- Cyclic Model for the Asymmetric Conjugate Addition of Organolithiums with Enoates
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The chiral diether ligand controlled asymmetric conjugate addition of organolithiums to nona-2,7-dienedioates preferentially proceeds via the s-cis conformation with coordination of the carbonyl oxygen atom to the lithium to give a lithium E-enolate intermediate. Subsequent intramolecular conjugate addition of the enolate also proceeds via a cyclic transition state involving the lithium and the s-cis-enoate, resulting in trans,trans-trisubstituted cyclohexanes with high enantiomeric excesses and yields.
- Nishimura, Katsumi,Fukuyama, Naoshi,Yamashita, Mitsuaki,Sumiyoshi, Takaaki,Yamamoto, Yasutomo,Yamada, Ken-Ichi,Tomioka, Kiyoshi
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- Catalytic enantioselective carboannulation with allylsilanes
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The first catalytic asymmetric carboannulation with allylsilanes is presented. The enantioselective [3+2] annulation is catalyzed using a scandium(III)/indapybox complex with tetrakis-[3,5-bis(trifluoromethyl)phenyl]- borate (BArF) to enhance catalytic activity and control stereoselectivity. Functionalized cyclopentanes containing a quaternary carbon center are derived from alkylidene oxindole, coumarin, and malonate substrates with high stereoselectivity. The enantioselective 1,4-conjugate addition and enantioselective lactone formation (by trapping of the β-silyl carbocation) is also described. It's a trap: The catalytic asymmetric carboannulation of alkylidene oxindole, coumarin, and malonate substrates with allylsilanes in the presence of a ScIII/BArF/indapybox catalyst affords functionalized cyclopentanes containing a quaternary carbon center with high stereoselectivity. Enantioselective allylation and asymmetric lactone formation by trapping of the β-silyl carbocation are also presented.
- Ball-Jones, Nicolas R.,Badillo, Joseph J.,Tran, Ngon T.,Franz, Annaliese K.
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- Unprotected vinyl aziridines: Facile synthesis and cascade transformations
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(Figure presented) Functionalized vinylaziridines, readily available from water-stable aziridine aldehydes have led to the construction of a variety of stereochemically rich heterobicycles. A cascade ring-opening/ring-contraction mechanism operates In the course of the process. These results underscore the notion that Interesting and useful nitrogen-mediated relay processes can arise when elements of strain are merged with the manifolds of enamine/iminium ion reactivity.
- Baktharaman, Sivaraj,Afagh, Nicholas,Vandersteen, Adelle,Yudin, Andrei K.
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- Catalytic Asymmetric Synthesis of Cyclopentene-spirooxindoles Bearing Vinylsilanes Capable of Further Transformations
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We report a scandium-catalyzed [3 + 2] annulation of alkylideneoxindoles with allenylsilanes for the enantioselective formation of cyclopentene-spirooxindoles containing vinylsilanes. Using a Sc(OTf)2/PyBOX/BArF complex, the spiroannulation of allenylsilanes affords products with >94:6 dr and >90:10 er. The effect of the counterion and ligand to control selectivity is discussed. The transformation of the vinylsilane is demonstrated using cross-coupling, epoxidation, and Tamao-Fleming oxidation reactions. A series of competition experiments provide a comparison of nucleophilicity between allyl- and allenylsilanes.
- Cobo, Angel A.,Armstrong, Brittany M.,Fettinger, James C.,Franz, Annaliese K.
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- Phosphonium-iodonim ylides in nucleophilic substitution reactions
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Properties of mixed phosphonium-iodonium ylides were investigated, and the compounds were shown to be capable to behave as O-nucleophiles in nucleophilic substitution reactions.
- Matveeva,Podrugina,Grishin,Pavlova,Zefirov
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- Asymmetric Catalytic Diverse Ring Opening/Cycloadditions of Cyclobutenones with (E)-Alkenyloxindoles and (E)-Dioxopyrrolidines
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Highly enantioselective ring-opening/cycloaddition reactions of cyclobutenones were achieved by employing chiral N,N′-dioxide/metal complexes as the catalysts. The Diels-Alder type cycloaddition with (E)-alkenyloxindoles yielded spirocyclohexaneoxindoles with excellent results. Meanwhile, a hetero-Diels-Alder process occurred with (E)-dioxopyrrolidines to afford spiropyrrolidinone-dihydropyranone derivatives.
- Luo, Yao,Zhang, Hang,Wang, Siyuan,Zhou, Yuqiao,Dong, Shunxi,Feng, Xiaoming
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- Mechanically induced solid-state generation of phosphorus ylides and the solvent-free wittig reaction
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We describe the nearly quantitative preparation of phosphorus ylides and the Wittig reaction occurring in the solid sate during high-energy mechanochemical processing. Initial insights into the details of the discovered chemical transformations indicate that high-energy mechanical processing supports the interaction of reacting centers by breaking crystallinity of the reactants and by providing mass transfer without a solvent. Copyright
- Balema, Viktor P.,Wiench, Jerzy W.,Pruski, Marek,Pecharsky, Vitalij K.
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- Synthesis and Structure of Mixed Phosphonium-iodonium Ylide
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A mixed phosphonium-iodonium ylide, phenyliodoniumethoxycarbonylmethylenetriphenyl-phosphorane borofluoride, was synthesized. Its structure was established by means of X-ray diffraction analysis. Temperature dependence of 1H, 13C, and 31P spectra of the ylide synthesized was investigated. A dynamic equilibrium between Z and E-isomers was observed.
- Matveeva,Podrugina,Grishin,Tkachev,Zhdankin,Aldoshin,Zefirov
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- Concentration-Dependent Main-Chain Dynamics of Sodium Polyacrylate As Probed by NMR in the Semidilute Regime
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Sodium polyacrylate chains exhibit reduced reorientational mobility in the semidilute regime as probed by frequency-dependent nuclear magnetic relaxation experiments.Nuclear magnetic relaxation rates of deuterons have been measured in aqueous solutions of methylene-deuteriated poly(acrylic acid) (CD2-PAA).Upon diluting a neutralized solution of CD2-PAA (sodium polyacrylate), a sharp increase of the transverse relaxation rate R2 was observed, whereas the longitudinal relaxation rate R1 remained unaffected.It is shown that in the semidilute regime slow motions with correlation times > 1E-8 s show up irrespective of the fast (internal) motions with correlations times ca. 1E-9 s.The origin of these slow motions is indicated by polyelectrolyte theory; the large correlation times are probably due to the enhanced (electrostatic) stiffness of the CD2-PAA chain in the semidilute regime.In concordance with this idea is the fact that the large correlation times decrease when a simple salt (NaCl) is added to the solution.An implication for the interpretation of counterion relaxation is discussed.
- Rijn, C. J. M. van,Jesse, W.,Bleijser, J. de,Leyte, J. C.
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- Synthesis of 5,6-dehydrokawain and some fluorinated analogues
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An efficient methodology for the synthesis of 6-styrenylpyrone in a four-step sequence is reported. The reactions were performed under catalyst-free conditions with mild and affordable reagents to produce 5,6-dehydrokawain and fluorinated derivatives in good to excellent overall yields (72–86%) on a multigram scale. Two novel difluorinated derivatives are reported here for the first time.
- Obi, Grace,Van Heerden, Fanie R.
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- Titanium(IV)-catalyzed stereoselective synthesis of spirooxindole-1-pyrrolines
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A stereoselective cyclization between alkylidene oxindoles and 5-methoxyoxazoles has been developed using catalytic titanium(IV) chloride (as low as 5 mol %) to afford spiro[3,3-oxindole-1-pyrrolines] in excellent yield (up to 99%) and diastereoselectivity (up to 99:1). Using a chiral scandium(III)-indapybox/BArF complex affords enantioenriched spirooxindole-1-pyrrolines where a ligand-induced reversal of diastereoselectivity is observed. This methodology is further demonstrated for the synthesis of pyrrolines from malonate alkylidene and coumarin derivatives.
- Badillo, Joseph J.,Ribeiro, Carlos J. A.,Olmstead, Marilyn M.,Franz, Annaliese K.
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- Formal synthesis of actinoranone using a one-pot semipinacol rearrangement/Wittig reaction
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Here, we report a formal synthesis of the marine cytotoxic meroterpenoid actinoranone. Key steps include a semipinacol rearrangement/Wittig reaction sequence and a chiral pool approach for the syntheses of the tetralone and the ocatalin fragments, respectively. The presented route provides access to the natural product in 14 steps in the longest linear sequence.
- Menger, Martina,Christmann, Mathias
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- Efficient and regioselective one-pot synthesis of S-vinyl dithiocarbamates from electron-deficient allenes, amines and CS2
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A novel and efficient one-pot procedure for the synthesis of S-vinyl dithiocarbamates from electron-deficient allenes, amines and CS2was presented. The reactions proceed at room temperature for 10–30?min without any catalyst to afford the products in high yields, excellent regioselectivity and stereoselectivity.
- Li, Ridong,Leng, Penglin,Liu, Bin,Wang, Xin,Ge, Zemei,Li, Runtao
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- PPh3-catalyzed β-selective addition of α-fluoro β-dicarbonyl compounds to allenoates
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A highly selective phosphine-catalyzed β-addition of α-fluoro β-dicarbonyl compounds to allenoates has been developed. Both α-fluoro β-diketones and α-fluoro β-keto esters prove to be competent fluorocarbon nucleophiles, giving a series of the β-addition products bearing a fluorinated quaternary carbon center in good to excellent yields and with excellent regioselectivities. A plausible reaction pathway is presented.
- Liu, Yong-Liang,Wang, Xiao-Ping,Wei, Jie,Li, Ya
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supporting information
(2021/12/02)
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- Blue Light-Emitting Diode-Mediated in Situ Generation of Pyridinium and Isoquinolinium Ylides from Aryl Diazoesters: Their Application in the Synthesis of Diverse Dihydroindolizine
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Blue light-emitting diode-mediated environmentally sustainable three component reactions among pyridine/isoquinoline 1/2, aryl diazoesters 3, and acrylic ester/3-alkenyl oxindoles 5/6 provide various dihydroindolizines 7 to 9 in excellent yield. The principle of the strategy is photolytic generation of nitrogen ylides from N-heteroarenes and aryl diazoesters and their subsequent [3 + 2] cycloaddition reaction with dipolarophiles. Detailed mechanistic analysis of the transformation through control experiments establishes this strategy as the foundation for the photolytic multicomponent reaction.
- Guha, Souvik,Maiti, Debajit,Prabakar, Tejas,Sar, Saibal,Sen, Subhabrata
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p. 11736 - 11747
(2021/09/02)
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- Catalytic Synthesis of 1 H-2-Benzoxocins: Cobalt(III)-Carbene Radical Approach to 8-Membered Heterocyclic Enol Ethers
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The metallo-radical activation of ortho-allylcarbonyl-aryl N-arylsulfonylhydrazones with the paramagnetic cobalt(II) porphyrin catalyst [CoII(TPP)] (TPP = tetraphenylporphyrin) provides an efficient and powerful method for the synthesis of novel 8-membered heterocyclic enol ethers. The synthetic protocol is versatile and practical and enables the synthesis of a wide range of unique 1H-2-benzoxocins in high yields. The catalytic cyclization reactions proceed with excellent chemoselectivities, have a high functional group tolerance, and provide several opportunities for the synthesis of new bioactive compounds. The reactions are shown to proceed via cobalt(III)-carbene radical intermediates, which are involved in intramolecular hydrogen transfer (HAT) from the allylic position to the carbene radical, followed by a near-barrierless radical rebound step in the coordination sphere of cobalt. The proposed mechanism is supported by experimental observations, density functional theory (DFT) calculations, and spin trapping experiments.
- De Bruin, Bas,De Zwart, Felix J.,Li, Zirui,Mathew, Simon,Wolzak, Lukas A.,Zhou, Minghui
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supporting information
p. 20501 - 20512
(2021/12/03)
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- Organocatalyzed [2+2] Cycloaddition Reactions between Quinone Imine Ketals and Allenoates
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A new cycloaddition reaction of quinone imine ketals (QIKs), which could be utilized to the construction of functionalized azaspirocyclics under mild conditions, is described. This transformation involved a [2+2] cycloaddition reaction between QIKs and allenoates catalyzed by DABCO, and then treatment with 1 N HCl in one-pot. The strategy could provide a practical route to access azetidine-fused spirohexadienones in good to excellent yields and with high E -selectivity.
- Liu, Teng,He, Chixian,Wang, Fan,Shen, Xiang,Li, Yongqin,Lang, Man,Li, Guijun,Huang, Chao,Cheng, Feixiang
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p. 518 - 526
(2020/10/12)
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- Selective Construction of C?C and C=C Bonds by Manganese Catalyzed Coupling of Alcohols with Phosphorus Ylides
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Herein, we report the manganese catalyzed coupling of alcohols with phosphorus ylides. The selectivity in the coupling of primary alcohols with phosphorus ylides to form carbon-carbon single (C?C) and carbon-carbon double (C=C) bonds can be controlled by the ligands. In the conversion of more challenging secondary alcohols with phosphorus ylides the selectivity towards the formation of C?C vs. C=C bonds can be controlled by the reaction conditions, namely the amount of base. The scope and limitations of the coupling reactions were thoroughly evaluated by the conversion of 21 alcohols and 15 ylides. Notably, compared to existing methods, which are based on precious metal complexes as catalysts, the present catalytic system is based on earth abundant manganese catalysts. The reaction can also be performed in a sequential one-pot reaction generating the phosphorus ylide in situ followed manganese catalyzed C?C and C=C bond formation. Mechanistic studies suggest that the C?C bond was generated via a borrowing hydrogen pathway and the C=C bond formation followed an acceptorless dehydrogenative coupling pathway. (Figure presented.).
- Liu, Xin,Werner, Thomas
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supporting information
p. 1096 - 1104
(2020/12/31)
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- Synthesis, in vitro cytotoxicity, and molecular docking study of novel 3,4-dihydroisoquinolin-1(2H)-one based piperlongumine analogues
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With the aim of expanding the scope of SAR on piperlongumine (PL), a naturally occurring anticancer molecule, we have designed a novel hybrid molecule bearing 3,4-dihydroisoquinolin-1(2H)-one and trans-cinnamic acids. The structure, based on hybridization strategy, is used for hybridization of naturally occurring scaffolds. We have synthesized 14 hybrid molecules by coupling 3,4-dihydroisoquinolin-1(2H)-one core with cinnamic acids using the mix anhydride approach. The newly synthesized inhibitors were evaluated for cell viability against breast cancer MCF-7 and cervical cancer HeLa cell lines. Furthermore, the active compounds were screened for their potential in breast cancer MDA-MB-231, cervical cancer C33A cell lines, prostate cancer DU-145, PC-3, and normal VERO cells. From the series, compound 10g was seen to inhibit MCF-7 cell growth significantly with GI50 50 = 20 μM) and C33A (GI50 = 3.2 μM). While the inhibitor 10i inhibits MCF-7 breast cancer cell growth GI50 = 3.42 μM along with inhibition of cell growth in MDA-MB-231 (GI50 = 30 μM), HeLa (GI50 = 7.67 μM), C33A (GI50 = 13 μM), DU-145 (GI50 = 6.45 μM), PC-3 (GI50 = 8.68 μM), and VERO (GI50 = 2.93 μM), respectively. Furthermore, molecular docking study demonstrated these compounds could bind tightly to the colchicine domain of tubulin through a network of favorable steric and electrostatic interactions and thus act as a tubulin polymerization inhibitor.
- Kulkarni, Mahesh R.,Lad, Nitin P.,Khedkar, Vijay M.,Gaikwad, Nitin D.
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p. 1359 - 1370
(2021/04/09)
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- Catalytic asymmetric [3+2] cycloaddition of isomünchnones with methyleneindolinones
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An efficient enantioselective [3+2] cycloaddition of isomünchnones with methyleneindolinones that are generated by anin situintramolecular addition of the carbonyl group to rhodium carbenes is realized with a chiralN,N′-dioxide/Zn(ii) complex as a Lewis acid. A series of chiral oxa-bridged 3-spiropiperidines are obtained in high yields with excellent dr and excellent ee values.
- Feng, Xiaoming,Hu, Xinyue,Lin, Lili,Wang, Kaixuan,Xu, Chaoran,Zhou, Yuqiao
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p. 8917 - 8920
(2021/09/10)
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- Enantioselective Rauhut–Currier Reaction with β-Substituted Acrylamides Catalyzed by N-Heterocyclic Carbenes
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β-Substituted acrylamides have low electrophilicity and are yet to be exploited in the enantioselective Rauhut–Currier reaction. By exploiting electron-withdrawing protection of the amide and moderate nucleophilicity N-heterocyclic carbenes, such substrates have been converted to enantioenriched quinolones. The reaction proceeds with complete diastereoselectivity, good yield, and modest enantioselectivity. Derivatizations are reported, as are computational studies, supporting decreased amide bond character with electron-withdrawing protection of the nitrogen.
- Pitchumani, Venkatachalam,Breugst, Martin,Lupton, David W.
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supporting information
p. 9413 - 9418
(2021/12/09)
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- Visible-Light-Assisted Gold-Catalyzed Fluoroarylation of Allenoates
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A strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of β-fluoroalkyl-containing cinnamate derivatives. The reaction proceeds through visible-light-promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio- and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.
- Feng, Chao,Tang, Hai-Jun,Zhang, Xinggui,Zhang, Yu-Feng
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supporting information
p. 5242 - 5247
(2020/02/28)
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- Catalytic Synthesis of 8-Membered Ring Compounds via Cobalt(III)-Carbene Radicals
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The metalloradical activation of o-aryl aldehydes with tosylhydrazide and a cobalt(II) porphyrin catalyst produces cobalt(III)-carbene radical intermediates, providing a new and powerful strategy for the synthesis of medium-sized ring structures. Herein we make use of the intrinsic radical-type reactivity of cobalt(III)-carbene radical intermediates in the [CoII(TPP)]-catalyzed (TPP=tetraphenylporphyrin) synthesis of two types of 8-membered ring compounds; novel dibenzocyclooctenes and unprecedented monobenzocyclooctadienes. The method was successfully applied to afford a variety of 8-membered ring compounds in good yields and with excellent substituent tolerance. Density functional theory (DFT) calculations and experimental results suggest that the reactions proceed via hydrogen atom transfer from the bis-allylic/benzallylic C?H bond to the carbene radical, followed by two divergent processes for ring-closure to the two different types of 8-membered ring products. While the dibenzocyclooctenes are most likely formed by dissociation of o-quinodimethanes (o-QDMs) which undergo a non-catalyzed 8π-cyclization, DFT calculations suggest that ring-closure to the monobenzocyclooctadienes involves a radical-rebound step in the coordination sphere of cobalt. The latter mechanism implies that unprecedented enantioselective ring-closure reactions to chiral monobenzocyclooctadienes should be possible, as was confirmed for reactions mediated by a chiral cobalt-porphyrin catalyst.
- Lankelma, Marianne,Zhou, Minghui,de Bruin, Bas,van der Vlugt, Jarl Ivar
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supporting information
p. 11073 - 11079
(2020/04/29)
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- Rh-Catalyzed diastereoselective desymmetrization of enone tethered-cyclohexadienones: Via tandem arylative cyclization
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The rhodium-catalyzed arylative cyclization of enone tethered-cyclohexadienones has been developed with high efficiency, thus providing cis-fused bicyclic enones in good yields and with excellent diastereoselectivities. Furthermore, this mild transformation has a broad range of substrate scope and excellent functional group tolerance. In addition, bicyclic products have an enone functionality, which can be a synthetically valuable handle for further transformations.
- Jadhav, Sandip B.,Thopate, Satish B.,Nanubolu, Jagadeesh Babu,Chegondi, Rambabu
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supporting information
p. 1937 - 1946
(2019/02/20)
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- Sulfinate-Engaged Nucleophilic Addition Induced Allylic Alkylation of Allenoates
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A strategically novel Pd-catalyzed nucleophilic addition induced allylic alkylation reaction (NAAA) of allenoates has been successfully accomplished. By judiciously integrating ZnCl2-promoted Michael addition with Pd-catalyzed allylic alkylation, allenoates readily undergo allyl-sunfonylation at the internal double bond, thus providing a straightforward avenue for the rapid assembly of a host of structurally diversified α-allyl-β-sufonylbut-3-enoate derivatives. The success of this transformation profits from a delicate control of the reaction kinetic of each elementary step, thanks to the synergistic interaction of Pd/Zn bimetallic system, thus suppressing either direct allylic sulfonylation or premature quenching of therein in situ generated ester enolate intermediate. Furthermore, by expanding the scope of workable Michael acceptor beyond those previously required doubly activated ones, such as methylenemalononitrile, the present work substantially enriches the repertoire of NAAA reactions.
- Lin, Ling-Zhi,Che, Yuan-Yuan,Bai, Peng-Bo,Feng, Chao
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supporting information
p. 7424 - 7429
(2019/10/02)
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- Metal-Free Transfer Hydroiodination of C-C Multiple Bonds
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The design and a gram-scale synthesis of a bench-stable cyclohexa-1,4-diene-based surrogate of gaseous hydrogen iodide are described. By initiation with a moderately strong Br?nsted acid, hydrogen iodide is transferred from the surrogate onto C-C multiple bonds such as alkynes and allenes without the involvement of free hydrogen iodide. The surrogate fragments into toluene and ethylene, easy-to-remove volatile waste. This hydroiodination reaction avoids precarious handling of hydrogen iodide or hydroiodic acid. By this, a broad range of previously unknown or difficult-to-prepare vinyl iodides can be accessed in stereocontrolled fashion.
- Chen, Weiqiang,Walker, Johannes C. L.,Oestreich, Martin
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supporting information
p. 1135 - 1140
(2019/01/11)
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- NHC-Catalyzed Aldol-Like Reactions of Allenoates with Isatins: Regiospecific Syntheses of γ-Functionalized Allenoates
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An N-heterocyclic carbene (NHC) catalyzed γ-specific aldol-like reaction between allenoates and isatins has been achieved under mild conditions, giving trisubstituted allene derivatives bearing isatin moiety in moderate to good yields with high diastereoselectivity and excellent atom efficiency. The DFT computations indicated that the formation of the γ-adduct was more energetically favorable than that of the α-adduct. The result reported herein opens a new route for NHC-promoted allenoate-involved reaction.
- Li, Sha,Tang, Ziwei,Wang, Yang,Wang, Dan,Wang, Zhanlin,Yu, Chenxia,Li, Tuanjie,Wei, Donghui,Yao, Changsheng
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supporting information
p. 1306 - 1310
(2019/02/26)
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- Phosphine-catalyzed dearomative [3+2] annulation of 3-nitroindoles and allenoates
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The efficient phosphine-catalyzed dearomative [3+2] annulation of 3-nitroindoles with allenoates has been successfully developed, providing a facile access to cyclopenta[b]indolines with good to excellent yields and high diastereoselectivities. This strategy features mild reaction conditions, high functional group tolerance, and scalability. Additionally, the 2-nitrobenzofuran and 2-nitrobenzothiophene were good dearomative [3+2] annulation partners.
- Liu, Kui,Wang, Gang,Cheng, Shao-Jie,Jiang, Wen-Feng,He, Cheng,Ye, Zhi-Shi
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supporting information
p. 1885 - 1890
(2019/06/21)
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- A Ba/Pd Catalytic System Enables Dehydrative Cross-Coupling and Excellent E-Selective Wittig Reactions
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A Ba/Pd cooperative catalysis system was developed to enable the dehydrative cross-coupling of allylic alcohols with P-ylides to occur directly and promote a subsequent Wittig reaction in one pot. A variety of multisubstituted 1,4-dienes were isolated in good to excellent yields with broad P-ylides (stabilized by both ester and ketone carbonyl groups) and aldehyde (aliphatic and aromatic) substrates with excellent E selectivity.
- Xie, Peizhong,Fu, Weishan,Cai, Xinying,Sun, Zuolian,Wu, Ying,Li, Shuangshuang,Gao, Cuiqing,Yang, Xiaobo,Loh, Teck-Peng
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supporting information
p. 7055 - 7059
(2019/09/12)
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- Synthetic method of Wittig reagent
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The invention discloses a synthetic method of a Wittig reagent. The synthetic method comprises the following steps: (1) by taking alpha-halogenated-ester and triarylphosphine as raw materials, carrying out reaction in a two-phase solvent in presence of a halogenated metal salt catalyst, splitting phase after reaction is finished, recycling and reusing an organic phase, crystallizing an aqueous phase to obtain quaternary phosphonium salt, and recycling and reusing mother liquid; and (2) carrying out reaction on the quaternary phosphonium salt obtained in the step (1) in the aqueous phase in presence of an alkali reagent, and cooling and crystallizing after reaction is finished, so that the Wittig reagent product is obtained. The synthetic method disclosed by the invention has the advantagesthat the whole reaction process and conditions are mild, operation is easy, yield is high, cost is low, and amount of three wastes is less, so that the synthetic method disclosed by the invention isapplicable to industrial production.
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Paragraph 0020; 0021; 0024; 0025; 0027; 0028; 0031; 0032
(2018/03/24)
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- Preparation method of 2-(4-aminocyclohexyl)-ethyl acetate
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The invention provides a preparation method of 2-(4-aminocyclohexyl)-ethyl acetate, and belongs to the field of pharmaceutical chemistry. According to the preparation method, 1, 4-cyclohexanedione istaken as an initial raw material, and Wittig reaction, condensation reaction, catalytic hydrogenation, and the like are carried out so as to obtain 2-(4-aminocyclohexyl)-ethyl acetate. The purity of obtained 2-(4-aminocyclohexyl)-ethyl acetate is high; it is beneficial for preparation of dopamine receptor ligand drugs; the raw materials are widely available; operation is simple; reaction conditions are mild; and industrial application prospect is promising.
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Paragraph 0058; 0059; 0060
(2018/09/08)
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- Method for synthesizing spiro compound of dihydro-1H-indene
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The invention provides a method for synthesizing a spiro compound 1 of dihydro-1H-indene. The method comprises the following steps: 1) reacting 3-methoxybenzaldehyde with carbethoxyethylidene triphenylphosphorane 2 in a halohydrocarbon solvent at room temperature to obtain a compound 3; 2) hydrogenating the compound 3 in an alcohol solvent in the presence of a catalyst to obtain a compound 4; 3) reacting the compound 4 with liquid bromine in a halohydrocarbon solvent to obtain a compound 5; 4) reacting the compound 5 with N-vinyl-2-pyrrolidone in an ether solvent in the presence of a strong alkali to obtain a compound 6; 5) refluxing the compound 6 in an aqueous diluted acid solution to perform a rearrangement reaction in order to obtain a compound 7; and 6) performing a cyclization reaction on the compound 7 in anhydrous toluene in the presence of butyl lithium at an appropriate temperature to obtain the compound 1. The method has the advantages of initiative synthesis route, ingenious design idea, easily available and cheap starting materials, mild synthesis process conditions in every step, easiness in industrial production, high yield of every step, and high overall yield of the product.
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Paragraph 0026; 0027; 0028
(2018/09/20)
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- Facile synthesis of α, β-unsaturated esters through a one-pot copper-catalyzed aerobic oxidation-Wittig reaction
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An efficient one-pot synthesis of α, β-unsaturated esters through the aerobic oxidation – Wittig tandem reaction of alcohols and phosphorous ylide is developed. This new method operates under mild reaction conditions, and uses CuI/TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidine-N-oxyl) as co-catalyst and air (O2) as the oxidant. It tolerates a wide range of functionalized benzylic alcohol and aliphatic alcohols.
- Ren, Cheng,Shi, Zhenyu,Ding, Weijie,Liu, Zhiqing,Jin, Huile,Yu, Xiaochun,Wang, Shun
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supporting information
p. 14 - 17
(2017/12/06)
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- Nickel-catalyzed, ligand-free, diastereoselective synthesis of 3-methyleneindan-1-ols
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Nickel-catalyzed, highly diastereoselective annulations between activated allenes and 2-acetylarylboronic acid or 2-formylarylboronic acids are reported. No ligand for nickel is required, and the reactions proceed efficiently at room temperature to give a broad range of substituted 3-methyleneindan-1-ols. Preliminary results of an enantioselective variant are also described.
- Panchal, Heena,Clarke, Christopher,Bell, Charles,Karad, Somnath Narayan,Lewis, William,Lam, Hon Wai
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supporting information
p. 12389 - 12392
(2018/11/20)
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- Asymmetric Reductive Carbocyclization Using Engineered Ene Reductases
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Ene reductases from the Old Yellow Enzyme (OYE) family reduce the C=C double bond in α,β-unsaturated compounds bearing an electron-withdrawing group, for example, a carbonyl group. This asymmetric reduction has been exploited for biocatalysis. Going beyond its canonical function, we show that members of this enzyme family can also catalyze the formation of C?C bonds. α,β-Unsaturated aldehydes and ketones containing an additional electrophilic group undergo reductive cyclization. Mechanistically, the two-electron-reduced enzyme cofactor FMN delivers a hydride to generate an enolate intermediate, which reacts with the internal electrophile. Single-site replacement of a crucial Tyr residue with a non-protic Phe or Trp favored the cyclization over the natural reduction reaction. The new transformation enabled the enantioselective synthesis of chiral cyclopropanes in up to >99 % ee.
- Heckenbichler, Kathrin,Schweiger, Anna,Brandner, Lea Alexandra,Binter, Alexandra,Toplak, Marina,Macheroux, Peter,Gruber, Karl,Breinbauer, Rolf
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supporting information
p. 7240 - 7244
(2018/06/15)
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- Regio- and Stereoselective Nickel-Catalyzed Coupling of Boronic Acids with Allenoates
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The Ni(II)-catalyzed cross-coupling of arylboronic acids with allenoates is documented. The high regio- and stereoselectivity of the process enables a wide range of β-aryl β,γ-unsaturated esters to be prepared in good to excellent yields (up to 95%) and high E / Z -selectivity. Additionally, [3+2]-cascade sequence was observed when 2-formylphenylboronic acid was employed.
- Liu, Yang,Daka, Mario,Bandini, Marco
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p. 3187 - 3196
(2018/08/17)
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- BIPOLAR TRANS CAROTENOID SALTS AND USES THEREOF
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PROBLEM TO BE SOLVED: To provide compounds useful in improving diffusivity of oxygen between red blood cells and body tissues in mammals including humans. SOLUTION: There is provided a compound which has a structure represented by YZ-TCRO-ZY and is not trans sodium crocetinate [where, Y is a cation; Z is a polar group which is associated with the cation; and TCRO is trans carotenoid skeleton], and preferably, Y is a monovalent metal ion selected from the group consisting of Na+, K+ and Li+, or is an organic cation selected from the group consisting of R4 N+ and R3S+ [R is H, or CnH2n+1(n is 1 to 10)]. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPO&INPIT
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Paragraph 0083; 0092; 0113
(2018/10/26)
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- Enantioselective Alkylation of 2-Oxindoles Catalyzed by a Bifunctional Phase-Transfer Catalyst: Synthesis of (?)-Debromoflustramine B
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A new bifunctional phase-transfer catalyst that employs hydrogen bonding as a control element was developed to promote efficient enantioselective SN2 reactions for the construction all-carbon quaternary stereocenters in high yield and excellent enantioselectivity (up to 97 % ee) utilizing the alkylation of a malleable oxindole substrate. The utility of the methodology was demonstrated through a concise and highly enantioselective synthesis of (?)-debromoflustramine B.
- Craig, Ryan,Sorrentino, Emiliano,Connon, Stephen J.
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supporting information
p. 4528 - 4531
(2018/03/21)
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- Cycloaddition of Fluorenone N-Aryl Nitrones with Methylenecyclopropanes and Sequential 1,3-Rearrangement: An Entry to Synthesis of Spirofluorenylpiperidin-4-ones
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A facile synthesis of various spirofluorenylpiperidin-4-ones has been achieved in good yields from fluorenone N-aryl nitrones and methylenecyclopropanes. This method involved an initial cycloaddition to form a 5-spirocyclopropane-isoxazoline, which underwent a highly selective 1,3-rearrangement to give the desired product. The stereochemistry of the spirofluorenylpiperidin-4-one could be controlled by the cycloaddition and sequential rearrangement strategy. Furthermore, the spirofluorenylpiperidin-4-ones could be not only prepared in one-pot procedure but also converted to useful scaffolds by reduction or oxidation conditions.
- Ma, Xiao-Pan,Zhu, Jie-Feng,Wu, Si-Yi,Chen, Chun-Hua,Zou, Ning,Liang, Cui,Su, Gui-Fa,Mo, Dong-Liang
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p. 502 - 511
(2017/04/26)
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- Biocatalytic access to nonracemic γ-oxo esters: Via stereoselective reduction using ene-reductases
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The asymmetric bioreduction of α,β-unsaturated γ-keto esters using ene-reductases from the Old Yellow Enzyme family proceeds with excellent stereoselectivity and high conversion levels, covering a broad range of acyclic and cyclic derivatives. Various strategies were employed to provide access to both enantiomers, which are versatile precursors of bioactive molecules. The regioselectivity of hydride addition on di-activated alkenes was elucidated by isotopic labeling experiments and showed strong preference for the keto moiety as activating/binding group as opposed to the ester. Finally, chemoenzymatic synthesis of (R)-2-(2-oxocyclohexyl)acetic acid was achieved in high ee on a preparative scale combining enzymatic reduction followed by ester hydrogenolysis.
- Turrini, Nikolaus G.,Cioc, Rǎzvan C.,Van Der Niet, Daan J. H.,Ruijter, Eelco,Orru, Romano V. A.,Hall, Mélanie,Faber, Kurt
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supporting information
p. 511 - 518
(2017/08/14)
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- Method for synthesizing 2,3-dihydropyrrole rings
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The invention discloses a method for synthesizing 2,3-dihydropyrrole rings from p-toluenesulfonyl imine and disubstituted allene under the condition of a phosphine catalyst. The method is a convenient route for synthesizing 2,3-dihydropyrrole ring compounds without a metal reagent, and an obtained hydrogenated pyrrole product is a common basic structure in certain bioactive molecules and has potential pharmacochemical study value. The method for synthesizing the 2,3-dihydropyrrole rings adopts mild conditions and simple and available raw materials, and 2-position different substituted 2,3-dihydropyrrole compounds can be prepared conveniently.
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Paragraph 0032; 0033
(2017/10/23)
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- Phosphine-Catalyzed Domino β/γ-Additions of Benzofuranones with Allenoates: A Method for Unsymmetrical 3,3-Disubstituted Benzofuranones
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A phosphine-catalyzed domino process of benzofuranones with allenoates has been developed which furnishes highly functionalized unsymmetrical 3,3-disubstituted benzofuranones in synthetically useful yields. The mechanism for the transformation is a tandem β-umpolung/γ-umpolung process.
- Huang, Zhusheng,Yang, Xiuqin,Yang, Fulai,Lu, Tao,Zhou, Qingfa
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supporting information
p. 3524 - 3527
(2017/07/17)
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- Photoinduced Intermolecular [4+2] Cycloaddition Reaction for Construction of Benzobicyclo[2.2.2]octane Skeletons
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A novel and efficient method for the synthesis of highly substituted benzobicyclo[2.2.2]octane skeletons has been explored. Under UV-light irradiation, o-divinylbenzenes underwent a pericyclic reaction to form the cyclic o-quinodimethane intermediates which were subsequently reacted with olefins through [4+2] addition to construct the benzobicyclo[2.2.2]octane skeletons in mild conditions. Gram scale reactions demonstrated the synthetic potential application of this protocol.
- Liu, Qiang,Wang, Junlei,Li, Dazhi,Yang, Chao,Xia, Wujiong
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p. 1389 - 1402
(2017/02/10)
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- ALKENES AS ALKYNE EQUIVALENTS IN RADICAL CASCADES TERMINATED BY FRAGMENTATIONS
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Disclosed are methods for rerouting radical cascade cyclizations by using alkenes as alkyne equivalents. The reaction sequence is initiated by a novel 1,2 stannyl shift which achieves chemo- and regioselectivity in the process. The radical “hopping” leads to the formation of the radical center necessary for the sequence of selective cyclizations and fragmentations to follow. In the last step of the cascade, the elimination of a rationally designed radical leaving group via β-C—C bond scission aromatizes the product without the need for external oxidant. The Bu3Sn moiety, which is installed during the reaction sequence, allows further functionalization of the product via facile reactions with electrophiles as well as Stille and Suzuki cross-coupling reactions. This selective radical transformation opens a new approach for the controlled transformation of enynes into extended polycyclic structures of tunable dimensions.
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Paragraph 0169; 0170
(2016/12/22)
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- Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of sulphone-based CRTh2 antagonists
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Monocyclic and bicyclic ring systems were investigated as the "core" section of a series of diphenylsulphone-containing acetic acid CRTh2 receptor antagonists. A range of potencies were observed and single-digit nanomolar potencies were obtained in both the monocyclic and bicyclic cores. Residence times for the monocyclic compounds were very short. Some of the bicyclic cores displayed better residence times. A methyl group in the northern part of the core, between the head and tail was a necessary requirement for the beginnings of long residence times. Variations of the tail substitution maximised potencies and residence times.
- Buil, Maria Antonia,Calbet, Marta,Castillo, Marcos,Castro, Jordi,Esteve, Cristina,Ferrer, Manel,Forns, Pilar,González, Jacob,López, Sara,Roberts, Richard S.,Sevilla, Sara,Vidal, Bernat,Vidal, Laura,Vilaseca, Pere
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p. 102 - 133
(2016/03/04)
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- New compd. and resistance inducer for plant
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PROBLEM TO BE SOLVED: To provide a novel compound and a resistance inducer for a plant using the same.SOLUTION: There are provided a compound represented by the general formula (1), where Xis a group represented by the general formula (1a) or (1b), Zis a monovalent group other than a hydrogen atom, Zis an electron-withdrawing group, Rand Rare a hydrogen atom and the like, m is an integer of 0 to 4, a plurality of Zmay be same or different each other when m is 2 to 4, Ris a hydrocarbon group which may have a substituent, and a resistance inducer for a plant containing the compound as an active ingredient.
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Paragraph 0076; 0077; 0079
(2017/03/25)
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- Novel multifunctional dopamine D2/D3receptors agonists with potential neuroprotection and anti-alpha synuclein protein aggregation properties
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Our ongoing drug development endeavor to design compounds for symptomatic and neuroprotective treatment of Parkinson's disease (PD) led us to carry out a structure activity relationship study based on dopamine agonists pramipexole and 5-OHDPAT. Our goal was to incorporate structural elements in these agonists in a way to preserve their agonist activity while producing inhibitory activity against aggregation of α-synuclein protein. In our design we appended various catechol and related phenol derivatives to the parent agonists via different linker lengths. Structural optimization led to development of several potent agonists among which (?)-8a, (?)-14 and (?)-20 exhibited potent neuroprotective properties in a cellular PD model involving neurotoxin 6-OHDA. The lead compounds (?)-8a and (?)-14 were able to modulate aggregation of α-synuclein protein efficiently. Finally, in an in vivo PD animal model, compound (?)-8a exhibited efficacious anti-parkinsonian effect.
- Luo, Dan,Sharma, Horrick,Yedlapudi, Deepthi,Antonio, Tamara,Reith, Maarten E.A.,Dutta, Aloke K.
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p. 5088 - 5102
(2016/10/22)
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- BIPOLAR TRANS CAROTENOID SALTS AND THEIR USE
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PROBLEM TO BE SOLVED: To provide trans carotenoid salt compounds useful for improving the diffusibility of oxygen between red blood cells and a body tissue in mammalian including human being, a method for producing them, a method for solubilizing them, and a method for using them. SOLUTION: There are provided compounds represented by the following formula, and are compounds not being trans sodium crocetinate: YZ-TCRO-ZY[Y denotes a cation; Z denotes a polar group coupled to the cation; TCRO denotes a trans carotenoid skeleton; preferably, as follows; Y denotes the monovalent metal ion of Na+,K+ or Li+ or R4 N+ or R3S+;R denotes H or CnH2n+1;n denotes the integer of 1 to 10;Z denotes a carboxyl group, a sulfuric acid group, a mono-phosphoric acid group, a di-phosphoric acid group, or a tri-phosphoric acid group; and TCRO denotes a group using isopronoid in which the single bond and double bond of straight chain carbon and carbon as exemplified by the following formula is repeated (X respectively independently denotes H, a straight chain/branched carbon chain substituted/non-substituted with 1 to 10C halogen or a halogen)]. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPO&INPIT
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Paragraph 0092; 0112-0113
(2018/10/31)
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- Titanocene(III) chloride mediated radical induced addition-elimination route to the synthesis of racemic and optically active trisubstituted tetrahydrofurans: Formal synthesis of magnofargesin and 7’-epimagnofargesin
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Titanocene(III) Chloride mediated radical induced synthesis of 4-benzylidene substituted tetrahydrofuran, a typical lignan skeleton, has been accomplished in good yield through addition-elimination route in racemic as well as in optically active forms. The method has been applied to the synthesis of furano lignans, magnofargesin (1) and 7’-epimagnofargesin (2) in optically active forms.
- Chakraborty,Mandal,Roy
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p. 1067 - 1079
(2016/07/19)
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- Synthesis and antimicrobial activity of N-aryl-4-(cyano/alkoxycarbonyl)-5-(pyridin-3-yl)-1H/3H-1,2,3-triazole derivatives
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A convenient synthesis of a new series of N-aryl-5-(pyridin-3-yl)-1H/3H-1,2,3-triazole-4-carbonitriles and alkyl N-aryl-5-(pyridin-3-yl)-1H/3H-1,2,3-triazole-4-carboxylic acid esters is reported. The newly synthesized 5-(pyridin-3-yl)-1,2,3-triazole derivatives are evaluated for their antibacterial and antifungal activity. Some of these triazole derivatives have exhibited moderate antimicrobial activity.
- Komsani, Jayaram Reddy,Avula, Sreenivas,Koppireddi, Satish,Koochana, Pranay Kumar,Usn, Murty,Yadla, Rambabu
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p. 764 - 772
(2015/05/13)
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- Α-calbonyl phosphorane manufacturing method
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PROBLEM TO BE SOLVED: To provide a new method for producing α-carbonyl phosphorane, which is industrially advantageous, and which brings about a high yield and high purity with a simple operation. SOLUTION: In the reaction to synthesize an α-carbonyl phosphorane represented by general formula (I) by making a base act on an aqueous solution of an α-carbonyl phosphonium salt represented by general formula (II), the crystal of the α-carbonyl phosphorane is easily deposited by conducting the reaction with previous addition of a water-insoluble organic solvent (in formulas, Ar represents an optionally substituted aryl group, R1represents a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group, R2represents an optionally substituted alkyl group or an optionally substituted aryl group, and X-represents a counter anion). COPYRIGHT: (C)2012,JPOandINPIT
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Paragraph 0031
(2016/12/22)
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- Design of leaving groups in radical C-C fragmentations: Through-bond 2c-3e interactions in self-terminating radical cascades
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Radical cascades terminated by β-scission of exocyclic C-C bonds allow for the formation of aromatic products. Whereas β-scission is common for weaker bonds, achieving this reactivity for carbon-carbon bonds requires careful design of radical leaving groups. It has now been found that the energetic penalty for breaking a strong σ-bond can be compensated by the gain of aromaticity in the product and by the stabilizing two-center, three-electron "half-bond" present in the radical fragment. Furthermore, through-bond communication of a radical and a lone pair accelerates the fragmentation by selectively stabilizing the transition state. The stereoelectronic design of radical leaving groups leads to a new, convenient route to Sn-functionalized aromatics.
- Mondal, Sayantan,Gold, Brian,Mohamed, Rana K.,Alabugin, Igor V.
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supporting information
p. 8664 - 8669
(2014/07/21)
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- Facile synthesis of Z -alkenes via uphill catalysis
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Catalytic access to thermodynamically less stable Z-alkenes has recently received considerable attention. These approaches have relied upon kinetic control of the reaction to arrive at the thermodynamically less stable geometrical isomer. Herein, we present an orthogonal approach which proceeds via photochemically catalyzed isomerization of the thermodynamic E-alkene to the less stable Z-isomer which occurs via a photochemical pumping mechanism. We consider two potential mechanisms. Importantly, the reaction conditions are mild, tolerant, and operationally simple and will be easily implemented.
- Singh, Kamaljeet,Staig, Shannon J.,Weaver, Jimmie D.
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supporting information
p. 5275 - 5278
(2014/05/06)
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- Catalyst-free synthesis of skipped dienes from phosphorus ylides, allylic carbonates, and aldehydes via a one-pot SN2′ allylation-wittig strategy
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A catalyst-free allylic alkylation of stabilized phosphorus ylides with allylic carbonates via a regioselective SN2′ process is presented. Subsequent one-pot Wittig reaction with both aliphatic and aromatic aldehydes as well as ketenes provides structurally diverse skipped dienes (1,4-dienes) in generally high yields and moderate to excellent stereoselectivity with flexible substituent patterns. This one-pot S N2′ allylation-Wittig strategy constitutes a convenient and efficient synthetic method for highly functionalized skipped dienes from readily available starting materials.
- Xu, Silong,Zhu, Shaoying,Shang, Jian,Zhang, Junjie,Tang, Yuhai,Dou, Jianwei
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p. 3696 - 3703
(2014/05/06)
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- NEUROPROTECTIVE AGENTS FOR TREATMENT OF NEURODEGENERATIVE DISEASES
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A compound having formula I is useful for treating a neurodegenerative disease: I, R1 is an C1-12 organyl group; is a C1-12 heterocyclic ring system containing 5 to 12 ring atoms and up to three heteroatoms individually selected from the group consisting of N, O, S, and Se; R2 are C1-12 organyl groups; R7, R8 are each independently, hydrogen (H), hydroxyl, oxo (i.e., carbonyl), C1-8 alkyl, C1-8 alkoxyl, C2-8 alkenyl, C2-10 alkynyl, C5-7 cycloalkyl, C5-7 cycloalkenyl, halo, C1-4 aldehyde, or -NR4q where R4 is H, C1-8 alkyl, C2-8 alkenyl, C4-8 cycloalkyl, C4-8 cycloalkenyl, or C6-10 aryl; o is 0, 1, 2, 3, or 4; A is a C6-12 aryl group, C5-12 heteroaryl group, or an optionally substituted 3-hydroxypyridin- 4(1H)-one; p is an integer from 1 to 6; and Zm is absent or a divalent linking moiety; and m is an integer representing the number of time Z is repeated.
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Paragraph 000147; 000148; 000136
(2014/06/23)
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- New ianthelliformisamine derivatives as antibiotic enhancers against resistant gram-negative bacteria
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A series consisting of ianthelliformisamimes A, B, and C as well as its synthetic analogues was prepared in high chemical yield, from 27 to 91%, using peptide coupling as the key step, and the compounds were evaluated for their in vitro antibiotic enhancer properties against resistant Gram-negative bacteria and clinical isolates. The mechanism of action of one of these derivatives against Pseudomonas aeruginosa when combined with doxycycline was precisely evaluated utilizing bioluminescence to measure ATP efflux and fluorescence to evaluate membrane depolarization.
- Pieri, Cyril,Borselli, Diane,Di Giorgio, Carole,De Méo, Michel,Bolla, Jean-Michel,Vidal, Nicolas,Combes, Sébastien,Brunel, Jean Michel
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p. 4263 - 4272
(2014/06/09)
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