Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• enolate and subsequent asymmetric α-functionalization with an electrophile (E). Reported asymmetric α-fluorination of β-ketoesters 1 using different chiral PTCs. Asymmetric α-fluorination of benzofuranones 4 with phosphonium salt PTC F1. Asymmetric α-fluorination of 1 with chiral phosphate-based catalysts

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• significantly contributed to the field of asymmetric synthesis [1][2][3][4][5][6]. In these catalysts, (thio)urea and tertiary amino functional groups cooperatively activate a nucleophile and an electrophile simultaneously, in a suitable spatial configuration. Thus, they enable various stereoselective addition

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• acceptor, with the product of the reaction termed glycoside. Examples of acceptor molecules in nature are other saccharides to form oligosaccharides, nucleobases to form nucleosides, and amino acid side chains to form glycoproteins. The donor is the electrophile in the reaction and, therefore, when

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• opinion, the observed difference in the regioselectivity of the (thio)carbamoylation and acylation of 2 may be due to different bulkiness of the reacting electrophile: the electrophilic center of the protonated iso(thio)cyanate is relatively unhindered and able to attack the electronically activated but

• sterically hindered pyrene 1-position, whereas the bulkier protonated acetyl trifluoroacetate (the postulated electrophile in the examined Friedel–Crafts acylation) attacks sterically the less hindered 4-position. Conclusion We found that triflic acid-promoted (thio)carbamoylation of 2 with aliphatic iso

Metal-free hydroarylation of the side chain carbon–carbon double bond of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles in triflic acid

• Anna S. Zalivatskaya,
• Dmitry S. Ryabukhin,
• Marina V. Tarasenko,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya,
• Elena V. Grinenko,
• Ludmila V. Osetrova,
• Eugeniy R. Kofanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2017, 13, 883–894, doi:10.3762/bjoc.13.89

• -diprotonated form D. The calculated electronic characteristics of species A–F revealed that the dication D has the highest electrophilicity index ω (7.48 eV) among the other cationic species, even including trication F (Table 1). Therefore, dication D is expected to be an extremely reactive electrophile

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• of DMAP (Figure 1D). In the first part of the suggested mechanism, the pyridine base substitutes the chloride to form a sulfonylpyridinium intermediate. This intermediate makes the sulfonyl group a better electrophile, hence, the attack of the primary amine in the second part of the mechanism becomes

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• of nanoparticle formation. Trapping of the iminium electrophile could allow oligomer formation and dehydration, leading to the formation of the sp3-enriched nanocrystalline core. In the second phase of the reaction, following the loss of bulk water, further carbonisation occurs and aromaticity is

• ., TTDDA or sugar-derived amine) or through the nucleophilic attack of an alcohol to the iminium electrophile, followed by rearrangement of the resulting imidate. The work by Mandal et al. has also recently sought to provide some insights into nanoparticle formation and PL mechanism for sugar-derived CDs

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• domino reactions of N-propargylamines 20 with isothiocyanates 21 developed by Castagnolo. Electrophile-mediated cyclization of N-propargylthioureas 55.

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• activate the terminal acetylene primarily, which then undergoes a nucleophilic addition to the iminium electrophile generated from the aldehyde and the amine. Among different transition metals, copper metal has been mostly explored as the catalyst to activate the terminal acetylene, though there is a

• this case, activation of the Csp–COOH occurs via decarboxylation followed by the coupling with an iminium electrophile to produce the propargylamine. Although the strategy is interesting, functionalized acetylene carboxylic acids are difficultly accessible and the reaction is less 'atom economic

Structure–efficiency relationships of cyclodextrin scavengers in the hydrolytic degradation of organophosphorus compounds

• Sophie Letort,
• Michaël Bosco,
• Benedetta Cornelio,
• Frédérique Brégier,
• Sébastien Daulon,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2017, 13, 417–427, doi:10.3762/bjoc.13.45

• the reaction with the propyl analog 8 (50% versus 35%), but suffered from a slightly lower regioselectivity. In fact, 4% of the 3-monosubstituted regioisomer of 9 was also formed, whereas less than 1% of the 3-monofunctionalized regioisomer of 10 was observed for the reaction with electrophile 8. Once

• the first group was introduced in position 2, the substitution reaction at O-3 on the adjacent unit A was performed. Due to the lower reactivity of this alcohol group, an excess of base and electrophile was required for this step. In addition, the presence of the sterically hindered trityl-protected

• decreased the yield of scavenger 3. The introduction of the methyl iodobenzoate substituent at O-3 was conducted starting from monohydroxy compound 15 [34]. After reaction with electrophile 12, compound 4 was obtained through oxidation and hydrolysis of intermediate 16 (Scheme 2) using the same experimental

Decarboxylative and dehydrative coupling of dienoic acids and pentadienyl alcohols to form 1,3,6,8-tetraenes

• Ghina’a I. Abu Deiab,
• Mohammed H. Al-Huniti,
• I. F. Dempsey Hyatt,
• Emma E. Nagy,
• Kristen E. Gettys,
• Sommayah S. Sayed,
• Christine M. Joliat,
• Paige E. Daniel,
• Rupa M. Vummalaneni,
• Andrew T. Morehead Jr,
• Andrew L. Sargent and
• Mitchell P. Croatt

Beilstein J. Org. Chem. 2017, 13, 384–392, doi:10.3762/bjoc.13.41

• ], nitro [26][27], or alkyne [21][28][29][30][31][32], Scheme 1), or use an aryl carboxylate [33][34] which typically requires the assistance of silver or copper(I) salts for the decarboxylative step. It is rare to use a pentadienyl electrophile [35], or to have a diene or simple alkene adjacent to the

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

• described in Scheme 1, the nature of the medium and the substrate strongly influence the course of the reaction. Then, in the absence of a proton source, the organolithium intermediate can cyclize or react with an electrophile giving the expected coupling products [23][24][25][26][27]. Metal dissolving

Highly bulky and stable geometry-constrained iminopyridines: Synthesis, structure and application in Pd-catalyzed Suzuki coupling of aryl chlorides

• Yi Lai,
• Zhijian Zong,
• Yujie Tang,
• Weimin Mo,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen,
• Liqun Jin,
• Wen-hua Sun and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 213–221, doi:10.3762/bjoc.13.24

• up to 325 °C. With these sterically hindered iminopyridine–palladium complexes Pd1 to Pd5 in hand, we firstly investigated their catalytic activity directly in Suzuki cross-coupling reactions with chlorobenzene as the electrophile. The reactions were performed under the previously reported conditions

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• of organocatalysis. While traditional hydrogen bond donors containing N–H and O–H moieties have been effectively used for electrophile activation, activation based on other types of non-covalent interactions is less common. This mini review highlights recent progress in developing and exploring new

• organic catalysts for electrophile activation through the formation of C–H hydrogen bonds and C–X halogen bonds. Keywords: C–H hydrogen bond; counteranion activation; electrophile activation; halogen bond donor; hydrogen bond donor; organocatalysis; Review Introduction Over the past century chemists

• the near future. Electrophile Activation by Hydrogen Bond Donors [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Early examples of C–H hydrogen bonds and their recent use in supramolecular chemistry [18][19][32][33][34]. Design of 1,2,3-triazole-based catalysts for trityl group transfer

A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• high levels of over-alkylation to quaternary amine salts observed. Using exactly four equivalents of the electrophile increased the yield to 30%, while adopting a modified Finkelstein procedure by adding catalytic sodium iodide gave a modest further increase in yield, to 39%. Adapting the Tsukube

Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

• Masahiro Torii,
• Kohsuke Kato,
• Daisuke Uraguchi and
• Takashi Ooi

Beilstein J. Org. Chem. 2016, 12, 2099–2103, doi:10.3762/bjoc.12.199

• reduced diastereoselectivity (Table 2, entries 1–4). Sterically demanding 2-tolualdehyde-derived imine 3f served as a good electrophile and the corresponding Mannich adduct 4af was isolated as virtually a single stereoisomer (Table 2, entry 5). 3-Thiophenyl aldimine 3g was also well tolerated, but a

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• nucleophilicity of DBU/DBN and highly electrophile p-nitrophenyl carbonate derivatives. The reactions proceeded even at room temperature and displayed the nucleophilic addition and substitution with the p-nitrophenyl carbonate derivative of 10-bromodecanol. These caprolactam derivatives may find application in

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

• Maurizio Selva,
• Alvise Perosa,
• Sandro Guidi and
• Lisa Cattelan

Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181

• nucleophile and the electrophile. Scheme 20 shows the proposed mechanisms for the exemplar transesterification of a generic alcohol ROH with DMC using [P8881][MeOCO2] as catalyst. The catalytic cooperative activation also explains the selective formation of cyclic or linear products of Scheme 20, without the

• catalysis by the ionic liquid. This type of ambiphilic catalysis is characterized by the nucleophile and the electrophile both being activated respectively by the anion and by the cation of the ionic liquid. Thirdly, organic carbonates – used as feedstocks or produced by transesterification – are valuable

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

• in Supporting Information File 1). The N-iPr product 15a was isolated in only 3% yield. This, therefore, indicates that the electrophile reacts faster with the oxide anion of 13. Repeating the reaction with 15-crown-5 to limit the effect of the sodium cation did not appreciably effect the product

Reactions of N,3-diarylpropiolamides with arenes under superelectrophilic activation: synthesis of 4,4-diaryl-3,4-dihydroquinolin-2(1H)-ones and their derivatives

• Larisa Yu. Gurskaya,
• Diana S. Belyanskaya,
• Dmitry S. Ryabukhin,
• Denis I. Nilov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 950–956, doi:10.3762/bjoc.12.93

• the large charge on C2 of the protonated carbonyl groups and its substantial contribution into LUMO (Figure 2), this carbon is not reactive, probably, due to steric reasons. A comparison of the electrophilicity indices ω of C1 and D1 (Table 2) revealed that the former is stronger electrophile. Also

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• enolate or equivalent is fixed due to their cyclic nature, thus facilitating the control of the stereoselectivity; iii) they are substituted at the α-position of the carbonyl and therefore, after reaction with an electrophile, a tetrasubstituted stereocenter is created and, iv) the resulting adducts can

• being necessary for catalyst activity (Figure 4a) [87][88][89]. In 2010 Zhong proposed that the presence of the ortho C–H bond of the aryl group could be the key for success because it could participate together with the thiourea function in the activation of the electrophile [90]. This proposal was in

Asymmetric α-amination of 3-substituted oxindoles using chiral bifunctional phosphine catalysts

• Qiao-Wen Jin,
• Zhuo Chai,
• You-Ming Huang,
• Gang Zou and
• Gang Zhao

Beilstein J. Org. Chem. 2016, 12, 725–731, doi:10.3762/bjoc.12.72

• face of the enolate, driving the electrophile to attack from the Si face. Conclusion In summary, we have realized enantioselective α-aminations of 3-substitued oxindoles with azodicarboxylates by using amino acid-derived bifunctional phosphine catalysts. These reactions afford a variety of chiral 2

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• on the distal nitrogen atom is likely preventing this nitrogen from attacking the electrophile and triggers an elimination process which would yield a byproduct like 29. Of particular interest, when benzophenone (Ph2CO) was used to trap the α-lithiation product of N-Boc-N’-alkylpiperazines, in

• -piperazine 57. In summary, promising progress has been made in the direct α-lithiation trapping of N-Boc-protected piperazines, including enantioselective versions. So far, these methods are limited by narrow electrophile scopes and often low enantioselectivities rendering further developments necessary

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• nitro-Michael addition; supported catalysts; thioureas; Introduction The use of chiral bifunctional thioureas that allow the simultaneous activation of a electrophile, by hydrogen bonding, and a nucleophile, by deprotonation, plays a major role in the stereoselective formation of C–C bonds in different

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• % ee) (Scheme 10b) [39]. Based on the experimental results, the authors proposed a bifunctional mode of activation (TS7), where the electrophile is fixed and activated by the thiourea framework through several hydrogen bonds. At the same time, the indole is oriented to attack the Re face of the Michael

• reaction pathway based on previously reported transition states (Figure 6). The catalyst ent-4 would activate and fix the electrophile through several hydrogen-bonding interactions with the NH groups of the thiourea. Simultaneously, the hydroxy group would be involved in the activation of the nucleophile