Α-diazo Carbonyl Research Articles

Modular Synthesis of Tetrasubstituted Vinyl Sulfides via One-Pot Sequential Carbene Transfer Reaction from Thiols with α-Diazo Carbonyl Compounds.

We present a one-pot reaction that offers an efficient approach to synthesizing tetrasubstituted vinyl sulfides with high stereoselectivity. This method involves the sequential Wolff rearrangement, ylide formation, and [1,4]-aryl transfer by utilizing aryl and alkyl thiols and α-diazo carbonyl compounds as substrates. Notably, this reaction features commercially available materials, straightforward operation, atom economy, and broad substrate scope. Moreover, the primary photophysical properties (aggregation-induced emission effect) of the products were also investigated, which might be useful in functional materials via structural modification.

Substrate-Controlled Divergent Synthesis of Benzimidazole-Fused Quinolines and Spirocyclic Benzimidazole-Fused Isoindoles.

A Rh(III)-catalyzed annulation of 2-arylbenzimidazoles with α-diazo carbonyl compounds via C-H activation/carbene insertion/intramolecular cyclization is explored. The switchable product selectivity is achieved by the use of distinct α-diazo carbonyl compounds. Benzimidazole-fused quinolines are obtained through [4 + 2] annulation exclusively when 2-diazocyclohexane-1,3-diones are used, where they act as a C2 synthon. Alternatively, diazonaphthalen-1(2H)-ones merely function as a one-carbon unit synthon to generate a quaternary center through [4 + 1] cyclization to afford spirocyclic benzimidazole-fused isoindole naphthalen-2-ones. A thorough mechanistic study reveals the course of the reaction.

Synthesis of Acyl Cyclopentaquinolinones through Simultaneous Construction of the Heterocyclic Scaffold and Introduction of the Acyl Group.

Presented herein is an effective and concise synthesis of acyl cyclopentaquinolinone derivatives via the cascade reactions of N-(o-ethynylaryl)acrylamides with α-diazo carbonyl compounds. The formation of product involves a visible light-induced radical formation from α-diazo carbonyl compound followed by its addition onto the acrylamide moiety to trigger double radical annulation, single-electron oxidation, and β-elimination. To our knowledge, this is the first example in which the cyclopentaquinolinone scaffold was constructed along with the introduction of an acyl group under visible light irradiation conditions. Compared with literature methods for similar purpose, this newly developed protocol has advantages such as readily accessible substrates, mild reaction conditions, valuable products, concise synthetic procedure, and high sustainability. With all these merits, this method is expected to find wide applications in the construction of related acyl heterocyclic skeletons.

Amphos-Mediated Conversion of Alkyl Azides to Diazo Compounds and One-Pot Azide-Site Selective Transient Protection, Click Conjugation, and Deprotective Transformation.

A one-pot conversion of alkyl azides to diazo compounds is outlined. After the reaction of α-azidocarbonyl compounds with Amphos, treatment of the resulting phosphazides with silica gel in a wet solvent afforded α-diazo carbonyl products. Through the azido group protection property of Amphos, inter- and intramolecular azide-site selective reactions of azido group protection, click functionalization, and deprotection of the diazo group have been demonstrated in one pot.

Enantioselective Zirconium-catalyzed Transformations

Abstract: The cheaper and less-toxic metals of group 4 compared with common metals used in catalysis are increasingly applied in catalysis, resulting in the development of many novel greener transformations. Zirconium is abundant, non-toxic, and exhibits a remarkably diversified chemical reactivity among these metals. Since the first asymmetric zirconium-catalyzed reaction disclosed by Nugent in 1992, a wide variety of chiral zirconium catalysts have been proven to be capable of promoting many types of highly enantioselective transformations, spanning from standard reactions, such as Friedel-Crafts reactions, cycloadditions, aldol reactions, Mannich reactions, epoxidations, nucleophilic additions to carbonyl compounds and derivatives, cyanations, ring-opening reactions, hydroxylations, hydroformylations, carboaluminations among others, to more modern and complex domino and tandem processes. This review aims to collect the major progress achieved in the field of enantioselective transformations of all types promoted by chiral zirconium catalysts, covering the literature since the beginning of 2003 and illustrating the power of these non-toxic catalysts to provide high enantioselectivity in almost all kinds of asymmetric organic reactions. It is divided into ten parts, focussing consecutively on enantioselective Friedel-Crafts reactions, cycloadditions, aldol reactions, Mannich reactions, epoxidations, additions of alkylzinc reagents to imines, cyanations, ring-opening reactions, hydroxylations, and domino/ tandem reactions. The diversity of these transformations well reflects that of the products synthesized. For example, chiral indole and pyrrole derivatives were prepared from Friedel-Crafts reactions; pyranones, pyridones and pyrazolidines from cycloadditions; β-hydroxy α-diazo carbonyl compounds, β- hydroxy (thio)esters and β-hydroxy-α-amino acid derivatives from aldol reactions; β-amino (thio)esters from Mannich reactions; functionalized epoxides from epoxidations; amines from additions of alkylzinc reagents to imines; amino nitriles from cyanations; 1,2-diamines and β-vinyloxy alcohols from ring-opening processes; 2- hydroxy 1-indanones from hydroxylations; various amines, 1,3-anti-diol monoesters, β-amino esters, α,β- dihydroxy acid derivatives, α-amino ketones, indoles, cyclopentane and aryl α-aminophosphonates from domino/ tandem reactions. Furthermore, the utility of these novel methodologies was demonstrated in the total synthesis of numerous essential bioactive products, such as (+)-prelactone C, (+)-9-deoxygoniopypyrone, (+)- coniine, vancomycin, (+)-fusarisetin A, mycolipenic acid, onchidin, indoxacarb, tachykinin receptor antagonists, cerebroprotecting agent MS-153, and L-erythro-sphingosine. : The advances achieved in the last three decades demonstrate that the non-toxicity, abundance, and efficiency of zirconium make its application in catalysis suiting the growing demand for more environmentally benign processes, offering the real opportunity to replace other toxic and expensive metals in the near future.

Comparison of metal-carbenoid reactions of β-2-five-membered heteroaryl substituted α,β-unsaturated ketones.

In this study, β-2-heteroaryl substituted (N-methyl 2-pyrrolyl, 2-thiophenyl, 2-furyl) α,β-unsaturated ketones were reacted with two α-diazo carbonyl compounds that had different characteristics (dimethyl diazo malonate and 1-diazo-1-phenyl-propane-2-one) in the presence of both copper and rhodium catalysts. In the case of reactions with N-methyl 2-pyrrolyl α,β-unsaturated ketones, the major product was the insertion derivative. However, in the reactions of 2-thiophenyl and 2-furyl α,β-unsaturated ketones with dimethyl diazomalonate (acceptor-acceptor disubstituted), only dihydrofuran products were formed over carbonyl ylides. When 2-thiophenyl and 2-furyl α,β-unsaturated ketones were reacted with 1-diazo-1-phenyl-propane-2-one (donor-acceptor disubstituted), 1-phenylpropane-1,2-dione was obtained under our reaction conditions.

Chitosan as a sustainable heterogeneous catalyst for the preparation of functionalized α-diazo carbonyl compounds

The food industry generates vast amounts of waste and one of the most abundant is the biopolymer chitin, which is the main constituent of crustacean shells and insect exoskeletons. The alkaline deacetylation of the N-acetyl-d-glucosamino units of chitin leads to chitosan, a stable, inexpensive, non-toxic, biocompatible, and biodegradable material of basic properties due to the presence of free amino groups. In the present study, we report the catalytic activity of commercially available chitosan as a sustainable heterogeneous catalyst for the preparation of α-diazo carbonyl compounds through the diazo transfer reaction to active methylene compounds using a sulfonyl azide as the diazo transfer reagent. Thus, 17 α-diazo carbonyl compounds were readily prepared under mild conditions in 50–92% yield after a simple work-up consisting of vacuum filtration to separate the insoluble catalyst and the sulfonamide byproduct. This procedure was also adapted to aqueous medium, making the process more environmentally benign. The recovery and recyclability of the biocatalyst were also addressed, with the catalytic activity being slightly reduced after four reuses depending on the substrate used. The synthetic potential of diazo carbonyl compounds was further demonstrated through the rhodium-catalyzed O–H insertion reactions.

Iron-Catalysed Carbene Transfer to Isocyanides as a Platform for Heterocycle Synthesis.

An iron-catalysed carbene transfer reaction of diazo compounds to isocyanides has been developed. The resulting ketenimines are trapped in situ with various bisnucleophiles to access a range of densely functionalized heterocycles (pyrimidinones, dihydropyrazolones, 1H-tetrazoles) in a one-pot process. The electron-rich Hieber anion ([Fe(CO)3 NO]- ) facilitates efficient catalytic carbene transfer from acceptor-type α-diazo carbonyl compounds to isocyanides, providing a cost-efficient and benign alternative to similar noble metal-catalysed processes. Based on DFT calculations a plausible reaction mechanism for activation of the α-diazo carbonyl carbene precursor and ketenimine formation is provided.

Three-component chemo-selective oxy-allylation of α-diazo carbonyl compounds: Access to α-ternary carboxylic esters

A synergistic Rh(II)/Pd(0) dual-catalyzed strategy that enabled three-component oxy-allylation of α-diazo esters, alcohols, and allylic benzoates was described. Trapping of active protic oxonium ylides with catalytic π-allyl Pd(II) intermediates was proposed for this reaction. More strikingly, water was also a suitable partner in this reaction involving a different allylic migratory insertion of palladium-carbenes. These transformations provided straightforward access to various α-ternary allylated carboxylic esters using simple and readily available starting materials under redox-neutral conditions, in which two new CO and CC bonds were generated successively at the carbene center.

Trans-Trifluoromethyltetrafluorosulfanyl Chloride: Selective Synthesis and Reaction with Diazo Compounds.

trans-Trifluoromethyltetrafluorosulfanyl chloride (trans-CF3SF4Cl) is a unique reagent for the incorporation of the CF3SF4 group into organic compounds. However, CF3SF4Cl was prepared from hazardous reagents or formed as mixture of trans and cis isomers in low yield. Herein, a silver-promoted selective synthesis of trans-CF3SF4Cl under safe gas-reagent-free conditions is described. Furthermore, the synthetic application of trans-CF3SF4Cl is demonstrated through the new trifluoromethyltetrafluorosulfanylation of α-diazo carbonyl compounds.

Highly Stereoselective Synthesis of Tetrasubstituted Vinyl Selenides via Rhodium-Catalyzed [1,4]-Acyl Migration of Selenoesters and Diazo Compounds.

Herein, we disclose a highly stereoselective Rh(II)-catalyzed 1,4-acyl rearrangement of selenium esters and α-diazo carbonyl compounds, which provides an efficient method for synthesizing tetrasubstituted vinyl selenides. Furthermore, this reaction also offers a synthetic tool for medium and large ring compounds.

H-F bond insertions into α-diazo carbonyl compounds.

A reaction for H-F bond insertion into α-diazo carbonyl compounds is reported. The protocol describes a simple reaction setup employing commercially available HF·pyr (Olah reagent) as the fluorine source. The method is rapid and practical, and allows access to a broad range of α-fluorinated carbonyl compounds in generally good yields.

Ternary Catalysis Enabled Three-Component Asymmetric Allylic Alkylation as a Concise Track to Chiral α,α-Disubstituted Ketones.

Multicomponent reactions that involve interception of onium ylides through Aldol, Mannich, and Michael addition with corresponding bench-stable acceptors have demonstrated broad applications in synthetic chemistry. However, because of the high reactivity and transient survival of these in situ generated intermediates, the substitution-type interception process, especially the asymmetric catalytic version, remains hitherto unknown. Herein, a three-component asymmetric allylation of α-diazo carbonyl compounds with alcohols and allyl carbonates is disclosed by employing a ternary cooperative catalysis of achiral Pd-complex, Rh2(OAc)4, and chiral phosphoric acid CPA. This method represents the first example of three-component asymmetric allylic alkylation through an SN1-type trapping process, which involves a convergent assembly of two active intermediates, Pd-allyl species, and enol derived from onium ylides, providing an expeditious access to chiral α,α-disubstituted ketones in good to high yields with high to excellent enantioselectivity. Combined experimental and computational studies have shed light on the mechanism of this novel three-component reaction, including the critical role of Xantphos ligand and the origin of enantioselectivity.

Modular and stereoselective synthesis of tetrasubstituted vinyl sulfides leading to a library of AIEgens

Tetraarylethylenes exhibit intriguing photophysical properties and sulfur atom frequently play a vital role in organic photoelectric materials and biologically active compounds. Tetrasubstituted vinyl sulfides, which include both sulfur atom and tetrasubstituted alkenes motifs, might be a suitable skeleton for the discovery of the new material molecules and drug with unique functions and properties. However, how to modular synthesis these kinds of compounds is still challenging. Herein, a chemo- and stereo-selective Rh(II)-catalyzed [1,4]-acyl rearrangements of α-diazo carbonyl compounds and thioesters has been developed, providing a modular strategy to a library of 63 tetrasubstituted vinyl sulfides. In this transformation, the yield is up to 95% and the turnover number is up to 3650. The mechanism of this reaction is investigated by combining experiments and density functional theory calculation. Moreover, the “aggregation-induced emission” effect of tetrasubstituted vinyl sulfides were also investigated, which might useful in functional material, biological imaging and chemicalnsing via structural modification.

Chemoselective Hydro(Chloro)pentafluorosulfanylation of Diazo Compounds with Pentafluorosulfanyl Chloride.

Pentafluorosulfanyl chloride (SF5 Cl) is the most prevalent reagent for the incorporation of SF5 group into organic compounds. However, the preparation of SF5 Cl often relies on hazardous reagents and specialized apparatus. Herein, we described a safe and practical synthesis of a bench-stable and easy-to-handle solution of SF5 Cl in n-hexane under gas-reagent-free conditions. The synthetic application of SF5 Cl was demonstrated through the unprecedented reaction with diazo compounds. The chemoselective hydro- and chloropentafluorosulfanylations of α-diazo carbonyl compounds were developed in the presence of K3 PO4 or copper catalyst, respectively. These reactions provide a direct and efficient access to various α-pentafluorosulfanyl carbonyl compounds of high value for potential applications.

Amino-modified Merrifield resins as recyclable catalysts for the safe and sustainable preparation of functionalized α-diazo carbonyl compounds

Amino-functionalized polystyrene polymers derived from Merrifield resins were prepared and characterized. These basic materials were successfully employed as heterogeneous catalysts in the diazo transfer reaction to 1,3-dicarbonyl compounds, furnishing the corresponding diazo compounds in good to excellent yields and in relatively short reaction times. In addition, the work-up and purification protocols are simple and do not generate large amounts of waste, which are important features in sustainable catalysis and environmentally benign processes. The feasibility of the recovery and reuse of the amino-modified catalysts was also verified, since they can be employed up to five times without appreciable loss of catalytic activity. This straightforward procedure can be readily scaled up to gram scale, enabling the wide application of this method. The synthetic potential was demonstrated through the two-step preparation of 2-amino-N-dodecylacetamide (ANDA), a small molecule of commercial relevance. • Amino-modified Merrifield resins were prepared and successfully applied as basic catalysts in the diazo transfer reaction. • The method furnishes the diazo compounds in good to excellent yields and in relatively short reaction times. • This procedure offers operational simplicity, reduced production of waste and facile recovery of the catalysts. • The heterogeneous catalysts can be employed up to five times without appreciable loss of catalytic activity. • The synthetic potential was demonstrated through the two-step preparation of 2-amino- N -dodecylacetamide (ANDA).

Diastereoselective trans Cyclopropanation of 3-Alkylidene Oxindoles with In Situ Generated α-Diazo Carbonyls or α,β-Unsaturated Diazo Compounds

AbstractAn efficient diastereoselective trans cyclopropanation of 3-alkylidene oxindoles with in situ generated α-diazo carbonyl compounds or α,β-unsaturated diazo compounds under metal-free conditions has been developed to synthesize 3-spirocyclopropyl-2-oxindole derivatives. The procedure is based on the 1,3-dipolar character of the corresponding diazo compounds under base-catalyzed conditions. The method has a wide substrate scope and uses easily available starting materials.

Gold-Catalyzed [3+2]-Annulations of α-Aryl Diazoketones with the Tetrasubstituted Alkenes of Cyclopentadienes: High Stereoselectivity and Enantioselectivity.

This work reports gold-catalyzed [3+2]-annulations of α-diazo ketones with highly substituted cyclopentadienes, affording bicyclic 2,3-dihydrofurans with high regio- and stereoselectivity. The reactions highlights the first success of tetrasubstituted alkenes to undergo [3+2]-annulations with α-diazo carbonyls. The enantioselective annulations are also achieved with high enantioselectivity using chiral forms of gold and phosphoric acid. Our mechanistic analysis supports that cyclopentadienes serve as nucleophiles to attack gold carbenes at the more substituted alkenes, yielding gold enolates that complex with chiral phosphoric acid to enhance the enantioselectivity.

Divergent functionalization of α,β-enones: catalyst-free access to β-azido ketones and β-amino α-diazo ketones.

A simple and practical method for the azidation of β-fluoroalkyl α,β-unsaturated ketones to access a wide variety of fluorinated nitrogenous carbonyl compounds is developed. Different from existing precedents, neither a metallic nor an organic catalyst was involved in our strategy. Judicious choice of solvents allows for the modulation of the reaction outcomes, delivering β-azido ketones or β-amino α-diazo ketones. The reaction system features environmental friendliness, mild conditions, simplicity and excellent functional group tolerance.

Chiral Cobalt(II) Complex Catalyzed Asymmetric [2,3]-Sigmatropic Rearrangement of Allylic Selenides with α-Diazo Pyrazoleamides

Organoselenium compounds, due to their high structural diversity, special function, and biological activities, have drawn attention in synthetic chemistry. Herein, a novel example of chiral N,N′-di...