Palladium(0)‐Catalyzed Regioselective Synthesis of Macrocycles from Allenes with a Nucleophilic Functionality and Organic Iodides

A highly regioselective synthesis of 15–20‐membered macrocycles via Pd(0)‐catalyzed coupling cyclization of allenes bearing a carbon or nitrogen nucleophilic functionality and organic iodides is reported. After oxidative addition and carbopalladation, anti‐π‐allyl palladium intermediates were formed, which was followed by the exclusive intramolecular nucleophilic attack at the terminal carbon atom of the allene moiety to afford products with yields ranging from 44–92% and E/Z ratios of up to 97/3.

     

Palladium‐Catalyzed Three‐Component Tandem Cyclization Reaction of 2‐(2,3‐Allenyl)acylacetates,Organic Halides,and Amines: An Effective Protocol for the Synthesis of 4,5‐Dihydro‐1H‐pyrrole Derivatives

A domino three‐component reaction of 2‐(2′,3′‐allenyl)acylacetates with aryl or alkenyl halides and aryl‐ or benzylamines afforded 4,5‐dihydro‐1H‐pyrrole derivatives highly chemo‐ and regioselectively in one pot through imine formation/imine‐enamine tautomerization under the catalysis of palladium(0) and toluenesulfonic acid monohydrate. A high diastereoselectivity was observed.     

Practical Enantioselective Synthesis of β‐Lactones Catalyzed by Aluminum Bissulfonamide Complexes

The development of an efficient and practical aluminum‐bissulfonamide complex catalyzed enantioselective formation of β‐lactones by [2+2] cycloaddition of ketene (generated in situ from acetyl bromide by dehydrobromination) with various α‐unbranched and ‐branched aliphatic aldehydes is presented. The methodology offers the advantage of operational simplicity not only as the ligand synthesis requires just a single sulfonylation step from commercially available enantiomerically pure diamines. The products are formed in high to excellent yields with ee values typically ranging from 78 to 90 % using 10 mol % of the bissulfonamide ligand. The key finding of this work was a remarkable rate acceleration by using an aluminum/ligand ratio of 1.5:1.     

Diastereoselective Synthesis of Six‐Membered Carbocyclic Spirooxindoles via 6π‐Electrocyclization of 3‐Dienylidene‐2‐ oxindoles

The Wittig reaction of isatin derivatives with Morita–Baylis–Hillman bromides of cinnamaldehydes afforded 3‐dienylidene‐2‐oxindoles. These trienes were converted into the corresponding spirooxindoles in a stereoselective manner in refluxing toluene in good yields. The diastereomeric spirooxindoles could be obtained stereoselectively by adding a catalytic amount of palladium(II) acetate via the palladium‐catalyzed isomerization of EEE‐trienes to ZEE‐trienes followed by a more facile 6π‐electrocyclization process. The obtained spirooxindoles could be further functionalized by palladium‐catalyzed oxidative arylation, thionation with Lawesson’s reagent, catalytic hydrogenation and Friedel–Crafts‐type reaction.

     

Stereoselective Palladium‐Catalyzed Alkenylation and Alkynylation of Thioglycosides

An efficient and unprecedented palladium‐catalyzed S‐glycosylation reaction of a range of alkenyl and alkynyl halides by using thiosugars as nucleophile partners has been established. With palladium diacetate in combination with Xantphos as the catalytic system, a variety of β‐alkenylthioglycosides as well as β‐alkynylthioglycosides can be prepared in good to excellent yields. The efficiency of this general protocol was well‐demonstrated by the formal synthesis of a leaf‐closure β‐glucosidase inhibitor.

     

Cyclopropanation of Strained Alkenes by Palladium‐Catalyzed Reaction of 3‐Trimethylsilyl‐ or 3‐Pinacolatoboryl‐1‐arylallyl Acetates

The palladium‐catalyzed cyclopropanation of strained alkenes with 3‐trimethylsilyl‐ or 3‐pinacolatoboryl‐1‐arylallyl acetate derivatives is described. This reaction gives cyclopropanation products in good to high yields with a single diastereomer, and the key step is likely to involve the formation of a palladacyclobutene complex from the α‐trimethylsilyl‐ or α‐pinacolatoboryl‐σ‐allylpalladium complex.     

Facile Synthesis of Polycyclic Fluorene Derivatives via a Palladium‐Catalyzed Coupling,Propargyl‐Allenyl Isomerization and Schmittel Cyclization Sequence

A stepwise process involving Sonogashira coupling, propargyl‐allenyl isomerization and Schmittel cyclization has been realized, leading to an efficient synthesis of polycyclic fluorene derivatives from readily available starting materials. The reaction features the formation of three new carbon‐carbon bonds to construct the benzene unit together with an efficient assembly of three or four rings in a single operative step.     

Regio‐ and Enantioselective Copper‐Catalyzed 1,4‐Conjugate Addition of Trimethylaluminium to Linear α,β,γ,δ‐Unsaturated Alkyl Ketones

A regio‐ and enantioselective copper‐catalyzed 1,4‐conjugate addition of trimethylaluminium to linear δ‐aryl‐substituted α,β,γ,δ‐unsaturated alkyl ketones was developed. A series of γ,δ‐unsaturated alkyl ketones were obtained in good yields with high regio‐ and enantioselectivity (up to 88% ee and 96:4 dr). Expansion of the reaction scope to substrates containing aromatic heterocycles also afforded good yields and enantioselectivities (up to 91% ee) with very high regioselectivities, exclusively providing the single 1,4‐products.

     

Palladium‐Catalyzed Regioselective γ‐Mono‐ and Diarylation of Acrylamide Derivatives with Aryl Halides

Palladium‐catalyzed direct mono‐ and diarylations involving C(sp³) H cleavage at the γ‐position of acrylamides are described. The monoarylation products can be obtained with ortho‐substituted aryl halides. Single crystal X‐ray diffraction has shown that the double bond has shifted towards the introduced aryl group to afford the γ‐arylated β,γ‐unsaturated amide products. A second arylation occurs when less sterically hindered aryl halides are employed. This chemistry offers a novel disconnection for the synthesis of γ‐arylated compounds.     

Gold(I)‐Catalyzed Decarboxylation of Propargyl Carbonates: Reactivity Reversal of the Gold Catalyst from π‐Lewis Acidity to σ‐Lewis Acidity

A cationic gold(I)‐catalyzed decarboxylative etherification of propargyl carbonates to selectively produce propargyl ethers is reported. In the reaction the gold(I) catalyst shows a distinct σ‐Lewis acidity rather than the commonly observed π‐Lewis acidity, and thus catalyzes the decarboxylation of a variety of propargyl carbonates to give the corresponding propargyl ethers with high selectivity. This reaction represents a rare example of the tunable reactivity of cationic gold(I) complexes between σ‐Lewis acidity and π‐Lewis acidity.

     

Copper‐Catalyzed Cyclization and Azidation of γ,δ‐Unsaturated Ketone O‐Benzoyl Oximes

An intramolecular imination/azidation sequence has been realized through the tetrakis(acetonitrile)copper(I) hexafluorophophate [Cu(CH₃CN)₄PF₆]‐catalyzed reaction of γ,δ‐unsaturated ketone O‐benzoyl oximes with trimethylsilyl azide (TMSN₃). The reaction proceeds via the copper‐mediated N O cleavage and subsequent C N forming 5‐exo cyclization. The thus formed intermediate is then azidated to afford the corresponding dihydropyrrole product. Preliminary mechanistic investigations suggest that the cyclization step does not involve a radical intermediate.

     

Recyclable Selective Palladium‐Catalyzed Synthesis of Five‐, Six‐ or Seven‐Membered Ring Lactones and Lactams by Cyclocarbonylation in Ionic Liquids

The ionic liquids, BMIM PF₆ or BMIM NTf₂, are used successfully for the palladium‐catalyzed cyclocarbonylation of 2‐allylphenols and anilines, 2‐vinylphenols, and 2‐aminostyrenes. The reaction proceeds cleanly and efficiently to afford high yields of lactones or lactams with good or excellent selectivity for one isomer. The ionic liquid containing the palladium catalyst, and ligand, is recyclable in all cases.     

Synthesis of Fused Cyclopentenones through Palladium‐Catalyzed Cyclization of 2‐Iodoaryl Allenols

A versatile strategy for the synthesis of fused cyclopentenones, key structural motifs in biologically relevant compounds such as indenones and indole alkaloids, has been established successfully through regioselective palladium‐catalyzed cyclization of 2‐iodoaryl allenols.

     

Ruthenium(II)‐Catalyzed Protocol for Preparation of Diverse α,β‐ and β,β‐Dihaloenones from Diazodicarbonyls

Efficient one‐step syntheses of α,β‐ and β,β‐dihaloenones were achieved by ruthenium(II)‐catalyzed reactions between cyclic or acyclic diazodicarbonyl compounds and oxalyl chloride or oxalyl bromide in moderate to good yields. This methodology offers several significant advantages, which include ease of handling, mild reaction conditions, one‐step reaction, and the use of an effective and non‐toxic catalyst. The synthesized compounds were further transformed into highly functionalized novel molecules bearing aromatic rings on the enone moiety using the Suzuki reaction.

     

Gold‐Catalyzed Synthesis of Dibenzopentalenes – Evidence for Gold Vinylidenes

A series of easily accessible arene‐1,2‐diynes, bearing one aryl substituent on one of the alkynyl groups, is readily converted to dibenzopentalenes in good yields by gold(I) catalysts. The participation of gold acetylides could be proven by the direct conversion to the corresponding gem‐diaurated dibenzopentalenes with a gold catalyst. From an experiment with a gold acetylide complex and stoichiometric amounts of the gold “catalyst” the corresponding gem‐diaurated complex of a dibenzopentalene could be obtained and characterized by X‐ray crystal structure analysis. Labelling studies with deuterated alkynes show the expected deuteration of the two remaining positions of the pentalene core. All this provides evidence for a dual activation mode of the reaction and gold(I) vinylidene complexes as intermediates of the catalytic cycle.     

Ruthenium‐Catalyzed Oxidation of the Porphyrin β,β′‐Pyrrolic Ring: A General and Efficient Approach to Porpholactones

We describe an efficient ruthenium‐catalyzed oxidation of the β,β′‐pyrrolic ring on the porphyrin periphery. Through the conversion of a β,β′‐double bond to a lactone moiety, the direct preparation of porpholactones from porphyrins is achieved, which previously suffered from needing toxic reagents, multiple synthetic steps and low yields. The generality of this method has been investigated with various porphyrins with different electronic and steric effects, even some metalloporphyrins, and so represents a general and efficient approach for the synthesis of the intriguing porpholactone derivatives.     

Highly Regio‐ and Diastereoselective Palladium‐Catalyzed Allylic Substitution. Synthesis of 3‐(2‐Aminobutylidene)‐ 4‐arylazetidin‐2‐ones

The palladium‐catalyzed benzylamine attack to a particular allylic moiety, the 3‐alkenyl‐3‐bromoazetidin‐2‐one is herein reported. This reaction shows interesting mechanistic aspects and allows us to introduce in one step and under high regio‐ and stereocontrol the amino function in the C3 side chain of non‐conventional β‐lactams, thus offering the opportunity for designing new potential glutamine syntethase inhibitors, such as Tabtoxin analogues.     

Novel,Stereoselective and Stereospecific Synthesis of Allenylphosphonates and Related Compounds via Palladium‐Catalyzed Propargylic Substitution

We have developed a novel method for the synthesis of allenylphosphonates and related compounds based on a palladium(0)‐catalyzed reaction of propargylic derivatives with H‐phosphonate, H‐phosphonothioate, H‐phosphonoselenoate, and H‐phosphinate esters. The reaction is stereoselective and stereospecific, and provides a convenient entry to a vast array of allenylphosphonates and their analogues with diverse substitution patterns in the allenic moiety and at the phosphorus center. Some mechanistic aspects of this new reaction were also investigated.