The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• ]. The scope of the anodic methoxylation has so far been limited to either acyclic or 4–6-membered ring sizes, the use of electrosynthetic approaches can also be applied to larger 7-membered ring systems, albeit less frequently [65][66]. β-Lactams (4-membered rings) undergo anodic oxidation of the carbon

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• obtained. These include the selective reduction of β-enamino ester enantiomers [14], enzyme-catalyzed kinetic resolution [15], and a variety of asymmetric syntheses, for example, the enantioselective syntheses of β-lactams followed by ring opening [16][17], or the enantioselective desymmetrization of

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• dichloromethane or tetrahydrofuran, the reaction of disubstituted ketenes and N-tosyl arylimines provided corresponding trans-β-lactams in moderate to excellent ee (up to 98%), diastereoselectivities (up to 99:1 dr), and yields (up to >99%). Of particular interest, this methodology facilitates the formation of

• diverse trans-β-lactams that are complimentary to the related cis-lactams. 2.10 [4 + 1] Annulations of MBH carbonates with dienes Phosphine-catalyzed asymmetric [4 + 1] annulations between MBH carbonates and activated dienes could be achieved when using the bifunctional phosphine G6 as the catalyst

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• eight benzyl protecting groups was accomplished using Pearlman’s catalyst under mild acidic conditions to give fumonisin B2 (20) [45][46][47][84]. Tricylic β-lactams (1997) β-Lactam antibiotics are the most prescribed and successful class of antibiotics developed and used in clinical practice. This

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• -groups to olefinic acid by either asymmetric epoxidation, dihydroxylation or aminohydroxylation [10][11][12][13][14][15], (ii) the asymmetric synthesis of β-lactams by a Staudinger reaction between ketene and imine to give the corresponding amino acids [16], and (iii) the Lewis acid catalyzed

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

• ease of preparation via IMCRs [27][28][29]. First, the β-lactams will be described followed by five-membered rings varying from pyrrolidines to tetrazoles based amide bond isosteres. Examples of the six-membered rings showing peptide like-properties are the piperazines, homoprolines, dihydropyrimidones

• and triazines, whereas azepines form an important class of seven-membered cyclic peptidomimetics. Four membered ring constraints β-Lactams The smallest class of cyclic peptidomimetics is that of the β-lactams. β-lactams are effective antibiotics [30] but also show inhibitory activities against serine

• - [31], elastase- [32][33][34][35], and HIV-1 protease [36] and papain [37]. For the design of β-lactams, the Staudinger reaction involving a [2 + 2] cycloaddition of ketenes and imines is the most common method used [38]. However, Ugi reactions starting form β-amino acids are also described. In 2002

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• Enzyme catalysis was presented earlier (Scheme 1) as a strategy for synthesising fluorinated β-lactams (4) [18]. At that time, we were interested in the effect that the fluorine substituents had on the reactivity of the β-lactam derivatives. However this work now merits further attention, because it also

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• Alexander Penger Cortney N. von Hahmann Alexander S. Filatov John T. Welch Department of Chemistry, University at Albany, SUNY, 1400 Washington Ave., Albany, NY 12222, USA 10.3762/bjoc.9.303 Abstract β-Lactams were diastereoselectively formed by the reaction of SF5-containing aldimines, or an SF5

• minimization of unfavourable hydrophobic interactions. Results and Discussion The use of fluoroalkylimines to form β-lactams has proven especially useful in synthesis [24][25][26] especially in the Ojima β-lactam synthon method [27][28][29] used to prepare docetaxel analogs [26]. The general utility of the

• familiar Staudinger reaction of imines to transform readily accessible aldehydes to β-lactams has been well reviewed [30][31][32][33], yet in spite of this familiarity, the mechanism of this process remains a topic of interest [34][35][36]. Previously, it has been shown that fluorinated imines can undergo

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• thermolysis perform intramolecular C–H insertions to produce α-halo-β-lactams. When carried out with α-bromodiazoacetamides bearing cyclic side chains, the thermolysis reaction affords bicyclic α-halo-β-lactams, in some cases in excellent yields, depending on the ring size and substitution pattern of the

• -bromodiazoacetamides to form α-bromo-β-lactams. Results The diazoacetamides 3a–f were synthesised from α-bromoacetamides 2a–f using a protocol published by Toma et al. [40], modified by exchanging the base employed in the original procedure (DBU) for 1,1,3,3-tetramethylguanidine (TMG). The use of TMG allowed for a

• -bromodiazoacetamides will rapidly lose their bright red colour at temperatures above 0 °C. As can be seen in Table 1, the obtained yields of the α-bromo-β-lactams 5a–f vary significantly throughout the series. Among the derivatives with aliphatic amide side chains, the yields increase dramatically with ring size

Polar reactions of acyclic conjugated bisallenes

• Reiner Stamm and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 36–48, doi:10.3762/bjoc.9.5

• transformations. Keywords: β-lactams; conjugated bisallenes; cyclopentenones; epoxidation; halogen addition; hydrohalogenation; ionic additions; metalation; Introduction Whereas the use of hexa-1,2,4,5-tetraene (1) and its derivatives in pericyclic reactions is well documented [2][3][4][5][6], relatively little

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

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

• variety of 2-amino-3-arylpropan-1-ols, anti-2-amino-3-aryl-3-methoxypropan-1-ols and anti-2-amino-1-arylpropan-1,3-diols were prepared selectively through elaboration of trans-4-aryl-3-chloro-β-lactams. In addition, a number of 2-(azidomethyl)aziridines was converted into novel 2-[(1,2,3-triazol-1-yl

• antiplasmodial activity against both a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodium falciparum with IC50-values of ≤25 μM. Keywords: aminopropanes; antimalarial activity; aziridines; β-lactams; ring opening; Introduction Malaria remains a major issue in health control, especially in

• efforts have been devoted to the preparation of structurally diverse analogues bearing a functionalized propane skeleton [6][7][8]. In that respect, we have been engaged in the stereoselective synthesis of syn-2-alkoxy-3-amino-3-arylpropan-1-ols 1 by reductive ring opening of the corresponding β-lactams

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• addition of acetic acid and 15 equivalents of ammonium acetate to the crude mixture resulted in a postcyclization leading to imidazolones 4, with spontaneous elimination of the initial chloroformate substituent (Scheme 2). Arndtsen also demonstrated that 3-amido-substituted β-lactams 7 can be obtained

• to the mesoionic compound 5 under these conditions. Subsequent addition of a second, different imine produced β-lactams 9 in good yields, after heating at 55 °C for 24 h (Scheme 4) [4]. As mentioned above, imidazolinium salts 12 can be obtained by a dipolar cycloaddition of münchnone intermediates

• nucleophilic partners. It is expected that further useful, new multicomponent processes in which amines play a central role will be developed in the near future. Synthesis of substituted amides. Synthesis of ketocarbamates and imidazolones. Access to β-lactams. Access to β-lactams with increased structural

Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

• Satish S. More,
• T. Krishna Mohan,
• Y. Sateesh Kumar,
• U. K. Syam Kumar and
• Navin B. Patel

Beilstein J. Org. Chem. 2011, 7, 831–838, doi:10.3762/bjoc.7.95

• ], pyrrolines [10][11][12][13][14], imidazolidinones [15], β-lactams [16][17][18] and azepines [19][20][21]. There is ample evidence in the literature to confirm that the syntheses and applications of the N-acyl, N-sulfonamide or N-benzyl protected C-vinylaziridines are of considerable interest in organic

Single enantiomer synthesis of α-(trifluoromethyl)-β-lactam

• Václav Jurčík,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2011, 7, 759–766, doi:10.3762/bjoc.7.86

• ; organofluorine building blocks; α-(trifluoromethyl)-β-lactam; Introduction β-Lactams (azetidin-2-ones) have played a prominent role in medicinal chemistry and many structural variants have been prepared and elaborated [1]. Similarly, the CF3 group is an ubiquitous substituent in pharmaceutical research, where

• -substituted β-lactams 5 would give a mixture of two stereoisomers which might be separated into their individual diastereoisomers 5 by chromatography. N-Benzyl deprotection of the individual diastereoisomers would then provide β-lactam 1 as a single enantiomer. At the outset, (S)-(α-phenyl)ethylamine (3a) was

• nitrate (CAN) oxidation offered a milder deprotection method [15]. The aza-Michael reaction proved straightforward to generate 4b and then cyclisation again using thionyl chloride and triethylamine gave β-lactams 5b in a 40% de, presumably again a thermodynamically biased isomer ratio. The

Advances in synthetic approach to and antifungal activity of triazoles

• Kumari Shalini,
• Nitin Kumar,
• Sushma Drabu and
• Pramod Kumar Sharma

Beilstein J. Org. Chem. 2011, 7, 668–677, doi:10.3762/bjoc.7.79

• occupies the most important place in the treatment of fungal diseases. The triazole derivatives noted below were synthesized by various groups and show antifungal activity. Novel 1,2,3-triazole-linked with β-lactam–bile acid conjugates were prepared via 1,3-dipolar cycloaddition reactions of azido β

• -lactams and terminal alkynes of bile acids in the presence of a Cu(I) catalyst (click chemistry) by Vatmurge et al. The synthesized compounds were evaluated for their antifungal activity against different fungal strains such as Candida albicans, Cryptococcus neoformans, Benjaminiella poitrasii, Yarrowia

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• Científicas (CSIC), Juan de la Cierva 3, 28006-Madrid, Spain 10.3762/bjoc.7.73 Abstract New gold-catalyzed methods using the β-lactam scaffold have been recently developed for the synthesis of different sized heterocycles. This overview focuses on heterocyclization reactions of allenic and alkynic β-lactams

• which rely on the activation of the allene and alkyne component. The mechanism as well as the regio- and stereoselectivity of the cyclizations are also discussed. Keywords: alkynes; allenes; gold; heterocyclizations; β-lactams; Introduction The chemistry of alkynes and allenes has been extensively

• (endo versus exo cyclizations) as well as it being one of the most rapid and convenient methods for the preparation of heterocycles. On the other hand, in addition to the key role that β-lactams play in medicinal chemistry, namely, their action against pathogenic bacteria, enzyme inhibition, or gene

The allylic chalcogen effect in olefin metathesis

• Yuya A. Lin and
• Benjamin G. Davis

Beilstein J. Org. Chem. 2010, 6, 1219–1228, doi:10.3762/bjoc.6.140

• favorable than the sulfur in allyl sulfides. While, as a single example, Kotetsu and co-workers have synthesized selenium-containing bicyclic β-lactams via RCM of an allyl selenide derivative, enhanced reactivity was unnoticed [39]. With a better understanding of the allylic chalcogen effect, olefin

Novel tetracyclic structures from the synthesis of thiolactone-isatin hybrids

• Renate Hazel Hans,
• Hong Su and
• Kelly Chibale

Beilstein J. Org. Chem. 2010, 6, No. 78, doi:10.3762/bjoc.6.78

• affects their reactivity and stability [26][27][28][29][30][31]. Furthermore, the use of bridged amides as scaffolds in medicinal chemistry has been explored [32][33][34][35][36][37]. Indeed, the enhanced electrophilicity or acylating ability of β-lactams is partially attributed to the distortion from