Cycloaddition Of Trimethylenemethane Research Articles

Palladium-Catalyzed [3 + 3] Cycloaddition of Trimethylenemethane with Azomethine Imines

A palladium-catalyzed [3 + 3] cycloaddition of trimethylenemethane (TMM) with azomethine imines has been developed to produce hexahydropyridazine derivatives under simple and mild conditions. The use of substituted TMM precursors highlights the difference of this system from previously reported [3 + 2] cycloaddition of TMMs under palladium catalysis. The present [3 + 3] cycloaddition reactions are also applicable to couplings with nitrones.

3+2] Cycloaddition of Trimethylenemethane and Its Synthetic Equivalents

AbstractFor Abstract see ChemInform Abstract in Full Text.

A “Chiral Aldehyde” Equivalent as a Building Block Towards Biologically Active Targets

Chiral gamma-aryloxybutenolides, readily accessible through dynamic kinetic asymmetric transformation (DYKAT) of racemic acyloxybutenolides, were utilized as "chiral aldehyde" building blocks for intermolecular cycloadditions and Michael reactions. Unprecedented selectivity in trimethylenemethane cycloadditions with this building block allowed an efficient synthesis of a novel metabotropic glutamate receptor 1 antagonist in development by the Bayer corporation. These studies further inspired work that culminated in the total synthesis of (+)-brefeldin A, a natural product with a range of significant biological properties. All of the stereochemistry in this target molecule was derived from two palladium-catalyzed asymmetric allylic alkylation reactions. The trans-alkenes were synthesized by a Julia olefination and a ruthenium-catalyzed trans-hydrosilylation-protodesilylation protocol. The route to (+)-brefeldin A lends itself to analogue syntheses and was completed in 18 steps in 6 % overall yield.

3+2] Cycloaddition of trimethylenemethane (TMM) to α,β-unsaturated γ-lactam. Preparation of 5,5-fused proline surrogates

Unsaturated lactam derived from ( S)-pyroglutaminol undergoes a totally stereoselective cycloaddition reaction with (2-(acetoxymethyl)-3-allyl)trimethylsilane in the presence of Pd(P(O iPr) 3) 4 in refluxing toluene. This step was efficiently used to introduced the 5,5-fused framework desired for the preparation of novel proline surrogates.

パラジウム触媒を用いたトリメチレンメタンとｐ‐ベンゾキノン類との［３＋２］付加環化反応

The reaction of trimethylenemethane with various alkyl-substituted p-benzoquinones was investigated. The reaction of 2, 5-di-tert-butyl-p-benzoquinone with 2-(trimethylsilylmethyl)allyl acetate(1) was conducted with palladium(0) as a catalyst to afford 1:1-C=C-cycloadduct 2 in good yield. Similarly, 1:1-C=C-cycloadducts 3, 4, 5 and 6 were obtained with 2, 6-di-tert-butyl-p-benzoquinone, 2, 3, 5, 6-tetramethyl-p-benzoquinone, 2, 3, 5-trimethyl-p-benzoquinone and 2-methyl-1, 4-naphthoquinone, respectively. On the other hand, the reaction with methyl-p-benzoquinone afforded the complicated mixture. As is the case with Diels-Alder reactions, the cycloaddition of trimethylenemethane with p-benzoquiones occurred towards C-C double bond. So, the reaction of trimethylenemethane with substituted p-benzoquinones is effective in the synthesis of methylenecyclopentane-fused cyclohexenediones having various substituents.

Evidence for a Concerted Mechanism in a Palladium Trimethylenemethane Cycloaddition

Carbon kinetic isotope effects were determined at natural abundance for the palladium trimethylenemethane cycloaddition of ester−amide 5. Substantial intermolecular 13C KIEs were observed for both olefinic carbons of 5. In contrast, a Michael addition to 5 exhibits a significant 13C KIE only at the carbon β to the ester group. Intramolecular KIEs determined for the product-determining step(s) for reaction of the Pd−TMM intermediate would require a surprising isotope-dependent selection between diastereomeric ring closures. These results cannot be reconciled with a stepwise cycloaddition mechanism but are readily interpreted in terms of a concerted cycloaddition.

Palladium-catalysed [3 + 2] cycloaddition of trimethylenemethane (TMM) and fullerene. Observation of the room-temperature fluorescence spectrum of the TMM-C60 adduct

The first synthesis of the parent TMM-C60 adduct 1 was achieved by means of Pd°-mediated [3 + 2] cycloaddition and its structure was unambiguously proved by spectroscopic means (1H and 13C NMR and MS); a pentane solution of the adduct 1 exhibited a fluorescence emission spectrum with λmax 704 nm and vibronic fine structure at ambient temperature.

Application of palladium-catalyzed [3 + 2] cycloaddition technology to the elaboration of kempane diterpenes. Stereocontrolled synthesis of (.+-.)-3.alpha.-hydroxy-7.beta.-kemp-8(9)-en-6-one and (.+-.)-3.beta.-hydroxykemp-7(8)-en-6-one

The total synthesis of three hydroxykempenones has been accomplished. The retrosynthetic elements of the strategy focused on setting four key stereocenters in rings A and B, followed by annulation of ring C and ultimate cyclization to construct the seven-membered ring, D. Since the target molecule carries eight contiguous stereogenic centers, proper attention to stereocontrolled processes was mandatory. The key features of the scheme include the palladium-catalyzed[3+2] cycloaddition of trimethylenemethane to an activated octalone with the complete control of π-facial selectivity, fully regiospecific monooxidation of a diol with ammonium molybdate uniquely at the secondary site to provide a key hydroxy ketone, hydroxyl-directed hydride reduction of the latter intermediate in order to override a contrary kinetic preference for nucleophilic attack, avoidance of Grob fragmentation in diaxial, monofunctionalized 1,3-diols, and selective deoxygenation of a diol

3 + 3] Cycloaddition of trimethylenemethane to activated aziridines: palladium-catalysed synthesis of piperidines

The zerovalent palladium complex [Pd(PPh 3) 4] catalyses the cycloaddition of trimethylenemethane to activated aziridines to give a high yield of 5-methylenepiperidines.

Asymmetric induction in the palladium catalyzed [3+2] cycloaddition reaction of trimethylenemethane with homochiral vinylsulfoxides

The palladium catalyzed [3+2] cycloaddition of trimethylenemethane with a variety of vinylsulfoxides led to cycloadducts in good to excellent chemical yields and with a good level of asymmetric induction.

ChemInform Abstract: Trimethylenemethane Metal Complexes

Publisher Summary This chapter discusses the developments and up-to-date review of trimethylenemethane metal complexes. Tris(carbonyl)-n4-trimethylenemethaneiron(0) was the first trimethylenemethane metal complex to be synthesized and was obtained from the reaction of 3-chloro-2-chloromethylprop-1-ene with [Fez2(CO)9] or Na2[Fe(CO)4]. The thermal extrusion of a simple molecule from an n3-allyl complex, to generate an n4-trimethylenemethane metal complex, was originally observed by Emerson. The ability of [Pd(PPh3)4] to promote the elimination of trimethylsilyl acetate from the allyl silane 31a and generate a highly reactive n3-trimethylenemethane palladium intermediate, which is considered to be of the form [Pd{n3-C(CH2)3}(PPh3)w2], was first observed by Trost and Chan. The structure of this complex has been substantiated by a single crystal X-ray study. A gas-phase electron diffraction study of tris(carbonyl)-n4-trimethylenemethaneiron establishes that the carbonyl ligands and a trigonalpyramidal trimethylenemethane ligand are in a staggered conformation about the iron with the central carbon being closer to the iron center than the outer methylene carbons. Initial studies have shown that iron trimethylenemethane complexes are susceptible to electrophilic attack. The cycloaddition of trimethylenemethane to alkenes can be envisaged as the Diels–Alder (471 + 2 π) reaction for the synthesis of five-membered rings. In the special cases of substituents that are good anion-stabilizing groups, the allyl carbonate 77 (Z = CN) serves as a suitable trimethylenemethane precursor.

ChemInform Abstract: Carboxylative Trimethylenemethane Cycloadditions Catalyzed by Palladium.

AbstractThe trimethylenemethane synthons (VI) are prepared from (I) via the trisilyl derivative (III).

Carboxylative trimethylenemethane cycloadditions catalyzed by palladium

Carboxylative trimethylenemethane cycloadditions catalyzed by palladium

Reactions between trimethylenemethane metal complexes and the carbon–nitrogen double bond: nickel and palladium catalysed synthesis of pyrrolidines

The d10 nickel complex [Ni{P(OEt)3}4] catalyses the cycloaddition of trimethylenemethane to the CN double bond of an imine to afford a high-yield synthesis of 4-methylenepyrrolidines.