- Radical Carbonyl Propargylation by Dual Catalysis
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Carbonyl propargylation has been established as a valuable tool in the realm of carbon–carbon bond forming reactions. The 1,3-enyne moiety has been recognized as an alternative pronucleophile in the above transformation through an ionic mechanism. Herein, we report for the first time, the radical carbonyl propargylation through dual chromium/photoredox catalysis. A library of valuable homopropargylic alcohols bearing all-carbon quaternary centers could be obtained by a catalytic radical three-component coupling of 1,3-enynes, aldehydes and suitable radical precursors (41 examples). This redox-neutral multi-component reaction occurs under very mild conditions and shows high functional group tolerance. Remarkably, bench-stable, non-toxic, and inexpensive CrCl3 could be employed as a chromium source. Preliminary mechanistic investigations suggest a radical-polar crossover mechanism, which offers a complementary and novel approach towards the preparation of valuable synthetic architectures from simple chemicals.
- Huang, Huan-Ming,Bellotti, Peter,Daniliuc, Constantin G.,Glorius, Frank
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supporting information
p. 2464 - 2471
(2020/12/07)
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- Three-Component, Interrupted Radical Heck/Allylic Substitution Cascade Involving Unactivated Alkyl Bromides
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Developing efficient and selective strategies to approach complex architectures containing (multi)stereogenic centers has been a long-standing synthetic challenge in both academia and industry. Catalytic cascade reactions represent a powerful means of rapidly leveraging molecular complexity from simple feedstocks. Unfortunately, carrying out cascade Heck-type reactions involving unactivated (tertiary) alkyl halides remains an unmet challenge owing to unavoidable β-hydride elimination. Herein, we show that a modular, practical, and general palladium-catalyzed, radical three-component coupling can indeed overcome the aforementioned limitations through an interrupted Heck/allylic substitution sequence mediated by visible light. Selective 1,4-difunctionalization of unactivated 1,3-dienes, such as butadiene, has been achieved by employing different commercially available nitrogen-, oxygen-, sulfur-, or carbon-based nucleophiles and unactivated alkyl bromides (>130 examples, mostly >95:5 E/Z, >20:1 rr). Sequential C(sp3)-C(sp3) and C-X (N, O, S) bonds have been constructed efficiently with a broad scope and high functional group tolerance. The flexibility and versatility of the strategy have been illustrated in a gram-scale reaction and streamlined syntheses of complex ether, sulfone, and tertiary amine products, some of which would be difficult to access via currently established methods.
- Bellotti, Peter,Glorius, Frank,Heidrich, Bastian,Huang, Huan-Ming,Pflüger, Philipp M.,Schwarz, J. Luca
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supporting information
p. 10173 - 10183
(2020/06/27)
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- Photocatalytic Reductive Radical-Polar Crossover for a Base-Free Corey–Seebach Reaction
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A metal-free generation of carbanion nucleophiles is of prime importance in organic synthesis. Herein we report a photocatalytic approach to the Corey–Seebach reaction. The presented method operates under mild redox-neutral and base-free conditions giving the desired product with high functional group tolerance. The reaction is enabled by the combination of photo- and hydrogen atom transfer (HAT) catalysis. This catalytic merger allows a C?H to carbanion activation by the abstraction of a hydrogen atom followed by radical reduction. The generated nucleophilic intermediate is then capable of adding to carbonyl electrophiles. The obtained dithiane can be easily converted to the valuable α-hydroxy carbonyl in a subsequent step. The proposed reaction mechanism is supported by emission quenching, radical–radical homocoupling and deuterium labeling studies as well as by calculated redox-potentials and bond strengths.
- Crespi, Stefano,Donabauer, Karsten,K?nig, Burkhard,Murugesan, Kathiravan,Rozman, Ur?a
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supporting information
p. 12945 - 12950
(2020/09/23)
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- Ligand-Controlled Regiodivergent Silylation of Allylic Alcohols by Ni/Cu Catalysis for the Synthesis of Functionalized Allylsilanes
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The first Ni/Cu-catalyzed regiodivergent synthesis of allylsilanes directly from allylic alcohols through modulating the steric and electronic properties of the ligands on the nickel catalyst has been developed. Good yields and excellent selectivity were obtained regardless of whether linear or α-branched allylic alcohols were utilized. Mechanistic studies indicate that an allyloxyboronate species is formed during the reaction, which likely serves as an activated intermediate toward the oxidative addition of the C(allyl)-O bond.
- Gan, Yi,Xu, Wei,Liu, Yuanhong
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supporting information
p. 9652 - 9657
(2019/11/28)
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- Continuous preparing method of aryl propionic aldehyde compound
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The invention discloses a continuous preparing method of an aryl propionic aldehyde compound. The method includes the following step of making a compound shown in the formula A and a compound shown inthe formula B have a reaction shown as follows in a tubular reactor in a solvent under the effect of a palladium catalyst, ligand and an organic base to prepare a compound shown in the formula C. Thepreparing method shortens the reaction time, reduces the consumption of the catalyst, is high in safety, ensures the product quality, reduces the cost, reduces the generation of a byproduct (tar), and is more suitable for industrial production.
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Paragraph 0121-0124
(2019/07/16)
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- N-Functionalised TsDPEN catalysts for asymmetric transfer hydrogenation; Synthesis and applications
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A series of Ru(II)/arene complexes containing N-alkylated derivatives of TsDPEN were prepared and tested in the asymmetric transfer hydrogenation (ATH) of ketones. The results demonstrated that a wide variety of functionality were tolerated on the basic amine of the TsDPEN ligand, without significantly disrupting the ability of the catalyst to catalyse hydrogen transfer reactions.
- Soni, Rina,Hall, Thomas H.,Morris, David J.,Clarkson, Guy J.,Owen, Matthew R.,Wills, Martin
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supporting information
p. 6397 - 6401
(2015/11/16)
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- Discovery of 5-substituted pyrrolo[2,3- d ]pyrimidine antifolates as dual-acting inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis: Implications of inhibiting 5-aminoimidazole-4- carboxamide ribonucleotide formyltransferase to AMPK activation and antitumor activity
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We synthesized 5-substituted pyrrolo[2,3-d]pyrimidine antifolates (compounds 5-10) with one-to-six bridge carbons and a benozyl ring in the side chain as antitumor agents. Compound 8 with a 4-carbon bridge was the most active analogue and potently inhibited proliferation of folate receptor (FR) α-expressing Chinese hamster ovary and KB human tumor cells. Growth inhibition was reversed completely or in part by excess folic acid, indicating that FRα is involved in cellular uptake, and resulted in S-phase accumulation and apoptosis. Antiproliferative effects of compound 8 toward KB cells were protected by excess adenosine but not thymidine, establishing de novo purine nucleotide biosynthesis as the targeted pathway. However, 5-aminoimidazole-4-carboxamide (AICA) protection was incomplete, suggesting inhibition of both AICA ribonucleotide formyltransferase (AICARFTase) and glycinamide ribonucleotide formyltransferase (GARFTase). Inhibition of GARFTase and AICARFTase by compound 8 was confirmed by cellular metabolic assays and resulted in ATP pool depletion. To our knowledge, this is the first example of an antifolate that acts as a dual inhibitor of GARFTase and AICARFTase as its principal mechanism of action.
- Mitchell-Ryan, Shermaine,Wang, Yiqiang,Raghavan, Sudhir,Ravindra, Manasa Punaha,Hales, Eric,Orr, Steven,Cherian, Christina,Hou, Zhanjun,Matherly, Larry H.,Gangjee, Aleem
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p. 10016 - 10032
(2014/01/17)
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- Cobalt-catalyzed 1,4-hydrobutadienylation of 1-aryl-1,3-dienes with 2,3-dimethyl-1,3-butadiene
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Round and round the olefin goes! A cobalt-catalyzed 1,4- hydrobutadienylation of a 1-aryl-substituted 1,3-diene with 2,3-dimethyl-1,3- butadiene yields 1,3,6-triene derivatives in excellent yield and chemoselectivity. The application of a bulky ligand (SchmalzPhos) leads to the selective formation of a single regio- and stereoisomer. Copyright
- Bohn, Martin A.,Schmidt, Anastasia,Hilt, Gerhard,Dindaroglu, Mehmet,Schmalz, Hans-Guenther
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supporting information; experimental part
p. 9689 - 9693
(2011/12/05)
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- Symmetrie macrocycles by a prins dimerization and macrocyclization strategy
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A tandem dimerization/macrocyclization reaction utilizing the Prins cyclization has been developed. This reaction develops molecular complexity through the formation of highly substituted dimeric tetrahydropyran macrocycles. Mild conditions utilizing rhen
- Gesinski, Michael R.,Tadpetch, Kwanruthai,Rychnovsky, Scott D.
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scheme or table
p. 5342 - 5345
(2010/02/28)
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- NEW CLASSICAL ANTIFOLATES
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The present invention is directed to antifolate compounds having the structure of formula (I). wherein: X is CHR9 or NR9; Y1, Y2, and Y3 independently are O or S; V1 and V2 independently are O, S, or NZ; Z is H, optionally substituted alkyl, optionally su
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Page/Page column 54
(2008/12/07)
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- 6-Membered heterocyclic compound and use thereof
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A compound represented by the general formula (I) or a salt thereof: [T represents oxygen atom and the like; V represents CH2 and the like; RO1 to RO4 represent hydrogen atom and the like; A represents a linear alkylene group or linear alkenylene group having 2 to 8 carbon atoms and the like; D represents carboxyl group and the like; X represents ethylene group, trimethylene group and the like; E represents —CH(OH)— group and the like; and W represent —U1—(RW1)(RW2)—U2—U3 group (U1 represents a single bond, an alkylene group having 1 to 4 carbon atoms and the like; RW1 and RW2 represent hydrogen atom and the like; U2 represents a single bond, an alkylene group having 1 to 4 carbon atoms and the like; and U3 represent an alkyl group having 1 to 8 carbon atoms and the like), or a residue of a carbon ring or heterocyclic compound], which can be utilized as an active ingredient of medicaments effective for prophylactic and/or therapeutic treatment of skeletal diseases such as osteoporosis and fracture, glaucoma, ulcerative colitis and the like.
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Page/Page column 217
(2008/06/13)
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- BIAROMATIC COMPOUNDS THAT MODULATE PPAR TYPE RECEPTORS, PROCESS FOR PREPARING THEM AND USE THEREOF IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS
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The invention relates to novel biaromatic compounds that correspond to the general formula (I) and also to the method for preparing them, and to their use in pharmaceutical compositions for use in human or veterinary medicine, especially in dermatology, a
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Page/Page column 43-44; 1/2
(2010/11/08)
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- Process for the synthesis C-2, C-3 substituted N-alkylated indoles useful as CPLA2 inhibitors
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The present invention provides method for making a compound of formula 1: comprising the steps of reacting compounds of formulas 2 and 3: to produce a compound of formula 4: wherein R1, R2, R3, R4 and R5 /
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Page/Page column 9-10
(2008/06/13)
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- Process for the synthesis of cPLA2 inhibitors
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A process for making the compound of formula (I) wherein Ac represents acetate; X represents O or CH2; Y represents C1-C6alkyl; and Z is selected from the group consisting of H, halogen, CN, CHO, CF3, OCF3
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Page/Page column 7-8
(2008/06/13)
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- Synthesis of classical and nonclassical 2-amino-4-oxo-6-benzylthieno-[2,3- d]pyrimidines as potential thymidylate synthase inhibitors
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A series of seven nonclassical 2-amino-4-oxo-6-substituted thieno[2,3-d]pyrimidines 2-8 and one classical N-[4-(2-amino-4-oxo-3,4- dihydrothieno[2,3-d]pyrimidin-6-ylmethyl)benzoyl]-L-glutamic acid 9 (Table I) were designed as the first in a series of 6-substituted 6-5 fused ring analogs as potential thymidylate synthase (TS) inhibitors and as antitumor agents. The target compounds were synthesized via a Heck coupling of appropriately substituted iodobenzenes and allyl alcohol followed by cyclization using cyanoacetate and sulfur powder to afford substituted thiophenes. The resulting thiophenes were then cyclocondensed with chloroformamidine hydrochloride to afford 2-amino-4-oxo-6-substituted thieno[2,3-d]pyrimidines 2-8 and 26. Hydrolysis of 26 followed by coupling with diethyl L-glutamate afforded 28. The classical analog 9 was obtained by hydrolysis of 28. None of the target compounds inhibited human recombinant thymidylate synthase at 23 μM except 9 for which the IC50 value was 100 μM.
- Gangjee, Aleem,Qiu, Yibin,Kisliuk, Roy L.
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p. 941 - 946
(2007/10/03)
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- Process for the preparation of pyrrolo[2,3-d]pyrimidines
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4(3H)-X-7H-Pyrrolo[2,3-d]pyrimidines in which X is =O or =NH are prepared by treating a 6-amino-4(3H)-X-pyrimidine with a unsubstituted or substituted 1-nitroalk-1-ene to yield a 6-amino-4(3H)-X-pyrimidine which is substituted in the 5-position by a 1-nitroalk-2-yl group; (ii) converting the 5-(1-nitroalk-2-yl)-6-amino-4(3H)-X-pyrimidine to the corresponding 5-(1-oxoalk-2-yl)-6-amino-4(3H)-X-pyr-imidine; and (iii) removing the elements of water from the 5-(1-oxoalk-2-yl)-6-amino-4(3H)-X-pyrimidine to effect cyclization. A typical embodiment involves treating 2,6-diamino-4(3H)-pyrimidone with 1-nitro-4-(4-ethoxycarbonylphenyl)-1-butene to yield 1 -nitro-2-(2,6-diamino-4(3H)-oxopyrimidin-5-yl)-4-(4-ethoxy-carbonylphenyl)butane which is then treated sequentially with base and acid, without isolation of the intermediate aldehyde, to form 4-[2-(2-amino-4(3H)-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid, a valuable known chemical intermediate for the preparation of N-[4-{2-(2-hydroxy-4-amino-7H-pyrrolo[2,3-d]-pyrimidin-5-yl)ethyl}benzoyl]glutamic acid.
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- A simple and concise synthesis of LY231514 (MTA)
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The pyrrolo[2,3-d]pyrimidine anticancer agent LY231514 (MTA, 1) has been prepared utilizing, as a key sequence, Michael condensation of 2,6-diamino- 4(3H)-pyrimidinone (as the donor) with the nitro olefin 8, followed by a Nef reaction that leads to the annulated pyrrole ring of 1.
- Taylor, Edward C.,Liu, Bin
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p. 4023 - 4026
(2007/10/03)
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- Novel methodology for the preparation of 5-substituted tetrahydro[2,3- d]pyrimidines
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A convenient, concise route for the preparation of tetrahydropyrido[2,3- d]pydmidines functionalized at the 5-position is presented starting from acyclic aldehydes. Key steps involve a high yielding Knoevenagel condensation, 1,4 conjugate addition with an
- Watson, Samuel E.,Taylor, Edward C.,Patel, Hemantkar
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p. 1897 - 1905
(2007/10/03)
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