Features of the behavior of 4-amino-5-carboxamido-1,2,3-triazole in multicomponent heterocyclizations with carbonyl compounds

• Eugene S. Gladkov,
• Katerina A. Gura,
• Svetlana M. Sirko,
• Sergey M. Desenko,
• Ulrich Groth and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2012, 8, 2100–2105, doi:10.3762/bjoc.8.236

• contain cross-peaks between pyrimidine NH and spiro-carbon, which is also in good correlation with structure 4. Analogous elucidations allowed the structures of compounds 7 and 9 to be established. Conclusion In summary, two types of heterocyclization reactions involving 4-amino-5-carboxamido-1,2,3

• '-cyclopentane}-3-carboxamide (4a) or 5,6,7,8-tetrahydro-4H-spiro{[1,2,3]triazolo[5,1-b]quinazoline-9,1'-cyclohexane}-3-carboxamide (4b) under all the conditions tested. The best results were observed in the case of microwave-assisted synthesis in methanol at 120 °C. Spirocompound 4c may be obtained by a

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• spiro-products 17 and 18 (Scheme 13). The sole formation of the annulated indole 18 as a single diastereoisomer suggests a mechanism that is strictly closer to the classical oxidative Heck reaction (pathway B) rather than to a Wacker-type reaction (pathway A). In fact, the formation of the product 18 is

• into the esters 50 by hydrolysis. The same reactivity was satisfactorily tested also on the 3-indolylallylcarboxamides 51, giving, however, compounds 49 and 50 already obtained from the substrates 48 (Scheme 29). The formation of 49 and 50 may be reasonably justified by the intervention of the spiro

• /esterification process through iminium intermediates. Cyclization of 3-indolylallylcarboxamides involving 1,2-migration of the acyl group from spiro-intermediates. Domino reactions of 2-indolylallylcarboxamides involving N–H functionalization. Cyclization/acyloxylation reaction of 3-alkenylindoles. Doubly

On the proposed structures and stereocontrolled synthesis of the cephalosporolides

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2012, 8, 1287–1292, doi:10.3762/bjoc.8.146

• report focuses on 5,5-spiroketal lactones of the cephalosporolide and related families (Figure 2) [26][27]. Cephalosporolides E and F are co-isolated as a mixture, and previous syntheses likewise produce these compounds as a mixture in the absence of methods to control the spiro-center [28][29][30

• structures of cephalosporolide E and F. Results and Discussion We recently reported the stereocontrolled synthesis of cephalosporolide H (reported structure) and its spiroketal isomer [32]. Our strategy featured the use of zinc salts to control the spiro-center using either steric biases or chelation

• cephalosporolide E for the first time in a stereocontrolled manner. Pheromone spiroketals. Reported structures of the cephalosporolides and penisporolides. Reported and synthesized cephalosporolide H isomers. Stereocontrol of oxygenated 5,5-spiroketals. Synthesis of the reported cephalosporolide H and its spiro

Expanding the chemical diversity of spirooxindoles via alkylative pyridine dearomatization

• Chunhui Dai,
• Bo Liang and
• Corey R. J. Stephenson

Beilstein J. Org. Chem. 2012, 8, 986–993, doi:10.3762/bjoc.8.111

• development [9][10][11]. To our knowledge, most studies of these types of molecules focus on spirooxindoles bearing a pyrrolidine ring at the 3-position of the oxindole core, while few reports expand to formulate the syntheses of other spiro rings. As part of our ongoing reaction-screening objective [12][13

• , spiro [1,3]oxazino compounds having a diene moiety within their molecular framework are susceptible to Diels–Alder (D–A) reactions [22]. Scheme 2 highlights three examples in which compound 3a was exposed to N-substituted maleimides in toluene at 150 °C under microwave irradiation for 0.5 h, and D–A

• structure of compound 3d. X-ray crystal structure of compound 8a. Unexpected alkylative pyridine dearomatization during our previous work on the synthesis of spirooxindole pyranochromenediones. Application of spiro [1,3]oxazino compound 3a in D–A reactions. Reaction of isatins 4 and 1,3-dicarbonyl compounds

Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

• Kieron M. G. O’Connell,
• Monica Díaz-Gavilán,
• Warren R. J. D. Galloway and
• David R. Spring

Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95

• centre is the key point of interest, as we believe that, with the judicious selection of appendages, it should allow us to access a range of bicyclic structures, including examples of fused, bridged and spiro bicycles. Preliminary studies into the utility of these substrates in a DOS context have yielded

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

• but with the intention of targeting a piperidin-2-one ring-containing polycyclic scaffold, cyclic imine 5a was added at the second stage. Tetracyclic spiro-lactam 2a was isolated in high enantiomeric purity (90% ee) in good chemical yield (62%, Scheme 8) [111][112]. For the products of the nitro

Synthetic approaches to multifunctional indenes

• Neus Mesquida,
• Sara López-Pérez,
• Immaculada Dinarès and
• Ermitas Alcalde

Beilstein J. Org. Chem. 2011, 7, 1739–1744, doi:10.3762/bjoc.7.204

• in which the (3-indenyl)acetic acid 7 was reduced to the corresponding alcohol 10 and transformed to tosylate 11. However, an attempt to convert the (3-indenyl)ethylsulfonate 11 into the advanced inden-5-amine 9 was ineffective, resulting in the formation of the spiro indene 12 instead, and hence

Access to pyrrolo-pyridines by gold-catalyzed hydroarylation of pyrroles tethered to terminal alkynes

• Elena Borsini,
• Gianluigi Broggini,
• Andrea Fasana,
• Chiara Baldassarri,
• Angelo M. Manzo and
• Alcide D. Perboni

Beilstein J. Org. Chem. 2011, 7, 1468–1474, doi:10.3762/bjoc.7.170

• terminal alkynes with pyrroles is shown in Scheme 2. It is highly probable that the products arise from the vinyl gold species B and F, in turn generated from alkynes 4 after coordination to AuCl3. The formation of F can result by a migration of the acyl group from the spiro center of the transient

• cationic spiro gold complex D, in turn generated by the attack of the more nucleophilic C-2 of the pyrrole nucleus on the intermediate A. On the other hand, complex B can arise from the direct attack of the pyrrolic C-3 on the activated species A or from the migration of the alkyl group on the spiro

Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols

• Michel Chiarucci,
• Mirko Locritani,
• Gianpiero Cera and
• Marco Bandini

Beilstein J. Org. Chem. 2011, 7, 1198–1204, doi:10.3762/bjoc.7.139

• be adaptable allowing a double lactonization event with 1j, hence providing spiro-lactone 2j in 93% yield. Apart from the generality on malonyl substrates, we decided to explore the applicability of the present methodology to less reactive monoester analogs [47]. In this context, readily available

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• formation of the 1,4-furan dipole (Scheme 21). In fact, a resonance structure of 60 can be envisaged entailing a gold–carbene and a carbonyl ylide 63. Upon 1,3-dipolar cycloaddition with the alkoxy vinyl ether, bridged bicycle 64 is formed. 1,2-Alkyl migration and bridge opening produces a spiro cation 66

When cyclopropenes meet gold catalysts

• Frédéric Miege,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2011, 7, 717–734, doi:10.3762/bjoc.7.82

• obtained (9m/9’m > 99:1) (33%) when the reaction was carried out at 10 °C (Scheme 5) [18][19]. The reaction was successfully extended to a variety of 3,3-disubstituted cyclopropenes (3-methyl-3-benzylcyclopropene, spiro[2.5]oct-1-ene, 3-benzyl-3-isopropylcyclopropene, 3-tert-butyl-3-methylcyclopropene) and

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• produce the (+)-DMDP (49) and (−)-bulgecinine (50) (Scheme 8). The starting point in the synthesis of (+)-broussonetine G, 53, was the same annulated oxazolone 48 which, after conversion into the Weinreb amide 51, was coupled with the alkyl bromide substituted spiro compound 52 (Scheme 9). In fact, the

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

• oxycyclization/hydroxylation of 2-azetidinone-tethered alkynols for the synthesis of non-fused, spiro, and fused oxabicyclic β-lactams has been reported [65]. Attempts at a cyclization reaction of terminal alkynols using gold catalysts failed. However, under the appropriate reaction conditions was found that

• order to determine whether the conclusions drawn from the homopropargylic alcohols 22 could be extrapolated to other alkynols, tertiary carbinols 24 were examined. Under similar gold-catalyzed conditions, spiro β-lactams 25 were obtained as single isomers in good yields (Scheme 13). To further probe the

• -azetidinone-tethered homopropargylic alcohols. Gold-catalyzed formation of spiro tetrahydrofuryl-β-lactam hemiacetals from 2-azetidinone-tethered homopropargylic alcohols. Gold-catalyzed formation of fused tetrahydrofuryl-β-lactam hemiacetals from 2-azetidinone-tethered bis- and tris-homopropargylic alcohols

The arene–alkene photocycloaddition

• Ursula Streit and
• Christian G. Bochet

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

• the core of Lancifodilactone F [70]. This triterpenoid contains three fused and one spiro cycle and is a very challenging target. Initial attempts to construct the fused seven-, six- and five-membered core were unsuccessful. Introduction of a trimethylsiloxy group on the tether and an oxygen

• mechanism involves the reaction of the olefin with the ipso position of the aromatic ring affording a spiro biradical intermediate. Recombination of these radicals proceeds further until formation of the final compound. Some years later, Kohmoto showed that similar enamides linked to a naphthyl moiety

• completely new reaction Sakamoto has proposed a mechanism involving a ζ-hydrogen abstraction to form a biradical intermediate (Scheme 35, E). The resulting biradical cyclizes to form the spiro compound F upon recombination of the biradical. Re-aromatization affords the carboxylate G, which further attacks

Rh(I)-catalyzed intramolecular [2 + 2 + 1] cycloaddition of allenenes: Construction of bicyclo[4.3.0]nonenones with an angular methyl group and tricyclo[6.4.0.0^1,5]dodecenone

• Fuyuhiko Inagaki,
• Naoya Itoh,
• Yujiro Hayashi,
• Yumi Matsui and
• Chisato Mukai

Beilstein J. Org. Chem. 2011, 7, 404–409, doi:10.3762/bjoc.7.52

• -en-6-one 11, instead the spiro[4.5]deca-1,6-diene derivative 12 was formed exclusively in 87% yield (Table 3, entry 1). After screening several reaction conditions, the tricyclic derivative 11 was obtained in 73% yield along with 12 (24%) when the reaction was carried out in the absence of AgBF4

• under a CO atmosphere (Table 3, entry 2). The [RhCl(CO)dppp]2-catalyzed reaction of 10 under a N2 atmosphere with or without AgBF4 produced the spiro product 12 in 93% and 91% yield, respectively, whereas no spiro product 12 was obtained under thermal conditions without a Rh(I)-catalyst (Table 3

• spiro[4.5]deca-1,6-diene system via β-elimination and subsequent reductive elimination [31][32]. In summary, we have developed the intramolecular Rh(I)-catalyzed PKTR between 1,1-disubstituted allene and 1,1-disubstituted alkene functionalities, which leads to the facile formation of bicyclo[4.3.0

Rh-Catalyzed rearrangement of vinylcyclopropane to 1,3-diene units attached to N-heterocycles

• Franca M. Cordero,
• Carolina Vurchio,
• Stefano Cicchi,
• Armin de Meijere and
• Alberto Brandi

Beilstein J. Org. Chem. 2011, 7, 298–303, doi:10.3762/bjoc.7.39

• )-catalyzed opening of the VCP moiety embedded in an azapolycyclic system occurs at high temperature (110–130 °C) to afford the corresponding 1,3-dienes in moderate yield (34–53%). Keywords: nitrogen heterocycles; rearrangement; rhodium; small ring systems; spiro compounds; Introduction The cyclopropyl

• (Scheme 6). Conclusion Azaheterocycles 14, 15 and 17 containing a spiro-annelated VCP moiety have been synthesized starting from cyclic nitrones and BCP by a three-step two-pot sequence consisting of a 1,3-dipolar cycloaddition, thermal rearrangement and Wittig methylenation. These compounds in the

• tetrahydrospiro[cyclopropane-1,1’(2’H,6’H)-pyrido[2,1-a]isoquinolin]-2’-one 8. Synthesis of 7’-oxohexahydro spiro[cyclopropane-1-8’(5’H)indolizines] 12. Olefination of spirocyclopropanated heterocyclic ketones 8, 12 and 16. Rearrangement of VCPs 15 and 17 catalyzed by Rh(PPh3)3Cl. Mechanism of the rearrangement

Total synthesis of (±)-coerulescine and (±)-horsfiline

• Mukund G. Kulkarni,
• Attrimuni P. Dhondge,
• Sanjay W. Chavhan,
• Ajit S. Borhade,
• Yunnus B. Shaikh,
• Deekshaputra R. Birhade,
• Mayur P. Desai and
• Nagorao R. Dhatrak

Beilstein J. Org. Chem. 2010, 6, 876–879, doi:10.3762/bjoc.6.103

• rearrangement protocol was applied to obtain 3-allyl oxindole. This oxindole was then converted to (±)-coerulescine and (±)-horsfiline. Keywords: alkaloids; Claisen rearrangement; Jones oxidation; spiro-oxindole; Wittig olefination; Introduction The spiro[pyrrolidin-3,3′-oxindole] ring system is a widely

• . The majority of these alkaloids have interesting biological activities and pharmacological properties [9]. However, a crucial observation, reported by Danishefsky et al. [10], found that the unnatural analogous 3 and 4 (Figure 1) of the spiro[pyrrolidin-3,3′-oxindole] possessed significant activity

• protocols. Several synthetic approaches have been developed for the synthesis of the spiro[pyrrolidin-3,3'-oxindole] framework for horsfiline and coerulescine [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34], both in racemic and enantiomeric forms. These

Synthesis of a novel analogue of DPP-4 inhibitor Alogliptin: Introduction of a spirocyclic moiety on the piperidine ring

• Arumugam Kodimuthali,
• Padala Lakshmi Prasunamba and
• Manojit Pal

Beilstein J. Org. Chem. 2010, 6, No. 71, doi:10.3762/bjoc.6.71

• compound C indicates that the key step would involve the condensation of two key intermediates, i.e., the piperidinyl derivative 9 and the appropriately substituted 6-chloro uracil derivative 11 (Figure 2). The intermediate 9 in turn could be synthesized via functional group manipulations of the spiro

• target compound C as the TFA salt. The 1H NMR spectra of compound C indicated the presence of a spiro cyclopropyl ring: the four cyclopropyl protons appeared as a series of four multiplets in the region δ 0.15–0.25, 0.30–0.40, 0.50–0.60 and 0.65–0.75, the vinylic proton of pyrimidine-2,4-dione moiety

Preparation, structures and preliminary host–guest studies of fluorinated syn-bis-quinoxaline molecular tweezers

• Markus Etzkorn,
• Jacob C. Timmerman,
• Matthew D. Brooker,
• Xin Yu and
• Michael Gerken

Beilstein J. Org. Chem. 2010, 6, No. 39, doi:10.3762/bjoc.6.39

• spirocyclic derivative 9b. Thus, reaction of the spiro-ketal 7b [28] with cyclooctadiene (6) furnished a mixture of 9b and 9b′ in excellent yield in the same ratio of isomers as observed in the previous case. Again, the endo,endo,syn-isomer 9b could not be satisfactorily separated from the endo,endo,anti

A thermally-induced, tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition approach to carbocyclic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2010, 6, No. 33, doi:10.3762/bjoc.6.33

• product containing this basic skeleton is welwitindolinone A isonitrile (4); a compound that has recently captured the attention of the synthetic community [3][4]. Spiro[cyclobutane-1,3'-indolin]-2'-ones (3, n = 0) have previously been prepared but the synthetic approach is mostly limited to simple

Enantioselective synthesis of tricyclic amino acid derivatives based on a rigid 4-azatricyclo[5.2.1.0^2,6]decane skeleton

• Matthias Breuning,
• Tobias Häuser,
• Christian Mehler,
• Christian Däschlein,
• Carsten Strohmann,
• Andreas Oechsner and
• Holger Braunschweig

Beilstein J. Org. Chem. 2009, 5, No. 81, doi:10.3762/bjoc.5.81

• considerable interest in recent years. Incorporated in peptides or proteins, they may increase the metabolic stability and allow the introduction of novel structural motifs [1][2][3][4]. ß-Turns, for example, result if conformationally constrained spiro- or bicyclic amino acids such as 1 [5], 2 [6], and 3 [7

A stable enol from a 6-substituted benzanthrone and its unexpected behaviour under acidic conditions

• Marc Debeaux,
• Kai Brandhorst,
• Peter G. Jones,
• Henning Hopf,
• Jörg Grunenberg,
• Wolfgang Kowalsky and
• Hans-Hermann Johannes

Beilstein J. Org. Chem. 2009, 5, No. 31, doi:10.3762/bjoc.5.31

• stable enol 4, which is converted by dehydrogenation into the benzanthrone derivative 7. Under acidic conditions 4 isomerises to the spiro compound 11 and the bicyclo[4.3.1]decane derivative 12. Furthermore, the formation of 7 and the hydrogenated compound 13 is observed. A mechanism for the formation of

• the reaction products is proposed and supported by DFT calculations. Keywords: consecutive reactions; intramolecular cyclization; molecular modelling; spiro compounds; X-ray structural analysis; Introduction Compounds for optoelectronic applications with electroluminescent (e.g. organic light

• under these reaction conditions. Spiro compound 11 (11% yield) was characterised by NMR spectroscopy, mass spectrometry and single crystal X-ray crystallography (see below). The 1H NMR spectrum (600 MHz) of 11 shows two aliphatic triplets at δ = 2.16 and 3.42 ppm (J = 6.2 Hz) which are assigned to the

A divergent asymmetric approach to aza-spiropyran derivative and (1S,8aR)-1-hydroxyindolizidine

• Jian-Feng Zheng,
• Wen Chen,
• Su-Yu Huang,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2007, 3, No. 41, doi:10.1186/1860-5397-3-41

• with the corresponding non-spiro analogue D, is a well known class of compounds possessing photochromic properties for use in the area of photochemical erasable memory,[10] and also found applications as self-development photography, actinometry, displays, filters, lenses of variable optical density

Allylsilanes in the synthesis of three to seven membered rings: the silylcuprate strategy

• Asunción Barbero,
• Francisco J. Pulido and
• M. Carmen Sañudo

Beilstein J. Org. Chem. 2007, 3, No. 16, doi:10.1186/1860-5397-3-16

• , react with CH2I2/Me3 Al at low temperature (-60°C to room temperature, then 48 h at r.t.) giving spiro-cyclopropanes 35–39 containing the spiro[2][4]heptanol moiety (Scheme 7). [20] High levels of stereoselectivity were found in all the examples studied. Formation of the spirocycle proceeds by a two

• -step pathway involving firstly, Me3Al-catalysed intramolecular cyclization of the oxoallylsilane and subsequent formation of a methylenecyclopentanolate, and then cyclopropanation. This unique mechanism enables the construction of hydroxylated bi-tri- and tetracyclic skeletons, bearing the spiro

• -cyclopropane moiety, from open chain allylsilanes in just one step. The high stereocontrol associated to the ring formation allows the synthesis of enantiomerically pure spiro-tricyclic alcohols containing an angular OH-group, such as 38 (Scheme 7). [20] The use of reagents different from organoaluminun