Hybrid macrocycle formation and spiro annulation on cis-syn-cis-tricyclo[6.3.0.0^2,6]undeca-3,11-dione and its congeners via ring-closing metathesis

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Rashid Ali

Beilstein J. Org. Chem. 2015, 11, 1123–1128, doi:10.3762/bjoc.11.126

• based macrocycle 6 involving Fischer indolization and ring-closing metathesis (RCM). Various spiro-polyquinane derivatives have been assembled via RCM as a key step. Keywords: aza-polyquiananes; Fischer indolization; macrocycles; ring-closing metathesis; spiropolyquinanes; Introduction Design and

• hydrogenation steps (Scheme 1). A variety of synthetic transformations involving tricyclic diones 5 and 2 were reported in the literature [47]. To expand the utility of building block 2 in organic synthesis, we conceived a simple retrosynthetic approach to macrocylic aza-polyquinane 6 and spiro-polyquinane

• its subsequent utility in assembling the macrocyclic system 6 via RCM. During this venture, we also found that the tricyclic dione 2 is a useful substrate for the synthesis of spiro-polyquinane derivative 7 via a six fold allylation followed by a three-fold RCM and a hydrogenation sequence. Results

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• produced when the olefin of the allylic substrate was terminally disubstituted. Further optimisation also produced viable one-pot syntheses of derivatives of the spiro(indoline-2,9'-pyrido[1,2-a]indol)-3-one (65%) and pyrido[1,2,3-s,t]indolo[1,2-a]azepino[3,4-b]indol-17-one (72%) heterocyclic systems. Ring

• -closing metathesis of the N,O-diallylic spiro structure and subsequent Claisen rearrangement gave rise to the new (1R,8aS,17aS)-rel-1,2-dihydro-1-vinyl-8H,17H,9H-benz[2',3']pyrrolizino[1',7a':2,3]pyrido[1,2-a]indole-8,17-(2H,9H)-dione heterocyclic system. Keywords: allylation; cascade reactions; indigo

• olefinic terminal position remains unsubstituted to achieve these outcomes. The addition of substituents to the terminal positions of the allyl reagents (crotyl, 1,1-dimethylallyl, cinnamyl) resulted in a change in the major product outcome to the known spiro heterocycles 14, 15 and 16, although with a

Attempts to prepare an all-carbon indigoid system

• Şeref Yildizhan,
• Henning Hopf and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 363–372, doi:10.3762/bjoc.11.42

• was treated with the Tebbe reagent, the dimer 23 was produced, presumably through a Cope reaction of the intermediately generated isomer 22. The bis-indene derivative 23 can be alkylated with 1,2-dibromoethane to produce a 1:1 mixture of the spiro compounds 24 and 25. Although 9 could be reductively

• the preparation of novel metallocene derivatives and also so far unknown. The other conceivable spiro isomer 28 seems to be a less likely product since its E-configurated double bond (within a seven-membered ring) should result in considerable strain (anti-Bredt hydrocarbon). When 23 was treated with

• seen from the X-ray structures, the former is the anti-spiro compound 24 (Figure 4) and the latter its syn-isomer 25 (Figure 5), with the former possessing the longer chromatographic retention time. Unfortunately, because of lack of material, no high quality NMR spectra of these two hydrocarbons could

Morita–Baylis–Hillman reaction of acrylamide with isatin derivatives

• Radhey M. Singh,
• Kishor Chandra Bharadwaj and
• Dharmendra Kumar Tiwari

Beilstein J. Org. Chem. 2014, 10, 2975–2980, doi:10.3762/bjoc.10.315

• ] including spiro frameworks [43][44][45][46]. It is therefore anticipated that the development of the MBH reaction using acrylamide and isatin would not only expand the scope of acrylamide, but would also contribute to the expansion of the synthetic potential of isatin. Results and Discussion Initially N

Palladium-catalyzed 2,5-diheteroarylation of 2,5-dibromothiophene derivatives

• Fatma Belkessam,
• Aidene Mohand,
• Jean-François Soulé,
• Abdelhamid Elias and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 2912–2919, doi:10.3762/bjoc.10.309

• et al. [38]. A fluorescent π-conjugate thiophene derivative bearing spiro[fluorene-9,4’-[4H]indeno[1,2-b]furan] substituents at C2 and C5 has been prepared in 46% yield by this reaction using Pd(OAc)2 (5 mol %) associated to PPh3 (10 mol %) as catalytic system [39]. A pyrrole derivative was coupled

One-pot four-component reaction for convenient synthesis of functionalized 1-benzamidospiro[indoline-3,4'-pyridines]

• Chao Wang,
• Yan-Hong Jiang and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2014, 10, 2671–2676, doi:10.3762/bjoc.10.281

• ; multicomponent reaction; one-pot reaction; spiro[indoline-3,4'-pyridine]; Introduction The spirooxindole system is the core structure of many natural products and pharmaceutically important structures with notable structural complexity and biological activities of great interest [1][2][3][4]. Accordingly, many

• reactions [19][20][21]. Recently, we and Perumal have demonstrated that the four-component reaction of arylamine, acetylenedicarboxylate, isatin and malononitrile can afford the spiro[indoline-3,4’-pyridine] derivatives in satisfactory yields [22][23][24]. We envisioned that functionalized spiro[indoline

• -3,4’-pyridine] derivatives can be synthesized by employing other nitrogen-containing nucleophiles such as hydrazine and imines in the similar four-component reactions. In fact, the four-component reaction of hydrazine, acetylenedicarboxylate, isatin and malononitrile for the formation of spiro

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• -1',2'-dihydro-2H,7b'H,9'H-spiro[pyrimidine-5,8'-quinolino[1,2-d][1,4]benzoxazepine]-2,4,6(1H,3H)-trione (rac-trans-7a): To a stirred solution of rac-5 (100 mg, 0.27 mmol) in chloroform (5 mL), anhydrous MgSO4 (150 mg, 1.25 mmol) and 1,3-dimethylbarbituric acid (60 mg, 0.38 mmol) were added and the

• (−9.32), 221 (−11.60). trans-2,2-Dimethyl-11'-nitro-2'-phenyl-1',2'-dihydro-7b'H,9'H-spiro[1,3-dioxane-5,8'-quinolino[1,2-d][1,4]benzoxazepine]-4,6-dione (rac-trans-7b): To the stirred solution of rac-5 (100 mg, 0.27 mmol) in chloroform (5 mL), anhydrous MgSO4 (150 mg, 1.25 mmol) and Meldrum’s acid (54

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

• conditions, the reactions worked efficiently to afford corresponding functionalized spirocyclic products with adjacent spiro-quaternary and tertiary stereocenters in good to excellent yields. These products were readily transformed into a variety of useful optically active amino acid analogues, including

• synthetic value of this methodology (Scheme 34). 2.3 [3 + 2] Annulations of allenes with azomethine imines Using the chiral catalyst D4, a cyclic phosphine featuring a spiro-skeleton, Guo, Kwon, and co-workers achieved asymmetric [3 + 2] annulation of an allenoate with an azomethine imine (Scheme 35) [69

• F1, but-3-yn-2-one reacted with a series of N-protected isatins in ethyl ether at −20 °C to afford enantioenriched spiro[furan-2,3´-indoline]-2´,4(5H)-diones with good to excellent ee's, albeit moderate yields. 2.7 [4 + 2] Annulations of allenes with activated imines Compared with phosphine-catalyzed

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• post-Ugi cyclization, namely an intramolecular aza-Michael [24] reaction, which afforded compound 18 bearing the privileged spiro-diketopiperazine scaffold (Scheme 2). Spiro-diketopiperazines are present in many natural products [38][39][40] and have recently received much attention as

Human dendritic cell activation induced by a permannosylated dendron containing an antigenic GM₃-lactone mimetic

• Renato Ribeiro-Viana,
• Elena Bonechi,
• Javier Rojo,
• Clara Ballerini,
• Giuseppina Comito,
• Barbara Richichi and
• Cristina Nativi

Beilstein J. Org. Chem. 2014, 10, 1317–1324, doi:10.3762/bjoc.10.133

• functionalized with an alkyne group by a Cu(I) azide–alkyne cycloaddition (CuAAC) reaction. Then, the mimetic 6 with a butyne group at the anomeric position, which is required for the conjugation to the glycodendron 7 (Scheme 1), was also prepared as already reported [33]. The synthesis of the tricyclic spiro

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• the identification of new potent and selective ligands of ionotropic and metabotropic glutamate receptors (GluRs). To this aim, bicycle compound Ib was designed and synthesised from D-serine as novel [2.3]-spiro analogue of L-Glu. This frozen amino acid derivative was designed to further limit the

• rotation around the C3–C4 bond present in the azetidine derivative Ia by incorporating an appropriate spiro moiety. The cyclopropyl moiety was introduced by a diastereoselective rhodium catalyzed cyclopropanation reaction. Keywords: Amino acids; carbenes; cyclopropanation; rhodium; spiro compounds

• reported to date. The preparation of compound Ib appears challenging due to both the need to control the stereochemistry of three contiguous chiral centers and the presence of a [2.3]-spiro junction connecting the cyclopropane moiety with a highly functionalized azetidine ring. Here, we describe the

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• -ylidenes spontaneously dimerize under ring cleavage of one of the N,N-bonds and ring closure to an indazole–indole spiro compound which possesses an exocyclic imine group. The E/Z isomers of the imines can be separated by column chromatography when methanol is used as eluent. We present results of a single

• crystal X-ray analysis of one of the E-isomers, which equilibrate in solution as well as in the solid state. Heating of the indazole–indole spiro compounds results in the formation of quinazolines by a ring-cleavage/ring-closure sequence (X-ray analysis). Results of DFT calculations are presented

• 12a,c,d by column chromatography employing methanol as eluent, and to characterize the separated species. The species in equilibrium proved to be spiro[indazole-3,2'-indolines], the exocyclic imine groups of which form Z- and E-isomers 13a–e and 14a–e, respectively. The equilibration of 14b is too

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