The first example of transition metal-catalyzed meta-selective CAr-H nitration of arenes is described. With the use of Ru3(CO)12 as the catalyst and Cu(NO3)2·3H2O as the nitro source, a wide spectrum of arenes bearing diversified N-heterocycles or oximido as the directing groups were nitrated with meta-selectivity exclusively. Mechanism studies have demonstrated the formation of a new 18e-octahedral ruthenium species as a key ortho-CAr-H metalated intermediate, which may be responsible for the subsequent meta-selective electrophilic aromatic substitution (SEAr). Moreover, this approach provides a fast-track strategy for atom/step economical synthesis of many useful pharmaceutical molecules.
The
development of C–H activation reactions that use inexpensive
and practical oxidants remains a significant challenge. Until our
recent disclosure of the β-lactonization of free aliphatic acids,
the use of peroxides in C–H activation reactions directed by
weakly coordinating native functional groups was unreported. Herein,
we report C(sp3)–H β-acetoxylation and γ-,
δ-, and ε-lactonization reactions of free carboxylic acids
enabled by a novel cyclopentane-based mono-N-protected
β-amino acid ligand. Notably, tert-butyl hydrogen
peroxide is used as the sole oxidant for these reactions. This reaction
has several key advantages over other C–H activation protocols:
(1) exclusive monoselectivity was observed in the presence of two
α-methyl groups; (2) aliphatic carboxylic acids containing α-hydrogens
are compatible with this protocol; (3) lactonization of free acids,
affording γ-, δ-, or ε-lactones, has been achieved
for the first time.
Reported herein is the distal γ‐C(sp3)−H olefination of ketone derivatives and free carboxylic acids. Fine tuning of a previously reported imino‐acid directing group and using the ligand combination of a mono‐N‐protected amino acid (MPAA) and an electron‐deficient 2‐pyridone were critical for the γ‐C(sp3)−H olefination of ketone substrates. In addition, MPAAs enabled the γ‐C(sp3)−H olefination of free carboxylic acids to form diverse six‐membered lactones. Besides alkyl carboxylic acids, benzylic C(sp3)−H bonds also could be functionalized to form 3,4‐dihydroisocoumarin structures in a single step from 2‐methyl benzoic acid derivatives. The utility of these protocols was demonstrated in large scale reactions and diversification of the γ‐C(sp3)−H olefinated products.
DNA-encoded library (DEL) technology has the potential to dramatically expedite hit identification in drug discovery owing to its ability to perform protein affinity selection with millions or billions of molecules...
We report the first example of Pd-catalyzed site-selective α-C(sp(3))-H oxidation/acetoxylation of amides through an unusual [4,6]-bicyclic metallacycle intermediate with 1-aminoanthraquinone as a new bidentate directing group. In addition to the distinct mechanism and high efficiency, the reaction is highly appealing due to the ample commercial source, low-cost, as well as easy removal and recycling of the auxiliary group.
A removable oxime-assisted meta-C-H nitration of arenes is reported. Mechanistic investigations and DFT calculations reveal a new monomeric octahedral ruthenium(II) complex is responsible for the meta-selective nitration. Dioxygen as a cooxidant is crucial for achieving high conversion and good yields. Moreover, the utility of the present reaction protocol is further showcased by the late-stage modification of the clinical CNS drugs Diazepam and Fluvoxamine.
A novel and efficient
approach for the C(sp2)–H
bond carbonylation of benzamides has been developed using stable and
inexpensive Co(OAc)2·4H2O as the catalyst
and the commercially available and easily handling azodicarboxylates
as the nontoxic carbonyl source. A broad range of substrates bearing
diverse functional groups were tolerated. This is the first example
where cobalt-catalyzed C(sp2)–H bond carbonylation
occurs with azodicarboxylate as the carbonyl source.
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