Selective Monomethylation of Anilines by Cu(OAc)<sub>2</sub>-Promoted Cross-Coupling with MeB(OH)<sub>2</sub>

González, Israel; Mosquera, Jesús; Guerrero, César; Rodríguez, Ramón Piloto; Cruces, Jacobo

doi:10.1021/ol802882k

Cited by 66 publications

(24 citation statements)

References 23 publications

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“…1d ) 30 – 32 . However, the application of the oxidative coupling to chemical glycosylation is challenged by a limited knowledge about reactions of C( sp 3 ) nucleophiles, as well as the unpredictability of stereochemical course in the C−O bond-forming step 33 – 36 . Phenols and amines with suitable nucleophilicity are optimal substrates for the coupling with C( sp 2 ) partners and only isolated examples of cross-coupling of trifluoroborates with aliphatic alcohols have been reported 37 , 38 .…”

Section: Introductionmentioning

confidence: 99%

Stereoselective oxidative glycosylation of anomeric nucleophiles with alcohols and carboxylic acids

Yang¹,

Zhu²,

Walczak³

2018

Nat Commun

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Oligosaccharides, one of the most abundant biopolymers, are involved in numerous biological processes. Although many efforts have been put in preparative carbohydrate chemistry, achieving optimal anomeric and regioselectivities remains challenging. Herein we describe an oxidative glycosylation method between anomeric stannanes and oxygen nucleophiles resulting in the formation of a C−O bond with consistently high anomeric control for glycosyl donors bearing a free C2-hydroxyl group. These reactions are promoted by hypervalent iodine reagents with catalytic or stoichiometric amounts of Cu or Zn salts. The generality of this transformation is demonstrated in 42 examples. Mechanistic studies indicate that the oxidative glycosylation is initiated by the hydroxyl-guided delivery of the hypervalent iodine and tosylate into the anomeric position, and results in excellent 1,2-trans selectivity. The unique mechanistic paradigm, high selectivities, and mild reaction conditions make this method suitable for the synthesis of oligosaccharides and for integration with other methodologies such as automated synthesis.

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Section: Introductionmentioning

confidence: 99%

Stereoselective oxidative glycosylation of anomeric nucleophiles with alcohols and carboxylic acids

Yang¹,

Zhu²,

Walczak³

2018

Nat Commun

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“…N -Methyl-4-(methylthio)aniline ( 161 ) and 5-chloro- N -methylpyridin-2-amine ( 162 ) were synthesized from the corresponding commercially available demethylated derivatives ( 154 and 160 , respectively) using the Chan-Lam selective monomethylation procedure, which involves copper(II)-promoted coupling of anilines and methylboronic acid [28] (Scheme S2 in the Supporting Information). Subsequently, 161 was oxidized to the sulfoxide ( 163 ) and sulfone ( 164 ) intermediates, as described above.…”

Section: Resultsmentioning

confidence: 99%

Development and characterization of 3-(benzylsulfonamido)benzamides as potent and selective SIRT2 inhibitors

Khanfar¹,

Quinti²,

Wang³

et al. 2014

European Journal of Medicinal Chemistry

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Inhibitors of sirtuin-2 deacetylase (SIRT2) have been shown to be protective in various models of Huntington's disease (HD) by decreasing polyglutamine aggregation, a hallmark of HD pathology. The present study was directed at optimizing the potency of SIRT2 inhibitors containing the neuroprotective sulfobenzoic acid scaffold and improving their pharmacology. To achieve that goal, 176 analogues were designed, synthesized, and tested in deacetylation assays against the activities of major human sirtuins SIRT1-3. This screen yielded 15 compounds with enhanced potency for SIRT2 inhibition and 11 compounds having SIRT2 inhibition equal to reference compound AK-1. The newly synthesized compounds also demonstrated higher SIRT2 selectivity over SIRT1 and SIRT3. These candidates were subjected to a dose-response bioactivity assay, measuring an increase in α-tubulin K40 acetylation in two neuronal cell lines, which yielded five compounds bioactive in both cell lines and eight compounds bioactive in at least one of the cell lines tested. These bioactive compounds were subsequently tested in a tertiary polyglutamine aggregation assay, which identified five inhibitors. ADME properties of the bioactive SIRT2 inhibitors were assessed, which revealed a significant improvement of the pharmacological properties of the new entities, reaching closer to the goal of a clinically-viable candidate.

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“…4‐Methyl‐ N ‐meth ylaniline (5e): Yellow liquid; 1 H NMR (400 MHz, CDCl 3 ): δ = 7.00 (d, J = 8.1 Hz, 2H), 6.55 (d, J = 8.4 Hz, 2H), 2.82 (s, 3H), 2.24 (s, 3H). 13 C{ 1 H} NMR (100 MHz, CDCl 3 ): δ = 147.28, 129.82, 126.63, 112.75, 31.25, 20.52.…”

Section: Methodsmentioning

confidence: 99%

N–Alkylation of Amines Catalyzed by a Ruthenium–Pincer Complex in the Presence of in situ Generated Sodium Alkoxide

et al. 2019

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We report the use of ruthenium–NNN‐pincer complexes of the type (R2NNN)RuCl2(PPh3) (R = tBu, iPr, Cy and Ph) for the catalytic N‐alkylation of primary amines under solvent‐free conditions. For the first time, the base that is required to promote these reactions is generated in situ from the alcohol by the use of sodium. The resulting sodium alkoxide regenerates the alcohol substrate while acting as the water scavenger thus mitigating the need of an additional base. Among the catalysts screened, (tBu2NNN)RuCl2(PPh3) (0.02 mol‐%) gives very high turnovers and good yields at 140 °C. The (tBu2NNN)RuCl2(PPh3) catalyzed N‐alkylation tolerates a variety of amine and alcohol substrates. While excellent turnover (29000) was obtained for the (tBu2NNN)RuCl2(PPh3) (0.002 mol‐%) catalyzed alkylation of aniline with cyclohexyl methanol, the turnovers obtained in the corresponding catalytic methylation of p‐anisidine was also very high (12000). The (tBu2NNN)RuCl2(PPh3) catalyzed reactions have also been accomplished under open‐vessel conditions resulting in a net dehydrogenative coupling reaction. This protocol has been used to transform benzene‐1,2‐diamines to benzimidazoles with high productivity (12000 turnovers). DFT studies indicate that while β‐hydride elimination is rate‐determining (RDTS: 24.31 kcal/mol) for the alcohol dehydrogenation segment which is endothermic, insertion of the imine is rate‐determining (RDTS: 11.26 kcal/mol) for its hydrogenation that is exothermic.

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Selective Monomethylation of Anilines by Cu(OAc)₂-Promoted Cross-Coupling with MeB(OH)₂

Cited by 66 publications

References 23 publications

Stereoselective oxidative glycosylation of anomeric nucleophiles with alcohols and carboxylic acids

Stereoselective oxidative glycosylation of anomeric nucleophiles with alcohols and carboxylic acids

Development and characterization of 3-(benzylsulfonamido)benzamides as potent and selective SIRT2 inhibitors

N–Alkylation of Amines Catalyzed by a Ruthenium–Pincer Complex in the Presence of in situ Generated Sodium Alkoxide

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Selective Monomethylation of Anilines by Cu(OAc)2-Promoted Cross-Coupling with MeB(OH)2

Cited by 66 publications

References 23 publications

Stereoselective oxidative glycosylation of anomeric nucleophiles with alcohols and carboxylic acids

Stereoselective oxidative glycosylation of anomeric nucleophiles with alcohols and carboxylic acids

Development and characterization of 3-(benzylsulfonamido)benzamides as potent and selective SIRT2 inhibitors

N–Alkylation of Amines Catalyzed by a Ruthenium–Pincer Complex in the Presence of in situ Generated Sodium Alkoxide

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Product

Resources

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Selective Monomethylation of Anilines by Cu(OAc)₂-Promoted Cross-Coupling with MeB(OH)₂