High Cis-selectivity Research Articles

A synthetic alternative to the type-II intramolecular 4 + 3 cycloaddition reaction.

Oxyallyl cations generated in situ from dihaloketones have been found to undergo the Favorskii rearrangement in preference to an intramolecular Type-II 4 + 3 cycloaddition reaction in trifluoroethanol and hexafluoropropan-2-ol solvents, generating acrylate esters with high cis selectivity. A synthetic alternative to the intramolecular Type-II 4 + 3 cycloaddition has been developed on the basis of intramolecular enolate alkylation to close a 7-membered ring with an exocyclic double bond.

Room Temperature Ionic Liquids Promoted Three‐Component Coupling Reactions: A Facile Synthesis of cis‐Isoquinolonic Acids.

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Room temperature ionic liquids promoted three-component coupling reactions: a facile synthesis of cis-isoquinolonic acids

Room temperature ionic liquids are found to catalyze efficiently the three component-coupling reactions of aldehydes, amines and homophthalic anhydride under mild and convenient conditions to afford the corresponding cis-isoquinolonic acids in excellent yields with high cis-selectivity.

Highly Active Single-Site Catalysts for the 1,4-cis Polymerization of Butadiene from Allylneodymium(III) Chlorides and Trialkylaluminiums – A Contribution to the Activation of Tris(allyl)neodymium(III) and the Further Elucidation of the Structure-Activity Relationship

To further elucidate the structure-reactivity relationship in the allylneodymium complex-catalyzed 1,4-cis polymerization of butadiene, the following catalyst systems are investigated in toluene more thoroughly: Nd(C3H5)2Cl·1,4-dioxane, Nd(C3H5)Cl2·2.5 tetrahydrofuran (THF)/5–30 AlMe3 and preformed Nd(C3H4R)3 in combination with 2 Ph3CCl, 2 Ph3CCl/5 AlEt3; 2 AlMe2Cl, 2 AlMe2Cl/30 AlMe3; 2 AlEt2Cl and 2 AlEt2Cl/10 AlEt3. From the catalytic activity, cis selectivity, polydispersity, degree of polymerization as a function of conversion, as well as the comparison of theoretical and experimental chain length and kinetic analysis, essential conclusions can be drawn concerning the formation reaction and structure of the real catalyst complex and the course of the polymerization reaction. For the combinations of Nd(C3H4R)3 with 2 AlMe2Cl/30 AlMe3, 2AlEt2Cl and 2 AlEt2Cl/10AlEt3, the rate law rP = kP[Nd][BD]2 is derived with the values for kP of 3.4 (at 35°C), 2.0 and 1.5 L2/(mol2·s1) (at 50°C), respectively. In each case the formation of a η3-butenyl bis(η4-butadiene)neodymium(III) complex [Nd(η3-C3H4R)(η4-C4H6)2(ClAlR′2C3H4R)2] (R′ = Me, Et) is assumed. The insertion reaction proceeds according to the π-allyl insertion mechanism, and the high cis-selectivity in accordance with the anti-cis and syn-trans correlation is a consequence of the preferential η4-cis coordination of butadiene.

Cis-Selective Asymmetric Cyclopropanation of Olefins Catalyzed by Five-Coordinate [RuCl(PNNP)]+ Complexes

The five-coordinate complex [RuCl(1a)]PF6 (3a; 1a = (S)-N,N‘-bis[2-(diphenylphosphino)benzylidene]-2,2‘-diamino-6,6‘-dimethylbiphenylene) catalyzes the cyclopropanation of styrene by decomposition of diazoesters. The cis cyclopropane derivative is formed with moderate selectivity (cis:trans ratio is 48:52), but high enantioselectivity (90−96% ee). The related species [RuCl(1b)]PF6 (3b; 1b = N,N‘-bis[2-(diphenylphosphino)benzylidene]-(1S,2S)-diaminocyclohexane) gives the cis product with selectivity up to 95% and enantioselectivity up to >99% ee. High cis selectivity is obtained also with 2,5-dimethyl-2,4-hexadiene as substrate. Complex 3a yields ethyl chrysanthemate with 94% cis selectivity and enantioselectivity up to 80% ee. The putative carbene intermediate trans-[RuCl(C(H)COOEt)(1b)]+ (11b) was prepared and characterized spectroscopically in solution. Its reaction with styrene gives the cyclopropane derivative with 98:2 cis:trans selectivity. The steric constraints in the transition states involving 11b and styrene were estimated by means of molecular modeling calculations. The relative total energies of the four diastereomeric aggregates follow the experimental enantio- and diastereoselectivity trends. The model proposed also predicts the correct absolute configuration of both cis and trans cyclopropane products.

Efficient synthesis of piperidine derivatives. Development of metal triflate-catalyzed diastereoselective nucleophilic substitution reactions of 2-methoxy- and 2-acyloxypiperidines.

Nucleophilic substitution reactions of 2-methoxy- and 2-acyloxypiperidines were investigated. First, new and efficient methods for the preparation of the starting piperidine derivatives were developed. N-Benzyloxycarbonyl-2-methoxypiperidine (3) and 3-substituted-2-acyloxy-N-benzyloxycarbonylpiperidines (4a-d), which are recognized as the simplest imino-sugars, were prepared and were examined as substrates for nucleophilic substitution reactions with silyl enolates under the influence of catalytic amounts of metal triflates (Sc(OTf)3, Sn(OTf)2, Cu(OTf)2, Hf(OTf)4, etc). Among the triflates tested, Sc(OTf)3 gave the best results. It was found that 2-acetoxy-3-benzyloxy-N-benzyloxycarbonylpiperidine (4a) reacted with silyl enolates to afford the 2-alkylated adducts in high cis-selectivity, while 2,3-diacyloxy-N-benzyloxycarbonylpiperidines (4b-d) showed transselectivity. The stereochemical assignments were carefully performed using NMR analysis, X-ray crystallography, and synthetic transformations. Febrifugine (1), a potent antimalarial alkaloid, was successfully synthesized from 2,3-diacetoxy-N-benzyloxycarbonylpiperidine (4b) on the basis of these diastereoselective nucleophilic substitution reactions.

A new preparation of cis-N-sulfonylaziridines from N-sulfonylaldimines using trimethylsilyldiazomethane

Trimethylsilyldiazomethane smoothly reacts with N-sulfonylaldimines to give 2-substituted N-sulfonyl-3-trimethylsilylaziridines in good yields with high cis selectivity.

InCl 3 catalyzed reactions of ethyl diazoacetate with aldimines: a highly diastereoselective synthesis of cis-aziridine carboxylates

InCl 3 catalyzed reactions of ethyl diazoacetate with aldimines give aziridine carboxylates under mild conditions, low catalyst loading and with high cis-selectivity.

Bu(3)SnH-Mediated Pinacol Coupling of 1,5- and 1,6-Dicarbonyl Compounds: Synthetic and Mechanistic Studies.

A new method is described for the intramolecular pinacol coupling of 1,5- and 1,6-dicarbonyl compounds, employing Bu(3)SnH as the stoichiometric reductant. The key steps in this pinacol cyclization are the addition of a tin ketyl to a carbonyl group and a subsequent intramolecular S(H)2 reaction. The isolation of 1,3-dioxa-2-stannolanes, along with other product and labeling studies, provides strong support for the proposed homolytic substitution step, which distinguishes the pinacol cyclization from other reductive cyclizations of tin ketyls, all of which proceed through abstraction of hydrogen from Bu(3)SnH in the final step. An interesting consequence of the S(H)2 pathway is very high cis selectivity in the cyclization of 1,5-dicarbonyl compounds. Mechanistic studies furnish evidence that the steps that precede homolytic substitution, including C-C bond formation, are reversible under the reaction conditions.

Asymmetric Aziridination over Ylides: Highly Stereoselective Synthesis of Acetylenyl‐N‐sulfonylaziridines

Phase-transfer conditions can be used to synthesize (−)- or (+)-cis-acetylenyl-N-sulfonylaziridines (for example 3) by the reaction of N-sulfonylimines(1) with chiral sulfonium propargylides (2) derived from D-(+)-camphor. High cis selectivity and yields as well as moderate to good ee values are characteristic for these aziridinations.

Diastereoselective Iodocarbocyclization Reaction of 2- or 3-Oxy-4-pentenylmalonate Derivatives.

1,2- Or 1,3-asymmetric induction in the iodocarbocyclization reaction of 4-pentenylmalonate derivatives having a stereogenic center at an allylic or a homoallylic position has been investigated. The iodocarbocyclization reactions of 3-oxy-4-pentenylmalonate derivatives proceeded with high cis-selectivity through stereoelectronic control of the oxygenated substituent at an allylic position. In the reaction of (S)-2-siloxy-4-pentenylmalonate, an excellent diastereoselectivity was achieved through the utilization of double stereodifferentiation with a chiral titanium catalyst. Furthermore, as an application of the present reaction, the asymmetric syntheses of cyclosarkomycin and a synthetic intermediate of brefeldin A from optically pure 2- and 3-oxy-4-pentenylmalonate derivatives are also described.

Erythro-Selective aldol-type reaction of N-sulfonylaldimines with methyl isocyanoacetate catalyzed by gold(I)

Reaction of N-tosylaldimines 1 with methyl isocyanoacetate in the presence of 1 mol % of AuCl( c-HexNC) gave 4-methoxycarbonyl-5-alkyl-2-imidazolines 2 with high (over 89%) cis selectivity. The cis-imidazolinecarboxylates were isomerized into trans isomers by treatment with triethylamine. Hydrolysis of the cis- and trans- imidazolinecarboxylates gave erythro- and threo- α, β-diamino acids, respectively.

Highly Stereoselective Cationic Cyclization Assisted by a Sulfenyl Group. Scope, Limitation, and Mechanism.

When 8-acetoxy-2-methyl-9-(phenylthio)-2-nonene (1a) was treated with an acid, followed by a base, alkylative cyclization proceeded to give a mixture of 1,2-disubstituted cyclohexanes: 2a, 3a, and 4a. The stereochemistry of the reaction was only slightly affected by the leaving group and the reaction conditions, such as the temperature, solvent, and acid. However, the bulkiness of the sulfenyl group had a great effect on the stereochemical course of the reaction. High trans selectivity was attained when 1c (a derivative of 1a with a bulkier sulfenyl group) was used as a substrate. On the other hand, the length and rigidity of the carbon chain of the substrate also had a major effect on the stereochemistry of the reaction; a high cis selectivity was observed when 10a (a one-carbon-fewer analog of 1a) or 15a (a derivative with one more double bond in the carbon chain than in 1a) was used as the substrate. The reaction proceeded via a 6,5- or 5,5-fused-ring intermediate. The sulfenyl-group-assisted reaction could be a useful method for the stereoselective cyclization of acetates of alpha-sulfenylated secondary alcohols.

Organometallic complex catalysis in water II. Water soluble organoruthenium(IV) catalysts for the emulsion polymerization of norbornene

The bis(allyl)ruthenium complexes [Ru( η 3: η3-C 10H 16)(OH 2)(O 2CCH 3)] +BF 4 − ( 2) and [Ru( η 3: η 3-C 10H 16)(OH 2)(O 3SCF 3) 2] ( 3b) were obtained by reaction of the dimeric chloro-bridged bis(allyl)ruthenium complex [(Ru( η 3: η 3-C 10H 16)( μ-Cl)Cl) 2] with the corresponding silver or sodium salts and their structure was determined by NMR and IR spectroscopy. Compounds 2 and 3b are water soluble and prove to be very active single component catalysts for the emulsion polymerization of norbomene. The polymerization only takes place by ring opening of the monomer. The high cis selectivity of 85–90% is unusual for ruthenium-based catalysts for the ring-opening polymerization of strained cyclo-olefins. The polymers thus produced have very high molecular weights ( M n ≈ 1.5 × 10 6 g mol −1) with a monomodal distribution and with polydispersities ranging from 2.0 to 2.5.

ChemInform Abstract: Iron Lewis Acid Catalyzed Reactions of Phenyldiazomethane and Olefins: Formation of Cyclopropanes with Very High cis Selectivity.

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Iron Lewis acid catalyzed reactions of phenyldiazomethane and olefins: Formation of cyclopropanes with very high cis selectivity

The iron Lewis acid, [(η 5-C 5H 5)Fe(CO) 2(THF)] + ( 1) catalyzes the cyclopropanation reaction of phenyldiazomethane with olefins to provide cis cyclopropanes in high selectivity.

Heterocycle Formation through Aza-Annulation: Stereochemically Controlled Syntheses of (.+-.)-5-Epitashiromine and (.+-.)-Tashiromine

N-alkylenamines, stabilized through conjugation with an electron-withdrawing group, undergo aza-annulation with acryloyl chloride to provide a convergent route for the construction of six-membered nitrogen heterocycles. In addition to enhancing the C-alkylation process of annulation relative to the competing N-acylation process, the electron withdrawing substituent controlled the regioselectivity of alkene formation in both the intermediate enamine and in the unsaturated lactam product. A variety of functional groups, which include -COMe, -COPh, -CO 2 R, -CONHPh, -CN, -P(O) (OEt) 2 , and -SO 2 Ph, were used to determine the effect of the electron-withdrawing substituents upon both the annulation reaction with acryloyl chloride and the subsequent hydrogenation process. When the enamide annulation product was stabilized through conjugation with ester or amide substituents, catalytic hydrogenation of the aza-annulation product resulted in the formation of vicinal stereocenters with high cis selectivity. The utility of this methodology was demonstrated by application of the condensation/aza-annulation/hydrogenation sequence as the key for construction and stereochemical control of the indolizidine ring system of (±)-tashiromine

Stereoselective synthesis of 2-oxazoline-4-carboxylates through Lewis acid-catalyzed formal [3+2] cycloadditions of 5-alkoxyoxazoles with aldehydes: catalytic effect of methylaluminum .beta.-binaphthoxide on cis-selectivity

The formal [3+2] cycloadditions of 5-methoxy-2-(p-methoxyphenyl)oxazole with benzaldehyde, para- and meta-substituted benzaldehydes, propanal, cinnamaldehyde, and heterocyclic carboxaldehydes in the presence of methylaluminum β-binaphthoxide gave the corresponding methyl 5-alkyl-2-(p-methoxyphenyl)-2-oxazoline-4-carboxylates with high cis-selectivity (up to 98%). The use of ortho-substituted benzaldehydes resulted in a decrease in the cis-selectivity. The reaction of 5-methoxy-2-(p-methoxyphenyl)oxazole with benzaldehyde in the presence of titanium(IV) chloride or tin(IV) chloride gave the corresponding trans-2-oxazoline-4-carboxylate with 85-86% trans-selectivity. The reaction of ethyl glyoxylate with 5-ethoxy-2-phenyloxazole catalyzed by a 1:1 mixture of titanium (IV) chloride and titanium tetraisopropoxide gave diethyl 2-phenyl-2-oxazoline-4,5-dicarboxylate with a preference for cis-selectivity (cis/trans = 84:6).The cis-selectivite of the reaction in the presence of methylaluminum β-naphthoxide can be explained by an antiperiplanar approach of the C4-C5 double bond of the oxazole to the aldehyde coordinated to the catalyst, followed by ring opening of the oxazole through a stepwise pathway involving zwitterionic intermediates

A practical and efficient multigram approach to daunomycinone and derivatives

(+/-)-Daunomycinone and (+/-)-4-demethoxydaunomycinone have been synthesized via two successive Diels-Alder reactions from naphthazarin. Key steps for the construction of the A-ring of the anthracyclinone are the Diels-Alder reaction of the BCD fragments with 1- tert-butoxy-3-trimethylsilyloxybuta-1,3-diene and further functionalisation of the hydrolysed product with trimethylsilylethynyl lithium, these steps allow multigram synthesis of the anthracyclinone with a very high cis-selectivity for the 7,9-hydroxy groups of the A-ring.

Diastereoselective ring-opening aldol-type reaction of 2,2-dialkoxycyclopropanecarboxylic esters with carbonyl compounds. 1. Synthesis of cis 3,4-substituted .gamma.-lactones

The Lewis acid-promoted reactions of 2,2-dialkoxycyclopropanecarboxylic esters 4a-c with aldehydes and unsymmetrical ketones to give γ-lactones were investigated. TiBr 4 is an excellent catalyst and gives cis 3,4-substituted γ-lactones in good yields with high diastereoselectivity. SnBr 4 promotes the reaction of 4a-c with aldehydes with high cis-selectivity, but does not promote the reaction of 4a with unsymmetrical ketones. ZrCl 4 is moderately trans-selective in the reaction of 4a with unsymmetrical ketones. Cis γ-lactones can be converted into their trans-isomers by treatment with NaOEt in EtOH