Synthesis of new chiral pincer-complex catalysts for asymmetric allylation of sulfonimines

Four new chiral pincer-complexes were prepared based on coupling of BINOL and TADDOL moieties with iodoresorcinol followed by oxidative addition of palladium(0). The X-ray analysis of complex 5a revealed that the BINOL rings form a well-defined chiral pocket around the palladium atom. This chiral environment can be further modified by γ-substitution of the BINOL rings. Preliminary studies for electrophilic allylation of sulfonimine 2 with allylstannane revealed that the presented chiral complexes are promising asymmetric catalysts for preparation of chiral homoallyl amines. The best result was achieved employing catalytic amounts of γ-Me BINOL complex 6 affording homoallyl amine 4 with 59% ee and 74% isolated yield.     

A novel synthesis of acyclonucleosides via allylation of 3-[1-(phenylhydrazono)-L-threo-2,3,4-trihydroxybut-1-yl]quinoxalin-2(1H)one

The allylation of 3-[1-(phenylhydrazono)-L-threo-2,3,4-trihydroxybut-1-yl]quinoxalin-2(1H)one (1) gave, in addition to the anticipated 1-N-allyl derivative (2), a dehydrative cyclized product, 1-N-allyl-3-[5-(hydroxymethyl)-1-phenylpyrazol-3-yl]quinoxalin-2-one (4) and its isomeric O-allyl derivative 3. The O-allyl group in 3 underwent acetolysis under acetylation conditions, in addition to the acetylation of the hydroxyl group, to afford 2-acetoxy-3-[5-(acetoxymethyl)-1-phenylpyrazol-3-yl]quinoxaline (8) instead of the O-acetyl derivative of 3. Allylation of the tri-O-acetyl derivative of 1 caused the elimination of a molecule of acetic acid in addition to N-allylation to give 1-N-allyl-3-[3,4-di-O-acetyl-2-deoxy-1-(phenylhydrazono)but-2-en-1-yl]quinoxalin-2-one (11). Hydroxylation of the allyl group gave a glycerol-1-yl acyclonucleoside which can be alternatively obtained by a displacement reaction of the tosyloxy group in 2,3-O-isopropylidene-1-O-(p-tolylsulfonyl)glycerol (14), followed by deisopropylidenation. 1-N-(2,3-Dibromopropyl)-3-[5-(hydroxymethyl)-1-(4-bromophenyl)pyrazol-3-yl]quinoxalin-2-one (15) underwent azidolysis to give a 2,3-diazido derivative. The assigned structures were based on spectral analysis. The activity of compounds 2, 4, 6, and 15 against hepatitis B virus was studied.     

Ultrasound-promoted palladium-catalyzed carbonyl allylation by allylic alcohols with tin(II) chloride in non-polar solvents

Heterogeneous ultrasound-promoted palladium-catalyzed carbonyl allylation by γ-substituted allylic alcohols with tin(II) chloride in non-polar solvents such as diethyl ether, diisopropyl ether and toluene was carried out stepwise (first, the formation of allylic tin intermediates by ultrasonication, followed by the allylation of aldehydes by the intermediates) to produce 1,4-disubstituted 3-buten-1-ols regioselectively in moderate yields. The regioselectivity (-selection) in the ultrasound-promoted reaction is the inverse of that (γ-selection) in the homogeneous palladiumcatalyzed carbonyl allylation in polar solvents such as 1,3-dimethyl-2-imidazolidinone, DMF, DMSO and ethylene glycol. The more bulky the γ-substituent, the higher is the -regioselectivity.     

Are the 11-oxo-steroids really so hindered towards organometallic compounds?

Allylation of an 11-oxo-steroid, the protected adrenosterone, was studied to examine more closely the steric hindrance of such a ketosteroid. While the beta face exhibits, as well known, a strong steric hindrance, the alpha side appears to be only relatively hindered. A high diastereoselectivity was observed in the addition of crotyl magnesium bromide.     

Synthesis of trans-fused tetrahydrooxepins: stereoselective allylation of sulfur or fluoro-substituted tetrahydrooxepins

An efficient route to the trans-fused tetrahydrooxepin corresponding to the E ring of ciguatoxin was developed. Wide screening of allylation reactions of sulfur or fluoro-substituted tetrahydrooxepin revealed that the optimum method for obtaining the beta-allylation product selectively was the use of a combination of allyltrimethylsilane and TiCl(4) with 6-fluoro-7-hydroxytetrahydrooxepin.     

Regioselective allylation of cyclomaltoheptaose (β-cyclodextrin) leading to per(2,6-di-O-hydroxypropyl-3-O-methyl)-β-cyclodextrin

The selective modification of cyclodextrins remains a real challenge to obtain well-defined structures. The targeted cycloheptakis-(1→4)-2,6-di-O-hydroxypropyl-3-O-methyl-α-d-glucopyranosyl [per(2,6-di-O-hydroxypropyl-3-O-methyl)-β-CD] was obtained by a three-step procedure. The selective allylation of the hydroxyl functions at the positions 2 and 6 was used as a first step. This reaction was revisited then enlarged to α and γ-CDs to determine new conditions for a one-step synthesis in high yield. The per(2,6-di-O-allyl)-β-CD derivative was then reacted with iodomethane to provide per(2,6-di-O-allyl-3-O-methyl)-β-CD. Oxidative hydroboration of the allyl functions was then carried out in order to obtain a new CD derivative with seven primary hydroxyl functions on each side of the truncated cone, having a similar reactivity.     

Anthraquinones and other constituents from the roots of Eremomastax speciosa (Hochst.) Cufod

The chemical investigation of the roots of Eremomastax speciosa (Hochst.) Cufod (Acanthaceae). led to the isolation of thirteen compounds including five anthraquinones 1,8-dihydroxy-3-methylanthraquinone (1), 1,8-dihydroxy-3-methoxy-6-methylanthraquinone (2), emodin (3), aloe emodin (4) and 8-O-D-glucopyranosideemodin (5); one phenylethanoid glucoside acteoside (6); one benzophenone 2,6-dimethoxybenzophenone (7); two pentacyclic triterpenoids lupeol (8) and betulinic acid (9); three phytosterols stigmasterol (10), β-sitosterol (11), and β-sitosterol-3-O-β-D-glucopyranoside (12) and one fatty acid hexadecanoid acid (13). All these compounds are firstly reported from the roots of E. speciosa. Emodin and acteoside were modified chemically through allylation reaction to afford 3-O-allylated emodin (3a) and a new perallylated acteoside derivative (6a), respectively. The structure of the isolated compounds as well as those of the allylated derivatives were established by means of spectroscopic methods: NMR analysis (¹H and ¹³C NMR, ¹H–¹H–COSY, HSQC and HMBC), high-resolution mass spectrometry (HR-ESI-MS) and by comparison with previously reported data. All those compounds were tested for their cytotoxic activity against the human cervix carcinoma KB-3-1 cells and their antioxidant activity, the allylated acteoside derivative and 2,6-dimethoxybenzophenone showed weak cytotoxicity while acteoside showed a good antioxidant activity. In addition, the chemotaxonomic significance of the isolated compound is discussed.     

Asymmetric catalysis 87. Enantioselective allylation of 1,5-dimethylbarbituric acid with Pd catalysts and new optically active PN ligands

The new PN ligands 5, 6 and 7 were prepared by Schiff base condensation of 2-formylphenyl(diphenyl)phosphine (1) with the optically active amines (R)-(−)-2-aminobutanol (2), (S)-(+)-2-aminobutanol (3) and (1S,2S)-2-amino- 1-phenyl-1,3-propanediol (4). These new ligands were used in the Pd catalysed allylation of 1,5-dimethylbarbituric acid with allylacetate. 5-Allyl-1,5-dimethylbarbituric acid was obtained with an optical induction of up to 12.7% ee.     

Stereo-controlled synthesis of functionalized tetrahydropyridines based on the cyanomethylation of 1,6-dihydropyridines and generation of anti-hepatitis C virus agents

Densely functionalized tetrahydropyridines were stereoselectively synthesized from 1,6-dihydropyridines. Exploiting a carbonyl group installed at the C3 position of the 1,6-dihydropyridine system, we devised a strategy for cyanomethylation at C2/C6 and subsequent divergent installation of an allyl group at C3/C5 in a highly regio- and stereo-controlled manner. This versatile protocol for programmable functionalization of the 1,6-dihydropyridine system allows the divergent and streamlined synthesis of multiply-substituted tetrahydropyridines as an important class of biologically and medicinally relevant scaffolds. Two of the N-heterocyclic compounds bearing an alkyl nitrile group showed anti-hepatitis C virus (HCV) activity.     

Metal-mediated allylation of enzymatically oxidized methyl α-D-galactopyranoside

The C-6 unit of methyl α-d-galactopyranoside was selectively modified by combining enzymatic oxidation with an indium-mediated allylation reaction. The Barbier-Grignard type reaction, where a carbonyl group reacts with an allyl halide, proceeds in aqueous solution, even with water as the only solvent; thus carbohydrates can be modified without the need for drying or protection-deprotection steps. The corresponding homoallyl alcohols are produced in high yields of >90% in the reactions with allyl bromide and cinnamyl chloride. The main products were isolated and characterized by GC-MS and NMR spectroscopy.