Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives

• Zhi-Cong Geng,
• Jian Chen,
• Ning Li,
• Xiao-Fei Huang,
• Yong Zhang,
• Ya-Wen Zhang and
• Xing-Wang Wang

Beilstein J. Org. Chem. 2012, 8, 1710–1720, doi:10.3762/bjoc.8.195

• ], and moreover, pyrazolidines can also be oxidized to afford pyrazolines [8][9][10][11][12] and pyrazoles [13][14][15]. The pyrazolidine structural unit is commonly constructed by [3 + 2] cycloaddition reactions using hydrazones [16][17][18][19][20][21][22][23] or azomethine amines [24][25][26][27] as

Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• -homolysine side chain to an azide [12][13][14] employing the Wong azidation [15] enables Huisgen [3 + 2]-cycloaddition [16] as an orthogonal coupling method. In order to build up the peptide sequence in the presence of Fmoc, Cbz and the azide, an acid-labile protecting group was required for temporary

• 4 from methanol. Functionalization of the β-tripeptide template The cyclic β-tripeptide template 4 has the potential for orthogonal functionalization at the side chains with up to three different moieties, by successive amide-bond formation and by employing the Huisgen [3 + 2]-cycloaddition

• reported, as well as the functionalization with the nucleobase recognition units thymine-1-yl acetic acid (6) and (N4-benzyloxycarbonyl)cytosine-1-yl acetic acid (7) (Figure 3). In all cases, the template contains a third option for functionalization by covalent attachment of molecules through [3+2

Metal–ligand multiple bonds as frustrated Lewis pairs for C–H functionalization

• Matthew T. Whited

Beilstein J. Org. Chem. 2012, 8, 1554–1563, doi:10.3762/bjoc.8.177

• -metal (or "Roper-type") carbenes with significant π backbonding, consistent with Roper's predicted patterns of reactivity for metal–carbon double bonds [75]. These Roper-type carbenes also reacted with organic azides and nitrous oxide via an apparent [3 + 2] cycloaddition [76][77], leading to oxygen

Chiral multifunctional thiourea-phosphine catalyzed asymmetric [3 + 2] annulation of Morita–Baylis–Hillman carbonates with maleimides

• Hong-Ping Deng,
• De Wang,
• Yin Wei and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 1098–1104, doi:10.3762/bjoc.8.121

• intermolecular [3 + 2] cycloaddition of MBH carbonates with methyleneindolinones to afford the corresponding spirocyclopentaneoxindoles in good yields and high ee values in 2011 [49]. Moreover, Lu and co-workers have recently explored a series of thiourea-phosphine catalysts derived from L-threonine, which are

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• example of a more complex alkyne. The azide–alkyne [3 + 2] cycloaddition was catalyzed with copper(II) sulfate pentahydrate and L-ascorbic acid in DMF overnight at room temperature. A solution of EDTA was added to remove the remaining copper cations from the resin. Resin cleavage under acidic conditions

High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

• Henning S. G. Beckmann,
• Heiko M. Möller and
• Valentin Wittmann

Beilstein J. Org. Chem. 2012, 8, 819–826, doi:10.3762/bjoc.8.91

• explanation for the observed binding affinities. Results and Discussion Synthesis of glycoclusters The Cu(I)-catalyzed [49][50] Huisgen [3 + 2] cycloaddition [51] of azides and alkynes (CuAAC) is a frequently used method for the covalent attachment of carbohydrate epitopes to azide- or alkyne-presenting

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

• Marc Enßle,
• Stefan Buck,
• Roland Werz and
• Gerhard Maas

Beilstein J. Org. Chem. 2012, 8, 433–440, doi:10.3762/bjoc.8.49

• rearrangement. The short-lived carbonyl ylides derived from methionine and S-benzylcysteine formed head-to-tail dimers by a [3 + 3]-cycloaddition and could be trapped with external dipolarophiles, while the S-allyl derivative 14c yielded the pentacyclic compound 17 by an intramolecular [3 + 2]-cycloaddition

• tetrahydrothiophene 16 (31% yield, two diastereomers), and carbonyl ylide 14c is trapped by an intramolecular [3 + 2]-cycloaddition to give the pentacyclic compound 17 (35% yield). The regioselectivity of the latter reaction was established by NMR studies: after assignment of proton resonances from HMBC spectra, a

• NOESY NMR experiment indicated the correlation shown in Scheme 6. Intramolecular [3 + 2]-cycloaddition reactions of a carbonyl ylide with a nonactivated but suitably positioned olefinic bond have been known for some time [3][27][28][29][30][31][32][33][34][35] and can be used for the construction of

Photochemical and thermal intramolecular 1,3-dipolar cycloaddition reactions of new o-stilbene-methylene-3-sydnones and their synthesis

• Kristina Butković,
• Željko Marinić,
• Krešimir Molčanov,
• Biserka Kojić-Prodić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2011, 7, 1663–1670, doi:10.3762/bjoc.7.196

• % yield). Keywords: [3 + 2] cycloaddition; isoindoles; nitrile imines; pyrazoles; sydnones; Introduction Sydnones belong to the group of five-membered heterocyclic compounds referred to as being "mesoionic" and have been widely studied since their discovery [1][2][3][4][5]. They can be represented as

• , namely, trans–cis and cis–trans isomerization of the stilbene moiety, and photolysis of the sydnone ring resulting in the formation of the nitrile imine intermediate. The nitrile imine species is, in intramolecular dipolar [3 + 2] cycloaddition, trapped by the cis- or trans-double bond of the stilbene

• proton C with tolyl (H-10) and H-5 protons was seen. In order to explain the diverse structures (14 and 15) and their formation mechanism, we analysed the possible ways of intramolecular [3 + 2] cycloaddition relating to the arrangement of the sydnone ring towards the cis and trans double bond (Figure 5

Ugi post-condensation copper-triggered oxidative cascade towards pyrazoles

• Aurélie Dos Santos,
• Laurent El Kaim,
• Laurence Grimaud and
• Caroline Ronsseray

Beilstein J. Org. Chem. 2011, 7, 1310–1314, doi:10.3762/bjoc.7.153

• Pyrazolidinones were prepared in a two-step sequence starting from α-hydrazonocarboxylic acids. After a four-component Ugi coupling, the resulting hydrazone was engaged in a copper triggered [3 + 2] cycloaddition/aerobic oxidation cascade. Keywords: aerobic oxidation; copper(II); [3 + 2] cycloaddition; hydrazone

• pyrazolidinone under oxidative conditions from simple hydrazone derivatives (Scheme 1) [13]. The cascade features a [3 + 2] cycloaddition coupled with an aerobic oxidation of the resulting pyrazolidine. A further oxidative coupling may be observed according to the substitution pattern of the starting acyl

• possible Ugi pathways to introduce an alkene moiety that is prone to undergo an intramolecular [3 + 2] cycloaddition with a hydrazone, we selected the Ugi coupling between α-hydrazonocarboxylic acids and allylamine as the most straightforward path. There are several reports on the use of hydrazones in Ugi

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• aforementioned mechanistic pathway [26]. According to the theoretical data, the formal (4 + 2) cycloaddition would indeed comprise a two-step process consisting of a dipolar (3 + 2) cycloaddition of the carbonyl ylide I to afford a carbene species III [27][28], followed by a 1,2-alkyl migration to yield the

• , when PtCl2 (under an atmosphere of CO) is used, the major products are 2,3-indoline-fused cyclopentenes 44, which arise from a formal (3 + 2) cycloaddition (lower arrow) [86]. Thus, the appropriate choice of a Pt or Au catalyst determines whether the allenyl intermediate 42 participates as a 2C- or as

• derived from DTBM-Segphos or, as recently demonstrated, with gold complexes derived from chiral phosphoramidites [88][89]. Also in 2007, L. Zhang and co-workers reported another formal intramolecular cycloaddition between alkenes and allenes, in particular a (3 + 2) cycloaddition between allenyl MOM

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

• proved to be less successful for more complex pyrroles of which atorvastatin was an example (Scheme 1). In order to prepare the 5-isopropylpyrrole derivative 16 a more efficient [3 + 2] cycloaddition of an acetylene component with an amido acid 13 was developed. Unfortunately, reacting ethyl

• product 16 albeit in only moderate yield (Scheme 3). By modification of the coupling partners a more defined dipolar [3 + 2] cycloaddition between N,3-diphenylpropynamide (22) and an in situ generated mesoionic species 21 furnished the desired product 23 regiospecifically [4] (Scheme 4). A further

Photocycloaddition of aromatic and aliphatic aldehydes to isoxazoles: Cycloaddition reactivity and stability studies

• Axel G. Griesbeck,
• Marco Franke,
• Jörg Neudörfl and
• Hidehiro Kotaka

Beilstein J. Org. Chem. 2011, 7, 127–134, doi:10.3762/bjoc.7.18

• isoxazole (7a), 5-methylisoxazole (7b), 3,5-dimethylisoxazole (7d) and 3,4,5-trimethylisoxazole (7e) were synthesized by reaction of the corresponding carbonyl compounds with hydroxylamine, while 3-methylisoxazole (7c) was obtained by the [3 + 2]-cycloaddition of acrylonitrile with the trimethylsilylester

Brønsted acid-promoted azide–olefin [3 + 2] cycloadditions for the preparation of contiguous aminopolyols: The importance of disiloxane ring size to a diastereoselective, bidirectional approach to zwittermicin A

• Hubert Muchalski,
• Ki Bum Hong and
• Jeffrey N. Johnston

Beilstein J. Org. Chem. 2010, 6, 1206–1210, doi:10.3762/bjoc.6.138

• , diastereoselective sequence of two [3 + 2] cycloaddition reactions promoted by triflic acid where the large 1,3-diol protecting group – the 1,1,3,3-tetraisopropoxydisiloxanylidene group (TIPDS) – plays a crucial role in facial discrimination. Results and Discussion Our approach to the preparation of enantiomerically

• ) HF·pyridine, THF, 0 °C to rt, 1 h. Substrate-controlled double [3 + 2] cycloaddition. Supporting Information Supporting Information File 184: Experimental procedures, 1H and 13C NMR spectra. Acknowledgments Funding provided by the National Science Foundation (CHE-0848856) is gratefully acknowledged. H.M. is

A surprising new route to 4-nitro-3-phenylisoxazole

• Henning Hopf,
• Aboul-fetouh E. Mourad and
• Peter G. Jones

Beilstein J. Org. Chem. 2010, 6, No. 68, doi:10.3762/bjoc.6.68

• obtained in 40% yield. Keywords: cinnamyl alcohol; furoxan derivatives; isoxazole derivatives; X-ray diffraction; Introduction The isoxazole ring system, which can be easily obtained by [3 + 2] cycloaddition of nitric oxides to alkynes, is of interest since it forms a part of various biodynamic agents

Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid

• Arne Homann,
• Riaz-ul Qamar,
• Sevnur Serim,
• Petra Dersch and
• Jürgen Seibel

Beilstein J. Org. Chem. 2010, 6, No. 24, doi:10.3762/bjoc.6.24

• ), followed by N-acylation with the activated ester 7 led to the alkyne 8 in a yield of 75% based on D-arabinose. A [3+2] cycloaddition reaction between N-tert-butyl nitrone 9 and 8 and subsequent base-catalyzed ring-opening and hydrolysis afforded N-(1-oxohex-5-ynyl)neuraminic acid (Neu5Hex, 3) in 38% yield

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33