High Stereoselectivity (high + stereoselectivity)

Distribution by Scientific Domains
Distribution within Chemistry

Selected Abstracts

Mechanistic insights into oxidosqualene cyclizations through homology modeling

Gasch, Tanja Schulz
Abstract 2,3-Oxidosqualene cyclases (OSC) are key enzymes in sterol biosynthesis. They catalyze the stereoselective cyclization and skeletal rearrangement of (3S)-2,3-oxidosqualene to lanosterol in mammals and fungi and to cycloartenol in algae and higher plants. Sequence information and proposed mechanism of 2,3-oxidosqualene cyclases are closely related to those of squalene-hopene cyclases (SHC), which represent functional analogs of OSCs in bacteria. SHCs catalyze the cationic cyclization cascade converting the linear triterpene squalene to fused ring compounds called hopanoids. High stereoselectivity and precision of the skeletal rearrangements has aroused the interest of researchers for nearly half a century, and valuable data on studying mechanistic details in the complex enzyme-catalyzed cyclization cascade has been collected. Today, interest in cyclases is still unbroken, because OSCs became targets for the development of antifungal and hypocholesterolemic drugs. However, due to the large size and membrane-bound nature of OSCs, three-dimensional structural information is still not available, thus preventing a complete understanding of the atomic details of the catalytic mechanism. In this work, we discuss results gained from homology modeling of human OSC based on structural information of SHC from Alicyclobacillus acidocaldarius and propose a structural model of human OSC. The model is in accordance with previously performed experimental studies with mechanism-based suicide inhibitors and mutagenesis experiments with altered activity and product specificity. Structural insight should strongly stimulate structure-based design of antifungal or cholesterol-lowering drugs. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 741,753, 2003 [source]

Highly Efficient and Practical Pyrrolidine,Camphor-Derived Organocatalysts for the Direct ,-Amination of Aldehydes

Pang-Min Liu
Abstract A series of pyrrolidine,camphor-derived organocatalysts (1,4) were designed and synthesised. These organocatalysts were used for direct ,-amination of aldehydes with dialkyl azodicarboxylates to give the desired ,-aminated products in high chemical yields (up to 92,%) and with high to excellent levels of stereoselectivity (up to >99,% ee). The reactions proceeded rapidly (within 5 min) with low catalyst loading (5 mol-%) at ambient temperature. Enantioselective aminations of asymmetric ,,,-disubstituted aldehydes in the catalytic system were studied, with reasonable to high stereoselectivities (up to 75,% ee) being obtained. The utility of this methodology was demonstrated with the synthesis of derivatives of ,-amino-,-butyrolactone and a tetrasubstitutedcyclohexane-derived amino alcohol with high stereoselectivities. Transition models were proposed for the asymmetric ,-amination reactions; they involve hydrogen-bond interactions between the nucleophilic enamine formed in situ and the nitrogen source. [source]

Hydrophobically Directed Aldol Reactions: Polystyrene-Supported L -Proline as a Recyclable Catalyst for Direct Asymmetric Aldol Reactions in the Presence of Water,

Michelangelo Gruttadauria
Abstract A simple synthetic methodology for the preparation of a polystyrene-supported L -proline material is reported, and this material has been used as catalyst in direct asymmetric aldol reactions between several ketones and arylaldehydes to furnish aldol products in high yields and stereoselectivities. Screening of solvents showed that these reactions take place only in the presence of water or methanol, at lower levels of conversion in the latter case. This solvent effect, coupled with the observed high stereoselectivities, has been explained in terms of the formation of a hydrophobic core in the inner surface of the resin, whereas the hydrophilic proline moiety lies at the resin/water interface. Such a microenvironment both promotes the aldol reaction and increases the stereoselectivity. Recycling investigations have shown that this material can be reused, without loss in levels of conversion and stereoselectivity, for at least five cycles. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source]

Asymmetric Synthesis of 2,3,4-Trisubstituted Functionalised Tetrahydrofurans via an Organocatalytic Michael Addition as Key Step

Dieter Enders
Abstract The organocatalytic Michael addition of various aldehydes to (2E,4E)-ethyl 5-nitropenta-2,4-dienoate has been achieved under the catalysis of diphenylprolinol trimethylsilyl ether furnishing the products in good to excellent yields (61,94%) and high stereoselectivities (dr up to >98:2, ee=97 to >99%). Starting from these Michael adducts, 2,3,4-trisubstituted functionalized tetrahydrofurans are available in two steps by reduction of the aldehyde followed by an intramolecular oxa-Michael addition in good yields (54,76%) and stereoselectivities (dr up to >95:5, ee=97 to >99%). [source]

Highly Efficient and Stereoselective Julia,Kocienski Protocol for the Synthesis of ,-Fluoro-,,,-unsaturated Esters and Weinreb Amides Employing 3,5-Bis(trifluoromethyl)phenyl (BTFP) Sulfones

Abstract ,-Fluoroacetates 3 and Weinreb amide 4, bearing a ,-[3,5-bis(trifluoromethyl)phenyl]sulfonyl (BTFP-sulfonyl) group at the ,-position, are employed in the highly stereoselective synthesis of ,-fluoro-,,,-unsaturated alkenoates and Weinreb amides, respectively. Aromatic and aliphatic aldehydes are condensed under extremely mild and simple reaction conditions using potassium carbonate in dimethylformamide at room temperature under solid-liquid phase-transfer catalysis conditions in good yields and high Z -diastereoselectivities, specially in the case of the fluorinated Weinreb amides. A detailed computational mechanistic study suggests a final non-concerted elimination of sulfur dioxide and 3,5-bis(trifluoromethyl)phenoxide and explains the observed high stereoselectivities for the reaction on the basis of thermodynamic and kinetic considerations. [source]

Tripeptides of the Type H- D -Pro-Pro-Xaa-NH2 as Catalysts for Asymmetric 1,4-Addition Reactions: Structural Requirements for High Catalytic Efficiency

Markus Wiesner Dr.
Abstract Analysis of the structural and functional requirements within the asymmetric peptidic catalyst H- D -Pro-Pro-Asp-NH2 led to the development of the closely related peptide H- D -Pro-Pro-Glu-NH2 as an even more efficient catalyst for asymmetric conjugate addition reactions of aldehydes to nitroolefins. In the presence of as little as 1,mol,% of H- D -Pro-Pro-Glu-NH2, a broad range of aldehydes and nitroolefins react readily with each other. The resulting ,-nitroaldehydes were obtained in excellent yields and stereoselectivities at room temperature. Within the structure of the peptidic catalysts, the D -Pro-Pro motif is the major contributor to the high stereoselectivities. The C-terminal amide and the spacer to the carboxylic acid in the side-chain of the C-terminal amino acid are responsible for the fine-tuning of the stereoselectivity. The peptidic catalysts not only allow for highly effective asymmetric catalysis under mild conditions, but also function in the absence of additives. Die sorgfältige Analyse der strukturellen und funktionalen Erfordernisse des peptidischen Katalysators H- D -Pro-Pro-Asp-NH2 führte zur Entwicklung des verwandten Peptids H- D -Pro-Pro-Glu-NH2, das einen noch effizienteren Katalysator für asymmetrische konjugierte Additionsreaktionen von Aldehyden an Nitroolefine darstellt. In Gegenwart von nur 1,mol,% von H- D -Pro-Pro-Glu-NH2 reagiert eine große Auswahl verschiedenster Aldehyde und Nitroolefine unter milden Bedingungen bereitwillig miteinander. Die entstehenden ,-Nitroaldehyde bilden sich in exzellenten Ausbeuten und Stereoselektivitäten bei Raumtemperatur. Innerhalb der Struktur des peptidischen Katalysators trägt das D -Pro-Pro Motiv am meisten zu den hohen Stereoselektivitäten bei. Das C-terminale Amid und der Linker vom Peptidrückgrat zur Carbonsäure in der Seitenkette der C-terminalen Aminosäure sind für die Feineinstellung der Stereoselektivitäten verantwortlich. Die peptidischen Katalysatoren sind nicht nur höchst effiziente asymmetrische Katalysatoren sondern benötigen im Gegensatz zu vielen anderen chiralen Katalysatoren auch keine Additive für ihre katalytische Effizienz. [source]

Organocatalytic Enantioselective Synthesis of Highly Functionalized Polysubstituted Pyrrolidines

Nerea Ruiz
Abstract The organocatalytic conjugate addition of different aldehydes to ,-nitroacrolein dimethyl acetal, generating the corresponding highly functionalized nitroaldehydes in high yields and with high stereoselectivities, has been studied in detail. These transformations have been achieved by using both readily available starting materials in a 1:1 ratio as well as commercially available catalysts at a 10,mol,% catalyst loading. Furthermore, a very short and efficient protocol has been devised for the preparation of highly enantioenriched pyrrolidines containing two or three contiguous stereocenters starting from the obtained Michael adducts. 3,4-Disubstituted pyrrolidines have been obtained in a single step by Zn-mediated chemoselective reduction of the nitro group followed by intramolecular reductive amination, and trisubstituted homoproline derivatives have been prepared by means of an olefination reaction and a cascade process involving chemoselective reduction of the nitro group followed by a fully diastereoselective intramolecular aza- Michael reaction. Se ha estudiado detalladamente la reacción de adición conjugada organocatalítica enantioselectiva de distintos aldehídos con el dimetil acetal de ,-nitroacroleina, obteniéndose los aductos correspondientes con excelente rendimiento y diastereo- y enantioselectividad. Esta transformación se lleva a cabo empleando cantidades equimolares de aldehído y nitroalqueno así como aminas secundarias quirales disponibles comercialmente como catalizadores en cantidad de 10,% molar. Además, se ha puesto a punto un protocolo sencillo y eficaz para la síntesis de pirrolidinas enantioenriquecidas conteniendo dos o tres estereocentros contíguos partiendo de los aductos Michael obtenidos. Así, se han preparado pirrolidinas 3,4-disustituidas desde sus precursores nitroaldehídicos a través de un proceso en cascada consistente en la reducción quemoselectiva del grupo nitro seguido de una reacción de aminación reductora intramolecular. Del mismo modo, partiendo de los mismos precursores, se han preparado derivados de homoprolina con tres centros estereogénicos mediante una reacción de Wittig seguida de un proceso en cascada de reducción/reacción aza-Michael intramolecular, cursando esta última con total diastereoselectividad. [source]

Stereodivergent Syntheses of Highly Substituted Enantiopure 4-Alkoxy-3,6-dihydro-2H -1,2-oxazines by Addition of Lithiated Alkoxyallenes to Carbohydrate-Derived Aldonitrones

Matthias Helms
Abstract Additions of lithiated alkoxyallenes to D -glyceraldehyde-based nitrones 1 and 2 did not provide the expected hydroxylamine derivatives. Instead, a novel [3+3] cyclization process furnished 4-alkoxy-3,6-dihydro-2H -1,2-oxazines 9,14 with excellent syn selectivities and in moderate to good yields. Through precomplexation of the nitrones the corresponding anti -configured 1,2-oxazines 9, 10 and 13 could be obtained with high stereoselectivity. The reactions of nitrones 3,6, derived from D -erythrose or D -threose, generally proceeded less diastereoselectively, but reasonable yields of anti -configured 1,2-oxazines such as anti - 17 and anti - 19 could be obtained under Lewis acid promotion conditions. This was also the case for reactions of the D -arabinose-derived nitrone 7, which provided the anti -1,2-oxazines 23 and 24 with excellent diastereoselectivity and in good yields. Bis-nitrone 8 and lithiated methoxyallene furnished a mixture of six compounds, among which the major componentwas the C2 -symmetric syn/syn -1,2-oxazine 29. The diastereoselectivities of these reactions are interpreted on the basis of Dondoni's model for reactions between organolithium compounds and nitrones. The mechanisms for formation of 1,2-oxazines and of side products are discussed. The method introduced here seems to be of broad applicability and an excellent tool for diastereoselective chain elongation of carbohydrate derivatives, affording stereodefined precursors of aminopolyols and other highly functionalized compounds. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source]

Asymmetric Synthesis of Isoquinoline Derivatives from Amino Acids

Oxana Sieck
Abstract Reaction of isoquinolines 1 with N -arylsulfonylamino acid fluorides 2 provides a highly stereoselective access to new dihydroimidazo[2,1 -a]isoquinolin-3-ones 5 via intermediate N -acylisoquinolinium salts 3. Addition reactions to the en-amine double bond, such as hydrogenation or epoxidation with dimethyldioxirane, leads to tetrahydroimidazo[2,1 -a]isoquinoline-3-ones 6, 7 and oxiranes 8, respectively. Opening of the oxirane ring of the 8 with nucleophiles allows the synthesis of hydroxytetrahydroimidazo[2,1 -a]isoquinolin-3-ones 10 or 12 or of the polycyclic 1,4-dioxane 13 in high stereoselectivity. The regioselectivity of the oxiran ring opening depends on the kind of nucleophile and the conditions. Reaction of dihydroisoquinoline with O -TBDMS-mandelic acid chloride 15 leads to a tetrahydrooxazolo[2,3 -a]isoquinoline 17 with opposite facial selectivity as compared with dihydroimidazo[2,1 -a]isoquinolin-3-ones 5. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source]

C-Glycosidations of a 2-Ketohexosyl Bromide with Electrophilic, Radical, and Nucleophilic Anomeric Carbons

Frieder W. Lichtenthaler
Abstract The susceptibility of acylated 2-ketohexosyl halides to C-homologation is demonstrated with the easily accessible tri- O -benzoyl-,- D - arabino -hexos-ulosyl bromide 1 as the model compound. C-Glycosidation with an electrophilic anomeric carbon requires prior carbonyl protection, to avoid carbonyl addition by the C-nucleophile, for example, as the cyanohydrin. Silver triflate-promoted reaction with the silylenol ether of acetophenone then efficiently yields the ,-phenacyl product. With thermal (AIBN) or photochemical induction, 1 smoothly generates an anomeric radical , comparatively electrophilic, due to its capto-dative substitution , which exclusively traps hydrogen in the presence of tributyltin and electron-deficient alkenes. With allyltributylstannanes, however, it reacts with high stereoselectivity to afford ,- C -allyl glycosiduloses. The ,-bromoketone functionality in ulosyl bromide 1 is susceptible to Reformatsky conditions: treatment with zinc-copper couple readily generates the 1,2-enolate, a most simple anomeric nucleophile, which effectively adds to aldehydes to give ,- C -hydroxyalkyl glycosiduloses or ,- C -disaccharides (with sugar aldehydes) with a high degree of double stereoselection. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source]

Highly Stereoselective Halocyclopropanation of ,,,-Unsaturated Amides


Abstract A convenient highly stereoselective synthesis of chloro- and bromocyclopropanamides from di- tri- or tetrasubstituted (E)- or (Z)-,,, - unsaturated amides with total or high stereoselectivity promoted by chromium dichloride or dibromide is described. The transformation of chlorocyclopropanamides into the corresponding ketones or amines is also reported. A mechanism to explain these transformations is proposed. [source]

Ruthenium-Indenylidene Complexes: Scope in Cross-Metathesis Transformations

Fabien Boeda
Abstract A comparative study examining the catalytic activity of a series of five indenylidene-containing ruthenium complexes in olefin cross-metathesis reactions is presented. Results reveal the greater efficiency of precatalyst 5, highlighting the key role of the N,N, -bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) ligand for this transformation. The scope of this precatalyst was investigated and several microwave experiments were carried out allowing for catalyst loadings as low as 0.1 mol%. Overall, cross-metathesis products were isolated in moderate to excellent yields with high stereoselectivity. [source]

A highly efficient synthesis of (Z)-1-aryl-2-silyl-1- stannylethenes and their conversion to (E)-2- arylethenyl-, (Z)-2-(2-pyridyl)ethenyl- and allenyl-silanes

Takanori Endo
Abstract A Pd(dba)2,P(OEt)3 combination allowed the silastannation of arylacetylenes, 1-hexyne or propargyl alcohols with tributyl(trimethylsilyl)stannane to take place at room temperature, producing (Z)-2-silyl-1-stannyl-1-substituted ethenes in high yields. Novel silyl(stannyl)ethenes were fully characterized by 1H-, 13C-, 29Si- and 119Sn-NMR as well as infrared and mass analyses. Treatment of a series of (Z)-1-aryl-2-silyl-1-stannylethenes and (Z)-1-(3-pyridyl)-2-silyl-1-stannylethene with hydrochloric acid or hydroiodic acid in the presence of tetraethylammonium chloride (TEACl) or tetrabutylammonium iodide (TBAI) led to the exclusive formation of (E)-trimethyl(2-arylethenyl)silanes with high stereoselectivity. A similar reaction of (Z)-1-(2-anisyl)-2-silyl-1-stannylethene also produced E -type trimethyl[2-(2-anisyl)ethenyl]silane, while (Z)-trimethyl [2-(2-pyridyl)ethenyl]silane was produced exclusively from (Z)-1-(2-pyridyl)-2-silyl-1-stannylethene. Protodestannylation of (Z)-1-[hydroxy(phenyl)methyl]-2-silyl-1-stannylethene with trifluoroacetic acid took place via the ,-elimination of hydroxystannane, providing trimethyl(3-phenylpropa-1,2-dienyl)silane quite easily. The destannylation products were also fully characterized. Copyright © 2007 John Wiley & Sons, Ltd. [source]

A Three-Component Reaction Based on a Remote-Group-Directed Dynamic Kinetic Aza-Michael Addition: Stereoselective Synthesis of Imidazolidin-4-ones

Zhenghu Xu Dr.
In control: An ,-amino amide reacted with an aldehyde and a Michael acceptor to form stable imidazolidin-4-ones with high stereoselectivity. A dynamic kinetic aza-Michael addition was discovered and applied to the three-component reaction to enforce high stereoselectivity. A remote group was incorporated to invert the reaction process and direct the reaction towards the desired product (see scheme). [source]

A Gold(I)-Catalyzed Intramolecular Reaction of Propargylic/Homopropargylic Alcohols with Oxirane

Lun-Zhi Dai
Abstract The gold(I)-catalyzed cycloisomerization of epoxy alkynes in the presence of a nucleophile is an efficient protocol to provide ketal skeletons with high stereoselectivity. An intramolecular reaction of propargylic/homopropargylic alcohols with oxirane to produce ketal/spiroketals in moderate yields under mild conditions has been reported. Moreover, the mechanism of this kind of reaction has been discussed on the basis of a series of control and 18O tracer experiments. [source]

Highly Efficient Synthesis of Stereodefined Multisubstituted 1,4-Dicyano- and 1-Cyano-1,3-butadienes and Their Reactions with Organolithium Reagents

Congyang Wang Dr.
Abstract Stereodefined multisubstituted 1-cyano- and 1,4-dicyano-1,3-butadiene derivatives were obtained in excellent yields of the isolated product from their corresponding monohalo- and dihalobutadienes and CuCN. This reaction proceeded with high stereoselectivity and retention of the stereochemistry of the starting halobutadienes. A study of the utility of the thus-obtained 1-cyano- and 1,4-dicyano-1,3-butadiene derivatives was demonstrated by their reactions with organolithium reagents. 2H -Pyrrole or iminocyclopentadiene derivatives were formed in high yields from 1-cyano-4-halo-1,3-butadienes and organolithium reagents. When 1,4-dicyano-1,3-butadienes were treated with organolithium reagents followed by trapping with electrophiles, a tandem process took place to afford 2H -pyrrolyl nitriles in excellent yields. Reduction of 1,4-dicyano-1,3-butadiene derivatives with LiAlH4 showed novel reaction patterns relative to normal nitriles. [source]

Intramolecular Reactions in Pseudo-Geminally Substituted [2.2]Paracyclophanes,

Lidija Bondarenko Dr.
Abstract A selection of pseudo-geminally substituted [2.2]paracyclophanes, the alkynes 6, 7, 10, 11,a, and 11,b and the alkenes 8 and 9 were prepared for the study of intraannular reactions between functional groups in direct juxtaposition. Whereas 9 and 10 provide the corresponding cyclobutane and cyclobutene derivatives on irradiation (12 and 13, respectively), the bis-alkynes 7 and 11,b do not lead to a cyclobutadiene intermediate. In the latter case the "half-closed" butadiene derivative 17 was isolated. A Paterno,Büchi reaction took place on irradiation of 8 and 6, although the oxetene intermediate 21 produced in the second example did not survive the reaction conditions (ring-opening to 22). Bromine addition to 9, 10, and 7 occurred with high stereoselectivity (formation of the dibromides 27, 30, and 33, respectively), and is rationalized by postulating the formation of the cationic intermediates 26, 29, and 32, respectively. To study the interaction of a carbocation with a facing triple bond, the alcohol 34 was prepared from 6. On acid treatment ring closure to the triply-bridged phane 38 took place, accompanied by the hydration of the triple bond to the ketoalcohol 37. In an interesting intraannular [2+3]cycloaddition reaction the bis-acetylene 11,a, on treatment with n -butyl lithium, provided the cyclopentadiene derivative 42. That the two triple bonds of a pseudo-geminal diacetylene can engage in a cyclization reaction leading to the cyclopentadienone complex 44 was also shown by treating 11,b with iron pentacarbonyl. [source]

Regio- and Stereoselective Palladium-Pincer Complex Catalyzed Allylation of Sulfonylimines with Trifluoro(allyl)borates and Allylstannanes: A Combined Experimental and Theoretical Study

Olov A. Wallner Dr.
Abstract Regio- and stereoselective palladium-pincer complex catalyzed allylation of sulfonylimines has been performed by using substituted trifluoro(allyl)borates and trimethylallylstannanes. The reactions provide the corresponding branched allylic products with excellent regioselectivity. The stereoselectivity of these processes is very high when trifluoro(cinnamyl)borate and trimethyl cinnamyl stannane are employed as allylic precursors; however, the reaction with trifluoro(crotyl)borate results in poor stereoselectivity. The major diastereomer formed in these reactions was the syn isomer, while the (previously reported) reactions with aldehyde electrophiles afforded the anti products, indicating that the mechanism of the stereoselection is dependent on the applied electrophile. Therefore, we have studied the mechanistic aspects of the allylation reactions by experimental studies and DFT modeling. The experimental mechanistic studies have clearly shown that potassium trifluoro(allyl)borate undergoes transmetallation with palladium-pincer complex 1,a affording an ,1 -allylpalladium-pincer complex (1,e). The mechanism of the transfer of the allyl moiety from palladium to the sulfonylimine substrate was studied by DFT calculations at the B3PW91/LANL2DZ+P level of theory. These calculations have shown that the electrophilic substitution of sulfonylimines proceeds in a one-step process with a relatively low activation energy. The topology of the potential energy surface in the vicinity of the transition-state structure proved to be rather complicated as nine different geometries with similar energies were located as first order saddle points. Our studies have also shown that the high stereoselectivity with cinnamyl metal reagents stems from steric interactions in the TS structure of the allylation reaction. In addition, these studies have revealed that the mechanism of the stereoselection in the allylation of aldehydes and sulfonylimines is fundamentally different. [source]

Palladium-Catalyzed Desulfitative Mizoroki,Heck Couplings of Sulfonyl Chlorides with Mono- and Disubstituted Olefins: Rhodium-Catalyzed Desulfitative Heck-Type Reactions under Phosphine- and Base-Free Conditions

Srinivas Reddy Dubbaka
Abstract New conditions have been found for the desulfitative Mizoroki,Heck arylation and trifluoromethylation of mono- and disubustituted olefins with arenesulfonyl and trifluoromethanesulfonyl chlorides. Thus (E)-1,2-disubstituted alkenes with high stereoselectivity and 1,1,2-disubstituted alkenes with 12:1 to 21:1 E/Z steroselectivity can be obtained. Herrmann's palladacycle at 0.1 mol,% is sufficient to catalyze these reactions, for which electron-rich or electron-poor sulfonyl chlorides and alkenes are suitable. If phosphine- and base-free conditions are required, 1 mol,% [RhCl(C2H4)2] catalyzes the desulfitative cross-coupling reactions. Contrary to results reported for [RuCl2(PPh3)2]-catalyzed coupling reactions with sulfonyl chlorides, the palladium and rhodium desulfitative Mizoroki,Heck coupling reactions are not inhibited by radical scavenging agents. Possible sulfones arising from the sulfonylation of alkenes at 60,°C are not desulfitated at higher temperatures in the presence of the Pd or Rh catalysts. De nouvelles conditions sont rapporteés pour les couplages désulfitants du type Mizoroki,Heck des chlorures d'arènesulfonyles et trifluorométhanesulfonyle avec des oléfines mono- et disubstitueés. La méthode permet la synthèse de (E)-alcènes 1,2-disubstitués avec haute stéréosélectivité et d'alkènes 1,1,2-trisubstitués avec des stéréosélectivités E/Z variant de 12:1 à 21:1. La palladacycle de Herrmann à 0.1 mol% est suffisant pour catalyser ces reactions qui peuvent engager des chlorures de sulfonyles et des alcènes soit riches ou pauvres en électron. Si des conditions sans phosphine et sans base sont requises, 1 mol,% de [RhCl(C2H4)2] est un excellent catalyseur pour ces couplages désulfitants. Contrairement à ce qui est rapporté pour des réactions analogues catalysées par [RuCl2(PPh3)2] et qui impliquent des intermédiaires radicalaires, les couplages du type Mizoroki,Heck désulfitants catalysés par des complexes de palladium ou de rhodium ne sont pas inhibés par des pièges à radicaux. De plus, les sulfones qui peuvent se former par sulfonylation des alcènes (60,oC) ne sont pas désulfitées à plus haute température en présence des catalyseurs au Pd ou au Rh. [source]

Vinyl Sulfoxides as Stereochemical Controllers in Intermolecular Pauson,Khand Reactions: Applications to the Enantioselective Synthesis of Natural Cyclopentanoids

Marta Rodríguez Rivero
Abstract The use of sulfoxides as chiral auxiliaries in asymmetric intermolecular Pauson,Khand reactions is described. After screening a wide variety of substituents on the sulfur atom in ,,,-unsaturated sulfoxides, the readily available o -(N,N -dimethylamino)phenyl vinyl sulfoxide (1,i) has proved to be highly reactive with substituted terminal alkynes under N -oxide-promoted conditions (CH3CN, 0,°C). In addition, these Pauson,Khand reactions occurred with complete regioselectivity and very high diastereoselectivity (de=86,>96,%, (S,RS) diastereomer). Experimental studies suggest that the high reactivity exhibited by the vinyl sulfoxide 1,i relies on the ability of the amine group to act as a soft ligand on the alkyne dicobalt complex prior to the generation of the cobaltacycle intermediate. On the other hand, both theoretical and experimental studies show that the high stereoselectivity of the process is due to the easy thermodynamic epimerization at the C5 center in the resulting 5-sulfinyl-2-cyclopentenone adducts. When it is taken into account that the known asymmetric intermolecular Pauson,Khand reactions are limited to the use of highly reactive bicyclic alkenes, mainly norbornene and norbornadiene, this novel procedure constitutes the first asymmetric version with unstrained acyclic alkenes. As a demonstration of the synthetic interest of this sulfoxide-based methodology in the enantioselective preparation of stereochemically complex cyclopentanoids, we have developed very short and efficient syntheses of the antibiotic (,)-pentenomycin I and the (,)-aminocyclopentitol moiety of a hopane triterpenoid. Se ha estudiado la utilización de sulfóxidos como auxiliares quirales en reacciones de Pauson,Khand intermoleculares. Tras considerar una amplia variedad de vinil sulfóxidos diferentemente sustituidos en el átomo de azufre, se ha encontrado que el o -(N,N -dimetilamino)fenil sulfóxido (1,i) presenta una elevada reactividad frente a alquinos terminales en reacciones de Pauson,Khand. Además, estas reacciones transcurren con regioselectividades completas y diastereoselectividades muy elevadas (ed=86,>96,%). Estudios teóricos y experimentales sugieren que la gran reactividad mostrada por el vinil sulfóxido 1,i se debe a la capacidad del grupo amino para coordinarse al complejo de dicobalto del alquino, favoreciendo así la posterior formación del cobaltaciclo intermedio. Por otro lado, estudios tanto teóricos como experimentales han demostrado que la elevada diastereoselectividad del proceso es consecuencia de la fácil epimerización termodinámica en la posición C-5 de las 5-sulfinil-2-ciclopentenonas finales. Teniendo en cuenta que hasta el momento la reacción de Pauson,Khand intermolecular estaba limitada al empleo de alquenos bicíclicos muy reactivos, principalmente norborneno y norbornadieno, este nuevo procedimiento constituye la primera versión asimétrica con alquenos acíclicos no tensionados. Como demostración de la utilidad sintética de esta nueva metodología en la preparación enantioselectiva de sistemas ciclopentánicos complejos, se han desarrollado síntesis muy eficaces del antibiótico (,)-pentenomicina I y de la unidad de aminociclopentitol de un triperpenoide. [source]

Simple Approach to the Highly Stereoselective Synthesis of trans -1,2-Cyclopropane Derivatives

Hui Zhang
Abstract In the presence of KF·2H2O, furoylmethyltriphenylarsonium bromide (1a) or thienoylmethyltriphenylarsonium bromide (1b) reacted with 2-[(un)substituted benzylidene]malononitrile (2) in chloroform at room temperature to give trans -3,3-dicyano-1-furoyl-2-[(un)substituted phenyl]cyclopropane (3a) or trans -3,3-dicyano-1-thienoyl-2-[(un)substituted phenyl]cyclopropane (3b) respectively in good yield with high stereoselectivity. The structures of product 3 were confirmed by IR, MS, 1H NMR, 1H- 1H COSY and microanalysis. The relative configuration of product 3 was determined by 1H- 1H NOESY technique. The mechanism for the formation of product 3 was also proposed. [source]

Diels-Alder Reactions of N -Functionalized Acryloyl , -Pyrrolidone Derivatives Using FeCl3·6H2O as an Efficient Catalyst under Solvent-free Conditions

Wen Pei
Abstract Diels-Alder reactions of N -functionalized acryloyl , -pyrrolidone derivatives were investigated, which were catalyzed by FeCl3·6H2O as an efficient catalyst under solvent-free conditions at room temperature. The corresponding cycloadducts with functionalized-pyrrolidone were prepared in high yield with high stereoselectivity by a green chemistry procedure. N -Functionalized acryloyl pyrrolidone derivatives, a kind of pyrrolidone-functionalized chelating ,,, -unsaturated ketone usable as a dienophile in Diels-Alder reaction, were synthesized by N -acylation procedure in ionic liquid as a novel synthetic method. [source]

Highly Stereoselective Synthesis of Phenylseleno- and p -Tolylsulfonyl Substituted 1,3-Dienes from Functionalized Allyl Alcohols

Mei-Hua Xie
Abstract Phenylseleno- and p -tolylsulfonyl substituted 1,3-dienes were conveniently prepared with high stereoselectivity by the elimination reaction of phenylseleno- and p -tolylsulfonyl substituted allyl alcohols in the presence of BF3 · Et2O in acetic anhydride. The products were characterized by 1H NMR, MS, IR and elemental analysis. The single crystal structure of 2a was determined by X-ray diffraction analysis. [source]