87482-75-5Relevant academic research and scientific papers
Ruthenium-Catalyzed α-Alkylation of Ketones Using Secondary Alcohols to β-Disubstituted Ketones
Thiyagarajan, Subramanian,Vijaya Sankar, Raman,Gunanathan, Chidambaram
supporting information, p. 7879 - 7884 (2020/11/02)
An assortment of aromatic ketones was successfully functionalized with a variety of unactivated secondary alcohols that serve as alkylating agents, providing β-disubstituted ketone products in good to excellent yields. Remarkably, challenging substrates such as simple acetophenone derivatives are effectively alkylated under this ruthenium catalysis. The substituted cyclohexanol compounds displayed product-induced diastereoselectivity. Mechanistic studies indicate the involvement of the hydrogen-borrowing pathway in these alkylation reactions. Notably, this selective and catalytic C-C bond-forming reaction requires only a minimal load of catalyst and base and produces H2O as the only byproduct, making this protocol attractive and environmentally benign.
Catalytic Cross-Coupling of Secondary Alcohols
Thiyagarajan, Subramanian,Gunanathan, Chidambaram
supporting information, p. 3822 - 3827 (2019/04/09)
Herein, an unprecedented ruthenium(II) catalyzed direct cross-coupling of two different secondary alcohols to β-disubstituted ketones is reported. Cyclic, acylic, symmetrical, and unsymmetrical secondary alcohols are selectively coupled with aromatic benzylic secondary alcohols to provide ketone products. A single catalyst oxidizes both secondary alcohols to provide selectively β-disubstituted ketones to broaden the scope of this catalytic protocol. Number of bond activation and bond formation reactions occur in selective sequence via amine-amide metal-ligand cooperation operative in Ru-MACHO catalyst. The product-induced diastereoselectivity was also observed. Kinetic and deuterium labeling experiments suggested that the aliphatic secondary alcohols undergo oxidation reaction faster than benzylic secondary alcohols, selectively assimilating to provide the cross-coupled products. Reactions are sensitive to steric hindrance. This new C-C bond forming methodology requires low catalyst load and catalytic amount of base. Notably, the reaction produces H2 and H2O as the only byproducts making the protocol greener, atom economical and environmentally benign.
Ruthenium-Catalyzed Direct Cross-Coupling of Secondary Alcohols to β-Disubstituted Ketones
Gunanathan, Chidambaram,Thiyagarajan, Subramanian
, p. 2027 - 2034 (2019/11/05)
The β-disubstituted ketone functionality is prevalent in biologically active compounds and in pharmaceuticals. A ruthenium-catalyzed direct synthesis of β-disubstituted ketones by cross-coupling of two different secondary alcohols is reported. This new protocol was applied to the synthesis of variety of β-disubstituted ketones from various cyclic, acyclic, symmetrical, and unsymmetrical secondary alcohols. An amine-amide metal-ligand cooperation in a Ru catalyst facilitates the activation and formation of covalent bonds in selective sequences to provide the products. Kinetic and deuterium-labeling experiments suggested that aliphatic alcohols oxidize faster than benzylic secondary alcohols. A plausible mechanism is proposed on the basis of mechanistic and kinetic studies. Water and H 2 are the only byproducts from this selective cross-coupling of secondary alcohols. 1 Introduction 2 Catalytic Self-or Cross-Coupling of Alcohols and Selectivity Challenges 3 Recent Developments in the Synthesis of β-Disubstituted Ketones 4 Scope of Ruthenium-Catalyzed Cross-Couplings of Secondary Alcohols 5 Mechanistic Studies and Proposed Mechanism 6 Conclusion.
Gram-Positive and Gram-Negative Antibiotic Activity of Asymmetric and Monomeric Robenidine Analogues
Russell, Cecilia C.,Stevens, Andrew,Pi, Hongfei,Khazandi, Manouchehr,Ogunniyi, Abiodun D.,Young, Kelly A.,Baker, Jennifer R.,McCluskey, Siobhann N.,Page, Stephen W.,Trott, Darren J.,McCluskey, Adam
, p. 2573 - 2580 (2018/11/27)
Desymmetrisation of robenidine (1: N′,2-bis((E)-4-chlorobenzylidene)hydrazine-1-carboximidhydrazide) and the introduction of imine alkyl substituents gave good antibiotic activity. Of note was the increased potency of two analogues against vancomycin-resistant Enterococci (VRE), one of which returned a MIC of 0.5 μg mL?1. Five analogues were found to be equipotent or more potent than the lead 1. Introduction of an indole moiety resulted in the most active robenidine analogue against methicillin-resistant S. aureus (MRSA), with a MIC of 1.0 μg mL?1. Imine C=NH isosteres (C=O/C=S) were inactive. Monomeric analogues were 16–64 μg mL?1 active against MRSA and VRE. An analogue that lacks the terminal hydrazide NH moiety showed modest Gram-negative activity at 64 μg mL?1. A 4-tert-butyl analogue was shown to be active against both Gram-positive and -negative strains at 16–64 μg mL?1. In general, additional modifications with aromatic moieties was poorly tolerated, except with concomitant introduction of an imine C-alkyl group. The activity of these analogues against MRSA and VRE ranged from 8 μg mL?1 to inactive (MIC>128 μg mL?1) with the naphthyl and indole analogues. Gram-negative activity was most promising with two compounds at 16 μg mL?1 against E. coli. Against P. aeruginosa, the highest activity observed was with MIC values of 32 μg mL?1 with another two analogues. Combined, these findings support the further development of the (E)-2-benzylidenehydrazine-1-carboximidamide scaffold as a promising scaffold for the development of antibiotics against Gram-positive and Gram-negative strains.
Peroxide promoted tunable decarboxylative alkylation of cinnamic acids to form alkenes or ketones under metal-free conditions
Ji, Jing,Liu, Ping,Sun, Peipei
supporting information, p. 7546 - 7549 (2015/05/04)
A tunable decarboxylative alkylation of cinnamic acids with alkanes was developed to form alkenes or ketones under transition metal-free conditions. In the presence of DTBP or DTBP/TBHP, the reaction gave alkenes and ketones respectively via a radical mechanism in moderate to good yields. This journal is
A STUDY OF THE NORRISH TYPE II REACTION IN THE SOLID STATE
Scheffer, John R.,Trotter, James,Omkaram, Nalamasu,Evans, Stephen V.,Ariel, Sara
, p. 169 - 196 (2007/10/02)
The solid state photochemistry of six α-cycloalkyl-p-chloroacetophenone derivatives (cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, exo-2-norbornyl and 1-adamantyl) is reported.All six undergo smooth type II photochemistry in the crystalline phase.The cyclization-to-cleavage ratios and the cis-to-trans cyclobutanol ratios are tabulated for each ketone, and the results are compared with the corresponding data from the solution photolyses.In general, the solid state medium was found to exert a relatively small effect on the product ratios.The γ-hydrogen atom to carbonyl oxygen abstraction distances, as well as the angular relationships between these two atoms, were determined from the X-ray crystal structure data for each ketone.The data showed that (1) six atom abstraction geometries other than chairlike can be accommodated, (2) abstraction can occur over distances much longer than previously supposed (up to 3.10 Angstroem), and (3) there is no strict requirement that the hydrogen undergoing abstraction be in the plane of the carbonyl oxygen n-orbital.Attempts were made to correlate the solid state structural data with the rate constants for hydrogen atom abstraction as determined in solution from Stern-Volmer quenching plots.The lack of any such correlation is interpreted as indicating a significant contribution to reaction in solution from non-minimum energy ketone conformations.
