Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• product 81 (Scheme 45). The yields are moderate; however excellent diastereo- and enantioselectivities were observed for the one-pot reaction [62]. In a similar fashion, an asymmetric multicatalytic cascade reaction involving the dienal 82 and unsaturated cyclic sulfonylimine 83 afforded spiro-fused

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• guest 14 and 15 by 5.1 kJ/mol and 18.2 kJ/mol, respectively) none of the spiro-bicyclic compounds shows a promising affinity to the bacterial ribosome. The same is true for guests 17 and 18. The introduction of the new aromatic cycle in the B ring increases the steric hindrance with far-reaching

Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

• Ming-Liang Zhang,
• Deng-Feng Yue,
• Zhen-Hua Wang,
• Yuan Luo,
• Xiao-Ying Xu,
• Xiao-Mei Zhang and
• Wei-Cheng Yuan

Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31

• -diones is mainly focused on three-component spiro-heterocyclization reactions [30][31][32]. However, for the catalytic asymmetric transformation, only one example of an aldol reaction of 1H-pyrrole-2,3-diones with ketones has been reported so far (Scheme 1) [33]. Recently, our group developed a chiral

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• present work, we describe a convenient synthesis of spiro-fused D-fructo- and D-psico-configurated oxazoline ligands and their application in asymmetric catalysis. The ligands were synthesized from readily available 3,4,5-tri-O-benzyl-1,2-O-isopropylidene-β-D-fructopyranose and 3,4,5-tri-O-benzyl-1,2-O

• benzylation, fully characterized and subjected to palladium catalyzed Suzuki–Miyaura coupling with 2-pyridineboronic acid N-phenyldiethanolamine ester to give the corresponding 2-pyridyl spiro-oxazoline (PyOx) ligands. The spiro-oxazoline ligands showed high asymmetric induction (up to 93% ee) when applied as

• ; carbohydrates; oxazolines; palladium; spiro compounds; Introduction The design of new chiral ligands for stereo-differentiating metal catalysts that enable asymmetric syntheses is still a highly active field of research in organic chemistry, for there is a continuously growing demand for enantiomeric pure

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• precursors to gain insight into the used building blocks for the unusual polyketide core [26]. Compound 9 features a trisketal structure in addition to the spiro-epoxide at C-14, which is believed to be the active part of the molecule for interaction with DNA. This was supported by the isolation of

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• ring closing metathesis to afford the bicyclic product 53. Finally, the RCM of the 1,4-adduct resulting from the addition of 3-butenylmagnesium bromide yielded the spiro compound 54. Interestingly, the conversion of bicyclic compound 40 catalyzed by the same system also occurred selectively in the 4

• converted to the spiro compounds 62 and 63 (Scheme 17). The same protocol was later applied to conjugated enynones featuring additional unsaturated units and a total regioselectivity towards the 1,4-adducts was recorded under the standard conditions (Scheme 17) [36]. The chiral polyconjugated products (64

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• spirooxazolines are stable and were obtained in good yield with high stereoselectivity due to the conformational rigidity imparted by the 3,4-isopropylidene group. Keywords: fructose; oxazoline; riboside; Ritter reaction; spiro; Introduction 2-Oxazolines represent a unique class of 5-membered heterocyclic

• spiro [42] 2-oxazolines [43] are limited, to the best of our knowledge. With our interest in the area of glycopeptides [44] and carbohydrates [45], and owing to the importance of ribosides in general and spiroribofuranoses [46] in particular for drug discovery, in this paper, we report the synthesis of

• spiro 2-substituted-2-oxazoline ribosides utilizing a Ritter-like reaction having the general structure 6 (Figure 1). Results and Discussion García Fernández et al. isolated the fused and spiroglycooxazolines by activating 1,2;4,5-di-O-isopropylidene-β-D-fructopyranose and 3,4,6-tri-O-benzyl or benzoyl

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• with the RCM product 78 in 71% (Scheme 15). Burnell and co-workers [20] have demonstrated the RRM of unsaturated spirocycles with two alkenyl chains by employing catalyst 2 to generate a unsaturated spiro-fused tricyclic system. In this context, the compounds 80 and 81 were subjected to RRM with

• 235 has been used in RRM. To this end, compound 235 was subjected to a RRM under the influence of catalyst 3 to deliver the spiro heterocyclic compound 236 (41%). Similarly, compound 237 was treated with catalyst 2 under the same reaction conditions to produce the spiro heterocycle 238 (91%) (Scheme

• the fruiting body of P. igniarius, is a well-known anticancer agent. To assemble the spiro-fused furanone core of phelligridin G, Wright and Cooper [55] have used a RRM process as a key step. Wittig olefination of furylbenzaldehyde derivative 265 using methyltriphenylphosphonium bromide in the

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• /fragmentation. Tin hydride-mediated cyclizations of 2-halo-N-(3-methyl-N-sulfonylindole)anilines provide spiro[indoline-3,3'-indolones] or spiro-3,3'-biindolines (derived from imine reduction), depending on the indole C2 substituent. Cyclizations of 2-haloanilide derivatives of 3-carboxy-N-sulfonyl-2,3

• -dihydropyrroles also presumably form spiro-imines as primary products. However, the lactam carbonyl group facilitates the ring-opening of these cyclic imines by a new pathway of hydration and retro-Claisen-type reaction, providing rearranged 2-(2'-formamidoethyl)oxindoles. Keywords: ene-sulfonamide; imine

• ; radical cyclization; radical fragmentation; spiro-indoles; Introduction Radical additions and cyclizations of ene-sulfonamides are useful reactions in a number of settings. The primary products of these reactions, α-sulfonamidoyl radicals, are often thought to undergo elimination reactions of sulfonyl

Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha,
• Ongolu Ravikumar and
• Jadab Majhi

Beilstein J. Org. Chem. 2015, 11, 1503–1508, doi:10.3762/bjoc.11.163

• -caprolactam from cyclohexanone oxime involving the BR. The activation energy for the BR is almost the same as that of the nucleophilic substitution at sp2 nitrogen. To synthesize various aza-arenes and cyclic imines, such as quinolines, aza-spiro compounds and dihydropyrroles, the intramolecular SN2-type

Spiro annulation of cage polycycles via Grignard reaction and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Mohammad Saifuddin,
• Rashid Ali and
• Gaddamedi Sreevani

Beilstein J. Org. Chem. 2015, 11, 1367–1372, doi:10.3762/bjoc.11.147

• Sambasivarao Kotha Mohammad Saifuddin Rashid Ali Gaddamedi Sreevani Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai-400 076, India, Phone: +91-22-2576 7160, Fax: +91(22)-2572 7152 10.3762/bjoc.11.147 Abstract A simple synthetic strategy to C2-symmetric bis-spiro

• antiviral properties [22]. Although, several methods are available for the construction of cage compounds [7][23][24][25][26][27][28][29][30][31][32][33], the synthesis of symmetrical spiro-cage molecule 7 seems to be a synthetic challenge due to the proximity of the two carbonyl groups in dione 10 which

• provides a hemiketal with various nucleophiles [34][35][36][37][38][39]. In view of various applications of cage molecules and the documented difficulties in their synthesis, we conceived a short synthetic route to C2-symmetric bis-spiro-pyrano cage compound 7. To this end, the Grignard addition and ring

Design and synthesis of fused polycycles via Diels–Alder reaction and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha and
• Ongolu Ravikumar

Beilstein J. Org. Chem. 2015, 11, 1259–1264, doi:10.3762/bjoc.11.140

• associated with one of the hydroxy groups (Figure 2). Later, the triallyl compound 5 was subjected to RRM in the presence of G-II catalyst (Figure 1) under ethylene atmosphere to deliver the hexacyclic rearranged product 6a in 70% yield and ring-closing spiro product 6b in 28% yield (Scheme 1). To expand

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