nakagawa,
• Masaya Tone,
• Hayato Inoue,
• Nansalmaa Otog,
• Ikuhide Fujisawa,
• Soda Chanthamath and
• Seiji Iwasa

Beilstein J. Org. Chem. 2019, 15, 357–363, doi:10.3762/bjoc.15.31

• cyclopropanation using various diazo compounds with Ru(II)-Amm-Pheox Several diazoacetates and diazoacetamides were tested for asymmetric intramolecular cyclopropanation reactions using Ru(II)-Amm-Pheox catalyst (cat. 2) in H2O/ether biphasic medium as shown in Table 1. A diazo compound derived from allyl

• corresponding bicyclic product in excellent yield with high enantioselectivity (Scheme 1, 2p). Even the sterically demanding trisubstituted olefin-based allyl diazo Weinreb amide was found to be an effective substrate for the intramolecular cyclopropanation in this catalytic system, providing the corresponding

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• thermodynamically favored, displays a high activation barrier compared to that of the acyclic allyl analog H. An even higher activation barrier was calculated in the case of the 3-methyl and 3-phenyl-substituted cyclopropenes, I’ and I’’, respectively, which indicates that the concerted [2,3]-sigmatropic

• resulting α-allenic carbocations 24a–c (Scheme 14) [48]. As a complementary strategy, our group examined the [3,3]-sigmatropic rearrangement of cyanates derived from cyclopropenylcarbinols [53]. The allyl cyanate to isocyanate rearrangement displays many interesting features such as the possibility to

• stereochemical outcome was in agreement with a six-membered transition state model TS5 in which the three atoms of the cyanate (O=C=N) moiety would be arranged in an almost linear fashion (an angle of 173° was calculated in the allyl cyanate to isocyanate transition state) [56] and the substituent at C4 would

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• ) underwent highly efficient CM with styrenes as well as vinyl and allyl organic derivatives in the presence of Ru-1 (Scheme 8). The reactions were performed in refluxing methylene chloride in the presence of usually 1 mol % of first generation Grubbs catalyst (Ru-1) and led to the formation of the expected

• metathesis and provided a series of examples of effective CM of DDSQ-2SiVi with styrenes and selected allyl derivatives (Scheme 11) [23]. Under optimized reaction conditions (Scheme 11), CM led to the exclusive formation of E-isomers and was not accompanied by competitive homometathesis. This selectivity was

• obtained thanks to the use of the Ru-1 catalyst, moderately active in homometathesis of the olefins studied. Effective transformation was observed for substituted styrenes. Expected products were isolated with yields in the range of 88–95%. When allyl derivatives (allyltrimethylsilane, allylbenzene and

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• ,3R)-2 involved attachment of allyl and vinyl groups to form (4R,5R)-42 which was next oxidized to diacid and finally esterified to give dimethyl ester of (2S,3R)-2 as the hydrochloride (Scheme 10) [59]. By formation of the pyrrolidine ring Important synthetic strategies towards 3-hydroxyglutamic

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• two carbon atoms at the C-1’ position as well as at other terminal positions. Thus, all three hydroxy groups were protected as allyl ethers which were subsequently converted into -CH2CH2OH units (Scheme 3). Activation of the free OH groups in 18 as mesylates 19 and subsequent reaction with tripodal

• (C-5’), 77.7 (C-4), 74.9, 74.2, 73.0, 72.7, 72.0, 71.5 (6 × OCH2Ph), 72.4 (C-1’), 71.37 (C-7’), 71.06 (C-6’), 70.7 (C-5), 69.9 (C-7), 69.7 (C-6), 58.4, 53.9, 53.6, 53.0, 52.9, 49.8 (6 × CH2N) ppm; HRMS (ESI) [M + H]+ calcd for C74H97N2O17, 1285.6787; found, 1285.6803. 1’,6,6’-Tri-O-allyl-2,3,3’,4,4

• ’-penta-O-benzylsucrose (17): To a solution of triol 2 (88 mg; 0.11 mmol) in toluene (3 mL), allyl bromide (56 μL, 0.66 mmole, 6 equiv) was added followed by 50% aq NaOH (3 mL), and the heterogeneous mixture was vigorously stirred at 50 °C for 18 h (TLC monitoring hexane/ethyl acetate 4:1). The mixture