The absolute stereochemistry of grenadamide

3-(2S-Heptylcycloprop-1S-yl)propanoic acid 2-phenylethanamide was synthesised from cis-cyclopropan-1,2-dimethanol via enzymatic desymmetrisation of the dibutyrate; it gave identical NMR spectroscopic data to those reported for grenadamide but had an equal and opposite absolute rotation, indicating that the latter is the 2R,1R-enantiomer.     

Catalytic cycloalumination of 1,2-dienes in the total synthesis of natural grenadamide and lyngbyoic acid

Russian Chemical Bulletin - An original method for the total synthesis of natural grenadamide and its precursor lyngbyoic acid with high stereoselectivity and yields was developed using the...     

Enantio- and diastereocontrolled conversion of chiral epoxides to trans-cyclopropane carboxylates: application to the synthesis of cascarillic acid, grenadamide and l-(-)-CCG-II

An efficient high yielding improved method for the enantio- and diastereoselective cyclopropanation of chiral epoxides using triethylphosphonoacetate and base (Wadsworth-Emmons cyclopropanation) is reported. The utility of this protocol is illustrated by concise and practical synthesis of cascarillic acid, grenadamide and L-(-)-CCG-II, a cyclopropane containing natural products.     

Synthesis of vinyl 1,2-diketones

A new route is outlined for preparation of vinyl 1,2-diketones via a three-step sequence. First, allylic alcohols are photooxidized by ¹O₂ to hydroperoxides, which are reduced to vinyl 1,2-diols. These vinyl 1,2-diols are oxidized to vinyl 1,2-diketones with oxoammonium salts, which are prepared in situ from organic nitroxyl radicals. The new route is short, avoids the use of protecting groups, and is generally applicable to obtain aliphatic or aromatic vinyl 1,2-diketones.     

Approaches to the preparation of (Z)-1,2-difluorostilbenes

Methodology directed at the preparation of (Z)-1,2-difluorostilbenes has been evaluated. For symmetrical (Z)-1,2-difluorostilbenes, photochemical isomerization of the isomeric (E)-1,2-difluorostilbenes, and HPLC separation of the mixture of stilbene isomers is a reasonable route to a particular (Z)-stilbene. An alternative approach to both symmetrical and/or unsymmetrical (Z)-1,2-difluorostilbenes has been developed via stereospecific Pd(0) coupling of (E)-1,2-difluoro-aryl-ethenyltributylstannanes under Stille-Liebiskind conditions with aryl idodies. The requisite arylstannanes can be obtained via the reported route developed by Davis or via (E)-1,2-difluorovinyltributylstannane - a new route described in this work. The methodology tolerates almost any functionality in the aryl ring, is easily carried out, is stereospecific and provides the first general route to (Z)-1,2-difluorostilbenes.     

Lewis acid-mediated displacements of alkoxydioxolanes: synthesis of a 1,2-dioxolane natural product

[formula: see text] Addition of electron-rich alkenes to the peroxycarbenium ions derived from Lewis acid-mediated ionization of 3-alkoxy-1,2-dioxolanes provides an efficient route for the synthesis of substituted 1,2-dioxolanes. The methodology is illustrated with a rapid synthesis of a 1,2-dioxolane natural product related to the plakinic acids.     

Copper-catalyzed enantioselective synthesis of trans-1-alkyl-2-substituted cyclopropanes via tandem conjugate addition-intramolecular enolate trapping

Cu-TolBINAP-catalyzed conjugate addition of Grignard reagents to 4-chloro-α,β-unsaturated esters, thioesters, and ketones leads to 4-chloro-3-alkyl-substituted thioesters and ketones in up to 84% yield and up to 96% ee upon protonation of the corresponding enolates at low temperature. Tandem conjugate addition-enolate trapping, however, yields trans-1-alkyl-2-substituted cyclopropanes in up to 92% yield and up to 98% ee. The versatility of this reaction is illustrated by the formation of key intermediates for the formal syntheses of cascarillic acid and grenadamide.     

Metal-free synthesis of 1,2-amino alcohols by one-pot olefin aziridination and acid ring-opening

A one-pot, two-step reaction comprising olefin aziridination and ring-opening of an aziridine intermediate to synthesize 1,2-amino alcohols has been developed. This reaction is suitable for several types of olefin. This methodology allows an efficient and highly stereoselective approach to various 1,2-amino alcohols, readily providing an alternative route to conventional vicinal amino alcohols.     

Iron-promoted C-C bond cleavage of 1,3-diketones: a route to 1,2-diketones under mild reaction conditions

A conceptual method for the preparation of 1,2-diketones is reported. The selective C-C bond cleavage of 1,3-diketones affords the 1,2-diketones in high yields under mild reaction conditions in air by the use of FeCl(3) as the catalyst and tert-butyl nitrite (TBN) as the oxidant without the use of solvent. The possible reaction mechanism is discussed. This protocol provides an expeditious route to the useful 1,2-diketones.     

Direct and Tandem Routes for the Copolymerization of Ethylene with Polar Functionalized Internal Olefins

Transition metal catalyzed ethylene copolymerization with polar monomers is a highly challenging reaction. After decades of research, the scope of suitable comonomer substrates has expanded from special to fundamental polar monomers and, recently, to 1,1‐disubstituted ethylenes. Described in this contribution is a direct and tandem strategy to realize ethylene copolymerization with various 1,2‐disubstituted ethylenes. The direct route is sensitive to sterics of both the comonomers and the catalyst. In the tandem route, ruthenium‐catalyzed ethenolysis can convert 1,2‐disubstituted ethylenes into terminal olefins, which can be subsequently copolymerized with ethylene to afford polar functionalized polyolefins. The one‐pot, two‐step tandem route is highly versatile and efficient in dealing with challenging substrates. This work is a step forward in terms of expanding the substrate scope for transition metal catalyzed ethylene copolymerization with polar‐functionalized comonomers.     

An efficient asymmetric synthesis of grenadamide

The cyclopropane containing natural product grenadamide has been prepared in six steps using (R)-5,5-dimethyl-oxazolidin-2-one as a chiral auxiliary for asymmetric synthesis. Key synthetic steps include the use of the β-hydroxyl group of a syn-aldol product as a ‘temporary’ stereocentre to control the facial selectivity of a directed cyclopropanation reaction, as well as the use of phenylethylamine as a nucleophile for the direct aminolysis of an N-acyl-oxazolidin-2-one intermediate.     

Synthesis of Green Colored Photochromic 6′-Arylamino Spiro [2H]Naphth[1,2-b]oxazines

The published route to a series of 6′-arylamino substituted photochromic spirooxazines has been investigated with improvements made to perform the synthesis in satisfactory yield. The route has been exemplified with several novel derivatives prepared (including hydroxyl functionalised). Additionally, a one-pot procedure for the conversion of suitably functionalized 1,2-naphthoquinones into the photochromic compounds is reported.     

DFT analysis of the mechanism of 1,2-dichloroethane dechlorination on supported Cu-Pt bimetallic catalysts

The reaction routes of 1,2-dichloroethane dechlorination to ethylene on discrete nanoclusters that served as models of the active sites of supported Cu-Pt catalysts were calculated. Two reaction pathways were predicted. The first route corresponds to sequential elimination of the chlorine atoms from 1,2-dichloroethane; this is a three-stage reaction that occurs via two stable intermediates (stepwise mechanism). The limiting stage is the stage that corresponds to the dissociation of the first C-Cl bond. The second channel corresponds to a simultaneous one-stage elimination of two chlorine atoms (direct mechanism). Both reaction routes are thermodynamically possible, but the stepwise process is more probable, in contrast to the process on monometallic Cu catalysts. For the stepwise process, the vibrational spectra of stable intermediates were calculated for identification of the latter. A set of spectral data characteristic for the stepwise mechanism were determined. The three-step molecular mechanism suggested for 1,2-dichloroethane dechlorination to ethylene is compared with several kinetic schemes known from the literature. Possible modifications of the reaction route that forms ethane and monochloroethane are analyzed.     

Expedient synthesis of pyrrolo[1,2-a]indoles: preparation of the core of yuremamine

Pyrrolo[1,2- a]indoles are conveniently prepared from tetrahydro-1,2-oxazines, which in turn are generated through the reaction of nitrones with 1,1-cyclopropanediesters. The synthetic route proves to be highly diastereoselective and provides access to the core of the recently discovered pyrrolo[1,2- a]indole natural product yuremamine.     

A Convenient Synthesis of Octahydro-pyrazino [ 1,2- a ] pyrazine

The recent research results suggest that a series of octahydro-pyrazino[ 1,2-a ]pyrazines are useful as antiallergic agents.[1] Gubert et al. [2] developed a route from 1,4-dibenzyl-2-ethoxycarbonylpiperazine for the synthesis of this ring system. Under their conditions, this ring system was obtained with a low overall yield in six steps. Optimization of synthetic route to this ring system is still desirable. In this paper, we presented an efficient synthesis of octahydropyrazino[1,2-a]pyrazine by a new and efficient method starting from 1,3-dichloro-2-propanol and N-tosylated diethylenetriamine. The structure of title compound was determined by spectroscopy and X-ray diffraction technique.     

Synthesis of disubstituted 1,2-dioxolanes, 1,2-dioxanes, and 1,2-dioxepanes

A route to cyclic peroxides containing 1,2-dioxolane, 1,2-dioxane or 1,2-dioxepane rings is described. These compounds present simpler structures related to the bicyclic core of stolonoxides, metabolites with marked cytotoxicity against several mammalian tumor cell lines, isolated from the marine tunicate Stolonica socialis. The key synthetic step consists in the intramolecular Michael addition of a secondary hydroperoxide group to an α,β-unsaturated ester.     

3-methylthio-1,2-dithiolylium salts—II: Reaction with 4-hydroxy-3h-pyran-2,6-dione. 1,3-bis-(1,2-dithiol-3-ylidene)-2-propanones

A simple route to the hitherto unknown 1,3-bis-(1,2-dithiol-3-ylidene)-2-propanones is reported: 3-Methylthio-1,2-dithiolylium salts condense with 4-hydroxy-3H-pyran-2,6-dione to 3,5-bis-(1,dithol-3-ylidene)pyran-2,4,6-triones, which are converted by acidic hydrolysis into the propanones.     

Synthesis of pyrido[1,2-a]indole malonates and amines through aryne annulation

Pyrido[1,2-a]indoles are known as medicinally and pharmaceutically important compounds, but there is a lack of efficient methods for their synthesis. We report a convenient and efficient route to these privileged structures starting from easily accessible 2-substituted pyridines and aryne precursors. A small library of compounds has been synthesized utilizing the developed method, affording variously substituted pyrido[1,2-a]indoles in moderate to good yields.     

Sequential cross-metathesis/cyclopropanation: short syntheses of (+/−)-cascarillic acid and (+/−)-grenadamide

The total synthesis of (+/−)-cascarillic acid has been achieved by a sequential cross-metathesis/Simmons-Smith cyclopropanation between, respectively, 1-octene with an appropriate unsaturated carboxylic acid. In parallel, a direct access to grenadamide was developed from 1-nonene with a readily available unsaturated amide. In both cases, the chemical yields were high (up to 98%) and the E/Z ratio was near 80/20. The synthesis of a dibromocyclopropane analogue has also been considered.     

A Facile method to transform trans-4-carboxy-3,4-dihydro-3-phenyl- 1(2H)-isoquinolones to indeno[1,2-c]isoquinolines

The indeno[1,2-c]isoquinolines are an important class of topoisomerase I inhibitors with anticancer activity. The condensation of Schiff bases with homophthalic anhydrides provides a mixture of cis- and trans-4-carboxy-3,4-dihydro-3-phenyl-1(2H)isoquinolones. Although the cis products can be readily converted to indeno[1,2-c]isoquinolines with thionyl chloride, the trans products do not afford indeno[1,2-c]isoquinolines using this method. The present report describes a route for conversion of the trans diastereomers to indeno[1,2-c]isoquinolines using selenoxide elimination and Friedel-Crafts cyclization chemistry.