The article discusses the use of methanol in tandem catalysis for the selective functionalization of ketones. It highlights the challenges and the need for developing efficient catalytic systems. The study focuses on the role of different ancillary ligands coordinated to a (NNC)Ru(II) catalyst and explores the synthesis of β-methylated alcohols from ketones through α-methylation followed by transfer hydrogenation using methanol. The optimized reaction conditions and the scope of the transformation are also presented.
Facts
- Methanol is a highly attractive candidate for synthesizing value-added products due to its easy accessibility.
- Transition-metal-catalyzed methanol dehydrogenation has been developed for transfer hydrogenation and methylation processes, but tandem catalysis with methanol remains underdeveloped.
- Tandem catalysis using alcohols as coupling partners has been explored, but the utilization of methanol as a transfer hydrogenation and methylating agent is desirable.
- Selective product formation from a single substrate is achieved by changing the catalyst system or reaction conditions. Selective functionalization of ketones with methanol for three possible products (alcohol, β-methylated alcohol, and α-methylated ketone) using a single catalyst has not been reported.
- Previous methods for β-methylation of alcohols with methanol required harsh reaction conditions and stoichiometric amounts of base, making an alternative route desirable.
- Transition metal-catalyzed α-methylation of ketones with methanol has been explored, but the tandem α-methylation of ketones followed by transfer hydrogenation to access β-methylated alcohols is not sufficiently explored.
- The transfer hydrogenation of sterically hindered α, α’-disubstituted or α, α’, α”-trisubstituted ketones to the corresponding secondary alcohols using methanol has not been explored extensively.
- The role of ancillary ligands coordinated to the (NNC)Ru(II) catalyst for alcohol dehydrogenation and related functionalization has not been properly investigated.
Methanol is a promising alcohol for the synthesis of value-added products due to its easy availability from various sources. It has a high hydrogen content, making it an excellent hydrogen donor. However, the higher dehydrogenation energy of methanol compared to long-chain alcohols poses challenges in its utilization. In recent years, progress has been made in transition-metal-catalyzed methanol dehydrogenation, enabling its use in transfer hydrogenation and methylation reactions. However, the tandem catalysis with methanol for C-methylation followed by transfer hydrogenation is still underdeveloped.
Tandem catalysis is a versatile approach for synthesizing valuable compounds using readily available starting materials. Several tandem protocols have been developed using alcohols as coupling partners. The article emphasizes the desirability of utilizing methanol as a transfer hydrogenation and methylating agent in tandem catalysis.
Selective product formation from a single substrate is a long-standing goal in synthetic chemistry. Achieving selectivity with a single catalyst and substrate by varying reaction conditions is highly desirable. The article highlights the lack of reported methods for selective functionalization of ketones with methanol using a single catalyst.
The authors discuss previous reports on β-methylation of alcohols with methanol, which required harsh reaction conditions and stoichiometric amounts of base. Therefore, an alternative route for synthesizing β-methylated alcohols using methanol is desired.
(NNC)Ru(II) Complex Catalyzed Selective Functionalization of Ketones with Methanol: Understanding the Role of Ancillary Ligands
Ganguli; Mandal; Pradhan; Deval; Kundu
Full text link: https://doi.org/10.1021/acscatal.3c01097
What this paper is about
- Using ketone as a substrate, its selective functionalization with methanol to the three possible products, corresponding alcohol, -methylated alcohol, and -methylated ketone using a single catalyst has not yet been reported.
- 79,24,3134 However, employing methanol, tandem -methylation of ketones followed by transfer hydrogenation of the methylated ketones to access methylated alcohols is not sufficiently explored.
- However, this protocol required a higher amount of catalyst loading along with the sequential addition of solvents in a one-pot manner.
What you can learn
- After performing the tandem transformation of ketones to methylated alcohols, next the selective transfer hydrogenation of ketones and aldehydes to alcohols using methanol was investigated.
- In order to minimize the formation of corresponding alcohols and methylated alcohols, the methylation of propiophenone was tested with a higher amount of base at a lower temperature.
- B in the presence of 0.5 equiv NaOH at 80C for 10 h was selected as the optimized condition for the methylation of propiophenone.
- H under the reaction conditions was indicated from the reactivity of in situ generated Ru-hydride from Cat.
- In summary, by utilizing a single cyclometalated Ru complex, an efficient and sustainable protocol was developed for the diverse functionalization of ketones to alcohols, methylated alcohols, and -methylated ketones by utilizing methanol as the hydrogen and C1 source.
- DFT calculations indicated a plausible 1,2-reduction pathway for the insertion of Ru-hydride into the CC bond of,-unsaturated ketone along with providing a support for the higher reactivity of the DMSO containingRu complex compared to the PPh 3 one.
FAQ
Q: What is selective functionalization?
A: Selective functionalization refers to a process in which specific chemical transformations are carried out on a target molecule while leaving other parts of the molecule unaffected. It allows for the controlled modification of specific functional groups or positions within a molecule.
Q: What is a catalyst?
A: A catalyst is a substance that speeds up a chemical reaction without being consumed in the process. It facilitates the reaction by lowering the activation energy required for the reaction to occur. In the context of the given data, a catalyst is used to facilitate the functionalization of ketones with methanol.
Q: What is a ketone?
A: A ketone is a type of organic compound that contains a carbonyl group (C=O) bonded to two carbon atoms. Ketones are commonly used as substrates in various chemical reactions and can undergo different functionalization reactions.
Q: What is tandem -methylation?
A: Tandem -methylation refers to a sequential process in which a ketone undergoes methylation multiple times in a row, resulting in the addition of multiple methyl groups to the molecule.
Q: What is transfer hydrogenation?
A: Transfer hydrogenation is a chemical reaction in which hydrogen is transferred from a hydrogen donor (typically a molecule or catalyst) to another molecule, leading to the reduction of the target molecule. In the given context, transfer hydrogenation is employed to convert methylated ketones to methylated alcohols.
Q: What are methylated ketones?
A: Methylated ketones are ketone compounds that have undergone methylation reactions, resulting in the addition of one or more methyl groups (-CH3) to the ketone structure.
Q: What are methylated alcohols?
A: Methylated alcohols are alcohol compounds that have undergone methylation reactions, leading to the addition of one or more methyl groups (-CH3) to the alcohol structure.
Q: What is catalyst loading?
A: Catalyst loading refers to the amount of catalyst used in a chemical reaction relative to the amount of the reactants or substrates. It is often optimized to achieve the desired reaction rate and efficiency.
Q: What is a one-pot manner?
A: One-pot manner refers to a synthetic approach where multiple reaction steps are performed sequentially in a single reaction vessel or system, without the need for intermediate purification or isolation steps. It allows for a more efficient and streamlined synthesis process.
