Pd(0)-catalyzed intramolecular Heck reaction: a versatile route for the synthesis of dibenzoazocinone derivatives

Two efficacious synthetic methodologies for the construction of medium-sized nitrogen heterocycles dibenzoazocinones have been developed. The phosphine-assisted protocol afforded better yields of the dibenzoazocinones (73-82%).     

An efficient intermolecular [Pd]-catalyzed C-C and intramolecular [Cu]-catalyzed C-O bonds formation: synthesis of functionalized flavans and benzoxepine

An efficient three-step strategy for the synthesis of functionalized flavans, starting from readily available 2-bromoiodobenzenes and aryl vinyl alcohols, is presented and successfully extended to benzoxepine. An intermolecular [Pd]-catalyzed C-C and an intramolecular [Cu]-catalyzed C-O bond formations have been employed as key transformations of the strategy.     

Application of Pd(0)-catalyzed intramolecular oxazine formation to the efficient total synthesis of (-)-anisomycin

The enantioselective total synthesis of (-)-anisomycin, a potent antibiotic agent, has been achieved. The key steps are a Pd(0)-catalyzed stereoselective intramolecular oxazine formation from d-tyrosine and pyrrolidine formation by catalytic hydrogenation of the oxazine.     

Stereoselective synthesis of bicyclo[3.1.1]heptane derivatives via intramolecular photocycloaddition reaction

Optically active 1,3-bridged cyclobutanes 10 of the bicyclo[3.1.1]heptane ring system and 1,2-bridged cyclobutanes 11 of the bicyclo[3.2.0]heptane ring system were produced by UV irradiation of alpha,beta,gamma,delta-unsaturated esters 9a and 9c-f. The preference of endo-stereochemistry at C-6 bridged head was observed in cross-adducts 10. On the other hand, irradiation of conjugated dienol 9b led via only parallel cycloaddition to 1,2-bridged cyclobutane 11.     

Pd(0)-catalyzed intramolecular Heck reaction: A general route for fused oxepine derivatives

A simple and facile approach for the synthesis of various structurally different tricyclic bent oxepine frameworks from a readily accessible precursor has been introduced. The synthesis of substituted oxepine derivative involved Pd(0)-catalyzed Heck reaction. This methodology enriches the literature for the large ring formation.     

Facile synthesis of benzofulvene derivatives from Baylis-Hillman adducts: In-mediated Barbier reaction combined with Pd(0)-catalyzed intramolecular Heck-elimination cascade

A facile synthesis of benzofulvene derivatives was carried out starting from the Baylis-Hillman adducts of 2-bromobenzaldehyde via the sequential bromination, In-mediated Barbier reaction with aldehyde, acetylation, Pd-catalyzed intramolecular Heck reaction, and the elimination of AcOH.     

Enantioselective total synthesis of isishippuric acid B via intramolecular Michael reaction

The first enantioselective total synthesis of isishippuric acid B bearing a novel 4,5-seco-6-norquadrane skeleton was accomplished from (R)-citronellal with use of a Diels-Alder cycloaddition and an intramolecular Michael addition as the ring-forming steps. Comparison of the optical rotation of the synthetic material with that of the natural product confirmed the absolute configuration of isishippuric acid B to be 1R, 2R, 8R, and 11R.     

Regioselective synthesis of C-prenylated flavonoids via intramolecular [1,3] or [1,5] shift reaction catalyzed by acidic clays

Prenyl side chain and dihydropyrano skeleton exists in many natural and synthetic biologically active flavonoids. A highly efficient and regioselective method for the synthesis of C-prenylated flavonoids via intramolecular [1,3] or [1,5] shift reaction of 5-O-prenylflavonoids catalyzed by Florisil or Montmorillonite clays is described. Florisil catalyzes intramolecular [1,5] shift reaction of 5-O-prenylflavonoids to obtain 8-C-prenylated flavonoids exclusively, Montmorillonite K10 exhibits the superior selectivity to promote intramolecular [1,3] shift reaction to obtain 6-C-prenylated flavonoids compared with Florisil and Montmorillonite KSF. This method provides a practical process to regioselective synthesize biologically important C-prenylated flavonoids in good yields using commercially available and inexpensive catalyst under mild conditions.     

Facile synthesis of benzo[4,5]furo[3,2-c]pyridines via palladium-catalyzed intramolecular Heck reaction

The heating of 4-chloropyridine with 2-bromophenol in either neat or DME as solvent gives rise to 2-bromophenoxy pyridines, which were treated with Pd(OAc)₂ and various ligands to afford functionalized benzo[4,5]furo[3,2-c]pyridines.     

Direct synthesis of chiral 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines via a catalytic asymmetric intramolecular aza-Friedel-Crafts reaction

The direct asymmetric intramolecular aza-Friedel-Crafts reaction of N-aminoethylpyrroles with aldehydes catalyzed by a chiral phosphoric acid represents the first efficient method for the preparation of medicinally interesting chiral 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines with high yields and high enantioselectivities. This strategy has been shown to be quite general toward various aldehydes and pyrrole derivatives.     

Exploiting the palladium[0]-catalysed Ullmann cross-coupling reaction in natural products chemistry: application to a total synthesis of the alkaloid (+/-)-aspidospermidine

Azide 14, available through the title cross-coupling process, has been converted, via the ring-fused aziridine 15, into the alkaloid aspidospermidine.     

Medium ring synthesis via intramolecular diels-alder reaction. I. The synthesis of bicyclo[6.4.O]dodecane systems

The regio- and stereocontrolled synthesis of $\text{cis}$-fused bicyclo[6.4.Oldodecane ring systems by the application of the Lewis acid-catalyzed intramolecular Diels-Alder reaction is described.     

Enantioselective synthesis of N-heterocycles via intramolecular Pd(0)-catalysed allylic amination

An efficient and stereoselective synthesis of pyrrolidine-, piperidine-, and azepane-type N-heterocycles is described by the intramolecular Pd(0)-catalysed cyclisation of amino allylic carbonates. The use of chiral ligands gave the corresponding heterocyclic derivatives having er values that were from moderate to good.     

Stereoselective synthesis of functionalized trisubstituted olefins via palladium(0)-catalyzed cross-coupling reaction

[reaction: see text]. A highly flexible and stereoselective protocol for the synthesis of branched (E)- and (Z)-trisubstituted alkenes has been developed. The key steps are hydrozirconation-iodination of (1-alkynyl)trimethylsilane followed by Negishi-type cross-coupling. The resultant (Z)-vinyl silane is iododesilylated and subjected to a second cross-coupling reaction to give the trisubstituted olefin. Model studies aimed at the construction of the C14-C15 (Z)-trisubstituted olefin of discodermolide and the C8-C9 (Z)-trisubstituted olefin of callystatin A and analogues are also described.     

Parallel strategies for the synthesis of annulated pyrido[3,4-b]indoles via Rh(I)- and Pd(0)-catalyzed cyclotrimerization

Two different pathways for the synthesis of annulated pyrido[3,4-b]indoles are reported using metal-catalyzed cyclotrimerization reactions. A stepwise process using Rh(I)-catalysis in the final step of the synthesis and a multicomponent, tandem catalytic approach using Pd(0)-catalysis both lead to complex nitrogen-containing heterocycles in good yields. Substituent effects are investigated for both pathways, demonstrating that the Pd(0)-catalyzed approach is more sensitive to electron-withdrawing groups.     

Copper(II)-catalyzed synthesis of benzo[f]pyrido[1,2-a]indole-6,11-dione derivatives via naphthoquinone difunctionalization reaction

Benzo[f]pyrido[1,2-a]indole-6,11-diones have been synthesized in high yields by copper(II)-catalyzed three-component reactions of acyl bromide, 1,4-naphthoquinone, and pyridine (or isoquinoline) via sp(2)-C-H difunctionalization of naphthoquinone followed by intramolecular cyclization and oxidative aromatization. In an attempt to expand the reaction scope and to help clarify the reaction mechanism, 1,3-dicarbonyl compounds are used in place of acyl bromides to take part in this reaction, and the benzo[f]pyrido[1,2-a]indole-6,11-diones derivatives are also obtained in excellent yields.     

Enantioselective total synthesis of (+)-asteriscanolide via Rh(I)-catalyzed [(5+2)+1] reaction

The total synthesis of (+)-asteriscanolide starting from two commercially available materials has been accomplished in 19 steps with a 3.8% overall yield. The key reaction is a chiral ene-vinylcyclopropane substrate induced Rh(I)-catalyzed [(5+2)+1] cycloaddition that efficiently constructs the [6.3.0] carbocyclic core with complete asymmetric induction.     

Towards the total synthesis of tangutorine by intramolecular Diels-Alder reaction

The syntheses of 3,5-disubstituted-2-sulfolenes, and their participation in Pictet-Spengler reactions to give precursors of tangutorine, are described.     

Diastereoselective synthesis of tetrahydrofurans via Palladium(0)-catalyzed [3 + 2] cycloaddition of vinylcyclopropanes and aldehydes

Palladium(0)-catalyzed cycloadditions of malonate-derived vinylcyclopropane 1 and aldehydes to afford 2,5-cis disubstituted tetrahydrofuran derivatives are described. Pd loadings as low as 0.5 mol % were effective in catalyzing the transformation with high yields and diastereoselectivities. Electron-poor aldehydes work best, suggesting that a mechanism involving an initial aldol reaction may be operative.