Enantioselective Ring-Closing C–H Amination of Urea Derivatives

Chem
2020.0

Abstract

An enantioselective intramolecular C(sp3)–H amination of N-benzoyloxyurea by using a chiral-at-metal ruthenium catalyst is reported, providing chiral 2-imidazolidinones in yields of up to 99% and with up to 99% ee. Catalyst loadings down to 0.05 mol % are feasible. Control experiments support a stepwise nitrene insertion mechanism through hydrogen atom transfer of a ruthenium nitrenoid intermediate followed by a radical recombination. Chiral 2-imidazolidinones are prevalent in bioactive compounds and can be converted to chiral vicinal diamines in a single step. The synthetic value of the new method is demonstrated for the synthesis of intermediates of the drugs levamisole and dexamisole, the bisindole alkaloids topsentine D and spongotine A, and a chiral organocatalyst. Direct C–H functionalization offers the prospect for streamlined synthesis with high atom economy. In this respect, the transition-metal-catalyzed enantioselective insertion of nitrenoids into prochiral sp3 C–H bonds is a powerful tool for the efficient construction of non-racemic chiral nitrogen-containing molecules. Intramolecular versions have been used to synthesize chiral nitrogen heterocycles, but cyclic urea is still elusive through enantioselective nitrenoid insertion chemistry. Here, we fill this gap and report an enantioselective intramolecular C(sp3)–H amination of N-benzoyloxyurea to provide chiral 2-imidazolidinones in high yields and with high enantioselectivities. The synthetic utility of this new method is illustrated with the catalytic asymmetric synthesis of medicinal agents, natural products, and a chiral organocatalyst. Our work emphasizes the usefulness of transition-metal-controlled asymmetric nitrene chemistry and the importance of tailored catalyst design. Here, we report the first catalytic asymmetric ring-closing C(sp3)–H amination of urea derivatives to construct chiral 2-imidazolidinones, which are prevalent in bioactive compounds and can be converted to chiral vicinal diamines. The simple and mild transformation is catalyzed by a recently developed chiral-at-ruthenium complex in high yields and with high enantioselectivities. Applications to the drugs levamisole and dexamisole, the bisindole alkaloids topsentine D and spongotine A, and a chiral organocatalyst demonstrate the synthetic value of this new method. © 2020 Elsevier Inc.

Knowledge Graph

Similar Paper

Enantioselective Ring-Closing C–H Amination of Urea Derivatives
Chem 2020.0
Stereoselective construction of β-, γ- and δ-lactam rings via enzymatic C–H amidation
Nature Catalysis 2023.0
A Short Total Synthesis of Benzophenanthridine Alkaloids via a Rhodium(III)-Catalyzed C–H Ring-Opening Reaction
The Journal of Organic Chemistry 2021.0
Cobalt-Catalyzed Enantioselective C–H Annulation of Benzylamines with Alkynes: Application to the Modular and Asymmetric Syntheses of Bioactive Molecules
Journal of the American Chemical Society 2023.0
Ruthenium-Catalyzed Regioselective Alkenylation/Tandem Hydroamidative Cyclization of Unmasked Quinazolinones Using Terminal Alkynes
The Journal of Organic Chemistry 2018.0
Formation of 6-Azaindoles by Intramolecular Diels–Alder Reaction of Oxazoles and Total Synthesis of Marinoquinoline A
Organic Letters 2020.0
Controlling stereoselectivity by enzymatic and chemical means to access enantiomerically pure (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinoline derivatives
Tetrahedron: Asymmetry 2013.0
Complex Polyheterocycles and the Stereochemical Reassignment of Pileamartine A via Aza-Heck Triggered Aryl C–H Functionalization Cascades
Journal of the American Chemical Society 2021.0
Rapid Construction of Hexacyclic Indolines via the Ru(II)-Catalyzed C–H Activation Initiated Cascade Cyclization of Phenidones with Enynones
Organic Letters 2022.0
Intramolecular Imino-ene Reaction of 2H-azirines with Alkenes: Rapid Construction of Spiro NH Aziridines from Vinyl Azides
Organic Letters 2018.0