First green protocols for the large-scale preparation of γ-diisoeugenol and related dihydro(1H)indenes via formal [3+2] cycloaddition reactions

Trans-isoeugenol and related styrenes (trans-isohomogenol or O-benzylated isoeugenol), important components of the essential oil of various tropical plants, dimerize easily in the presence of catalytic amounts of BF₃·OEt₂ in poly(ethylene glycol) with M_n = 400 (PEG-400) or SiO₂-OSO₃H in MeCN via formal [3+2] cycloaddition reaction to give respective natural products (diisoeugenol and its O-substituted analog) with the 1,2-trans-2,3-trans-configuration in excellent yields. γ-Diisoeugenol scale-up preparation has also been described.     

A facile synthesis of isoindolo[2,1-a]quinolin-11-one via [4+2] reactions of N-acyliminium intermediates with olefines

A facile synthesis of isoindolo[2,1-a]quinolin-11-one has been developed to attain new molecules of this family via [4+2] reactions of N-acyliminium cation, produced from 2,3-dihydro-3-hydroxy-2-arylisoindol-1-one, in the presence of BF₃·OEt₂ with olefins in moderate to good yields at ambient temperature.     

Microwave-assisted aza-Prins reaction. Part 1: facile preparation of natural-like 3-azabicyclo[3.3.1]non-6-enes

A facile and operationally simple route to diastereomerically pure, natural-like 3-azabicyclo[3.3.1]non-6-enes via microwave-assisted, BF₃·OEt₂-promoted aza-Prins reaction has been developed. Complexity-generating transformations based on these products involving reactive functionalities introduced during the aza-Prins step have been developed.     

Three-component imino Diels-Alder reaction with essential oil and seeds of anise: generation of new tetrahydroquinolines

A simple and efficient one-pot method for the synthesis of 4-anisyl-2-phenyl-1,2,3,4-tetrahydroquinoline derivatives using a three-component imino Diels-Alder cycloaddition (Povarov reaction) between anilines, benzaldehyde, and trans-anethole in the presence of acidic catalysts is shown. New substituted tetrahydroquinolines are reported and their direct preparation from the anise essential oil is described. Also, a simple procedure of the same tetrahydroquinolines from the anise seeds under supercritical fluid (CO₂) conditions has been reported.     

Selective reduction of aromatic azides in solution/solid-phase and resin cleavage by employing BF3·OEt2/EtSH. Preparation of DC-81

An efficient method for the reduction of aromatic azides in both solution and solid-phase has been developed by employing BF₃·OEt₂/EtSH. This report also describes resin cleavage employing this reagent system. Further, this protocol has been utilized for the solution as well as the solid-phase synthesis of pyrrolo[2,1-c][1,4]benzodiazepines, including the naturally occurring antibiotic DC-81 and fused [2,1-b]quinazolinones.     

A practical approach to the fused β-carboline system. Asymmetric synthesis of indolo[2,3-a]indolizidinones via a diastereoselective intramolecular α-amidoalkylation reaction

Fused β-carboline systems, as indolo[2,3-a]indolizidinones, indolo[2,3-a]quinolizidinones, their 2-oxa analogues, and benzo[a]indolo[2,3-a]indolizidinones are prepared efficiently via an RLi addition-N-acyliminium ion cyclisation sequence on readily available imides. In an enantioselective variant of these α-amidoalkylation reactions, the addition of MeLi to a chiral non-racemic imide derived from tryptophan yielded an oxo amide, which was cyclised diastereoselectively upon treatment with BF₃·OEt₂, to afford 5,11b-trans-indoloindolizidinone in moderate yield and high ee (99%).     

BF3·OEt2-catalyzed tandem Prins Friedel-Crafts reaction: a novel synthesis of sugar fused diarylhexahydro-2H-furo[3,2-b]pyrans

d-Glucose based homoallylic alcohol reacts smoothly with various aldehydes in the presence of arenes and a catalytic amount of BF₃·OEt₂ under mild conditions to afford a novel series of 5,7-diaryl-hexahydro-2H-furo[3,2-b]pyrans in good yields with high cis-selectivity.     

Intramolecular 1,3-dipolar cycloaddition of unsaturated nitrones derived from methyl α-d-glucopyranoside

The intramolecular 1,3-dipolar cycloaddition of unsaturated nitrones derived from methyl α-d-glucopyranoside with 2-furaldehyde has been studied. This cycloaddition was found to afford three 9-oxa-1-azabicyclo[4.2.1]nonane diastereomers in a 3:1:1 ratio [with the principal isomer possessing a (3S,4R,5S,6S,8S) configuration, determined by NMR spectroscopy]. The effects of different Lewis acid catalysts (MgCl₂, ZnCl₂ and BF₃·OEt₂) on yields and diastereomeric ratios have been examined in detail. The best result (90% yield) was achieved when MgCl₂ was present (in toluene, 120 °C bath temperature, 12 h). The stereoselectivity of the 1,3-dipolar cycloaddition was not significantly altered under the conditions investigated.     

Nucleophilic alkynylation of N-bis(trimethylsilyl)methyl aldimines

N-Bis(trimethylsilyl)methyl aldimines undergo nucleophilic addition reaction with premixed lithium alkynides/BF₃·OEt₂ to give moderate to good yields of N-bis(trimethylsilyl)methyl propargyl amines.     

Skeletal Wagner-Meerwein rearrangement of perhydro-3a,6;4,5-diepoxyisoindoles

An investigation of a skeletal Wagner-Meerwein rearrangement of variously substituted or quinoline-annulated 3a,6;4,5-diepoxyisoindol-1-ones is reported. Optimum reaction conditions (Ac₂O, BF₃·OEt₂, rt) were discovered for the formation of the target 4,6-epoxycyclopenta[c]pyridines in 40-80% yields. It was shown that the direction of the sigmatropic rearrangement of 3a,6;4,5-diepoxyisoindol-1-ones depended dramatically on the carboxyl group position (exo-/endo-) in the oxabicyclo[2.2.1]heptane moiety. The spatial structure of previously unknown 7,9-epoxycyclopenta[4,5]pyrido[1,2-a]quinolines derived from Wagner-Meerwein rearrangement of 2,11b-epoxyoxireno[6,7]isoindolo[2,1-a]quinolines was established based on the X-ray analysis data. The skeletal rearrangement proceeded regio- and stereospecifically in all the cases examined due to the absence of the epimerization of the carbon atoms adjacent to the carbocation centres.     

Microwave-assisted aza-Cope rearrangement of N-allylanilines

The aza-Cope rearrangement of N-allylanilines is described. The use of BF₃·OEt₂ and microwave irradiation allows to run the transformation under mild conditions and in reaction times of minutes.     

Highly stereocontrolled synthesis of fluorinated 2,6-trans dihydropyrans via Prins cyclization

A highly efficient method for the synthesis of fluorinated 2,6-trans dihydropyrans via BF₃·Et₂O-promoted Prins cyclization of allenic alcohols and aldehydes is developed. Various 2,6-trans fluorodihydropyrans are obtained in moderate to good yields with excellent diastereoselectivities.     

Total syntheses of (±)-cis- and (±)-trans-neocnidilides

Total syntheses of two antimicrobial natural products (±)-cis-neocnidilide and (±)-trans-neocnidilide starting from a readily preparable cyclohexa[b]-fused 5-oxabicyclo[2.1.1]hexane derivative are presented. The diastereomeric tetrahydrofuran tricarboxylate epimers obtained from a BF₃·OEt₂ promoted Grob-type fragmentation of the oxa-bicycle derivative were converted into title natural products by employing pyridinium dichromate/acetic anhydride mediated bis-oxidative cleavage reaction.     

New synthesis of cis-3,4-diaryl-1-tosylpyrrolidines

Unsymmetrically substituted cis-3,4-diarylpyrrolidines are synthesized in nearly 25% overall yields starting from 4-aryl-1,2,5,6-tetrahydropyridines by iterative reactions using the combination of m-chloroperoxybenzoic acid (MCPBA) and boron trifluoride etherate (BF₃·OEt₂) followed by Grignard addition, elimination and hydrogenation sequence.     

Tandem Parham cyclisation--α-amidoalkylation reaction in the synthesis of the isoindolo[1,2-a]isoquinoline skeleton of nuevamine-type alkaloids

C-12b substituted isoindolo[1,2-a]isoquinolones 4 are prepared efficiently via a tandem Parham cyclisation--α-amidoalkylation reaction. Thus, Parham cyclisation on imide 1 generates a 12b-hydroxy isoindolo[1,2-a]isoquinolone, which is an immediate precursor of an N-acyliminium ion. Intermolecular alkylation with different π-nucleophiles (allyl silanes or enol ethers) is accomplished upon treatment with Lewis acids (BF₃·OEt₂, TiCl₄) to obtain nuevamine-type derivatives in high yields (69-95%) under mild conditions.     

Agariblazeispirol C from the cultured mycelia of the fungus, Agaricus blazei, and the chemical conversion of blazeispirol A

Agariblazeispirol C, which has a unique steroidal skeleton, has been isolated from the cultured mycelia of Agaricus blazei (Agaricaceae). The structure of agariblazeispirol C was established to be (23S,24S)-13,23-cyclo-25-hydroxy-14β-methyl-18-nor-des-A-ergosta-5,7,9,11,17(20)-pentaen-22-one by comparison of extensive 1D and 2D NMR spectral data with those of agariblazeispirols A and B. At the same time, agariblazeispirol C was synthesized by the reaction of blazeispirol A with BF₃·OEt₂ along with some interesting compounds.     

One-pot synthesis of pyrrolidino- and piperidinoquinolinones by three-component aza-Diels-Alder reactions of in situ generated N-arylimines and cyclic enamides

An efficient synthesis of hexahydropyrrolo[3,2-c]quinolin-2-ones and hexahydropyridino[3,2-c]quinolin-2-ones has been developed in moderate to high yields by one-pot two-step aza-Diels-Alder reactions of N-arylimines, formed in situ from anilines and benzaldehydes, with cyclic enamides, formed in situ from 5-hydroxypyrrolidin-2-ones and 6-hydroxypiperidin-2-ones by BF₃·OEt₂-promoted dehydration in dichloromethane at room temperature. The hexahydropyrrolo[3,2-c]quinolin-2-ones were formed as a single exo-stereoisomer in most cases and hexahydropyridino[3,2-c]quinolin-2-ones were formed as a mixture of exo- and endo-isomers favoring the endo-diastereomer.     

Microwave-promoted synthesis of polyhydroxydeoxybenzoins in ionic liquids

A microwave-promoted synthesis of polyhydroxydeoxybenzoins and -phenylpropanones has been developed, using bis{(trifluoromethyl)sulfonyl}amine (HNTf₂) or BF₃·OEt₂ in an ionic liquid solvent.     

Catalytic asymmetric dihydroxylation of substituted trans-stilbene derivatives: implications of the variation of enantioselectivities on the mechanism of OsO4 addition to olefins

The OsO₄ catalyzed asymmetric dihydroxylation of substituted trans-stilbene derivatives using 9-O-acetyldihydrocinchonidine as chiral ligand gives the corresponding diols with lower enantioselectivity in the case of substrates containing electron-donating and electron-withdrawing substituents. The Hammett correlations of the enantiomeric ratios exhibit non-linear plots, in accordance with the conclusion that the reaction involves a 1,3-dipolar type [3+2] cycloaddition transition state.     

trans-Spanning ferrocene amidodiphosphine ligand: Synthesis, palladium complexes and catalytic use in Suzuki-Miyaura cross-coupling

Amide coupling between [2-(diphenylphosphino)phenyl]methylamine and 1′-(diphenylphosphino)ferrocene-1-carboxylic acid (Hdpf) afforded a novel diphosphine-amide, 1-{N-[(2-(diphenylphosphino)phenyl)methyl]carbamoyl}-1′-(diphenylphosphino)ferrocene (1), which was subsequently studied as a ligand for palladium(II) complexes. Depending on the metal precursor, the following complexes were isolated: [PdCl₂(1-κ²P,P′)] (2), [PdCl(Me)(1-κ²P,P′)] (3), [(μ-1){PdCl₂(PBu₃)}₂] (4) and [(μ-1){PdCl(L^NC)}₂] (L^NC = 2-[(dimethylamino-κN)methyl]phenyl-κC¹), featuring this ligand either as a trans-chelating or as a P,P′-bridging donor. The crystal structure of 2·1.25CH₂Cl₂ was established by X-ray crystallography, corroborating that 1 coordinates as a trans-spanning diphosphine without any significant distortion to the coordination sphere. Complex 2 together with a catalyst prepared in situ from 1 and palladium(II) acetate were tested in Suzuki-Miyaura reaction of aryl bromides with phenylboronic acid in dioxane.