Palladium-catalyzed Cyclocarbonylation Research Articles

Hydroxylamines: From Synthetic Intermediates to Synthetic Targets.

ConspectusSynergy between the teaching and research activities of a University should be a source of new ideas, each informing the other. A classroom discussion gave rise to our concept of using hydroxylamines as a form of "tethered nitrogen" for alkaloid synthesis. The "tether" temporarily connects a nucleophilic nitrogen atom to the substrate, rendering an intermolecular reaction intramolecular, thus providing stereo- and regiochemical control for C-N bond formation. In the context of the synthesis of 1,3-amino alcohols, this necessitated the synthesis of isoxazolidines. This concept led to the exploration of methods for the synthesis of these heterocycles beyond the well-established 1,3-dipolar cycloadditions. The first two methods developed based upon this concept were palladium catalyzed cyclocarbonylation and silver catalyzed allene cyclization. These new methods were applied to two syntheses of sedamine and the synthesis of three Nuphar alkaloids. Intramolecular aza-Michael addition, combined with the use of cross-metathesis to generate the substrates, gave access to both isoxazolidines and tetrahydro-1,2-oxazines. This new method made possible a synthesis of monomorine with high stereochemical control. The extension to more complex alkaloids required the incorporation of additional chemistry. Combining allene cyclization with iminium ion chemistry allowed the extension to the more complex piperidine alkaloids porantheridine and sedinine. In these cases, successful stereocontrol relied on the ability to predict the conformation of the intermediates and the trajectory of the nucleophilic attack, which may be sterically or stereoelectronically controlled. Inspection of our collection of methods revealed that we had good methods for cis-3,5-disubstituted isoxazolidines and trans-3,6-disubstituted tetrahydro-1,2-oxazines. Inspired by earlier work involving iminium ions, methods were developed to provide the complementary trans-isoxazolidines and cis-oxazines, using an allylation reaction. This, combined with our interest in applications of hydroformylation, led to the synthesis of 5-hydroxysedamine. Venturing away from piperidines, this method was successfully applied to the synthesis of the β-amino acid antibiotic negamycin. Use of N,O-heterocycles as intermediates naturally sparked an interest in N,O-heterocycles as synthetic targets, as there are many natural products that contain the hydroxylamine moiety, often incorporated into an isoxazolidine or 1,2-oxazine ring. As the presence of the hydroxylamine moiety cannot be fully demonstrated using the usual spectroscopic methods, total synthesis can be employed to bridge this logical gap. A synthesis of raistrickindole A, utilizing an intramolecular Mitsunobu reaction of a hydroxamic acid to form a 1,2-oxazine, confirmed the structure of this diketopiperazine natural product. A synthesis of preisomide, using an aza-Michael addition to form the required 1,2-oxazine, also confirmed the structure of this natural product.

Recyclable palladium-catalyzed cyclocarbonylation between benzyl chlorides and salicylic aldehydes towards coumarins

A novel and practical route to coumarin derivatives has been developed via the heterogeneous Pd-catalyzed carbonylative reaction and subsequent intramolecular condensation process starting from commercially easily available benzyl chlorides and salicylic aldehydes. Reactions were performed in the existence of 2 mol% of an SBA-15-immobilized bidentate phosphine palladium complex [SBA-15-P,P-PdCl2] in dioxane at 110 °C with Et3N as base under 10 bar of CO to afford a wide range of coumarin derivatives mostly with good to high yields. Importantly, this new heterogenized palladium complex was easy to recover via filtration of the reaction mixture, and was recyclable up to 8 times without apparent drop in its catalytic performance.

Recyclable Heterogeneous Palladium-Catalyzed Cyclocarbonylation of 2-Iodoanilines with Acyl Chlorides in the Biomass-Derived Solvent 2-Methyltetrahydrofuran.

A highly efficient, green palladium-catalyzed cyclocarbonylation of 2-iodoanilines with acyl chlorides has been developed that proceeds smoothly in a biomass-derived solvent 2-methyltetrahydrofuran with N,N-diisopropylethylamine as base at 100 °C under 20 bar of carbon monoxide using an 2-aminoethylamino-modified MCM-41-anchored palladium acetate complex [2N-MCM-41-Pd(OAc)2] as a heterogeneous catalyst, yielding a wide variety of 2-substituted 4H-3,1-benzoxazin-4-one derivatives in good to excellent yields. This supported palladium catalyst could be facilely obtained by a two-step procedure from easily available starting materials and readily recovered via a simple filtration process and recycled at least 8 times without any apparent decrease in catalytic efficiency. The developed methodology not only avoids the use of toxic solvents such as tetrahydrofuran and dimethylformamide but also solves the basic problem of expensive palladium catalyst recovery and reuse and prevents effectively palladium contamination of the desired product.

Pd-Catalyzed Cyclocarbonylation of Allylic Alcohol under Benign Conditions with Ionic Liquid as Stabilizer.

Homogeneous palladium-catalyzed (Pd-catalyzed) cyclocarbonylation of unsaturated allylic alcohols and alkynols in the presence of hydrogen forms lactone products with important applications in the food, perfume, and polymer industry. In this work, the cyclocarbonylation of 2-methyl-3-buten-2-ol was studied for the first time using a very active Pd-DPEphos (bis[(2-diphenylphosphino)phenyl]ether) catalyst in the presence of the ionic liquid (IL) [BMIM]Cl (1-butyl-3-methylimidazolium chloride) in dichloromethane to selectively produce 4,4-dimethyl-γ-butyrolactone. The effect of different parameters such as temperature, gas partial pressures, time of reaction, substrate and ligand concentrations were investigated and found to provide optimal conditions for lactonization (95 °C, 28 bar (CO/H2/N2: 20/5/3)), 18 h, 0.1 M substrate, and 16 mol% DPEphos), which were significantly milder than previously reported systems for cyclocarbonylation. Importantly, the study further showed that presence of the IL in the reaction mixture provided stabilization of the catalyst system and prevented formation of Pd-black, which allowed reuse of the catalytic system in consecutive reactions after intermediate extraction of the lactone product.

Palladium-catalyzed carbonylative synthesis of indoloisoindoloquinazolinone derivatives by using CO as a carbonyl source

An efficient synthesis of indolo[1,2-c]isoindolo[2,1-a]quinazolin-5(16aH)-one derivatives through palladium-catalyzed cyclocarbonylation reaction of 6-(2-bromoaryl)-5,6-dihydroindolo[1,2-c]quinazolines with the use of CO as a carbonyl source under atmospheric pressure has been disclosed. More intriguingly, the above-mentioned products can also be obtained directly from a one-pot two-step tandem reaction of 2-(1H-indol-2-yl)anilines and 2-bromobenzaldehydes, which are the precursors of 6-(2-bromoaryl)-5,6-dihydroindolo[1,2-c]quinazolines, under an atmospheric CO pressure in modest yields.

Preparation of cis-Fused Tetrahydropyranyl Lactones via Palladium-Catalysed Cyclocarbonylation of Enediols

The stereoselective palladium-catalysed cyclocarbonylation of hex-5-ene-1,4-diols affords cis-fused bicyclic lactones only. Ring-opening with N,O-dimethylhydroxylamine hydrochloride gives the corresponding Weinreb amides, and their subsequent recyclisation provides advanced synthons for the prospective synthesis of decarestrictine L. The relative configurations of all the prepared tetrahydropyrans are determined by NOESY. The attempted transformations of lactones into methyl ketones leads to an unexpected furan, the formation of which is discussed.

Selectivity controlled by ligand tuning in the palladium-catalysed cyclocarbonylation: Synthesis of new γ and δ lactones from a natural sesquiterpene

The cyclocarbonylation of homoallylic alcohols, derived from α-atlantone, catalysed by [Pd(Cl2)L2]/SnCl2] system, afforded new γ and δ lactones as the main products with high selectivities. The regiochemical control depends on the nature of phosphines involved. Catalysts based on monophosphines with large cone angles such as tricyclohexyl phosphine produce the six-membered ring lactones with selectivities up to 80%, while diphosphines with wide bite angle such as xantphos are found to favor the five-membered ring lactones with up to 99% selectivity. Monocrystals of the γ and δ lactones suitable for X-ray diffraction analysis have been obtained and the stereochemistry of the lactones 5a,a′ and 6 have been elucidated. This study is the first example of an attractive catalytic transformation of one single natural sesquiterpene easily available from bio-renewable resources to obtain either γ- or δ-lactones.

A convenient regioselective synthesis of cyclopentadienones via palladium-catalyzed [2+2+1] cyclocarbonylation of alkynes

A simple and efficient synthesis of cyclopentadienones via palladium-catalyzed cyclocarbonylation of alkynes under atmospheric pressure of carbon monoxide has been developed. The transformation was carried out under mild and ligand-free conditions, a wide range of substrates and exceptional functional group tolerance.

Palladium‐Catalyzed Cyclocarbonylation of 2‐Halobenzaldehyde and Hydrazines: A Facile Synthesis of 2‐Aminoisoindolin‐1‐ones

AbstractAn efficient procedure for the synthesis of 2‐aminoisoindolin‐1‐ones via a palladium‐catalyzed three‐component reaction of 2‐halobenzaldehydes, hydrazines and carbon monoxide is reported. This cyclocarbonylation process can be performed smoothly under 1 atmospheric pressure of carbon monoxide to afford 2‐aminoisoindolin‐1‐ones in moderate to excellent yields.

ChemInform Abstract: Palladium‐Catalyzed Intermolecular Cyclocarbonylation of 2‐Iodoanilines with the Michael Acceptor, Diethyl Ethoxycarbonylbutendienoate.

AbstractHighly functionalized dihydroquinolines are formed if the triester (IIa) is used.

ChemInform Abstract: Palladium‐Catalyzed Intermolecular Cyclocarbonylation of 2‐Iodoanilines with N‐Toluenesulfonyl Aldimines.

AbstractOptimized conditions are developed for the synthesis of dihydroquinazolines.

Palladium-catalyzed intermolecular cyclocarbonylation of 2-iodoanilines with N-toluenesulfonyl aldimines

A single step synthesis of 2,3-dihydro-4(1H)-quinazolinones is described using palladium-catalyzed cyclocarbonylation of 2-iodoanilines with N-toluenesulfonyl aldimines.

ChemInform Abstract: Synthesis of Benzo‐Fused Five‐ and Six‐Membered Heterocycles by Palladium‐Catalyzed Cyclocarbonylation.

Abstract A novel and simple synthetic methodology, based on palladium-catalyzed cyclocarbonylation reaction, is presented for preparing five- and six-membered benzo-fused heterocycles. A mechanism for the process is also proposed and discussed.

Synthesis of benzo-fused five- and six-membered heterocycles by palladium-catalyzed cyclocarbonylation

A novel and simple synthetic methodology, based on palladium-catalyzed cyclocarbonylation reaction, is presented for preparing five- and six-membered benzo-fused heterocycles. A mechanism for the process is also proposed and discussed.

ChemInform Abstract: Construction of Polycyclic Compounds by Cyclocarbonylation. Part 6. Palladium-Catalyzed Cyclocarbonylation of 3-(Heteroaryl)allyl Acetates.

ChemInform Abstract: Construction of Polycyclic Compounds by Cyclocarbonylation. Part 6. Palladium-Catalyzed Cyclocarbonylation of 3-(Heteroaryl)allyl Acetates.

ChemInform Abstract: Novel Synthesis of Phenol Derivatives by Palladium-Catalyzed Cyclocarbonylation of Penta-2,4-dienyl Acetates.

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ChemInform Abstract: Palladium Catalyzed Cyclocarbonylation of 3,3-Diarylallyl Acetates.

Abstract Palladium-catalyzed cyclocarbonylation of 3,3-diarylallyl acetates afforded 4-aryl-substituted 1-naphthyl acetates where the cyclization occurred selectively on the more electron-rich ring.

Palladium-Catalyzed Cyclocarbonylation of Arynes with Methyl Allyl Carbonates: Selective Synthesis of 1H-Inden-1-ones

A selective protocol for the synthesis of 2-methylene-3-substituted-2,3-dihydro-1H-inden-1-ones and 2-benzylidene-2,3-dihydro-1H-inden-1-ones has been developed via palladium-catalyzed cyclocarbonylation reactions of arynes with allyl carbonates and carbon monooxide (CO). It is noteworthy that the selectivity of this new route is depended on both substrates and ligands.

Palladium-Catalyzed Cyclocarbonylation of o-Iodoanilines with Imidoyl Chlorides to Produce Quinazolin-4(3H)-ones

A wide variety of substituted quinazolin-4(3H)-ones were prepared in 63-91% yields by the palladium-catalyzed cyclocarbonylation of o-iodoanilines with imidoyl chlorides and carbon monoxide. The reaction is believed to proceed via in situ formation of an amidine, followed by oxidative addition, CO insertion, and intramolecular cyclization to give the substituted quinazolin-4(3H)-ones.

Dramatic Effects of Ionic Liquids on the Palladium-Catalyzed Cyclocarbonylation of Enynols with Thiols

Palladium-catalyzed carbonylation reactions of enynols with thiols in ionic liquids afford monocarbonylated 6-membered-ring lactones in high yields and good selectivity. These results are significantly different from those obtained when conducting the reaction in THF. The recyclability of the catalytic system was also investigated.