Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• secondary amines, as well as aryl and alkyl-substituted alkynes (Scheme 2). It is noteworthy that the approach tolerated challenging substrates such as formaldehyde, o-substituted benzaldehydes, and secondary aromatic amines. Moreover, the PS–NHC–Ag(I) catalyst was proven to be reusable at least 12 times

• ., o-substituted benzaldehydes) gave worse results. Other strengths of the approach are the ultralow catalyst loading (0.236 mol % gold) and the great TON (>400). Periodic mesoporous organosilicas (PMOs), properly functionalized with HS/SO3H [29] or alkylimidazolium [30], were recently used as support

Secondary amine-initiated three-component synthesis of 3,4-dihydropyrimidinones and thiones involving alkynes, aldehydes and thiourea/urea

• Jie-Ping Wan,
• Yunfang Lin,
• Kaikai Hu and
• Yunyun Liu

Beilstein J. Org. Chem. 2014, 10, 287–292, doi:10.3762/bjoc.10.25

• thiourea and alkyne were not successful. On the other hand, benzaldehydes with ortho- and meta-substitution could also react with thioureas and propiolates to give the corresponding DHPMs 5l–5p. However, compared with thiourea, urea has been found to undergo a similar transformation more toughly, and DHPMs

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

Bis(benzylamine) monomers: One-pot preparation and application in dendrimer scaffolds for removing pyrene from aqueous environments

• Olivia N. Monaco,
• Sarah C. Tomas,
• Meghan K. Kirrane and
• Amy M. Balija

Beilstein J. Org. Chem. 2013, 9, 2320–2327, doi:10.3762/bjoc.9.266

• sterically hindered benzaldehydes 2b–g could also be utilized to prepare the corresponding bisimine products (Table 1, compounds 3b–g). Minimal impact on the overall yield of the reaction was observed upon varying the benzaldehyde concentration or substituting absolute ethanol for methanol; however, elevated

• . Bisamine products were obtained with electron-deficient, electron-rich, and sterically hindered benzaldehydes (Table 2, Compounds 4b–h). The formation of 4f was difficult, resulting in lower overall yields and longer reaction times, possibly due to the electron-withdrawing properties of the nitro group [13

• benzaldehydes that resulted in unstable imines. An unprecedented first-generation bisamine-based dendrimer 6 was prepared but was found to degrade readily in organic solvents. More stable second-generation dendrimers composed of hybrid dendrons 8 and one of the three tri-phenol cores 5, 9, and 10 were

Regioselective carbon–carbon bond formation of 5,5,5-trifluoro-1-phenylpent-3-en-1-yne

• Motoki Naka,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2013, 9, 2182–2188, doi:10.3762/bjoc.9.256

• and limitation of this procedure were investigated. A number of carbonyl compounds were employed as electrophiles for the anions generated from the enyne 4. Benzaldehydes with electron-donating (Table 2, entries 2 and 3) as well as -withdrawing (Table 2, entry 4) substituents at the para position were

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• is variable. Our optimal conditions for the reaction were heating at 65 °C with a flow rate of 1 mL/min, this corresponding to a product conversion of 90%, as determined by GC analysis. Performing the reaction under these conditions using three substituted benzaldehydes as substrates, we obtained

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• built from the reaction of methyl 5-iodosalicilate (40) with ethyl bromoacetate (41) followed by ester hydrolysis and cyclization to afford 5-iodo-3-coumaranone (42), which, after condensation with the proper benzaldehydes, gave the aurone scaffold 43, which could be radiolabeled (Scheme 3C). As for the

NHC-catalysed highly selective aerobic oxidation of nonactivated aldehydes

• Lennart Möhlmann,
• Stefan Ludwig and
• Siegfried Blechert

Beilstein J. Org. Chem. 2013, 9, 602–607, doi:10.3762/bjoc.9.65

• yields. We assume that the oxygen concentration in the reaction solution is relatively similar due to the rather low solubility of O2 in organic solvents. However, vigorously shaking or stirring is essential. For hydroxy-substituted benzaldehydes only moderate yields (64%) could be achieved, even with

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• -annulation cascade reaction with N,N-(dialkylamino)benzaldehydes, a process in which a 1,5-hydride shift occurs followed by larger ring formation [16]. After the evaluation of different Brønsted acid catalysts, diphenylphosphate (20 mol %) was identified as a suitable catalyst for the reaction. Toluene again

• was the solvent of choice, and microwave irradiation was used for a shorter reaction time. The scope of the reactions was broad allowing different indoles and a variety of N,N-(dialkylamino)benzaldehydes to be employed, and the products 3 were obtained in good to excellent yields (Scheme 4) [16]. For

Synthesis of a novel chemotype via sequential metal-catalyzed cycloisomerizations

• Bo Leng,
• Stephanie Chichetti,
• Shun Su,
• Aaron B. Beeler and
• John A. Porco Jr.

Beilstein J. Org. Chem. 2012, 8, 1338–1343, doi:10.3762/bjoc.8.153

• ). The chemotypes discovered in initial pilot studies have been further developed into library scaffolds and identified as biologically interesting structures [6]. Herein, we report the expanded utility of alkynyl o-benzaldehydes through a sequential metal-catalyzed cycloisomerization process to afford a

• novel polycyclic cyclopropane chemotype. Results and Discussion In an effort to further explore the utility of alkynyl o-benzaldehydes as scaffolds for reaction screening, we designed a focused reaction screen with diynyl benzaldehyde [7] substrate 3. Based on the cycloisomerization/addition reactions

• synthesis of alkynyl o-benzaldehydes: 2-(3-(but-2-ynyloxy)prop-1-ynyl)benzaldehyde. To a solution of 2-bromobenzaldehyde (2.0 g, 10.8 mmol) and 1-(prop-2-ynyloxy)but-2-yne (1.4 g, 13 mmol) in Et3N (68 mL), was added tetrakis(triphenylphosphine)palladium(0) (0.38 g, 0.32 mmol). The reaction mixture was

Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity

• Matthias D’hooghe,
• Stéphanie Vandekerckhove,
• Karen Mollet,
• Karel Vervisch,
• Stijn Dekeukeleire,
• Liesbeth Lehoucq,
• Carmen Lategan,
• Peter J. Smith,
• Kelly Chibale and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2011, 7, 1745–1752, doi:10.3762/bjoc.7.205

• prepared by treatment of N-(arylmethylidene)alkylamines (synthesized in high yields through condensation of the corresponding benzaldehydes with the appropriate primary amines in CH2Cl2 in the presence of anhydrous MgSO4) with 1.5 equiv of chloroacetyl chloride and 3 equiv of 2,6-lutidine in benzene

Synthesis of diverse dihydropyrimidine-related scaffolds by fluorous benzaldehyde-based Biginelli reaction and post-condensation modifications

• Bruno Piqani and
• Wei Zhang

Beilstein J. Org. Chem. 2011, 7, 1294–1298, doi:10.3762/bjoc.7.150

• Bruno Piqani Wei Zhang Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Boulevard, Boston, MA 02125, USA 10.3762/bjoc.7.150 Abstract Dihydropyrimidinones and dihydropyrimidinethiones generated from the Biginelli reactions of perfluorooctanesulfonyl-attached benzaldehydes

• diversity-oriented synthesis of biaryl-substituted dihydropyrimidinone 5, thiazolopyrimidine 6, and dihydropyrimidine 7 compounds (Scheme 1). The perfluorooctanesulfonyl-attached benzaldehydes 1 were used as a key component for the Biginelli reactions [6]. The Biginelli products 4 were used as a common

• extractions (F-SPE) for purification [7]. The perfluorooctanesulfonyl group served as a phase tag for F-SPE and also as a convertible linker for the Suzuki coupling to introduce biaryl functionality to the heterocyclic skeletons [8][9][10][11][12]. Result and Discussion Fluorous benzaldehydes 1 were prepared

Novel synthesis of pseudopeptides bearing a difluoromethyl group by Ugi reaction and desulfanylation

• Jingjing Wu,
• Hui Li and
• Song Cao

Beilstein J. Org. Chem. 2011, 7, 1070–1074, doi:10.3762/bjoc.7.123

• group (PhS) with Bu3SnH/AIBN according to our previous research, and the desired difluoromethyl-containing pseudopeptide was successfully obtained [27]. To demonstrate the scope of the method, several different substituted anilines, substituted benzaldehydes, isocyanides and this novel difluorinated

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

Novel carbazole–pyridine copolymers by an economical method: synthesis, spectroscopic and thermochemical studies

• Aamer Saeed,
• Madiha Irfan and
• Shahid Ameen Samra

Beilstein J. Org. Chem. 2011, 7, 638–647, doi:10.3762/bjoc.7.75

• synthesized by a modified Chichibabin reaction, i.e., by the condensation of diacetylated N-alkylcarbazoles with 3-substituted benzaldehydes in the presence of ammonium acetate in refluxing acetic acid. All the polymers were characterized by FTIR, 1H NMR, 13C NMR, UV–vis spectroscopy, fluorimetry, TGA and DSC

• recrystallization. The diacetylated carbazole monomers were heated under reflux with various 3-substituted benzaldehydes and ammonium acetate in glacial acetic acid in a modified Chichibabin reaction to assemble the pyridine ring in situ and afford the desired polymers (Scheme 2) [27]. The construction of the

• pyridine ring in situ by reaction of diacetylated carbazole monomers with different benzaldehydes and ammonium acetate may be envisaged by the complex sequence shown in Scheme 3 which involves protonation, enolization, deprotonation, dehydration, the nucleophilic addition of ammonia, intramolecular

The arene–alkene photocycloaddition

• Ursula Streit and
• Christian G. Bochet

Beilstein J. Org. Chem. 2011, 7, 525–542, doi:10.3762/bjoc.7.61

• exposure to light but, depending on the substitution pattern, other reactive sites may be involved. Carbonyl groups are also known to undergo different types of photochemistry. Thus, benzophenones, acetophenones and benzaldehydes are not only used as sensitizers but can, under specific circumstances, also

• allyloxy, acrylic or allenyloxy substituted anthraquinones, benzophenones or benzaldehydes indeed give potentially interesting benzoxepines. There is little doubt that arene photochemistry will continue to help the synthetic chemist to assemble complex and challenging targets in the coming years

• benzoxepine by Jones et al. Photocycloaddition observed by Griesbeck et al. Mechanism proposed by Griesbeck et al. Intramolecular photocycloaddition of allenes to benzaldehydes.

SbCl₃-catalyzed one-pot synthesis of 4,4′-diaminotriarylmethanes under solvent-free conditions: Synthesis, characterization, and DFT studies

• Ghasem Rezanejade Bardajee

Beilstein J. Org. Chem. 2011, 7, 135–144, doi:10.3762/bjoc.7.19

• other hand, electron-rich groups such as para-methoxy decrease the product yield (Table 1, entries 10–11). Surprisingly, benzaldehydes with two or even three deactivating methoxy groups react with N,N-dimethylaniline to produce the corresponding products in moderately good yields (Table 1, entries 13–14

• variety of aryl and heteroaryl aldehydes under solvent-free conditions to give substituted triarylmethanes. Using SbCl3 as catalyst, even electron-rich benzaldehydes such as 3,4,5-trimethoxybenzaldehyde gave the corresponding products in good yields. Operational simplicity, high yields, and the ability to

Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in propylene carbonate

• Michael North and
• Marta Omedes-Pujol

Beilstein J. Org. Chem. 2010, 6, 1043–1055, doi:10.3762/bjoc.6.119

• dichloromethane is also consistent with a less tightly organized transition state, again consistent with only one of the reaction components interacting with the catalyst. To investigate this further, a Hammett analysis was undertaken using a range of substituted benzaldehydes. Hammett analysis It is well

• -substituted benzaldehydes with their substituent constants can be used to investigate the relative importance of Lewis acid and Lewis base catalysis in a catalysed reaction. This methodology was developed using the asymmetric addition of TMSCN to aldehydes catalysed by complexes including 1, 2 and 6 (Figure 7

• -substituted benzaldehydes were determined (Table 5) and used to construct a Hammett plot (Figure 9). All of the aldehydes included in Table 5 gave nonracemic cyanohydrin trimethylsilyl ethers, confirming that in each case the reaction was catalysed by complex 2. In most cases the enantiomeric excess of the

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

• monoperfluoroalkyl thio derivatives. With iron powder as a catalyst bis(SRF)-derivatives can be obtained (Scheme 9). Similarly, methyl benzoates and benzaldehydes with two and especially three hydroxyl groups form bis(CF3S)-substituted derivatives without of catalyst. Analogous reactions are observed with aniline

Synthesis of spiroannulated and 3-arylated 1,2,4-trioxanes from mesitylol and methyl 4-hydroxytiglate by photooxygenation and peroxyacetalization

• Axel G. Griesbeck,
• Lars-Oliver Höinck and
• Jörg M. Neudörfl

Beilstein J. Org. Chem. 2010, 6, No. 61, doi:10.3762/bjoc.6.61

• exception of the adamantane derivative 5d which has a remarkably shorter O-O bond distance. 4-Arylated 1,2,4-trioxanes The 1,2,4-trioxanes 10 were formed in moderate to good yields, with the Hock-type cleavage product from the ß-hydroperdiol as the only side-product, from 4 and substituted benzaldehydes

Prins fluorination cyclisations: Preparation of 4-fluoro-pyran and -piperidine heterocycles

• Guillaume G. Launay,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2010, 6, No. 41, doi:10.3762/bjoc.6.41

• of substituted benzaldehydes 4. Electron withdrawing groups on the aromatic ring led to the more efficient reactions (Table 1, entries a–g) to generate 4-fluoropyrans 5 with conversions of 65–73%. Diastereoselectivities were however, modest with d.r’s of between 1.9 : 1 and 5.4 : 1. With electron

Gold film- catalysed benzannulation by Microwave- Assisted, Continuous Flow Organic Synthesis (MACOS)

• Gjergji Shore,
• Michael Tsimerman and
• Michael G. Organ

Beilstein J. Org. Chem. 2009, 5, No. 35, doi:10.3762/bjoc.5.35

• benzaldehydes [36] A 10 mL round-bottom flask was charged with Pd(PPh3)4 (0.0375 mmol), CuI (0.075 mmol), and purged with argon. To it were added consecutively: THF (6 mL), Et3N (1.5 mmol), the aryl bromide (0.75 mmol), and the alkyne (0.9 mmol). The solution was then heated to 70 °C and stirred for 6–13 h

• chromatography. 2-(2-Phenylethynyl)benzaldehyde (1a). Following the general procedure for the synthesis of benzaldehydes, column chromatography (10% diethyl ether in pentane) provided 141 mg of product as a pale-brown oil (91%, yield). 1H NMR (300 MHz, CDCl3): δ 10.67 (s, 1H), 7.96 (d, J = 7.8 Hz, 1H), 7.63 (t

• the general procedure for the synthesis of benzaldehydes, column chromatography (10% diethyl ether in pentane) provided 142 mg of the product as a pale-yellow oil (89%, yield). 1H NMR (300 MHz, CDCl3): δ 10.63 (s, 1H), 7.95 (d, J = 8.1 Hz, 1H), 7.66–7.51 (m, 3H), 7.43 (t, J = 7.8 Hz, 1H), 7.34 (dd, J

Convenient methods for preparing π-conjugated linkers as building blocks for modular chemistry

• Jiří Kulhánek,
• Filip Bureš and
• Miroslav Ludwig

Beilstein J. Org. Chem. 2009, 5, No. 11, doi:10.3762/bjoc.5.11

• easily accessible as a pure (E)-product from the pinacol ester of 4-formylphenylboronic acid and diethyl benzylphosphonate through the Horner–Wadsworth–Emmons reaction in 76% yield [36], methoxy and N,N-dimethylamino substituted (E)-4-bromostilbenes were synthesized from the corresponding benzaldehydes

Enantioselective nucleophilic difluoromethylation of aromatic aldehydes with Me₃SiCF₂SO₂Ph and PhSO₂CF₂H reagents catalyzed by chiral quaternary ammonium salts

• Chuanfa Ni,
• Fang Wang and
• Jinbo Hu

Beilstein J. Org. Chem. 2008, 4, No. 21, doi:10.3762/bjoc.4.21

• aldehydes with halogen substitution (Table 3, entries 3, 5–9) showed better enantioselectivity than those with methyl and methoxy substituents (Table 3, entries 11,12). Among the halogenated benzaldehydes that were tested, the reaction with 2-chlorobenzaldehyde showed an enantiomeric excess up to 64% (Table

• enantioselective difluoromethylation of aromatic aldehydes with Me3SiCF2SO2Ph and PhSO2CF2H. The enantioselectivity is substrate-dependent and for 2-chlorinated benzaldehydes, an ee up to 64% was obtained. The easy preparation of the chiral cinchonium salts and the convenient experimental procedure make the