Oxime Acetates Research Articles

Redox‐Divergent Synthesis of Fluoroalkylated Pyridines and 2‐Pyridones through Cu‐Catalyzed N−O Cleavage of Oxime Acetates

AbstractCu‐catalyzed redox‐divergent [3+3] coupling of oxime esters with β‐CF3 enones and acrylates is described. This redox‐neutral coupling with enones and acrylates affords trifluoromethylated pyridines and pyridones, respectively. Under reductive conditions, difluoromethylated pyridines, difluoromethlated pyridones, and trifluoromethylated dihydropyridones are obtained. The reactions occur under mild conditions with broad substrate scope and regio/redox selectivity.

Redox-Divergent Synthesis of Fluoroalkylated Pyridines and 2-Pyridones through Cu-Catalyzed N-O Cleavage of Oxime Acetates.

Cu-catalyzed redox-divergent [3+3] coupling of oxime esters with β-CF3 enones and acrylates is described. This redox-neutral coupling with enones and acrylates affords trifluoromethylated pyridines and pyridones, respectively. Under reductive conditions, difluoromethylated pyridines, difluoromethlated pyridones, and trifluoromethylated dihydropyridones are obtained. The reactions occur under mild conditions with broad substrate scope and regio/redox selectivity.

Access to Amidines and Arylbenzimidazoles: Zinc‐Promoted Rearrangement of Oxime Acetates

AbstractAn efficient and straightforward zinc‐promoted rearrangement of oxime acetates with arylamines for the synthesis of amidines has been developed under mild conditions. This process involves N−O/C−C bond cleavages and C−C/C−N bond formations. Various oxime acetates and arylamines are suitable for this transformation. Furthermore, diverse arylbenzimidazoles could also be prepared through simple one‐pot procedure.magnified image

Synthesis of polysubstituted pyridines from oxime acetates using NH4I as a dual-function promoter.

Pyridine formation with oxime acetates as the building blocks under metal-free conditions is described. Ammonium iodide has proved to be a highly efficient promoter for oxime N-O bond reduction and subsequent condensation reactions, whereby it played a dual-function role in the transformation. While the three-component reaction of oxime acetates, benzaldehydes, and 1,3-dicarbonyls proceeded well with the assistance of a stoichiometric amount of ammonium iodide, the condensation of oximes and acroleins was enabled by using a catalytic initiator to afford substituted pyridines. By this protocol, substituted pyridine products were generated in moderate to excellent yields with tolerance towards a broad range of functional groups.

Copper-catalyzed synthesis of thiazol-2-yl ethers from oxime acetates and xanthates under redox-neutral conditions.

A novel copper-catalyzed annulation of oxime acetates and xanthates for the synthesis of thiazol-2-yl ethers with remarkable regioselectivity has been developed. Various oxime acetates, whether derived from aryl ketones or alkyl ketones, or natural product cores are suitable for this conversion. Unique dihydrothiazoles were also obtained when both reaction sites were methine. Mechanistic studies indicated that imino copper(iii) intermediates were involved. In addition, this protocol proceeded under redox-neutral conditions and did not require additives or ligands.

An efficient access to β-ketosulfones via β-sulfonylvinylamines: metal-organic framework catalysis for the direct C-S coupling of sodium sulfinates with oxime acetates.

A copper-based framework Cu2(OBA)2(BPY) was synthesized and used as a recyclable heterogeneous catalyst for the synthesis of β-sulfonylvinylamines from sodium sulfinates and oxime acetates via direct C–S coupling reaction. The transformation was remarkably affected by the solvent, and chlorobenzene emerged as the best option. This Cu-MOF displayed higher activity than numerous conventional homogeneous and MOF-based catalysts. The catalyst was reutilized many times in the synthesis of β-sulfonylvinylamines without considerably deteriorating in catalytic efficiency. These β-sulfonylvinylamines were readily converted to the corresponding β-ketosulfones via a hydrolysis step with aqueous HCl solution. To the best of our knowledge, this direct C–S coupling reaction to achieve β-sulfonylvinylamines was not previously conducted with a heterogeneous catalyst.

Copper-catalyzed coupling of oxime acetates and aryldiazonium salts: an azide-free strategy toward N-2-aryl-1,2,3-triazoles

An azide-free strategy for the synthesis of N-2-aryl-1,2,3-triazoles via copper-catalyzed coupling of oxime acetates and aryldiazonium tetrafluoroborates.

Reactivity and Synthetic Applications of α‐Functionalized Oxime Acetates: Divergent Access to Fulleropyrrolidines and Mono‐ and Disubstituted 1‐Fulleropyrrolines via Copper‐Catalyzed Redox‐Neutral N‐Heteroannulation with [60]Fullerene

AbstractThe unique reactivity and synthetic applications of oxime acetate derivatives with N, O and S substituents at the α‐position are disclosed for the first time, which leads to 2‐substituted fulleropyrrolidines and mono‐ and disubstituted 1‐fulleropyrrolines via copper‐catalyzed redox‐neutral N‐heteroannulation reactions with C60. This transformation is operationally simple and has a broad substrate scope and good functional group tolerance. Theoretical calculations at the level of B3LYP/6‐31G(d) were performed to elucidate the chemoselectivity of the reaction.magnified image

Copper‐Catalyzed C(sp3)−H/C(sp3)−H Cross‐Dehydrogenative Coupling with Internal Oxidants: Synthesis of 2‐Trifluoromethyl‐Substituted Dihydropyrrol‐2‐ols

AbstractThe first oxidative C(sp3)−H/C(sp3)−H cross‐dehydrogenative coupling (CDC) reaction promoted by an internal oxidant is reported. This copper‐catalyzed CDC reaction of oxime acetates and trifluoromethyl ketones provides a simple and efficient approach towards 2‐trifluoromethyldihydropyrrol‐2‐ol derivatives in a highly diastereoselective manner by cascade C(sp3)−C(sp3) bond formation and cyclization. These products were further transformed into various significant and useful trifluoromethylated heterocyclic compounds, such as trifluoromethylated furan, thiophene, pyrrole, dihydropyridazine, and pyridazine derivatives. A trifluoromethylated analogue of an Aβ42 lowering agent was also synthesized smoothly. Preliminary mechanistic studies indicated that this reaction involves a copper(I)/copper(III) catalytic cycle with the oxime acetate acting as an internal oxidant.

Copper-Catalyzed C(sp3 )-H/C(sp3 )-H Cross-Dehydrogenative Coupling with Internal Oxidants: Synthesis of 2-Trifluoromethyl-Substituted Dihydropyrrol-2-ols.

The first oxidative C(sp3 )-H/C(sp3 )-H cross-dehydrogenative coupling (CDC) reaction promoted by an internal oxidant is reported. This copper-catalyzed CDC reaction of oxime acetates and trifluoromethyl ketones provides a simple and efficient approach towards 2-trifluoromethyldihydropyrrol-2-ol derivatives in a highly diastereoselective manner by cascade C(sp3 )-C(sp3 ) bond formation and cyclization. These products were further transformed into various significant and useful trifluoromethylated heterocyclic compounds, such as trifluoromethylated furan, thiophene, pyrrole, dihydropyridazine, and pyridazine derivatives. A trifluoromethylated analogue of an Aβ42 lowering agent was also synthesized smoothly. Preliminary mechanistic studies indicated that this reaction involves a copper(I)/copper(III) catalytic cycle with the oxime acetate acting as an internal oxidant.

Concise Synthesis of Spiro[indoline‐3,2′‐pyrrolidine] and 1‐Azacarbazole Derivatives via Copper‐Catalyzed Cyclization of Indoles

AbstractA high‐yielding, copper‐catalyzed dearomatization reaction of indole from 2‐methylindole‐derived oxime acetates was realized, providing access to structurally novel spiro[indoline‐3,2′‐pyrrolidine] derivatives in 67–98% yields. When the C‐2 position of the indole was not substituted, azacarbazole derivatives were obtained in moderate yields. This transformation provides an efficient approach to access nitrogen‐containing spiroindolenine and azacarbazole derivatives with wide substrate scope.magnified image

Synthesis of Highly Substituted Pyridines through Copper-Catalyzed Condensation of Oximes and α,β-Unsaturated Imines.

A copper-catalyzed condensation reaction of oxime acetates and α,β-unsaturated ketimines to give pyridine derivatives is reported. The reaction features mild conditions, high functional-group compatibility, and high regioselectivity with respect to unsymmetrical oxime acetates, thus allowing the preparation of a wide range of polysubstituted pyridines, many of which are not readily accessible by conventional condensation methods.

Synthesis of Highly Substituted Pyridines through Copper‐Catalyzed Condensation of Oximes and α,β‐Unsaturated Imines

AbstractA copper‐catalyzed condensation reaction of oxime acetates and α,β‐unsaturated ketimines to give pyridine derivatives is reported. The reaction features mild conditions, high functional‐group compatibility, and high regioselectivity with respect to unsymmetrical oxime acetates, thus allowing the preparation of a wide range of polysubstituted pyridines, many of which are not readily accessible by conventional condensation methods.

Iron-Catalyzed Synthesis of 2H-Imidazoles from Oxime Acetates and Vinyl Azides under Redox-Neutral Conditions.

A novel and versatile method for the synthesis of 2H-imidazoles via iron-catalyzed [3 + 2] annulation from readily available oxime acetates with vinyl azides has been developed. This denitrogenative process involved N-O/N-N bond cleavages and two C-N bond formations to furnish 2,4-substituted 2H-imidazoles. This protocol was performed under mild reaction conditions and needed no additives or ligands. Furthermore, this is a green reaction involving oxime acetate as internal oxidant, acetic acid, and nitrogen as byproducts.

Synthesis of enaminones via copper-catalyzed decarboxylative coupling reaction under redox-neutral conditions.

A novel copper-catalyzed C(sp3)-H oxidative functionalization of aromatic oxime acetates with α-oxocarboxylic acids was reported. This process involved N-O/C-C bond cleavages and C-C bond formations to furnish substituted enaminones under redox-neutral conditions. The oxime acetates served as both reactants and internal oxidants. Furthermore, this transformation also features good functional group tolerance and needs no ligands or additional bases.

ChemInform Abstract: Copper‐Catalyzed Coupling of Oxime Acetates with Isothiocyanates: A Strategy for 2‐Aminothiazoles.

AbstractThe reaction tolerates aryl‐ and alkyl substituted oxime acetates and isothiocyanates, and offers access to 4‐substituted as well as 4,5‐disubstituted 2‐aminothiazoles.

Copper-Catalyzed Coupling of Oxime Acetates with Isothiocyanates: A Strategy for 2-Aminothiazoles.

A new strategy for 2-aminothiazoles is developed via the copper-catalyzed coupling of oxime acetates with isothiocyanates. Various 4-substituted and 4,5-disubstituted 2-aminothiazoles were formed smoothly under mild reaction conditions. This process involved copper-catalyzed N-O bond cleavage, activation of vinyl sp(2) C-H bonds, and C-S/C-N bond formations. It is noteworthy that the oxime acetates were used not only as a substrate but also as a single oxidant.

Beckmann Fragmentation and Successive Carbon-Carbon Bond Formation Using Grignard Reagents via Phosphonium Salt Intermediates.

The intermediates formed during the Beckmann fragmentation of α-alkoxy and α-alkoxy-α-alkyl oxime acetates have been successfully trapped as phosphonium salts, which were subsequently reacted with a variety of Grignard reagents to give the corresponding substituted products in good yields. Notably, this reaction proceeded smoothly even from α-alkoxy-α-alkyl oxime acetates.

ChemInform Abstract: Cu‐Catalyzed Three‐Component Cascade Annulation Reaction: An Entry to Functionalized Pyridines.

A concise copper-catalyzed N–O bond cleavage/C–C/C–N bond formation procedure has been described for the synthesis of multisubstituted pyridines. Various oxime acetates, activated methylene compounds, and a wide range of aldehydes bearing aryl, heteroaryl, vinyl, and trifluoromethyl groups were employed to provide the tri- or tetrasubstituted pyridines with flexible substitution patterns. Moreover, this method features inexpensive catalysts, no need for extra oxidant, and high step-enconomy, which make it pratical and attractive.

Internal Oxidant‐Triggered Aerobic Oxygenation and Cyclization of Indoles under Copper Catalysis

AbstractA concise synthesis of pyrazolo[1,5‐a]indole derivatives by copper‐catalyzed aerobic oxygenation and cyclization of indoles with oxime acetates is described. This protocol represents an elegant example of N‐1, C‐2, and C‐3 tri‐functionalization of indoles in one‐pot. Mechanistic studies indicate the reaction proceeds through a radical procedure. Oximes as an internal oxidant have been demonstrated to be a driver to initiate aerobic oxidation, which provides a new oxidative pattern for C‐H functionalization even with high atom‐ and step‐economy.