Showing papers on "Annulation published in 1997"

Antibody-Catalyzed Enantioselective Robinson Annulation

Abstract: The Skaggs Institute for Chemical Biologyand the Department of Molecular BiologyThe Scripps Research Institute10550 North Torrey Pines Road, La Jolla, California 92037Laboratory for Bioorganic ChemistryThe Sloan-Kettering Institute for Cancer Research1275 York AVenue, New York, New York 10021ReceiVed March 25, 1997We report an antibody that is remarkable in that it catalyzesboth steps of an important synthetic transformation, the Rob-inson annulation. The Robinson annulation which accomplishes,in net terms, the conversion of a f c occupies a key role inorganic synthesis.

Enantioselective Synthesis of Functionalized Tropanes by Rhodium(II) Carboxylate-Catalyzed Decomposition of Vinyldiazomethanes in the Presence of Pyrroles

Abstract: A series of enantiomerically enriched tropanes was synthesized by the rhodium(II) octanoate-catalyzed reaction of various N-BOC-protected pyrroles with vinyldiazomethanes. The overall 3 + 4 annulation occurs by a tandem cyclopropanation/Cope rearrangement. Asymmetric induction was best achieved in these transformations by using either (S)-lactate or (R)-pantolactone as a chiral auxiliary on the vinyldiazomethanes. Reactions carried out with the chiral catalyst tetrakis[N-(4-tert-butylbenzenesulfonyl)-(L)-prolinato]dirhodium (2) provided moderate asymmetric induction, but also resulted in the formation of isomeric azabicyclooctane side products. The utility of the synthetic process was demonstrated through the asymmetric synthesis of (−)-anhydroecgonine methyl ester and (−)-ferruginine.

Utilization of the Intramolecular Cycloaddition-Cationic pi-Cyclization of an Isomünchnone Derivative for the Synthesis of (+/-)-Lycopodine

Abstract: A new annulation sequence leading to the tetracyclic skeleton of the Lycopodium family of alkaloids is effected by using the tandem cycloaddition-cationic pi-cyclization reaction of an isomunchnone dipole as the key strategic element. Synthesis of the required alpha-diazo imide precursor involved treating 5-methylcyclohex-2-en-1-one with the organocopper reagent derived from 3-methoxybenzyl chloride in the presence of chlorotrimethylsilane. Ozonolysis of the resulting silyl enol ether followed by a Wittig reaction and conversion to the desired alpha-diazo imide was carried out using standard malonylacylation and diazotization procedures. Treatment of the alpha-diazo imide with rhodium(II) perfluorobutyrate afforded a transient 1,3-dipole which subsequently cycloadded across the tethered pi-bond. The resulting cycloadduct was treated with BF(3).2AcOH to give a rearranged tetracyclic compound derived from a Pictet-Spengler-type cyclization of an N-acyliminium ion. The rearranged product was subsequently converted into a key intermediate previously used for the synthesis of (+/-)-lycopodine.

Formation of Dihydropyridone- and Pyridone-Based Peptide Analogs through Aza-Annulation of β-Enamino Ester and Amide Substrates with α-Amido Acrylate Derivatives

Abstract: The aza-annulation of β-enamino ester and amide substrates with the mixed anhydride of 2-acetamidoacrylic acid was used for the efficient construction of highly substituted α-acetamido δ-lactam products. With the α-acetamido substituent, lactam functionality, and γ-carboxylate group, these δ-lactam products represent an interesting class of conformationally restricted dipeptide analogs. The framework of this lactam hub is structurally related to that of an α-amino acid coupled with a β-amino acid. When α-amino esters derived from naturally occurring amino acids were used in the enamine formation step, subsequent aza-annulation led to branched peptide surrogates with two C-termini that extended from a common N-terminus. Oxidation of the aza-annulation products resulted in the generation of a planar system with peptide functionality radiating from the 1, 3, and 5 positions of the pyridone hub. Alternatively, pyridone products could be formed directly from the enamino amides by reaction with 2-phenyl-4-(etho...

Synthesis of 2,5-Disubstituted Furans via Palladium-Catalyzed Annulation of Alkyl 3-Oxo-6-heptynoates

Abstract: The reaction of the readily available alkyl 3-oxo-6-heptynoates with aryl halides in the presence of K2CO3 and catalytic amounts of Pd(PPh3)4 at 100 °C provides a valuable new route to 2,5-disubstituted furans 3. Most probably, the furan ring is generated through an annulation reaction promoted by σ-arylpalladium complexes generated in situ and involving the nucleophilic attack of the ketonic oxygen across the carbon−carbon triple bond coordinated to palladium, followed by the base-catalyzed isomerization of the resultant stereoisomeric 2,5-dialkylidenetetrahydrofuran intermediates 4 and 5. The reaction is highly chemoselective. No evidence was obtained of carboannulation products. The reaction temperature has proven to be crucial for the success of the methodology. The K2CO3:alkyne ratio also affects the reaction outcome. The highest yields of furan derivatives have been obtained with aryl halides containing electron-withdrawing substituents, very likely because the higher acidity of the methylene proton...

alpha-(Arylthio)imidoyl Radicals: [3 + 2] Radical Annulation of Aryl Isothiocyanates with 2-Cyano-Substituted Aryl Radicals.

Abstract: A novel cascade radical reaction is described involving aryl isothiocyanates and 2-cyanoaryl radicals. The mechanism entails the formation of an α-(arylthio)imidoyl radical, a 5-exo-dig cyclization onto a cyano group, and a final 6-membered ring closure of an iminyl radical. The competitive 5-membered spiro-cyclization of the iminyl, leading to an isomeric product, was only observed in the case of a disubstituted aryl isothiocyanate. The whole process involves a rare example of [3 + 2] radical annulation and allows the one-pot synthesis of tetracondensed nitrogen heterocycles in good yields.

Structure‐Activity Relations for Imidazo‐pyridine‐Type Inhibitors of β‐D‐Glucosidases

Abstract: The triazole 7 and the known gluco- and manno-configurated imidazoles 10 and 11 have been prepared by annulation of the azole ring to the aldonothiolactam 14 in a Hg(OAc)2-promoted reaction with either hydrazine-carbaldehyde or aminoacetaldehyde dimethyl acetal. Depending upon the reaction conditions, the synthesis of the imidazoles yielded mostly the gluco-imidazole 19 or a mixture of the gluco/manno epimers 19/20. In contrast to the triazole 4, the isomeric triazole 7 proved a good inhibitor of retaining β-glucosidases from sweet almonds and from Caldocellum saccharolyticum. This observation and the qualitative correlation between basicity and inhibitory power of the tetrahydropyridoazoles provide further evidence for the hypothesis of the ‘lateral protonation’ of glycosides by (some) retaining β-glucosidases.

Benzotriazole-Assisted Aromatic Ring Annulation: Efficient and General Syntheses of Polysubstituted Naphthalenes and Phenanthrenes.

Abstract: (Benzotriazol-1-ylmethyl)benzenes and -naphthalenes 1a−f, easily accessible from benzyl bromides and benzotriazole, readily undergo lithiation and subsequent 1,4-addition to α,β-unsaturated aldehyd...

Stereocontrolled Synthesis of Cyclic Ethers by Intramolecular Hetero-Michael Addition. 6. A Computational Study of the Annelation to 2,3-Disubstituted Tetrahydropyrans

Abstract: A computational study at the ab initio level of the cyclization of (E)- and (Z)-7-hydroxy-4-substituted-2,3-unsaturated esters leading to 2,3-disubstituted tetrahydropyrans has been performed. The study showed the requirement of coordination between the pre-tetrahydropyranyl oxygen and that of the carbonyl of the α,β-unsaturated ester with the cation of the base used to obtain a suitable transition state model. The calculations using the 6-31G*//3-21G basis set show different relative stabilities for the final products and transition states leading to them. The 6-31+G* basis set was used as a calibration of the less energetic transition states. A model assuming a pre-chair conformation locating the chiral inductor equatorial and approaching the α,β-unsaturated ester in axial mode for the E isomer and equatorial for the Z geometry rationalizes the experimental results. The scope and limitations of the model applied to 2,3,5,6-functionalized cases are discussed.

[3 + 2] Annulation of Allylidenetriphenylphosphorane with 1,2-Diacylethylenes and 1,2-Diacylacetylenes: A One-Step Synthesis of Tri- and Tetrasubstituted Cyclopentadienes and Fulvenes

Abstract: Allylidenetriphenylphosphoranes underwent [3 + 2] annulation with 1,2-diacylethylenes at room temperature to give cyclopentadienes 11−17 having various substituents except for (Z)-3-acetylacrolein (18) which gave cyclohexadiene 19 derived from [3 + 3] annulation as the sole annulation product. The resulting cyclopentadienes were mixtures of the corresponding double-bond isomers which arose through an equilibrium process from the initially formed 1,3-dienes a under the weakly basic reaction conditions. Similar reactions of the phosphoranes with 1,2-diacylacetylenes afforded substituted fulvenes 24, 25, and 28 directly without the attendant formation of the corresponding benzene derivatives which come from another possible [3 + 3] annulation. The observed high level of the preference for the [3 + 2] annulation is discussed on the basis of the semiempirical PM3 MO calculations. The calculations suggested that the course of the annulation may be kinetically controlled at the oxaphosphetane-forming step of the...

Solid-Supported Heterocumulenes: Preparation and Crystal Structure of Azaaplysinopsins

Abstract: Annulation of carbodiimides 6a,b, on alumina solid support, selectively gives (Z)-hydantoins 8a,b determined on the basis of X-ray analysis while thermal cyclization affords, after purification, 8a,b with imidazolones 10a,b. In the imidazopyrimidine series, thermal reaction of heterocumulenes 6d yields, via a Dimroth rearrangement, the dipyridoimidazolic compound 11. In all cases, mechanisms for the observed cyclizations have been proposed.

2-Aminobuta-1,3-dienes as annulation reagents for 4-quinolones and benzothiopyran-4-ones: an attractive route for the highly diastereoselective synthesis of acridine- and thioxanthene-derivatives

Abstract: Enamines regioselectively add to the CN+-bond of 4-silyloxyquinolinium triflates with high yields, and the BF3·Et2O mediated annulations of 4-quinolones with 2-aminobuta-1,3-dienes proceed with high diastereoselectivity to give substituted 1,2,3,4,4a,9,9a,10-octahydroacridine-3,9-dione derivatives; 4-silyloxy-1-benzothiopyrylium triflates and benzothiopyran-4-ones behave analogously.