D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• .14.182 Abstract Phosphinooxazoline (PHOX) ligands are an important class of ligands in asymmetric catalysis. We synthesized ten novel D-fructose-derived spiro-fused PHOX ligands with different steric and electronic demand. The application of two of them was tested in asymmetric allylic alkylation. The

• pyridyloxazoline (PyOx) ligands in which the sugar moiety was linked to pyridine via an annulated oxazoline, 3, as well as via a spiro-fused oxazoline, 4. We found that the spiro-fused ligands gave higher enantioselectivities (up to 93% ee) than the annulated ligands (up to 66% ee) in allylic substitution [20][21

• ][22]. This led us to extend the concept of spiro-fused carbohydrate oxazolines for asymmetric synthesis by developing new types of carbohydrate-based PHOX ligands. Herein, we present ten novel spiro-PHOX ligands containing diphenylphosphino groups, 5, which can be synthesized in four to six steps

Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• followed by a ring-expansion rearrangement. In the rearrangement reaction, the phenyl substituent in the initially formed spiro-triazolium adducts 16 underwent a [1,2]-migration from C(3) to the electron-deficient N(2). This led to the ring expansion from 6-membered piperidine to 7-membered diazepine

• cannot be isolated by now [31]. Then, the nitrogen atom of the nitrile approaches to the central electron-deficient carbon atom in 14 to form a Ritter-type nitrilium salt 15 [48]. Salt 15 then undergoes a concerted but asynchronous cyclization [49] to afford the initial spiro-substituted adduct 16, which

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• functionalized benzocoumarins to spirocyclic lactones. In 2015, Du and co-workers [74] reported a spirocyclization of diarylacetylenes to fused spiro polycyclic compounds through a hypervalent iodine-mediated cascade annulation reaction. In this reaction, the Lewis acid BF3·Et2O acts as catalyst which activates

• ) in presence of 3.0 equivalents of TFA as an additive in dichloromethane (Scheme 17). The fused tricyclic compound 53 was obtained as major product in 55% yield along with the spiro compound 54 as a minor product in 8% yield. In 2009, Zhang and co-workers [89] reported an efficient method for the

• synthesis of spiro β-lactams via oxidative dearomatization reactions. In this report, the synthesis of spiro β-lactams 56 were achieved successfully by the oxidative cyclization of p-substituted phenols 55 using PIDA (15) as an electrophile and copper(II) sulfate pentahydrate as an additive in the presence

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• -epoxides, 2,3-epoxyalcohols as well as their OTMS, OTs and OPh derivatives. Reactions of 1-oxa-spiro[2.5]octane and 2-phenyloxirane (styrene oxide) with thiophenol both gave near quantitative yields of the hydroxy sulfides, with substitution occurring nearly exclusively at the sterically less hindered β

Recent advances in phosphorescent platinum complexes for organic light-emitting diodes

• Cristina Cebrián and
• Matteo Mauro

Beilstein J. Org. Chem. 2018, 14, 1459–1481, doi:10.3762/bjoc.14.124

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• Amarendar Reddy Maddirala Peter R. Andreana Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USA 10.3762/bjoc.14.74 Abstract The synthesis of spiro[indoline-3,2'-pyrrole]-2,5'(1'H)-diones and

• spiro[indoline-3,2'-pyrrolidine]-2,5'-diones, via a post-Ugi-domino transamidation/cyclization sequential process, has been achieved in three sequential steps utilizing a one-pot reaction protocol. The variation in carboxylic acid substrates allows for the generation of new chiral racemic quaternary

• synthetic method for these molecules that allows for structural diversity is also important but not necessarily trivial. For these and other reasons, we became interested in synthesizing spiro[indoline-3,2'-pyrrole]-2,5'(1'H)-dione and spiro[indoline-3,2'-pyrrolidine]-2,5'-dione scaffolds (a class of

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• are also known to undergo oligomerization in the absence of dienophiles and nucleophiles via an oxo-Diels–Alder protocol (Table 4). During the syntheses of 1,4,9,10-anthradiquinones with potential antitumor activity, Kucklaender et al. isolated new spiro derivatives 38 [77]. These latter spirocyclic

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• -alkynoates with N-bromosuccinimide (NBS) at rt [34], where those reactions proceed via radical spiro-cyclization and then radical 1,2-carboxyl group migration, were reported. On the other hand, diaryliodonium salts are very useful for the C-arylation of active CH groups, the O-arylation of OH groups, and the

• occurs to form aryl 3-aryl-2-propynoate 2 (1st step). The bromocyclization of aryl 3-aryl-2-propynoate 2 with TBAB and Na2S2O8 proceeds via a bromoradical addition to the triple bond to form very reactive vinyl radical I [47]. Ipso-cyclization of the vinyl radical I occurs to form spiro radical

• intermediate II. Then, β-cleavage of the spiro radical intermediate II proceeds to form carboxyl radical III. 6-Exo-trig cyclization of the carboxyl radical III onto the aromatic ring takes place to form adduct radical IV, which would be rapidly oxidized by Na2S2O8 to form cation intermediate V. Smooth

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

• % could be attained for the sky-blue B4-based devices. Still based on the combination of acridan and 10H-phenoxaborin units, a complete isolation of the two units could be realized in B6 by directly functionalizing the 10H-phenoxaborin core with a spiro-type acridan group [38]. Using this strategy, pure

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• product 4,5-dihydro-1H-pyrazolo[3,4-b]pyridine-6(7H)-one 53 was formed due to C–O bond cleavage from cyclic ester 51. Bazgir et al. [56] described the synthesis of spiro[indoline-3,4'-pyrazolo[3,4-b]pyridine]-2,6'(1'H)-diones 55 by an efficient three-component procedure from the reaction of 5

• described the construction of spiro[indoline-3,4'-pyrazolo[3,4-b]pyridine] derivatives 57 from the multicomponent reaction of 5-amino-3-hydroxy-1-phenyl-1H-pyrazole (46), ketones 56 and isatin 54 in water/acetic acid (3:1) at 90 °C (Scheme 12). Quiroga et al. [58] reported the synthesis of the pyrazolo[3,4

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• ; spiro compounds; synthetic methods; Introduction Molecular structures based on partially or exhaustively hydrogenated indole and benzofuran cores are omnipresent in nature. Both types of ring systems are found in a variety of important biologically active natural products [1][2][3][4][5][6][7][8][9][10

• spirocondensation of 5-alkoxycarbonyl-1H-pyrrole-2,3-diones (serving as 1,2-bis-electrophiles) with cyclic ketazinones (serving as either 1,3-C,N- or 1,3-C,O-bis-nucleophiles). Results and Discussion Previously, we demonstrated a convenient approach towards spiro[indole-3,2’-pyrroles] 3 based on catalyst-free

• in tautomeric form 18 (Scheme 5). Surprisingly, an alternative direction of spirocyclization involving the reaction of tautomeric form 19 and affording lactam rings proceeded exclusively. The corresponding spiro[indole-3,2’-pyrroles] 21 were obtained exclusively in good yields (Scheme 5). The

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides

• Neha Rana,
• Manish Kumar,
• Vinod Khatri,
• Jyotirmoy Maity and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2017, 13, 2078–2086, doi:10.3762/bjoc.13.205

• , which is a key precursor for the synthesis of different types of bicyclic/spiro nucleosides, led to the formation of an inseparable 1:1 mixture of the desired product and 4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-xylofuranose. A convenient environment friendly Novozyme®-435 catalyzed selective

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• -workers demonstrated the potential of asymmetric cation-based phase-transfer catalysis to control the absolute configuration of the newly-installed stereogenic centre in this rearrangement reaction [141]. By using their spiro-quaternary ammonium salt catalyst B5 they were able to control the Neber

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• combination of heterogeneous polymer-supported bi-metallic platinum/iridium alloyed nanoclusters and 5,5’,6,6’-tetrahydroxy-3,3,3’,3’-tetramethyl-1,1’-spiro-bisindane (TTSBI) facilitated a one-pot condensation and oxidative dehydrogenation of o-aminobenzylamine to generate quinazoline derivatives 79 under

• dehydrogenation of tetrahydroisoquinolines. Ruthenium-catalyzed polycyclic heteroarenes. Plausible mechanism of the ruthenium-catalyzed dehydrogenation. Bi-metallic platinum/iridium alloyed nanoclusters and 5,5’,6,6’-tetrahydroxy-3,3,3’,3’-tetramethyl-1,1’-spiro-bisindane (TTSBI) for the synthesis of quinazolines

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• for binding divalent metal cations and a modest increase in M2+ binding affinity correlated with increased alkycarboxylate tether length. Keywords: carboxylate ligand; merocyanine; metal binding; photochromism; spiropyran; Introduction Spiropyrans are a class of spiro-fused indolochromene (e.g

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• spiroindanone 50 has been proposed by Estévez et al. [38]. Thus, starting from 2,2-disubstituted-1-indanone 49, the spiro-1-indanone 50 was formed via cyclization using HBr/AcOH and next converted in a sequence of reactions to the biologically active benzopyronaphthoquinone 51 (Scheme 18). Endothelins are 21

• carbene is an outstanding protocol for the synthesis of polyhydroxylated spiro- or fused 1-indanones [49]. Thus, the imidazole-based carbene catalyzed the conversion of phthalaldehydes 72 to dihydroxyspiro[indane-2,1′-isobenzofuran]-3-ones 73, whereas triazole-based carbene catalyzed the conversion of 72

• quaternary center with high diastereoselectivity as a consequence of the Stetter–Aldol–Aldol (SAA) reaction sequence. The Stetter–Aldol–Aldol conversion of the phthaldialdehyde derivatives 75 and o-formyl substituted chalcones 76 using the thiazole based carbene 78 as a precatalyst allowed to obtain spiro

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• stereospecific cyclic adducts. Keywords: L-proline; ninhydrin; sarcosine; spiropyrrolidine; 5-vinylindazole; 5-vinylindole; Introduction The [3 + 2] cycloaddition between azomethine ylides and olefins/acetylene as dipolarophiles is an important reaction to access a number of novel heterocyclic spiro scaffolds

• of biological importance [1][2]. The regio- and stereoselective construction of spiro compounds by utilizing the 1,3-dipolar cycloaddition reaction of azomethine ylides has been reported [3][4][5][6]. However, unlike the previous reports, the present method is concise and facilitates the one-pot

• in the construction of functionalized spiro compounds. We report herein the facile synthesis of novel spiropyrrolidine compounds through a one-pot three-component reaction involving N-substituted vinylindole/indazole, ninhydrin and sarcosine/L-proline. The present multicomponent reaction (MCR) leads

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• Farmaco, Università di Catania, Viale A. Doria, 95100 Catania, Italy Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100 Pavia, Italy 10.3762/bjoc.12.278 Abstract A series of spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones has been synthesized by 1,3-dipolar cycloaddition of N

• be linked to the inhibition of the protein–protein p53-MDM2 interaction. Docking measurements support the biological data. Keywords: antitumor agents; DFT studies; 1,3-dipolar cycloaddition; docking studies; spiro-compounds; Introduction The p53 tumor suppressor protein is a transcriptional factor

• construction of the spiro[isoxazolidin-isoindolinone] system. The synthetic scheme (Figure 2) exploits the strategy of the 1,3-dipolar cycloaddition of nitrones on the substrate isoindolin-3-methylene-1-one 2, obtained by a recent methodology of a PdI2 catalyzed aminocarbonylation-N-heterocyclization of 2

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• ; nitrogen heterocycles; spiro compounds; Introduction A global trend in modern organic chemistry is the design of molecular systems with various degrees of complexity to maximize the incorporation of useful properties while optimizing cost and efficiency [1]. A very extended and powerful approach for

• interest to synthesize the other types of spiro compounds such as the 2,3’-spiropyrrolidinyloxindole structure which is isosteric with the 3,3’-spiropyrrolidinyloxindole and to study the diastereoselectivity of its formation. It could be expected that the cycloaddition of more bulky azomethine ylides

• the {1H-13C}HMBC spectrum of 4f, the N(1’)Me protons (2.17 ppm) correlate with the C-5’ (57.52 ppm) and spiro C-2’ (80.29 ppm) carbons; the proton of C(4’)H (4.63 ppm) of the pyrrolidine ring correlates with the spiro carbon C-3’ (68.47 ppm) and the carbon atoms of the C(5’)H2 and C(7)=O (167.31 ppm

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• nucleophilic, but in this case the stereoablative step in the mechanism leads to an electrophilic intermediate. The use of Cu(box) complex 9 rendered the reaction enantioselective, forming C-3 quaternary oxindole 12 in 91% ee (up to 94% ee for related substrates). This strategy is useful for constructing spiro

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• of homoallylic brosylates 174a–c or spiro cyclopropyl carbinols 175a–c in the THF/H2O2 system, resulting in the increase in the ring size by two atoms and the formation of hydroperoxy oxabicyclo derivatives 176a–c (Table 11). The mechanism of the solvolysis of 174 or 175 in the THF/H2O2 system

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• , 3,4-dihydroxy-L-phenylalanine (L-DOPA), 4-coumaric acid or caffeic acid. Grisanes. Many fungal spirobenzofuranones contain the grisane (191) moiety as the central structural motif (Scheme 26a). The spiro linkage between the B and C rings is installed by oxidative phenol coupling starting from type II

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• species from 2-aminopyridine and isatin which then undergoes a formal [4 + 1] cycloaddition with isocyanide to generate a spiro intermediate b. The spiro compound then undergoes a retro-aza–ene reaction via a [1,5]-hydride shift resulting in an aromatic imidazo[1,2-a]pyridine having an isocyanate

Synthesis of ferrocenyl-substituted 1,3-dithiolanes via [3 + 2]-cycloadditions of ferrocenyl hetaryl thioketones with thiocarbonyl S-methanides

• Grzegorz Mlostoń,
• Róża Hamera-Fałdyga,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 1421–1427, doi:10.3762/bjoc.12.136

• -Tetramethyl-8-thia-5,6-diazaspiro[3.4]oct-5-en-2-one (3c) [20] and spiro[1,3,4-thiadiazole-2(5H),2’-tricyclo[3.3.1.13,7]decane] (3d) [21] were obtained by known methods according to the literature protocols. Diazomethane was prepared in a 5 mmol scale either from N-nitroso-N-methylurea or from N

• -Ferrocenyl-5-(selenophen-2-yl)spiro[1,3-dithiolane-4,2’-tricyclo[3.3.1.13,7]decane] (5l); 4-Ferrocenyl-4-(selenophen-2-yl)spiro[1,3-dithiolane-2,2’-tricyclo[3.3.1.13,7]decane] (6l): Isolated as a mixture of regioisomers. Yield: 393 mg (73%; crude product ratio 67:33). Yellow solid; IR (KBr) ν: 3085 (w), 3072

3,6-Carbazole vs 2,7-carbazole: A comparative study of hole-transporting polymeric materials for inorganic–organic hybrid perovskite solar cells

• Wei Li,
• Munechika Otsuka,
• Takehito Kato,
• Yang Wang,
• Takehiko Mori and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2016, 12, 1401–1409, doi:10.3762/bjoc.12.134

• performances. So far, 2,2’,7,7’-tetrakis(N,N-di(p-methoxyphenyl)amino)-9,9-spirobifluorene (spiro-OMeTAD) is regarded as the most conventional solid state hole transporter for the PSCs [6][7][8][9][10]. Despite the high PCEs conferred by this hole transporting layer, spiro-OMeTAD has several limitations, such