694-54-2Relevant articles and documents
Hemiacetal anions: A model for tetrahedral reaction intermediates
Baer, Susan,Brinkman, Elizabeth A.,Brauman, John I.
, p. 805 - 812 (1991)
A deprotonated hemiacetal ion is used as a model intermediate for nucleophilic addition reactions at a carbonyl group. The acidity of the cyclic hemiacetal 2-hydroxytetrahydropyran has been estimated to be ΔGoacid ≥ 351 ± 2 kcal/mol. The basicity of the deprotonated ion was found to be 347 ± 2 kcal/mol, different from the acidity by 4 kcal/mol. This difference is ascribed to an isomerization reaction in the ion. The electron affinity of the neutral radical corresponding to removal of an electron from the ion was measured with use of electron photodetachment spectroscopy and was found to be 49.6 ± 2.5 kcal/mol. The structure of the isomerized ion is assigned as a hydrogen bond stabilized enolate ion. The implications of the strong acidity of the hemiacetal for the stability of tetrahedral reaction intermediates are discussed. Thermochemical arguments suggest that tetrahedral adducts of this type are often global minima on the reaction potential surface. The addition reactions of different alkoxide-alcohol complexes with benzaldehyde are discussed in terms of the stability of the corresponding tetrahedral addition product.
Three-Step Synthesis of 3-Aminoseptanoside Derivatives by Using Lithiated Methoxyallene and δ-Siloxynitrones
Jasiński, Marcin,Utecht, Greta,Fruziński, Andrzej,Reissig, Hans-Ulrich
, p. 893 - 905 (2016)
A three-step approach to enantiomerically pure 3-aminoseptanoside derivatives by addition of lithiated methoxyallene to δ-silylated aldopentose-derived nitrones, followed by Bronsted acid mediated cyclization and chemoselective N-O bond scission is presented. For the addition of the methoxyallene anion leading to 3,6-dihydro-1,2-oxazines, excellent syn-diastereoselectivities were observed in the case of d-xylose- and l-arabinose-derived nitrones, whereas the d-ribose analogue provided syn- and anti-configured products in an approximately 2:1 ratio. Subsequent proton-induced reactions provided the corresponding dimethyl ketals as kinetic products, which slowly converted into bicyclic oxepanoides formed in a highly cis-selective manner. The final reductive ring opening was performed in good yields by using an excess of samarium(II) iodide. With a selected compound it was demonstrated that this type of product is a suitable precursor for the preparation of polyfunctionalized oxepanopyrrolidine derivatives.
A novel and general α-regioselective and highly enantioselective prenylation of aldehydes
Cheng, Hin-Soon,Loh, Teck-Peng
, p. 4990 - 4991 (2003)
This communication describes a novel and general method for the α-regioselective prenylation of carbonyl compounds. This method which employs chiral γ-prenyl-1,5 diol as the prenyl source using a catalytic amount of Lewis or Bronsted acid affords the products in excellent enantioselectivies (up to 98% ee) and good yields (up to 95% yield). Furthermore, the reaction is highly chemoselective, reacting selectively with the aldehyde without affecting the enone and the α,β-unsaturated ester functionalities. Detailed mechanistic studies disclose the facile epimerization of aromatic alcohol in dichloromethane in the presence of In(OTf)3. The use of non-polar solvents such as hexane in the presence of In(OTf)3 or TfOH effectively suppresses this epimerization. Copyright
Total synthesis of (±)-quinolizidine 217A
Pearson,Suga
, p. 9910 - 9918 (1998)
Several 1,4-disubstituted quinolizidines have been isolated in minute quantities from the skin of certain poisonous frogs and toads. The structures of these alkaloids have been proposed mainly on the basis of MS and IR spectroscopic data. We report the first total synthesis of a naturally occurring alkaloid of this type, quinolizidine 217A. After examination of several azide-based routes, the cyclization of an azide onto an ester- bearing alkene provided a 3,4,5,6-tetrahydropyridine that was reduced in a stereoselective fashion to produce a cis-2,6-disubstituted piperidine (25 → 31 → 32). Transformation of 32 into quinolizidine 217A (2) and its C(1) epimer (41) were accomplished in a straightforward fashion. Synthetic quinolizidine 217A was found to be identical to the natural alkaloid, confirming its stereostructure. Compound 41 has the same stereostructure as that proposed for the alkaloid quinolizidine 207I, a compound whose configuration was recently revised as a result of synthetic studies by Momose et al., who synthesized a 1,4-disubstituted quinolizidine with the configuration previously proposed for quinolizidine 207I and found the synthetic material to be epimeric with the natural material. Compound 41 should provide a useful point of comparison for future studies on the stereostructure of natural or synthetic quinolizidine 207I.
Oxasqualenoids from Laurencia viridis: Combined spectroscopic-computational analysis and antifouling potential
Cen-Pacheco, Francisco,Santiago-Benítez, Adrián J.,García, Celina,álvarez-Méndez, Sergio J.,Martín-Rodríguez, Alberto J.,Norte, Manuel,Martín, Victor S.,Gavín, José A.,Fernández, José J.,Daranas, Antonio Hernández
, p. 712 - 721 (2015)
The chemical study of the red alga Laurencia viridis has led to the isolation of four new polyether triterpenoids: 28-hydroxysaiyacenol B (2), saiyacenol C (3), 15,16-epoxythyrsiferol A (4), and 15,16-epoxythyrsiferol B (5). The structures of 2 and 3 were established mainly by NMR data analysis and comparison with the well-known metabolite dehydrothyrsiferol (1). However, due to the existence of a nonprotonated carbon within the epoxide functionality, stereochemical assignments in 4 and 5 required an in-depth structural study that included NOESY data, J-based configuration analysis, comparison with synthetic models, and DFT calculations. The biological activities of the new metabolites and other related oxasqualenoids were evaluated for the first time against a panel of relevant biofouling marine organisms, and structure-activity conclusions were obtained.
Mechanistically Guided Design of an Efficient and Enantioselective Aminocatalytic α-Chlorination of Aldehydes
Hutchinson, George,Alamillo-Ferrer, Carla,Burés, Jordi
supporting information, p. 6805 - 6809 (2021/05/29)
The enantioselective aminocatalytic α-chlorination of aldehydes is a challenging reaction because of its tendency to proceed through neutral intermediates in unselective pathways. Herein we report the rational shift to a highly selective reaction pathway involving charged intermediates using hexafluoroisopropanol as solvent. This change in mechanism has enabled us to match and improve upon the yields and enantioselectivities displayed by previous methods while using cheaper aminocatalysts and chlorinating agents, 80-95% less amount of catalyst, convenient temperatures, and shorter reaction times.
6-HETEROARYLOXY BENZIMIDAZOLES AND AZABENZIMIDAZOLES AS JAK2 INHIBITORS
-
Paragraph 1066; 1067, (2021/11/13)
The present disclosure provides 6-heteroaryloxy benzimidazole and azabenzimidazole compounds and compositions thereof useful for inhibiting JAK2.
Size- And Shape-Selective Catalysis with a Functionalized Self-Assembled Cage Host
Da Camara, Bryce,Hooley, Richard J.,Ngai, Courtney,Woods, Connor Z.
, p. 12862 - 12871 (2021/09/28)
A self-assembled Fe4L6 cage with internally oriented carboxylic acid functions was shown to catalyze a variety of dissociative nucleophilic substitution reactions that proceed via oxocarbenium ion or carbocation intermediates. The catalytic behavior of the cage was compared to that of other small acid catalysts, which illustrated large differences in reactivity of the cage-catalyzed reactions, dependent on the structure of the substrate. For example, only a 5% cage confers a 1000-fold rate acceleration of the thioetherification of vinyldiphenylmethanol when compared to the rate with free carboxylic acid surrogates but only a 52-fold acceleration in the formation of small thioacetals. Multiple factors control the variable reactivity in the host, including substrate inhibition, binding affinity, and accessibility of reactive groups once bound. Simple effective concentration increases or the overall charge of the cage does not explain the variations in reactivity shown by highly similar reactants in the host: small differences in structure can have large effects on reactivity. Reaction of large spherical guests is highly dependent on substitution, whereas flat guests are almost unaffected by size and shape differences. The cage is a promiscuous catalyst but has strong selectivity for particular substrate shapes, reminiscent of enzymatic activity.
Dual C(sp3)-H Functionalization of Cyclic Ethers via Singlet Oxygen-Mediated Ring Opening and Ring Closing
Yuan, Xu,Yu, Xianglin,He, Kun,Zhang, Ruihan,Xiao, Weilie,Lin, Jun,Zhan, Zhajun,Cheng, Xiaohong,Shao, Zhihui,Jin, Yi
supporting information, p. 8267 - 8272 (2021/10/25)
A metal-free dual C(sp3)-H bond functionalization of saturated cyclic ethers via photooxidative singlet oxygen-mediated ring opening and ring closing has been developed, providing a method for generating hydrobenzofurans/pyrans/dioxins. Mechanistic studies have confirmed that ring-opening intermediates were effectively generated by singlet oxygen-mediated C(sp3)-H activation and efficiently reacted with aldehydes and activated methylene compounds to form a wide array of products with high diastereoselectivities (up to >95:5 dr). This study is a rare example of α,β-dual C(sp3)-H bond functionalization of ethers.
A new catalytic approach for aerobic oxidation of primary alcohols based on a Copper(I)-thiophene carbaldimines
Lagerspets, Emi,Valbonetti, Evelyn,Eronen, Aleksi,Repo, Timo
, (2021/06/03)
We report here novel Cu(I) thiophene carbaldimine catalysts for the selective aerobic oxidation of primary alcohols to their corresponding aldehydes and various diols to lactones or lactols. In the presence of the in situ generated Cu(I) species, a persistent radical (2,2,6,6-tetramethylpiperdine-N-oxyl (TEMPO)) and N-methylimidazole (NMI) as an auxiliary ligand, the reaction proceeds under aerobic conditions and at ambient temperature. Especially the catalytic system of 1-(thiophen-2-yl)-N-(4-(trifluoromethoxy)phenyl)methanimine (ligand L2) with copper(I)-iodide showed high reactivity for all kind of alcohols (benzylic, allylic and aliphatic). In the case of benzyl alcohol even 2.5 mol% of copper loading gave quantitative yield. Beside high activity under aerobic conditions, the catalysts ability to oxidize 1,5-pentadiol to the corresponding lactol (86% in 4 h) and N-phenyldiethanolamine to the corresponding morpholine derivate lactol (86% in 24 h) is particularly noteworthy.
