Tuning Triplet Energy Transfer of Hydroxamates as the Nitrene Precursor for Intramolecular C(sp3)-H Amidation

Reported herein is the design of a photosensitization strategy to generate triplet nitrenes and its applicability for the intramolecular C-H amidation reactions. Substrate optimization by tuning physical organic parameters according to the proposed energy transfer pathway led us to identify hydroxamates as a convenient nitrene precursor. While more classical nitrene sources, representatively organic azides, were ineffective under the current photosensitization conditions, hydroxamates, which are readily available from alcohols or carboxylic acids, are highly efficient in accessing synthetically valuable 2-oxazolidinones and γ-lactams by visible light. Mechanism studies supported our working hypothesis that the energy transfer path is mainly operative. © 2020 American Chemical Societ

Multidimensional Screening Accelerates the Discovery of Rhodium Catalyst Systems for Selective Intra- and Intermolecular C-H Amidations

We report herein a series of tailored (CpRh)-Rh-X(LX)Cl catalyst systems for the outer-sphere C-H amidations discovered by high-throughput experimentation. Using a diverse repertoire of Cp-tunable group 9 [(CpXCl2)-Cl-M](2) precatalysts in combination with bidentate LX-type co-ligands, we have established a premixing protocol for the fast and convenient in situ generation of an array of half- sandwich metal complexes. Benefitting from the designed multidimensional approach to simultaneously screen the metal center, Cp-X, LX-type co-ligands, and nitrene precursors, optimal CpXRh(III)(LX) catalysts were quickly identified for intra- and intermolecular C-H amidations and also for an enantioselective transformation using N-tosyloxycarbamates as the nitrenoid precursor.11Nsciescopu

Modular Tuning of Electrophilic Reactivity of Iridium Nitrenoids for the Intermolecular Selective α-Amidation of β-Keto Esters

© 2020 American Chemical Society We report herein an Ir-catalyzed intermolecular amino group transfer to β-keto esters (amides) to access α-aminocarbonyl products with excellent chemoselectivity. The key strategy was to engineer electrophilicity of the putative Ir-nitrenoids by tuning electronic property of the κ2-N,O chelating ligands, thus facilitating nucleophilic addition of enol π-bonds of 1,3-dicarbonyl substrates11sci

Iridium-Catalyzed Migratory Terminal C(sp3)-H Amidation of Heteroatom-Substituted Internal Alkenes via Olefin Chain Walking

Hydroamination facilitated by metal hydride catalysis is an appealing synthetic approach to access valuable nitrogen-containing compounds from readily available unsaturated hydrocarbons. While high regioselectivity can be achieved usually for substrates bearing polar chelation groups, the reaction involving simple alkenes frequently provides nonselective outcomes. Herein, we report an iridium-catalyzed highly regioselective terminal C-(sp(3))-H amidation of internal alkenes utilizing dioxazolones as an amino source via olefin chain walking. Most notably, this mechanistic motif of double bond migration to the terminal position operates not only with dialkyl-substituted simple alkenes including styrenes but also with heteroatom-substituted olefins such as enol ethers, vinyl silanes, and vinyl borons, thus representing the first example of the terminal methyl amidation of the latter type of alkenes through a nondissociative chain walking process.11Nsciescopu

Visible-Light Induced C(sp2)−H Amidation with an Aryl–Alkyl σ-Bond Relocation via Redox-Neutral Radical–Polar Crossover

© 2021 Wiley-VCH GmbH.We report an approach for the intramolecular C(sp2)−H amidation of N-acyloxyamides under photoredox conditions to produce δ-benzolactams with an aryl-alkyl σ-bond relocation. Computational studies on the designed reductive single electron transfer strategy led us to identify N-[3,5-bis(trifluoromethyl)benzoyl] group as the most effective amidyl radical precursor. Upon the formation of an azaspirocyclic radical intermediate by the selective ipso-addition with outcompeting an ortho-attack, radical–polar crossover was then rationalized to lead to the rearomative ring-expansion with preferential C−C bond migration.11Nsciescopu

Energy-transfer-induced [3+2] cycloadditions of N–N pyridinium ylides

Photocycloaddition is a powerful reaction to enable the conversion of alkenes into high-value synthetic materials that are normally difficult to obtain under thermal conditions. Lactams and pyridines, both prominent in pharmaceutical applications, currently lack effective synthetic strategies to combine them within a single molecular structure. Here we describe an efficient approach to diastereoselective pyridyl lactamization via a photoinduced [3+2] cycloaddition, based on the unique triplet-state reactivity of N–N pyridinium ylides in the presence of a photosensitizer. The corresponding triplet diradical intermediates allow the stepwise radical [3+2] cycloaddition with a broad range of activated and unactivated alkenes under mild conditions. This method exhibits excellent efficiency, diastereoselectivity and functional group tolerance, providing a useful synthon for ortho-pyridyl γ- and δ-lactam scaffolds with syn-configuration in a single step. Combined experimental and computational studies reveal that the energy transfer process leads to a triplet-state diradical of N–N pyridinium ylides, which promotes the stepwise cycloaddition. [Figure not available: see fulltext.]. © 2023, The Author(s), under exclusive licence to Springer Nature Limited.11Nsciescopu

Quantitative Analysis on Two-Point Ligand Modulation of Iridium Catalysts for Chemodivergent C-H Amidation

The transition-metal-catalyzed nitrenoid transfer reaction is one of the most attractive methods for installing a new C-N bond into diverse reactive units. While numerous selective aminations are known, understanding complex structural effects of the key intermediates on the observed chemoselectivity is still elusive in most cases. Herein, we report a designing approach to enable selective nitrenoid transfer leading to sp(2) spirocyclization and sp(3) C-H insertion by cooperative two-point modulation of ligands in the (CpIr)-Ir-X(III)(kappa(2)-chelate) catalyst system. Computational analysis led us to interrogate structural motifs that can be attributed to the desired mechanistic dichotomy. Multivariate linear regression analysis on the perturbation on the eta(5)-cyclopentadienyl ancillary (Cp-X) and LX coligand, wherein we prepared over than 40 new catalysts for screening, allowed for construction of an intuitive yet robust statistical model that predicts a large set of chemoselective outcomes, implying that the catalysts' structural effects play a critical role on the chemoselective nitrenoid transfer. On the basis of this quantitative analysis, a new catalytic platform is now established for the unique lactam formation, leading to the unprecedented chemoselective reactivity (up to >20:1) toward a diverse array of competing sites, such as tertiary, secondary, benzylic, allylic C-H bonds, and aromatic pi system.© 2020 American Chemical Society11Nsciescopu

Sequential C−H Borylation and N-Demethylation of 1,1′-Biphenylamines: Alternative Route to Polycyclic BN-Heteroarenes

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Described herein is an unprecedented access to BN-polyaromatic compounds from 1,1′-biphenylamines by sequential borane-mediated C(sp 2 )−H borylation and intramolecular N-demethylation. The conveniently in situ generated Piers’ borane from a borinic acid reacts with a series of N,N-dimethyl-1,1′-biphenyl-2-amines in the presence of PhSiH 3 to afford six-membered amine-borane adducts bearing a C(sp 2 )−B bond at the C2′-position. These species undergo an intramolecular N-demethylation with a B(C 6 F 5 ) 3 catalyst to provide BN-isosteres of polyaromatics. According to computational studies, a stepwise ionic pathway is suggested. Photophysical characters of the resultant BN-heteroarenes shown them to be distinctive from those of all-carbon analogues ⓒ 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinhei

Controlled Relay Process to Access N-Centered Radicals for Catalyst-free Amidation of Aldehydes under Visible Light

Nitrogen-centered radicals have attracted increasing attention as a versatile reactive intermediate for diverse C-N bond constructions. Despite the significant advances achieved in this realm, the controllable formation of such species under catalyst-free conditions remains highly challenging. Here, we report a new relay process involving the slow in situ generation of a photoactive N-chloro species via C-N bond formation, which subsequently enables mild and selective access to N-centered radicals under visible light conditions. The utility of this approach is demonstrated by the conversion of aldehydes to amides, employing N-chloro-N-sodio carbamates as a practical amidating source. This synthetic operation obviates the need for catalysts, external oxidants, and coupling reagents that are typically required in related processes, consequently allowing high functional group tolerance and excellent applicability for late-stage functionalization.11Nsciescopu

Versatile Cp*Co(III)(LX) Catalyst System for Selective Intramolecular C-H Amidation Reactions

© 2020 American Chemical Society Herein, we report the development of a tailored cobalt catalyst system of Cp*Co(III)(LX) toward intramolecular C-H nitrene insertion of azidoformates to afford cyclic carbamates. The cobalt complexes were easy to prepare and bench-stable, thus offering a convenient reaction protocol. The catalytic reactivity was significantly improved by the electronic tuning of the bidentate LX ligands, and the observed regioselectivity was rationalized by the conformational analysis and DFT calculations of the transition states. The superior performance of the newly developed cobalt catalyst system could be broadly applied to both C(sp2)-H and C(sp3)-H carbamation reactions under mild conditions11sci