The first copper-catalyzed intramolecular C(sp(3))-H and C(sp(2))-H oxidative amidation has been developed. Using a Cu(OAc)2 catalyst and an Ag2CO3 oxidant in dichloroethane solvent, C(sp(3))-H amidation proceeded at a terminal methyl group, as well as at the internal benzylic position of an alkyl chain. This reaction has a broad substrate scope, and various β-lactams were obtained in excellent yield, even on gram scale. Use of CuCl2 and Ag2CO3 under an O2 atmosphere in dimethyl sulfoxide, however, leads to 2-indolinone selectively by C(sp(2))-H amidation. Kinetic isotope effect (KIE) studies indicated that C-H bond activation is the rate-determining step. The 5-methoxyquinolyl directing group could be removed by oxidation.

A biocompatible photooxygenation catalyst that can selectively oxygenate and degrade the pathogenic aggregation of Alzheimer's disease (AD)-related amyloid-b peptide (Ab) under near-infrared light irradiation has been developed. The catalyst oxygenates Ab embedded under the skin of a living mouse and diminishes the intact Ab level in an AD-model mouse brain. The new catalyst is potentially applicable for the treatment of peripheral amyloid diseases and AD.

Aerobic, site-selective C(sp3)–H oxygenation using a novel N-oxyl radical directing activator (chemically reactive directing group) is described.

Chemo-and site-selective hydrosilylation of αor β-hydroxy amides using organocatalyst B(C 6 F 5 ) 3 and commercially available hydrosilanes is described. This transformation is operative under mild conditions and tolerates a wide range of functional groups. The reaction was applied for selective reduction of a specific amide group of the therapeutically important cyclic peptide cyclosporin A, demonstrating the potential usefulness of this catalytic method in late-stage structural transformations of drug lead molecules.

The first copper-catalyzed intramolecular C(sp 3 ) À H and C(sp 2 ) À H oxidative amidation has been developed. Using a Cu(OAc) 2 catalyst and an Ag 2 CO 3 oxidant in dichloroethane solvent, C(sp 3 )ÀH amidation proceeded at a terminal methyl group, as well as at the internal benzylic position of an alkyl chain. This reaction has a broad substrate scope, and various blactams were obtained in excellent yield, even on gram scale. Use of CuCl 2 and Ag 2 CO 3 under an O 2 atmosphere in dimethyl sulfoxide, however, leads to 2-indolinone selectively by C(sp 2 )À H amidation. Kinetic isotope effect (KIE) studies indicated that CÀH bond activation is the rate-determining step. The 5methoxyquinolyl directing group could be removed by oxidation.Lactams (cyclic amides) and related compounds are important partial structures of natural products, such as penicillin and cephalosporin, and drugs such as ezetimibe [1] and piperacillin [2] (b-lactam antibiotics, Figure 1). The Beckmann rearrangement, [3] Schmidt reaction, [4] cyclization of amino acids, [5] and iodolactamization [6] are well-known synthetic Angewandte Chemie

The site-selective cleavage of peptide bonds is an important chemical modification that is useful not only for the structural determination of peptides, but also as an artificial modulator of peptide/protein function and properties. Here we report site-selective hydrolysis of peptide bonds at the Ser and Thr positions with a high conversion yield. This chemical cleavage relies on Sc(iii)-promoted N,O-acyl rearrangement and subsequent hydrolysis. The method is applicable to a broad scope of polypeptides with various functional groups, including a post-translationally modified peptide that is unsuitable for enzymatic hydrolysis. The system was further extended to site-selective cleavage of a native protein, Aβ1-42, which is closely related to the onset of Alzheimer's disease.

The regioselective conversion of an unactivated C(sp(3))-H bond of a methylene carbon (CH2) into a C-O single bond is an attractive reaction in organic synthesis. Herein, we present a strategy for a regio- and oxidation state-selective aerobic C-H oxidation based on an N-hydroxyamide-derived directing activator (DA), which is attached to a hydroxy group in alcohol substrates. The DA reacts with NOx species generated in situ from NaNO2, a Brønsted acid, and aerobic oxygen, and effectively generates an amidoxyl radical from the N-hydroxy moiety of the DA. Then, the amidoxyl radical promotes site-selective intramolecular C-H abstraction from methylenes with γ- (or δ-) selectivity. The thus-generated methylene radicals are trapped by molecular oxygen and NO. This process results in the predominant formation of nitrate esters as products, which suppresses undesired overoxidation. The products can be easily converted into alcohols after hydrogenolysis.

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