- C -Methylation of Alcohols, Ketones, and Indoles with Methanol Using Heterogeneous Platinum Catalysts
-
A versatile, selective, and recyclable heterogeneous catalytic method for the methylation of C-H bonds in alcohols, ketones, and indoles with methanol under oxidant-free conditions using a Pt-loaded carbon (Pt/C) catalyst in the presence of NaOH is reported. This catalytic system is effective for various methylation reactions: (1) the β-methylation of primary alcohols, including aryl, aliphatic, and heterocyclic alcohols, (2) the α-methylation of ketones, and (3) the selective C3-methylation of indoles. The reactions are driven by a borrowing-hydrogen mechanism. The reaction begins with the dehydrogenation of the alcohol(s) to afford aldehydes, which subsequently undergo a condensation reaction with the nucleophile (aldehyde, ketone, or indole), followed by hydrogenation of the condensation product by Pt-H species to yield the desired product. In all of the methylation reactions explored in this study, the Pt/C catalyst exhibits a significantly higher turnover number than other previously reported homogeneous catalytic systems. Moreover, it is demonstrated that the high catalytic activity of Pt can be rationalized in terms of the adsorption energy of hydrogen on the metal surface, as revealed by density functional theory calculations on different metal surfaces.
- Siddiki, S. M. A. Hakim,Touchy, Abeda S.,Jamil, Md. A. R.,Toyao, Takashi,Shimizu, Ken-Ichi
-
p. 3091 - 3103
(2018/04/14)
-
- A Convenient Ruthenium-Catalysed α-Methylation of Carbonyl Compounds using Methanol
-
An efficient ruthenium catalyst is reported, for the first time, to catalyse the α-methylation of ketones and esters using methanol as a green methylating agent. The in situ generated catalyst from the complexes [RuCp*Cl2]2or [RuCp*Cl2]nwith dpePhos provided up to quantitative yields in the presence of only 20 mol% of lithium tert-butoxide (LiO-t-Bu) as a base. Regioselective mono- or multi-methylation could be effectively controlled by temperature. This catalyst system was also effective for the one-pot sequential α-alkylation–α-methylation of methyl ketones and conjugate reduction–α-methylation of α,β-unsaturated ketones to synthesise α-branched ketones. An application of the α-methylation of esters using the ruthenium catalyst was demonstrated for an alternative catalytic synthesis of Ketoprofen. (Figure presented.).
- Dang, Tuan Thanh,Seayad, Abdul Majeed
-
supporting information
p. 3373 - 3380
(2016/11/13)
-
- Switching from S- to R-selectivity in the Candida antarctica lipase B-catalyzed ring-opening of ω-methylated lactones: Tuning polymerizations by ring size
-
Novozym 435-catalyzed ring-opening of a range of ω-methylated lactones demonstrates fascinating differences in rate of reaction and enantioselectivity. A switch from S- to R-selectivity was observed upon going from small (ring sizes ≤7) to large lactones (ring sizes ≥8). This was attributed to the transition from a cisoid to a transoid conformational preference of the ester bond on going from small to large lactones. The S-selectivity of the ring-opening of the small, cisoid lactones was low to moderate, while the R-selectivity of the ring-opening of the large transoid lactones was surprisingly high. The S-selectivity of the ring-opening of the small, cisoid lactones combined with the established R-selectivity of the transesterification of (aliphatic) secondary alcohols prevented polymerization from taking place. Ring-opening of the large, transoid lactones was R-selective with high enantioselectivity. As a result, these lactones could be polymerized, without exception, by straightforward kinetic resolution polymerization, yielding the enantiopure R-polyester with excellent enantiomeric excess (>99%).
- Van Buijtenen, Jeroen,Van As, Bart A. C.,Verbruggen, Marloes,Roumen, Luc,Vekemans, Jef A. J. M.,Pieterse, Koen,Hilbers, Peter A. J.,Hulshof, Lumbertus A.,Palmans, Anja R. A.,Meijer
-
p. 7393 - 7398
(2008/02/08)
-
- Enzyme-mediated enantioface-differentiating hydrolysis of α-substituted cycloalkanone enol esters
-
A new type of enzymatic hydrolysis, enantioface-differentiating hydrolysis of enol esters, is disclosed. As a result of screening, Pichia miso IAM 4682, a type of yeast, was selected as the best strain to perform the enantioselective hydrolysis of enol esters to give α-chiral ketones. For example, incubation of 1-acetoxy-2-methylcyclohexene (4a) with P. miso afforded (S)-2-methylcyclohexanone (5) in high optical yield. This enzymatic hydrolysis is applicable to various α-substituted cycloalkanone enol esters, and thereby chiral six-, eight-, ten-, and twelve-membered-ring ketones of 70-96% enantiomeric excess (ee) are easily prepared.
- Matsumoto, Kazutsugu,Tsutsumi, Seiji,Ihori, Tamiko,Ohta, Hiromichi
-
p. 9614 - 9619
(2007/10/02)
-
- Medium-ring Ketone Synthesis. Synthesis of Eight- to Twelve-membered Cyclic Ketones based on the Intramolecular Cyclization of Large-Membered Lactam Sulfoxides or Sulfones
-
An effective general method for the construction of medium-ring ketones from the corresponding ω-bromocarboxylic acids is described.When the diamide disulfide 10 was treated with NaBH4 and NaH in 2-propanol, reductive cleavage of the sulfur-sulfur bond and concomitant intramolecular coupling of the resulting thiolate anion with the terminal bromide took place and the large-ring lactam sulfide 7, which was the key intermediate for the synthesis of medium-ring ketones, was obtained.Although lithium diisopropyl amide (LDA) treatment of 11 followed by reductive desulfurization provided cycloundecanone (13d) in only 19.5percent yield, intramolecular cyclization of the α-methylated analogues 17 with LDA proceeded smoothly and the keto sulfoxides 18 were obtained in quantitative yields.In the case of the lactam sulfones 21, tert-BuOK was effective as a base for the intramolecular cyclization, affording the keto sulfones 22 in quantitative yields.The keto sulfoxides 18 and sulfones 22 were subjected to reductive desulfurization with Al-Hg to yield medium-ring ketones 19 and 13, respectively, in high yields.Keywords - medium-ring ketone; intramolecular cyclization; large-ring lactam sulfide; bis(2-methylaminophenyl) disulfide; 2-methylaminobenzenethiol; reductive desulfurization; sulfur-stabilized carbanion; active methylene
- Ohtsuka, Yasuo,Oishi, Takeshi
-
p. 454 - 465
(2007/10/02)
-
- Preparation of Macrocyclic Lactones by Ring Closure of Cesium Carboxylates
-
A series of ω-halo fatty acids, the longest being 16-iodohexadecanoic acid, was prepared by oxidation of the corresponding ketones with m-chloroperbenzoic acid in boiling chloroform, followed by ring opening usually with hydrogen iodide in acetic acid at 100 deg C.Solutions of these acids in dimethylformamide (DMF) at concentrations of 5E-3 - 5E-2 M were treated with an equivalent amount of dry Cs2CO3.The solutions were stirred at 40 deg C overnight.Workup of the reaction mixture produced a mixture of (macro)cyclic lactone (macrolide) and its dimer (dilide).For the case of 16-iodohexanoic acid the lactone was isolated in 85percent yield.Yields for other large ring macrolides were also excellent.It was demonstrated that substitution by carboxylate on a secondary halide also goes well to afford the corresponding macrolide with no detectable amount of elimination.The effects of ring size, concentration, and solvent on the ring closure of the cesium carboxylates formed in situ were investigated.DMF is the best solvent of those investigated for the ring closure.Cesium carboxylates also undergo more readily ring closure and in far better yield than the carboxylates of lithium, sodium, potassium, rubidium, silver, thallium, magnesium, strontium, or barium.The S-lactone of ricinelaidic acid was prepared optically pure in 80percent yield from optically pure mesylate of R-ricinelaidic acid, which was treated with cesium carbonate in dry DMF.This demonstrates that the ring closure proceeds with the anticipated SN2 inversion at the hydroxyl-bearing carbon atom.With the same approach optically pure S-zearalenone was protected and subjected to ring opening, and the hydroxyl group was activated as mesylate.Some racemization was found to occur in the ring-opening step.On treatment of this material with dry cesium carbonate in DMF, the desired ring closure took place in 80percent yield to provide an excess of the protected R enantiomer of zearalenone.On the basis of these results, some speculations are made concerning the action of cesium in promoting ring closure to macrocyclic lactones.
- Kruizinga, Wim H.,Kellogg, Richard M.
-
p. 5183 - 5189
(2007/10/02)
-
- Metalation of 1,3-Dithiolanes. Mercaptan Synthesis and Carbonyl Transposition
-
The reaction of 1,3-dithiolanes with n-butyllithium results in fragmentation to the corresponding thiocarbonyl compound followed by furhter reaction with n-butyllithium.All four types of thiocarbonyl reactions are observed: reduction, S-addition, C-addition, double addition.Synthetic applications of this reaction for the synthesis of secondary mercaptans and 1,2-carbonyl transposition (23 -> 24a-c) are described.
- Wilson, Stephen R.,Georgiadis, Gregory M.,Khatri, Hiralal N.,Bartmess, John E.
-
p. 3577 - 3583
(2007/10/02)
-
- Methylation of cyclohexanone with simultaneous dehydrogenation
-
Catalytic process for alkylating ketones carrying at least one methyl or methylene group in α-position to the carbonyl group by reacting them with primary alcohols in the presence of copper and/or silver catalysts.
- -
-
-