Α-imino Carbene Research Articles

Synthesis of Piperidin-4-one Derivatives via α-Imino Rhodium Carbene-Initiated 1,2-Aryl/Alkyl Migration and Annulation.

Valuable piperidin-4-one derivatives were synthesized in excellent yields via an α-imino carbene-initiated cascade reaction involving 1,2-aryl/alkyl migration and annulation. The excellent selectivity of alkyl migration was attributed to the neighboring group participation of 2-bromoethyl. Features such as high efficiency, excellent migrating selectivity, broad substrate scope, and convenient one-pot procedure qualified this protocol as an effective tool for piperidine derivative synthesis. The product could be transformed to a bioactive molecule easily. The migration-annulation reaction of α-imino carbene provided a powerful strategy for heterocycle construction.

Regiodivergent Synthesis of Oxadiazocines via Dirhodium-Catalyzed Reactivity of Oxazolidines and α-Imino Carbenes

AbstractUsing electron-rich or electron-poor N-substituted oxazolidines as substrates, selective formation of either ammonium or oxonium ylides is possible in the presence of α-imino carbenes. As such, treatment of 5-membered oxazolidine precursors with N-sulfonyl-1,2,3-triazoles under dirhodium catalysis (2 mol%) affords the regiodivergent synthesis of either 8-membered 1,3,6- or 1,4,6-oxadiazocines upon the initial N or O reactivity with the carbene.

Synthesis of α-Amino Cyclobutanones via Formal 1,3-Hydroxy Migration Triggered by Formation of α-Imino Rhodium Carbene.

Formal intramolecular 1,3-OH migration of α-imino carbene was achieved producing a unique zwitterion, and the subsequent selective annulation afforded α-amino cyclobutanone. Features such as readily available substrates, mild reaction conditions, a time-saving procedure, excellent functional group compatibility, and valuable transformations of the products qualified this unique protocol as an efficient tool for the synthesis of strained cyclic compounds. Density functional theory calculations were in good agreement with experimental observations, and a plausible mechanism is presented.

Generation of Functionalized Azepinone Derivatives via a (4 + 3)-Cycloaddition of Vinyl Ketenes and α-Imino Carbenes Derived from N-Sulfonyl-triazoles.

An intermolecular RhII-catalyzed, formal (4 + 3)-cycloaddition between vinyl ketenes and N-sulfonyl-1,2,3-triazoles for the construction of azepinone products is described. Employing vinyl ketenes as a 1,4-dipolar surrogate, instead of the more commonly used dienyl moieties, allows for the intermolecular and selective formation of azepinone products over a potential (3 + 2)-cycloadduct under mild reaction conditions allows for the generation of azepinone products in up to 98% yield.

Gold-Catalyzed Nitrene Transfer from Benzofuroxans to N-Allylynamides: Synthesis of 3-Azabicyclo[3.1.0]hexanes.

The gold-catalyzed reaction between benzofuroxans, functioning as nitrene transfer reagents, and N-allylynamides leads to 3-azabicyclo[3.1.0]hexan-2-imines. This highly selective annulation proceeds smoothly under mild conditions (5 mol % Ph3PAuNTf2, PhCl, 60 °C) and exhibits high functional group tolerance (21 examples, ≤96% yields). The obtained cyclopropanated products represent a useful synthetic platform with an easily modulated substitution pattern as illustrated by their postmodifications. Intramolecular cyclopropanation of gold α-imino carbene intermediates is suggested as a key step of the catalytic cycle.

Access to Chiral Rigid Hemicyanine Fluorophores from Tröger Bases and α-Imino Carbenes.

Chiral hemicyanine fluorophores are afforded in three steps only from Tröger bases via α-imino carbene additions, an original aminal deprotection and Cu(II)-mediated oxidation. The stable benzodiazepinoindolium salts are readily isolated and present (chir)optical properties that can be fine-tuned by late-stage cross-coupling functionalization. The hemicyanine character of dyes was rationalized using first principles.

Rhodium-Catalyzed Annulation of α-Imino Carbenes with α,β-Unsaturated Ketones: Construction of Multisubstituted 2,3-Dihydropyrrole/pyrrole Rings.

An efficient annulation of α-imino rhodium carbenes with α,β-unsaturated ketones has been developed to generate multisubstituted 2,3-dihydropyrrole derivatives. Using the optimized catalyst, this approach is compatible with both cyclic and normal linear α,β-unsaturated ketones. Further detosylation in the presence of base could produce multisubstituted pyrroles. The new method has the potential to enable the rapid construction of bioactive molecules containing pyrrole rings.

Polycyclic Indoline-Benzodiazepines through Electrophilic Additions of α-Imino Carbenes to Tröger Bases.

Polycyclic indoline‐benzodiazepines can be accessed through the intermolecular reaction of Tröger bases with N‐sulfonyl‐1,2,3‐triazoles. Under RhII catalysis, α‐imino carbenes are generated and a subsequent cascade of [1,2]‐Stevens, Friedel–Crafts, Grob, and aminal formation reactions yield the polycyclic heterocycles as single isomers (d.r.>49:1, four stereocenters including two bridgehead N atoms). Further ring expansion by insertion of a second α‐imino carbene leads to elaborated polycyclic 9‐membered‐ring triazonanes.

Copper-Catalyzed P-H Insertions of α-Imino Carbenes for the Preparation of 3-Phosphinoylindoles.

A highly efficient P-H insertion of α-imino copper carbene into H-phosphine oxides, leading to 3-phosphinoylindoles with a broad substrate diversity and good chemoselectivity, is established. This methodology provides a rapid and efficient approach for the C (sp2)-P bond formation via the P-H insertion strategy. The stereoselective P-H insertion of α-imino copper carbene represents a unique example of asymmetric P-H insertion, affording P-stereogenic 3-phosphinoylindoles with high stereoselectivities.

Enantioselective Intermolecular C-H Functionalization of Allylic and Benzylic sp(3) C-H Bonds Using N-Sulfonyl-1,2,3-triazoles.

The enantioselective intermolecular sp(3) C-H functionalization at the allylic and benzylic positions was achieved using rhodium-catalyzed reactions with 4-phenyl-N-(methanesulfonyl)-1,2,3-triazole. The optimum dirhodium tetracarboxylate catalyst for these reactions was Rh2(S-NTTL)4. The rhodium-bound α-imino carbene intermediates preferentially reacted with tertiary over primary C-H bonds in good yields and moderate levels of enantioselectivity (66-82% ee). This work demonstrates that N-sulfonyltriazoles can be applied to the effective C-H functionalization at sp(3) C-H bonds of substrates containing additional functionality.

Rhodium-Catalyzed Synthesis of 4-Bromo-1,2-dihydroisoquinolines: Access to Bromonium Ylides by the Intramolecular Reaction of a Benzyl Bromide and an α-Imino Carbene.

Highly functionalized 4-bromo-1,2-dihydroisoquinolines were synthesized from readily available 4-(2-(bromomethyl)phenyl)-1-sulfonyl-1,2,3-triazoles. A bromonium ylide is proposed as the key intermediate, which can be formed by the intramolecular nucleophilic attack of the benzyl bromide on the α-imino rhodium carbene formed in the presence of the rhodium catalyst.

ChemInform Abstract: Rhodium‐Catalyzed Synthesis of 2,5‐Epoxybenzo[f][1,4]oxazepines by Tandem Reaction of 1‐Sulfonyl‐1,2,3‐triazoles and Salicylaldehydes.

Readily available 1-sulfonyl-1,2,3-triazoles were converted into α-imino carbenes in the presence of catalytic amounts of rhodium(II) salts. The carbenes underwent a tandem reaction with salicylaldehydes to provide a series of functionalized 2,5-epoxybenzo[f][1,4]oxazepines in high yields.

The synthesis of pyrroles and oxazoles based on gold α-imino carbene complexes

Cationic gold complexes of α-oximimino carbenes have been identified to react with weak nucleophiles including enol ethers and nitriles. These findings allowed us to develop the highly efficient synthesis of pyrroles and oxazoles.

Synthesis of 2,5-epoxy-1,4-benzoxazepines via rhodium(II)-catalyzed reaction of 1-tosyl-1,2,3-triazoles and salicylaldehydes

The α-imino carbenes generating from 1-tosyl-1,2,3-triazoles have exhibited unique reactivities. A novel and efficient route for the construction of oxa-bridged 2,5-epoxy-1,4-benzoxazepines through a rhodium(II)-catalyzed tandem process of triazoles and salicylaldehydes has been developed. The oxazoles are obtained when 2-methanesulfonamidyl benzaldehyde is used instead of salicylaldehydes.

Rhodium-Catalyzed Synthesis of 2,5-Epoxybenzo[f][1,4]oxazepines by Tandem Reaction of 1-Sulfonyl-1,2,3-triazoles and Salicylaldehydes

Readily available 1-sulfonyl-1,2,3-triazoles were converted into α-imino carbenes in the presence of catalytic amounts of rhodium(II) salts. The carbenes underwent a tandem reaction with salicylaldehydes to provide a series of functionalized 2,5-epoxybenzo[f][1,4]oxazepines in high yields.

Rhodium-catalyzed synthesis of multi-substituted furans from N-sulfonyl-1,2,3-triazoles bearing a tethered carbonyl group

The efficient synthesis of highly functionalized furan derivatives from 1-sulfonyl-1,2,3-triazoles with a pendent carbonyl group is reported. The process involves an intramolecular trapping of α-imino carbene and subsequent aromatization.

Synthesis of N-acylamidines via rhodium-catalyzed reaction of nitrosobenzene derivatives with N-sulfonyl-1,2,3-triazoles.

α-Imino rhodium carbene, readily generated from N-sulfonyl-1,2,3-triazole, underwent cycloaddition and subsequent rearrangement with a nitrosobenzene derivative to afford N-acylamidine. The unprecedented C-C bond cleavage of α-imino carbene was facilitated by the weakness of the N-O bond.