Ruthenium-Catalyzed α-Alkylation of Ketones Using Secondary Alcohols to β-Disubstituted Ketones

Thiyagarajan, S.; Sankar, Raman Vijaya; Gunanathan, Chidambaram

doi:10.1021/acs.orglett.0c02787

Cited by 40 publications

(27 citation statements)

References 42 publications

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“…It also was later incorporated for further stereoselective studies, utilizing a chiral phosphine ligand to control the facial selectivity of hydride deposition to the enone intermediate, resulting in enantioenriched products as shown in Scheme ( 65 – 67 ). , The diastereoselective dialkylation of methyl ketones using diols to obtain cycloalkanes has also been performed with manganese , and iron catalysis . A recent study from Gunanathan and co-workers successfully demonstrated the alkylation of unsubstituted and unhindered acetophenone compounds with secondary alcohols by employing Ru-Macho as the catalyst and, contrary to previous reports, using a catalytic amount of base …”

Section: C–c Bond-forming Processesmentioning

confidence: 99%

“…140 A recent study from Gunanathan and co-workers successfully demonstrated the alkylation of unsubstituted and unhindered acetophenone compounds with secondary alcohols by employing Ru-Macho as the catalyst and, contrary to previous reports, using a catalytic amount of base. 141 The research discussed so far is predominantly limited to methyl ketone substrates using benzyl or long chain n-alkyl alcohols as alkylating agents. The ability to perform methylation to form α-branched products via the borrowing hydrogen method remained a challenge for many years due to the same reasons discussed earlier for N-methylation.…”

Section: ■ Introductionmentioning

confidence: 99%

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Borrowing Hydrogen for Organic Synthesis

et al. 2021

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Borrowing hydrogen is a process that is used to diversify the synthetic utility of commodity alcohols. A catalyst first oxidizes an alcohol by removing hydrogen to form a reactive carbonyl compound. This intermediate can undergo a diverse range of subsequent transformations before the catalyst returns the “borrowed” hydrogen to liberate the product and regenerate the catalyst. In this way, alcohols may be used as alkylating agents whereby the sole byproduct of this one-pot reaction is water. In recent decades, significant advances have been made in this area, demonstrating many effective methods to access valuable products. This outlook highlights the diversity of metal and biocatalysts that are available for this approach, as well as the various transformations that can be performed, focusing on a selection of the most significant and recent advances. By succinctly describing and conveying the versatility of borrowing hydrogen chemistry, we anticipate its uptake will increase across a wider scientific audience, expanding opportunities for further development.

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Section: C–c Bond-forming Processesmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Borrowing Hydrogen for Organic Synthesis

et al. 2021

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“…In 2020, a ruthenium pincer catalyzed α‐alkylation of ketones using unactivated secondary alcohols to β‐branched ketones was achieved by Gunanathan and co‐workers (Scheme 22). [28] Contrary to previously reported procedures, this strategy explored the utility of unsubstituted and nonhindered acetophenone compounds with a variety of secondary alcohols as alkylating agents. Remarkably, challenging substrates such as simple acetophenone derivatives were effectively alkylated under this ruthenium catalysis.…”

Section: The α‐Alkylation Of Ketonesmentioning

confidence: 99%

Recent Advances for Alkylation of Ketones and Secondary Alcohols Using Alcohols in Homogeneous Catalysis

2022

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The alkylation of ketones or secondary alcohols using alcohols as alkylating agents via hydrogen borrowing strategy presents a powerful method for the synthesis of �-alkylated ketones. In this review, we summarize the progress catalyzed by Ir, Pd, Rh, Ru, Mn, Fe, Co, Ni, and Cu catalysts for the α-alkylation of ketones with alcohols and crosscoupling of secondary alcohols with alcohols from 2017 to 2021. A wide range of ketones (aromatic and aliphatic ketones) and alcohols (benzylic and aliphatic primary alcohols, aromatic and aliphatic secondary alcohols, alkenyl alcohols, and diols) are well tolerated. Furthermore, we also discuss current challenges and propose perspectives on the coming development in this filed. The objective of the present review is to give an overview on recent advances for α-alkylation of ketones with alcohols and β-alkylation of secondary alcohols with alcohols. Finally, we hope that this review will give inspirations on alkylation of ketones or secondary alcohols with alcohols.

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“…A comparison of the performances of reported protonresponsive catalysts was made (see, Scheme S2). It is apparent that 1 exhibits better catalytic efficacy in terms of lower base loading and higher TON and TOF values for both α-alkylation of ketones [38,110,121,[135][136][137][138] and β-alkylation of secondary alcohols. [87,94,104,106,139]…”

Section: β-Alkylation Of Secondary Alcohols Using Primary Alcoholsmentioning

confidence: 99%

A Proton‐Responsive Pyridyl(benzamide)‐Functionalized NHC Ligand on Ir Complex for Alkylation of Ketones and Secondary Alcohols

Kaur

Reshi

Patra

et al. 2021

Chemistry A European J

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A Cp*Ir(III) complex (1) of a newly designed ligand L 1 featuring a proton-responsive pyridyl(benzamide) appended on N-heterocyclic carbene (NHC) has been synthesized. The molecular structure of 1 reveals a dearomatized form of the ligand. The protonation of 1 with HBF 4 in tetrahydrofuran gives the corresponding aromatized complex [Cp*Ir(L 1 H)Cl]BF 4 (2). Both compounds are characterized spectroscopically and by X-ray crystallography. The protonation of 1 with acid is examined by 1 H NMR and UV-vis spectra. The proton-responsive character of 1 is exploited for catalyzing α-alkylation of ketones and β-alkylation of secondary alcohols using primary alcohols as alkylating agents through hydrogen-borrowing methodology. Compound 1 is an effec-tive catalyst for these reactions and exhibits a superior activity in comparison to a structurally similar iridium complex [Cp*Ir(L 2 )Cl]PF 6 (3) lacking a proton-responsive pendant amide moiety. The catalytic alkylation is characterized by a wide substrate scope, low catalyst and base loadings, and a short reaction time. The catalytic efficacy of 1 is also demonstrated for the syntheses of quinoline and lactone derivatives via acceptorless dehydrogenation, and selective alkylation of two steroids, pregnenolone and testosterone. Detailed mechanistic investigations and DFT calculations substantiate the role of the proton-responsive ligand in the hydrogen-borrowing process.À OH/=O, À CH 2 /=CH and À NH/ = N motifs on pyridine, [25][26][27] bipyridine, [28][29][30][31][32] bipyrimidine [33] and azole-pyridine/ pyrimidine [34][35][36][37] are particularly effective. Some of the representative examples that have been employed for catalyzing (de) hydrogenation and alkylation reactions are given in Scheme 1. Yamaguchi and co-workers reported a Cp*Ir(III) compound with

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Ruthenium-Catalyzed α-Alkylation of Ketones Using Secondary Alcohols to β-Disubstituted Ketones

Cited by 40 publications

References 42 publications

Borrowing Hydrogen for Organic Synthesis

Borrowing Hydrogen for Organic Synthesis

Recent Advances for Alkylation of Ketones and Secondary Alcohols Using Alcohols in Homogeneous Catalysis

A Proton‐Responsive Pyridyl(benzamide)‐Functionalized NHC Ligand on Ir Complex for Alkylation of Ketones and Secondary Alcohols

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