[Back to Contents Page]

 

Letters in Organic Chemistry, Volume 1, No. 4, 2004

 

Contents

 

Organocatalysis Gathers Pace Pp. 292-296

(Highlights in organic chemistry)

Matthew L. Clarke

[Abstract]

 

Total Syntheses of Macrosphelides C, F, G and H Pp.297-307

Yuichi Kobayashi, Yong-Gang Wang, and Hukum P. Acharya

[Abstract]  

 

Toward the Synthesis of Reidispongiolide A: An Improved Stereocontrolled Synthesis of the C23-C35 Fragment of Reidispongiolide A Pp.308-312

Angela Zampella, Valentina Sepe, Rosa D’Orsi and Maria Valeria D'Auria

[Abstract]  

 

Stereoselective Synthesis of 3-Alkylated cis-1,2-Cyclobutanediols and Derivatives by Norrish-Yang Photocyclisation Pp.313-315

Axel G. Griesbeck, Peter Cygon and Johann Lex

[Abstract]  

 

Synthesis and Mitochondrial Complex I Activity of Annonaceous Trans and Cis Solamins Precursors Pp.316-322

Julie Defretin, Christophe Gleye, Diego Cortes, Xavier Franck, Reynald Hocquemiller and Bruno Figadere

[Abstract]  

 

A Direct Route to Erythrinanes via α-Amidoalkylation, Conjugate Addition and Ring-Closing Metathesis Reactions Pp.323-325

Inaki Osante, Nuria Sotomayor and Esther Lete

[Abstract]  

 

Rapid Syntheses of Nitroheterocycles that Bear a Diethyl Methylenemalonate Group β to a Nitro Group Pp.326-330

Maxime D. Crozet, Patricia Perfetti, Mustapha Kaafarani, Michel P. Crozet and Patrice Vanelle

[Abstract]  

 

Asymmetric Hydroxylation of (S,S)-(+)-Pseudoephedrine Phenylacetamide Enolates Pp.331-334

Efraim Reyes, Luisa Carrillo, Jose L. Vicario and Dolores Badia

[Abstract]  

 

Michael Addition of Nitroalkanes to Optically Active Acrylates Mediated by Cetyltrimethylammonium Hydroxide (CTAOH) Pp.335-339

Roberto Ballini, Dennis Fiorini, Alessandro Palmieri and Marino Petrini

[Abstract]  

 

Imino-Ketenimines on an Ortho-Benzylic Scaffold. Nitrogen to Carbon [1,3] Shift of an Ortho-Functionalized Benzyl Group Pp.340-342

Mateo Alajarin, Angel Vidal and Fulgencio Tovar

[Abstract]  

 

One-Pot Synthesis of 1-[(1-Phenyl-1-Dialkoxyphosphoryl)-Methyl]-2- Pyrrolidinone Pp.343-345

Petri A. Turhanen, Pasi Soininen and Jouko J. Vepsalainen

[Abstract]  

 

Reductive Coupling of Aldehydes with Nitriles Promoted by Titanium Tetraiodide Pp.346-348

Makoto Shimizu and Hiroshi Goto

[Abstract]  

 

3,4,6-Trisubstituted-2-Pyrone Synthesis via the Nucleophilic Addition of 2-Alkyl Meldrum’s Acid to Alkynyl Ketone Pp.349-352

Iwao Hachiya, Hitoshi Shibuya, Kazuma Hanai and Makoto Shimizu

[Abstract]  

 

Double Nucleophilic Addition of Ketene Silyl Acetals to α,β-Unsaturated Imines: Factors Controlling the Regioselectivity Pp.353-356

Makoto Shimizu, Hiroshi Kurokawa and Atsushi Takahashi

[Abstract]  

 

Titanocene(II)-Promoted Reaction of Thioacetals with Styrenes: Stereoselective Formation of (E)-β-Substituted Styrene Derivatives Pp.357-359

Akira Tsubouchi, Emi Nishio, Koutaro Arai and Takeshi Takeda

[Abstract]  

 

Niobium (V) Chloride Mediated Preparation of β-Chloro-α,β-Unsaturated Ketones Pp.360-364

Mauricio Gomes Constantino, Valdemar Lacerda Junior, Luiz Carlos da Silva Filho and

Gil Valdo Jose da Silva

[Abstract]  

 

Tandem Intramolecular Carbolithiation-Lithium/Zinc Transmetallation: A Synthetically Versatile Combination Pp.365-368

M. Yus and R. Ortiz

[Abstract]  

 

Behaviour of Thiophenes Substituted with Electron-Withdrawing Groups in Cycloaddition Reactions Pp.369-371

Claudia Della Rosa, Elisa Paredes, Marķa Kneeteman and Pedro M.E. Mancini

[Abstract]  

 

Evaluation of Sulfonamides in the Protection of Phenylisoserine for the Semisynthesis of Taxol® Pp.372-375

Peter G.M. Wuts, Rui L. Gu and Jill M. Northuis

[Abstract]  

 

The Role of the exo-Anomeric Effect in the Stereoselective Oxidation of 1-Thioglycosides: A Contribution in the α-D-Glucopyranoside Series Using Xray Crystallography Pp.376-380

Maria Chiara Aversa, Anna Barattucci, Paola Bonaccorsi, Giuseppe Bruno,Placido Giannetto and Patrick Rollin

[Abstract]  

 

Human Low-Density Lipoprotein Oxidation: Hypochlorous Acid Leads to the Generation of Lysophosphatidylcholines Under Acidic Conditions Pp.381-390

Olaf Zschornig, Christian Bergmeier, Rosmarie Suß, Klaus Arnold, and Jurgen Schiller

[Abstract]  

 

Abstracts

 

[Back to top] Organocatalysis Gathers Pace

(Highlights in organic chemistry)

Matthew L. Clarke

 

Organocatalysis is one of the most vibrant research areas in synthetic chemistry at present. In this short review, some of the impressive recent advances in organocatalysis are discussed. Papers published in 2004 describing the use of (i) enamine type activation of aldehydes and ketones, and (ii) catalysis that proceeds by the formation of hydrogen bonds are highlighted.

 

[Back to top] Total Syntheses of Macrosphelides C, F, G and H

Yuichi Kobayashi, Yong-Gang Wang, and Hukum P. Acharya

 

The title macrosphelides were synthesized by using two-step conversion of furans into γ-oxo-α,β-unsaturated carboxylic acids as a key step. In the case of macrosphelide H, AcCH2 group at C(3) was constructed from CH2=CHCH2 by Wacker oxidation under modified conditions.

 

[Back to top] Toward the Synthesis of Reidispongiolide A: An Improved Stereocontrolled Synthesis of the C23-C35 Fragment of Reidispongiolide A

Angela Zampella, Valentina Sepe, Rosa D’Orsi and Maria Valeria D'Auria

 

An improved synthesis of the C23-C35 moiety of reidispongiolide A has been completed. An intermolecular Nozaki-Hiyama-Kishi coupling was employed for the union of C23-C30 and C31-C35 fragments. A discussion on the factors influencing the stereochemical outcome of (E)-crotylboration reactions of α-methyl-β-alkoxy aldehydes is also presented.

 

[Back to top] Stereoselective Synthesis of 3-Alkylated cis-1,2-Cyclobutanediols and Derivatives by Norrish-Yang Photocyclisation

Axel G. Griesbeck, Peter Cygon and Johann Lex

 

The photocyclisation of enantiomerically pure a-heteroatom-substituted b-methyl butyrophenones 1 results in Norrish II cleavage and in Norrish II / Yang cyclisation products, cyclobutanols 2, the latter being formed with excellent diastereoselectivities and with relative yields which were strongly depending on the Hbonding activity of the a-substituent.

 

[Back to top] Synthesis and Mitochondrial Complex I Activity of Annonaceous Trans and Cis Solamins Precursors

Julie Defretin, Christophe Gleye, Diego Cortes, Xavier Franck, Reynald Hocquemiller and Bruno Figadere

 

The efficient synthesis of the common C1-C32 precursor of trans and cis solamins has been achieved with the longest linear sequence of 7 steps from pentadecalactone. The key transformations rely on the iron (III) catalysed Grignard coupling reaction with a vinyl bromide, and the Sharpless asymmetric dihydroxylation. Mitochondrial complex I activity of these annonaceous synthetic precursors highlighted the crucial influence of the terminal butenolide, as well as the tetrahydrofuanic pattern.

 

[Back to top] A Direct Route to Erythrinanes via α-Amidoalkylation, Conjugate Addition and Ring-Closing Metathesis Reactions

Inaki Osante, Nuria Sotomayor and Esther Lete

 

A direct route to erythrinanes has been completed by a sequence that involves diastereoselective conjugate addition on a α,β−unsaturated lactam, followed by a ring-closing metathesis reaction to construct ring A. The synthesis of the key intermediates C-10b functionalized dihydropyrroloisoquinolines is achieved via Parham cyclisation and α-amidoalkylation reactions.

 

[Back to top] Rapid Syntheses of Nitroheterocycles that Bear a Diethyl Methylenemalonate Group β to a Nitro Group

Maxime D. Crozet, Patricia Perfetti, Mustapha Kaafarani, Michel P. Crozet and Patrice Vanelle

 

Rapid syntheses of nitroheterocycles that bear a diethyl methylenemalonate group β to a nitro group starting from easily available nitroheterocyclic sulfones and involving, a one-pot substitution-elimination with either diethyl bromomalonate or an original direct olefination with diethyl ketomalonate, gave moderate yields in nitroimidazole series. An SRN1 reaction followed by a base-mediated nitrous acid elimination gave fairly good yields in nitrothiazole series. Because of the accessibility of the reagents, these syntheses are interesting alternatives to Knoevenagel reaction.

 

[Back to top] Asymmetric Hydroxylation of (S,S)-(+)-Pseudoephedrine Phenylacetamide Enolates

Efraim Reyes, Luisa Carrillo, Jose L. Vicario and Dolores Badia

 

Enantioenriched α-hydroxy acids and esters have been synthesized by oxidation of (S,S)-(+)-pseudoephedrine arylacetamide enolates with different reagents. We have found that the oxidation of these enolates proceeds with good yields and diastereoselectivities and, interestingly, we have also noticed that the use of different oxidation reagents allows the selective preparation of any of the two possible epimers of the target α-hydroxy amides. We have also optimized a mild procedure for the removal of the chiral auxiliary and therefore for the obtention of enantioenriched α-hydroxy acids, which were also easily converted into the corresponding α-hydroxy esters. The developed methodology becomes a promising field of research due to the potentiality of the reaction, which a priori should allow the stereodivergent synthesis of a wide variety of α-hydroxy carbonyl compounds.

 

[Back to top] Michael Addition of Nitroalkanes to Optically Active Acrylates Mediated by Cetyltrimethylammonium Hydroxide (CTAOH)

Roberto Ballini, Dennis Fiorini, Alessandro Palmieri and Marino Petrini

 

Nitroalkanes react with chiral acrylates in the presence of a catalytic amount (10% mol) of CTAOH in small amount of water as solvent. Although only modest levels of diastereoselectivity can be observed in this process, the obtained Michael adducts can be easily transformed into interesting building blocks as γ-amino acids and cyclic hydroxycarbamates.

 

[Back to top] Imino-Ketenimines on an Ortho-Benzylic Scaffold. Nitrogen to Carbon [1,3] Shift of an Ortho-Functionalized Benzyl Group

Mateo Alajarin, Angel Vidal and Fulgencio Tovar

 

Thermolysis of C,C-disubstituted N-(2-benzylideneamino)benzyl ketenimines in solution provided 2,2-disubstituted 3-(2-benzylideneamino)phenylpropionitriles by [1,3] migration of the substituted benzyl group from nitrogen to carbon in the ketenimine fragment.

 

[Back to top] One-Pot Synthesis of 1-[(1-Phenyl-1-Dialkoxyphosphoryl)-Methyl]-2- Pyrrolidinone

Petri A. Turhanen, Pasi Soininen and Jouko J. Vepsalainen

 

A novel one-pot method to 1-[(1-phenyl-1-dialkoxyphosphoryl)-methyl]-2-pyrrolidinones (1a-c), where R=Me, Et, n-Hex, from the benzaldehyde (2), 4-aminobutyric acid (3) and dialkyl phosphite (4a-c) has been developed with reasonable 61-80% yields. Preparation of 4-{[(dimethoxyphosphoryl)-phenyl-methyl]-amino}-butyric acid (5) with high 85% yield is also described. Unexpected large 5JHP coupling constants 3.35, 3.37 and 3.15 Hz for compounds 1a-c, respectively, were observed.

 

[Back to top] Reductive Coupling of Aldehydes with Nitriles Promoted by Titanium Tetraiodide

Makoto Shimizu and Hiroshi Goto

 

Titanium tetraiodide promoted reductive coupling reaction of aldehydes with nitriles gave a-hydroxy imines in good yields.

 

[Back to top] 3,4,6-Trisubstituted-2-Pyrone Synthesis via the Nucleophilic Addition of 2-Alkyl Meldrum’s Acid to Alkynyl Ketone

Iwao Hachiya, Hitoshi Shibuya, Kazuma Hanai and Makoto Shimizu

 

3,4,6-Trisubstituted-2-pyrone synthesis via the nucleophilic addition of 2-alkyl Meldrum’s acid to alkynyl ketone has been developed. The reaction of 2-alkyl Meldrum’s acid with alkynyl ketones provided 3,4,6-trisubstituted-2-pyrones in good yields. The reaction of dialkynyl ketones gave 6-alkynyl-2-pyrones.

 

[Back to top] Double Nucleophilic Addition of Ketene Silyl Acetals to a,b-Unsaturated Imines: Factors Controlling the Regioselectivity

Makoto Shimizu, Hiroshi Kurokawa and Atsushi Takahashi

 

The regioselectivity of the double nucleophilic addition of ketene silyl acetals to α,β-unsaturated imines was highly depended on the subtle difference of the reactivity of the ketene silyl acetals, and the factors were mainly derived from the ability of the ketene silyl acetals to undergo the silicon-aluminum exchange reaction, where the aluminum enolate preferentially underwent 1,4-addition.

 

[Back to top] Titanocene(II)-Promoted Reaction of Thioacetals with Styrenes: Stereoselective Formation of (E)-β-Substituted Styrene Derivatives

Akira Tsubouchi, Emi Nishio, Koutaro Arai and Takeshi Takeda

 

(E)-β-Substituted styrenes were obtained stereoselectively by the titanocene(II)-promoted desulfurizative coupling of thioacetals with styrenes. It is suggested that the reaction proceeds through the regioselective formation of a titanacyclobutane intermediate, followed by β-elimination.

 

[Back to top] Niobium (V) Chloride Mediated Preparation of β-Chloro-α,β-Unsaturated Ketones

Mauricio Gomes Constantino, Valdemar Lacerda Junior, Luiz Carlos da Silva Filho and

Gil Valdo Jose da Silva

 

β-Chloro-α,β-unsaturated ketones or β-ethoxy-α,β-unsaturated ketones, depending on the solvent used, are conveniently prepared in one step and in good yields by treating cycloenones 1 - 10 with niobium pentachloride.

 

[Back to top] Tandem Intramolecular Carbolithiation-Lithium/Zinc Transmetallation: A Synthetically Versatile Combination

M. Yus and R. Ortiz

 

The carbolithiation of 1-lithiohex-5-ene (2) gives cyclopentylmethyllithium (3), which after treatment with zinc dibromide yields a solution of the corresponding organozinc reagent (5). The palladium(II)-catalysed acylation of this compound with several acyl chlorides yields the expected ketones (6). By a copper(I)-promoted reaction of compound (5) with different allylic or propargylic chlorides or bromides, a very clean SN2’ reaction takes place giving the expected olefins (7) or allenes (8), respectively. The palladium(II)-catalysed arylation of intermediate (5) with different aryl bromides or iodides affords the corresponding substituted arenes (9). Finally, the copper(I)-promoted conjugate addition of compound (5) to some α,β-unsaturated ketones gives the expected ketones (10), without any contamination of the corresponding 1,2-adducts.

 

[Back to top] Behaviour of Thiophenes Substituted with Electron-Withdrawing Groups in Cycloaddition Reactions

Claudia Della Rosa, Elisa Paredes, Marķa Kneeteman and Pedro M.E. Mancini

 

Substituted thiophenes can act as dienophiles in normal electron demand Diels-Alder reactions, nitro being one of the substituents. Cycloaddition with Danishefsky’s diene provides the benzothiophene derivatives with nitro side selectivity, α-substituted substrates being the more dienophilic. The reaction with isoprene leads mainly to the corresponding (pyrrol-1-yl)thiophenes.

 

[Back to top] Evaluation of Sulfonamides in the Protection of Phenylisoserine for the Semisynthesis of Taxol®

Peter G.M. Wuts, Rui L. Gu and Jill M. Northuis

 

The 4-nitrophenylsulfonyl, the benzothiazolsulfonyl and the anthracenesulfonyl protecting groups were evaluated in the protection of the phenylisoserine side chain, as part of a semisynthesis of paclitaxel. The mechanism for the cleavage of the anthracenesulfonyl group using thiols was also examined, and found to proceed by an addition elimination pathway, which is in contrast to the reported reductive mechanism. The use of the siamyldimethylsilyl group for protection of baccatin III is discussed and compared with the triethylsilyl group.

 

[Back to top] The Role of the exo-Anomeric Effect in the Stereoselective Oxidation of 1-Thioglycosides: A Contribution in the a-D-Glucopyranoside Series Using Xray Crystallography

Maria Chiara Aversa, Anna Barattucci, Paola Bonaccorsi, Giuseppe Bruno,Placido Giannetto and Patrick Rollin

 

X-Ray crystallographic analysis of an enantiopure 1-thio-a-D-glucopyranoside S-oxide clearly supports the role of the exo-anomeric effect in determining the highly stereoselective oxidation of a- thioglycosides to (RS) sulfoxides. Ab-initio and DFT calculations point out the relevance of the anomeric effect, due to the presence of sulfur at position 1, in determining some structural characteristics of aldohexosyl sulfoxides.

 

[Back to top] Human Low-Density Lipoprotein Oxidation: Hypochlorous Acid Leads to the Generation of Lysophosphatidylcholines Under Acidic Conditions

Olaf Zschornig, Christian Bergmeier, Rosmarie Suß, Klaus Arnold, and Jurgen Schiller

 

The oxidative modification of the lipid moiety of low-density lipoproteins (LDL) by reactive oxygen species (ROS) is assumed to play an important role in the pathogenesis of atherosclerosis. In this study MALDI-TOF MS and 31P NMR spectroscopy were used in order to investigate the effects of HOCl and hydroxyl radicals on LDL. Incubations of LDL with HOCl were performed at different pH values and acidic conditions favored the yield of oxidation products.

 

An increased content of lysophosphatidylcholine (LPC) as a stable reaction product was only detected when HOCl was used, whereas HO radicals led to the disappearance of all peaks in the mass spectrum. Therefore, it is concluded that the content of LPC in LDL preparations can be used as an important diagnostic criterion of HOCl-induced LDL modifications. Accordingly, phospholipases are no prerequisite of LPC generation.