- Electronically tuneable orthometalated RuII–NHC complexes as efficient catalysts for C–C and C–N bond formations via borrowing hydrogen strategy
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The catalytic activities of a series of simple and electronically tuneable cyclometalated RuII–NHC complexes (2a–d) were explored in various C–C/N bond formations following the borrowing hydrogen process. Slight modifications in the ligand backbone were noted to tune the activities of these complexes. Among them, the complex 2d featuring a 1,2,4-triazolylidene donor with a 4-NO2–phenyl substituent displayed the highest activity for the coupling of diverse secondary and primary alcohols with a low catalyst loading of 0.01 mol% and a sub-stoichiometric amount of inexpensive KOH base. The efficacy of this simple system was further showcased in the challenging one-pot unsymmetrical double alkylation of secondary alcohols using different primary alcohols. Moreover, the complex 2d also effectively catalyses the selective mono-N-methylation of various aromatic and aliphatic primary amines using methanol to deliver a range of N-methyl amines. Mechanistically, the β-alkylation reaction follows a borrowing hydrogen pathway which was established by the deuterium labelling experiment in combination with various control experiments. Intriguingly, in situ1H NMR and ESI-MS analyses evidently suggested the involvement of a Ru–H species in the catalytic cycle and further, the kinetic studies revealed a first order dependence of the reaction rate on the catalyst as well as the alcohol concentrations.
- Illam, Praseetha Mathoor,Rit, Arnab
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- Potassium Base-Catalyzed Michael Additions of Allylic Alcohols to α,β-Unsaturated Amides: Scope and Mechanistic Insights
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We report herein the first KHMDS-catalyzed Michael additions of allylic alcohols to α,β-unsaturated amides through allylic isomerization. The reaction proceeds smoothly in the presence of only 5 mol% of KHMDS to afford a variety of 1,5-ketoamides in high yields. Mechanistic investigations, including experimental and computational studies, reveal that the KHMDS-catalyzed in-situ generation of the enolate from the allylic alcohol through a tunneling-assisted 1,2-hydride shift is the key to the success of this transformation. (Figure presented.).
- Kurouchi, Hiroaki,Sai, Masahiro
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p. 3585 - 3591
(2021/06/27)
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- Synthesis of α-Alkylated Ketones via Selective Epoxide Opening/Alkylation Reactions with Primary Alcohols
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A new method for converting terminal epoxides and primary alcohols into α-alkylated ketones under borrowing hydrogen conditions is reported. The procedure involves a one-pot epoxide ring opening and alkylation via primary alcohols in the presence of an N-heterocyclic carbene iridium(I) catalyst, under aerobic conditions, with water as the side product.
- Gen?, Serta?,Gülcemal, Süleyman,Günnaz, Salih,?etinkaya, Bekir,Gülcemal, Derya
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p. 5229 - 5234
(2021/07/19)
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- Iridium-Catalyzed Alkylation of Secondary Alcohols with Primary Alcohols: A Route to Access Branched Ketones and Alcohols
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Under borrowing hydrogen conditions, NHC-iridium(I) catalyzed the direct or one-pot sequential synthesis of α,α-disubstituted ketones via the alkylation of secondary alcohols with primary alcohols is reported. Notably, the present approach provides a new method for the facile synthesis of α,α-disubstituted ketones and featured with several characteristics, including a broad substrate scope, using easy-to-handle alcohols as starting materials, and performing the reactions under aerobic conditions. Moreover, the selective one-pot formation of β,β-disubstituted alcohols was achieved by the addition of an external hydrogen source to the reaction mixture.
- Gen?, Serta?,Gülcemal, Süleyman,Günnaz, Salih,?etinkaya, Bekir,Gülcemal, Derya
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p. 9139 - 9152
(2020/08/14)
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- Iron-Catalyzed Ligand Free α-Alkylation of Methylene Ketones and β-Alkylation of Secondary Alcohols Using Primary Alcohols
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Herein, we demonstrate a general and broadly applicable catalytic cross coupling of methylene ketones and secondary alcohols with a series of primary alcohols to disubstituted branched ketones. A simple and nonprecious Fe2(CO)9 catalyst enables one-pot oxidations of both primary and secondary alcohols to a range of branched gem-bis(alkyl) ketones. A number of bond activations and formations selectively occurred in one pot to provide the ketone products. Coupling reactions can be performed in gram scale and successfully applied in the synthesis of an Alzehimer's drug. Alkylation of a steroid hormone can be achieved. A single catalyst enables sequential one-pot double alkylation to bis-hetero aryl ketones using two different alcohols. Preliminary mechanistic studies using an IR probe, deuterium labeling, and kinetic experiments established the participation of a borrowing-hydrogen process using Fe catalyst, and the reaction produces H2 and H2O as byproducts.
- Alanthadka, Anitha,Bera, Sourajit,Banerjee, Debasis
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p. 11676 - 11686
(2019/10/02)
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- Catalyst-Free Decarboxylative Fluorination of Tertiary β-Keto Carboxylic Acids
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Decarboxylative fluorination of tertiary β-keto carboxylic acids was performed using an electrophilic fluorinating reagent. The reaction proceeded in the absence of a catalyst or base to yield the corresponding α-fluoroketones with tertiary fluorocarbons in good to high yields. Considering that the α-fluorination of asymmetrical ketones often causes problems with the regioselectivity between the α- and α′-positions, this method could be a good alternative to the α-fluorination of simple ketones for the synthesis of tertiary fluoroketones.
- Katada, Misaki,Kitahara, Kazumasa,Iwasa, Seiji,Shibatomi, Kazutaka
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p. 2408 - 2411
(2018/11/23)
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- Nickel-Catalyzed Hydrogen-Borrowing Strategy for α-Alkylation of Ketones with Alcohols: A New Route to Branched gem-Bis(alkyl) Ketones
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The α-alkylation of ketones using an earth-abundant and nonprecious NiBr2/L1 system is reported. This nickel-catalyzed reaction could be performed in gram scale and successfully applied in the synthesis of donepezil (Alzheimer's drug) and functionalization of steroid hormones and fatty acid derivatives. Synthesis of N-heterocycles, methylation of ketones, and one-pot double alkylation to bis-hetero aryl ketones using two different alcohols with a single catalyst broadens the scope of the catalytic protocol. Preliminary mechanistic studies using defined Ni-H species and deuterium-labeling experiments established the participation of the borrowing-hydrogen strategy.
- Das, Jagadish,Singh, Khushboo,Vellakkaran, Mari,Banerjee, Debasis
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p. 5587 - 5591
(2018/09/25)
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- Mn(ii)-catalysed alkylation of methylene ketones with alcohols: Direct access to functionalised branched products
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Herein an operationally simple alkylation of methylene ketones with primary alcohols is reported. Use of an inexpensive and earth abundant Mn/1,10-phenanthroline system enables direct access to a series of functionalised branched ketones including one-pot sequential double alkylation and Alzheimer's drug donepezil. Preliminary mechanistic investigation, determination of the rate and order of reactions and deuterium labeling experiments support the participation of the hydrogen-borrowing strategy for the ketone alkylation.
- Kabadwal, Lalit Mohan,Das, Jagadish,Banerjee, Debasis
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p. 14069 - 14072
(2019/01/03)
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- An increased understanding of enolate additions under mechanochemical conditions
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Very little is known about enolate addition chemistry under solver-free mechanochemical conditions. In this report, we investigated the ability to selectively form products arising from the primary, secondary, and tertiary enolates under solvent-free conditions. Using potassium tert-butoxide as the base and primary, secondary, and tertiary electrophiles, we were able to generate various enolate addition products including, 1,3,3,3-Tetraphenyl-2,2-dimethyl-1-propanone; a molecule we did not observe under traditional solution-based conditions.
- Hopgood, Heather,Mack, James
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- Ruthenium-NHC Catalyzed α-Alkylation of Methylene Ketones Provides Branched Products through Borrowing Hydrogen Strategy
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The α-alkylation of a broad range of methylene ketones was achieved using a ruthenium(II)-NHC catalyst under borrowing hydrogen conditions. Primary alcohols served as alkylating agents and could be used in a one-to-one stoichiometry with respect to the ketone. The selectivity of the process for methyl over branched ketones enabled a one-pot double alkylation protocol utilizing two different alcohols with a single catalyst. Moreover, this methodology could be applied directly to the one-step synthesis of donepezil, the best-selling drug for the treatment of Alzheimer's disease.
- Schlepphorst, Christoph,Maji, Biplab,Glorius, Frank
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p. 4184 - 4188
(2016/07/12)
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- One-pot synthesis of multifunctionalized cyclopropanes
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A facile one-step synthetic protocol toward multifunctionalized cyclopropanes 4 is developed from substituted chalcones 1 and sulfones 2 in good yields via a [2C+1C] annulation.
- Chang, Meng-Yang,Chen, Yi-Chia,Chan, Chieh-Kai
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p. 2257 - 2263
(2014/03/21)
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- CHEMICAL COMPOUNDS
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Compounds of formula (I):wherein variable groups are as defined within; for use in the inhibition of 11betaHSD1 are described
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- Unexpected double benzylation of acetophenone under phase transfer catalysis conditions, acidity or π-π interaction effect?
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A π-π interaction in the transition state of the benzylation of 1,3-diphenyl-1-propanone, the monobenzylation product of acetophenone, is proposed according to chemical, kinetic and theoretical approaches. Evidence for the existence of this kind of interaction in a transition state has been provided for the first time. The results obtained cannot be explained solely by the increased acidity but by considering the existence of a π-π interaction.
- Diez-Barra, Enrique,De la Hoz, Antonio,Loupy, Andre,Martinez-Gonzalez, Alfonso,Martinez-Merino, Victor,Merino, Sonia,Paugam, Renee,Sanchez-Verdu, Prado,Sansoulet, Jean,Torres, Jose
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p. 3659 - 3668
(2007/10/03)
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- On the π-π interaction in the benzylation of ketones
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The benzylation of a set of nine ketones provides enough information to establish how the ketone structure affects the existence of a π-π interaction. The presence of a phenyl moiety starting from the a-carbon atom and flexibility in cyclic ketones are st
- Diez-Barra, Enrique,Merino, Sonia,Sanchez-Verdu, Prado,Torres, Jose
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p. 11437 - 11448
(2007/10/03)
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- α-Benzylation of Ketones by Reaction with Benzylamine. Regioselective Reduction of C-C Double Bonds in Cohjugated Enones
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Prolonged reaction of some ketones with benzylamine at reflux converts them into α-benzyl derivatives by a route involving Aldol condensation of the related ketimine with benzaldimine followed by exclusive reduction of the resultant C-C double bond.Reduction does not occur when pure benzylamine is used under oxygen-free nitrogen, however the inclusion of a trace of benzaldehyde restores the efficiency of the reaction.Treatment of several ketones in this manner established the scope of the process.When the reaction was extended to the reduction of α,β-unsaturated enones again using benzylamine, reaction times were shorter and the product yield greater.The possibility that the reductive step was an intramolecular 1,5-hydrogen transfer was studied.
- Armesto, Diego,Esteban, Soledad,Horspool, William M.,Martin, Juan-Antonio F.,Martinez-Alcazar, Paz,Perez-Ossorio, Rafael
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p. 751 - 755
(2007/10/02)
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- SELECTIVE REDUCTION OF C-C DOUBLE BONDS IN CONJUGATED ENONES BY BENZYLAMINE. A VARIANT OF THE SOMMELET REACTION
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Prolonged reaction of some ketones with benzylamine at reflux converts them into α-benzyl derivatives by a route involving aldol condensation of the related ketimine with benzaldimine followed by exclusive reduction of the resultant C-C double bond by hydride transfer from benzylamine.This efficient procedure is a variant of the Sommelet reaction for the synthesis of aldehydes.
- Armesto, Diego,Horspool, William M.,Martin, Juan Antonio F.,Perez-Ossorio, Rafael
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p. 5217 - 5220
(2007/10/02)
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