One of the great things about being a volunteer at the British Motor Museum is that we get the chance to become involved in a wide range of other activities besides our normal duties and projects. This blog gives a brief overview of what else some of us have been up to over the last six months.
The Classic Virgins Experience Day is perhaps one of the best examples of this, where volunteers have now become an integral part of this popular one day course. Put simply, the day is for members of the public who have an interest in owning a classic car, but need more knowledge and experience of what it actually entails. Theory and basic maintenance sessions are given as well as rides in a variety of classic cars – some owned by the volunteers themselves. The next Classic Virgins will be held on 22 April, details of which can be found here.
An event that always attracts a large number of volunteers is the Lancaster Insurance Classic Motor Show at the NEC in November. On your feet, manning a stand from 10am. until 6pm. – talking classic cars is dream ticket for some of our volunteers. However, as only three volunteers are required for each of the show's three days, a ballot is necessary to select the lucky nine.
The Museum's popular annual Christmas Lecture took place on 3 December and featured Steve Liddle, Principal Aerodynamicist at Renault Sport F1 Racing. Following his lecture and a brief lunch break, delegates returned to put what they'd learned into practice, by building some simple small electric model cars, incorporating their own take on what they'd learned regarding aerodynamic efficiency. This is where four of our volunteers played their part, as following a training day in November, they were well briefed to have an enjoyable time helping and advising with the model building.
Whilst we, as do most volunteers, give up our free time to get involved in projects we have an interest in, it's always nice to be rewarded or recognised. The British Motor Museum is very good at that and once again we were all invited to their annual Christmas Dinner on 19 December. Prior to that, a day trip down to Luton to visit Vauxhall's Heritage Centre was also arranged for us all. This was particularly interesting as the centre only opens by appointment and two guides were on duty to show us around and explain the history of the exhibits.
Finally, it was nice to be recognised at the inaugural West Midlands Volunteers Awards, organised by the West Midlands Museum Development. Held at the Birmingham Hippodrome back in September and hosted by local BBC journalist Sarah Falkard, the Museum had two finalists in the eight categories. The first was the Project Award, for this very blog and the second for Working Together, for the whole team at the new Collections Centre. Whilst we didn't come away with the top prize in either category it was nice for our work to be recognised and to come away with nomination placques. The three of us who went had a good night out as well!


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CC BY-NC-ND 4.0 · SynOpen 2022; 06(04): 270-285
Recent Progress on the [3+2] Cycloaddition Route for the Synthesis of All-Carbon Quaternary Stereocentres
Ani Deepthi ∗
Maneesh Mohan
Meenakshy C. Balachandran
M.M. and M.C.B. thank the University of Kerala for Research Fellowships.
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Construction of all-carbon quaternary centres is an important task in organic synthesis. In spite of the challenges associated with Csp3–Csp3 bond construction in a sterically constrained environment, significant advances have been made in this area. Among the latter, both catalytic and noncatalytic [3+2] cycloaddition approaches have gained wide attention recently. This short review summarizes the [3+2] cycloaddition reactions reported during the period 2016–2022 for the synthesis of molecules possessing one or more all-carbon quaternary stereocentres.
all-carbon - quaternary - stereocentres - [3+2] cycloaddition - cyclization
Ani Deepthi was born in Kerala, India. After securing an MSc degree in Applied Chemistry from Cochin University of Science and Technology, she undertook her PhD degree working under the guidance of Dr Vijay Nair in CSIR-NIIST, Thiruvananthapuram and carried out post-doctoral studies at the National University of Singapore with Prof. Suresh Valiyaveettil. Currently, she is an Assistant Professor at the Department of Chemistry, University of Kerala. Her research interests include synthesis of small molecules possessing bioactive or photoactive properties, chemosensors, and isolation and semisynthetic modification of natural products. She has 32 publications in-peer reviewed journals and two students have secured their PhD under her guidance.
Maneesh Mohan was born in Alappuzha, Kerala, India. He received his BSc. degree in 2011 from Sree Narayana College, Cherthala and MSc. degree in 2016 from Sree Narayana College, Chengannur. He then worked as a Government Guest Lecturer at Sree Narayana College, Kollam and later worked as a Project Assistant II at CSIR-NIIST, Thiruvananthapuram, Kerala. He secured his MPhil. degree from the Department of Chemistry, University of Kerala and is currently pursuing his Ph.D under the guidance of Dr. Ani Deepthi. His research interests include synthesis and in vitro anticancer evaluation of beta carboline-based spiro-heterocycles.
Meenakshy Chandrika Balachandran was born in Kuzhithurai, Tamil Nadu, India. She received her B.Sc. degree in 2018 from University College, Palayam, Thiruvananthapuram and M.Sc. Degree in 2020 from H.H. The Maharaja's College for Women, Vazhuthacaud, Thiruvananthapuram. She qualified in the joint CSIR-UGC NET in 2020 and is currently carrying out her doctoral research under the guidance of Dr. Ani Deepthi at the Department of Chemistry, University of Kerala, Kariavattom. Her research focuses on the synthesis of dispiro-heterocyclic compounds and their anti-cancer properties.
All-carbon quaternary centres refer to stereogenic carbon centres attached to four different neighbouring carbons.[1] [2] Such carbon centres have a special importance owing to their ubiquitous presence in natural products and to their specificity in biological systems due to their structural diversity and enhanced conformational constraints, which makes them suitable targets for protein binding. For example, spirocyclic compounds have found increased utility in drug discovery because of their three-dimensional structural uniqueness.[3] Figure [1] shows some examples of biologically active molecules containing all-carbon quaternary spiro-centres. Fredericamycin A,[4a] first isolated from Streptomyces griseus ATCC49344, is known for its potent activity against P388 mouse leukaemia, CD8F mammary tumours and B16 melanoma in vivo; whereas coleophomone D,[4b] isolated from Stachybotrys parvispora Hughes, is known for its antibacterial and antihypertensive properties. Elatol displays antibiofouling, antibacterial and antifungal properties and is also cytotoxic against HeLa and Hep-2-human carcinoma cell lines.[5a] Colletoic acid is an inhibitor of human 11β-hydroxy steroid dehydrogenase type I (11β-HSD1 inhibition is a new therapeutic approach for type I diabetes mellitus),[5b] and horsfiline, an oxindole alkaloid, is a therapeutic agent.[5c]
Figure 1 Some biologically active molecules containing all-carbon quaternary stereocentres
Given the importance of generating quaternary stereogenic carbon centres, especially as spirocyclic molecules, numerous efforts have been made for developing efficient methods for their stereocontrolled synthesis.[6] [7] [8] [9] [10] [11] Asymmetric [3+2] cycloadditions have created a niche in organic chemistry.[12] Recently Wang and Liu catalogued all-carbon [3+2] cycloaddition methods for natural product synthesis in which they invoke the importance of the strategy to create complex scaffolds of biological interest.[13] In this review, we present selected [3+2] cycloaddition reactions that lead to formation of one or more all-carbon quaternary stereocentres reported during the period 2016–2022. These have been classified into different categories (i) based on the substrate used to generate the 1,3-dipolar species, (ii) those involving allyl-palladium intermediates, (iii) those involving phosphine-allenoate zwitterionic intermediates, and (iv) those involving radical pathways, nitrones, nitrile oxides and nitronate salts, although certain examples can be included in more than one group in this classification.
Classification based on Substrate used to Generate the 1,3-Dipole
Suitably Substituted Cyclopropanes
Previous studies have shown that vinyl cyclopropanes (VCPs), when catalytically activated by palladium or by other transition metals, generate a 1,3-dipolar intermediate that can, in turn, form five-membered rings with various dipolarophiles via [3+2] cycloaddition reactions.[14] However, due to the challenges associated with the short lifetime of the intermediate in the presence of phosphine ligands, asymmetric versions of these reactions have great significance.[15] In this context, recently developed synergistic catalysis proved to be advantageous, wherein the vinyl cyclopropane is activated by a palladium catalyst while the dipolarophile is activated by a second catalyst. For instance, Jørgensen and co-workers in 2016 developed a protocol in which the activated vinyl cyclopropane reacts with the dipolarophile that is, in turn, activated by an organocatalyst. The methodology resulted in the synthesis of densely substituted cyclopentanes with up to four contiguous stereocentres in high yields and with excellent stereoselectivities. For example, vinyl cyclopropane 1 reacted with cinnamaldehyde 2 in the presence of benzoic acid in acetonitrile to yield the product 3 (Scheme [1]). Here, the vinyl cyclopropane is activated by palladium while the α,β-unsaturated aldehyde is activated as the iminium ion formed by reaction with the organocatalyst 4. More specifically, oxidative addition of Pd(0) catalyst facilitates ring opening of the vinyl cyclopropane, yielding a π-allyl palladium intermediate 5 and, in parallel, condensation of catalyst 4 and cinnamaldehyde 2 leads to the formation of the iminium ion 6. Intermediates 5 and 6 combine to generate the [3+2] cycloadduct 3.[16]
Concurrently, there were also successful efforts by Vitale and co-workers to employ iminium/enamine organocatalysis also with Pd(0) activation of vinyl cyclopropanes for the enantioselective synthesis of polysubstituted cyclopentanes by the formal [3+2] cycloaddition of vinyl cyclopropanes with enals,[17] even though generation of molecules containing all-carbon quaternary centres was not reported.
Scheme 1 Combined palladium and organocatalysis to synthesise multisubstituted cyclopentanes containing an all-carbon stereocentres
In 2020, a synergistic bimetallic catalytic system comprising palladium and rhodium catalysts was used by Du and co-workers for the enantioselective synthesis of multisubstituted spirocyclopentane oxindoles containing an all-carbon quaternary stereocentre. In this reaction, α,β-unsaturated 2-acyl imidazole 8 underwent [3+2] cycloaddition with spirovinyl cyclopropanyl-2-oxindole 7 in the presence of palladium and chiral rhodium catalysts to yield the 3-spirocyclopentane-2-oxindole derivative 9 in high yield (Scheme [2]). Here, the zwitterionic π-allyl palladium intermediate formed from 7 attacks the Re-face of the bidentate N,O-coordinated intermediate generated by the coordination of rhodium to compound 8, facilitating the formation of the product 9 as the major isomer (Scheme [2]).[18]
Scheme 2 Bimetallic catalysis to generate an all-carbon spirocentre
Enantioselective ring-openings of other suitably substituted cyclopropanes have also emerged as a powerful strategy for five-membered ring construction.[19] An intramolecular [3+2] annulation reaction of cyclopropanes was reported by Chen, Yang and co-workers in 2016 (Scheme [3]).[20] In this reaction, an amide linker was used for the annulation and TiCl4 was used as the Lewis acid. The coordination of the two carbonyl groups of substrate 10 to titanium(IV) probably facilitates the ring-opening of the cyclopropane, generating a dicarbonyl anion that, in turn, attacks the enone moiety to furnish the six-membered lactam ring and finally leads to dihydroquinolinone 11.
Scheme 3 Synthesis of dihydroquinolinones
Donor–acceptor cyclopropane 12 was used for the synthesis of pharmaceutically relevant azabicyclo[3.2.1]octane 15, bearing two all-carbon quaternary stereogenic centres at the bridgehead positions, by reduction of imine 14 and subsequent deprotection and intramolecular amidation. The imine was, in turn, synthesized by MgI2 catalysed [3+2] cycloaddition of donor–acceptor cyclopropane 12 with azadiene 13 in dichloromethane (Scheme [4]).[21]
Scheme 4 Synthesis of quaternary bridgehead stereocentres
Wang and co-workers in 2019 used the [3+2] annulation strategy to construct an all-carbon stereocentre by conducting the 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) mediated reaction of cyanocyclopropane carbonate 16 and (E)-3-aryl-2-cyano acrylate 17. The reaction takes place by the initial deprotonation of cyclopropane 16, which ring opens to form an ylide intermediate. The [3+2] annulation of the ylide to acrylate 17 leads to the cycloadduct 18 after a tautomerization step (Scheme [5]).[22]
Scheme 5 DBU-mediated [3+2] cycloaddition to construct cyclopentanes
Aminocyclopropanes have recently emerged as suitable reaction partners that can undergo annulation with alkenes and cyclopropenes under photocatalysis. In 2019, Waser and co-workers reported the [3+2] annulation reaction of cyclopropenes with cyclopropyl aniline 20 using photocatalysis. The catalyst used was 2,4,5,6-tetrakis(diphenylamino)isophthalonitrile (4DPAIPN). The transformation proved to be highly efficient, and diastereoselectivity was further improved by choosing bulky cyclopropyl aniline and difluorocyclopropenes (Scheme [6]).[23] Subsequently, in 2020, a highly diastereoselective and enantioselective [3+2] cycloaddition of cyclopropyl amine with α-alkyl styrenes was reported by Ooi and co-workers using photocatalysis to yield cyclopentanes containing all-carbon quaternary stereocentres. Here, iridium-polypyridyl complexes were used as photocatalysts and the reaction is initiated by capture of the anionic component of the photocatalyst by the cyclopropyl urea 22, generating a chiral supramolecular ion pair. Under irradiation, single electron transfer (SET) from the substrate to the excited-state cationic iridium generates a radical cation that undergoes stereoselective bond formation with the α-alkyl styrene 23 within the restrictions of the asymmetric environment created by the chiral anion.
Scheme 6 [3+2] Annulation of cyclopropene with aminocyclopropane
A representative reaction for synthesis of the cyclopentane 24 is depicted in Scheme [7].[24] The Waser group also reported the use of the amino cyclopropane monoester 25 for [3+2] annulation with suitably substituted indoles using silyl bistriflimide as catalyst (Scheme [8]). The method was successfully applied for the construction of a non-symmetrical all-carbon quaternary centre at the acceptor position of the cyclopropane in good yield and diastereoselectivity, as exemplified in Scheme [8].[25]
Scheme 7 Photocatalysed enantioselective urea-tethered cyclopentane synthesis
Construction of an all-carbon quaternary stereocentre at the α-position of aza-arenes was reported by Jiang and co-workers by synergistic photoredox and Brönsted acid catalysis. Scheme [9] shows a representative reaction of cyclopropyl aniline 20 with 2-(1-phenylvinyl)pyridine 28 that leads to 29. It was found that there were remarkable differences in enantioselectivity when using electron-withdrawing or electron-donating substituents on the aromatic ring of the 2-(1-arylvinyl)pyridine, which led to the proposition of a ternary transition state with the chiral Brönsted acid acting as the bifunctional catalyst. The chiral Brönsted acid catalyst used was an iminodiphosphoric acid that co-catalyses the reaction along with the photocatalyst, dicyanopyrazine (DPZ).[26]
Scheme 8 [3+2] Annulation of indole with aminocyclopropane
Scheme 9 Photocatalysed enantioselective pyridine tethered cyclopentane synthesis
# 2.2
3-Homoacyl Coumarins
Lin and co-workers have utilized the all-carbon 1,3-dipole precursor 3-homoacyl coumarin 30, in stereoselective [3+2] cycloaddition reactions in the presence of a squaramide catalyst. Initially indandione alkylidene 31 was used as the dipolarophilic partner, which led to the synthesis of coumarin/indandione fused spirocyclopentanes 32, bearing four contiguous stereocentres.[27a] Later these workers used alkylidene oxindoles as the dipolarophilic partner to yield a cycloadduct containing five contiguous stereocentres of which one is an all-carbon quaternary spirocentre.[27b] The reaction takes place via initial activation of the homoacyl coumarin 30 by deprotonation to provide a conjugate acid-base pair with H-bonding interactions. The Re-face of activated coumarin then adds to the Re-face of the alkylidene oxindole 33 to generate a Michael adduct that ultimately leads to product 34 (Scheme [10]). Lin's group has also employed the strategy for the enantioselective synthesis of spiropyrazolone fused cyclopenta[c]chromen-4-ones.[27c] The reaction occurs by [3+2] cycloaddition of 3-homoacyl coumarin 30 with α,β-unsaturated pyrazolone 35 in the presence of a cinchona alkaloid-derived hydrogen-bonding catalyst and benzoic acid. Excellent yields of spiropyrazolones of the type 36 were obtained in a highly enantioselective manner. All these reactions are summarized in Scheme [10].
Scheme 10 Homoacyl coumarin in [3+2] cycloaddition yielding all-carbon spirocentres
Isatin-Based (Trifluoromethyl)imines
Isatin-based (trifluoromethyl)imines were reported to undergo [3+2] annulations with alkenes efficiently in the presence of metal catalysts in conjunction with organocatalysts. A Brönsted base and Lewis acid co-operatively catalysed asymmetric 1,3-dipolar cycloaddition reaction was reported to yield a series of trifluoromethyl substituted 2,3-pyrrolidinyl dispiro-oxindoles with high enantioselectivity. The reaction was initiated by deprotonation of 37 by the complex generated from the organocatalyst and Et2Zn, accompanied by release of ethane. This was followed by coordination of methylene indolinone 38 to the zinc from the less-hindered face. Michael addition followed by Mannich reaction led to an intermediate complex, from which the final product 39 was released by proton exchange and the catalytic cycle continued (Scheme [11]).[28]
Scheme 11 Zinc complex mediated all-carbon spirocentre formation
In another report, isatin-based (trifluoromethyl)imines were reported to undergo [3+2] cycloaddition with unsaturated 4-benzylidene chromanones 40 promoted by the organocatalyst DABCO. The authors could also achieve up to 69% enantiopurity for the spirooxindole-chromanone hybrid 41 using Takemoto's bifunctional thiourea catalyst 42, via formation of an 'exo' transition state (Scheme [12]).[29] Concurrently Knipe and co-workers reported the use of cinchona-derived thiourea catalyst 43 for the synthesis of spiropyrrolidine oxindoles with excellent enantioselectivities. Some of the examples reported contained molecules with all-carbon quaternary stereocentres, as exemplified in the synthesis of 45 and 47 (Scheme [13]).[30]
Scheme 12 DABCO mediated all-carbon spirocentre formation
Scheme 13 Use of thiourea catalyst
Iminoesters and Isocyanoesters
Zhang and co-workers in 2017 reported a copper(I) catalysed asymmetric exo-selective [3+2] cycloaddition of β-trifluoromethyl β,β-disubstituted enone 49 with azomethine ylides (generated from glycine ketinimine 48), leading to the synthesis of chiral pyrrolidines bearing a trifluoromethylated quaternary carbon centre. The chiral ligand used in the reaction was (S)-MeO-DTBM-Biphep 53 and the copper salt used was Cu(CH3CN)4BF4 (Scheme 14). The reaction was found to be general for a wide range of enones and acyclic azomethine ylides. Moreover, the products formed could be oxidized to 3H-pyrroles using 2,3-dichloro-5,5-dicyano-1,4-benzoquinone (DDQ) and converted into N-hydroxy pyrroles and nitrones using m-CPBA in varying efficiencies.[31] Later, the same group reported the Cu(I)-Ming-Phos-catalysed enantioselective [3+2] cycloaddition of glycine ketinimine with β-trifluoromethyl enone 50, which yielded the highly functionalized pyrrolidine 52 containing an all-carbon quaternary stereocentre in 95% enantiomeric excess (Scheme [14]).[32]
Scheme 14 Copper(I) catalysed [3+2] cycloaddition for synthesis of multi-substituted pyrrolidines. Reagents and conditions: (i) Cu(CH3CN)4BF4 (5.0 mol%), Ligand (5.5 mol%), Cs2CO3 (50 mol%), THF.
Subsequently, ligand-controlled [3+2] cycloaddition of iminoesters leading to chiral pyrrolidines with adjacent or discrete quaternary stereocentres with at least one all-carbon stereocentre was reported by the same group. Scheme [15] depicts a representative reaction of α-methyl-iminoester 55 and β,β-disubstituted enone 56 in the presence of a copper catalyst and chiral ligands L1 or L2, yielding 57a or 57b as the major product, depending on the ligand. Computational studies provided insights into the regioselective control. When ligand L1 was used, the phosphorus and nitrogen atoms of the ligand remained coordinated to the Cu(I) throughout the process, yielding 57a in higher amounts, while a switch in regioselectivity was observed when L2 was used due to formation of a Cu–Oenone bond, with the amine nitrogen atom of L2 dissociating from Cu(I) centre.[33] The same group has also reported the synthesis of optically active dihydropyrroles containing an all-carbon quaternary stereocentre by copper-catalysed [3+2] cycloaddition of 56 with isocyanoesters of the type 58, and maximum yields and enantioselectivities were obtained using (R)-DTBM-Seg-Phos as catalyst. Scheme [16] shows a representative example for the synthesis of the dihydropyrrole 59.[34]
Scheme 15 Ligand-controlled [3+2] cycloaddition of iminoesters leading to chiral pyrrolidines
Scheme 16 Copper-catalyzed [3+2] for synthesis of dihydropyrrole bearing an all-carbon stereocentre. Reagents and conditions: (i) CuBF4 (CH3CN)4 (5 mol%), Ligand (5.5 mol%) (ii) K2CO3 (50 mol%), MTBE, –40 °C, 12 h.
Aldehydes and Isatins
Aldehydes and isatins are versatile substrates to generate azomethine ylides. For instance, construction of an all-carbon spiro quaternary centre was reported by Boudriga and co-workers in 2019 during the diastereoselective synthesis of dispiropyrrolo[2,1-a]isoquinoline-fused pyrrolidine-2,5-diones by [3+2] cycloaddition of the cyclic diketone-based tetrahydroisoquinolinium N-ylide. In this reaction, the azomethine ylide formed from isatin 60 and 1,2,3,4-tetrahydroisoquinoline 61 approaches the (E)-3-arylidene-1-phenyl-pyrrolidine-2,5-dione 62 in an exo-manner to yield products 63 and 64, both containing a spiro quaternary carbon centre, as depicted in Scheme [17].[35] Concurrently, Yan and co-workers reported that acetic acid can act as a catalyst to facilitate the formation of azomethine ylides from aromatic aldehydes and pyrrolidine, which, in turn, undergo [3+2] cycloaddition with 3-arylidene indolin-2-one or with 2-arylidene-1,3-indanedione to yield the corresponding functionalised pyrrolidines containing a spiro all-carbon quaternary stereocentre. In this reaction, the iminium ion 70, formed from aromatic aldehyde and pyrrolidine, undergoes a [1,3]-hydride shift yielding an enamine intermediate 72. The latter then undergoes an aldol type reaction with a second molecule of aldehyde 65 followed by dehydration and deprotonation, yielding a conjugated azomethine ylide 67 that finally participates in [3+2] cycloaddition with the alkene 68 to yield cycloadduct 69, as shown in Scheme [18].[36]
Scheme 17 Tetrahydroisoquinoline based azomethine ylide [3+2] to construct an all-carbon quaternary spirocentre
Scheme 18 Construction of an all-carbon quaternary stereocentre by acetic acid catalysis
Reaction of Allyl Palladium Intermediates
Palladium-catalysed [3+2] cycloaddition of 5-vinyl oxazolidinones and trisubstituted alkenes using chiral ammonium–phosphine ligands was reported by Takashi and co-workers in 2016. The reaction takes place by an initial intermolecular addition of an allyl palladium species to the alkene, generating a zwitterionic intermediate. Subsequent ring closure and bond formation between the two reactive sites of the intermediate yields a product possessing three contiguous stereogenic centres, including two all-carbon quaternary centres. A phosphine ligand incorporating a quaternary ammonium halide component was used to assist Pd-halide contact. A representative reaction of oxazolidinone 73 with (E)-ethyl 2-cyano-3-phenylacrylate 74 leading to product 75 is shown in Scheme [19].[37]
Scheme 19 Synthesis of multisubstituted pyrrolidines via [3+2] cycloaddition of allyl palladium intermediates with acrylates
Nucleophilic 1,3-dipolar π-allyl palladium intermediates generated from vinyl ethylene carbonates have been found to be efficient reaction partners. For instance, synthesis of spirooxindoles with two contiguous all-carbon stereocentres was reported by Hu and co-workers by the palladium-catalysed [3+2] cycloaddition of methylene indolinone with vinyl ethylene carbonate. The reaction takes place through the initial formation of the Pd-π-allyl intermediate 79, which undergoes [3+2] cycloaddition with methylene indolinone 76 by intramolecular nucleophilic attack to yield 3,3′-tetrahydrofuryl spirooxindole 78 (Scheme [20]).[38] Recently, the 1,3-dipolar π-allyl palladium intermediate generated from vinyl ethylene carbonate was also reacted with chalcones under rhodium catalysis, leading to formation of tetrahydrofuran derivatives possessing an all-carbon quaternary stereocentre. The asymmetric bimetallic catalysis was achieved using a chiral rhodium complex catalyst along with Pd2(dba)3·CHCl3 and was demonstrated using α,β-unsaturated 2-acyl imidazole 81 and racemic phenyl vinyl carbonate 77 as cycloaddition partners. The reaction takes place by the activation of the α,β-unsaturated 2-acyl imidazole substrate 81 by the chiral rhodium complex through bidentate coordination. The zwitterionic π-allyl intermediate approaches the double bond of the rhodium complex through its Si-face. Subsequent coordination-dissociation and electron neutralization generates an intermediate that undergoes substitution with 81, releasing the target 1,2,3,4-tetrahydrofuran molecule 82 (Scheme [21]).[39]
Scheme 20 Palladium-catalyzed all-carbon spirocentre formation
Scheme 21 Synthesis of tetrahydrofuran containing an all-carbon stereocentre
Very recently, Zi and co-workers used vinyl methylene cyclic carbonates of the type 83 to generate vinyl-substituted palladium-oxyallyl species that undergo enantioselective inverse electron-demand [3+2] cycloaddition with electron-deficient nitroalkenes of type 84. A hydrogen-bond-donating ligand was used to construct the cyclopentanone 86 containing an all-carbon quaternary stereocentre in a highly stereoselective manner. The optimised ligand for achieving maximum enantiomeric excess was found to be Fe-Ur-Phos 85, which contains a urea moiety. The latter facilitates the hydrogen-bond formation between the chiral catalyst and nitro group of 84, which imparts the stereocontrol of the reaction (Scheme [22]).[40]
Scheme 22 Ferrocene-based catalyst for enantioselective cyclopentanone synthesis
Liu and co-workers recently reported cooperative catalysis mediated by a palladium catalyst and urea-tertiary amine organocatalyst for the [3+2] cycloaddition between γ-methylidene-δ-valerolactones of type 87 and β-nitrostyrene 88. The reaction occurs by the initial generation of a 1,4-dipole from 87 by oxidative addition of palladium, facilitated by CO2 release and followed by intermolecular Michael addition to the species generated from the nitro-olefin. The strong hydrogen bonding between the urea-tertiary amine catalyst 89 and the nitro-olefin helps in the Re-face attack of the zwitterionic π-allyl intermediate onto the nitro-olefin, providing good control of the stereochemistry of the all-carbon quaternary stereocentre. Subsequent intramolecular cyclisation affords the final product 90 (Scheme [23]).[41]
Scheme 23 Urea-tertiary amine catalysis. Reagents and conditions: (i) Pd2(dba)3·CHCl3 (5 mol%), Ligand (22 mol%), 89 (5 mol%), 4 Å MS, THF, –10 °C.
Reaction of Phosphine-Allenoate Zwitterionic Species
Scheme 24 [3+2] Annulation of N-tosylimines with allenoates
It is well known that phosphines can add to alkynoates and allenoates to generate zwitterions that, in turn, can undergo [3+2] cycloaddition with alkenes and alkynes.[42] Asymmetric versions of such reactions using chiral phosphine catalysts have been widely explored[43] and the strategy has been utilised for the synthesis of all-carbon quaternary stereocentres.[44] An enantioselective [3+2] annulation of α-substituted allenoates of the type 91 with β,γ-unsaturated N-tosyl imine 92 in the presence of a phosphine catalyst was reported by Lu and co-workers. The reaction resulted in the formation of cyclopentene 93, containing an all-carbon quaternary centre. The reaction takes place via initial activation of the allenoate by attack of the phosphine, generating intermediate 94 that then undergoes [3+2] annelation with the N-tosyl imine, leading to product 93 after proton shift (Scheme [24]).[45] Recently Liu and co-workers used this strategy for the regioselective synthesis of CF3-substituted quaternary carbon-centred molecules in moderate to good yields. The reaction occurs through initial nucleophilic addition of the phosphine onto the allenoate, yielding the zwitterionic intermediate 98 that undergoes α-addition to the double bond of 96 to yield the anionic intermediate 99, which, in turn, cyclises to 100. Final 1,2-proton transfer and β-elimination of the catalyst yields the target cyclopentene 97 (Scheme [25]).[46]
Scheme 25 Phosphine-catalysed cyclopentane synthesis
Scheme 26 l -Isoleucine derived amide phosphine catalysed reaction
Yao and co-workers reported a stereoselective and enantioselective trimerization of γ-aryl-3-butynoates catalysed by l-isoleucine-derived amide phosphine to yield cyclopentenones bearing an all-carbon quaternary stereocentre. The reaction occurs by addition of the phosphine to the allenoate (formed by isomerisation of the alkyne 102) to form zwitterionic intermediate 105, which, in turn, reacts with another molecule of allenoate to yield intermediate 106 followed by intramolecular Michael addition to yield 107. After a 1,2-H shift and expulsion of the catalyst, 109 is obtained, leading eventually to the final product 104 containing an all-carbon quaternary stereocentre (Scheme [26]).[47] Very recently Takao and co-workers also utilised this strategy for the synthesis of cyclopentene molecules possessing all-carbon quaternary stereocentres using Oppolzer's camphor sultam 113 as one of the reaction partners.[48] The camphor sultam acts as a chiral auxiliary in this reaction, which is subsequently removed by chemoselective hydrolysis using alkaline hydrogen peroxide to furnish carboxylic acid 115 in 94% yield (Scheme [27]). The high regioselectivity is probably due to the bulkiness of the camphor sultam. The authors have also applied this strategy for the formal synthesis of R-(–)-puraquinonic acid.
In another earlier report, Morita–Baylis–Hillman (MBH) carbonates were used instead of allenoates to generate zwitterionic intermediates using nucleophilic phosphines. The latter reacted with MBH carbonate 117 to yield the salt 119 that, in turn, was deprotonated by the tert-butoxide to form species 120. The dispirobisoxindole 118, containing two all-carbon quaternary stereocentres, was formed by [3+2] cycloaddition of isoindigo 116 with 120 through formation of intermediates 121 and 122 (Scheme [28]).[49]
Miscellaneous Cycloaddition Reactions
In 2017, Li and co-workers reported that an allene-tethered electron-deficient olefin underwent intramolecular [3+2] cycloaddition in the presence of benzene thiol to yield [3.3.0]bicyclic systems containing vicinal quaternary carbon stereocentres. The intramolecular cascade reaction is initiated by an electrophilic benzene thiol radical 123, affording a thermodynamically stable tertiary radical 124, by adding to the central sp-carbon atom of the allene 121. Subsequent attack of this radical to the α,β-unsaturated double bond via a 5-exo-trig-cyclisation led to radical intermediate 125 that then underwent a 5-endo-trig-cyclisation to generate 126. The latter in the next step abstracts a hydrogen atom from the benzene thiol and is converted into the final product 122 (Scheme [29]).[50]
Scheme 27 Camphor sultam as chiral auxiliary. Reagents and conditions: (i) n-Bu3P (30 mol%), toluene, 0 °C (ii) LiOH, aq H2O2, THF/H2O, RT.
Scheme 28 Reaction of MBH carbonate in the presence of phosphine
Scheme 29 Synthesis of bicyclic [3.3.0] compounds containing vicinal all-carbon stereocentres
An intramolecular silyl-nitronate cycloaddition was reported by Veselovsky and co-workers for the enantioselective synthesis of substituted cyclopentanones containing an all-carbon quaternary stereocentre. Henry reaction of 4-methyl pentenal 127 with nitromethane in the presence of the chiral catalyst 128 yields the unsaturated nitro alcohol 129. The latter is then converted into silyl ether 130 that, when treated with 1,1,1,3,3,3-hexamethyldisilazane (HMDS), yielded cyclopentaisoxazolidinone 132 through formation of the nitronate 131 by a stereoselective intramolecular cycloaddition with trans-disposition of the OTBS substituent relative to the annulated isoxazolidinone ring. Further transformation of 132 by exposure to sodium methoxide led to ring opened oximes 134a and 134b (anti/syn ratio 12:1 by 1H NMR analysis) through nitroso tautomerism. Final deoximation of the oximes by trituration with periodic acid resulted in the cycloalkanone 135 (Scheme [30]).[51]
Scheme 30 Synthesis of cyclopentanones via intramolecular silyl-nitronate cycloaddition
A formal 1,3-dipolar cycloaddition of 3-ylidene oxindoles of the type 136 with aryl diazomethane 140 (generated from benzaldehyde 65 and tosyl hydrazine 137) was reported by Babu and co-workers in 2018.[52] In this reaction, the intermediate cycloadduct 141 underwent decomposition in the aprotic solvent to deliver 3-spirocyclopropyl-2-oxindole 138, containing an all-carbon quaternary stereocentre. It was also observed that, in the presence of protic solvent, the cycloadduct 141 tautomerizes to form 142 which, in turn, is oxidised to the corresponding spiropyrazole oxindole. The latter then undergoes spontaneous rearrangement to pyrazoloquinazolinone 139. Thus, a solvent-controlled switchable product selectivity was demonstrated, as depicted in Scheme [31].
Scheme 31 Synthesis of 3-spirocyclopropyl-2-oxindole 138 and pyrazoloquinazolinone 139
Gao and co-workers, in 2019, reported the application of a [3+2] cycloaddition strategy for the construction of the core skeleton of calyciphylline A alkaloids. Herein, nitrone-induced [3+2] cycloaddition was used for the construction of the cis-hydroindole A–C rings containing an all-carbon quaternary centre at C5. Scheme [32] shows a representative construction of the stereogenic C5 centre of an important precursor to himalensine A[53] [54] in which a cycloheptene substrate 143 is treated with N-benzylhydroxylamine resulting in a nitrone intermediate that, on intramolecular 1,3-dipolar cycloaddition through 6-exo-cyclisation with the α,β-unsaturated ester, results in cycloadduct 144, an important precursor containing the all-carbon quaternary centre of himalensine A 145.
Scheme 32 Intramolecular nitrone-ene [3+2] cycloaddition for construction of a precursor to the himalensine alkaloids
Gao and co-workers, in 2019, reported the asymmetric total synthesis of (–)-viridin and (–)-viridiol (Figure [2]), both containing a quaternary all-carbon stereocentre at C-10. The strategy involved the synthesis of compound 146 from L-ribose, which was then transformed into the unsaturated ester 147 by ruthenium-catalysed cross-metathesis. Treatment of 147 with hydroxylamine hydrochloride generated oxime 148, which was converted into nitrile oxide 149 with chloramine-T. Subsequent intramolecular [3+2] cycloaddition generated isooxazoline 150, which, on reductive hydrogenolysis and hydrolysis, yielded ketone 151. Wittig reaction of the latter produced compound 152, which, on reaction with dimethyl hydroxylamine hydrochloride (DMHH), yielded the Weinrib amide 153. This reacted with the anion of dihydroindenol 154 to yield 155 as a mixture of diastereomers at C17 (see Figure [2]). Compound 155 was converted into the desired tetracyclic core 156, containing an all-carbon quaternary stereocentre at C10, using a metal-catalysed hydrogen atom transfer (MHAT) strategy with the help of cobalt-salen catalyst 158 and phenyl silane. Selective removal of the TES group using Dowex resin followed by oxidation with Dess–Martin periodinane (DMP) yielded compound 157, which was converted into viridin and viridiol (Scheme [33]).[55]
Figure 2 Structures of viridin and viridiol
Scheme 33 Sequential synthesis of viridiol precursor
Effective ways of constructing all-carbon stereocentres have been reported in the past five years using [3+2] cycloaddition strategies involving metal-catalysed, organocatalysed, photocatalysed, base/acid-mediated, and thermal [3+2] cycloadditions, leading to products containing one or more all-carbon stereocentres. We believe that this review along with other reviews in this period,[56] [57] [58] [59] [60] [61] will provide insight for organic chemists wishing to construct molecules containing all-carbon quaternary stereocentres.
The authors thank the University of Kerala for provision of facilities.
1 Fuji K. Chem. Rev. 1993; 93: 2037
2 Christoffers J, Mann A. Angew. Chem. Int. Ed. 2001; 40: 4591
3 Bora D, Kaushal A, Shankaraiah N. Eur. J. Med. Chem. 2021; 215: 113263
4a Chen Y, Luo Y, Ju J, Wendt-Pienkowski E, Rajski SR, Shen B. J. Nat. Prod. 2008; 71: 431
4b Nicolaou KC, Montagnon T, Vassilikogiannakis G. Chem. Commun. 2002; 2478
5a White DE, Stewart IC, Grubbs RH, Stoltz BM. J. Am. Chem. Soc. 2008; 130: 810
5b Sawada T, Nakada M. Org. Lett. 2013; 15: 1004
5c Jossang A, Jossang P, Hadi HA, Sevenet T, Bodo B. J. Org. Chem. 1991; 56: 6527
6 Riant O, Hannedouche J. Org. Biomol. Chem. 2007; 5: 873
7 Cozzi PG, Hilgraf R, Zimmermann N. Eur. J. Org. Chem. 2007; 5969
8 Bella M, Gasperi T. Synthesis 2009; 1583
9 Quasdorf KW, Overman LE. Nature 2014; 516: 181
10 Corey EJ, Guzman-Perez A. Angew. Chem. Int. Ed. 1998; 37: 388
11 Willis MC. J. Chem. Soc., Perkin Trans. 1 1999; 1765
12 Hashimoto T, Maruoka K. Chem. Rev. 2015; 115: 5366
13 Wang Z, Liu J. Beilstein J. Org. Chem. 2020; 16: 3015
For reviews on the synthesis and reactivity of VCPs, see:
14a Ganesh V, Chandrasekharan S. Synthesis 2016; 48: 4347
14b Brownsey DK, Gorobets E, Derksen DJ. Org. Biomol. Chem. 2018; 16: 3506
15a Trost BM, Morris PJ, Sprague SJ. J. Am. Chem. Soc. 2012; 134: 17823
15b Mei L.-Y, Wei Y, Shi M, Xu Q. Organometallics 2013; 32: 3544
15c Xie M.-S, Wang Y, Li J.-P, Du C, Zhang Y.-Y, Hao E.-J, Zhang Y.-M, Qu G.-R, Guo H.-M. Chem. Commun. 2015; 51: 12451
16 Halskov KS, Nӕsborg L, Tur F, Jørgensen KA. Org. Lett. 2016; 18: 2220
17 Laugeois M, Ponra S, Ratovelomanana-Vidal V, Michelet V, Vitale MR. Chem. Commun. 2016; 52: 5332
18 Wan Q, Chen L, Li S, Kang Q, Yuan Y, Du Y. Org. Lett. 2020; 22: 9539
19 Pirenne V, Muriel B, Waser J. Chem. Rev. 2021; 121: 227
20 Xiao J.-A, Xia PJ, Zhang X.-Y, Chen X.-Q, Ou G.-C, Yang H. Chem. Commun. 2016; 52: 2177
21 Verma K, Banerjee P. Adv. Synth. Catal. 2017; 359: 3848
22 Dai C, Li M, Chen M, Luo N, Wang C. J. Chem. Res. 2019; 43: 43
23 Muriel B, Gagnebin A, Waser J. Chem. Sci. 2019; 10: 10716
24 Uraguchi D, Kimura Y, Ueoka F, Ooi T. J. Am. Chem. Soc. 2020; 142: 19462
25 Pirenne V, Robert EG. L, Waser J. Chem. Sci. 2021; 12: 8706
26 Yin Y, Li Y, Gonçalves TP, Zhan Q, Wang G, Zhao X, Qiao B, Huang K.-W, Jiang Z. J. Am. Chem. Soc. 2020; 142: 19451
27a Chen Y.-R, Ganapuram MR, Hsieh K.-H, Chen K.-H, Karanam P, Vagh SS, Liou Y.-C, Lin W. Chem. Commun. 2018; 54: 12702
27b Vagh SS, Karanam P, Liao C.-C, Liu T.-H, Liou Y.-C, Edukondalu A, Chen Y.-R, Lin W. Adv. Synth. Catal. 2020; 362: 1679
27c Khairnar PV, Su Y.-H, Edukondalu A, Lin W. J. Org. Chem. 2021; 86: 12326
28 Yi Y, Hua Y.-Z, Lu H.-J, Liu L.-T, Wang M.-C. Org. Lett. 2020; 22: 2527
29 Li Z, Lu Y, Tian YP, Hao X.-X, Liu X.-W, Zhou Y, Liu X.-L. Tetrahedron 2021; 98: 132297
30 Duffy C, Roe WE, Harkin AH, McNamee R, Knipe PC. New J. Chem. 2021; 45: 22034
31 Xu B, Zhang Z.-M, Liu B, Xu S, Zhou L.-J, Zhang J. Chem. Commun. 2017; 53: 8152
32a Xu B, Zhang Z.-M, Xu X, Liu B, Xiao Y, Zhang J. ACS Catal. 2017; 7: 210
32b Liu B, Zhang Z.-M, Xu B, Xu S, Wu H.-H, Zhang J. Adv. Synth. Catal. 2018; 360: 2144
33 Xu S, Zhang Z.-M, Xu B, Liu B, Liu Y, Zhang J. J. Am. Chem. Soc. 2018; 140: 2272
34 Xu B, Zhang Z.-M, Zhou L, Zhang J. Org. Lett. 2018; 20: 2716
35 Boudriga S, Haddad S, Askri M, Soldera A, Knorr M, Strohmann C, Golz C. RSC Adv. 2019; 9: 11082
36 Huang Y, Fang H.-L, Huang Y.-X, Sun J, Yan C.-G. J. Org. Chem. 2019; 84: 12437
37 Imagawa N, Nagato Y, Ohmatsu K, Ooi T. Bull. Chem. Soc. Jpn. 2016; 89: 649
38 Wang J, Zhao L, Rong Q, Lv C, Lu Y, Pan X, Zhao L, Hu L. Org. Lett. 2020; 22: 5833
39 Ming S, Qurban S, Du Y, Su W. Chem. Eur. J. 2021; 27: 12742
40 Zhang Y, Qin T, Zi W. J. Am. Chem. Soc. 2021; 143: 1038
41 Gao C, Zhang T, Li X, Wu J.-D, Liu J. Org. Chem. Front. 2022; 9: 2121
42 Zhang C, Lu X. J. Org. Chem. 1995; 60: 2906
43a Wei Y, Shi M. Org. Chem. Front. 2017; 4: 1876
43b Ni H, Chan W.-L, Lu Y. Chem. Rev. 2018; 118: 9344
43c Guo H, Fan YC, Sun Z, Wu Y, Kwon O. Chem. Rev. 2018; 118: 10049
44 Li H, Lu Y. Asian J. Org. Chem. 2017; 6: 1130
45 Ni H, Yao W, Lu Y. Beilstein J. Org. Chem. 2016; 12: 343
46 Chen G.-S, Zhang J.-W, Li Z.-D, Zhao Y.-L, Liu Y.-L. Org. Chem. Front. 2020; 7: 3399
47 Gao Y, Zhang J, Shan W, Fei W, Yao J, Yao W. Org. Lett. 2021; 23: 6377
48 Oga M, Takamatsu Y, Ogura A, Takao K. J. Org. Chem. 2022; 87: 8788
49 Ren H.-X, Peng L, Song X.-J, Liao L.-G, Zou Y, Tian F, Wang L.-X. Org. Biomol. Chem. 2018; 16: 1297
50 Li S, Zhang P, Li Y, Lu S, Gong J, Yang Z. Org. Lett. 2017; 19: 4416
51 Lozanova AV, Stepanov AV, Zlokazov MV, Veselovsky VV. ARKIVOC 2017; (iii): 217
52 Ramu G, Krishna NH, Pawar G, Sastry KN. V, Nanubolu JB, Babu BN. ACS Omega 2018; 3: 12349
53 Zhong J, He H, Gao S. Org. Chem. Front. 2019; 6: 3781
54 Shi H, Michaelides IN, Derses B, Jakubee P, Nguyen QN. N, Paton RS, Dixon DJ. J. Am. Chem. Soc. 2017; 139: 17755
55 Ji Y, Xin Z, He H, Gao S. J. Am. Chem. Soc. 2019; 141: 16208
56 Ling T, Rivas F. Tetrahedron 2016; 72: 6729
57 Zeng X.-P, Cao Z.-Y, Wang Y.-H, Zhou F, Zhou J. Chem. Rev. 2016; 116: 7330
58 Feng J, Holmes M, Krische MJ. Chem. Rev. 2017; 117: 12564
59 Xu P.-W, Yu J.-S, Chen C, Cao Z.-Y, Zhou F, Zhou J. ACS Catal. 2019; 9: 1820
61 Wang Z. Org. Chem. Front. 2020; 7: 3815
Ani Deepthi
Department of Chemistry, University of Kerala, Kariavattom campus
Thiruvananthapuram 695581, Kerala state
Email: anideepthi@gmail.com
Received: 22 July 2022
Accepted Manuscript online:
Article published online:
© 2022. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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redpajama_set_name: RedPajamaCommonCrawl


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redpajama_set_name: RedPajamaGithub


Pond Dye is part of the complete program to transform your pond or dugout into a beautiful body of water. Why use Pond Dye? Algae and aquatic weeds require sunlight to grow and pond dye shades the pond from the UV Light which helps shade the pond, keep the water temperature cooler and slow the growth of the algae and aquatic weeds. The dye is beautiful looking and comes in 2 colours- natures blue and black dyemond.
These water-soluble packets are so easy to use. There is no need to rip or tear the packets you simply throw them into the water and watch the plastic dissolve, releasing the dye into your pond. No mess!


text:
Text Reviews Theatrical Review
Theatrical Review: The Road
Post author By Darren Goodhart
No Comments on Theatrical Review: The Road
When I wrote a review for 2012, I made mention of the fact that while it's special effects were spectacular, there just seemed to be a little something odd that it's escape-by-the-seat-of your-pants popcorn movie thrill-ride was being viewed as entertainment considering that it's backdrop was hundreds of thousands of people meeting their certain death…
Well, think of The Road as the story of people who weren't lucky enough to get to go on that roller coaster.
It's actually much, much more than that, but that was something that certainly popped into my head after watching it.
The Road from director John Hillcoat adapted from a novel by Cormac McCarthy tells the story of a father and son trying to survive after a global cataclysm has occurred and it takes the harder and darker path in it's tale of survival while still trying to maintain their humanity. There's no explanation for what has occurred and there's no government team that's seen as the path of salvation, it's probably way closer to what you and I would actually face if such things were to really occur.
And it's a really great little film with a very good performance from it's lead actor, Viggo Mortenson. But, even though I had criticisms with 2012 one thing that it surely offered up was conversation afterwards of what you'd really do in something like this, and The Road does that as well.
It's extremely dark stuff, though and that's certainly not the thing for some in the potential viewing audience out there. There is a subtle message of hope here by the film's end, but you literally have to go through hell and high water to get there.
Viggo Mortenson plays the father, never called anything other than "Poppa" by his young son. I've often said in conversations with some friends that Tom Hanks is the closest thing that we have to a James Stewart today in films, well with that in mind, the more and more that I see of Viggo Mortenson, the more that I'm convinced that he's the closest to what we have now that's like Kirk Douglas in his prime. This is really a thoughtful performance from Mortenson, another good mark from him in an ever-increasing amount of good roles that he's taken on. Kodi Smit-McPhee is the young actor who plays his son, and he's certainly up to the task of keeping pace with Mortenson, and there is a great chemistry between the two that's a very natural thing between a father and son. At one point, Poppa says to his son, "You must think I'm from another world." and the moment he said that, I couldn't help but think of my own relationship with my father. In addition, Charlize Theron plays the wife and mother, seen only in flashbacks, and there's some nice walk-ons by both Robert Duvall and Guy Pearce- it's all good and solid work, with Theron getting the best of it as a mother who's delivered after the apocalypse has happened and who struggles with the idea of trying to survive with her husband and son during this.
It's really a terrific movie, but it's by no means a feel-good movie. It's very bleak and very dark and from what I understand, very true to it's source, so if you don't want to see something this dark, then you probably shouldn't, but for me, I think it's right up there with The Hurt Locker as one of the better things that I've seen this year. I wouldn't be surprised to see Viggo Mortenson get an Oscar nomination for this, his performance is certainly worth it. Without a doubt, highly, highly recommended.
By Darren Goodhart
Darren Goodhart is a 44-year old St. Louis-based Graphic Designer and Illustrator (and former comic book artist) who's been seeing movies all his life, but on an almost weekly basis in theatres for the last 20 years and owns nearly 1,000 DVDs for his home theatre. He's learned a lot about film over the 20 year period, and has taken his appreciation beyond the mainstream. His favorite types of film are mostly genre entertainment, but he also enjoys a wide range of drama, action and cult-y stuff from around the world, and is currently re-discovering a love affair with lower budget exploitation and genre films from the 70s and early 80s. He doesn't try to just dismiss any film, but if there's a bias against one, he'll certainly tell you that in the space of his reviews.
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text:
Port Orange Police Department
Man Finds Abandoned Garbage Bag of Kittens
By Christy Caplan | July 9, 2019
Police in Port Orange, Florida are looking for the person that left a garbage bag full of kittens in a ditch.
What I don't understand is why this happened. Why would someone leave kittens to die on the side of a street when an animal rescue organization would take them in a heartbeat? There are so many rescues that would take these kittens in and provide vet care for these sweet creatures!
The News-Journal reports that Robert Mosley was on his morning walk in a Port Orange neighborhood on Sunday morning when he heard a lot of meowing. We included the 911 call below! Mosley saw a garbage bag moving in a ditch.
"I tore open the bag and there were six kittens in the bag," Mosley said. "The bag was tied up and only had a hole in it like somebody poked a finger in it."
There were six kittens that appeared wet and cold were in the bag and a foul odor of urine emanated from the plastic garbage bag, the report states.
Port Orange Animal Control Officers are seeking information pertaining to a litter of kittens abandoned over the weekend...
Posted by Port Orange Police Department on Monday, July 8, 2019
Here's the 911 call.
The six kittens included two black and white, a black one, a calico, a tortoiseshell one and an orange and white one, authorities said.
The News-Journal Online article states that the cats were taken to a veterinarian where they are being cared for by the clinic's staff.
"I was horrified by it," said Mosley, a cat lover. "I just can't believe that someone has the heart to do such a thing."
Port Orange police said they are asking the public to help with information about the kittens.
These poor kittens were left in a trash bag in a ditch by some horrible person. This is a case of animal cruelty that this Daytona Beach community is keeping top of mind so this person serves time!
If these kittens needed medical attention they could have been dropped at the local animal shelter, humane society or a call to animal services would have been a great solution. The shelter could neuter the kittens and all the littermates easily could have been put up for adoption.
A first-time cat owner can always call community resources with questions.
We know these little kittens are having a cuddle with their new caretakers and we are so grateful!
Staff note: Anyone with information is asked to contact Animal Control Officer Jennifer Macsar at 386-506-5836 or via email at [email protected] or call Volusia County Central Dispatch at 386-248-1777.
Please let us know what you think about this story. We know it's so horrible, leave us a comment below.
WATCH NOW: Neglected Pit Bull Gets Second Chance as Firehouse Pup


Yes I have family on the Spain/Portugal border and they tell me it's been unusually hot for weeks already, even by their standards, and the coming week looks like early August rather than mid June with temperatures regularly over 40C.
Closer to home, interesting to see the GEFS mean has uppers of 12C or above from this Saturday all the way to next Saturday for the south. A quite notable heatwave starting to look possible, if the Atlantic fails to breakthrough mid next-week. Several days up to 30C possible in the south.
Although varying in detail the ecm is pretty much on the same page as the gfs. At T144 it has also promoted the upper trough west of Iberia resulting in a surface analysis of low pressure to the NW and SW disrupting the ridging north east and pushing the high cell over the UK north east and then east.This is the starof the tricky period previously mentioned. The ecm has the surface low tracking NE bringing inclement weather to Scotland on Thursday Thereafter showery outbreaks, albeit light, as the latter comes under a slack low pressure area. As also mentioned previously this is a long way from being resolved and just a watching brief at the moment.
Sunday a similar spread but temps a degree or two higher in the SE region.
Monday perhaps the concentration of the higher temps a little further south and west and certainly in the SE 29-30C quite widespread, Thereafter some cooler temps (relatively) but some more WAA on Thursday (29C again) but absolutely no point in looking in detail in this area until the analysis is sorted and the uncertainty resolved.
Today we are faced with the very real possibility that the warmth/heat may be very slow to leave, perhaps even lasting late on into next week!
Laughably it is predicting 22/23c in places with 15c 850s. Yeah, ok then GFS!
A very decent spell of weather on the way. Summer 2017 starting off well!
As a matter of interest why is 22/23C in places and 15C 850s necessarily laughable?
Continental flow, high 850s, thicknesses >564 dam, no rain, zero CAPE (no instability) and only high cloud....do you really think temps will only reach 23c if that all verifies? Come on!
We all know these GFS predicted maxes are usless....in the May hot spell they were consistently 3-5c under the actual maxima. I expect similar here if that verifies.
Looking very good indeed for a long very warm settled spell.
Don't come on me. I said necessarily wrong, If you can accurately forecast lapse rates 8 days down the line you are a far better man than me.
I would go further and say all model predicted max 8 days down the line are useless so why bother making a comment in the first place which requires you to make a stab at the lapse rate when the surface analysis is not even sorted? I wasn't suggesting the gfs was right.
Because the south coast yesterday reached 23c in hazy sunshine, a southerly breeze and 8c isotherm. 22-23 degrees with 15c isotherm a week inside the longest day of the year with a hot preceeding weekend would not, absolutely no way generate 22-23c. Would be looking at the very least 25c pushing 30 in places.
Today for example, 21 degrees progged in a fresh Westerly airflow in 7 degree upper air temps. Now tell me that if you double that upper air temp, a very warm humid southerly or south Easterly air flow with a preceeding weekend of 30 degree temps would only generate 22 or 23 degrees. Nonsense. I'm sorry but utter laughable.
So I'm not allowed to possibly speculate on the possible temperatures in 8 days time, but you are allowed to unequivocally state it will be 29c in 7 days time? What exactly is the difference here?
Stop being so pernickety for the sake of it, and lighten up, it's a model discussion forum!
Let's get one thing absolutely clear here. I couldn't give a toss whether you speculate on max temps for Xmas day and I haven't unequivocally stated anything. I merely brought the subject up in the first place because from a meteorological point of view it is not laughable or unreasonable so your comment when read by people without your knowledge could be very misleading.
I'm perfectly light thank you but thanks for reminding me this is a model discussion forum. Irony is no longer on the agenda.
And back to sensible informative & polite model discussion please.
The good news is that the GFS has gradually been pulled into line over the last couple of days, and its consistent backing of the cooler outcome has been pegged back so much that now only 3/20 members go with the idea.
The outlook is far from certain into next week, with finer details determining whether it just ends up pleasant, or remains hot. Will we get a thundery breakdown? The ensembles don't really fancy it at the moment, with very little in the way of ppn forecast.
The GFS will come round over the next few days on its temp at surface level. Although like others have pointed out, it's crap at getting it right. But it has a habit of this including in winter when it over doea it and they are much lower. Remember the GFS is not a high res model. You want to be looking at them for a rough guide on temperatures. Also have to take into account Urban heat island effect, Heathrow is a prime example of this usually being 2-3 degrees warmer than anywhere else.
It does look as though we are kicking summer 2017 off with a cracking start, we can't complain after the spring we just had.
Given what we were looking at a week ago we have come a long way.
The EPS 850mb mean and contours. The question is, as already noted, whether the trough will track far enough east to affect the UK by the weekend The eps currently (operative word) is indicating that it may well with the flow veering south west. And of course even if it does it is not necessarily all doom and gloom.
Laughably [GFS] is predicting 22/23c in places with 15c 850s. Yeah, ok then GFS!
I'd say UKMO is a nice halfway house at +144 in that it has GFS' better alignment of lows and highs for persisting the settled conditions going forward, but ECM's less vigorous circulation around the high which would mean less inland extent of a cooler surface flow moderated by the N. Sea - this stronger flow being what leads to GFS predicting 22-23*C maximums for quite a few with 15*C 850s on Friday; although the isobars are aligned to bring a flow from the SE, the surface flow is more toward the E as a result of frictional effects with the sea and then land.
The most widespread heat in summer occurs when a ridge becomes fairly weak in terms of SLP but with this being more to do with high temperatures (warmer air is less dense so less pressure from it at the surface) than the subsidence from aloft weakening - and that latter component can further intensify the heat via adiabatic warming (dry air warms as it sinks because the pressure rises as it does so and if you compress gases, there is more energy per unit space and so higher temps... oops I'm going a bit scientific lecture on you all!).
In this light the ECM run is almost that 'pressure cooker' scenario, but it remains more aggressive with the Atlantic lows so doesn't quite get there - as I've said before this may be MJO-related, although forcing form that should be pretty weak and day 10 shows this with the upstream pattern looking ready to push a new ridge across the UK from the Azores days 11-14.
I have been admiring the westward extent of the heat plume early next week - over halfway toward the Azores and over sea temps already widely over 1*C above the LTA. Could be some reinforcement of the SST anomaly pattern that already promotes such intense and extensive heat plumes... a positive feedback that could spell trouble for Europe this season. I hate to say it but it feels like 2017 is well placed to challenge 2003 in many respects. Hopefully Europeans have made adaptations since then that can reduce the health impacts.
Next Thursday more and more being modelled as a very hot day in the southern half, possibly less so further north but doubts over that for me.
The Brecon Beacons, can get very hot there under the right conditions. Hope for nice summer weather for your holiday, some good pubs down there. Yes, site boss Paul mentioned in his up and coming heatwave page that the initial warm air mass will invade Southern Britain from a more westerly source ( Ireland ). Will be interesting watching that heat plume develop out to the SW next week. Could produce up some amazing charts, hopefully.
This is not the thread for it but as the subject of the European heatwave of 2003 has been broached with regard to the forthcoming possible heat wave some links to the aforementioned for anyone who is not familiar with the syn optics and impacts.
Certainly the very dry weather contributed to the 2003 heatwave....it has been abnormally dry here in the UK through much of the spring, though I'm not sure about Western Europe as a whole.
Spain has been blowtorch hot recently, with temps in the usual spots of Seville/Cordoba in the low to mid 40s. Whether this is leading to a repeat of 2003 conditions, or is just a short heat burst remains to be seen. It looks like remaining very hot for another week at least, before both the GFS and ECM sweep away the excess heat towards Italy.
It'll be interesting to see, I don't think anyone thought this summer would be anything like a 2003 style heat fest (barring Nathan Rao & James Madden, but then again they think every summer will be this hot!).
Will the weather catch everyone off guard again!?


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Iowa Park police release name of boy killed in train accident this morning
Police have released the name of an Iowa Park boy killed Saturday morning in a train accident in Iowa Park.
Iowa Park police release name of boy killed in train accident this morning Police have released the name of an Iowa Park boy killed Saturday morning in a train accident in Iowa Park. Check out this story on timesrecordnews.com: https://www.timesrecordnews.com/story/news/2019/12/14/iowa-park-boy-killed-train-accident-saturday-morning/2651591001/
Trish Choate, Wichita Falls Times Record News Published 4:07 p.m. CT Dec. 14, 2019 | Updated 5:51 p.m. CT Dec. 14, 2019
An Iowa Park police vehicle is shown in this Dec. 1, 2018, file photo working an incident in the city. (Photo: CHRISTOPHER WALKER/TIMES RECORD NEWS)
A 12-year-old Iowa Park boy named Shawn Sargent died instantly around 9 a.m. Saturday morning after being struck by a BNSF train in Iowa Park, according to police.
"As far as we can tell by interviewing some of the witnesses, it appears that he was trying to beat the train," Iowa Park police Chief Steven Davis said.
The accident happened in about the 400 block of West Highway, which isn't a crossing, Davis said.
Sargent was attempting to cross the tracks out in the open, the chief said.
"Anytime we lose a child, it's horrible," he said.
With Christmas near, it's a really bad situation, Davis said.
The railroad tracks were closed from about 9 a.m. to 1 p.m. Saturday, Davis said.
The investigation is ongoing, the chief said.
The Iowa Park Police Department is working in conjunction with BNSF Railway, which has its own police department, in a joint investigation, Davis said.
The Wichita County Sheriff's Department assisted IPPD today, he said.
Read or Share this story: https://www.timesrecordnews.com/story/news/2019/12/14/iowa-park-boy-killed-train-accident-saturday-morning/2651591001/
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St. Pete Programmers World No. 1
By Andrey Musatov
Mar. 14 2001 00:00
St. Petersburg universities finished first and third in an IBM-sponsored world computer programming championship in Vancouver, Canada, on Saturday.
The first-place team — made up of Nikolai Durov, Oleg Eterevsky and Andrei Lopatin, third-year students in the mathematics and mechanics department at St. Petersburg State University, or -SPbGU — also won last year in Orlando, Florida.
More than 13,000 computer science and engineering students and faculty from more than 70 countries competed in regional preliminary contests held from last September through December. The top 17 teams earned places in the finals.
The Commonwealth of Independent States was represented by six teams — including the St. Petersburg Institute of Fine Mechanics and Optics, which won third place, and Moscow State University and Ural State University, each of which tied with 15 other teams for 14th place.
The object of the contest, said Alexander Alexeyev, a fifth-year student and a coach of the SPbGU team, was to create a computer program that could solve as many tasks as possible in five hours.
"In order to win, we had to create a computer program that could solve some mathematical problems and pass a few mathematical tests," Alexeyev said in a telephone interview Tuesday.
"Our team solved six problems and did it two hours earlier than the Virginia Tech [team], which got second place."
According to Alexeyev, training the team was quite difficult.
"Our technical base was very poor, and we simply did not have enough computers," he said. "The only computer classroom also was used by other students," he said.
"Our training program, in order to get used to the competition, included five-hour sessions spent exercising on old problems that were used in previous contests."
According to Alexeyev, new tasks had to be created often in order to ensure the students would be ready for any problems encountered in the contest.
But despite the technical problems, the team was well prepared for the contest in other ways — the SPbGU students were bright guys long before the they entered the university, Alexeyev said. They started participating in mathematical competitions while they were still in school — and did quite well.
"A large part of their talent was due to very good basic mathematical knowledge given in school," Alexeyev said. "That is one of the strongest points of Russian education. Michigan University, for instance, may have stronger technical facilities, but the smartest guys come from Russia."
Alexeyev himself works as a programmer at a St. Petersburg firm. However, he refused to say how much he earns or discuss the professional plans of his winning team.
The members of the Russian teams cannot be reached for comment until Friday, when they return from abroad. The universities have paid for their trips to and from Vancouver, while the Association for Computing Machinery paid for living expenses during the contest.
As for the team from SPbGU, they're doing a little traveling around Europe to celebrate the victory, Alexeyev said.


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James owns and operates a cabinet shop specializing in fine furniture, reproductions, and custom architectural fixtures. He is a master cabinetmaker, writes for woodworking magazines and loves giving advice to new woodworkers. He also teaches woodworking throughout the country in colleges, woodworker clubs, woodworking schools and seminars.
James owns and operates a cabinet shop specializing in fine furniture, reproductions, and custom architectural fixtures.
He is a master cabinetmaker, writes for woodworking magazines and loves giving advice to new woodworkers. He also teaches woodworking throughout the country in colleges, woodworker clubs, woodworking schools and seminars.


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William "Will" Boli Bagrou (* 19. Juni 1996 in Salt Lake City, Utah) ist ein US-amerikanischer Fußballspieler.

Karriere
Bagrou spielte zunächst an der Mercer University. Diese verlieh ihn 2017 kurzzeitig an die U-23 der Seattle Sounders. Zur Saison 2018 wechselte er zum Viertligisten Birmingham Hammers. Zur Saison 2019 wechselte er zur drittklassigen Reserve von Orlando City. Sein Debüt für Orlando B in der USL League One gab er im März 2019, als er am ersten Spieltag jener Saison gegen den FC Tucson in der Startelf stand und in der 76. Minute durch Luc Granitur ersetzt wurde. Im Mai 2019 erzielte er bei einer 4:1-Niederlage gegen den North Texas SC sein erstes Tor in der USL League One. Bis Saisonende kam er zu 23 Einsätzen für Orlando und erzielte drei Tore.

Im Februar 2020 wechselte er zum österreichischen Regionalligisten ATSV Stadl-Paura. Nach sieben Einsätzen für den Verein in der Regionalliga verließ er Stadl-Paura in der Winterpause 2020/21.

Weblinks

Einzelnachweise

Fußballspieler (Seattle Sounders FC)
Fußballspieler (Orlando City)
Fußballspieler (ATSV Stadl-Paura)
US-Amerikaner
Geboren 1996
Mann

redpajama_set_name: RedPajamaWikipedia