Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• carbenoid insertions using spiro-bisimine ligand L25 at cryogenic temperatures (Scheme 39A). Ollevier, however, focused on making these reactions more general under ligand-free conditions at ambient temperature, and without the asymmetric component (Scheme 39B). The substrate scope was already broad

Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes

• Zeguo Fang,
• Nawaf Al-Maharik,
• Peer Kirsch,
• Matthias Bremer,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65

• (Figure 2). Therefore, the aim of the study was to prepare these target liquid crystals and evaluate their properties relative to each other, to establish if there were any obvious structure–activity relationships to emerge for the design of positive or negative dielectric materials. Also the fixed spiro

• . The synthesis of the diastereoisomers of spiro LC candidates 11a and 11b also started from ketone 15 as illustrated in Scheme 4. Treatment of ketone 15 with methylenetriphenylphosphine which was generated in situ from methyltriphenylphosphonium bromide (PPh3CH3Br), generated exo-methylene cyclohexane

• , 9 and 10, were found to be small, whereas the spiro-cyclopropane 11a had a significantly, decreased Δn. As discussed, either positive or negative dielectric anisotropy is an important parameter related to the driving voltage of LC displays and in order to reduce energy consumption, good materials

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• esters with AgSCF3 for the synthesis of trifluoromethylthiolated coumarins (Scheme 1b) [28]. In 2016, Liu exploited the tandem trifluoromethylthiolation/cyclization of N-arylpropiolamides to construct the SCF3-substituted spiro[4,5]trienones (Scheme 1c) [29]. In the same year, Zhang and Chen disclosed

Synthesis of six-membered silacycles by borane-catalyzed double sila-Friedel–Crafts reaction

• Yafang Dong,
• Masahiko Sakai,
• Kazuto Fuji,
• Kohei Sekine and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2020, 16, 409–414, doi:10.3762/bjoc.16.39

• 9,9-dihydro-5-silafluorene (2f), which gave the spiro-type phenoxasilin 3f in 96% yield. We then investigated the scope of the starting biaryl ethers used in the reaction as well as related derivatives thereof using dihydrodiphenylsilane (2a, Scheme 3). Pyrrolidine-substituted diaryl ether 1b was

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• -oxazaphosphorine ligands with a P-center and backbone chirality (Scheme 24). Spiro-1,3-amino alcohol compounds 124 were synthesized according to a literature procedure [107]. For the synthesis of the mono-N-methylated amino alcohol ligands a cooled solution of dichlorophenylphosphine was treated with triethylamine

• and mono-N-methylated spiro 1,3-amino alcohols 124. The mixture was equilibrated under reflux allowing P-center inversion and an uneven mixture of diastereoisomers 125 and 127 was obtained. Treating the mixture with borane·dimethyl sulfide gave a mixture of diastereoisomers in a ratio of 2:5. The

• protocol with free amine spiro-amino alcohol derivative 124 gave compounds 125 and 127 (R = H) in low yields. An optimized procedure was used where dichlorophenylphosphine and borane·dimethyl sulfide in tetrahydrofuran were premixed at −78 °C. The temperature was then raised to 25 °C before neutralizing

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• approach. The polyfunctional molecular scaffolds were tested on the cyclopentenone reactivity to further expand the skeletal diversity, demonstrating the utility of this combined approach in generating novel spiro compounds as starting material for the generation of chemical libraries. The chemoinformatics

• Pauson–Khand conditions (Table 1,entry 14). The synthetic utility of the spiro derivatives resulting from the combined KA2/Pauson–Khand process to generate second-generation molecular scaffolds was tested on compound 5 by applying representative reactions on the enone structural motif (Scheme 3). The

• even more efficient in increasing the three-dimensional character of these compounds, as spiro tricyclic products were found to be more shifted towards the sphere-disc region of this chemical space, especially if compared to their corresponding starting materials (see Figure 4, compounds 5 and 26 with

Facile regiodivergent synthesis of spiro pyrrole-substituted pseudothiohydantoins and thiohydantoins via reaction of [e]-fused 1H-pyrrole-2,3-diones with thiourea

• Aleksandr I. Kobelev,
• Nikita A. Tretyakov,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Michael Rubin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 2864–2871, doi:10.3762/bjoc.15.280

• , Kansas 66045, United States Department of Chemistry, North Caucasus Federal University, ul. Pushkina 1a, Stavropol 355009, Russian Federation 10.3762/bjoc.15.280 Abstract A highly divergent synthesis of regioisomeric thiohydantoins and pseudothiohydantoins spiro-fused to a pharmacologically valuable

• pyrrole-2-one fragment involving the reaction of [e]-fused 1H-pyrrole-2,3-diones with thioureas was developed. The obtained spiro pseudothiohydantoin derivatives were found to undergo a pseudothiohydantoin–thiohydantoin rearrangement. The reactions were shown to proceed under catalyst-free conditions in

• rearrangement (PTR, Scheme 1) [8][9][10][11], which is a special case of a quite poorly investigated iminothiolactone–thiolactam rearrangement [12][13][14][15][16]. This reaction offers attractive opportunities for the design of libraries of regioisomeric hydantoin-based compounds for drug discovery. Spiro

Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation

• Sambasivarao Kotha,
• Gaddamedi Sreevani,
• Lilya U. Dzhemileva,
• Milyausha M. Yunusbaeva,
• Usein M. Dzhemilev and
• Vladimir A. D’yakonov

Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269

• inducers in the HeLa, Hek293, U937, Jurkat, and K562 cell lines. Keywords: apoptosis; biologically active; [2 + 2 + 2] cycloaddition; flow cytometry; spiro thiazolidinedione; Introduction Heterocyclic compounds play a vital role in the metabolism of all living cells. Thus, most of the biologically active

• synthesis of thiazolidinedione derivatives is refluxing chloroacetic acid (2) with thiourea (1), followed by a Knoevenagel condensation with an aldehyde (Scheme 1) [25]. Results and Discussion Limited reports are available dealing with the synthesis of spiro derivatives of thiazolidine-2,4-diones [26][27

• bromide (6a) in the presence of Mo(CO)6 in acetonitrile at 90 °C under microwave irradiation (MWI) conditions to give the co-trimerized spiro derivative 8a (Scheme 2). The free NH moiety of thiazolidinedione 3 was alkylated using alkyl or aryl halides in the presence of Et3N using DCM as solvent. To our

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• conformation [5]. Amongst these, the use of sugar-derived TAAs in peptidomimetics is less explored. The linear tri-/tetrapeptides and spiro-peptides at the anomeric position of mannofructose are known [6][7][8]. Stick and co-workers have reported the synthesis of tetrasubstituted sugar furanoid amino acid

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• co-workers [71] described the one-pot asymmetric gem-chlorofluorination of active methylene compounds by using a copper(II) complex with a chiral spiro 2-pyridyl monooxazoline ligand (SPYMOX). The corresponding α-chloro-α-fluoro-β-keto esters were isolated with up to 92% ee (Scheme 29a). This

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• effect may be useful for structural studies by means of PELDOR or DQC [5]. We recently reported the synthesis of sterically shielded pyrrolidine nitroxide 1 via a stereospecific consecutive assembly of two spiro-(2-hydroxymethyl)cyclopentane moieties. These procedures included the addition of pent-4

• with only one spiro(2-hydroxymethyl)cyclopentane moiety. The rates of reduction of the new nitroxides with ascorbate were measured. Results and Discussion Aldonitrones 5b,c were prepared similarly to the well-known synthesis of 5,5-dimethyl-1-pyrroline-1-oxide (DMPO, 5a) [9][10] from nitrocyclohexane

• performed for reductive isoxazolidine ring opening [15][16] producing aminoalcohols 9a–c in 85–95% yields (Scheme 2). We have previously reported that oxidation of secondary amines with a spiro(2-hydroxymethyl)cyclopentane moiety at the α-carbon with the H2O2/WO42− system is ineffective whereas conversion

Design of a double-decker coordination cage revisited to make new cages and exemplify ligand isomerism

• Sagarika Samantray,
• Sreenivasulu Bandi and
• Dillip K. Chand

Beilstein J. Org. Chem. 2019, 15, 1129–1140, doi:10.3762/bjoc.15.109

• formation of PdL2-type spiro and Pd3L4-type double-decker complexes that is reversible under appropriate conditions. Subsequently, other research groups (Chand, Clever, Crowley and Yoshizawa groups) published Pd3L4-type cages [24]. This design has been further explored by Crowley et al. for the synthesis of

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• . This is a good partner for a cycloaddition with an imine such as 99 that would give rise to the spiro β- and γ-lactam derivative 101 in a diastereoselective manner. Indeed, a seminal contribution also made use of a similar Pd-catalysed carbonylation followed by amide formation and cyclization in a

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• -arylpropanoic acids. The interaction of 2-amino-4-arylimidazoles with aromatic aldehydes or isatins and acyclic methylene active compounds has led to the formation of pyrrolo[1,2-c]imidazole-6-carbonitriles, pyrrolo[1,2-с]imidazole-6-carboxylates and spiro[indoline-3,7'-pyrrolo[1,2-c]imidazoles], which can be

• of Leucetta Sp. and Clathrina Sp. are presented by achiral imidazole alkaloids from the group of benzyl substituted 2-aminoimidazole (dorimidazole A (I), naamine A (II)), fused cyclic systems (2-amino-2-deoxykealiiquinone (III)) and spiro-linked compounds ((−)-spirocalcaridine B (IV)) [2]. Agelas Sp

• . Aeruginosa [22][23]. We have used 4-aryl-substituted 2-aminoimidazoles described by the authors of the aforementioned works as polyfunctional building blocks for the formation of different fused and spiro-linked heterocyclic systems. Last ones are able to act as precursors in the synthesis of the substances

Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

• Aleksandr I. Kobelev,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• and Discussion Previously, we reported an efficient catalyst-free synthesis of spiro[thiazolo-5,2'-pyrroles] 1 via interaction of pyrrolobenzoxazinetriones (PBTs) 2 with thiobenzamide (Scheme 2) [17][18]. In continuation of this research [17][18], and in order to extend the scope of the reaction, we

• attempted to involve the simplest aliphatic thioamide, thioacetamide, in the interaction with PBTs 2. As a result, we obtained the expected spiro[thiazolo-5,2'-pyrroles] 3, which were found to exist in a form with an exo-methylene group according to the NMR spectra (Scheme 3) [19]. Unfortunately, the

• addition of water did not affect the yield of compound 4a or even slightly lowered it. Having determined the optimal conditions of the reactions, we turned our attention to the main distinction of the proposed pathways of formation of compounds 4 – the particle that interacted with the spiro[thiazolo-5,2

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• these catalysts for extensive reactions, including the synthesis of bis(indolyl)methane derivatives, β-amino carbonyl compounds, 14H-dibenzo[a,j]xanthene derivatives, 1,8-dioxodecahydroacridine derivatives, xanthene derivatives, pyrimido[4,5-b]quinoline derivatives, spiro-isatin derivatives, spiro

• -sulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium) chloride (C4(DABCO-SO3H)2·4Cl, 31) and its applications in the synthesis of spiro-oxindole derivatives 36 and 37 was described. C4(DABCO-SO3H)2·4Cl 31 acted as an efficient, cheap, and reusable nanocatalyst for synthesis of 2-amino-4H-pyran derivatives 36

• ), and 1-naphthol (34d)), and malononitrile (35) in water at 90 °C. Isatin (32) and acenaphthenequinone (33) were reacted with C–H activated acids 20a,b, 23, and 34a–c and malononitrile (35) to form the corresponding spiro-isatin derivatives 36 and spiro-acenaphthenequinone derivatives 37 under mild and

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• , which enables them to undergo a high variety of reactions and functionalizations [15]. Combining the chromene core with the 1,2,3-triazole structural motif has led to some interesting new molecules [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Very recently, spiro-fused

Design and synthesis of C₃-symmetric molecules bearing propellane moieties via cyclotrimerization and a ring-closing metathesis sequence

• Sambasivarao Kotha,
• Saidulu Todeti and
• Vikas R. Aswar

Beilstein J. Org. Chem. 2018, 14, 2537–2544, doi:10.3762/bjoc.14.230

• ) reaction [11][12], and rearrangement of spiro-ketones, nucleophilic substitutions of alkenes, and photochemical addition reactions. Multicomponent reactions (MCRs) are also used for the synthesis of hetero-propellanes [13][14]. Recently, heterocyclic propellanes have been reviewed [15][16]. Our group also

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• %). Finally, the spiro compound 30 was subjected to the SM coupling using two different boronic acids to produce the aryl substituted spiro compounds such as 31 (96%) and 32 (79%) (Scheme 4). Along similar lines, we have also demonstrated the synthesis of bis-spirocycles such as 37 by adopting a double RCM

• product 35 was subjected to SM coupling using phenylboronic acid (36) to afford the cross-coupling product 37 (97%, Scheme 5). In another instance, a simple synthetic approach to spiro-fluorene derivative 41 was described involving a serial usage of RCM and SM coupling [37]. To this end, bromofluorene 38

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