Oxonium Ylide Research Articles

Rh(II)/Pd(0) Dual Catalysis: Regiodivergent Transformations of Alkylic Oxonium Ylides

A Rh(II)/Pd(0) dual-catalysis strategy that promotes the regio-divergent transformations of alkylic oxonium ylides from α-diazo-β-ketoesters has been developed. Polyfunctionalized dihydrofuran-3-ones with an O-substituted quaternary carbon center and 2,3-disubstituted benzofurans can be selectively obtained in good to excellent yields at room temperature via one-pot synthesis. The reaction mechanism was further investigated by the control, stepwise, and crossover experiments.

Enantioselective Multicomponent Reaction for Rapid Construction of 1,2,5-Triol Derivatives with Vicinal Chiral Centers.

1,2,5-Triol derivatives with vicinal chiral centers have been synthesized from simple starting materials by one-pot method in good yields and with an excellent enantioselectivity. This process was promoted by a chiral secondary amine and iridium(I) cocatalyzed three-component reaction of aryldiazoacetates and alcohols with enals as electrophiles followed by a reduction with NaBH4. Iridium(I)-associated oxonium ylide intermediates were efficiently generated and successfully trapped by the amine-activated enals via a selective 1,4-addition manner, generating enantioselective three-component coupling products.

Gold-Catalyzed [2,3]-Sigmatropic Rearrangement: Reaction of Aryl Allyl Alcohols with Diazo Compounds.

A gold-catalyzed [2,3]-sigmatropic rearrangement reaction has been developed. The intermolecular rearrangement occurs between in situ generated donor-acceptor gold-carbenes and cinnamyl alcohols via tandem oxonium ylide formation. The desired rearranged product has been accomplished selectively over more conventional O-H insertion, cyclopropanation, cycloaddition, and C-H functionalization products under mild, open-air conditions. The scope of the work has been illustrated by synthesizing a new class of substrates that can be used for constructing complex molecular targets.

Evidence for heterolytic cleavage of a cyclic oxonium ylide: implications for the mechanism of the Stevens [1,2]-shift.

Formation and rearrangement of several oxonium ylides containing cyclopropylcarbinyl migrating groups were studied. Efficient ring-contraction by [1,2]-shift to form cyclopropane-substituted cyclobutanones was observed, with no competing cyclopropane fragmentation. Substitution with the hypersensitive mechanistic probe (trans,trans-2-methoxy-3-phenylcyclopropyl)methyl led to cyclopropane fragmentation via an apparent heterolytic pathway, providing the first evidence for ion pair intermediates from ylide cleavage, and suggesting a possible alternative heterolytic mechanism for the Stevens [1,2]-shift.

Stereoselective Synthesis of Oxabicyclo[2.2.1]heptenes via a Tandem Dirhodium(II)-Catalyzed Triazole Denitrogenation and [3 + 2] Cycloaddition.

A novel synthetic strategy for the diastereoselective synthesis of structurally diverse oxabicyclo[2.2.1]heptenes has been developed, featuring a tandem reaction combining a Rh-catalyzed triazole denitrogenation and a novel type of [3 + 2] cycloaddition reaction. This tandem reaction was thought to proceed via a five-membered oxonium ylide intermediate, which was formed by the intramolecular nucleophilic attack of the carbonyl group on the α-imino metallocarbene followed by an inter- or intramolecular [3 + 2] dipolar cycloaddition with a range of alkynes and alkenes.

Tandem O–H Insertion/[1,3]-Alkyl Shift of Rhodium Azavinyl Carbenoids with Benzylic Alcohols: A Route To Convert C–OH Bonds into C–C Bonds

Alcohols are among the most abundant and commonly used organic feedstock in industrial processes and academic research. The first tandem O-H insertion/[1,3]-alkyl shift reaction reported is between benzylic alcohols and rhodium azavinyl carbenoids derived from N-sulfonyl-1,2,3-triazoles, which provides a strategically novel way of cleaving C-OH bonds and forming C-C bonds. The substrate scope is broad, capable of covering 1°-, 2°-, and 3°-benzylic alcohols. Moreover, it constitutes a new and powerful synthetic method for constructing α-aminoketones. Mechanistic studies suggest that a [1,3]-alkyl shift of oxonium ylides is responsible for cleavage of the C-OH bonds.

ChemInform Abstract: A Transformation of Cyclopropyl Carbene: A Highly Enantioselective Three‐Component Reaction via Trapping Oxonium Ylide by Imine.

Abstract A transformation of cyclopropyl carbene generated from 2-cyclopropyl-2-diazoacetate via oxonium ylide was found by trapping the resulting ylide with imine. The asymmetric three-component reaction of cycloproyl diazoacetates, benzenemethanols and imines afforded a rapid and efficient method to synthesize complex cyclopropane derivatives with excellent diastereoselectivity and enantioselectivity.

ChemInform Abstract: Rhodium‐Catalyzed Cycloaddition of Carbonyl Ylides for the Synthesis of Spiro[furo[2,3‐a]xanthene‐2,3′‐indolin]‐2′‐one Scaffolds.

An intramolecular cycloaddition of oxonium ylides generated from 3-diazooxindole and a bifunctional substrate i.e. 2-methyl-2-(4-methylpent-3-en-1-yl)-2H-chromene-3-carbaldehyde has been achieved using 5 mol% of Rh2(OAc)4 to produce highly substituted 3,3,5a-trimethyl-3a,5,5a,11b-tetrahydro-3H,4H-spiro[furo[2,3-a]xanthene-2,3′-indolin]-2′-ones in good yields with high diastereoselectivity. This is the first example of the synthesis of biologically relavant polycyclic frameworks from readily accessible precursors.

ChemInform Abstract: Total Synthesis of (+)‐Tanikolide by a Traceless Stereoinduction Method Using Rhodium(II)‐Catalyzed Oxonium Ylide Formation—[2,3]‐Sigmatropic Rearrangement and NHC‐Catalyzed Ring‐Expansion Lactonization.

The total synthesis of (+)-tanikolide was accomplished by a traceless stereoinduction method using the key steps of a Rh(II)-catalyzed oxonium ylide formation–[2,3]-sigmatropic rearrangement and an N-heterocyclic carbene-catalyzed ring-expansion lactonization of tetrahydrofurfural. This synthetic route is applicable to the divergent synthesis of tanikolide analogues.

Enantioselective trapping of oxonium ylide intermediates by N-benzhydryl-α-imino ester: Synthesis of β-tetrasubstituted α-amino acids

A synergistic rhodium(II)/phosphoric acid catalyzed three component reaction of 3-diazooxindoles, alcohols and N-benzhydryl-α-imino ester is developed for the efficient construction of chiral β-alkoxy Cβ-tetrasubstituted α-amino acid derivatives in good yields and with excellent diastereoselectivities and high enantioselectivities. The synthetic application of the resulting products was illustrated by reducing with Pd/C under H2 atmosphere followed reacting with CSCl2 at room temperature to rapid afford 3-spirocyclic oxindole in a good yield with a chirality retainment. The three-component reaction is proposed to proceed through an electrophilic trapping of the oxonium ylides by N-benzhydryl-α-imino ester.

ChemInform Abstract: Synergistic Rhodium/Phosphoric Acid Catalysis for the Enantioselective Addition of Oxonium Ylides to ortho‐Quinone Methides.

AbstractA novel and highly stereoselective method for the domino‐type reaction of diazoesters with in situ generated ortho‐quinone methides to furnish functionalized benzofuran derivatives with three contiguous stereogenic centers is reported.

A transformation of cyclopropyl carbene: a highly enantioselective three-component reaction via trapping oxonium ylide by imine

A transformation of cyclopropyl carbene generated from 2-cyclopropyl-2-diazoacetate via oxonium ylide was found by trapping the resulting ylide with imine. The asymmetric three-component reaction of cycloproyl diazoacetates, benzenemethanols and imines afforded a rapid and efficient method to synthesize complex cyclopropane derivatives with excellent diastereoselectivity and enantioselectivity.

ChemInform Abstract: Divergent Synthesis of Multisubstituted Tetrahydrofurans and Pyrrolidines via Intramolecular Aldol‐Type Trapping of Onium Ylide Intermediates.

AbstractThe corresponding title compounds are obtained through a metal—carbene‐induced oxonium ylide or ammonium ylide formation followed by an intramolecular aldol‐type trapping of these active intermediates.

Total Synthesis of (+)-Tanikolide by a Traceless Stereoinduction Method Using Rhodium(II)-Catalyzed Oxonium Ylide Formation–[2,3]-Sigmatropic Rearrangement and NHC-Catalyzed Ring-Expansion Lactonization

The total synthesis of (+)-tanikolide was accomplished by a traceless stereoinduction method using the key steps of a Rh(II)-catalyzed oxonium ylide formation–[2,3]-sigmatropic rearrangement and an N-heterocyclic carbene-catalyzed ring-expansion lactonization of tetrahydrofurfural. This synthetic route is applicable to the divergent synthesis of tanikolide analogues.

Synergistic Rhodium/Phosphoric Acid Catalysis for the Enantioselective Addition of Oxonium Ylides to ortho‐Quinone Methides

AbstractWe report herein a powerful and highly stereoselective protocol for the domino‐type reaction of diazoesters with ortho‐quinone methides generated in situ to furnish densely functionalized chromans with three contiguous stereogenic centers. A transition‐metal and a Brønsted acid catalyst were shown to act synergistically to produce a transient oxonium ylide and ortho‐quinone methide, respectively, in two distinct cycles. These intermediates underwent subsequent coupling in a conjugate‐addition–hemiacetalization event in generally good yield with excellent diastereo‐ and enantioselectivity.

Synergistic Rhodium/Phosphoric Acid Catalysis for the Enantioselective Addition of Oxonium Ylides to ortho-Quinone Methides.

We report herein a powerful and highly stereoselective protocol for the domino-type reaction of diazoesters with ortho-quinone methides generated in situ to furnish densely functionalized chromans with three contiguous stereogenic centers. A transition-metal and a Brønsted acid catalyst were shown to act synergistically to produce a transient oxonium ylide and ortho-quinone methide, respectively, in two distinct cycles. These intermediates underwent subsequent coupling in a conjugate-addition-hemiacetalization event in generally good yield with excellent diastereo- and enantioselectivity.

ChemInform Abstract: Pd(II)‐Catalyzed Formal [4 + 1] Cycloaddition Reactions of Diazoacetates and Aryl Propargyl Alcohols to Form 2,5‐Dihydrofurans.

AbstractThe presented cycloaddition is an auto‐tandem catalytic process which proceeds via an intermolecularly formed oxonium ylide which is trapped by the activated alkyne.

Divergent Synthesis of Multisubstituted Tetrahydrofurans and Pyrrolidines via Intramolecular Aldol-type Trapping of Onium Ylide Intermediates.

This paper reports a divergent strategy for the synthesis of multisubstituted tetrahydrofurans and pyrrolidines, starting from easily accessible β-hydroxyketones or β-aminoketones to react with diazo compounds. Under Rh(II) catalysis, this transformation is proposed to proceed through a metal-carbene-induced oxonium ylide or ammonium ylide formation followed by an intramolecular aldol-type trapping of these active intermediates. A series of highly substituted tetrahydrofurans and pyrrolidines are synthesized in high yields with good to excellent diastereoselectivities. Preliminary biological evaluations revealed that both types of heterocycles show good PTP1B inhibitory activities.

Pd(II)-catalyzed formal [4+1] cycloaddition reactions of diazoacetates and aryl propargyl alcohols to form 2,5-dihydrofurans.

A Pd(II)-catalyzed formal [4+1] cycloaddition of aryl diazoacetates and aryl propargyl alcohols is reported to afford 2,5-dihydrofuran derivatives as the dominant product over other traditional ones. The auto-tandem catalytic process is proposed to occur via Pd(II)-catalyzed intermolecular oxonium ylide formation and subsequent intramolecular trapping of the ylide with Pd(II)-activated alkynes.

ChemInform Abstract: Trapping of Carboxylic Oxonium Ylides with N‐Boc Imines for the Facile Synthesis of β‐Amino Alcohol Derivatives.

A Rh2(OAc)4-catalyzed three-component reaction of carboxylic acids, α-diazoacetophenones, and N-Boc imines has been developed to efficiently produce β-amino alcohol derivatives. Oxonium ylides generated from carboxylic acids and metal carbenoids have been intercepted by electrophiles for the first time.