Jean-Claude Rossier

A short route to furanosesquiterpenes using a new siloxyfuran building block. The synthesis of freelingnite and dehydrolasiosperman

Abstract The utility of 2-( tert -butyldimethylsiloxy)-3-methylfuran for the regioselective assembly of furanosesquiterpenes is demonstrated by the syntheses of (±)-freelingnite and dehydrolasiosperman.

cis-Disubstituted Cyclopropanes via Asymmetric Catalytic Cyclopropenation: Synthesis of Cyclopropyl-dehydroamino Acids and of Dictyopterene C′

The cyclopropenation of diethoxypropyne (1) with methyl diazoacetate in the presence of [Rh₂{(2S)‐mepy}₄] (mepy=methyl 5‐oxopyrrolidine‐2‐carboxylate) proceeds with >95% ee. The resulting cyclopropenecarboxylate 2 underwent stereoselective hydrogenation to the cis‐cyclopropane 3. Hydrolysis of the acetal function of 3 liberated the formyl cyclopropenecarboxylate 4, which was transformed by Wittig reaction with the phosphonate 5 to afford dehydroamino acid 6 as a mixture of (Z)‐ and (E)‐isomers in various proportions. The (Z)‐isomer 6a was hydrolyzed, and the structure and the absolute configuration of the (Z)‐dicarboxylic acid 7a were established by X‐ray crystallography. The cis‐divinylcyclopropane 11 (ee>95%), in turn, was synthesized from 4 via Wittig reaction to afford 8, which was transformed to the aldehyde 10 and subjected to a second Wittig reaction. Thermolysis of 11 afforded (+)‐dictyopterene C′ (12) in quantitative yield.

Transition-Metal-Catalyzed Carbenoid Reactions of Sulfonium Ylides

Olefins undergo cyclopropanation with diphenylsulfonium (ethoxycarbonyl)methylide (=diphenylsulfonium 2‐ethoxy‐2‐oxoethylide; 3a) in the presence of chiral CuI or RhII catalysts. trans/cis Ratios and ees of the cyclopropanes 6 obtained with this ylide in the presence of a chiral CuI catalyst 7 are identical with those obtained with ethyl diazoacetate (4). In the case of catalysis with RhII, the trans/cis ratios of the cyclopropanes as well as the enantioselectivity change slightly upon going from the ylide 3a to diazoacetate 4.

The chemotherapy of rodent malaria. XLVIII. The activities of some synthetic 1,2,4-trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. Part 1: Studies leading to the development of novel cis-fused cyclopenteno derivatives

The new Chinese antimalarial blood schizontocide, artemisinin, derived from the plant Artemisia annua, displays a high level of activity against polyresistant Plasmodium falciparum. Several synthetic 1,2,4-trioxanes were examined in a search for compounds that exhibit a similar type of action against drug-resistant parasites. This paper, the first of a series, describes the examination of these trioxanes against drug-sensitive and drug-resistant malaria parasites in a rodent model, using artemisinin and arteether as comparison standards. Cis-fused cyclohexeno-1,2,4-trioxanes (10-17) substituted with various side-chains revealed for the most part variable but weak antimalarial activity. On the other hand, cis-fused cyclopenteno-1,2,4-trioxanes (18-19) showed greater activity, 19 showing about 1/30th of the activity of arteether against drug-sensitive Plasmodium berghei in vivo, thereby providing a clue to the structure-activity relationship.

An unusual stereospecific epoxidation with “per-amberlyst 15®”

Abstract 4-Methyl-4-naphthoquinol and its 5-methyl derivative on treatment with per-Amberlyst 15 are converted to the corresponding cis-2,3-epoxides in high yields. The latter structure was determined by X-ray crystallography.

The osmium-catalyzed asymmetric dihydroxylation of cis-fused cyclopenteno-1,2,4-trioxanes

Submission of racemic, cis-fused cyclopenteno-1,2,4-trioxanes (1 and 1-ent) to catalytic amounts of K2OsO4 and (DHQD)2PHAL and 1.2 equivalents of N-methylmorpholine N-oxide in aqueous acetone at 20°C (hybrid AD-mix-β) for 2 h gave the (-)-enantiomer, 1-ent (ee 95%) in 30% yield. The same reaction, but with (DHQ)2PHAL, (hybrid AD-mix-α) afforded the (+)-enantiomer, 1 (ee 95%) in 25% yield after 2.7 h reaction. Similar, efficient kinetic resolution of the racemic di-p-fluoro analogues (2 and 2-ent) was also achieved with the same reagents.

1,2,4-Trioxanes as masked, dual purpose, functional groups

Scission reductrice de trioxannes-1,2,4 condenses en glycols et cetones ou aldehydes par Zn/acide acetique

The reaction of trimethylsilyl α-trimethylsilylperoxy esters with ketones and aldehydes. A simple, efficient synthesis of 1,2,4-trioxan-5-ones

The title compounds readily react in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulphonate to give the corresponding 3,6-substituted 1,2,4-trioxan-5-ones in good yields.

Gas-phase stability of tertiary carbenium ions and rates of solvolysis of tertiary derivatives

The stability of tertiary carbenium ions was determined in the gas phase by ion cyclotron resonance (ICR) and by dissociative proton attachment (DPA). The rate constants for solvolysis of bridgehead derivatives correlate well with the stabilities of bridgehead carbenium ions, as determined by DPA and by ICR, but the ICR data of strained ions do not correlate, indicating rearrangements under the conditions of the ICR experiment. Simple acyclic tertiary derivatives solvolyze faster than predicted on the grounds of the stability of the respective carbenium ions. The effect of nucleophilic solvent participation on the rate of methanolysis of tertiary derivatives was investigated with (R)-3-chloro-3,7-dimethyloctane (17), which reacts with 77% inversion and 23% racemization. Copyright

Eliminative ring fission of 1,2,4-trioxan-5-ones. A new approach to α-keto acids

6-Mono-R-substituted 1,2,4-trioxan-5-ones readily undergo base-catalysed O–O bond cleavage to furnish α-keto acids (RCOCOOH) in high yields even when the R-substituents are bulky.