- Substituted 9-Anthraldehydes from Dibenzocycloheptanol Epoxides via Acid-Catalyzed Epoxide Opening/Semipinacol Rearrangement
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Starting from benzaldehyde derivatives, the corresponding dibenzocycloheptenol could be prepared in five steps. Under both substrate (secondary vs tertiary alcohol and the substituents on the aromatic ring(s)) and condition control, the subsequent epoxidation and acid-catalyzed epoxide opening/semipinacol rearrangement/aromatization afforded the corresponding 9-anthraldehydes in good yields, up to 88% over two steps. The presence of the electron-withdrawing group(s) on the aromatic ring(s) suppressed the rate of the epoxidation while the subsequent semipinacol rearrangement step required heating; the presence of the electron-donating group(s), on the other hand, frequently led to the decomposition during the epoxidation. From the mechanistic studies, the semipinacol rearrangement of the epoxide could precede the ionization at the bisbenzylic position, yielding the aldehyde intermediate. The ensuing dehydrative aromatization led to the formation of 9-anthraldehyde. Conversely, nucleophilic addition to the aldehyde and dehydrative aromatization with concomitant loss of formic acid led to anthracene.
- Phumjan, Tanawat,Songthammawat, Poramate,Jongcharoenkamol, Jira,Batsomboon, Paratchata,Ruchirawat, Somsak,Ploypradith, Poonsakdi
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p. 13322 - 13349
(2021/09/13)
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- Sequential Addition of Amines to Nitrile and Carbon-Carbon Multiple Bond: A Route to 7-Amino-5 H-dibenzo[ c,e]azepines
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A rare earth metal-catalyzed sequential inter- and intramolecular C-N bond formation of 2-nitrile-2′-alkenyl(alkynyl)biphenyls with amines has been developed, which provides a straightforward and efficient access to a range of new functional dibenzo[c,e]azepines. This represents the first examples of direct construction of seven-membered azaheterocycle from unsaturated nitriles and amines. Such transformations have the advantages of avoiding the use of additives, easily available starting materials, step- and high atom-economy, mild reaction conditions, and high selectivity.
- Hu, Kun,Liu, Ruiting,Zhou, Xigeng
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supporting information
p. 6946 - 6950
(2021/09/11)
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- Olefination via Cu-Mediated Dehydroacylation of Unstrained Ketones
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The dehydroacylation of ketones to olefins is realized under mild conditions, which exhibits a unique reaction pathway involving aromatization-driven C-C cleavage to remove the acyl moiety, followed by Cu-mediated oxidative elimination to form an alkene between the α and β carbons. The newly adopted N′-methylpicolinohydrazonamide (MPHA) reagent is key to enable efficient cleavage of ketone C-C bonds at room temperature. Diverse alkyl- and aryl-substituted olefins, dienes, and special alkenes are generated with broad functional group tolerance. Strategic applications of this method are also demonstrated.
- Dong, Guangbin,Xu, Yan,Zhou, Xukai
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supporting information
p. 20042 - 20048
(2021/12/03)
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- Enantioselective Construction of Spiro Quaternary Carbon Stereocenters via Pd-Catalyzed Intramolecular α-Arylation
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We herein report the development of a sterically hindered and electron-rich P-chiral monophosphorus biaryl ligand that has enabled a general and efficient enantioselective intramolecular α-arylation, providing access to a wide series of [4.4], [4.5], and [4.6]-spirocycles with chiral benzylic quaternary carbons in high yields with good to excellent enantioselectivities. A pronounced water effect on enantioselectivity is observed.
- Wu, Ting,Kang, Xuehua,Bai, Heng,Xiong, Wenrui,Xu, Guangqing,Tang, Wenjun,Tang, Wenjun
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supporting information
p. 4602 - 4607
(2020/06/29)
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- Stereoselective Convergent Synthesis of Tetrahydro-5 H-benzo[c]fluorene via Nine-Membered Ring-Closing Metathesis and Transannular Acid-Mediated Cyclization/Nucleophilic Addition
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The diene methyl ethers or acetates, constructed from the Li-Br exchange/addition reactions of 2-vinylbenzaldehydes and 2-(but-3-en-1-yl)bromoarenes followed by etherification or acetylation of the corresponding alcohols, smoothly underwent the ring-closi
- Lekky, Anek,Ruengsatra, Tanachote,Ruchirawat, Somsak,Ploypradith, Poonsakdi
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p. 5277 - 5291
(2019/05/10)
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- Direct synthesis of dialkylarylvinylsilane derivatives: Metathesis of dialkylaryl-iso-propenylsilane and its application to tetracyclic silacycle dye synthesis
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The metathesis of dialkylarylvinylsilane, which has not been accomplished to date, is achieved using dialkylaryl-iso-propenylsilane as a substrate. In addition, we discovered that the reason why the metathesis of a ruthenium carbene complex and dialkylarylvinylsilane is difficult is the formation of a carbide complex.
- Yoshioka, Shohei,Takehara, Tsunayoshi,Matsuzaki, Tsuyoshi,Suzuki, Takeyuki,Tsujino, Hirofumi,Uno, Tadayuki,Tsutsumi, Yasuo,Murai, Kenichi,Fujioka, Hiromichi,Arisawa, Mitsuhiro
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supporting information
p. 14070 - 14073
(2019/11/25)
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- Intramolecular Acetyl Transfer to Olefins by Catalytic C?C Bond Activation of Unstrained Ketones
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A rhodium-catalyzed intramolecular acetyl-group transfer has been achieved through a “cut and sew” process. The challenge arises from the existence of different competitive pathways. Preliminary success has been achieved with unstrained enones that contain a biaryl linker. The use of an electron-rich N-heterocycilc carbene (NHC) ligand is effective to inhibit undesired β-hydrogen elimination. Various 9,10-dihydrophenanthrene derivatives can be prepared with excellent functional-group compatibility. The 13C-labelling study suggests that the reaction begins with cleavage of the unstrained C?C bond, followed by migratory insertion and reductive elimination.
- Rong, Zi-Qiang,Lim, Hee Nam,Dong, Guangbin
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supporting information
p. 475 - 479
(2018/02/21)
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- The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor
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The process development and kilogram-scale synthesis of beclabuvir (BMS-791325, 1) is described. The convergent synthesis features the use of asymmetric catalysis to generate a chiral cyclopropane fragment and coupling with an indole fragment via an alkyl
- Bien, Jeffrey,Davulcu, Akin,Delmonte, Albert J.,Fraunhoffer, Kenneth J.,Gao, Zhinong,Hang, Chao,Hsiao, Yi,Hu, Wenhao,Katipally, Kishta,Littke, Adam,Pedro, Aghogho,Qiu, Yuping,Sandoval, Maria,Schild, Richard,Soltani, Michelle,Tedesco, Anthony,Vanyo, Dale,Vemishetti, Purushotham,Waltermire, Robert E.
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p. 1393 - 1408
(2018/09/06)
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- Intramolecular Crossed [2+2] Photocycloaddition through Visible Light-Induced Energy Transfer
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Herein, we present the intramolecular [2+2] cycloadditions of dienones promoted through sensitization, using a polypyridyl iridium(III) catalyst, to form bridged cyclobutanes. In contrast to previous examples of straight [2+2] cycloadditions, these efficient crossed additions were achieved under irradiation with visible light. The reactions delivered desired bridged benzobicycloheptanone products with excellent regioselectivity in high yields (up to 96%). This process is superior to previous syntheses of benzobicyclo[3.1.1]heptanones, which are readily converted to B-norbenzomorphan analogues of biological significance. Electrochemical, computational, and spectroscopic studies substantiated the mechanism of triplet energy transfer and explained the unusual regiocontrol.
- Zhao, Jiannan,Brosmer, Jonathan L.,Tang, Qingxuan,Yang, Zhongyue,Houk,Diaconescu, Paula L.,Kwon, Ohyun
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supporting information
p. 9807 - 9810
(2017/08/03)
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- Synthesis of Bridged Cyclopentane Derivatives by Catalytic Decarbonylative Cycloaddition of Cyclobutanones and Olefins
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Herein, we report an intramolecular rhodium-catalyzed decarbonylative coupling between cyclobutanones and alkenes that proceeds by C?C activation and provides a distinct approach to a diverse range of saturated bridged cyclopentane derivatives. In this reaction, cyclobutanones serve as cyclopropane surrogates, reacting in a formal (4+2?1) transformation. To demonstrate the efficacy of this method, it was applied in a concise synthesis of the antifungal drug Tolciclate.
- Zhou, Xuan,Ko, Haye Min,Dong, Guangbin
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supporting information
p. 13867 - 13871
(2016/10/26)
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- Tandem Pd-catalyzed C-C coupling/recyclization of 2-(2-bromoaryl)cyclopropane-1,1-dicarboxylates with primary nitro alkanes
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The first successful synthesis of 1H-2,3-benzoxazine 3-oxides has been described. The efficiency of the approach is provided by the C-C-coupling of 2-(2-bromoaryl)cyclopropane-1,1-dicarboxylates with primary nitroalkanes catalyzed by Pd(dba)2/JohnPhos system followed by in situ recyclization of the intermediates. Several representative transformations allowing selective modification of the nitronate as well as malonate functionalities in the resulting compounds are demonstrated.
- Mikhaylov, Andrey A.,Dilman, Alexander D.,Novikov, Roman A.,Khoroshutina, Yulia A.,Struchkova, Marina I.,Arkhipov, Dmitry E.,Nelyubina, Yulia V.,Tabolin, Andrey A.,Ioffe, Sema L.
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supporting information
p. 11 - 14
(2015/12/23)
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- An Efficient Synthesis of Benzazocines by Gold(I)-Catalyzed Tandem 1,2-Acyloxy Shift/[3+2] Cycloaddition of Terminal 1,9-Enynyl Esters
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An effective synthesis of structurally diverse benzazocines was accomplished in good to excellent chemical yields (55–82 %) through a gold(I)-catalyzed cascade reaction involving tandem 1,2-acyloxy shift/[3+2] cycloaddition of terminal 1,9-enynyl esters. The reaction proceeds under extremely mild conditions and represents one of the relatively few transition-metal-catalyzed intramolecular cycloaddition reactions for the synthesis of benzazocines.
- Feng, Shangbiao,Wang, Zhengshen,Zhang, Weiwei,Xie, Xingang,She, Xuegong
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supporting information
p. 2167 - 2172
(2016/08/12)
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- Cycloaddition Reaction of Vinylphenylfurans and Dimethyl Acetylenedicarboxylate to [8 + 2] Isomers via Tandem [4 + 2]/Diradical Alkene-Alkene Coupling/[1,3]-H Shift Reactions: Experimental Exploration and DFT Understanding of Reaction Mechanisms
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An experimental test of designed [8 + 2] reaction of vinylphenylfuran and dimethyl acetylenedicarboxylate (DMAD) has been carried out, showing that the reaction gave unexpected addition products under different conditions. When the reaction was conducted under thermal conditions in toluene, expoxyphenanthrene, which was named as a [8 + 2] isomer, was generated. The scope of this reaction has been investigated in the present study. In addition, experiments and DFT calculations have been conducted to investigate how the reaction between vinylphenylfuran and DMAD took place. Surprisingly, the reaction did not involve the expected [8 + 2] intermediate, o-quinodimethane. Instead, the reaction starts from intermolecular Diels-Alder reactions between DMAD and the furan moiety of vinylphenylfuran, followed by unexpected intramolecular alkene-alkene coupling. This step generates a diradical species, which then undergoes [1,3]-H shift to give the experimentally observed expoxyphenanthrene. DFT calculations revealed that, the [8 + 2] cycloadduct cannot be obtained because the [1,5]-H shift process from the [1,5]-vinyl shift intermediate is disfavored kinetically compared to the [1,3]-H shift to the [8 + 2] isomer.
- Chen, Kai,Wu, Feng,Ye, Lijuan,Tian, Zi-You,Yu, Zhi-Xiang,Zhu, Shifa
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p. 8155 - 8168
(2016/09/28)
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- A route to the 9,10-secosteroid astrogorgiadiol featuring a key sp 2-sp3 Suzuki type cross-coupling
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The described semi-synthetic route differs from the previously published approaches by an original C-7-C-8 disconnection. The kinetic enol triflate of Grundmann ketone was chosen as the CD-ring platform on which to couple an A-ring synthon via a challengi
- Médard, Guillaume
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p. 186 - 196
(2014/01/06)
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- CN-assisted oxidative cyclization of cyano cinnamates and styrene derivatives: A facile entry to 3-substituted chiral phthalides
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The asymmetric dihydroxylation (AD) of o-cyano cinnamates and styrene derivatives leads to efficient construction of chiral phthalide frameworks in high optical purities. This unique reaction is characterized by unusual synergism between CN and osmate groups resulting in rate enhancement of the AD process. The method is amply demonstrated by the synthesis and the structural/stereochemical assignment of the natural products.
- Reddy, R.Santhosh,Kiran, I. N. Chaithanya,Sudalai, Arumugam
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supporting information; experimental part
p. 3655 - 3661
(2012/05/31)
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- Copper-catalyzed recycling of halogen activating groups via 1,3-halogen migration
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A Cu(I)-catalyzed 1,3-halogen migration reaction effectively recycles an activating group by transferring bromine or iodine from a sp2 to a benzylic carbon with concomitant borylation of the Ar-X bond. The resulting benzyl halide can be reacted in the same vessel under a variety of conditions to form an additional carbon-heteroatom bond. Cross-over experiments using an isotopically enriched bromide source support intramolecular transfer of Br. The reaction is postulated to proceed via a Markovnikov hydrocupration of the o-halostyrene, oxidative addition of the resulting Cu(I) complex into the Ar-X bond, reductive elimination of the new sp3 C-X bond, and final borylation of an Ar-Cu(I) species to turn over the catalytic cycle.
- Grigg, R. David,Van Hoveln, Ryan,Schomaker, Jennifer M.
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supporting information
p. 16131 - 16134,4
(2020/09/09)
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- Synthesis of heterocycles via Pd-ligand controlled cyclization of 2-chloro-N-(2-vinyl)aniline: Preparation of carbazoles, indoles, dibenzazepines, and acridines
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The Pd-catalyzed condensation of 2-bromostyrene and 2-chloroaniline derivatives yields stable diphenylamine intermediates, which are selectively converted to five-, six-, or seven-membered heteroaromatics (indoles, carbazoles, acridines, and dibenzazepines). The selectivity of these intramolecular transformations is uniquely ligand-controlled and offers efficient routes to four important classes of heterocycles from a common precursor.
- Tsvelikhovsky, Dmitry,Buchwald, Stephen L.
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supporting information; experimental part
p. 14048 - 14051
(2011/01/04)
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- Eleven amino acid glucagon-like peptide-1 receptor agonists with antidiabetic activity
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Glucagon-like peptide 1 (GLP-1) is a 30 or 31 amino acid peptide hormone that contributes to the physiological regulation of glucose homeostasis and food intake. Herein, we report the discovery of a novel class of 11 amino acidGLP-1 receptor agonists. These peptides consist of a structurally optimized 9- mer, which is closely related to the N-terminal 9 amino acids ofGLP-1, linked to a substituted C-terminal biphenylalanine (BIP) dipeptide. SAR studies resulted in 11-mer GLP-1R agonists with similar in vitro potency to the native 30-mer. Peptides 21 and 22 acutely reduced plasma glucose excursions and increased plasma insulin concentrations in a mouse model of diabetes. These peptides also showed sustained exposures over several hours in mouse and dog models. The described 11-mer GLP-1 receptor agonists represent a new tool in further understanding GLP-1 receptor pharmacology that may lead to novel antidiabetic agents.
- Mapelli, Claudio,Natarajan, Sesha I.,Meyer, Jean-Philippe,Bastos, Margarita M.,Bernatowicz, Michael S.,Lee, Ving G.,Pluscec, Jelka,Riexinger, Douglas J.,Sieber-McMaster, Ellen S.,Constantine, Keith L.,Smith-Monroy, Constance A.,Golla, Rajasree,Ma, Zhengping,Longhi, Daniel A.,Shi, Dan,Xin, Li,Taylor, Joseph R.,Koplowitz, Barry,Chi, Cecilia L.,Khanna, Ashish,Robinson, Gordon W.,Seethala, Ramakrishna,Antal-Zimanyi, Ildiko A.,Stoffel, Robert H.,Han, Songping,Whaley, Jean M.,Huang, Christine S.,Krupinski, John,Ewing, William R.
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experimental part
p. 7788 - 7799
(2010/06/16)
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- 2-PHENYL INDENE DERIVATIVES USEFUL AS ESTROGEN RECEPTOR LIGANDS
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The invention provides a compound of formula (I) or a pharmaceutically acceptable ester, amide, solvate or salt thereof, including a salt of such an ester or amide, and a solvate of such an ester, amide or salt. The invention also provides also provides the use of such compounds in the treatment or prophylaxis of a condition associated with a disease or disorder associated with estrogen receptor activity. Formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 are as defined in the specification, and wherein either the bond between the C1and C2 carbon atoms is a double bond or the bond between the C2 and C3 carbon atoms is a double bond, R2 being absent when the bond between the C1 and C2 carbon atoms is a double bond.
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Page/Page column 30
(2008/06/13)
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- Process for the preparation of amino acids useful in the preparation of peptide receptor modulators
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The present invention provides process useful for the preparation of intermediates which are useful in the preparation of amino acids useful in preparing peptide receptor modulators, for example agonists or partial agonists of such peptide receptors. Such
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Page/Page column 2; 4; 6
(2010/02/15)
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- Synthesis of a phenolic analog of aphidicolin. Diminished stereoselection in intramolecular 6-exo Heck reactions of substrates having a hydrocarbon tether
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Spirotetracycle 14, generated by intramolecular Heck cyclization of 13, was converted to the phenolic analog 20 of aphidicolin. That the nature of the tether connecting insertion partners can dramatically alter diastereoselection in intramolecular Heck reactions is also demonstrated.
- Abelman, Matthew M.,Kado, Noriyuki,Overman, Larry E.,Sarkar, Achintya K.
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p. 1469 - 1471
(2007/10/03)
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- Oxygenated phenanthrenes via quinol ketals: Cyclization vs. migration
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2-methoxyphenanthrenes were prepared by reaction of lithiated 2-bromostyrenes with quinone monoketals followed by acid-mediated cyclization of the resulting p-arylquinol ketals. Substitution at the bromostyrene side-chain or the quinone monoketal ring had only a modest effect on yields, but oxygen substitution on the bromostyrene aromatic nucleus resulted in a competing 1,2-aryl migration arising during the quinol ketal cyclization step. The extent of this rearrangement was found to be a function of the Lewis acid/solvent system employed.
- Morrow, Gary W.,Marks, Tina M.,Sear, Debra L.
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p. 10115 - 10124
(2007/10/02)
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