Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes

• Rongwei Jin,
• Charles Beromeo Bheeter and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 1239–1245, doi:10.3762/bjoc.10.123

• . However, a complete conversion of 2-bromonitrobenzene was observed. 2-Bromoaniline was found to be unreactive and was recovered. It should be noted that no amination reaction of 2-bromoaniline due to self-coupling was observed. From 2-(trifluoromethyl)bromobenzene, a very similar mixture of regioisomers

• regioisomers a and b were obtained after column chromatography. On the other hand, the use of 2-bromo-1,3-dichlorobenzene allowed to obtain very selectively the desired 5-arylation product 8b. Only traces of the C2-arylated thiophene 8a and a low amount of 2,5-diarylated product 8c were detected by 1H NMR and

• unfavourable C5 position of 3-substituted thiophenes. These less favoured regioisomers can be selectively obtained in moderate to good yields using a range of 3-substituted thiophenes, as chloro, ester, acetyl or ethyl acetate substituents are tolerated. Moreover, the sequential catalytic C5 and C2 arylations

Synthesis of ethoxy dibenzooxaphosphorin oxides through palladium-catalyzed C(sp²)–H activation/C–O formation

• Seohyun Shin,
• Dongjin Kang,
• Woo Hyung Jeon and
• Phil Ho Lee

Beilstein J. Org. Chem. 2014, 10, 1220–1227, doi:10.3762/bjoc.10.120

• -dimethoxyphenyl group at 2-position turned out to be compatible with the Pd-catalyzed oxidative cyclization. There are no regioisomers formed due to steric effects. Substrate 3c bearing a chloro group was selectively cyclized to afford 4c in 64% yield. To our delight, the present method worked equally well even

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• ] or AIBN radical [77][78][83][235][236]) or transition metal activation. Depending on the regioselectivity of the procedure, the addition of P–H to the triple bond results in the formation of two regioisomers (Scheme 36). The product that results from the Markovnikov addition of P–H corresponds to the

cis–trans Isomerization of silybins A and B

• Michaela Novotná,
• Radek Gažák,
• David Biedermann,
• Florent Di Meo,
• Petr Marhol,
• Marek Kuzma,
• Lucie Bednárová,
• Kateřina Fuksová,
• Patrick Trouillas and
• Vladimír Křen

Beilstein J. Org. Chem. 2014, 10, 1047–1063, doi:10.3762/bjoc.10.105

• were shown to be regioisomers of isosilybins A (5) and B (6) [10] (Figure 2). Other authors reported 2,3-cis-isomers of silybin [11][12], the relative configuration of which were corroborated by 1H NMR coupling constants, i.e., J2,3 of ca. 11 Hz in the trans-isomers and 2–3 Hz in the cis-isomers

Visible light mediated intermolecular [3 + 2] annulation of cyclopropylanilines with alkynes

• Theresa H. Nguyen,
• Soumitra Maity and
• Nan Zheng

Beilstein J. Org. Chem. 2014, 10, 975–980, doi:10.3762/bjoc.10.96

• 21 in 52% yield. The fused indoline motif was formed via an intramolecular Heck reaction under Fu’s conditions [41] to provide a mixture of two olefinic regioisomers 22, which were converted to saturated fused indoline 23 under standard catalytic hydrogenation conditions in a combined yield of 40

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• the dienophile, at least two regioisomers can be visualized for these compounds. Based on our characterization results, only one regioisomer, where the substitution was at position 5 of the isoindoloquinoline ring, was exclusively formed in these reactions. Inverse-electron demand hetero-Diels–Alder

• regioselectivity, Table 1, entries 6 and 14 with 3-chloro-4-fluoroaniline and entries 8 and 15 with 2-naphthylamine as the starting materials were capable of forming additional regioisomers, but the reaction appeared to be regioselective again in these cases, each producing only one regioisomer. These observations

Additive-assisted regioselective 1,3-dipolar cycloaddition of azomethine ylides with benzylideneacetone

• Chuqin Peng,
• Jiwei Ren,
• Jun-An Xiao,
• Honggang Zhang,
• Hua Yang and
• Yiming Luo

Beilstein J. Org. Chem. 2014, 10, 352–360, doi:10.3762/bjoc.10.33

• ethanol at room temperature (Table 1). It smoothly went until completion. Interestingly, the two regioisomers 4a and 5a were obtained with modest yield and poor regioisomeric ratio (Table 1, entry 1), which is quite different from the reaction of chalcone. Generally, only a single regioisomer 4′,5

• electron-deficient β-carbon of benzylideneacetone during the cycloaddition leading to two regioisomers [31]. In the presence of water, transition state A is favored due to the formation of an intermolecular hydrogen bonding between water and two carbonyl groups in the reaction substrates, while transition

• -dipolar cycloaddition to prepare two regioisomers in high yields, we tested two reaction conditions (conditions A: 5.0 equiv H2O as an additive; conditions B: 2.0 equiv 4-NO2PhCOOH as additive) for all substrates. As shown in Table 3, the reactions between benzylideneacetone with the azomethine ylides

Tuning the interactions between electron spins in fullerene-based triad systems

• Maria A. Lebedeva,
• Thomas W. Chamberlain,
• E. Stephen Davies,
• Bradley E. Thomas,
• Martin Schröder and
• Andrei N. Khlobystov

Beilstein J. Org. Chem. 2014, 10, 332–343, doi:10.3762/bjoc.10.31

• suggest that this difference alone is too small to explain the position of these features. We note also that 2 and 5 are mixtures of two regioisomers of the pyrrolidine functionalised C70 [19], in a ratio of 6:4 as determined by 1H NMR spectroscopy (see Experimental section). It is possible that these

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• , substituted by electron-donating or -withdrawing groups and heteroaromatic halides occurred in moderate to good yields (41% to 64% over two steps) with a preference for the para- over meta-regioisomers (2.3:1 to 5.7:1 ratio). Using the same methodology, the preparation and reactivity in tandem Diels–Alder

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• in the formation of a bridged tetracycle after initial Heck coupling followed by carbo-palladation and subsequent β-hydride elimination [69][70][71]. Double bond regioisomers (between C7 & C8 or C13 & C14) were obtained. Oxidation with DDQ yielded the 1,6-unsaturated ketone 72. Selective epoxidation

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• for proline as a substrate (Table 1, entries 1 and 3). The 1,3-dipolar cycloaddition of unsymmetrical dipolarophiles such as acrylamides can occur via the two pathways A and B leading to the formation of the regioisomers 4 and 4’. In our case, spirooxindol 4 is exclusively formed. All new cycloadducts

• dipolarophiles 5 with non-stabilized azomethine ylides generated from isatins 1 and sarcosine/proline has led to spiropyrrolidines 6a,6b and spiropyrrolizidines 6c–6h in moderate to good yields. In this reaction also two regioisomers can be expected, but in all experiments solely the regioisomer 6 is isolated

Continuous-flow Heck synthesis of 4-methoxybiphenyl and methyl 4-methoxycinnamate in supercritical carbon dioxide expanded solvent solutions

• Phei Li Lau,
• Ray W. K. Allen and
• Peter Styring

Beilstein J. Org. Chem. 2013, 9, 2886–2897, doi:10.3762/bjoc.9.325

• used was either styrene to yield the stilbenes 1 or methyl acrylate to yield the cinnamate ester 2. For each reaction there are three possible regioisomers. The thermodynamically favoured trans- (t) isomer is most common in standard organic solvents although under certain conditions the cis- (c) isomer

Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

• James A. B. Laurenson,
• John A. Parkinson,
• Jonathan M. Percy,
• Giuseppe Rinaudo and
• Ricard Roig

Beilstein J. Org. Chem. 2013, 9, 2660–2668, doi:10.3762/bjoc.9.301

• overlaps with the published syntheses of 6-deoxy-6-fluorohexoses from methyl sorbate [13]. The main benefits of the crotonic acid route are the absence of regioisomers as the double bond is installed after the asymmetric oxidation and the potential to deliver all of the 6-deoxy-6-fluorohexose isomers, as

Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis

• Yumeng Xi,
• Boliang Dong and
• Xiaodong Shi

Beilstein J. Org. Chem. 2013, 9, 2537–2543, doi:10.3762/bjoc.9.288

• , though in low yield. Two regioisomers were isolated, which were assigned as 8a and 8b (Scheme 3A). Diphenylacetylene gave trace amounts of the desired product under the identical conditions. Several diketones were tested to explore the scope of nucleophiles. The 1,3-cyclohexanedione derivative worked

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• for the aspired synthesis [10][11][12][13]. A classical synthesis was published in 1988 by Hansen where a silyl-substituted diene 3 was used for the [4 + 2]-cycloaddition (Scheme 1) [14]. Starting from bisquinone 4 the annulated ring system 5 is obtained in a 1:1 mixture of cis-endo regioisomers

• . Subsequent aromatization of the C-ring and several additional steps generated the daunomycin aglycon 6 and the corresponding isodaunomycin aglycone (dependent on the regioisomers) in a total of 16 steps. In 2003, Saá published a concise route to anthraquinone derivatives by using an intramolecular dehydro

Regioselective 1,4-trifluoromethylation of α,β-unsaturated ketones via a S-(trifluoromethyl)diphenylsulfonium salts/copper system

• Satoshi Okusu,
• Yutaka Sugita,
• Etsuko Tokunaga and
• Norio Shibata

Beilstein J. Org. Chem. 2013, 9, 2189–2193, doi:10.3762/bjoc.9.257

• of regioisomers (C2/C3 1.1:1) [22]. We disclose herein the regioselective 1,4-addition of the CF3 group into simple conjugated acyclic enones including chalcones using S-(trifluoromethyl)diphenylsulfonium salt 3 and a copper system in 11–37% yields (12 examples). Results and Discussion We initiated

• regioisomers and/or byproducts was detected in a crude mixture analyzed by 19F NMR. Under the best conditions shown in entry 10, we re-examined the reaction, but in the presence of TEMPO. The product formation was inhibited by TEMPO and O-trifluoromethylated TEMPO was detected in 2% by 19F NMR analysis (Table

• of CuCF3 species to provide the 1,4-adduct 2 in low to moderate yield. Although the true reactive species including CF3 radical and/or CuCF3 are not clear, the naked CF3 radical should be ruled out since high regioselectivity was observed, otherwise, a 1:1 mixture of regioisomers (C2/C3) should be

Sequential Diels–Alder/[3,3]-sigmatropic rearrangement reactions of β-nitrostyrene with 3-methyl-1,3-pentadiene

• Peter A. Wade,
• Alma Pipic,
• Matthias Zeller and
• Panagiota Tsetsakos

Beilstein J. Org. Chem. 2013, 9, 2137–2146, doi:10.3762/bjoc.9.251

• substitution patterns. We were also interested in determining the double bond specificity of the Denmark Diels–Alder reaction for unsymmetrical dienes. Previous work on cyclopentadiene and cyclohexadiene has shown that the reaction can be quite specific to give one of two possible regioisomers [11][12]. In the

• case of 1-(2-propenyl)cyclohexene only one of four possible regioisomers was observed [1]. However, it was not clear what the outcome would be for a simple open-chain conjugated diene. Consequently, cycloaddition reactions of 3-methyl-1,3-pentadiene were examined. This diene has both trisubstituted and

• monosubstituted double bonds allowing for cycloaddition to give up to four regioisomers. It is commercially available both as an E,Z-mixture and as the pure E-isomer. The Z-isomer can be obtained from the E,Z-mixture by selective removal of the E-isomer via cycloaddition with maleic anhydride [13]. Results and

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

• Pablo Morán-Poladura,
• Eduardo Rubio and
• José M. González

Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249

• arising from the migratory cyclization against that deriving from a straight iodoalkyne arylation reaction. As for the substituents on the amine ring, more electron-donating ones gave rise to the formation of the heterocycle featuring a distribution of regioisomers that indicates less iodine shift. In

Acid, silver, and solvent-free gold-catalyzed hydrophenoxylation of internal alkynes

• Marcia E. Richard,
• Daniel V. Fraccica,
• Kevin J. Garcia,
• Erica J. Miller,
• Rosa M. Ciccarelli,
• Erin C. Holahan,
• Victoria L. Resh,
• Aakash Shah,
• Peter M. Findeis and
• Robert A. Stockland Jr.

Beilstein J. Org. Chem. 2013, 9, 2002–2008, doi:10.3762/bjoc.9.235

• solvent. Microwave heating with 1 or 7 as the catalyst (14.0 μmol, 5%). The yield of the addition product and ratio of regioisomers was determined by 1H NMR spectroscopy using anisole as an internal standard. Hydrophenoxylation of unactivated internal alkynes.a Supporting Information Supporting

Continuous flow photocyclization of stilbenes – scalable synthesis of functionalized phenanthrenes and helicenes

• Quentin Lefebvre,
• Marc Jentsch and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 1883–1890, doi:10.3762/bjoc.9.221

• also tolerated, but nitro- and amino groups containing stilbenes showed low conversion or decomposition. Meta-substituted substrates gave inseparable regioisomers, and ortho-substitution led to low conversion. In the case of substrate 1e, a separable 1:1 mixture of regioisomers 2e and 2e’ was obtained

• , entry 3), whereas the reaction in acetonitrile resulted in a separable 1:1 mixture of regioisomers 2k and 2k’ (Table 4, entry 4). Finally, we decided to apply our photo-flow methodology in the synthesis of functionalised [5]helicenes and [6]helicenes. We identified 3-acetyl-9,10-dimethoxyphenanthrene

Stability of SG1 nitroxide towards unprotected sugar and lithium salts: a preamble to cellulose modification by nitroxide-mediated graft polymerization

• Guillaume Moreira,
• Laurence Charles,
• Mohamed Major,
• Florence Vacandio,
• Yohann Guillaneuf,
• Catherine Lefay and
• Didier Gigmes

Beilstein J. Org. Chem. 2013, 9, 1589–1600, doi:10.3762/bjoc.9.181

• presence of a mixture of cellobiose mono, di- and tri-acroylated, acrylic acid (resulting from the hydrolysis of acryloyl chloride), and free cellobiose. It is noteworthy that this reaction is not regioselective, so that several regioisomers are formed, which are very difficult to separate and quantify. BB

• reactive, but all regioisomers are possible. (Reversible) redox system of nitroxide. Hydrolysis of DMA in the presence of LiCl. Disproportionation of nitroxide 1 by acid treatment. Experimental redox potential of the oxidation (Eox) and of the reduction (Ered) in DMF and MeOH.a Acknowledgements The

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• preserved in the transformation. Aliphatic epoxides are opened selectively (>95:5) at the terminal position. Although very high regioselectivity with respect to the alkyne is observed when R1 = Ph and R2 = Me, attempts to differentiate between aliphatic alkyne substituents lead to mixture of regioisomers

Coupling of C-nitro-NH-azoles with arylboronic acids. A route to N-aryl-C-nitroazoles

• Marta K. Kurpet,
• Aleksandra Dąbrowska,
• Małgorzata M. Jarosz,
• Katarzyna Kajewska-Kania,
• Nikodem Kuźnik and
• Jerzy W. Suwiński

Beilstein J. Org. Chem. 2013, 9, 1517–1525, doi:10.3762/bjoc.9.173

• consistent with the analysis of regioisomers of 1-substituted-C-nitropyrazoles presented by Larina and Lopyrev in their review on nitroazoles [35]. Table 1 contains exemplified structures of 3-nitro-, 4-nitro- and 5-nitropyrazole derivatives and shows the differences in chemical shifts of carbon atoms in

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• of only 75%, whereas the use of additives at rt (conditions B) proved more efficient, with a yield of 97% (Table 1, entry 12). Triazoles 23–26 were obtained selectively as 1,4-disubstituted regioisomers. To understand the differences between the results obtained with the three different

Thiourea-catalyzed Diels–Alder reaction of a naphthoquinone monoketal dienophile

• Carsten S. Kramer and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 1414–1418, doi:10.3762/bjoc.9.158

• ]. Thereby, a mixture of regioisomers was always isolated. Regioisomer 5 was obtained diastereoselectively pure, the other isomer was received in a 3:1 (Table 1, entry 1) or 4:1 (Table 1, entry 2) mixture of 2a and 2b. The rather harsh conditions and the lack of selectivity in the cycloaddition of dienophile