6301-54-8Relevant academic research and scientific papers
Conformational Studies by Dynamic Nuclear Magnetic Resonance. 59. Stereodynamics of Conformational Enantiomers in the Atropisomers of Hindered Naphthylcarbinols
Casarini, Daniele,Lunazzi, Lodovico,Mazzanti, Andrea
, p. 3315 - 3323 (1997)
Naphthyldialkylmethanols ArRR'COH (Ar = 1-naphthyl or 1-naphthyl-2-methyl) exist as a pair of atropisomers created by the restricted rotation about the Ar-COH bond.They can be detected by low-temperature NMR spectroscopy but can also be separated as stable compounds at room temperature if both the alkyl substituents are bulky tert-butyl groups (one such example is provided by compound 1, R = R' = But with Ar = 1-naphthyl).The free energies of activation (ΔG%) for the interconversion of these atropisomers were found to vary between 7.6 kcal mol-1 (as in 7, R = R' = Me, Ar = 1-naphthyl-2-methyl) and 32.9 kcal mol-1 (as in 1).The syn-periplanar (sp) or anti-periplanar (ap) structires were assigned either by means of difference NOE experiments or by taking advantage of the H-8 chemical shifts which are vastly different in the two atropisomers.Depending on the substituents the more stable species at the equilibrium can be either the sp or the ap atropisomer.When R = R' = Pri and R = R' = Et (respectively 2 and 3 if Ar = 1-naphthyl), the sp atropisomers adopt an asymmetric conformation, thus creating a pair of conformational enantiomers which interchange by rotating the isopropyl or the ethyl groups about the appropriate sp3-sp3 bonds, with ΔG% values of 7.2 and 6.1 kcal mol-1, respectively.On the contrary the corresponding 3-ap and 2-ap atropisomers adopt a symmetric (meso) conformation, as predicted by molecular mechanics calculations.In the case of R=Pri, R'=Et, and Ar=1-naphthyl (10-sp atropisomer), two asymmetric conformers were found to be appreciably populated (ratio 9:1 at -135 deg C).
Direct α-Arylation of Alcohols with Aryl Halides through a Radical Chain Mechanism
Aoki, Kohei,Yonekura, Kyohei,Ikeda, Yuko,Ueno, Ryota,Shirakawa, Eiji
supporting information, p. 2200 - 2204 (2020/05/05)
Alcohols were found to be arylated directly at their α-C?H bond with aryl halides in the presence of a base and a substoichiometric amount of t-BuOOt-Bu through a homolytic aromatic substitution mechanism. (Figure presented.).
Preparation of Quaternary Centers via Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling of Tertiary Sulfones
Ariki, Zachary T.,Maekawa, Yuuki,Nambo, Masakazu,Crudden, Cathleen M.
supporting information, p. 78 - 81 (2018/01/17)
We describe the development of a nickel-catalyzed Suzuki-Miyaura cross-coupling of tertiary benzylic and allylic sulfones with arylboroxines. A variety of tertiary sulfones, which can easily be prepared via a deprotonation-alkylation route, were reacted to afford symmetric and unsymmetric quaternary products in good yields. We highlight the use of either BrettPhos or Doyle's phosphines as effective ligands for these challenging desulfonative coupling reactions. The utility of this methodology was demonstrated in the concise synthesis of a vitamin D receptor modulator analogue.
Selective reaction of benzyl alcohols with HI gas: Iodination, reduction, and indane ring formations
Matsumoto, Shoji,Naito, Masafumi,Oseki, Takehisa,Akazome, Motohiro,Otani, Yasuhiko
, p. 7254 - 7259 (2017/11/24)
Reactions of benzyl alcohols with HI in solvent-free conditions were examined. Three types of reactions (iodination, reduction, and ring formation) occurred depending on the degree of crowding around the benzyl position and the benzylic stabilization of substrates. Results also showed that the ring formation to give indanes proceeded efficiently when HI was used, and that compounds with electron-rich aromatic rings gave indane derivatives in good yields.
Discovery of flexible naphthyltriazolylmethane-based thioacetic acids as highly active uric acid transporter 1 (URAT1) inhibitors for the treatment of hyperuricemia of gout
Zhang, Xiansheng,Wu, Jingwei,Liu, Wei,Liu, Yuqiang,Xie, Yafei,Shang, Qian,Zhou, Zhixing,Xu, Weiren,Tang, Lida,Wang, Jianwu,Zhao, Guilong
, p. 260 - 281 (2017/05/31)
Background: Gout is the most common inflammatory arthritis, which, if left untreated or inadequately treated, will lead to joint destruction, bone erosion and disability due to the crystal deposition. Uric acid transporter 1 (URAT1) was the promising therapeutic target for urate-lowering therapy. Objective: The goal of this work is to understand the structure-activity relationship (SAR) of a potent lesinurad-based hit, sodium 2-((5-bromo-4-((4-cyclopropyl-naphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetate (1c), and based on that discover a more potent URAT1 inhibitor. Methods: The SAR of 1c was systematically explored and the in vitro URAT1 inhibitory activity of synthesized compounds 1a-1t was determined by the inhibition of URAT1-mediated [8-14C]uric acid uptake by human embryonic kidney 293 (HEK293) cells stably expressing human URAT1. Results: Twenty compounds 1a-1t were synthesized. SAR analysis was performed. Two highly active URAT1 inhibitors, sodium 2-((5-bromo-4-((4-n-propylnaphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetate (1j) and sodium 2-((5-bromo-4-((4-bromonaphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetate (1m), were identified, which were 78- and 76-fold more active than parent lesinurad in in vitro URAT1 inhibitory assay, respectively (IC50 values for 1j and 1m were 0.092 μM and 0.094 μM, respectively, against human URAT1 vs 7.18 μM for lesinurad). Conclusion: Two highly active URAT1 inhibitors were discovered. The SAR exploration also identified more flexible naphthyltriazolylmethane as a novel molecular skeleton that will be valuable for the design of URAT1 inhibitors, as indicated by the observation that many of the synthesized naphthyltriazolylmethane-bearing derivatives (1b-1d, 1g, 1j and 1m) showed significantly improved UART1 inhibitory activity (sub-micromolar IC50 values) as compared with lesinurad which has the rigid naphthyltriazole skeleton.
The lewis base-catalyzed silylation of alcohols-a mechanistic analysis
Patschinski, Pascal,Zhang, Cong,Zipse, Hendrik
, p. 8348 - 8357 (2015/03/18)
Reaction rates for the base-catalyzed silylation of primary, secondary, and tertiary alcohols depend strongly on the choice of solvent and catalyst. The reactions are significantly faster in Lewis basic solvents such as dimethylformamide (DMF) compared with those in chloroform or dichloromethane (DCM). In DMF as the solvent, the reaction half-lives for the conversion of structurally similar primary, secondary, and tertiary alcohols vary in the ratio 404345:20232:1. The effects of added Lewis base catalysts such as 4-N,N-dimethylaminopyridine (DMAP) or 4-pyrrolidinopyridine (PPY) are much larger in apolar solvents than in DMF. The presence of an auxiliary base such as triethylamine is required in order to drive the reaction to full conversion.
Observation of 1,3-diketones formation in the reaction of bulky acyl chlorides with methyllithium
Zhang, Jian,Yang, Nianfa,Yang, Liwen
experimental part, p. 6415 - 6423 (2012/09/08)
The formation of 1,3-diketones was observed in the reactions of bulky acyl chlorides with methyllithium. The reaction products depend on the steric hindrance around the carbonyl group of the acyl chloride and the electronic effect of the group(s) linked to the carbonyl. When the steric hindrance around the carbonyl group of the acyl chloride is big enough, the 1,3-diketone is the only product. In the case of the moderate hindrance around the carbonyl group of the acyl chloride, a moderate yield of 1,3-diketone is obtained and some tertiary alcohol is generated. When there is no steric hindrance around the carbonyl group of the acyl chloride, the tertiary alcohol is the only product. When the steric hindrance around the carbonyl group is moderate and an electron-donating group is connected to the carbonyl of the acyl chloride, all three products-ketone, 1,3-diketone and tertiary alcohol-can be isolated from the reaction mixture after long reaction times.
Improved preparative route toward 3-arylcyclopropenes
Sherrill, William M.,Kim, Ryan,Rubin, Michael
, p. 8610 - 8617 (2008/12/21)
A convenient preparative protocol for the synthesis of various 3-arylcyclopropenes in a multigram scale is disclosed. Optimization of the reaction conditions and isolation procedures allowed for significant improvement of the chemical yields of these strained products. The described protocol was used for efficient preparation of a series of 3-methyl-3-arylcyclopropenes possessing different substituents in the aromatic ring. The effect of substitution in the aryl group on the stability of 3-arylcyclopropenes, as well as the corresponding precursors, is discussed.
Unusual inhibition effect of 1-(1-naphthyl)-1-methylethylhydroperoxide on the liquid-phase oxidation of isopropylarenes. GC-MS and theoretical studies of the thermal decomposition of 1-naphthyl- and 1-anthryl-1- methylethylhydroperoxides
Mazurkiewicz, Roman,Zawadiak, Jan,Orlinska, Beata,Hefczyc, Barbara,Stec, Zbigniew,Grymel, Miroslawa,Fiedorow, Piotr,Koroniak, Henryk
, p. 289 - 295 (2012/12/22)
All five possible 1-aryl-1methylethylhydroperoxides derived from naphthalene and anthracene were synthesized and their thermal decomposition in GC-MS conditions was investigated to explain the unusual inhibition effect of 1-(1-naphthyl)-1-methylethylhydroperoxide on the liquid-phase oxidation of isopropylarenes. 2-(1-Aryloxy)propenes were identified as the main decomposition products of 1-(1-naphthyl)-1-methylethylhydroperoride and 1-(1-anthryl)-1- methylethylhydroperoxide. The relatively unstable 2-aryloxypropenes have thus far never been described as thermal decomposition products of 1-aryl-1-methylethylhydroperoxides. The plausible mechanism of the formation of 2-(1-aryloxy)propenes was proposed on the basis of AM-1 calculations of the possible rearrangement paths of the alkoxy radicals derived from the investigated hydroperoxides. The mechanism explains the inhibition effect of 1-(1-naphthyl)-1-methylethylhydroperoxide on the oxidation of isopropylarenes.
Highly alkyl-selective addition to ketones with magnesium ate complexes derived from Gignard reagents
Hatano, Manabu,Matsumura, Tokihiko,Ishihara, Kazuaki
, p. 573 - 576 (2007/10/03)
(Chemical Equation Presented) A highly efficient alkyl-selective addition to ketones with magnesium ate complexes derived from Grignard reagents and alkyllithiums is described. The nucleophilicity of R in R3MgLi is remarkably increased compared to that of the original RLi or RMgX, while the basicity of R3MgLi is decreased. Furthermore, a highly R-selective addition to ketones is demonstrated using RMe2MgLi in place of R 3MgLi.
