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

Additive-assisted regioselective 1,3-dipolar cycloaddition of azomethine ylides with benzylideneacetone

• Chuqin Peng,
• Jiwei Ren,
• Jun-An Xiao,
• Honggang Zhang,
• Hua Yang and
• Yiming Luo

Beilstein J. Org. Chem. 2014, 10, 352–360, doi:10.3762/bjoc.10.33

• -phenyl-pyrrolo(spiro-[2.3′]-1′-benzyloxindole)-spiro-[4.3″]-1″-benzyloxindoles in good regioselectivity. Our continued interest in the regioselective 1,3-dipolar cycloaddition of azomethine ylides prompted us to further investigate the regioselectivity of the 1,3-dipolar cycloaddition using α,β

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution

• Kazutaka Shibatomi,
• Takuya Okimi,
• Yoshiyuki Abe,
• Akira Narayama,
• Nami Nakamura and
• Seiji Iwasa

Beilstein J. Org. Chem. 2014, 10, 323–331, doi:10.3762/bjoc.10.30

• α-chloro-α-fluoro-β-keto esters via the sequential chlorination–fluorination of β-keto esters with the Cu(II) complex of SPYMOX [9], a spiro chiral oxazoline ligand developed by our research group [9][10][11][12]. In that study, we succeeded in determining the absolute stereochemistry of the α

Decandrinin, an unprecedented C₉-spiro-fused 7,8-seco-ent-abietane from the Godavari mangrove Ceriops decandra

• Hui Wang,
• Min-Yi Li,
• Félix Zongwe Katele,
• Tirumani Satyanandamurty,
• Jun Wu and
• Gerhard Bringmann

Beilstein J. Org. Chem. 2014, 10, 276–281, doi:10.3762/bjoc.10.23

• , University of Würzburg, Am Hubland, Würzburg 97074, Germany Government Degree College at Amadala valasa, Srikakulam District, Andhra Pradesh 532185, India 10.3762/bjoc.10.23 Abstract Decandrinin (1), an unprecedented C9-spiro-fused 7,8-seco-ent-abietane, was obtained from the bark of an Indian mangrove

• isolation and structural elucidation of an unprecedented C9-spiro-fused 7,8-seco-ent-abietane, named decandrinin (1) (Figure 1), from the bark of an Indian mangrove, C. decandra, collected in the estuary of Godavari, Andhra Pradesh. The absolute stereostructure of 1 was established by HRMS (ESI), extensive

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• (DMAPP) through 28 to yield 29, (Scheme 6) [40][41][42] the spiro-oxindole 30 was synthesized. The system underwent a cis-aryl-vinyl-cyclopropane rearrangement [43] to give 31 followed by rearomatization in 4–12 hours at room temperature yielding tricycle 32. The formation of the obtained tricyclic

• oxindole was crucial for the stereochemical control of the spiro-indolinone system in 138, it was removed in the next step using radical conditions. Horner–Wadsworth–Emmons olefination on the carbonyl moiety followed by protection of the oxindole gave intermediate 139. Conjugate addition of methylamine and

• of the amide under basic conditions. Cyclization and Ley–Griffith oxidation [150] took place, followed by deprotection of the alcohol to give spiro-oxindole 176. The formation of the remaining tetrahydropyran was much in line with Fukuyama’s synthesis, utilizing the same oxymercuration/reductive

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• the assigned relative stereochemistry. Therefore, the relative stereochemistry could be as shown in Figure 1. The NH-proton of the oxindole moiety appeared as a singlet between 10.38–10.86 ppm. The 13C NMR spectra of compounds 4a–4g showed characteristic peaks at 71–73 ppm due to the spiro carbon

• pyrrolidine/pyrrolizidine ring give singlets at 10.25 and 12.67 ppm, respectively. Therefore, the correct stereochemistry can be drawn as shown in Figure 3. The 13C NMR spectrum of compound 6c shows a characteristic peak at 73 ppm due to the spiro carbon nucleus. A single crystal X-ray study of compound 6a

• compounds 7a–7c (Scheme 2). The unexpected structure of rearranged product 7a was confirmed by 1H, 13C and 2D NMR spectroscopy (Table 3). The main feature of the 13C spectra of compounds 7a–7c is the absence of the signal of the 3C-spiro nucleus. The 1H NMR spectrum of compound 7a displays a singlet at 5.30

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

• acetic anhydride and pyridine at room temperature (Scheme 2). It should be emphasized that a mixture of dioxolanes 5 and 6 in a ratio of 7:3 is formed already in the first step [232]. The photooxygenation of oxazolidines 7a–d through the formation of hydroperoxides 8a–d gives spiro-fused oxazolidine

• '-indene] (75a) and 5-hydroperoxy-3',4'-dihydro-2'H-spiro[[1,2]dioxolane-3,1'-naphthalene] (75b), were synthesized by the ozonolysis of 1-allyl-1-hydroperoxy-2,3-dihydro-1H-indene (72a) and 1-allyl-1-hydroperoxy-1,2,3,4-tetrahydronaphthalene (72b), respectively, in an Et2O/CF3CH2OH system (2:1). The

• methyl 2-(4-methoxy-4-(triethylsilylperoxy)cyclohexyl)acetate (108) with 2-methyleneadamantane (109) produced adamantane-2-spiro-3’,8’-methoxycarbonylmethyl-1’,2’-dioxaspiro[4.5]decane (110) in 40% yield (Scheme 28) [258]. The use of easily accessible triethylsilylperoxyacetals 111 as the starting

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• isatinimines led to the formation of the spiro-azetidines 3k (14%) and 3l (28%, Table 1, entries 11 and 12). Remarkably, in the former case an intramolecular cyclization of the nitrilium ion upon the electron rich p-methoxyphenyl group took place and led to the formation of the bis(imino)tetrahydroquinoline 8

Four-component reaction of cyclic amines, 2-aminobenzothiazole, aromatic aldehydes and acetylenedicarboxylate

• Hong Gao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 2934–2939, doi:10.3762/bjoc.9.330

• spiro compounds by using the in situ generated Huisgen 1,4-dipoles [17][18][19][20][21][22][23][24]. During these research works, we noticed that even through the cyclic secondary amines such as pyrrolidine, piperidine and morpholine also reacted with electron-deficient alkynes to give the Huisgen 1,4

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• , affording 5-, 6-membered lactams and spiro-lactams 61 in excellent yields and high trans diastereoselectivity (Scheme 16). 4.2 The hydroarylation reaction In addition to methylene active compounds, electron-rich benzenes and heteroaromatics can be added to gold activated alkenes under suitable conditions

Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

• Verena Weidmann,
• Mathias Schaffrath,
• Holger Zorn,
• Julia Rehbein and
• Wolfgang Maison

Beilstein J. Org. Chem. 2013, 9, 2233–2241, doi:10.3762/bjoc.9.262

• is a suitable method to predict at least relative BDH-values of C–H bonds of the spiro compounds at hand. In absolute terms, B3LYP underestimates the BDH systematically by 2.9–4.6 kcal/mol. The experimental observation as summarized in Scheme 3, e.g., the selective oxidation in 2-position of an allyl

• that a BHD298 of around 80 kcal/mol (CBS-QB3) seems to be a threshold that might be used as a guideline to decide whether an allylic oxidation of spiro compounds related to 11 and 12 with PSA takes places or not. As a further test on the substrate scope of the reaction, we were interested in the

Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines

• Amit Kumar,
• Dipak D. Vachhani,
• Sachin G. Modha,
• Sunil K. Sharma,
• Virinder S. Parmar and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2013, 9, 2097–2102, doi:10.3762/bjoc.9.246

• only the R-isomer of the Ugi-adduct 5a to simplify the discussion. The cationic gold coordinates with the terminal alkyne which becomes activated for a nucleophilic attack. This can occur from both sides of the indole core. When the attack occurs from the back side of the indole core, spiro

• intermediate B will be formed. However, in this spiro intermediate the intramolecular trapping of the imminium ion by the amidic NH is sterically impossible and thus the intermediate reopens to intermediate A. If the attack takes place from the front side of the indole core, intermediate C is formed 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

• by the spiro connection of the three- and the five-membered rings. Following these rules, a Möbius type coarctate fragmentation with two five-ring terminators (10 electrons) should proceed as a photochemical reaction, and a corresponding fragmentation with a seven- and a five-ring (12 electrons

• chelotropic elimination of 1,3-dioxolan-2-ylidene is not likely. This carbene has been generated from a norbornadiene spiro ketal, and it cleanly fragmented into CO2 and ethylene [30]. Theoretical calculations support the low barrier for fragmentation [31]. We explain the different reaction behaviour of our

Thiourea-catalyzed Diels–Alder reaction of a naphthoquinone monoketal dienophile

• Carsten S. Kramer and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 1414–1418, doi:10.3762/bjoc.9.158

• . Unless stated otherwise, all commercially available compounds (Acros, Fluka, Aldrich) were used as received. Ethyl 4-((tert-butyldimethylsilyl)oxy)-5,8-dimethoxy-2-methyl-10-oxo-4,4a,9a,10-tetrahydro-1H-spiro[anthracene-9,2'-[1,3]dioxolane]-9a-carboxylate (2a): In a small flask dienophile 3 (23.1 mg

A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

• Mitsuhiro Ueda,
• Yoshitaka Uenoyama,
• Nozomi Terasoma,
• Shoko Doi,
• Shoji Kobayashi,
• Ilhyong Ryu and
• John A. Murphy

Beilstein J. Org. Chem. 2013, 9, 1340–1345, doi:10.3762/bjoc.9.151

• of this spiro structure is of continued interest for synthetic chemists. Recently, Comesse and Daïch reported the synthesis of 4,4-spirocyclic oxindole γ-lactams by tandem spirocyclization via nucleophilic halide displacement and amide coupling [4]. Shaw and co-workers reported the synthesis of 4,4

• -5-methoxyphenyl)-4-methylbenzenesulfonamide (1b) with CO gave the corresponding spiro lactam 2b in 53% yield (Table 1, entry 2). N-(2-(Azidomethyl)allyl)-N-(2-iodophenyl)methanesulfonamide (1c) showed a comparable reactivity with 1a and 1b (Table 1, entry 3). The reaction of 1-(2-(azidomethyl

• )allyloxy)-2-iodobenzene (1d) also gave the spiro benzofuran lactam 2d in 58% yield (Table 1, entry 4). On the other hand, 2-(azidomethyl)allyl(2-iodophenyl)sulfane (1e) gave a low yield of the corresponding spiro thiobenzofuran lactam (19%, Table 1, entry 5), which may be rationalized by the less effective

Interplay of ortho- with spiro-cyclisation during iminyl radical closures onto arenes and heteroarenes

• Roy T. McBurney and
• John C. Walton

Beilstein J. Org. Chem. 2013, 9, 1083–1092, doi:10.3762/bjoc.9.120

• spectroscopy. Iminyls with suitably placed arene or heteroarene acceptors underwent cyclisations yielding phenanthridine-type products from ortho-additions. For benzofuran and benzothiophene acceptors, spiro-cyclisation predominated at low temperatures, but thermodynamic control ensured ortho-products

• derivatives [1][2]. Spiro-cyclisations in which tethered radicals add to the ipso-C-atoms of the rings are less common, although minor spiro-products not infrequently accompany the main ortho-ones in Pschorr syntheses [3][4][5]. Cyclisations onto arenes by N-centred radicals are rarer, but iminyl radical ArC

• attention. Iminyl cyclisations have also been utilised in natural-product syntheses [10][16][25][26]. Iminyl radical spiro-cyclisations onto aromatics have been reported in a few cases, and spiro-intermediates have occasionally been proposed in mechanistic explanations [15][18][27][28][29]. Although a

Facile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction

• Qin Fu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 918–924, doi:10.3762/bjoc.9.105

• Qin Fu Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.9.105 Abstract A series of functionalized spiro[indoline-3,2'-oxiran]-2-ones was efficiently synthesized by Darzens reaction of phenacyl bromides with isatins both with N

• -alkyl groups and without N-substituent in the presence of potassium carbonate as a base catalyst. When two equivalents phenacyl bromides were used in the reaction, the N-substitution reaction of isatin also finished with the formation of spiro-oxirane-oxindoles. Keywords: Darzens reaction; isatin

• ; oxindole; oxirane; spiro-epoxyoxindole; spirooxindole; Introduction The spirooxindole unit is a privileged heterocyclic motif that forms the core structure of a large family of natural alkaloids and many pharmacological agents with important bioactivity and interesting structural properties [1][2][3][4][5

Synthesis of functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] via one-pot four-component reactions

• Li-Juan Zhang,
• Qun Wu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 846–851, doi:10.3762/bjoc.9.97

• malononitrile afforded the functionalized spiro[indoline-3,4’-pyridine] derivatives in good yields. Similar reactions with ethyl cyanoacetate successfully afforded the functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] as the main products according to the structures of the

• arylamines and other primary amines. Keywords: 1,4-dihydropyridine; electron-deficient alkyne; four-component reaction; isatin; one-pot reaction; spiro compound; Introduction β-Enaminones and β-enamino esters represent important synthetic building blocks for the development of versatile carbon–carbon bond

• [12][13][14][15][16][17][18][19][20][21][22][23]. Recently, Perumal and we have both developed an efficient synthetic procedure for functionalized spiro[indoline-3,4’-pyridines] by domino reactions of in situ generated β-enamino esters, isatin and malononitrile with triethylamine as the base catalyst

Synthesis of 2,3-dihydronaphtho[2,3-d][1,3]thiazole-4,9-diones and 2,3-dihydroanthra[2,3-d][1,3]thiazole-4,11-diones and novel ring contraction and fusion reaction of 3H-spiro[1,3-thiazole-2,1'-cyclohexanes] into 2,3,4,5-tetrahydro-1H-carbazole-6,11-diones

• Lidia S. Konstantinova,
• Kirill A. Lysov,
• Ljudmila I. Souvorova and
• Oleg A. Rakitin

Beilstein J. Org. Chem. 2013, 9, 577–584, doi:10.3762/bjoc.9.62

• reaction of anthracene-1,4-diones 4 led unexpectedly to the corresponding 2-thioxo-2,3-dihydroanthra[2,3-d][1,3]thiazole-4,11-diones 10. The reaction of 3H-spiro[1,3-thiazole-2,1'-cyclohexanes] 1d, 2d with Et3N in chlorobenzene under reflux yielded 2,3,4,5-tetrahydro-1H-carbazole-6,11-diones 15, 16, i.e

• formation of thiol 17 followed by the dihydropyrrole ring closure under the impact of both quinone and amine groups and the generation of the aromatic pyrrole cycle with hydrogen sulfide extrusion by the action of base (triethylamine). Although, to the best of our knowledge, the transformation of 3H-spiro

• -ethyldiisopropylamine in the reaction of 2-(methylamino)anthracene-1,4-diones with sulfur monochloride was discovered and explained. 3H-Spiro(thiazol-2,1'-cyclohexanes) underwent a new ring contraction and fusion reaction resulting in the formation of tetrahydroindoles. Experimental Melting points were determined on a

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• -diol on one of the alkenes would in principle result in the formation of a cyclic ketal. Spiro and cyclic ketals are ubiquitous in pheromones and in marine natural products [51]. The comparatively long effective lifetime of radicals generated under the conditions of the xanthate transfer may be

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• containing lactam, bicyclic, and spiro-bicyclic scaffolds, support was provided for the hypothesis that the bioactive conformation of PLG is a type II β-turn. In addition, studies with peptidomimetics designed to mimic either a type VI β-turn or polyproline II helix conformation yielded molecules that were

• able to modulate dopamine receptors because of their ability to place the carboxamide NH2 pharmacophore in the same topological space as that seen in the type II β-turn. Extensive studies with the spiro-bicyclic PLG peptidomimetics also established that both positive and negative modes of modulation

• changes in the spiro-bicyclic dopamine receptor modulators are capable of causing major changes in the modulatory activity of PLG peptidomimetics. Keywords: allosteric modulation; dopamine D2 receptor; peptidomimetic; Pro-Leu-Gly-NH2; spiro-bicyclic scaffold; Review There has been an increasing effort

Synthesis of spiro[dihydropyridine-oxindoles] via three-component reaction of arylamine, isatin and cyclopentane-1,3-dione

• Yan Sun,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 8–14, doi:10.3762/bjoc.9.2

• Yan Sun Jing Sun Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.9.2 Abstract A fast and convenient protocol for the synthesis of novel spiro[dihydropyridine-oxindole] derivatives in satisfactory yields was developed by the three

• scope of this novel reaction is briefly discussed. Keywords: arylamine; cyclopentanedione; isatin; multicomponent reaction; spiro compound; Introduction The spirooxindole is among the most important class of naturally occurring substances, characterized by highly pronounced biological properties, and

• ][13][14]. Considering the above reports, and as part of our program aimed at developing new multicomponent reactions for the construction of complex heterocyclic compounds, we wish in this work to report the efficient synthesis of unprecedented cyclopentyl-fused spiro[dihydropyridine-oxindoles] by the

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