Carbohydrate-derived spiroketals: stereoselective synthesis of di-D-fructose dianhydrides via intramolecular aglycon delivery

[reaction: see text] A one-pot synthesis of C(2)-symmetric di-d-fructose dianhydrides having the 1,6,9,13-tetraoxadispiro [4.2.4.2]tetradecane skeleton has been accomplished via intramolecular aglycon delivery from (6 --> 6) xylylene-tethered fructofuranose precursors. The stereochemical outcome of the glycosylation-spiroketalization process is governed by the geometrical constraints imposed by the rigid tetracyclic structure of the final compound.     

Carbohydrate-derived spiroketals: stereoselective synthesis of di-d-fructose dianhydrides

A one-pot synthesis of di-d-fructose dianhydrides (DFAs) having the 1,6,9,13-tetraoxadispiro[4.2.4.2]tetradecane and 1,7,10,15-tetraoxadispiro[5.2.5.2]hexadecane skeleton has been accomplished. The methodology relies on the ability of per-O-protected 1,2-O-isopropylidene β-d-fructofuranose and β-d-fructopyranose derivatives to undergo a tandem acetal cleavage-intermolecular glycosylation-intramolecular spiroketalization process by reaction with suitable acid promoters, such as boron trifluoride etherate or trifluoromethanesulfonic acid, in apolar organic solvents. Spirocyclization proceeds then under irreversible reaction conditions to give binary mixtures of di-d-fructofuranose (α,α and α,β diastereomers) or di-d-fructopyranose 1,2′:2,1′ dianhydrides (β,β and α,β), respectively, the stereochemical outcome being dependent on the non-participating or participating character of the protecting groups. Thus, benzylated and allylated derivatives afford, preferentially, the non-symmetric DFAs (α,β), with diastereomeric excess up to 92%. In contrast, the use of participating benzoyl groups favours the C₂-symmetric diastereomer in both series.     

Pechmann reaction promoted by boron trifluoride dihydrate

The Pechmann reaction of substituted phenols 1a-e with methyl acetoacetate (2) can be activated by boron trifluoride dihydrate (3) to give the corresponding 4-methyl- coumarin derivatives 4a-e in excellent yield (98-99 %).     

Stereoselective synthesis of nonsymmetrical difructose dianhydrides from xylylene-tethered d-fructose precursors

Nonsymmetrical furanose-pyranose difructose dianhydrides (DFAs), a class of cyclic disaccharides present in foodstuffs, have been prepared in high yield by connecting the reacting monosaccharide moieties through a xylylene bridge prior to triflic acid-promoted bis-spiroketalization. The reaction can then proceed either intra- or intermolecularly, both the regio- and the stereoselectivity being strongly dependent on the spacer length. Noteworthy, the longer m- and p-xylylene positional isomers led to the thermodynamic α-d-fructofuranose β-d-fructopyranose 1,2′:2,1′-dyanhydride 1, the major DFA in commercial caramel, in a stereoselective manner. The shorter o-xylylene tether afforded preferentially the elusive contra-thermodynamic β-d-fructofuranose α-d-fructopyranose diastereomer 2, a trace constituent of caramel. The results have been rationalized in terms of stereoelectronic and conformational properties and offer new perspectives for the preparation of pure DFA standards for analytical and nutritional studies.     

A ring opening reaction of oxetanes with lithium acetylides promoted by boron trifluoride etherate

Several substituted oxetanes were treated with lithium acetylides in the presence of boron trifluoride etherate to give f-hydroxyacetylenes. The reaction conditions were varied and several synthetic features of the present reaction were revealed.     

Favorski type rearrangement in the lead tetraacetate oxidation of enamines promoted by boron trifluoride

Favorski type rearrangement has been achieved in the lead tetraacetate oxidation of enamines in the presence of boron trifluoride etherate and alcohol.     

Catalysis of olefin isomerizations by boron trifluoride

The kinetics of isomerization of butenes by boron trifluoride with acetic acid or methanol as cocatalysts have been re-examined. The results, over a wide concentration range, and at temperatures from ?20 to +20°C, are consistent with previous data, but it is shown that the previously suggested mechanism cannot apply. By using deuterated acetic acid as cocatalyst it has been found that isomerization exactly parallels protonation, which is consistent with a mechanism involving a classical carbonium ion.     

An iodoetherification-dehydroiodination strategy for the synthesis of complex spiroketals from dihydroxyalkene precursors

Dihydroxyalkenes or their monoprotected alcohol derivatives are transformed to 5,5- and 5,6-spiroketals through a sequence involving an initial iodocyclization, followed by a silver triflate mediated spiroketalization step on the derived hydroxy-iodoether.     

Practical carbonyl-ene reactions of alpha-methylstyrenes with paraformaldehyde promoted by a combined system of boron trifluoride and molecular sieves 4A

[reaction: see text] A combined system of boron trifluoride and molecular sieves is an efficient promoter for the carbonyl-ene reaction of alpha-methylsyrenes with paraformaldehyde. The coexistence of BF3 x OEt2 and molecular sieves 4A is essential for obtaining high yields of ene products.     

Stereoselective synthesis of CD-ring precursors of vitamin D derivatives

Two expedious and useful approaches to the construction of Vitamin D trans-hydrindane building blocks are proposed. These involve the desymmetrization of the anti meso-acetylmethyldivinylcyclopentane 3 which proceeds through either the selective formation of epoxyketone 5 and intramolecular enolate cyclisation or a xanthate groupe transfer mediated radical cyclization to furnish trans-hydrindanes 7 and 16 respectively. Epoxyketone 5 is prepared by means of a three-step reaction process including reduction of the ketone moiety, bishomoallylic alcohol-directed epoxidation and Dess-Martin oxidation. Alternatively, an asymmetric reduction using borane/tetrahydrofuran complex and (R)-2-methyl-CBS-oxazaborolidin made accessible the epoxyketone in good optical purity. The xanthate 16 can undergo a Johnson sulfoximine ketone resolution that allows access to both enantiomers. Various derivatizations of 16 to more elaborated synthetic intermediates are also reported.     

Boron trifluoride promoted reaction of benzenesulphenanilides with alkenes-arylaminosulphenylation of alkenes.

The addition of benzenesulphenanilides to alkenes in the presence of boron trifluoride provides a practicable synthetic procedure for the arylaminosulphenylation of alkenes.     

Stereoselective synthesis of 25-hydroxyvitamin D2 side chain via the acetal template route

A highly stereoselective synthesis of the side chain of 25-hydroxyvitamin D₂ and 1α,25-dihydroxyvitamin D₂ is described.     

Donor-acceptor complexes of dipyrrolylmethenes with boron trifluoride as intermediates in the synthesis of Bodipy

The formation of donor-acceptor complexes of dipyrrolylmethene and structurally similar biladiene-a,c with boron trifluoride was studied by electronic absorption, IR, and ¹H NMR spectroscopies as well as by quantum chemical calculations. It was shown that the formation of donor-acceptor complexes is the first step of the synthesis of the corresponding boron fluoride chelate complexes (Bodipy). The hydrogen bond N—H...F—B additionaly stabilizes the donor-acceptor complexes. The stability constants, geometric parameters, and energy characteristics of the donoracceptor complexes were determined; the two-step mechanism of Bodipy synthesis was analyzed.     

Stereoselective synthesis of optically active cyclitol precursors via a chemoenzymatic method

Racemic α′-acetoxy α,β-unsaturated cyclohexanone has been converted to the corresponding enantiomerically enriched α′-hydroxylated and acetoxylated compounds with 97% ee via enzymatic resolution with PLE. OsO₄-Catalyzed dihydroxylation of enantiomerically enriched α′-acetoxylated compound afforded a single diastereomer in 85% chemical yield. The absolute configuration of 2,3,6-triacetoxycylohexanone was determined by X-ray diffraction analysis. Subsequent Luche reduction allowed us to obtain corresponding syn-type cyclitol precursors in a highly stereoselective manner as expected.     

Crystallization during polymerization of diazomethane. I. The boron trifluoride catalyzed reaction

The polymerization and crystallization of diazomethane was analyzed starting with various monomer and catalyst concentrations by following the monomer concentration and analysis of the solid polymethylene produced. Electron microscopy, thermal analysis, x-ray diffraction, and viscometry and density determinations were used to characterize the crystals as produced and after etching with nitric acid. The crystals have a fibrillar and a lamellar component and show no regular chain folding of the molecules. The overall process follows only very approximately the path expected for an ideal living-polymer system capable of reaction in solution and in the solid state. For more detailed correspondence, it was necessary to assume two reaction paths and two crystallization paths.     

Stereospecific cyclopropanation of highly substituted C-C double bonds promoted by CrCl2. Stereoselective synthesis of cyclopropanecarboxamides and cyclopropyl ketones

We describe herein a CrCl(2)-promoted cyclopropanation of alpha,beta-unsaturated amides. This reaction can be carried out on (E)- or (Z)-alpha,beta-enamides in which the C-C double bond is di-, tri-, or tetrasubstituted. In all cases the process is completely stereospecific and only a single diastereoisomer is obtained. In addition, cyclopropyl ketones were readily prepared by reaction of the cyclopropanecarboxamides (derived from morpholine) obtained with a range of organolithium compounds. A mechanism has been proposed to explain the cyclopropanation reaction.     

Oxidation of alkenes with hydrogen peroxide, catalyzed by boron trifluoride. Synthesis of vicinal methoxyalkanols

In oxidation of alkenes with the BF₃-H₂O₂ system, boron trifluoride induces transfer of available oxygen from hydrogen peroxide, accompanied by the formation of epoxides. The oxidation in methanol occurs as a one-pot two-step process involving epoxidation of the C=C bond followed by opening of the oxirane ring, with the formation of methoxyalkanols.     

Stereoselective synthesis of cis-2,6-bis-hydroxyalkyl-tetrahydropyrans by the permanganate promoted oxidative cyclisation of 1,6-dienes

The first examples of permanganate promoted oxidative cyclisations of 1,6-dienes are described, providing exclusively cis-2,6-bis-hydroxyalkyl-tetrahydropyrans. In addition, good levels of asymmetric induction have been attained using dienoyl sultam substrates.