- Borylation of Unactivated C(sp3)-H Bonds with Bromide as a Traceless Directing Group
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A palladium-catalyzed alkyl C-H borylation with bromide as a traceless directing group is described, providing a convenient approach to access alkyl boronates bearing a β-all-carbon quaternary stereocenter. The protocol features a broad substrate scope, excellent site selectivity, and good functional group tolerance.
- Zhang, Ge,Li, Meng-Yao,Ye, Wen-Bo,He, Zhi-Tao,Feng, Chen-Guo,Lin, Guo-Qiang
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supporting information
p. 2948 - 2953
(2021/05/05)
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- Enantioselective Desymmetrization of 2-Aryl-1,3-propanediols by Direct O-Alkylation with a Rationally Designed Chiral Hemiboronic Acid Catalyst That Mitigates Substrate Conformational Poisoning
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Enantioselective desymmetrization by direct monofunctionalization of prochiral diols is a powerful strategy to prepare valuable synthetic intermediates in high optical purity. Boron acids can activate diols toward nucleophilic additions; however, the design of stable chiral catalysts remains a challenge and highlights the need to identify new chemotypes for this purpose. Herein, the discovery and optimization of a bench-stable chiral 9-hydroxy-9,10-boroxarophenanthrene catalyst is described and applied in the highly enantioselective desymmetrization of 2-aryl-1,3-diols using benzylic electrophiles under operationally simple, ambient conditions. Nucleophilic activation and discrimination of the enantiotopic hydroxy groups on the diol substrate occurs via a defined chairlike six-membered anionic complex with the hemiboronic heterocycle. The optimal binaphthyl-based catalyst 1g features a large aryloxytrityl group to effectively shield one of the two prochiral hydroxy groups on the diol complex, whereas a strategically placed "methyl blocker"on the boroxarophenanthrene unit mitigates the deleterious effect of a competing conformation of the complexed diol that compromised the overall efficiency of the desymmetrization process. This methodology affords monoalkylated products in enantiomeric ratios equal or over 95:5 for a wide range of 1,3-propanediols with various 2-aryl/heteroaryl groups.
- Estrada, Carl D.,Ang, Hwee Ting,Vetter, Kim-Marie,Ponich, Ashley A.,Hall, Dennis G.
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supporting information
(2021/04/07)
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- Customized Buchwald-Type Phosphines Bearing an "Inverted" Pyrimidinium Betaine as an Aryl Group Surrogate - Synthesis and Coordination Chemistry with Gold(I)
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A new ligand scaffold inspired by Buchwald-type phosphines is disclosed. Its design consists of the formal replacement of the distal aryl group of the original archetype by a pyrimidinium betaine connected to the o-phosphinophenyl moiety through the C-5 position of its malonate subunit. A productive synthetic pathway towards this phosphine is described along with its ability to coordinate to a gold(I) center. A weak bonding interaction between the metal center and the malonate group is observed in the solid state.
- No?l-Duchesneau, Ludovik,Lugan, No?l,Lavigne, Guy,Labande, Agnès,César, Vincent
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p. 1752 - 1758
(2015/04/14)
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- One-Pot Base-Mediated Synthesis of Functionalized Aza-Fused Polycyclic Quinoline Derivatives
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A new one-pot protocol has been developed for the facile and efficient synthesis of aza-fused polycyclic quinolines (e.g., pyrrolo[1,2-a]quinolines) by the base-catalyzed reaction of 2-formylpyrroles and 2-halophenylacetonitriles. This reaction proceeded under transition metal-free conditions and showed high functional group tolerance, with the desired products being formed in good yields.
- Jiang, Zeng-Qiang,Miao, Da-Zhuang,Tong, Yao,Pan, Qiang,Li, Xiao-Tong,Hu, Ren-He,Han, Shi-Qing
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supporting information
p. 1913 - 1921
(2015/06/30)
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- Synthesis of α-aryl esters and nitriles: Deaminative coupling of α-aminoesters and α-aminoacetonitriles with arylboronic acids
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Transition-metal-free synthesis of α-aryl esters and nitriles using arylboronic acids with α-aminoesters and α-aminoacetonitriles, respectively, as the starting materials has been developed. The reaction represents a rare case of converting C(sp3)-N bonds into C(sp3)-C(sp2) bonds. The reaction conditions are mild, demonstrate good functional-group tolerance, and can be scaled up. Touch base: A transition-metal-free protocol for the synthesis of α-aryl esters and nitriles by deaminative coupling is presented. Strong bases and transition-metal catalysts are not needed. The new synthetic method uses readily available starting materials and demonstrates wide substrate scope.
- Wu, Guojiao,Deng, Yifan,Wu, Chaoqiang,Zhang, Yan,Wang, Jianbo
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supporting information
p. 10510 - 10514
(2016/02/18)
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- A chemoselective Reformatsky-Negishi approach to α-haloaryl esters
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A practical synthesis of α-haloaryl esters has been achieved via a chemoselective Negishi coupling of poly-halogenated aromatics and Reformatsky reagents in the presence of catalytic Pd(dba)2 and Xantphos. This chemistry tolerates a variety of aryl halides and was successfully applied to the synthesis of Ibuprofen. The α-haloaryl ester products, exemplified by ethyl 2-(4-bromo-2-chlorophenyl)acetate (3a), can be further functionalized via palladium or copper catalysis to afford an array of α-aryl esters.
- Wong, Brian,Linghu, Xin,Crawford, James J.,Drobnick, Joy,Lee, Wendy,Zhang, Haiming
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p. 1508 - 1515
(2014/02/14)
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- Regio- and chemoselective C-H chlorination/bromination of electron-deficient arenes by weak coordination and study of relative directing-group abilities
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It's all relative: A practical and efficient PdII-catalyzed regio- and chemoselective chlorination/bromination has been developed for the facile synthesis of a broad range of aromatic chlorides. The reaction demonstrates excellent reactivity, good functional-group tolerance, and high yields. A preliminary study was conducted to evaluate relative directing-group abilities of various functionalities. Copyright
- Sun, Xiuyun,Shan, Gang,Sun, Yonghui,Rao, Yu
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supporting information
p. 4440 - 4444
(2013/05/22)
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- COMPOUNDS FOR THE TREATMENT OF CNS DISORDERS
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The invention relates to novel cycloalkyl- or cycloalkenyl-substituted pyrazolopyrimidinones of formula (I), wherein ā is selected from the group A1 consisting of a C3-C8-cycloalkyl group or a C4-C8-cycloalkenyl group, whereby the members of C3-C8-cycloalkyl group being selected from the group of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl and cyclooctanyl; and the members of the C4-C8-cycloalkenyl group, being selected from cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclopentadienyl, cyclohexadienyl, cycloheptadienyl, cyclooctadienyl, cycloheptatrienyl, cyclooctathenyl, cyclooctatetraenyl. The new compounds shall be used for the manufacture of medicaments, in particular medicaments for improving perception, concentration, learning and/or memory in patients in need thereof. Chemically, the compounds are characterised as pyrazolopyrimidinones with a cycloalkyl-moiety directly bound to the 1 position of the pyrazolopyrimidinone and a second substituent in the 6 position which is bound via an optionally substituted methylene-bridge. Further aspects of the present invention refer to a process for the manufacture of the compounds and their use for producing medicaments.
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Page/Page column 40
(2012/05/20)
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- BIPHENYLACETAMIDE DERIVATIVE
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The present invention provides a compound of formula (I) or a salt thereof, wherein R1, R2 and R3 are independently selected from the group consisting of hydrogen atom, fluorine atom, chlorine atom, bromine atom, C1-6 alkyl, C1-6 alkoxy substituted with fluorine atom, and others; R4 and R5 are independently selected from the group consisting of hydrogen atom, fluorine atom, chlorine atom, C1-6 alkyl, C1-6 alkoxy substituted with fluorine atom, and others; R6 and R7 are independently selected from the group consisting of hydrogen atom, fluorine atom, methyl, ethyl, hydroxy group, and others; and R8 and R9 are independently selected from the group consisting of hydrogen atom, C1-6 alkyl, and others, which is useful as an agent for treating or preventing various types of epilepsy including partial seizures and/or generalized seizures.
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Page/Page column 12
(2011/10/04)
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- Discovery and optimization of a biphenylacetic acid series of prostaglandin D2 receptor DP2 antagonists with efficacy in a murine model of allergic rhinitis
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Biphenylacetic acid (5) was identified through a library screen as an inhibitor of the prostaglandin D2 receptor DP2 (CRTH2). Optimization for potency and pharmacokinetic properties led to a series of selective CRTH2 antagonists. Compounds demonstrated potency in a human DP2 binding assay and a human whole blood eosinophil shape change assay, as well as good oral bioavailability in rat and dog, and efficacy in a mouse model of allergic rhinitis following oral dosing.
- Scott, Jill M.,Baccei, Christopher,Bain, Gretchen,Broadhead, Alex,Evans, Jilly F.,Fagan, Patrick,Hutchinson, John H.,King, Christopher,Lorrain, Daniel S.,Lee, Catherine,Prasit, Peppi,Prodanovich, Pat,Santini, Angelina,Santini, Brian A.
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scheme or table
p. 6608 - 6612
(2011/12/04)
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- 1-HETEROCYCLYL-1,5-DIHYDRO-PYRAZOLO[3,4-D] PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE AS PDE9A MODULATORS
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The invention relates to novel 1,6-disubstituted pyrazolopyrimidinones, Formula (I) with Hc is a mono-, bi- or tricyclic heterocyclyl group, the ring members of which are carbon atoms and at least 1, preferably 1, 2 or 3, heteroatom(s), which are selected from the group of nitrogen, oxygen and sulphur, which is in the form of -S(O)r - with r being 0, 1 or 2, and - said heterocyclyl group is or comprises 1 non-aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member and - said heterocyclyl group is bound to the scaffold by said 1 non- aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member. According to one aspect of the invention the new compounds are for the manufacture of medicaments, in particular medicaments for the treatment of conditions concerning deficits in perception, concentration, learning or memory. The new compounds are also for the manufacture of medicaments for the treatment of Alzheimer's disease.
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Page/Page column 163
(2009/10/30)
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- Synthesis of ring-fused oxazolo- and pyrazoloisoquinolinones by a one-pot Pd-catalyzed carboxamidation and aldol-type condensation cascade process
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(Chemical Equation Presented) A three-component cascade process is described for the synthesis of ring-fused oxazolo- and pyrazoloisoquinolinones by a one-pot carboxamidation/aldol-type condensation reaction. The cascade process involves Pd-catalyzed carboxamidation of an aryl halide/active methylene compound with oxazolidinone or pyrazolidinone, and subsequent intramolecular base-catalyzed cyclization/dehydration through an aldol-type condensation process, to give ring-fused oxazolo- and pyrazoloisoquinolinones. This methodology provides an easy one-step approach to these important classesof nitrogen-containing heterocycles and can tolerate a wide array of functional groups, including ester, nitrile, methoxy, and halide.
- Chouhan, Gagan,Alper, Howard
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supporting information; experimental part
p. 6181 - 6189
(2009/12/24)
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- Direct one-pot synthesis of phenanthrenes via Suzuki-Miyaura coupling/aldol condensation cascade reaction
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(Chemical Equation Presented) We have developed an efficient cascade reaction, a Suzuki-Miyaura coupling followed by an aldol condensation, for the construction of phenanthrene derivatives using microwave irradiation. For example, the reaction of methyl 2-bromophenylacetamide with 2- formylphenylboronic acid in the presence of a palladium catalyst and a base provided a biaryl intermediate, which underwent in situ cyclization to afford the corresponding phenanthrene in high yield.
- Young, Ha Kim,Lee, Hyuk,Yeong, Joon Kim,Bum, Tae Kim,Heo, Jung-Nyoung
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p. 495 - 501
(2008/09/17)
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- Synthesis of indenes by the palladium-catalyzed carboannulation of internal alkynes
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(Chemical Equation Presented) A number of highly substituted indenes have been prepared in good yields by treating functionally substituted aryl halides with various internal alkynes in the presence of a palladium catalyst. The reaction is believed to proceed by regioselective arylpalladation of the alkyne and subsequent nucleophilic displacement of the palladium in the resulting vinylpalladium intermediate.
- Zhang, Daohua,Eul, Kgun Yum,Liu, Zhijian,Larock, Richard C.
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p. 4963 - 4966
(2007/10/03)
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- 1,2-disubstituted-6-oxo-3-phenyl-piperidine-3-carboxamides and combinatorial libraries thereof
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The invention relates to combinatorial libraries containing two or more novel piperidine-3-carboxamide derivative compounds, methods of preparing the piperidine-3-carboxamide derivative compounds and piperidine-3-carboxamide derivative compounds bound to a resin
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- PHENYLALKYL DERIVATIVES, WITH PHARMACEUTICAL ACTIVITY
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A phenylalkyl derivative of the formula STR1 wherein R a to R. sub.f, A and B are substituents and n is the number 0 or 1.These phenylalkyl derivatives possess angiotensin antagonist activity.
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- SYNTHESIS OF ESTERS BY RHODIUM(I) CATALYZED BORATE ESTER-BENZYLIC BROMIDE CARBONYLATION REACTIONS
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Benzylic halides react with trialkylborates and carbon monoxide, in the presence of 1,5-hexadienerhodium chloride dimer, to give esters in excellent yields.The reaction is applicable to the synthesis of primary, secondary and even tertiary esters.
- Woell, James B.,Alper, Howard
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p. 3791 - 3794
(2007/10/02)
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- 1,2-Dihydro-2-imino-1-(bromophenylalkyl)pyrimidines
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Compounds of the formula SPC1 Exhibit central nervous system stimulating properties and act as muscle relaxants.
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