Bismuth Triflate Research Articles

Sustainable catalytic rearrangement of terpene-derived epoxides: towards bio-based biscarbonyl monomers.

Seeking a sustainable and selective approach for terpene modification, a catalyst deconvolution approach was applied to the Meinwald rearrangement of (+)-limonene oxide as a model substrate to yield dihydrocarvone. In order to identify the most suitable catalyst and reaction conditions, different Lewis acids were evaluated. Bismuth triflate proved to be the most active catalyst under mild reaction conditions, with a low catalyst loading (1 mol%) and a relatively short reaction time (3 h). The optimized reaction conditions were subsequently transferred to other terpene-based epoxides, yielding different bio-based biscarbonyl structures, which constitute interesting and valuable substances, e.g. for polymer synthesis or as fragrances. Monoepoxides derived from (R)-(-)-carvone and (+)-dihydrocarvone rearranged to the desired products with high selectivities and yields. γ-Terpinene dioxide could be transformed in a double rearrangement to the respective biscarbonyl in moderate yields. A better result was achieved for limonene dioxide after further adjustment of the protocol to reach acceptable yields with a low catalyst loading of 0.1 mol% using 2-methyl tetrahydrofuran as a sustainable solvent. Compared to many procedures described in the literature, this procedure represents a step towards an increased sustainability in terpene modification by considering several principles of Green Chemistry, such as renewable resources, catalysis and mild reaction conditions for elementary chemical transformations. This article is part of a discussion meeting issue 'Science to enable the circular economy'.

Regioselective Bismuth‐Catalyzed Synthesis of Pyranocoumarins and Furocoumarins from 4‐Hydroxycoumarins and Propargyl Alcohols

An efficient method for the bismuth‐catalyzed regioselective synthesis of pyranocoumarins and furocoumarins has been developed from the reaction of 4‐hydroxycoumarins with propargyl alcohols. The reaction proceeds through sequential propargylation and intramolecular cyclization reactions catalyzed by bismuth(III) triflate.

Reaction behaviour of arylamines with nitroalkenes in the presence of bismuth(iii) triflate: an easy access to 2,3-dialkylquinolines.

We report the reaction behaviour of arylamines with nitroalkenes in the presence of bismuth(iii) triflate (10 mol%) and diacetoxyiodobenzene (10 mol%). We obtained 2,3-dialkylquinoline derivatives instead of the expected 3-alkylindole derivatives. The present reaction is an alternative approach for the synthesis of 2,3-dialkylquinoline derivatives under milder conditions. Furthermore, we establish the mechanistic pathway by theoretical calculations using Gaussian 09 software [B3LYP/6-311+G(d,p)], which shows that the conventional aza-Michael reaction is preferred over Michael addition. Aliphatic nitroalkenes behave in a different manner than aromatic nitroalkenes. An aza-Michael adduct gives rise to an imine by the elimination of water which may tautomerize to the corresponding enamine. The resulting imine and enamine intermediates react together to afford the desired quinoline derivatives. This protocol has the advantages of consecutive formation of one C-N and two C-C bonds, high regioselectivity, broad substrate-scope and good yields.

Resolution of Racemic α-Hydroxyphosphonates: Bi(OTf)3-Catalyzed Stereoselective Esterification of α-Hydroxyphosphonates with (+)-Dibenzoyl-l-tartaric Anhydride.

A practical and efficient method has been developed for the preparation of optically active α-hydroxyphosphonates through resolution of the racemates. Treatment of racemic diethyl 1-hydroxy-1-phenylmethylphosphonate (1) with (+)-dibenzoyl-L-tartaric anhydride gave two diastereomeric esters 2 and 3 in the presence of bismuth triflate (15 mol %) in an 86:14 ratio. The two diastereomeric esters were separated by simple column chromatography, and the structure for the major diastereomer was determined by X-ray crystallographic analysis. Simple hydrolysis of the isolated major diastereomer in the usual manner afforded (R)-O,O-diethyl-1-[hydroxyl(phenyl)methyl] phosphonate 1. The advantages of the present method are that the operation is simple and easy to handle, along with rapid and good yield preparations of both enantiomers of the racemic α-phosphonates 1. Diastereoselective reactions of various racemic α-hydroxyphosphonates with d-Bz-L-TA in the presence of Bi(OTf)3 are also described.

A New Method for the Preparation of Bis(alkylamino)maleonitriles from Aliphatic Isocyanides with TMSCN and Bi(OTf)3

Bis(alkylamino)maleonitriles are starting materials for the synthesis of a number of important intermediates, including porphyrazines that serve as dyes, pigments, and models of biologically active substances; hence, the development of improved methods for their preparation is important. Herein, we report a facile new method for the preparation of bis(alkylamino)maleonitriles from isocyanides. Treatment of tert-alkyl isocyanides with trimethylsilyl cyanide (TMSCN) and trimethylsilyl triflate (TMSOTf) in the presence of bismuth(III) triflate [Bi(OTf)3] afforded the corresponding bis(alkylamino)maleonitriles in moderate yields. tert-Alkyl isocyanides bearing a variety of functional groups, including halide, ether, ester, imide, amide, and carbamate, are tolerated under the developed reaction conditions. To the best of our knowledge, this is the first report of a synthetic method for the preparation of bis(alkylamino)maleonitriles in a single step from tertiary alkyl isocyanides.

Catalytic, Tunable, One-Step Bismuth(III) Triflate Reaction with Alcohols: Dehydration Versus Dimerization.

Bi(OTf)3·xH2O is a powerful catalyst for the dehydration of tertiary alcohols into alkenes in apolar solvents. The reaction proceeds smoothly and selectively, with amounts as low as 0.01 mol % catalyst, in yields up to 93%. Moreover, in polar solvents, Bi(OTf)3·xH2O (0.1–1 mol %) selectively catalyzes the dimerization of the alcohols instead, forming new C–C bonds, in yields up to 96%. This mild, efficient, economic, and eco-friendly method is applicable across different chemical classes and amenable to several functional groups.

Synthesis of α-Arylated Cycloalkanones from Congested Trisubstituted Spiro-epoxides: Application of the House–Meinwald Rearrangement for Ring Expansion

A three-step sequence for the synthesis of α-arylated cyclohexanones and the most challenging cycloheptanones is reported. First, an efficient one-pot synthesis of β,β'-disubstituted benzylidene cycloalkanes (styrenes) using the palladium-catalyzed Barluenga reaction from readily available feedstock chemicals is described. Furthermore, an epoxidation followed by the House-Meinwald rearrangement (HMR) of spiro-epoxides is reported to produce a number of α-arylated cycloalkanones upon ring expansion. Reactions catalyzed by bismuth triflate underwent quasi-exclusively ring expansion for all substrates (electronically poor and rich), with yields ranging from 15% to 95%, thus demonstrating the difficulty of achieving ring enlargement for electron-deficient spiro-epoxides. On the other hand, by means of catalysis with aluminum trichloride, the rearrangement of spiro-epoxides proceeded typically in high yields and with remarkable regioselectivity on a broader substrate scope. In this case, a switch of regioselectivity was achieved for spiro-epoxides with electron-withdrawing substituents which enable the method to be successfully extended to some chemospecific arene shifts and the synthesis of aldehydes bearing a α-quaternary carbon. While the HMR has been extensively studied for smaller ring enlargement, we are pleased to report herein that larger cyclohexanones and cycloheptanones can be obtained efficiently from more sterically demanding trisubstituted spiro-epoxides bearing electron-releasing and electron-neutral arene substituents.

Bismuth(III) Triflate Catalyzed Three-Component Reactions of Indoles, Ketones, and α-Bromoacetaldehyde Acetals Enable Indole-to-Carbazole Transformation.

A three-component reaction of indoles, α-bromoacetaldehyde acetals, and ketones was developed by using bismuth(III) triflate as the catalyst to realize a straightforward approach for synthesizing carbazole derivatives. The reaction was established mechanistically through the autotandem catalysis of Bi(OTf)3 in the following two steps: (i) Friedel-Crafts-type alkylation of indole with α-bromoacetaldehyde acetal, which produced a tryptaldehyde-type intermediate and (ii) [4 + 2] annulation of this intermediate with the ketone component.

Microwave-assisted Michael-type addition of 1-(arylsulfonyl)-pyrroles and -indoles to methyl vinyl ketone using bismuth triflate as catalyst

Microwave-assisted Michael-type addition of 1-(arylsulfonyl)-pyrroles and -indoles to methyl vinyl ketone using bismuth triflate as catalyst

Modular synthesis of new C-aryl-nucleosides and their anti-CML activity

The C-aryl-ribosyles are of utmost interest for the development of antiviral and anticancer agents. Even if several synthetic pathways have been disclosed for the preparation of these nucleosides, a direct, few steps and modular approaches are still lacking. In line with our previous efforts, we report herein a one step - eco-friendly β-ribosylation of aryles and heteroaryles through a direct Friedel-Craft ribosylation mediated by bismuth triflate, Bi(OTf)3. The resulting carbohydrates have been functionalized by cross-coupling reactions, leading to a series of new C-aryl-nucleosides (32 compounds). Among them, we observed that 5d exerts promising anti-proliferative effects against two human Chronic Myeloid Leukemia (CML) cell lines, both sensitive (K562-S) or resistant (K562-R) to imatinib, the “gold standard of care” used in this pathology. Moreover, we demonstrated that 5d kills CML cells by a non-conventional mechanism of cell death.

An Acid-Catalyzed Addition and Dehydration Sequence for the Synthesis of Heteroarylated Steroidal Dienes.

Additions of heteroarenes to hormone steroids containing an α,β-unsaturated ketone are reported. Additions of a range of electron-rich heteroarene nucleophiles, including indoles, a pyrrole, and a thiophene, to a variety of commercially available steroids and subsequent dehydration formed 3-heteroarylated steroidal dienes in up to 93% yield. This atom-economical reaction sequence occurs under mild reaction conditions in the presence of catalytic bismuth triflate.

Electronic effect of substituents on anilines favors 1,4-addition to trans-β-nitrostyrenes: access to N-substituted 3-arylindoles and 3-arylindoles.

A simple and an efficient method for the regioselective synthesis of N-alkyl/aryl/H 3-arylindole derivatives from N-substituted anilines and trans-β-nitrostyrenes has been described using 10 mol% of bismuth(iii) triflate as a catalyst in acetonitrile at 80 °C. The present protocol profits from the formation of new C-C and C-N bonds, broad substrate scope and moderate to good yields.

Liquid-Crystalline Properties of Thioesters

An extension of a new method for forming thioesters with mesomorphic properties has been described, whereby the treatment of aryl tert-butylthioethers with long-chain acid chlorides in the presence of bismuth triflate afforded simple derivatives in good yields. This method in the case of 1-cyanoazulenes was, however, complicated by a competitive Friedel–Crafts-type acylation side reaction at the 3-position. Long-chain derivatives of cyanobiphenyl attached through a thioester linkage exhibited mesophases comparable with their ester analogues. The use of shorter chains to decorate the cyanobiphenyl moiety did not produce mesophasic behaviour, unlike their ester analogues. The cyanobiphenyl derivatives showing mesophasic behaviour were studied by small-angle X-ray diffraction, showing alignment for molecules possessing a smectic A phase. It was found that the layer spacing in the smectic A phase was ~1.5 times the length of the molecule, owing to antiparallel pairing arising from π-stacking between neighbouring units. Calculations suggest these derivatives should exhibit large dielectric anisotropy; however, instability made an exact value difficult to determine. For potential use in a liquid crystal display (LCD), the thioester holds some promise, although this may be limited by the relative stability of the thioester functionality.

Bismuth Triflate-Catalyzed Vinylogous Nucleophilic 1,6-Conjugate Addition of para-Quinone Methides with 3-Propenyl-2-silyloxyindoles.

A highly diastereoselective vinylogous nucleophilic 1,6-conjugate addition reaction of para-quinone methides with 3-propenyl-2-silyloxyindoles by a bismuth triflate catalyst has been developed. A number of diphenylmethane type compounds functionalized with oxindole motifs was obtained with excellent yields (up to 99%) and very good diastereoselectivities (up to Z/E > 99:1).

Desymmetrization of Hepta-1,6-dien-4-ol by a Highly Stereo­selective Tandem Prins–Ritter Cyclization: Access to New THP Acetamides

Prins–Ritter cyclization performed from hepta-1,6-dien-4-ol and various aldehydes, promoted by bismuth(II) triflate, afforded N-(tetrahydropyranyl)acetamides in moderate to high yields. Subsequent Wacker-type oxidation using Dess–Martin periodinane (DMP) delivered the corresponding ketones.

Bismuth(III) triflate: An Efficient Catalyst for the Synthesis of Diverse Biologically Relevant Heterocycles

AbstractLast decade has seen a tremendous applications of bismuth(III) trifluoromethanesulfonate [Bi(OTf)3] as an efficient, cheap, environmentally benign, Lewis acidic catalyst for the various organic transformations. On the other hand heterocycles are very common in naturally occurring compounds and are the privileged structural subunit of many marketed drug molecules. The present review summarizes the applications of bismuth(III) triflate as a catalyst for the synthesis of diverse biologically relevant heterocycles reported so far.

Tuning the Reactivity of Functionalized Diallylic Alcohols: Brønsted versus Lewis Acid Catalysis.

The chemodivergent reactivity of bifunctional, enol thioether-containing diallylic alcohols in acidic medium is disclosed, highlighting the difference between strong Lewis acid and mild Brønsted acid catalysis. In the presence of bismuth(III) triflate, allylic alcohol activation affords diversely substituted cyclopentenones in a Nazarov-type electrocyclization, whereas activation of the thioenol ether by p-toluenesulfonic acid provides an entry to α-sulfenylated β,γ-unsaturated ketones. Both methods represent a facile access to the corresponding products under mild conditions, using inexpensive and non-toxic catalytic systems.

Catalytic Conjugate Addition of Electron-Rich Heteroarenes to β,β-Disubstituted Enones.

Catalytic conjugate additions of heteroarenes to β,β-disubstituted enones are reported. Additions of a range of heteroarene nucleophiles, including furans, indoles, a pyrrole, and a thiophene, to a variety of β,β-disubstituted enones occur to form the corresponding ketone products containing heteroarylated, all-carbon quaternary centers in up to 90% yield. These reactions occur under mild reaction conditions in the presence of low loadings of bismuth triflate.

Studies in Cyclization of Aromatic Epoxy-acyclicpolyprenes: Lewis Superacids and Titanocene Chloride

Two catalytic cascade cyclization methods (radical and 'cationic) to obtain aromatic polycyclic diterpenes hydroxylated at C3 starting from aromatic epoxypolyprenes were developed. The catalytic use of the Lewis superacid bismuth triflate produces a good yield of cyclized 2 from epoxypolyprene 3. This researchmay well direct future efforts to the synthesis of bioactive natural products.

Efficient microwave-assisted direct C-benzoylation of phenols and naphthols with benzoic acid catalyzed by bismuth triflate under solvent-free or ionic liquid conditions

An efficient and simple route for the synthesis of ortho-hydroxyaryl ketones has been developed. The microwave-assisted direct C-benzoylation of phenols and naphthols in the presence of metal triflates afforded the corresponding ortho-hydroxyaryl ketones in moderate to excellent yields. Bismuth triflate showed the best catalytic performance compared to other metal triflates. The protocol has advantages including short reaction times, high chemoselectivity towards C-acylation, and simple work-up. Additionally, bismuth triflate can be easily recovered and reused several times without significant loss of catalytic performance.