- C-Arylglucoside synthesis: Triisopropylsilane as a selective reagent for the reduction of an anomeric C-phenyl ketal
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Reduction of tetra-O-benzyl-protected 1C-phenylglucoside using triethylsilane and BF3·OEt2 has been reported (Czernecki, S.; Ville, G. J. Org. Chem. 1989, 54, 610-612) to give exclusively 2,3,4,6-tetra-O-benzyl-β-1C-phenyl-1-deoxyglucoside. We have determined that this reduction actually gives a 4:1 mixture of anomers (β:α). We observed that the selectivity of the reduction is influenced by the steric bulk of the silane. The use of triisopropylsilane as a reducing agent gives >35:1 ratio (β:α) of 2,3,4,6-tetra-O-benzyl-β-1C-phenyl-1- deoxyglucoside.
- Ellsworth, Bruce A.,Doyle, Abigail G.,Patel, Manorama,Caceres-Cortes, Janet,Meng, Wei,Deshpande, Prashant P.,Pullockaran, Annie,Washburn, William N.
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- Glycosyl Cross-Coupling with Diaryliodonium Salts: Access to Aryl C -Glycosides of Biomedical Relevance
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A stereospecific cross-coupling reaction of anomeric nucleophiles with diaryliodonium triflates resulting in the synthesis of aryl C-glycosides is reported. This process capitalizes on a stereoretentive reaction of configurationally stable C1 stannanes and is promoted by a palladium catalyst in the presence of a bulky phosphine ligand that suppresses the undesired β-elimination. The utility of this reaction has been demonstrated in the preparation of a series of C-glycosides derived from common saccharides resulting in exclusive transfer of anomeric configuration from the anomeric nucleophile to the product, and in the synthesis of empagliflozin, a commercial antidiabetic drug.
- Yi, Duk,Zhu, Feng,Walczak, Maciej A.
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p. 1936 - 1940
(2018/04/12)
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- Highly Stereospecific Cross-Coupling Reactions of Anomeric Stannanes for the Synthesis of C-Aryl Glycosides
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We demonstrate that configurationally stable anomeric stannanes undergo a stereospecific cross-coupling reaction with aromatic halides in the presence of a palladium catalyst with exceptionally high levels of stereocontrol. In addition to a broad substrat
- Zhu, Feng,Rourke, Michael J.,Yang, Tianyi,Rodriguez, Jacob,Walczak, Maciej A.
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p. 12049 - 12052
(2016/10/03)
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- β-Selective C-arylation of silyl protected 1,6-anhydroglucose with arylalanes: The synthesis of SGLT2 inhibitors
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The stereoselective arylation of hydroxy protected 1,6-anhydro-β-d-glucose with arylalanes to provide β-C-arylglucosides is reported. Modification of triarylalanes, Ar3Al, with strong Br?nsted acids (HX) or AlCl3 produced more reactive arylating agents, Ar2AlX, while the incorporation of alkyl dummy ligands into the arylating agents was also viable. Me3Al and i-Bu2AlH were found useful in the in situ blocking of the C3-hydroxyl group of 2,4-di-O-TBDPS protected 1,6-anhydroglucose. The utility of the method was demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin.
- Henschke, Julian P.,Wu, Ping-Yu,Lin, Chen-Wei,Chen, Shi-Feng,Chiang, Pei-Chen,Hsiao, Chi-Nung
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p. 2295 - 2309
(2015/09/21)
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- β-Selective C-Arylation of Diisobutylaluminum Hydride Modified 1,6-Anhydroglucose: Synthesis of Canagliflozin without Recourse to Conventional Protecting Groups
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The β-selective phenylation of benzyl and boronate protected 1,6-anhydroglucose and the direct phenylation of unprotected 1,6-anhydroglucose (10), pretreated with i-Bu2AlH, i-Bu3Al, Et3Al, Me3Al, or n-octyl3Al, with triphenylalane or aryl(chloro)alanes is reported. The utility of the unprotected version of the method is demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin (1a), from commercially available 10 in one C-C bond-forming step. This approach circumvents the need for conventional protecting groups, and therefore no formal protection and deprotection steps are required. (Chemical Presented).
- Henschke, Julian P.,Lin, Chen-Wei,Wu, Ping-Yu,Tsao, Wen-Shing,Liao, Jyh-Hsiung,Chiang, Pei-Chen
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p. 5189 - 5195
(2015/05/27)
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- Diastereoselective Ni-catalyzed Negishi cross-coupling approach to saturated, fully oxygenated C-alkyl and C-aryl glycosides
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A Ni-catalyzed Negishi cross-coupling approach to C-glycosides is described with an emphasis on C-aryl glycosides. The combination of NiCl 2/PyBox in N,N′-dimethylimidazolidinone (DMI) enabled the synthesis of C-alkyl glycosides under mild reaction conditions. Moderate yields and β-selectivities were obtained for C-glucosides, and good yields and high α-selectivities were the norm for C-mannosides. For C-aryl glycosides, reactions employing Ni(COD)2/tBu-Terpy in N,N-dimethylformamide (DMF) were typically high yielding and provided C-glucosides with high β-selectivities (1:>10 α:β) and C-mannosides in moderate α-selectivities (3:1 α:β); α-C-aryl glycosides could be obtained by the combination of Ni(COD) 2/PyBox in DMF (>20:1 α:β). The collective studies suggest that stereochemical control of the C-glycosides is dependent on the substrate and catalysts combination. The Negishi protocol displays excellent functional group tolerance, as demonstrated by its use in the first total synthesis of the natural product salmochelin SX.
- Gong, Hegui,Gagne, Michel R.
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supporting information; scheme or table
p. 12177 - 12183
(2009/02/05)
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- An efficient synthesis of β-C-glycosides based on the conformational restriction strategy: Lewis acid promoted silane reduction of the anomeric position with complete stereoselectivity
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(Chemical Equation Presented) The reduction of glyconolactols having an anomeric carbon substituent by Et3SiH/TMSOTf proceeded with complete stereoselectivity to produce the corresponding β-C-glycosides when the substrates were conformationally restricted in the 4C 1-chair form by a 3,4-O-cyclic diketal or a 4,6-O-benzylidene protecting group. Thus, the efficient construction of β-C-glycosides was achieved on the basis of the conformation restriction strategy.
- Terauchi, Masaru,Abe, Hiroshi,Matsuda, Akira,Shuto, Satoshi
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p. 3751 - 3754
(2007/10/03)
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- SYNTHESIS OF C-GLUCOPYRANOSIDES ON THE BASIS OF THE REACTION OF ORGANOALUMINUM COMPOUNDS WITH A 2,3,4,6-TETRA-O-BENZYL-α-D-GLUCOPYRANOSIDE
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The reaction of 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl bromide with organoaluminum compounds containing various radicals leads to C-glucopyranosides in ca. 40-80 percent yields.High stereoselectivity of the reaction (α:β = 90:10) is observed when trial
- Tolstikov, G. A.,Prokhorova, N. A.,Spivak, A. Yu.,Khalilov, L. M.,Sultanmuratova, V. R.
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p. 1858 - 1863
(2007/10/02)
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- C-Glycosides. 7. Stereospecific C-Glycosylation of Aromatic and Heterocyclic Rings
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Stereospecific C-glycosylation of aromatic and heterocyclic rings can be realized by reacting the corresponding organolithium derivatives with benzylated lactones and reducing the so-obtained lactols with triethylsilane in the presence of boron trifluorid
- Czernecki, S.,Ville, G.
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p. 610 - 612
(2007/10/02)
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- Synthesis of C-Glucosides by Reactions of Glucosyl Halides with Organocuprates.
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Lithium dimethylcuprate reacts with trans-2-chloro-6-methyltetrahydropyran (1) via nucleophilic substitution predominantly with inversion of configuration to afford cis-2,6-dimethyltetrahydropyran (2).Similarly, lithium dialkylcuprates displace protected α-glucosyl bromides (5) with inversion to afford the β-C-glucosides, β-1-alkyl-1,5-anhydroglucitols (6).In contrast, Grignard reagents gave mixtures of α- and β- glucosides 6 and 7, while organolithium reagents gave only elimination to 9.
- Bihovsky Ron,Selick Caryn,Giusti Irena
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p. 4026 - 4031
(2007/10/02)
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- ORGANOMETALLICS IN ORGANIC SYNTHESIS. APPLICATIONS OF A NEW DIORGANOZINC REACTION TO THE SYNTHESIS OF C-GLYCOSYL COMPOUNDS WITH EVIDENCE FOR AN OXONIUM-ION MECHANISM
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The mechanistic and stereochemical features of a new organozinc-based substitution process 1,R2)-SPh + R32Zn --> heteroatom-C-(R1,R2,R3)>, first discovered during a total synthesis of the alkaloid mycotoxin α-cyclopiazonic acid, are described.Phenyl thioglycosides were valuable substrates in studying the nature of this reaction process.Since these sulfur compounds are converted into C-glycosyl compounds with some degree of stereoselectivity, the organozinc chemistry does provide a new entry to these biologically active substances.
- Kozikowski, Alan P.,Konoike, Toshiro,Ritter, Allen
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p. 109 - 124
(2007/10/02)
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