6624-04-0Relevant articles and documents
Electronically tuneable orthometalated RuII–NHC complexes as efficient catalysts for C–C and C–N bond formations via borrowing hydrogen strategy
Illam, Praseetha Mathoor,Rit, Arnab
, p. 67 - 74 (2022/01/19)
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.
Synthesis of α-Alkylated Ketones via Selective Epoxide Opening/Alkylation Reactions with Primary Alcohols
Gen?, Serta?,Gülcemal, Süleyman,Günnaz, Salih,?etinkaya, Bekir,Gülcemal, Derya
, p. 5229 - 5234 (2021/07/19)
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.
Potassium Base-Catalyzed Michael Additions of Allylic Alcohols to α,β-Unsaturated Amides: Scope and Mechanistic Insights
Kurouchi, Hiroaki,Sai, Masahiro
, p. 3585 - 3591 (2021/06/27)
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.).
Iridium-Catalyzed Alkylation of Secondary Alcohols with Primary Alcohols: A Route to Access Branched Ketones and Alcohols
Gen?, Serta?,Gülcemal, Süleyman,Günnaz, Salih,?etinkaya, Bekir,Gülcemal, Derya
, p. 9139 - 9152 (2020/08/14)
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.
Iron-Catalyzed Ligand Free α-Alkylation of Methylene Ketones and β-Alkylation of Secondary Alcohols Using Primary Alcohols
Alanthadka, Anitha,Bera, Sourajit,Banerjee, Debasis
, p. 11676 - 11686 (2019/10/02)
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.
Nickel-Catalyzed Hydrogen-Borrowing Strategy for α-Alkylation of Ketones with Alcohols: A New Route to Branched gem-Bis(alkyl) Ketones
Das, Jagadish,Singh, Khushboo,Vellakkaran, Mari,Banerjee, Debasis
supporting information, p. 5587 - 5591 (2018/09/25)
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.
Mn(ii)-catalysed alkylation of methylene ketones with alcohols: Direct access to functionalised branched products
Kabadwal, Lalit Mohan,Das, Jagadish,Banerjee, Debasis
supporting information, p. 14069 - 14072 (2019/01/03)
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.
Catalyst-Free Decarboxylative Fluorination of Tertiary β-Keto Carboxylic Acids
Katada, Misaki,Kitahara, Kazumasa,Iwasa, Seiji,Shibatomi, Kazutaka
, p. 2408 - 2411 (2018/11/23)
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.
An increased understanding of enolate additions under mechanochemical conditions
Hopgood, Heather,Mack, James
, (2017/06/08)
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.
Ruthenium-NHC Catalyzed α-Alkylation of Methylene Ketones Provides Branched Products through Borrowing Hydrogen Strategy
Schlepphorst, Christoph,Maji, Biplab,Glorius, Frank
, p. 4184 - 4188 (2016/07/12)
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.
