The Ugi four-component reaction as a concise modular synthetic tool for photo-induced electron transfer donor-anthraquinone dyads

• Sarah Bay,
• Gamall Makhloufi,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 1006–1016, doi:10.3762/bjoc.10.100

• -only systems 10 were also prepared by Ugi 4CR from the amino derivatives 4 and acetaldehyde (9), in moderate to good yield, with acetic acid (6) and tert-butyl isocyanide (7) as the corresponding acid and isonitrile components (Scheme 2). The appearance of single signal sets in the 1H and 13C NMR

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• benzaldehyde provided acid 13b in 28% yield and the main product of this reaction was an adduct of acid 1 with benzaldehyde which was isolated from the reaction mixture as ammonium salt 15 in 60% yield. Reaction with acetaldehyde was less successful and generated aminophosphinic acid 13c in low yield (<10

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

• ]. In 2009, the group of Dömling reported an Ugi-approach towards the synthesis of Bacillamide C (Scheme 42) [109]. (R)-Bacillamide C is a natural product with algicidal and antibacterial properties [97]. It was shown that a stereoselective reaction between Schöllkopf’s isocyanide, acetaldehyde

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• phenylglycine derived carbamate 7c. Indeed, if the excess of Selectride was quenched with acetaldehyde after reduction of 7a, the oxazolidine 10a was obtained (under the basic reaction conditions) as the major product. The outcome of the Cbz-cleavage strongly depended on the activity of the commercial Pd/C

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• -methoxybenzyloxy)acetaldehyde was expected to provide a tetra-functionalized Baylis–Hillman adduct (+)-16 from which grandiamide D can be obtained. A rearrangement of this common intermediate should be able to provide dasyclamide, which on oxidation, should give gigantamide A. Results and Discussion The synthetic

• entire pathway leading to the synthesis of (±)-grandiamide D is portrayed in Scheme 3. The reaction between ethyl bromoacetate (12) and p-methoxybenzyl alcohol in the presence of NaH (Scheme 3) furnished the desired ester 13 which on reduction with DIBAL-H provided 2-((4-methoxybenzyl)oxy)acetaldehyde

• (+)-grandiamide D (5). We assumed that the asymmetric Baylis–Hillman reaction [15] would be an ideal way to introduce chirality. Reaction between acryloyl sultam 19, and 2-((4-methoxybenzyl)oxy)acetaldehyde (14) in DMF [12], afforded cyclic product 20, which was then treated as such with TEA in ethanol to afford

Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde

• Haijun Qu,
• Xuejian Li,
• Fan Mo and
• Xufeng Lin

Beilstein J. Org. Chem. 2013, 9, 2846–2851, doi:10.3762/bjoc.9.320

• condensation of imine 5 with substituted acetaldehyde 2. This could then undergo an iodine-catalytic intramolecular cyclisation to afford the final dihydropyrimidinone 4. Based on the observations above, a preliminary investigation on the catalytic asymmetric version was performed. Recently, our group has

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• via a condensation between acetaldehyde and ammonia, nitric acid mediated oxidation then converts this to nicotinic acid (1.12) [24]. Although the initial pyridine formation is high yielding, this process is not without environmental issues due to the large excess of nitric acid and high temperatures

• flow process at their main plant in Visp, Switzerland. An alternative process is based on the availability of 3-picoline (1.15) which is generated as a major side product in the synthesis of pyridine prepared from formaldehyde, acetaldehyde and ammonia in a gas phase reaction (Scheme 3) [25]. The 3

• rosiglitazone (1.40) with its structure only differing in the substitution pattern of the parent pyridine ring. Its synthesis begins with the hydroxymethylation of 2-methyl-5-ethylpyridine (1.11), a commodity chemical obtained from the condensation of acetaldehyde with ammonium acetate (Scheme 12) [43]. At

Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support

• Jagdish D. Tibhe,
• Hui Fu,
• Timothy Noël,
• Qi Wang,
• Jan Meuldijk and
• Volker Hessel

Beilstein J. Org. Chem. 2013, 9, 2168–2179, doi:10.3762/bjoc.9.254

• and aliphatic aldehydes [37][38][39]. The same enzyme can also catalyze the reverse reaction, i.e. the cleavage of threonine into glycine and acetaldehyde [40][41][42]. Fesko et al. conducted kinetic and thermodynamic studies using the phenylserine synthesis from glycine and benzaldehyde as a model

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• provided some early studies to establish the conversion of amine radical cations to iminium ions. In 1980, Giannotti and Whitten reported that irradiation of triethylamine with three ruthenium polypyridyl complexes using visible light in the presence of water yielded acetaldehyde, presumably formed by the

• ion 12 that is hydrolyzed to acetaldehyde. Although the authors were not able to detect amine radical cation 12 spectroscopically, they were able to use ESR (electron spin resonance) techniques to detect Ru(I) and α-amino radical 11 with the aid of a spin trap, nitrosodurene. In 2010, Stephenson and

Thermochemistry and photochemistry of spiroketals derived from indan-2-one: Stepwise processes versus coarctate fragmentations

• Götz Bucher,
• Gernot Heitmann and
• Rainer Herges

Beilstein J. Org. Chem. 2013, 9, 1668–1676, doi:10.3762/bjoc.9.191

• as 1:27. Figure 4 shows an infrared spectrum of the pyrolysis products. The organic products include formaldehyde (FA), acetaldehyde (AA), ethene (ET), o-xylylene (XY), benzocyclobutene (BC), styrene (ST), and indan-2-one (IN). Some peaks could not be assigned. The assignment of the pyrolysis

• facile decay mechanism for 1. The primarily formed benzyl-dialkoxymethyl biradical 4 should undergo a very facile ring-opening reaction to yield an ester biradical 7, which can either cleave into ethylene, carbon dioxide and o-xylylene (XY), or eliminate acetaldehyde (AA) to yield an acyl-benzyl

• ), ca. 40 °C (2), and ca. 60 °C (3). The argon used was of 99.999% purity. In pyrolysis experiments, the length of the pyrolysis zone was ca. 5 cm. Reference IR spectra of benzocyclobutene, styrene, indan-2-one, acetaldehyde, formaldehyde, ethene and propene in Ar matrices were independently measured

Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• catalytic amounts as initiators of free-radical chains. The use of aldehydes for the activation of NHPI in an aerobic co-oxidative process was first reported by Einhorn and co-workers in 1997 [51]. The combination of stoichiometric amounts of acetaldehyde with catalytic quantities of NHPI promoted the

• amount of acetaldehyde to 10% mol ratio with respect to the alkyl aromatic [58][59] (Scheme 21). Thus, while the NHPI/AQ catalytic system was particularly effective in converting alkylaromatics to the corresponding carbonyl derivatives, this approach represents a valuable alternative when hydroperoxides

• are the desired products. Even if the presence of a polar solvent is crucial to maintain the polar catalyst in solution, it was possible to conduct the aerobic oxidation of cumene at 70 °C in the presence of 1% NHPI, 2% of acetaldehyde, and with a volume ratio cumene/CH3CN of 5/2, achieving the

Isotopically labeled sulfur compounds and synthetic selenium and tellurium analogues to study sulfur metabolism in marine bacteria

• Nelson L. Brock,
• Christian A. Citron,
• Claudia Zell,
• Martine Berger,
• Irene Wagner-Döbler,
• Jörn Petersen,
• Thorsten Brinkhoff,
• Meinhard Simon and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 942–950, doi:10.3762/bjoc.9.108

• ][15] followed by its conversion into its CoA-thioester by DmdB and oxidation by the FAD-dependent dehydrogenase DmdC. The addition of water to 3-(methylthio)acryloyl-CoA by the enoyl-CoA hydratase DmdD results in a hemithioacetal, which collapses under release of acetaldehyde, carbon dioxide and MeSH

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• acetaldehyde) and reductive (imine to amine) activity of the photocatalyst [48]. The reaction was also applied to the alkylation of aniline and piperidine. Use of a microsystem conferred a number of advantages over the same reaction under batch conditions: dialkylation could be suppressed as monoalkylated

N-Heterocyclic carbene-catalyzed direct cross-aza-benzoin reaction: Efficient synthesis of α-amino-β-keto esters

• Takuya Uno,
• Yusuke Kobayashi and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2012, 8, 1499–1504, doi:10.3762/bjoc.8.169

• electrophilicity relative to aromatic aldehydes [40][46][47][50]. To our delight, this methodology was found to be also suitable for the enolizable aliphatic aldehydes. Under the optimal reaction conditions (Table 1, entry 5), acetaldehyde and other primary alkyl aldehydes bearing functional groups such as ether

Photoreactions of cyclic sulfite esters: Evidence for diradical intermediates

• Rick C. White,
• Benny E. Arney Jr. and
• Heiko Ihmels

Beilstein J. Org. Chem. 2012, 8, 1208–1212, doi:10.3762/bjoc.8.134

• irradiation of the cyclic sulfite 8 for 3 h in acetonitrile gave phenyl acetaldehyde (3a), bibenzyl (4) and toluene (7) in Scheme 2; however, in contrast to the results of the photoreaction of the cyclic carbonate ester 1a under similar conditions, the oxirane 2a was not detected as a reaction product. The

• biradical BR2 with a conformation that is unfavorable for oxirane formation, but enables efficient hydrogen migration to result in aldehyde 3a. Theoretical calculations have confirmed that acetaldehyde derivatives may be formed upon rearrangement of the 1,3-oxyethandiyl [20][21] and that a subsequent

• a Büchi 510K and are uncorrected. Phenyl benzyl ketone, diphenyl acetaldehyde, diphenylmethane, benzil, phenyl acetaldehyde, and bibenzyl were obtained commercially (Aldrich) and used as received. Styrene glycol sulfite was prepared by adding thionyl chloride (2.5 g, 21 mmol) in diethyl ether (50 mL

Identification and isolation of insecticidal oxazoles from Pseudomonas spp.

• Florian Grundmann,
• Veronika Dill,
• Andrea Dowling,
• Aunchalee Thanwisai,
• Edna Bode,
• Narisara Chantratita,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 749–752, doi:10.3762/bjoc.8.85

• nitrogen labeling also occurs when 14N-tryptamine, leucine or phenylalanine is fed indicates an efficient transaminase activity in both strains, as one would indeed expect for a bacterial strain living on proteinogenic substrates such as insects. Indole acetaldehyde was also fed in 13C-labeled medium, but

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• reaction. Thus acetaldehyde (3b), anisaldehyde (3c) and glyoxylic acid (3d) were chosen as representative aliphatic, aromatic and functionalised aldehydes, respectively, and reacted with Michael adducts 6a and 6d under the conditions described above with allylamine. High diastereoselectivities were

Efficient, highly diastereoselective MS 4 Å-promoted one-pot, three-component synthesis of 2,6-disubstituted-4-tosyloxytetrahydropyrans via Prins cyclization

• Naseem Ahmed and
• Naveen Kumar Konduru

Beilstein J. Org. Chem. 2012, 8, 177–185, doi:10.3762/bjoc.8.19

• ). We further extended our method to aliphatic aldehydes (e.g., acetaldehyde) and hetero aromatic aldehydes (e.g., pyrrole aldehyde, furfural). Under optimal reaction conditions they reacted smoothly with homoallylic alcohols to afford the corresponding tetrahydropyran derivatives which show almost the

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• formate decarboxylase (BFD) catalyzing the (S)-selective aldol condensation of benzaldehyde (33) and acetaldehyde (32) with formation of (S)-2-hydroxy-1-phenyl-propanone (34) (Scheme 11). In the second vessel the intermediate (S)-34 was asymmetrically reduced by recLb-alcohol dehydrogenase (ADH) and the

Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis

• Inhee Cho,
• Labros Meimetis,
• Lee Belding,
• Michael J. Katz,
• Travis Dudding and
• Robert Britton

Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154

• , Figure 3) was also produced, but was readily separable from the desired product by flash chromatography. Unfortunately, reaction of the tetralithio intermediate 8 with carbonyl electrophiles (e.g., acetone, acetaldehyde, diethyl carbonate, valeraldehyde, cyclohexanal, crotonaldehyde, formaldehyde, DMF

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• performed on a cyclohexenone derivative prior to the Fischer indole synthesis (Scheme 27) [38]. The required imidazole 187 itself can be prepared via a variety of methods. For example, a process involving acetaldehyde, glyoxal and ammonium carbonate furnishes the desired compound in an excellent 95% yield

The preparation of 3-substituted-1,5-dibromopentanes as precursors to heteracyclohexanes

• Bryan Ringstrand,
• Martin Oltmanns,
• Jeffrey A. Batt,
• Aleksandra Jankowiak,
• Richard P. Denicola and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2011, 7, 386–393, doi:10.3762/bjoc.7.49

• -4-pentylcyclohexyl)acetaldehyde (9) [49]. The aldehyde was reduced with NaBH4 and subsequently brominated with PBr3 to give 1-bromo-2-(trans-4-pentylcyclohexyl)ethane (10) in overall yield of 42% (Scheme 9). Bromide 10 has been reported in the literature, but experimental details are lacking [50][51

Molecular rearrangements of superelectrophiles

• Douglas A. Klumpp

Beilstein J. Org. Chem. 2011, 7, 346–363, doi:10.3762/bjoc.7.45

• thought to be involved. In superacidic media, substrates such as ethylene glycol (159) are diprotonated and form the bis-oxonium ions, i.e., 160 as a stable species at −80 °C. When the solution is warmed to 25 °C, protonated acetaldehyde (162) is formed (Scheme 32). The conversion may occur by one of

Synthesis of new C^α-tetrasubstituted α-amino acids

• Andreas A. Grauer and
• Burkhard König

Beilstein J. Org. Chem. 2009, 5, No. 5, doi:10.3762/bjoc.5.5

• ), which bears a secondary carbon atom in the β-position, gives increased product yields. The best results were obtained for the unbranched n-butyraldehyde (2) and acetaldehyde (7) with yields of 36% and 28%, respectively, (entries 5 and 6). Methacrylaldehyde (8, entry 7) as an example of an unsaturated

• cis-product in which the two protons point to opposite sides of the ring no NOE cross peak occurs. The occurrence of the NOE cross peak confirms that the main diastereomer is trans configured. The diastereoselectivity of the reaction varies. For acetaldehyde (7) a ratio of to 2/1 in favour of the

• hydroxide (225 mg, 1.50 mmol, 1.2 equiv) and acetaldehyde (7, 70 µl, 1.25 mmol, 1 equiv). The product was purified with a 80:20 mixture of PE:diethyl ether (Rf = 0.1) to give 15 as a colourless oil in 28% yield (105 mg, 0.93 mmol). The product was obtained as an inseparable mixture of the cis and trans

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• group reported the total synthesis of (+)-bullatacin (311) via a diastereoselective [3+2] annulation reaction (Scheme 43) [104]. Racemic aldehyde 314, which was prepared from allylsilane (±)-312 and α-benzyloxy acetaldehyde (313), was treated with the highly enantiomerically enriched allylsilane 315 in