- General [4 + 1] Cyclization Approach to Access 2,2-Disubstituted Tetrahydrofurans Enabled by Electrophilic Bifunctional Peroxides
-
A general [4 + 1] cyclization reaction of carbonyl nucleophiles with 2-iodomethylallyl peroxides, which function as unique electrophilic oxygen synthons, for the synthesis of a broad range of 2,2-disubstituted tetrahydrofurans is achieved under operationally simple conditions. The unprecedented asymmetric version of such reaction is also realized via chiral auxiliary-assisted cyclization, thus providing a distinct approach to access chiral tetrahydrofurans with high diastereoselectivities. The new method can be applied to the synthesis of core structure of posaconazole drug.
- Gao, Min,Zhao, Yukun,Zhong, Chen,Liu, Shengshu,Liu, Pengkang,Yin, Qi,Hu, Lin
-
supporting information
p. 5679 - 5684
(2019/08/01)
-
- Reactivity Profiles of Diazo Amides, Esters, and Ketones in Transition-Metal-Free C-H Insertion Reactions
-
Vinyl cations derived from diazo ketones participate in transition-metal-free C-H insertion reactions, but the corresponding amide and ester analog exhibit divergent reactivity profiles. Whereas cations formed from diazo ketones undergo a rearrangement and C-H insertion sequence, those from diazo amides do so less efficiently and tend to be competitively trapped before the insertion step occurs. Diazo esters undergo several rearrangement steps and fail to insert. DFT calculations reveal that this disparity stems from two factors: differing levels of electrostatic stabilization of the initially formed vinyl cation by the adjacent carbonyl oxygen and predistortion of the ketone and amide systems toward C-H insertion. The computational data is in strong agreement with experimental results, and this study explains how structural and electronic factors determine the outcome of reactions of diazo carbonyl-derived vinyl cations.
- Cleary, Sarah E.,Li, Xin,Yang, Li-Cheng,Houk,Hong, Xin,Brewer, Matthias
-
supporting information
p. 3558 - 3565
(2019/02/26)
-
- Intermolecular acetoxyaminoalkylation of α-diazo amides with (diacetoxyiodo)benzene and amines
-
Multicomponent reactions of diazo compounds have attracted much attention in recent years. Such transformations are generally conducted by applying transition metal catalysis and involve the corresponding metal carbenes as key intermediates. In this letter, a metal-free three-component intermolecular acetoxyaminoalkylation of α-diazo amides with tertiary aryl amines and (diacetoxyiodo)benzene is presented.
- D?ben, Nadine,Yan, Hong,Kischkewitz, Marvin,Mao, Jincheng,Studer, Armido
-
supporting information
p. 7933 - 7936
(2019/01/04)
-
- Novel 5-oxo-hexahydroquinoline derivatives: Design, synthesis, in vitro P-glycoprotein-mediated multidrug resistance reversal profile and molecular dynamics simulation study
-
Overexpression of the efflux pump P-glycoprotein (P-gp) is one of the important mechanisms of multidrug resistance (MDR) in many tumor cells. In this study, 26 novel 5-oxo-hexahydroquinoline derivatives containing different nitrophenyl moieties at C4 and various carboxamide substituents at C3 were designed, synthesized and evaluated for their ability to inhibit P-gp by measuring the amount of rhodamine 123 (Rh123) accumulation in uterine sarcoma cells that overexpress P-gp (MES-SA/Dx5) using flow cytometry. The effect of compounds with highest MDR reversal activities was further evaluated by measuring the alterations of MES-SA/Dx5 cells’ sensitivity to doxorubicin (DXR) using MTT assay. The results of both biological assays indicated that compounds bearing 2-nitrophenyl at C4 position and compounds with 4-chlorophenyl carboxamide at C3 demonstrated the highest activities in resistant cells, while they were devoid of any effect in parental nonresistant MES-SA cells. One of the active derivatives, 5c, significantly increased intracellular Rh123 at 100 μM, and it also significantly reduced the IC50 of DXR by 70.1% and 88.7% at 10 and 25 μM, respectively, in MES-SA/Dx5 cells. The toxicity of synthesized compounds against HEK293 as a noncancer cell line was also investigated. All tested derivatives except for 2c compound showed no cytotoxicity. A molecular dynamics simulation study was also performed to investigate the possible binding site of 5c in complex with human P-gp, which showed that this compound formed 11 average H-bonds with Ser909, Thr911, Arg547, Arg543 and Ser474 residues of P-gp. A good agreement was found between the results of the computational and experimental studies. The findings of this study show that some 5-oxo-hexahydroquinoline derivatives could serve as promising candidates for the discovery of new agents for P-gp-mediated MDR reversal.
- Shahraki, Omolbanin,Edraki, Najmeh,Khoshneviszadeh, Mehdi,Zargari, Farshid,Ranjbar, Sara,Saso, Luciano,Firuzi, Omidreza,Miri, Ramin
-
p. 407 - 418
(2017/02/26)
-
- Direct synthesis of polysubstituted 2-aminothiophenes by Cu(ii)-catalyzed addition/oxidative cyclization of alkynoates with thioamides
-
A facile and direct synthetic method was developed for the construction of structurally important 2-aminothiophenes in moderate to excellent yields (up to 91%), via Cu(ii)-catalyzed addition/oxidative cyclization of readily available thioamides with alkynoates under an air atmosphere. This journal is
- Ge, Li-Shi,Wang, Zheng-Lin,An, Xing-Lan,Luo, Xiaoyan,Deng, Wei-Ping
-
supporting information
p. 8473 - 8479
(2014/12/10)
-
- Organocatalytic enantio- and diastereoselective conjugate addition to nitroolefins: When ketoamides surpass ketoesters
-
Our findings on the bifunctional squaramide-catalyzed enantioselective conjugate addition of ketoamides to nitroolefins are disclosed. It appears that simple acyclic methylene ketoamides, unlike the extensively studied ketoesters, afford the products in excellent diastereoselectivities, and maintain high yields and enantioselectivities. Moreover, competition and kinetic studies were conducted to rationalize the observed reactivity and selectivity. The high level of diastereocontrol, along with the amenability of the amide group to postfunctionalization, dramatically increase the synthetic usefulness of the transformation.
- Du, Haiying,Rodriguez, Jean,Bugaut, Xavier,Constantieux, Thierry
-
supporting information
p. 8458 - 8466
(2014/07/08)
-
- Method for preparing chiral diphosphines
-
The invention concerns a method for preparing a compound of formula (1) wherein: A represents naphthyl or phenyl optionally substituted; and Ar1, Ar2independently represent a saturated or aromatic carbocyclic group, optionally substituted.
- -
-
-
- Zinc carbenoid-mediated chain extension of β-keto amides
-
The reaction of β-keto amides with ethyl(iodomethyl)zinc provides access to a wide variety of γ-keto amides, including primary, secondary, and tertiary amides. Although the reaction of α-substituted β-keto amides are in many cases unsatisfactory, the method can be applied to a broad spectrum of substrates that possess imide and olefinic functionality.
- Hilgenkamp, Ramona,Zercher, Charles K
-
p. 8793 - 8800
(2007/10/03)
-
- Asymmetric hydrogenation method of a ketonic compound and derivative
-
The present invention relates to a process for the asymmetric hydrogenation of a ketonic compound and derivative. The invention relates to the use of optically active metal complexes as catalysts for the asymmetric hydrogenation of a ketonic compound and derivative. The process for the asymmetric hydrogenation of a ketonic compound and derivative is characterized in that the asymmetric hydrogenation of said compound is carried out in the presence of an effective amount of a metal complex comprising as ligand an optically active diphosphine corresponding to one of the following formulae: STR1
- -
-
-
- Reactions of Aryliminodimagnesium with Some N,N-Dimethylcarboxamides and Benzonitriles Affording Various Types of Amidines. Correction of Previous Results on Formamidine Formation from N,N-Dimethylformamide
-
Some symmetrical and unsymmetrical form- and benzamidines were prepared by the reaction of ArN(MgBr)2 with Ar'CN, HCONMe2 and related compounds in tetrahydrofuran.
- Okubo, Masao,Tanaka, Mikio,Murata, Yuri,Tsurusaki, Nobuyuki,Omote, Yasumasa,et al.
-
p. 1965 - 1968
(2007/10/02)
-
- Preparation and pharmacologic activity of amido- derivatives of 3-methyl-3,4-dihydro benzo- and pyrido-1,2,4-triazin-3-acetic acids
-
Thirteen amidoderivatives of 3-methyl-3,4-dihydro-6-R-benzo-1,2,4-triazin-3-yl-acetic acids and of 3-methyl-3,4-dihydro-pyrido [3,2-e]/[3,4-e]-1,2,4-triazin- 3-yl-acetic acids were prepared and submitted to a wide pharmacological screening. The dihydrobenzotriazine and dihydropyridotriazine moieties were endowed with a wide pharmacogenic capacity; in fact, several compounds exhibited high antiinflammatory [(I c), (I d), (II d), (V f), (VI f)], diuretic [(I f), (I g), (I h)] and antihypertensive activities [(I d), (III d)], as well as minor effects on the C.N.S.
- Boido,Novelli,Savelli,Sparatore,Russo,Filippelli,Susanna,Marmo
-
p. 279 - 301
(2007/10/02)
-
- LACTONISIERUNG VON MAKROLID-SECOSAEUREN MIT "PUSH-PULL ACETYLENEN"
-
A highly efficient method for the macrolactonization of seco-acids is described.Seco-acids are converted into stable enolesters 3 by the acetylene 1, which are cyclized under proton or Lewis acid catalysis.This new method has been successfully applied to the lactonization of the 7-epi-brefeldin A seco-acids 8a, b.
- Gais, H.-J.
-
p. 273 - 276
(2007/10/02)
-
- A Versatile New Synthesis of Quinolines and Related Fused Pyridines. Part 12. A General Synthesis of 2-Chloropyridines and 2-Pyridons
-
The Vilsmeier formylation of tertiary and secondary enamides leads to 2-pyridons and 2-chloropyridines, respectively.The reaction appears to be quite general allowing substitution in the 1-, 3-, 5-, or 6-position or combinations of these.The major limitation arises with enamides which are unsymmetrically substituted on the double bond with alkyl groups, when mixtures can result.Attempts to introduce a 4-substituent by a variation of the Vilsmeier reagent had limited success.
- Meth-Cohn, Otto,Westwood, Keith T.
-
p. 1173 - 1182
(2007/10/02)
-
- ORGANOMETALLIC INDUCED SELF-CONDENSATION OF CARBOXAMIDES
-
N,N-Disubstituted carboxamides containing α-hydrogen atoms undergo self-condensation reaction simply on treatment with Grignard reagents or n-BuLi in THF at room temp.The reaction is considerably influenced by steric hindrance at the α-carbon and the condensing agent utilized.A possible Claisen-type mechanism is also reported.
- Babudri, F.,Ciminale, F.,Nunno, L. Di,Florio, S.
-
p. 557 - 561
(2007/10/02)
-
