- 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
-
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.
-
supporting information
(2021/04/07)
-
- Palladium-Catalyzed Asymmetric Allylic Alkylation of 4-Substituted Isoxazolidin-5-ones: Straightforward Access to β2,2-Amino Acids
-
We report here an unprecedented and highly enantioselective palladium-catalyzed allylic alkylation applied to 4-substituted isoxazolidin-5-ones. Ultimately, the process provides a straightforward access to β2,2-amino acids bearing an all-carbon quaternary stereogenic center in great yields and a high degree of enantioselectivity.
- Nascimento de Oliveira, Marllon,Arseniyadis, Stellios,Cossy, Janine
-
supporting information
p. 4810 - 4814
(2018/03/21)
-
- Synthesis and odor properties of Phantolide analogues
-
Phantolide analogues 1a–1d were newly synthesized to evaluate their odor profiles. The enantiomers of 1a and 1b were also synthesized. Both (S) enantiomers of 1a and 1b had musk odor although weakly, and but neither of the (R) enantiomers 1a and 1b had mu
- Kawasaki, Masashi,Kuroyanagi, Saki,Ito, Takuya,Morita, Hiroyuki,Tanaka, Yasuo,Toyooka, Naoki
-
p. 2089 - 2099
(2017/03/17)
-
- Protonation and transformations of α-diazo-β-dicarbonyl compounds in superacids: generation of the strongest carbon-centered cationic electrophiles at the protonation of diazomalonates in Friedel–Crafts reactions
-
Protonation of diazodiketones N2C(COR)2in Br?nsted superacids (TfOH, FSO3H, TfOH–SbF5) gives rise to stable and non-reactive O,O-diprotonated at carbonyl oxygens species N2C(C(=OH+)R)2, which were studied by means of1H and13C NMR. Diazomalonates N2C(CO2Alk)2, contrary to diazodiketones, react with TfOH or HF, releasing nitrogen and producing triflates of oxymalonates TfOCH(CO2Alk)2or fluoromalonates FCH(CO2Alk)2, respectively. Diazoketoesters N2C(COR)(CO2Alk) react in the same way only with TfOH, but not with HF. The reactions of diazomalonates with arenes ArH (benzene, toluene, xylenes) in TfOH solution yield corresponding Friedel–Crafts reaction products ArCH(CO2Alk)2. According to performed DFT calculations, trication+CH(C(=OH+)OMe)2, a possible intermediate, which is derived from protonation of dimethyl diazomalonate, should be the strongest cationic carbon-centered electrophile known up to date.
- Satumov, Eugeniy T.,Medvedev, Jury J.,Nilov, Denis I.,Sandzhieva, Maria A.,Boyarskaya, Irina A.,Nikolaev, Valerij A.,Vasilyev, Aleksander V.
-
p. 4835 - 4844
(2016/07/18)
-
- New efficient ligand-free, copper nanoparticle catalyzed coupling reactions of aryl halides with diethyl malonate to produce α-arylation of malonates
-
Recently synthesized copper nanoparticles (Cu NP) were used to catalyze coupling of aryl halides with diethyl malonates to produce α-aryl malonates. Synthetic conditions, including solvents, relative amounts of reactants, catalyst, and temperature, etc. h
- Pai, Gita,Chattopadhyay, Asoke P.
-
p. 1475 - 1482
(2013/06/27)
-
- Copper(I) enolate complexes in α-arylation reactions: Synthesis, reactivity, and mechanism
-
Copper is all bound up: The copper-catalyzed α-arylation of carbonyl compounds occurs through oxidative addition of iodoarenes to the C-bound Cu I enolate species 1 to form an aryl-CuIII intermediate (see scheme). Computational results provide insight into the origins of the relative reactivity of various CuI enolate complexes in the reactions with iodoarenes. Copyright
- Huang, Zheng,Hartwig, John F.
-
supporting information; experimental part
p. 1028 - 1032
(2012/03/09)
-
- Practical synthesis of 2-arylacetic acid esters via palladium-catalyzed dealkoxycarbonylative coupling of malonates with aryl halides
-
A new palladium-based system was developed that catalyzes the coupling of aryl halides with diethyl malonates in the presence of mild bases. In the course of the reaction, the intermediately formed diethyl arylmalonate is directly converted into the arylacetic acid ester via liberation of carbon dioxide and an alkanol. This cross-coupling/dealkoxycarbonylation process provides an efficient and high-yielding synthetic entry to diversely functionalized arylacetic acid esters. Two complementary protocols were developed, one of which is optimal for electron-rich, the other for electron-poor aryl halides. Both make use of low loadings of palladium(0) bis(dibenzylideneacetone) (0.5 mol%)/tri-tert-butylphosphonium tetrafluoroborate (1.1 mol%) as the catalyst and diethyl malonate as the reaction solvent. The new procedures are particularly effective for sterically hindered substrates. Copyright
- Song, Bingrui,Rudolphi, Felix,Himmler, Thomas,Goossen, Lukas J.
-
experimental part
p. 1565 - 1574
(2011/08/03)
-
- C-arylation reactions catalyzed by CuO-nanoparticles under ligand free conditions
-
CuO-nanoparticles were found to be an excellent heterogeneous catalyst for C-arylation of active methylene compounds using various aryl halides. The products were obtained in good to excellent yield. The catalyst can be recovered and reused for four cycles with almost no loss in activity.
- Kidwai, Mazaahir,Bhardwaj, Saurav,Poddar, Roona
-
scheme or table
(2010/07/15)
-
- Copper(I)-catalyzed C-C and C-O coupling reactions using hydrazone ligands
-
Copper-catalyzed C-C coupling reaction of aryl iodides with diethylmalonate in toluene at 90C gave arylated malonates using 5 mol% of CuI with hydrazone 1a as a ligand in good yields under an aerobic atmosphere. We also found CuI/hydrazone 1b in toluene to be an efficient catalytic system for C-O coupling reactions of aryl bromides with phenols to give aryl ethers in good yields at 110C under an aerobic atmosphere.
- Mino, Takashi,Yagishita, Fumitoshi,Shibuya, Masanori,Kajiwara, Kenji,Shindo, Hiroaki,Sakamoto, Masami,Fujita, Tsutomu
-
experimental part
p. 2457 - 2460
(2010/01/07)
-
- Enzymatic desymmetrization of prochiral 2-substituted-1,3-diamines: Preparation of valuable nitrogenated compounds
-
A wide range of prochiral 1, 3-diamines were first efficiently synthesized and subsequently desymmetrized by using lipase from Pseudomonas cepacia as catalyst and diallyl carbonate as alkoxycarbonylating agent. In all cases, the amino carbamates of R-configuration were recovered. Final selective cleavage of the N-allyloxycarbonyl moiety was carried out under mild reaction conditions, which demonstrates the high versatility and potential of this chemoenzymatic route as a source of intermediates in the synthesis of related optically active nitrogenated derivatives.
- Rios-Lombardia, Nicolas,Busto, Eduardo,Garcia-Urdiales, Eduardo,Gotor-Fernandez, Vicente,Gotor, Vicente
-
supporting information; body text
p. 2571 - 2574
(2009/07/25)
-
- 4-Amino-5-aryl-6-arylethynylpyrimidines: Structure-activity relationships of non-nucleoside adenosine kinase inhibitors
-
A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT-702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-ylpyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed.
- Matulenko, Mark A.,Paight, Ernest S.,Frey, Robin R.,Gomtsyan, Arthur,DiDomenico Jr., Stanley,Jiang, Meiqun,Lee, Chih-Hung,Stewart, Andrew O.,Yu, Haixia,Kohlhaas, Kathy L.,Alexander, Karen M.,McGaraughty, Steve,Mikusa, Joseph,Marsh, Kennan C.,Muchmore, Steven W.,Jakob, Clarissa L.,Kowaluk, Elizabeth A.,Jarvis, Michael F.,Bhagwat, Shripad S.
-
p. 1586 - 1605
(2008/02/01)
-
- CuI/L-proline-catalyzed coupling reactions of aryl halides with activated methylene compounds
-
(Chemical Equation Presented) The arylation of ethyl acetoacetate, ethyl benzoyl acetate, and diethyl malonate under the catalysis of Cul/L-proline in DMSO proceeds smoothly at 40-50°C in the presence of Cs2CO 3 to provide the 2-aryl
- Xie, Xiaoan,Cai, Guorong,Ma, Dawei
-
p. 4693 - 4695
(2007/10/03)
-
- Design and synthesis of 4-(α-hydroxymalonyl)phenylalanine as a new phosphotyrosyl mimetic and its use in growth factor receptor bound 2 Src-homology 2 (Grb2 SH2) domain-binding peptides
-
A new phosphotyrosyl mimetic 4-(α-hydroxymalonyl)phenylalanine and its incorporation into a Grb2 SH2 domain-binding tripeptide are presented. In whole-cell studies using malonyl ethyl ester prodrug derivatives, it was observed that the 4-(α-hydroxymalonyl
- Kang, Sang-Uk,Worthy, Karen M.,Bindu, Lakshman K.,Zhang, Manchao,Yang, Dajun,Fisher, Robert J.,Burke Jr., Terrence R.
-
p. 5369 - 5372
(2007/10/03)
-
- First heterogeneously palladium catalysed α-arylation of diethyl malonate
-
Pd exchanged NaY zeolites ([Pd(0)]-, [Pd(II)]- and entrapped [Pd(NH3)4]) exhibit a good activity towards the α-arylation of carbonyl compounds using different para-substituted aryl bromides. Low Pd-concentrations (only 2 mol%) are required to observe interesting activity. The catalysts can easily be separated from the reaction mixture and reused without any loss in activity. For large-scale applications the alternative use of an insoluble base as K2CO3 seems to be promising. The electronic nature of the aryl halides plays a limited role concerning the rate of the reaction.
- Djakovitch, Laurent,K?hler, Klaus
-
p. 101 - 107
(2007/10/03)
-
- ARYLATION OF DIETHYL MALONATE VIA NUCLEOPHILIC SUBSTITUTION REACTIONS WITH CYCLOPENTADIENYLIRON COMPLEXES OF CHLOROARENES
-
Reaction of an η6-chloroarene-η5-cyclopentadienyliron hexafluorophosphate with diethyl malonate in the presence of K2CO3 in THF/DMSO gave a corresponding SNAr product, η6-diethyl arylmalonate-η5-cyclopentadienyliron hexafluorophosphate, which, upon pyrolic sublimation, resulted in the liberation of the arylated malonic ester.Such esters prepared in the present work included RPhCH(COOEt)2, with R = o-, m- or p-CH3, 2,6-(CH3)2, or o-, m- or p-Cl.
- Abd-El-Aziz, Alaa S.,Lee, Choi Chuck,Piorko, Adam,Sutherland, Ronald G.
-
p. 291 - 300
(2007/10/02)
-
- COPPER(I)-PROMOTED COUPLING REACTION OF ARYL HALIDES WITH SODIUM DIETHYLMALONATE
-
Copper(I)-promoted coupling reaction of aryl halides with sodium diethylmalonate occured smoothly in dioxane.The qualitative trends in the activity of copper(I) salt followed the order: CuBr > CuI > CuBF4(CH3CN)4 > CuCl.The activity was lowered in the presence of coordinating molecule such as acetonitrile, pyridine, NaI, phosphine, and sulfide.The reaction was generally applicable to aryl halides with various substituents.
- Setsune, Jun-ichiro,Matsukawa, Kimihiro,Wakemoto, Hirofumi,Kitao, Teijiro
-
p. 367 - 370
(2007/10/02)
-