Generation Of Ylides Research Articles

Enantioselective Synthesis of the Spirotropanyl Oxindole Scaffold through Bimetallic Relay Catalysis.

Spirotropanyl oxindole alkaloids like alstonisine and chitosenine show a wide range of bioactivites. We report the first enantioselective synthesis of the spirotropanyl oxindole scaffold by means of a bimetallic relay catalysis strategy. A new class of E-oximino α-diazo ketones was developed for the intramolecular generation of transient azomethine ylides catalyzed by an achiral RhII complex and a subsequent intermolecular 1,3-dipolar cycloaddition catalyzed by a chiral N,N'-dioxide NdIII Lewis acid complex. The enantioselectively catalyzed transformation has broad scope and yields the desired spirotropanyl oxindole cycloadducts in high yields and with very high enantio- and diastereoselectivity.

Post-Ugi Cascade Transformations for Accessing Diverse Chromenopyrrole Collections.

Employing a build/couple/pair strategy, a serendipitous one-pot protocol for the diastereoselective construction of diverse collections of chromenopyrroles is described. This methodology features an unprecedented five-step cascade including azomethine ylide generation followed by in situ intramolecular [3 + 2]-cycloaddition. Furthermore, this protocol was extended to access enantiopure chromenopyrroles using amino acids as chiral auxiliary. Moreover, postpairing reactions were employed to increase the diversity and complexity of our pilot compound collections.

Efficient generation of an oxidopyrylium ylide using a Pd catalyst and its [5+2] cycloadditions with several dipolarophiles.

An efficient method for the generation of an oxidopyrylium ylide from 6-acetoxy-6-acetoxymethyl-2H-pyran-3(6H)-one using a Pd catalyst and [5+2] cycloadditions of the resulting ylide are described. Among substituted styrene derivatives as dipolarophiles, electron-rich styrenes showed higher yield (up to 80%). The [5+2] cycloaddition reactions can also be applied to exo-methylene cyclic compounds, and an improved method for the synthesis of polygalolide intermediate has been demonstrated.

Direct Wittig Olefination of Alcohols.

A base-promoted transition metal-free approach to substituted alkenes using alcohols under aerobic conditions using air as the inexpensive and clean oxidant is described. Aldehydes are relatively difficult to handle compared to corresponding alcohols due to their volatility and penchant to polymerize and autoxidize. Wittig ylides are easily oxidized to aldehydes and consequently form homo-olefination products. By the strategy of simultaneously in situ generation of ylides and aldehydes, for the first time, alcohols are directly transferred to olefins with no need of prepreparation of either aldehydes or ylides. Thus, the di/monocontrollable olefination of diols is accomplished. This synthetically practical method has been applied in the gram-scale synthesis of pharmaceuticals, such as DMU-212 and resveratrol from alcohols.

Carbonyl Ylides Derived from Palladium Carbenes: The Impressive Fluorine Effect

AbstractThe first example for the generation of carbonyl ylides from palladium carbenes is reported. Systematic investigation of the substituents attached to the carbonyl group indicates that the employment of trifluoromethyl group as the substituent is very critical for the success of this transformation. The remarkable fluorine effect on the reactivity is very impressive, which allows the construction of various trifluoromethylated oxiranes in high yields and diastereoselectivities.magnified image

Rh2(OAc)4-catalyzed reaction of 2-(2-carbonylvinyl)-3-phenyl-2H-azirines with diazo esters

Rh2(OAc)4-catalyzed reaction of 2-(2-carbonylvinyl)-3-phenyl-2H-azirines with diazo esters proceeds through an intermediate generation of azirinium ylide suffering a nonstereoselective ring opening to form (3Z)- and (3E)-2-azahexa-1,3,5-trienes. The former depending on configuration of the C 5 =C 6 bond may undergo cyclization either in derivative of 2,3-dihydropyridine, or in pyrrolium ylide that isomerizes into a derivative of 1H-pyrrole. According to DFT calculation, the preferred formation of pyrroles at increasing volume of Z-substituent at the atom C 6 and of substituents at the atom C 1 of 2-azahexatriene occurs due to the destabilization of more sterically loaded transition states of 1,6-cyclization.

Redesign of a Pyrylium Photoredox Catalyst and Its Application to the Generation of Carbonyl Ylides.

We report the exploration into photoredox generation of carbonyl ylides from benzylic epoxides using newly designed 4-mesityl-2,6-diphenylpyrylium tetrafluoroborate (MDPT) and 4-mesityl-2,6-di-p-tolylpyrylium tetrafluoroborate (MD(p-tolyl)PT) catalysts. These catalysts are excited at visible wavelengths, are highly robust, and exhibit some of the highest oxidation potentials reported. Their utility was demonstrated in the mild and efficient generation of carbonyl ylides from benzylic epoxides that otherwise could not be carried out by current common photoredox catalysts.

General Approach toward Aspidospermatan-Type Alkaloids Using One-Pot Vilsmeier-Haack Cyclization and Azomethine Ylide Cycloaddition.

The development of a new one-pot reaction sequence afforded the tricyclic core of several aspidospermatan-type alkaloids from a linear, densely functionalized substrate. The key sequence features a highly chemoselective formamide activation that triggered a Vilsmeier-Haack cyclization, followed by an azomethine ylide generation and intramolecular cycloaddition. The choice of nucleophile, azomethine ylide precursor, and dipolarophile was crucial to the success of the sequence.

Gold-Catalyzed [3+2]/Retro-[3+2]/[3+2] Cycloaddition Cascade Reaction of N-Alkoxyazomethine Ylides.

A novel cascade reaction has been developed for the synthesis of 2,6-methanopyrrolo[1,2-b]isoxazoles based on the gold-catalyzed generation of an N-allyloxyazomethine ylide. This reaction involves sequential [3+2]/retro-[3+2]/[3+2] cycloaddition reactions, thus providing facile access to fused and bridged heterocycles which would be otherwise difficult to prepare using existing synthetic methods. Notably, this reaction allows the efficient construction of three C-C bonds, one C-O bond, one C-N bond and one C-H bond, as well as the cleavage of one C-C bond, one C-O bond and one C-H bond in a single operation. The intermolecular cycloaddition of an N-allyloxyazomethine ylide and the subsequent application of the product to the synthesis of tropenol is also described.

Synthesis of Functionalized 3-Spiro[cyclopropa[a]pyrrolizine]- and 3-Spiro[3-azabicyclo[3.1.0]hexane]oxindoles from Cyclopropenes and Azomethine Ylides via [3 + 2]-Cycloaddition.

3-Spiro[cyclopropa[a]pyrrolizine]- and 3-spiro[3-azabicyclo[3.1.0]hexane]oxindoles were prepared in moderate to high yields via one-pot three-component reactions using substituted isatins, α-amino acids, and cyclopropenes. The key step is an intramolecular [3 + 2]-cycloaddition reaction of an in situ generated azomethine ylide onto a cyclopropene. Both N-substituted and N-unsubstituted α-amino acids, dipeptide Gly-Gly, and also benzylamine were used as the amine component for the azomethine ylide generation. The anticancer activity of some of the obtained compounds against human leukemia K562 cell line was evaluated by flow cytometry in vitro.

Tandem Brook Rearrangement/Silicon Polonovski Reaction via Oxidative Generation of Ammonium Ylides.

A tandem Brook rearrangement/silicon Polonovski reaction has been achieved by in situ generation of ammonium ylides via the oxidation of α-silyl-tertiary amines. Furthermore, we found that the oxidation of N-(1-cyano-1-silyl)methyl-tertiary amines with peracids induced the tandem Brook rearrangement/silicon Polonovski reaction/fragmentation to give formamide derivatives in moderate yields.

ChemInform Abstract: Nucleophilic Difluoromethylation Using (Bromodifluoromethyl)trimethylsilane.

A combination of (bromodifluoromethyl)trimethylsilane (Me3SiCF2Br), triphenylphosphine, and DMPU serves as a source of difluorinated phosphorus ylide Ph3P═CF2 under mild conditions. The system was used to effect nucleophilic difluoromethylation of ketones and nitro alkenes. The reaction efficiency is believed to be associated with Lewis acidic activation of the substrates by a silylium species formed upon generation of the phosphorus ylide.

Iron(II) N-heterocyclic carbene complexes in catalytic one-pot Wittig reactions: Mechanistic insights

An iron(II) N-heterocyclic carbene (NHC) complex is applied as catalyst for aldehyde olefination with ethyl diazoacetate (EDA) in the presence of triphenylphosphine. The reaction leads to high olefin yields with very good E-selectivities. The key step of the reaction is the catalytic in situ generation of a phosphorus ylide. Mechanistic studies reveal two possible pathways for the formation of the Wittig reagent with respect to the carbene source being the metal carbene (NHC)FeIVCH(CO2Et), and phosphazine, Ph3PNNCH(CO2Et). Based on the experimental observations a new mechanism for the transformation of phosphazine is proposed.

ChemInform Abstract: Synthesis of Substituted Pyrrolo[2,1‐a]isoquinolines by Gold‐Catalyzed Domino Cyclization of Alkynyl Iminoesters.

A novel gold-catalyzed double cyclization leading to a biologically important pyrroloisoquinoline skeleton was established. The reaction sequence involving 6-exo-dig cyclization of alkynyl iminoester and [3+2] cycloaddition of azomethine ylide proceeded smoothly in the presence of 0.5–1.0 mol% (CyJohnPhos)AuCl/AgOTf at 65 or 80 °C. This strategy with (–)-phenylmenthol-derived iminoester enables a generation of chiral azomethine ylide in situ to construct an optically active pyrroloisoquinoline in a highly diastereoselective manner. An alkyne and alkenes with electron-withdrawing group could be utilized as dipolarophiles. Iminoesters having terminal and internal alkynes were applied as reaction substrates to afford the corresponding pyrroloisoquinolines.

Nucleophilic Difluoromethylation Using (Bromodifluoromethyl)trimethylsilane.

A combination of (bromodifluoromethyl)trimethylsilane (Me3SiCF2Br), triphenylphosphine, and DMPU serves as a source of difluorinated phosphorus ylide Ph3P═CF2 under mild conditions. The system was used to effect nucleophilic difluoromethylation of ketones and nitro alkenes. The reaction efficiency is believed to be associated with Lewis acidic activation of the substrates by a silylium species formed upon generation of the phosphorus ylide.

ChemInform Abstract: Copper(I) Catalyzed Diastereoselective Multicomponent Synthesis of Spiroindolo‐pyrrolidines/‐imidazolidines/‐triazolidines from Diazoamides via Azomethine Ylides.

AbstractThe novel method to synthesize highly substituted spiroindolo‐pyrrolidines/‐imidazolidines/‐triazolidines is efficiently catalyzed by Cu(I)TC.

The Synthesis of Two Regioisomeric Aldehydes with a Tetrahydrobenzo[b]thiophene Scaffold and Their Application in Solvent-Free Intramolecular 1,3-Dipolar Cycloaddition Reactions

The paper describes synthesis of two regioisomeric 2-amino-3-formyl and 3-amino-2-formyl substituted derivatives of tetrahydrobenzo[b] thiophene and their preparation for subsequent thermally-initiated reactions with secondary amines for generation of azomethine ylides; these azomethine ylides entered into intramolecular 1,3-dipolar cycloadditions. In this way, two series of new fused heterocyclic compounds were prepared, having three stereogenic centres. The compounds were identified and their structures determined.

Synthesis of Substituted Pyrrolo[2,1-a]isoquinolines by Gold-Catalyzed Domino Cyclization of Alkynyl Iminoesters

A novel gold-catalyzed double cyclization leading to a biologically important pyrroloisoquinoline skeleton was established. The reaction sequence involving 6-exo-dig cyclization of alkynyl iminoester and [3+2] cycloaddition of azomethine ylide proceeded smoothly in the presence of 0.5–1.0 mol% (CyJohnPhos)AuCl/AgOTf at 65 or 80 °C. This strategy with (–)-phenylmenthol-derived iminoester enables a generation of chiral azomethine ylide in situ to construct an optically active pyrroloisoquinoline in a highly diastereoselective manner. An alkyne and alkenes with electron-withdrawing group could be utilized as dipolarophiles. Iminoesters having terminal and internal alkynes were applied as reaction substrates to afford the corresponding pyrroloisoquinolines.

Copper(I) catalyzed diastereoselective multicomponent synthesis of spiroindolo-pyrrolidines/-imidazolidines/-triazolidines from diazoamides via azomethine ylides.

Investigations of regio-, chemo- and diastereoselective studies on three- as well as four-component reactions using diazooxindoles, imines, aldehydes, amines, alkenes, alkynes or diazenes in the presence of copper(I) thiophene-2-carboxylate are performed to furnish spiroindolo-pyrrolidine/-imidazolidine/-triazolidine ring systems in good yields. A mixture of products was obtained when unsymmetrical alkenes were used as dipolarophiles. This study demonstrates the successful generation of intermolecular azomethine ylides from copper(I) carbenoids and their subsequent 1,3-dipolar cycloaddition reactions with various dipolarophiles, such as olefins (C=C), imines (C=N), diazenes (N=N) in a stereoselective manner. Single-crystal X-ray analyses were performed to establish unambiguously the structure and stereochemistry of spiroheterocyclic ring systems.

ChemInform Abstract: ′On‐water′ Generation of Carbonyl Ylides from Diazoamides: Rhodium(II) Catalyzed Synthesis of Spiroindolo‐Oxiranes and ‐Dioxolanes with an Interesting Diastereoselectivity.

Abstract The ‘on-water’ generation of carbonyl ylide dipoles from diazoamides in the presence of rhodium(II) acetate dimer as the catalyst was demonstrated for the first time to synthesize spiroindolo-oxiranes and -dioxolanes. Unusual generation of carbonyl ylides with aromatic aldehydes having electron-withdrawing substituents and 1,3-dipolar cycloaddition reactions with aromatic aldehydes having electron-donating substituents were described in water with complete diastereoselectivity. This discovery provides an environmentally friendly way to generate carbonyl ylide dipoles and to synthesize substituted spiro-heterocycles in water with stereoselectivity, avoiding the use of toxic halogenated organic solvents.