bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycosylidene Carbenes. Part 19. Regioselective glycosidation of allyl 2‐deoxy‐2‐phthalimido‐D‐allopyranosides
Authors: Briner Karin , Bernet Bruno , Maloisel Jean‐Luc , Vasella Andrea
Published: December 2004

The regio‐ and stereoselectivity of the glycosidation of the partially protected mono‐alcohols 3 and 7, the diols 2 and 8, and the triol 4 by the diazirine 1 have been investigated. Glycosidation of the α‐D‐diol 2 (Scheme 2) gave regioselectively the 1,3‐linked disaccharides 11 and 12 (80%, α‐D/β‐D 9:1), whereas the analogous reaction with the βD‐anomer 8 led to a mixture of the anomeric 1,3‐ and 1,4‐linked disaccharides 13 (12.5%), 14 (16%), 15 (13%), and 16 (20.5%; Table 2). Protonation of the carbene by OH–C(4) of 2 is evidenced by the observation that the α‐D‐mono‐alcohol 3 did not react with 1 under otherwise identical conditions, and that the β‐D‐alcohol 7 yielded predominantly the β‐D‐glucoside 18 (52%) besides 14% of 17. Similarly as for the glycosidation of the diol 2, the influence of the H‐bond of HOC(4) on the direction of approach of the carbene, the role of HOC(4) in protonating the carbene, and the stereoelectronic control in the interception of the ensuring oxycarbenium cation are evidenced by the reaction of the triol 4 with 1 (Scheme 3), leading mostly to the α‐D‐configurated 1,3‐linked disaccharide 19 (41%), besides its anomer 20 (16%), and some 4‐substituted β‐D‐glucoside 21 (9%). No 1,6‐linked disaccharides could be detected. In agreement with the observed reactivity, the 1H‐NMR and IR spectra reveal a strong H‐bond between HOC(3) and the phthalimido group in the α‐D‐, but not in the β‐D‐allosides. The different H‐bonds in the anomeric phthalimides are in keeping with the results of molecular‐mechanics calculations.
Preparation and Transmetallation of a Triphenylstannyl β‐D‐Glucopyranoside: A highly stereoselective route to β‐D‐C‐glycosides via glycosyl dianions
Authors: Frey Oliver , Hoffmann Matthias , Wittmann Valentin , Kessler Horst , Uhlmann Peter , Vasella Andrea
Published: December 2004

The triphenylstannyl β‐D‐glucopyranoside 4 was synthesized in one step from the 1,2‐anhydro‐α‐D‐glucopyranose 3 with (triphenylstannyl)lithium (Scheme 1). Transmetallation of 4 with excess BuLi, followed by quenching the dianion 7 with CD3OD gave (1S)‐1,5‐anhydro‐3,4,6‐tri‐O‐benzyl‐[1‐2H]‐D‐ glucitol (8) in 81% yield (Scheme 2). Trapping of 7 with benzaldehyde, isobutyraldehyde, or acroleine gave the expected β‐D‐configurated products 11, 12, and 13 in good yields. Preparation of C‐acyl glycosides from acid chlorides, such as acetyl or benzoyl chloride was not practicable, but addition of benzonitrile to 7 yielded 84% of the benzoylated product 14. Treatment of 7 with MeI led to 15 (30%) along with 40% of 18, C‐alkylation being accompanied by halogen‐metal exchange. Prior addition of lithium 2‐thienylcyanocuprate increased the yield of 15 to 50% and using dimethyl sulfate instead of MeI led to 77% of 15. No α‐D‐anomers could be detected, except with allyl bromide as the electrophile, which yielded in a 1:1 mixture of the anomers 16 and 17.
Quantum Chemical Investigation of the Structure and Reactivity of Indole Derivatives of Tricarbonylchromium(0)
Authors: Furet Eric , Savary François , Weber Jacques , Kündig Ernst Peter
Published: December 2004

In a theoretical investigation of the structure and reactivity of indole derivatives of tricarbonylchromium(0), we have used two different semi‐empirical quantum chemical models derived from the extended Hückel molecular‐orbital (EHMO) formalism. The first one, based on the atom‐superposition and electron‐delocalization (ASED) method, is used to optimize the geometry of the systems; it is shown to lead to results in satisfactory agreement with experiment in the case of the complex for which X‐ray structural data are available, the average errors being 0.03–0.05 Å for bond distances and 5° for bond angles. The second one consists of a local reactivity index, made of the intermolecular interaction energy between the organometallic substrate and a model reactant. It is seen that this procedure is able to reproduce the experimental trends as to the most reactive regions of the systems investigated towards nucleophilic and electrophilic addition reactions.
Synthesis of Aristotelia‐Type Alkaloids. Part XIII. Total syntheses of (+)‐makonine, (+)‐aristotelinone, and (+)‐11,12‐didehydroaristoteline
Authors: Stahl Reto , Galli Renato , Güller Rolf , Borschberg Hans‐Jürg
Published: December 2004

The oxidative transformation of synthetic (+)‐aristoteline ((+)‐6) into other metabolites which had been isolated from Aristotelia species was investigated. Thus, treatment of (+)‐6 with I2 as the single oxidant furnished the naturally occurring indole alkaloids (+)‐makonine ((+)‐9),(+)‐aristotelinone ((+)‐11), or (+)‐11, 12‐didehydroaristoteline ((+)‐7) in good yields, the selectivity of the oxidation process depending on the chosen reaction conditions.
A Practical Synthesis of (2S, 3R)‐3‐Amino‐2‐methylpentanoic Acid from L‐Aspartic Acid
Authors: Jefford Charles W. , McNulty James
Published: December 2004

L‐Aspartic acid by successive N‐tosylation, anhydride formation, and reduction was converted into (3S)‐3‐(tosylamino)butano‐4‐lactone (4). Electrophilic methylation of 4, subsequent iodo‐esterification and nucleophilic methylation, followed by saponification and deprotection, gave (2S, 3R)‐3‐amino‐2‐methylpentanoic acid (2) with an ee of > 99% in seven steps and in an overall yield of 34%.
Insertion Reactions of [ReH(CO)5–n(PMe3)n] Complexes (n = 2–4) with aldehydes, CO2, and activated acetylenes
Authors: Nietlispach Daniel , Veghini Dario , Berke Heinz
Published: December 2004

The complexes of the type [ReH(CO)5–n(PMe3)n] (n = 4, 3) were reacted with aldehydes, CO2, and RCCCOOMe (R = H, Me) to establish a phosphine‐substitutional effect on the reactivity of the Re–H bond. In the series 1–3, benzaldehyde showed conversion with only 3 to afford a (benzyloxy)carbonyltetrakis(trimethylphosphine)rhenium complex 4. Pyridine‐2‐carbaldehyde allowed reaction with all hydrides 1–3. With 1 and 2, the same dicarbonyl[(pyridin‐2‐yl)methoxy‐O, N]bis(trimethylphosphine)rhenium 5b was formed with the intermediacy of a [(pyridin‐2‐yl)methoxy‐O]‐ligated species and extrusion of CO or PMe3, respectively. The analogous conversion of 3 afforded the carbonyl[(pyridin‐2‐yl)methoxy‐O,N]tris(trimethylphosphine)rhenium (1) 7b. While 1 did not react with CO2, 2 and 3 yielded under relatively mild conditions the formato‐ligated [Re(HCO2)(CO)(L)(PMe3)3] species (8 (L = CO) and 9 (L = PMe3)). Methyl propiolate and methyl butynoate were transformed, in the presence of 1, to [Re{C(CO2Me)CHR}(CO)3(PMe3)2] systems (10a (R = H), and 10b(R = Me)), with prevailing α‐metallation and trans‐insertion stereochemistry. Similarly, HC≡CCO2Me afforded with 2 and 3, the α‐metallation products [Re{C(CO2Me)CH2}(CO)(L)(PMe3)3] 11 (L = CO) and 12(L = PMe3). The methyl butyonate insertion into 2 resulted in formation of a mixture of the (Z)‐ and (E)‐isomers of [Re{C(CO2Me)CHMe} (CO)2(PMe3)3] (13a,b). In the case of the conversion of 3 with MeCCCO2Me, a Re–H cis‐addition product [Re{(E)‐C(CO2Me)CHMe}(CO)(PMe3)4] (14) was selectively obtained. Complex 11 was characterized by an X‐ray crystal‐structure analysis.
Chemische Reaktionen mit Fischer‐Carben‐Komplexen des 1,6‐Methano[10]annulens
Authors: Neidlein Richard , Gürtler Stephan , Krieger Claus
Published: December 2004

Reactions of Fischer Carbene Complexes of 1,6‐Methano[10]annulene

The new Fischer carbene complexes 7, 8, and 10 of 1,6‐methano[10]annulene as well as the bis(carbene) complex 15, were readily available in moderate yields by using the classical Fischer method (Schemes 1 and 2). The complexes 5 and 7 reacted easily with several alkynes under benzo‐annulation conditions (Dötz reaction). Depending on the workup conditions, the new benzoquinones 16 and 17 (Scheme 5), hydroquinones 19 and 20 (Scheme 6), and protected hydroquinones 23–25 (Schemes 6 and 7) were synthesized. Surprisingly, in one run we were able to isolate the air‐stable [Cr(η6‐arene)(CO)3] complex 26 (Scheme 7). The X‐ray structure and NMR data of 26 established a remarkable perturbation of the 10π perimeter of the 1,6‐methano[10]annulene part in the hydroquinones 19–26, but no evidence of a σ‐homoaromatic “bis(trinorcaradiene)” system. The first double Dötz reaction of 15 with hex‐3‐yne resulted in the formation of the “anti”‐dibenzo‐annulated 1,6‐methano[10]annulene 32 (Scheme 8), which does not exist furthermore as a π‐homoaromatic system, but as its σ‐homoaromatic valence isomer.
Diazoaldehyde Chemistry. Part 1. Transdiazotization of Acylacetaldehydes in Neutral‐to‐Acidic Medium. A Direct Approach to the Synthesis of α‐Diazo‐β‐oxoaldehydes
Authors: Sezer Özkan , Anaç Olcay
Published: December 2004

First ever non‐deformylating transdiazotization of acylacetaldehydes was achieved: the reactions of 2‐azido‐l‐ethylpyridinium tetrafluoroborate (4) with acylacetaldehydes3proceeded partially without deformylation to yield 16 new α‐diazo‐β‐oxoaldehydes1along with diazomethyl ketones2, especially in the presence of NaOAc (Scheme 1, Tables 1and2). The product distribution was substituent‐dependent and could be correlated quantitatively. This new diazotization reaction appears as an alternative, direct, and more general method for the synthesis of these diazooxoaldehydes. α‐Oxocycloalkanecarbaldehydes5gave only traces (if any) of α‐diazocycloalkanones7, and rearrangement products6were isolated (Scheme 2). Mechanisms of the reactions are discussed (Schemes 4and5).
Glycosylidene Carbenes. Part 20. Synthesis of deprotected, spiro‐linked C‐glycosides of C60
Authors: Uhlmann Peter , Harth Eva , Naughton Andrew B. , Vasella Andrea
Published: December 2004

Mannosylidenation of buckminsterfullerene (C60; 1) with the 2,3‐di‐O‐benzyl‐4,6‐O‐benzylidene‐protected diazirine 7 and the 2,3:4,6‐di‐O‐isopropylidene‐protected diazirine 8 leads to the spiro‐linked C ‐glycosides 6 and 10 in 44 and 31% yield, respectively (Scheme). The diazirine 8 was prepared in five steps from 2,3:4,6‐di‐O‐iso‐propylidene‐α‐D‐mannopyranose (11) via the oximes 12, the (Z)‐hydroximolactone 13, the mesylate 14, and the diaziridines 15. Deprotection of the mannosylidenated fullerenes 6 and 10 under acidic conditions gave the partially deprotected diol 9 (97%) and the unprotected mannosylidenated fullerene 16 (73%), respectively. The mannosylidene‐fullerenes 6, 9, 10, and 16 possess a 6–6 ring‐bridged σ‐homoaromatic structure.
Conformational Features of 7,8,13β,14α‐Tetrahydro‐N7‐methylcorysaminium, a biosynthetic intermediate to the protopine‐type alkaloid corycavine
Authors: Kamigauchi Miyoko , Noda Yuko , Iwasa Kinuko , Nishijo Zjujiro , Ishida Thoshimasa , In Yasuko
Published: December 2004

The crystal structure of (±)‐7,8,13β,14α‐tetrahydro‐N7‐(13C)methylcorysaminium iodide (13C‐3a·I) was investigated by X‐ray analysis and thus the relative configuration (7S*,13S*,14S*) established (Fig. 1). The conformation of 3a was shown to have a cis‐junction of the B/C rings and the rings A and D in an antiperiplanar position relative to the C(13)C(14) bond (‘anti‐cis’), a twisted half‐chair for ring B, and a half‐chair for ring C (Figs. 2 and 3). Conformation analysis by 1H‐NMR data indicated that the crystal conformation of 3a is also the preferred one in MeOH solution.
Les β‐cétonitriles groupes protecteurs de la fonction amine. Préparation d'amino‐alcools
Authors: Abarbri Mohamed , Guignard Alain , Lamant Maurice
Published: December 2004

β‐Ketonitrile‐Derived Protecting Groups of the Amino Function. Synthesis of Amino Alcohols

The amino group of natural L‐amino acid esters is protected by condensation with 2‐oxocyclopentanenitrile (1) or 2‐formyl‐2‐phenylacetonitrile (10). Only the ester group of the formed cyanoenamino esters 2 and 11 reacts with nucleophilic reagents such as organometallics (RMgX, RLi), borohydrides, or metal amides, whereas the cyanoenamino group is unchanged (Schemes 1 and 2). Cyanoenamino alcohols obtained by reduction of cyanoenamino esters 2 are hydrolyzed under acidic conditions to amino alcohols with retention of the configuration of the starting amino acid. This sequence of reactions allows to prepare derivatives of L‐tyrosinol from (−)‐L‐tyrosine (see, e.g., Scheme 4). Cyanoenamino esters 11 are readily methylated at the N‐atom to give N‐methylated cyanoenamino esters (Scheme 3). This property is exploited on the way of a multistep procedure to obtain N‐methylated amino alcohols homologous to natural (−)‐(1R,2S)‐ephedrine.
Selectivity in Rhodium(II)‐Catalyzed Rearrangements of cycloprop‐2‐ene‐1‐carboxylates
Authors: Müller Paul , Gränicher Christian
Published: December 2004

The course of the thermocatalytic rearrangement of cycloprop‐2‐ene‐1‐carboxylates in the presence of dirhodium(II) tetrakis(perfluorobutyrate) ([Rh2(pfb)4]) was investigated by varying the substituents of the cyclopropene ring. Product composition is markedly influenced by the number, nature, and position of the substituents, which determine the regio‐ and stereoselectivity of the cyclopropene‐ring cleavage. A mechanism is proposed in which attack of the electrophilic RhII species is concerted with disrotatory ring opening of the incipient cyclopropyl cation and affords a metal‐complexed vinylcarbene. The chemoselectivity of the latter is consistent with that of other carbenes generated in the presence of [Rh2(pfb)4].
Synthesis of Benz[a]azulenes Substituted at the Benzo Ring
Authors: Fallahpour Reza‐Ali , Hansen Hans‐Jürgen
Published: December 2004

It is shown that the thermal electrocyclic ring‐closure reaction of 1,2‐di[(E)‐prop‐1‐enyl]benzene to yield 2,3‐dimethylnaphthalene (cf. Scheme 1) [10] can successfully be applied also to the synthesis of benz[a]azulenes (cf. Schemes 2 and 3). Starting materials are methyl 4,6,8‐trimethylazulen‐2‐yl ketone (6) and the corresponding 2‐carbaldehyde 5, which, in a Horner‐Emmons reaction, are transformed into the (azulen‐2‐yl)‐acrylates (E)‐8 and (E)‐7, respectively. Vilsmeier formylation of these compounds, followed by the Horner‐Emmons reaction leads to the formation of the bisacrylates (E,E)‐11 and (E,E)‐12, respectively. In an alternative reaction, (E)‐8, on treatment with dimethyl acetylenedicarboxylate (ADM) in the presence of [RuH2(PPh3)4], can be transformed into the methoxycarbonyl‐substituted bisacrylates (E,E)‐ and (E,Z)‐17. All three bisacrylates, on heating at 180–190° in p‐cymene, undergo cyclization to yield the corresponding dihydrobenz[a]azulenes 13, 14, and 18, respectively, which could easily be dehydrogenated on heating in the presence of Pd/C. The new benz[a]azulenes 15, 16, and 19 are fully characterized.
Unprecedented Ring Contractions in Cytochalasans: Formation of [10]cytochalasans and a cyclohepta[4,5]benz[1,2‐d]isoindole derivative
Authors: Boutellier Markus , Zürcher Werner , Tamm Christoph
Published: December 2004

A series of transformations of cytochalasin D (1; zygosporin A) was carried out. After treatment of the diol 7 with mesyl chloride and pyridine, and subsequent chromatography on silica gel, the 17‐acetyl derivatives 12 and 13, the first members of the hitherto unknown [10]cytochalasans, were obtained. The alcohol 8 was converted to the chlorosulfinate 18 under the same conditions. Replacement of pyridine by triethylamine in the mesylation reaction led to the cyclohepta[4,5]benz[1,2‐d]isoindole derivative 20, also representing a novel ring system.
Synthesis of Aristotelia‐Type Alkaloids. Part XV. Total synthesis of (+)‐hobartinol
Authors: Dobler Markus , Anderson James C. , Juch Mathias , Borschberg Hans‐Jürg
Published: December 2004

Synthetic (+)‐makomakine (6) was transformed in six steps into (+)‐17R,18R)‐17,18‐dihydrohobartine‐17,18‐diol ((+)‐5) with an overall yield of 38% (Scheme 2). This compound was shown to be identical with natural hobartinol, a monoterpene indole alkaloid from Aristotelia australasica, originally believed to be the (17S)‐epimer 1. At the same time, the synthesis of (+)‐5 delineates the hitherto unknown absolute configuration of this metabolite.
Stereoselective Synthesis of 2,4,6‐Trimethylcyclohex‐4‐ene‐1,3‐diol Derivatives and of polypropionate fragments with four contiguous stereogenic centers
Authors: Bialecki Maciej , Vogel Pierre
Published: December 2004

The Diels‐Alder adduct (±)‐3 of 2,4‐dimethylfuran and 1‐cyanovinyl acetate was converted stereoselectively into benzyl 6‐(4‐chlorophenylsulfonyl)‐1,3‐exo,5‐trimethyl‐7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐exo‐yl (26) and ‐2‐endo‐yl ether (36). Addition of LiAlH4 to the latter led to the 3‐O‐benzyl derivatives 28 and 37 of (1RS,2SR,3SR,6SR)‐ and (1RS,2SR,3RS,6SR)‐5‐(4‐chlorophenylsulfonyl)‐2,4,6‐trimethylcyclohex‐4‐ene‐1,3‐diol, respectively. Methylenation of 6‐exo‐(4‐chlorophenylthio)‐1‐methyl‐5‐methylidene‐7‐oxabicyclo[2.2.1]heptan‐2‐one (16), obtained by reaction of (±)‐3 with 4‐Cl‐C6H4SCl and saponification gave, 6‐exo‐(4‐chlorophenylthio)‐1‐methyl‐3,5‐dimethylidene‐7‐oxabicyclo [2.2.1]heptan‐2‐one (43), the reduction of which with K‐Selectride afforded 6‐exo‐(4‐chlorophenylthio)‐1,3‐endo‐dimethyl‐5‐methylidene‐7‐oxabicyclo[2.2.1]heptan‐2‐endo‐ol (44). The 3‐O‐benzyl derivative 48 of (1RS,2RS,3RS,6SR)‐5‐(4‐chlorophenylsulfonyl)‐ 2,4,6‐trimethylcyclohex‐4‐ene‐1,3‐diol was derived from 44 via based‐induced oxa‐ring opening of benzyl 6‐endo‐(4‐chlorophenylsulfonyl)‐1,3‐endo‐5‐endo‐trimethyl‐7‐oxabicyclo[2.2.1]hept‐2‐endo‐yl ether (49). Benzylation of 28, followed by reductive desulfonylation and oxidative cleavage of the cyclohexene moiety afforded (2RS,3SR,4RS,5RS)‐3,5‐bis(benzyloxy)‐2,4‐dimethyl‐6‐oxoheptanal (32).
The X‐Ray Crystal Structures of a 1,9‐ and a 7,8‐Diels‐Alder monoadduct of C70
Authors: Seiler Paul , Herrmann Andreas , Diederich François
Published: December 2004

Accurate low‐temperature X‐ray crystal structures of the isomeric Diels‐Alder monoadducts of C70 1a, bridged at the [6,6] bond between C(1) and C(9), and 1b, bridged at the [6,6] bond between C(7) and C(8), have been determined. The latter structure is the first one solved for a 7,8‐C70 monoadduct. The C1‐symmetrical 1a and Cs‐symmetrical 1b co‐crystallize with CS2 molecules in the space groups P21/c and Pnma, respectively, and the distances between bridgehead atoms are 1.603(3) and 1.584(3) Å. The degree of pyramidalization of atoms involved in [6,6] bonds near the ‘unsubstituted’ pole and near the equator of the fullerene was estimated; it is shown for the unsubstituted pole region that atoms corresponding to C(1) and C(9) are slightly more pyramidal than those corresponding to C(7) and C(8), in agreement with ab initio calculations obtained for the C70 spheroid. Some aspects of the crystal packings are discussed.
Crystal Structures of Two Modifications of [3,O‐didehydro‐mebmt1, val2]‐cyclosporin and comparison of three different X‐ray data sets
Authors: Pohl Ehmke , Herbst‐Irmer Regine , Sheldrick George M. , Dauter Zbigniew , Wilson Keith S. , Bölsterli Johann J. , Bollinger Pietro , Kallen Jörg , Walkinshaw Malcolm D.
Published: December 2004

The crystal structure of [3,O‐didehydro‐MeBmt1, Val2]cyclosporin (PSC‐833; 1) was investigated by X‐ray analysis. Data were collected from two different crystal modifications. Modification I crystallizes in P3121, a = b = 21.419 (2) Å, c = 32.101 (3) Å with one molecule in the asymmetric unit, modification II in P3221, a = b = 21.313 (2) Å, c = 62.053(3) Å with two molecules per asymmetric unit. This non‐immunosuppressive analogue of cyclosporin A adopts a similar backbone conformation to that found in the crystal structure of cyclosporin A and other analogues. Three different data sets of modification I were collected using an Enraf‐Nonius‐CAD4 diffractometer with CuKα radiation at 20°, a Stoe‐Siemens four‐circle diffractometer with MoKα radiation at − 120°, and an EMBL image‐plate scanner with synchrotron radiation at 12°. The quality of the data sets was evaluated by internal consistency, independent structure solution, and refinement. The structural parameters reported here for modification I are based on the synchrotron data.
Molecular Clefts Derived from 9,9′‐spirobi[9H‐fluorene] for enantioselective complexation of pyranosides and dicarboxylic acids
Authors: Cuntze Jens , Owens Linda , Alcázar Victoria , Seiler Paul , Diederich François
Published: December 2004

The molecular clefts (R)‐ and (S)‐3, incorporating 9,9′‐spirobi[9H‐fluorene] as a spacer and two N‐(5,7‐dimethyl‐1,8‐naphthyridin‐2‐yl)carboxamide (CONH(naphthy)) units as H‐bonding sites were prepared via the bis(succinimid‐N‐yl esters) of (R)‐and (S)‐9,9′‐spirobi[9H‐fluorene]‐2,2′‐dicarboxylic acid (5). Derivative 6, with one CONH(naphthy) unit and one succinimid‐N‐yl ester residue allowed easy access to spirobifluorene clefts with two different H‐bonding sites, as exemplified by the synthesis of 4. Binding studies with (R)‐ and (S)‐3 and optically active dicarboxylic acids in CDCl3 exhibited differences in free energy of the formed diastereoisomeric complexes (Δ(ΔGº)) between 0.5 and 1.6 kcal mol−1 (T 300 K). Similar enantioselectivities were observed with the spirobifluorene clefts (R)‐ and (S)‐1, bearing two N‐(6‐methylpyridin‐2‐yl)carboxamide (CONH(py)) H‐bonding sites. The thermodynamic quantities ΔHº and ΔSº for the recognition processes with (R)‐ and (S)‐1 were determined by variable‐temperature 1H‐NMR titrations and compared to those with (R)‐ and (S)‐2, which have two CONH(py) moieties attached to the 6,6′‐positions of a conformationally more flexible 1,1′‐binaphthyl cleft. All association processes showed high enthalpic driving forces which are partially compensated by unfavorable changes in entropy. Pyranosides bind to the optically active clefts 1 and 3 in CDCl3 with −ΔGº = 3.0–4.3 kcal mol−1. Diastereoisomeric selectivities up to 1.2 kcal mol−1 and enantioselectivities up to 0.4 kcal mol−1 were observed. Cleft 4 and N‐(5,7‐dimethyl‐1,8‐naphthyridin‐2‐yl)acetamide (25) complexed pyranosides 22–24 as effectively as 3 indicating that only one CONH(naphthy) site in 3 associates strongly with the sugar derivatives. Based on the X‐ray crystal structure of 3, a computer model for the complex between (S)‐3 and pyranoside 22 was constructed. Molecular‐dynamics (MD) simulations showed that differential geometrical constraints are at the origin of the high enantioselectivity in the complexation of dicarboxylic acid (S)‐7 by (R)‐ and (S)‐1 and (R)‐ and (S)‐3.
Total Synthesis of Crenulatan Diterpenes: Strategy and stereocontrolled construction of a bicyclic keto‐lactone building block
Authors: He Wei , Pinard Emmanuel , Paquette Leo A.
Published: December 2004

The bicyclic keto lactone 26 was synthesized for the purpose of developing a viable route to marine diterpenes of the crenulatan type. Following the efficient conversion of (S)‐citronellol (5) to the allylated alcohol 9a (Scheme 2), the αβ‐unsaturated lactone 12 was efficiently accessed in preparation for stereocontrolled conjugate addition. The hydroxymethyl equivalent most suited to this task was (i‐PrO)Me2SiCH2MgCl, which gave 13 predominantly in the presence of CuI and Me3SiCl. Once the OH group was deprotected (→ 14), it proved an easy matter to implement acid‐catalyzed isomerization to lactone 15, oxidation of which gave the pivotal aldehyde 16. Condensation of 16 with PhSeCH2Li led via 21 to 22 (Scheme 3). Once the OH group was protected (→ 22b), it proved possible to effect aldolization with crotonaldehyde (→ 23). Exposure of 23 to acid gave the sub‐target compound 25. Its subsequent oxidation and thermal activation resulted in sequential selenoxide elimination with Claisen rearrangement (→ 26). The structural features of 26 require that a chair‐like transition state be adopted during the [3.3]sigmatropic event. With the clarification of these issues, a highly serviceable and more advanced assault on the crenulatans should prove capable of being mounted.
Synthesis of Potential Inhibitors of Ethylene Biosynthesis: The diastereoisomers of 1‐amino‐2‐bromocyclopropanecarboxylic acid
Authors: Wick Lukas , Tamm Christoph , Boller Thomas
Published: December 2004

The preparation of the diastereoisomers of 1‐amino‐2‐bromocyclopropanecarboxylic acid is described using the methyl (1RS, 5SR)‐2‐oxo‐3‐oxabicyclo[3.1.0]hexane‐1‐carboxylate 5 as starting material. The key step is the oxidation of 9 with subsequent radical introduction of bromine according to the Barton procedure. The 2‐bromo‐cyclopropanecarboxylates cis‐11 and trans‐11 were obtained as diastereoisomer mixture in a ratio of 3:1. They were converted into cis‐ and trans‐esters 12 and the acids 13.
Synthesis of Galactose‐ and N‐Acetylglucosamine‐Derived Tetrazoles and their evaluation as β‐glycosidase inhibitors
Authors: Heightman Thomas D. , Ermert Philipp , Klein Daniela , Vasella Andrea
Published: December 2004

The title compounds 6 and 7 have been prepared from the known 2,3‐di‐O‐benzyl‐4,6‐O‐benzylidene‐D‐galactose (18) and N2‐acetyl‐tri‐O‐benzyl‐D‐glucosamine oxime (29) in eight and six steps, respectively. The azidonitrile leading to the benzylated galacto‐tetrazole 16 was prepared from 14 and cyclized under the conditions of its formation (Scheme 1). The alcohol 13 was obtained by oxidation of 10 followed by reduction. Better yields and diastereoselectivities were realized, when the benzylidene‐protected D‐galacto‐alcohol 20 was subjected to oxido‐reduction, yielding the L‐altro‐alcohol 22 via the ketone 21 (Scheme 2). Treatment of the corresponding tosylate 24 with NaN3 yielded the tetrazole 25, which was deprotected to 6. The tetrabenzyl ether 16 (from 14, or from 25 via 27) was reduced to 28 and deprotected to give the known deoxygalactostain 8 (Scheme 2). Oxidation of the hydroxynitrile 30, derived from 29, followed by reduction of 32 yielded mostly the L‐ido‐hydroxynitrile (Scheme 3), which was tosylated and treated with NaN3 to give the tetrazole 35a and its manno‐isomer 36a, while Al(N3)3 yielded (E)‐ and (Z)‐38 (Scheme 4). The intermediate azide 39 was isolated besides 40 when NH4N3/DMF was used; thermolysis of 39 gave mostly 35a, which was deprotected to 7, besides some elimination product 41. Both 6 and 7 are stable in the pH range 1–10; at pH 12, 6 is unaffected but, 7 shows some epimerization to the manno‐configurated isomer 43. The tetrazole 6 is a competitive inhibitor of the β‐galactosidases from E. coli (K1 = 1 μM, pH 6.8) and bovine liver (K1 = 0.8 μM, pH 7.0); the N‐acetyl‐β‐D‐glucosaminidase from bovine kidney is competitively inhibited by 7 (K1 ≊ 0.2 μM, pH 4.1).
Pteridines. Part CVI. Isolation and characterization of limipterin (1‐O‐(L‐erythro‐biopterin‐2′‐yl)‐β‐N‐acetylglucosamine) and its 5,6,7,8‐tetrahydro derivative from green sulfur bacterium Chlorobium limicola f. thiosulfatophilum NCIB 8327
Authors: Cha Ki W. , Pfleiderer Wolfgang , Yim Jeongbin J.
Published: December 2004

A new pteridine compound was isolated from green sulfur photosynthetic bacteria, Chlorobium limicola f. thiosulfatophilum NCIB 8327. The structure of this pterin derivative was established to be 1‐O‐(L‐erythro‐5,6,7,8‐ tetrahydropterin‐2′‐yl)‐β‐N‐acetylglucosamine (1) from 1H‐NMR and CD spectra as well as from various mass spectrometric techniques and chemical‐cleavage techniques. Upon acid hydrolysis of 1, equimolar amounts of biopterin (2) and N‐acetylglucosamine were produced. The structure of the hydrolysis product 2 was confirmed by comparing its NMR, UV, CD, and MS and its chromatographical behavior with those of an authentic specimen. N‐Acetylglucosamine was identified by an enzymatic hydrolysis experiment as well as by NMR and thin layer chromatography. Electrospray (ES), fast‐atom‐bombardment (FAB), and thermospray (TS) mass spectrometry of 1 yielded an MH+ at m/z 441. Periodate‐oxidation experiments of the intact molecule 1 and of its hydrolysis product 2 are consistent with the proposed structure. Differential I2 oxidation experiments with the native compound showed that the in vivo oxidation state of this pterin is its tetrahydro form. We propose the trivial name ‘limipterin’ for this new compound.
1‐Lithio‐2,2‐diphenyl‐1‐(phenylsulfonyl)ethen: Synthese und Kristallstruktur
Authors: Müller Jürgen , Neuburger Markus , Zehnder Margareta
Published: December 2004

Syntheses and Crystal Structure of 1‐Lithio‐2,2‐diphenyl‐1‐(phenylsulfonyl)ethene

Crystals of [1‐lithio‐2,2‐diphenyl‐1‐(phenylsulfonyl)ethene]– N,N,N′,N′ ‐tetramethylethylenediamine (2/2) (2) were prepared by addition of BuLi to 1,1‐diphenyl‐2‐(phenylsulfonyl)ethene (1) in the presence of N,N,N′,N′ ‐tetramethylethylenediamine (TMEDA) at low temperature. The X‐ray structure analysis shows a centrosymmetric dimer bridged over an eight‐membered (LiOSO)2 ring. There are no Li–C contacts to the C(α) atoms. Both Li cations are tetracoordinated via the sulfonyl O‐atoms and the N‐atoms of the TMEDA ligand. The X‐ray structure analysis of 1,1‐diphenyl‐2‐(phenylsulfonyl)ethene (1) also was determined to compare interatomic distances and angles.
The Low‐Temperature UV/VIS Absorption Spectrum of [14]Annulene
Authors: Baumann Harold , Oth Jean F. M.
Published: December 2004

The UV/VIS absorption spectrum of [14]annulene was measured in 3‐methylpentane at room and liquid‐N2 temperatures and interpreted by the CNDO/S‐CI method. This comparison between experiment and theory supports a structure with π‐bond delocalization for this molecule.
Acyclic Tetraethynylethene Molecular Scaffolding: Multinanometer‐sized linearly conjugated rods with the poly(triacetylene) backbone and cross‐conjugated expanded dendralenes
Authors: Boldi Armen M. , Anthony John , Gramlich Volker , Knobler Carolyn B. , Boudon Corinne , Gisselbrecht Jean‐Paul , Gross Maurice , Diederich François
Published: December 2004

Derivatives of fully cross‐conjugated tetraethynylethene (3,4‐diethynylhex‐3‐ene‐1,5‐diyne) 1 are versatile precursors to multinanometer‐sized molecular rods with all‐C‐backbones. Oxidative polymerization (CuCl, N,N,N′,N′‐tetramethylethylenthylenediamine (TMEDA), O2) of the trans‐bis‐deprotected trans‐bis(triisopropylsilyl)‐protected tetraethynylethene 2 yielded, after end‐capping with phenylacetylene, the remarkably stable, soluble oligomers 3–7 with a persilylethynylated poly(triacetylene) (PTA) backbone [(CCCRCRCC)n] and a length of 19.4 (3), 26.8 (4), 34.3 (5), 41.8 (6), and 49.2 (7) Å (Scheme 1). These compounds underwent facile one‐electron reductions with the number of reversible reduction steps being equal to the number of tetraethynylethene moieties in each molecular rod. Oxidative Eglinton‐Glaser homo‐coupling of tetraethynylethenes 8–10 with a single free ethynyl group provided the fully silyl‐protected 3,4,9,10‐tetraethynyl‐substituted dodeca‐3,9‐diene‐1,5,7,11‐tetraynes 11–13 (Scheme 2) and, after alkyne deprotection, the novel hydrocarbon 14, a C20H6 isomer, and its partially silyl‐protected derivative 15. Oxidative hetero‐coupling between two different tetraethynylethene derivatives, one with a single and the other with two free terminal ethynyl groups, yielded the extended chromophores 16–21 composed of 3 or 4 tetraethynylethene moieties (Scheme 3). The linearly conjugated oligomers 16 and 17 with the PTA backbone are isomeric to 19 and 20, respectively, which are members of the cross‐conjugated expanded dendralenes, i.e., dendralenes with butadiynediyl fragments inserted between each pair of double bonds [(CCC(CR2)CC)n]. The electronic absorption spectra of these compounds were compared and analyzed in terms of the competition between linear and cross‐conjugation in determining the extent of π‐electron delocalization. Although steric factors on π‐electron conjugation remain to be clarified, this analysis strongly suggests that cross‐conjugation is not an efficient mechanism for π‐electron delocalization. All extended acetylenic‐olefinic chromophores considered in this study exhibited remarkably high stability and did not decompose when exposed to laboratory air and light for months. In agreement with this observation, electrochemical studies demonstrated that the compounds are difficult to oxidize with the oxidation potentials in THF (0.1M(Bu4N)PF6) being higher than 1.0 V (vs. the ferrocene/ferrocenium couple).
Stereoselective Partial Synthesis of (+)‐Pisiferic Acid
Authors: Geiwiz Jürgen , Haslinger Ernst
Published: December 2004

(+)‐Pisiferic acid (1), an antibiotic active against Gram‐negative and Gram‐positive bacteria, was synthesized starting from dehydroabietic acid (2) or abietic acid (26). The terpene ring system was functionalized and a Barton reaction used to oxidize Me(20). The intermediates of this photochemical reaction were isolated and characterized.
Elektronentransfer und Ionenpaar‐Bildung. 40. Mitteilung. Einkristall‐Struktur von Bis(Natrium‐1,1′‐Biphenyl‐2‐thiolat‐Diglyme): Ein Zwischenprodukt der reduktiven Ringöffnung von Dibenzothiophen
Authors: Bock Hans , Arad Claudia , Näther Christian , Havlas Zdenek , Göbel Ilka , John Andreas , Kleine Markus
Published: December 2004

Electron Transfer and Ion Pair Formation Single Crystal Structure of Bis(sodium 1,1′‐biphenyl‐2‐thiolate‐diglyme): An Intermediate in the Reductive Ring Opening of Dibenzothiophene

On Na‐metal reduction of dibenzothiophene, the five‐membered sulfur ring opens to form a colorless 1,1′‐biphenyl‐2‐thiolate sodium salt, which, according to its single‐crystal structure determination, is a dimer containing a four‐membered, twice diglyme‐solvated ring (diglyme···Na⊕⊖SR)2. Additional measurements provide the following information: cyclic voltammetry in aprotic MeCN solution shows one quasi‐reversible electron transfer at E = −2.58 V. The dibenzothiophene radical anion can be generated in aprotic THF solution at a K mirror and characterized by an 81‐line ESR spectrum and its simulation. This blue species is also the first UV/VIS detectable one before the solution changes via green (due to blue + yellow color mixing) to yellow, yielding across an isosbestic point a second and diamagnetic compound. All of the above results suggest a consecutive two‐electron reduction followed by an intersystem protonation, M + (e⊖) → M.⊖ (blue) + (e⊖) → (M⊖⊖, yellow?) + (H⊕) → MH⊖ (colorless), to yield the crystallized and structurally characterized reaction intermediate. The diglyme‐solvated sodium‐salt dimer provides a basis for a quantum‐chemical discussion of some facets of the most likely microscopic reduction pathway.
Bortrifluorid‐katalysierte Umsetzung von 3‐Amino‐2H‐azirinen mit Amiden: Bildung von 4,4‐disubstituierten 4H‐Imidazolen
Authors: Arnhold Franziska , Chaloupka Stanislav , Linden Anthony , Heimgartner Heinz
Published: December 2004

Boron Trifluoride Catalyzed Reaction of 3‐Amino‐2H‐azirines and Amides: Formation of 4,4‐Disubstituted 4H‐Imidazoles

Reaction of trifluoroacetamide and 3‐amino‐2H‐azirines 1 in refluxing MeCN affords 4‐amino‐2‐(trifluoromethyl)‐4H‐imidazoles 5 in fair yields (Scheme 3). Less acidic amides do not react with 1 under similar conditions. Therefore, a procedure involving BF3‐catalysis has been elaborated: the aminoazirine 1 in CH2Cl2 at −78° is treated with BF3 · Et2O and then with a solution of the sodium salt of an amide in THF, prepared by addition of sodium hexamethyldisilazane at −78°. The 4H‐imidazoles of type 5 are formed in ca. 50% yield (Scheme 4). Reaction mechanisms for this ring enlargement of 1 are proposed in Schemes 5 and 6.
Lacton‐Bildung durch ringerweiternde Fragmentierung von Epoxycyclodecanon‐Derivaten
Authors: Stojanova Diana S. , Hesse Manfred
Published: December 2004

Lactones from Epoxycyclodecanone Derivatives by Ring Enlargement Involving Fragmentation Reactions

A stereospecific ring‐enlargement reaction of alkyl esters of 2,3‐epoxy‐1‐(3‐hydroxypropyl)‐10‐oxocyclo‐decanecarboxylic‐acid derivatives is described, involving Grob fragmentation of in situ formed hemiacetals. The assignment of the relative configuration of the starting materials was accomplished on the basis of 1H‐NMR data. The rearrangement of the epoxides 9 and 10 (with cis‐orientation of the ester group and the epoxide ring, Scheme 1) gives the lactone 15 as the single and as the major product, respectively, with (Z)‐configuration of the newly formed CC bond. A concerted reaction mechanism is assumed. The formation of a small amount of 12 from 10 is probably due to a competitive two‐step carbanion pathway. The reaction of the diastereoisomers 7 and 8 leads to the lactones 11 and 12, respectively, as the only ring‐enlargement products (Scheme 1), with (E)‐configuration of the newly formed CC bond. On the basis of our results, we cannot distinguish in this case between a concerted and a two‐step carbanion mechanism. This type of reaction takes place only in the presence of an ester group; no ring enlargement was detected in case of compound 20 (Scheme 3), which is the de(alkoxycarbonyl) derivative of 9. The eliminative opening of the epoxide ring in the epoxylactone 17 affords 11 as the single product (Scheme 2). A carbanion mechanism was assumed for this reaction.
Kupfer(II)‐chlorid‐katalysierte ‘Carben‐Dimerisierung’ von 1‐Halogeno‐1‐Lithiocyclopropanen: Ein einfacher Zugang zu Bi(cyclopropylidenen)
Authors: Loosli Thomas , Borer Markus , Kulakowska Iga , Minger Andrea , Neuenschwander Markus , Engel Peter
Published: December 2004

Copper(II)‐Chloride Catalyzed ‘Carbene Dimerization’ of 1‐Halogeno‐1‐lithiocyclopropanes: A Simple Access to Bi(cyclopropylidenes)

A series of 13 bi(cyclopropylidenes) 11 are prepared in a simple one‐pot reaction by halogeno‐lithio exchange between 1,1‐dibromocyclopropanes 1a–n and BuLi, in most cases at −95°, to give 1‐bromo‐1‐lithiocyclopropanes 2a–n, followed by treatment with CuCl2 at low temperature and a simple workup at room temperature (Scheme 3c and Table 1). The yields of bi(cyclopropylidenes) 11 strongly depend on reaction parameters, as explicitly shown for the conversion 1f →→ 11f (Tables 2–8). Mixed couplings between two different carbenoids are possible (Scheme 4), while diastereoselectivity of the active transition‐metal complex seems to be low. The structures of bi(cyclopropylidenes) 11 are confirmed by spectroscopic data as well as by X‐ray analysis of an isolated crystalline diastereoisomer of 11k (Fig. 1).
Novel Naamidine‐Type Alkaloids and Mixed‐Ligand Zinc(II) Complexes from a Calcareous Sponge, Leucetta sp., of the Coral Sea
Authors: Mancini Ines , Guella Graziano , Debitus Cécile , Pietra Francesco
Published: December 2004

As compounds from a calcareous sponge, Leucetta sp., of the Coral Sea, we isolated a series of novel naamidine‐type alkaloids, 6–10, which are oxidized at a single benzylic position. We also report on the first marine, mixed‐ligand metal complex 5 and on the first natural metal complexes 3 and 4 derived from classical naamidines, i.e., 1 and 2. The latter are also present in free form in the sponge.
Design, synthesis, and anti‐ Trypanosoma cruzi evaluation of a new class of cell‐growth inhibitors structurally related to Fenoxycarb
Authors: Schvartzapel Andrea J. , Fichera Laura , Esteva Mónica , Rodriguez Juan B. , Gros Eduardo G.
Published: December 2004

Several compounds, structurally related to the insect‐growth regulator Fenoxycarb (1), were designed and synthesized. These compounds were tested as growth inhibitors of Trypanosoma cruzi cells (epimastigotes). Compounds 6, 16, 18, and 22 were very active against T. cruzi making them promising good candidates either for blood‐bank sterilization of Chagas'‐disease surveillance, while compounds 11, 12, 13, and 19 showed a moderate degree of activity.
Azetidin‐3‐ones from (S)‐α‐Amino Acids and Their Reactions with Nucleophiles: Preparation of some azetidine‐containing amino‐alcohol and amino‐acid derivatives
Authors: Podlech Joachim , Seebach Dieter
Published: December 2004

The reactions of azetidin‐3‐ones 6–10, readily available from the amino acids L‐alanine, L‐phenylalanine, L‐valine, L‐lysine, and L‐aspartic acid, via the corresponding diazo ketones, with nucleophilic reagents such as complex hydrides, Grignard compounds, an ester enolate, and a Wittig ylide give the expected products 11–19 in good yields and mostly in high diastereoselectivities. New amino‐alcohol, γ‐amino‐ and γ‐amino‐β‐hydroxy‐carboxylic‐acid derivatives of known configurations are thus available.
Metal Complexes with Macrocyclic Ligands. Part XL. Syntheses and silver(I) complexes of mono‐ and disubstituted dithiadiazamacrocycles
Authors: Riesen Pascale C. , Kaden Thomas A.
Published: December 2004

A series of N2S2‐macrocycles with ring sizes varying between 12 and 16, as well as two 12‐membered N2S2‐rings with a pendant carboxylic and amino group, respectively, were synthesized. Their complexation properties towards Ag+ were studied by pH titrations and by potentiometry with a silver electrode. The observation that 1:1 ([AgLH2]3+, [AgLH]2+, [AgL]+) and 1:2 species ([AgL2H2]3+, [AgL2H]2+, [AgL2]+) were formed is interpreted by postulating that Ag+ can bind either to the S‐donors only, or to both the N‐ and S‐atoms. The most stable complex [AgL]+ in the series of the nonfunctionalized macrocycles was found for the 12‐membered N2S2‐ring 3. The stability of it increased when an additional donor group was introduced into the side chain. The highest formation constant (logβ110 = 14.43(1)) was obtained with the 12‐membered ring 12 carrying the ethanamine side chain. In view of a radiochemical application, all Ag+ complexes were tested in blood serum for their stability, but were not stable enough against transmetallation.
Electrochemistry of Mono‐ through Hexakis‐adducts of C60
Authors: Boudon Corinne , Gisselbrecht Jean‐Paul , Gross Maurice , Isaacs Lyle , Anderson Harry L. , Faust Rüdiger , Diederich François
Published: December 2004

The first systematic electrochemical study by cyclic voltammetry (CV) and rotating‐disk electrode (RDE) of the changes in redox properties of covalent fullerene derivatives (2–11) as a function of increasing number of addends is reported. Dialkynylmethanofullerenes 2–4 undergo multiple, fullerene‐centered reduction steps at slightly more negative potentials than C60 (1; see Table and Fig. 1). The two C‐spheres in the dumbbell‐shaped dimeric fullerene derivative 4 show independent, identical redox characteristics. This highlights the insulating character of the sp3‐C‐atoms in methanofullerenes which prevent through‐bond communication of substituent effects from the methano bridge to the fullerene sphere. In the series of mono‐ through hexakis‐adducts 5–11, formed by tether‐directed remote functionalization, reductions become increasingly difficult and more irreversible with increasing number of addends (see Table and Fig. 2). Whereas, in 0.1M Bu4NPF6/CH2Cl2, the first reduction of mono‐adduct 5 occurs reversibly at −1.06 V vs. the ferrocene/ferricinium couple (Fc/Fc+), hexakis‐adduct 11 is reduced irreversibly only at − 1.87 V. Hence, with incremental functionalization of the fullerene, the LUMO of the remaining conjugated framework is raised in energy. Reduction potentials are also dependent on the relative spatial disposition of the addends on the surface of the fullerene sphere. Observed UV/VIS spectral changes and changes in the chemical reactivity along the series 5–11 are in accord with the results of electrochemical measurements. Further, with increasing number of addends, the oxidation of derivatives 5–11 becomes more reversible. Whereas oxidations are increasingly facilitated upon going from mono‐adduct 5 (+1.22 V) to tris‐adduct 7 (+0.90 V), they occur at nearly the same potential (+0.95 to +0.99 V) in the higher adducts 8–11. This indicates that the oxidations occur in these compounds at a common sub‐structural element, for which a ‘cubic’ cyclophane is proposed (see Fig. 3). This sub‐structure is fully developed in hexakis‐adduct 11.
Two‐State Reactivity in Organometallic Gas‐Phase Ion Chemistry
Authors: Shaik Sason , Danovich David , Fiedler Andreas , Schröder Detlef , Schwarz Helmut
Published: December 2004

In contrast to organic reactions, which can almost always be described in terms of a single multiplicity, in organometallic systems, quite often more than one state may be involved. The phenomenon of two states of different multiplicities that determine the minimum‐energy pathway of a reaction is classified as two‐state reactivity (TSR). As an example, the ion/molecule reactions of ‘bare’ transition‐metal‐monoxide cations with dihydrogen and hydrocarbons have been analyzed in terms of the corresponding potential‐energy hypersurfaces. It turns out that, besides classical factors, such as the barrier heights, the spin‐orbit coupling factor is essential, since curve crossing between the high‐ and low‐spin states constitutes a distinct mechanistic step along the reaction coordinates. Thus, TSR may evolve as a new paradigm for describing the chemistry of coordinatively unsaturated transition‐metal complexes. This concept may contribute to the understanding of organometallic chemistry in general and for the development of oxidation catalysts in particular.
Reaction of Hydroxymethyl‐ and Alkyl‐Substituted Azulenes with Manganese Dioxide
Authors: Fallahpour Reza‐Ali , Sigrist Rolf , Hansen Hans‐Jürgen
Published: December 2004

It is shown that the 2‐(hydroxymethyl)‐1‐methylazulenes 6 are being oxidized by activated MnO2 in CH2Cl2 at room temperature to the corresponding azulene‐1,2‐dicarbaldehydes 7 (Scheme 2). Extension of the MnO2 oxidation reaction to 1‐methyl‐ and/or 3‐methyl‐substituted azulenes led to the formation of the corresponding azulene‐1‐carbaldehydes in excellent yields (Scheme 3). The reaction of unsymmetrically substituted 1,3‐dimethyl‐azulenes (cf. 15 in Scheme 4) with MnO2 shows only little chemoselectivity. However, the observed ratio of the formed constitutionally isometric azulene‐1‐carbaldehydes is in agreement with the size of the orbital coefficients in the HOMO of the azulenes. The reaction of guaiazulene (18) with MnO2 in dioxane/H2O at room temperature gave mainly the expected carbaldehyde 19. However, it was accompanied by the azulene‐diones 20 and 21 (Scheme 5). The precursor of the demethylated compound 20 is the carbaldehyde 19. Similarly, the MnO2 reaction of 7‐isopropyl‐4‐methyalazulene (22) as well as of 4,6,8‐trimethylazulene (24) led to the formation of a mixture of the corresponding azulene‐1,5‐diones and azulene‐1,7‐diones 20/23 and 25/26, respectively, in decent yields (Schemes 6 and 7). No MnO2 reaction was observed with 5,7‐dimethylazulene.
Synthesis of an Isotopically Isomeric Mixture of 1,4,6,8‐Tetramethyl[13C2]azulene and Its Thermal Reaction with Dimethyl Acetylenedicarboxylate
Authors: Fallahpour Reza‐Ali , Hansen Hans‐Jürgen
Published: December 2004

Sodium [1,3‐13C2]cyclopentadienide in tetrahydrofuran (THF) has been prepared from the corresponding labelled [13C2]cyclopentadiene which was synthesized from 13CO2 and (chloromethyl)trimethylsilane (cf. Scheme 10) according to an established procedure. It could be shown that the acetate pyrolysis of cis‐cyclopentane‐1,2‐diyl diacetate (cis‐22) at 550 ± 5° under reduced pressure (60 Torr) gives five times as much cyclopentadiene as trans‐22. The reaction of sodium [1,3‐13C2]cyclopentadienide with 2,4,6‐trimethylpyrylium tetrafluoroborate in THF leads to the formation of the statistically expected 2:2:1 mixture of 4,6,8‐trimethyl[1,3a‐13C2], ‐[2,3a‐13C2]‐, and ‐[1,3‐13C2]azulene (20; cf. Scheme 7 and Fig. 1). Formylation and reduction of the 2:2:1 mixture [13C2]‐20 results in the formation of a 1:1:1:1:1 mixture of 1,4,6,8‐tetramethyl[1,3‐13C2]‐, ‐[1,3a‐13C2]‐, ‐[2,3a‐13C2]‐, ‐[2,8a‐13C2]‐, and ‐[3,8a‐13C2]azulene (5; cf. Scheme 8 and Fig. 2). The measured 2J(13C, 13C) values of [13C2]‐20 and [13C2]‐5 are listed in Tables 1 and 2. Thermal reaction of the 1:1:1:1:1 mixture [13C2]‐5 with the four‐fold amount of dimethyl acetylenedicarboxylate (ADM) at 200° in tetralin (cf. Scheme 2) gave 5,6,8,10‐tetramethyl‐[13C2]heptalene‐1,2‐dicarboxylate ([13C2]‐6a; 22%), its double‐bond‐shifted (DBS) isomer [13C2]‐6b (19%), and the corresponding azulene‐1,2‐dicarboxylate 7 (18%). The isotopically isomeric mixture of [13C2]‐6a showed no 1J(13C,13C) at C(5) (cf. Fig. 3). This finding is in agreement with the fact that the expected primary tricyclic intermediate [7,11‐13C2]‐8 exhibits at 200° in tetralin only cleavage of the C(1)C(10) bond and formation of a C(7)C(10) bond (cf. Schemes 6 and 9), but no cleavage of the C(1)C(11) bond and formation of a C(7)C(11) bond. The limits of detection of the applied method is ≥96% for the observed process, i.e., [1,3a‐13C2]‐ 5 + ADM→ [7,11‐13C2]‐8→[1,6‐13C2]‐9 →[5,10a‐13C2]‐6a (cf. Scheme 6).