- Integrating Metal-Catalyzed C-H and C-O Functionalization to Achieve Sterically Controlled Regioselectivity in Arene Acylation
-
One major goal of organometallic chemists is the direct functionalization of the bonds most recurrent in organic molecules: C-H, C-C, C-O, and C-N. An even grander challenge is C-C bond formation when both precursors are of this category. Parallel to this is the synthetic goal of achieving reaction selectivity that contrasts with conventional methods. Electrophilic aromatic substitution (EAS) via Friedel-Crafts acylation is the most renowned method for the synthesis of aryl ketones, a common structural motif of many pharmaceuticals, agrochemicals, fragrances, dyes, and other commodity chemicals. However, an EAS synthetic strategy is only effective if the desired site for acylation is in accordance with the electronic-controlled regioselectivity of the reaction. Herein we report steric-controlled regioselective arene acylation with salicylate esters via iridium catalysis to access distinctly substituted benzophenones. Experimental and computational data indicate a unique reaction mechanism that integrates C-O activation and C-H activation with a single iridium catalyst without an exogenous oxidant or base. We disclose an extensive exploration of the synthetic scope of both the arene and the ester components, culminating in the concise synthesis of the potent anticancer agent hydroxyphenstatin.
- Serratore, Nicholas A.,Anderson, Constance B.,Frost, Grant B.,Hoang, Truong-Giang,Underwood, Steven J.,Gemmel, Philipp M.,Hardy, Melissa A.,Douglas, Christopher J.
-
supporting information
p. 10025 - 10033
(2018/07/21)
-
- Efficient Aryl Migration from an Aryl Ether to a Carboxylic Acid Group To Form an Ester by Visible-Light Photoredox Catalysis
-
We have developed a highly efficient aryl migration from an aryl ether to a carboxylic acid group through retro-Smiles rearrangement by visible-light photoredox catalysis at ambient temperature. Transition metals and a stoichiometric oxidant and base are avoided in the transformation. Inspired by the high efficiency of this transformation and the fundamental importance of C?O bond cleavage, we developed a novel approach to the C?O cleavage of a biaryl ether to form two phenolic compounds, as demonstrated by a one-pot, two-step gram-scale reaction under mild conditions. The aryl migration exhibits broad scope and can be applied to the synthesis of pharmaceutical compounds, such as guacetisal. Primary mechanistic studies indicate that the catalytic cycle occurs by a reductive quenching pathway.
- Wang, Shao-Feng,Cao, Xiao-Ping,Li, Yang
-
supporting information
p. 13809 - 13813
(2017/10/24)
-
- A new group of potential antituberculotics: N-(2-pyridylmethyl) salicylamides and N-(3-pyridylmethyl)salicylamides
-
As a part of our systematic study of antimycobacterially active derivatives of salicylamides, a series of nineteen derivatives of N-(2-pyridylmethyl) salicylamides and N-(3-pyridylmethyl)salicylamides was synthesised. The compounds exhibited in vitro activity against Mycobacterium tuberculosis and M. avium. Their lipophilicity, RM, was measured by thin layer chromatography on silica gel impregnated with trioctadecylsilane and the logarithm of the partition coefficient (octanol-water), logP, was calculated. Both the parameters of lipophilicity correlated. The quantitative relationship between the structure and antimycobacterial activity was calculated. Antimycobacterial activity increased with an increase in lipophilicity. The N-(2-pyridylmethyl)salicylamide derivatives were more active than the derivatives of isomeric N-(3-pyridylmethyl)salicylamides. The geometry of compounds was calculated and the calculation was verified by measuring the length of the hydrogen bond between hydroxyl and carbonyl groups on the salicylic moiety.
- Petrlikova, Eva,Waisser, Karel,Palat Jr., Karel,Kunes, Jiri,Kaustova, Jarmila
-
experimental part
p. 52 - 59
(2012/01/14)
-
- Synthesis, molecular modeling and biological evaluation of PSB as targeted antibiotics
-
We described here the design, synthesis, molecular modeling, and biological evaluation of a series of peptide and Schiff bases (PSB) small molecules, inhibitors of Escherichia coli β-Ketoacyl-acyl carrier protein synthase III (ecKAS III). The initial lead compound was reported by us previously, we continued to carry out structure-activity relationship studies and optimize the lead structure to potent inhibitors in this research. The results demonstrated that both N-(2-(3,5-dichloro-2-hydroxybenzylideneamino)propyl)-2-hydroxybenzamide (1f) and 2-hydroxy-N-(2-(2-hydroxy-5-iodobenzylideneamino)propyl)-4-methylbenzamide (3e) posses good ecKAS III inhibitory activity and well binding affinities by bonding Gly152/Gly209 of ecKAS III and fit into the mouth of the substrate tunnel, and can be as potential antibiotics agent, displaying minimal inhibitory concentration values in the range 0.20-3.13 μg/mL and 0.39-3.13 μg/mL against various bacteria.
- Cheng, Kui,Zheng, Qing-Zhong,Hou, Jin,Zhou, Yang,Liu, Chang-Hong,Zhao, Jing,Zhu, Hai-Liang
-
experimental part
p. 2447 - 2455
(2010/06/19)
-
- Mixed anhydrides of carbamic and hydroxamic acids
-
A base precursor represented by the following general formula (A) or (B): STR1 wherein A1, A2, A5, A6, A7, and A8 each represents a hydrogen atom, an alkyl group, a substituted alkyl group, a cycloalkyl group, an alkenyl group, an aralkyl group, an aryl group, a substituted aryl group, an acyl group, or a heterocyclic group, and A1 and A2 can combine to form a ring and two of A5, A6, A7, and A8 can combine to form a ring, A3 and A4 each represents a hydrogen atom, an alkyl group, a substituted alkyl group, a cycloalkyl group, or an aralkyl group, and A3 and A4 can combine to form a ring or A3 and A4 can be a double bond forming an imino group from STR2 and X represents a nucleophilic group.
- -
-
-