bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enantioselective Allylic Substitution Catalyzed by Chiral [Bis(dihydrooxazole)]palladium Complexes: Catalyst structure and possible mechanism of enantioselection
Authors: Matt Peter Von , Lloyd‐Jones Guy C. , Minidis Alexander B. E. , Pfaltz Andreas , Macko Ludwig , Neuburger Markus , Zehnder Margareta , Rüegger Heinz , Pregosin Paul S. 
Published: December 2004

AbstractAllylpalladium complexes with chiral bis(dihydrooxazole) ligands were studied as catalysts for the enantioselective allylic substitution reaction of rac‐1,3‐diphenylprop‐2‐enyl acetate (rac‐5) with the anion of dimethyl malonate (Scheme 1). Using enantiomerically pure (S,E)‐1‐(4‐tolyl)‐3‐phenylprop‐2‐enyl acatete ((S)‐25) as substrate, the reaction was shown to proceed by a clean ‘syn’ displacement of acetate by dimethyl malonate (Scheme 6). The [Pd11(η3‐allyl)] complex 18 and the analogous [Pd(η3‐1,3‐diphenylallyl)] complex 20, both containing the same bis(dihydrooxazole) ligand, were characterized by X‐ray structure analysis and by NMR spectroscopy in solution. The structural data reveal that steric interactions of the allyl system with the chiral ligand result in selective electronic activation of one of the allylic termini. The higher reactivity of one allylic terminus toward nucleophilic attack is reflected in a significantly longer PdC bond and a shift of the corresponding 13C‐NMR resonance to higher frequency.
Synthesis of Polypropionate Fragments Containing Tertiary‐Alcohol Moieties. Cross‐aldolisations with lithium enolates of 7‐oxabicyclo[2.2.1]heptan‐2‐one derivatives
Authors: Kernen Philippe , Vogel Pierre 
Published: December 2004

AbstractThe Diels‐Alder adduct of 2,4‐dimethylfuran to 1‐cyanovinyl (1′R)‐camphanate ((+)‐(1R,2S,4R)‐2‐exo‐cyano‐1,5‐dimethyl‐7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐endo‐yl (1′R)‐camphanate ((+)‐1)) was converted into (+)‐2,7‐dideoxy‐2,4‐di‐C‐methyl‐L‐glycero‐ ((+)‐6) and ‐D‐glycero‐L‐altro‐heptono‐1,4‐lactone ((+)‐7), into (−)‐(3R,4R,5R,6S)‐3,4:5,7‐bis(isopropylidenedioxy)‐4,6‐dimethylheptan‐2‐one ((−)‐22), and into (+)‐(2R,3R,4R,5S,6S)‐3,4:5,6‐bis(isopropylidenedioxy)‐2,4‐dimethylheptanal ((+)‐34). Condensation of ((+)‐34 with the lithium enolate of (−)‐(1R,4R,5S,6R)‐6‐exo‐[(tert‐butyl)dimethylsilyloxy]‐1,5‐endo‐dimethyl‐7‐oxabicyclo[2.2.1] heptan‐2‐one ((−)‐38; derived from (+)‐1) gave a 3:2 mixture of aldols (+)‐39 and (+)‐40 (mismatched pairs of a α‐methyl‐substituted aldehyde and (E)‐enolate) whereas the reaction of (±)‐34 with (±)‐38 gave a 10:1 mixture of aldols (±)‐41 and (±)‐39. A single aldol, (−)‐44, was obtained to condensing (+)‐34 with the lithium enolate of (+)‐(1S,4S,5S,6S)‐5‐exo‐(benzyloxy)‐1,5‐endo‐dimethyl‐7‐oxabicyclo[2.2.1]heptan‐2‐one ((+)‐43; derived from (−)‐(1S,2R,4S)‐2‐exo‐cyano‐1,5‐dimethyl‐7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐endo‐yl (1′S)‐camphanate ((−)‐3)). All these cross‐aldolisations are highly exo‐face selective for the bicyclic ketones. The best stereochemical matching is obtained when the lithium enolates and α‐methyl‐substituted aldehydes can realize a ‘chelated transition state’ that obeys the Cram and Felkin‐Anh models (steric effects). Polypropionate fragments containing eleven contiguous stereogenic centres and tertiary‐alcohol moieties are thus prepared with high stereoselectivity in a convergent fashion. The chiral auxiliaries ((1R)‐ and (1S)‐camphanic acid) are recovered at the beginning of the syntheses.
Synthesis of a Masked p ‐Quinone Methide β ‐Lactam as an active metabolite of nocardicins
Authors: Hakimelahi Gholam H. , Tsay Shwu‐Chen , Hwu Jih Ru 
Published: December 2004

AbstractNocardicin A analogues 30, 34, and 38 as well as the highly strained quinone methide 43 were synthesized. β ‐Lactam 34 was found biologically active against several Gram‐negative microorganisms in vitro; pyridinium N‐oxide derivative 38 possessed activity against Gram‐positive S. aureus bacterium. Masked p‐quinone methide β ‐lactam 43 exhibited significant antimicrobial activity in vitro. A mechanism involving an oxidation in vivo is proposed for the unprecedented biological properties of nocardicins.
Synthese von Tetradecano‐14‐lacton durch Ringerweiterung
Authors: Kostova Kalina , Hesse Manfred 
Published: December 2004

Synthesis of Tetradecano‐14‐lactone by Ring EnlargementThe aldehyde 3, prepared by ozonolysis of 2‐allyl‐2‐nitrocyclododecanone, gave the ring‐enlargement product 5(85%) by treatment with (i‐Bu)2AlH. Its transformation to the tetradecano‐14‐lactone (8) via the aldol ester 6 and other routes (best is reduction with Bu3SnH, AlBN, toluene) was difficult. Remarkable is the smooth denitrification of 3 (loss of HNO2) to the conjugated dione 4 by chromatography on silica gel or base treatment.
The Decomposition of cis‐Fused Cyclopenteno‐1,2,4‐Trioxanes induced by Ferrous Salts and some oxophilic reagents
Authors: Jefford Charles W. , Favarger France , Vicente Maria Da Graça H. , Jacquier Yvan 
Published: December 2004

AbstractTwo cis‐fused cyclopenteno‐1,2,4‐trioxanes, 1a and 1b, were subjected to Zn in AcOH or FeCl2 · 4H2O in MeCN. In the first case, the main course was deoxygenation to give cyclopentanone (18) and the 1,4‐diphenyl‐ or 1,4‐bis(4‐fluorophenyl)cyclopent‐3‐ene‐1,2‐diol 10 (Scheme 5). In the second case, isomerization chiefly occurred resulting in the formation of a dimer 9 of the respective 3,5‐diaryl‐5‐hydroxycyclopent‐2‐enyl 5‐hydroxypentanoates 8 (Scheme 3).
Ein neuer Zugang zu 2′‐O‐Alkylribonucleosiden und Eigenschaften deren Oligonucleotide
Authors: Martin Pierre 
Published: December 2004

A New Access to 2′‐O‐Alkylated Ribonucleosides and Properties of 2′‐O‐Alkylated OligoribonucleotidesA general access to 2′‐O‐alkylated ribonucleosides using the key intermediate 5 is presented. The incorporation of 2′‐O‐‘ethyleneglycol’‐ and 2′‐O‐‘glycerol’‐substituted (i.e., 2′‐O‐(2‐hydroxyethyl)‐ and 2′‐O‐(2,3‐dihydroxypropyl)‐substituted) ribonucleosides into oligonucleotides affords a new generation of oligonucleotides with high affinity for RNA, high specificity, and increased nuclease resistance.
Syntheses of the Enantiomers of γ‐Cyclogeranic Acid, γ‐Cyclocitral, and γ‐Damascone: Enantioselective protonation of enolates
Authors: Fehr Charles , Galindo José 
Published: December 2004

Abstract(R)‐and (S)‐γ‐cyclogeranic acid ((R)‐and (S)‐9, resp.) were obtained by resolution of the racemate, and their absolute configurations determined by chemical correlation. The γ‐acids (R)‐and (S)‐9 were converted into (R)‐and (S)‐methyl γ‐cyclogeranate ((R)‐and (S)‐6, resp.), and (R)‐and (S)‐γ‐damascone ((R)‐and (S)‐5, resp.). A more direct entry to (R)‐and (S)‐9 consisted in the enantioselective protonation of a thiol ester enolate with (−)‐ or (γ)‐N‐isopropylephedrine((−)‐ or (γ)‐20) and subsequent hydrolysis of the (R)‐and (S)‐S‐phenyl γ‐thiocyclogeranate ((R)‐ and (S)‐24, resp.; 97% ee). The esters (R)‐ and (S)‐24 were also used as precursors of (R)‐ and (S)‐γ‐damascone ((R)‐ and (S)‐5, resp.). Alternatively, (S)‐5 (75% ee) was obtained by enantioselective protonation of ketone enolate 29 with (−)‐N‐isopropylephedrine ((−)‐20). Organoleptic evaluation demonstrated that the (S)‐enantiomers of methyl γ‐cyclogeranate and γ‐damascone are markedly superior to their (R)‐enantiomers.
First Use of Benzyl Phosphites in the Michaelis‐Arbuzov Reaction synthesis of mono‐, Di‐, and triphosphate analogs
Authors: Saady Mourad , Lebeau Luc , Mioskowski Charles 
Published: December 2004

AbstractBenzyl phosphites were used in the Micaelis‐Arbuzov reaction. Special experimental conditions allowed preparation of a set of phosphonate analogs of mono‐, di‐, and triphosphate. Furthermore, regioselective monodeprotection makes these molecules useful building blocks for the synthesis of analogs of polyphosphorylated compounds of biological interest (e.g. nucleotides), after removal of all phosphonate benzyl ester groups under very mild conditions and high yields.
Reactivity of 5,10:8,14‐Disecosteroids: An unusual rearrangement of cyclodecene‐1,4‐dione systems to five‐membered‐ring spiro‐γ‐lactones
Authors: Lorenc Ljubinka , Bondarenko‐Gheorghiu Lidija , Krstić Natalija , Fuhrer Hermann , Kalvoda Jaroslav , Mihailović Mihailo Lj. 
Published: December 2004

AbstractUpon heating in AcOH, the stereoisomeric (Z)‐ and (R)‐6,9‐dioxocyclodex‐3‐enyl derivatives, 5 and 6, respectively, obtained by HgO/I2 oxidation of 5‐hydroxy‐8‐oxo‐8,14‐seco‐5α‐androstane‐3β,17β‐diyl diacetate (3), undergo an unusual intramolecular rearrangement to give the corresponding unsaturated (5R,9R)‐ and (5R,9S)‐spiro‐lactones 7 and 8, respectively. Hydroxylation of the CC bond in 7 and 8, and subsequent glycol cleavage of the resulting diols 9 and 10 afforded the epimeric spiro‐lactones (5R,9S)‐11 and (5R,9R)‐14, respectively, and in both cases, the ring‐D‐containing fragments 12 and 13.
Carbenoid Reactions in Rhodium(II)‐Catalyzed Decomposition of Iodonium Ylides
Authors: Müller Paul , Fernandez Daniel 
Published: December 2004

AbstractThe intermediacy of metallocarbenes in decomposition reactions of iodonium ylides with [Rh2(OAc)4] was established by comparison with reactions of the corresponding diazo compounds. The sensitivity of the RhII‐catalyzed intermolecular cyclopropane formation from substituted styrenes and bis(methoxycarbonyl)(phenyliodono)methanide (1a) or dimethyl diazomalonate (1b) is identical. The Hammett plot (with σ+) has a slope of −0.47. Iodonium ylides and diazo compounds afford the same products in [Rh2(OAc)4]‐catalyzed cyclopropane formations, cycloadditions, and intramolecular CH insertions, and exhibit the identical selectivity in intramolecular competitions for cyclopropane formation and insertion. The intramolecular CH insertion of the ylide 20c, when carried out in the presence of a chiral catalyst ([Rh2{(−)‐(S)‐ptpa}4]), results in formation of 21a having an ee of 67%, identical to the ee obtained with the diazo compound 20b.
Efficient Control of the Stereoselectivity in Reactions of 2‐Oxy‐Substituted Benzylic Radicals
Authors: Moufid Nadira , Renaud Philippe , Hassler Carla , Giese Bernd 
Published: December 2004

AbstractThe stereoselectivity in reactions of 2‐oxy‐substituted radicals of type B was investigated. As expected, minimization of allylic 1,3‐strain was the major controlling factor. Under standard conditions, only a modest level of stereoselectivity was observed. E.g., deuteration of the benzylated radical (R1 = benzyl) gave diastereoisomer ratios ≤ 2:1. Use of a bulky protective group on the O‐atom (R1 = (t‐Bu)Ph2Si) enhanced slightly the selectivity (ratio 4.1:1). However, a dramatic increase of the stereoselectivity (ratio 13:1) was obtained, when the reaction was performed with the free alcohol after treatment with bulky methylaluminium bis(phenoxide) derivatives (methyl‐aluminium bis[2,6‐di(tert‐butyl)‐4‐methylphenoxide] (MAD) and methylaluminium bis(2,6‐diphenylphenoxide) (MAPH)).
exo/endo‐Selectivity in the Reaction of ‘Bare’ FeO+ with Bicyclo[2.2.1]heptane (Norbornane)
Authors: Schwarz Joseph , Schwarz Helmut 
Published: December 2004

Abstract‘Bare’ FeO+ reacts in the gas phase with norbornane with collision efficiency, and the most prominent cationic products correspond to [FeC5H6]+ (32%), [FeC7H8]+ (19%), [FeC3H6O]+ (19%) and [FeC6H6]+ (14%), which are structurally characterized by ligand exchange as well as collision‐induced dissociation experiments. Circumstantial evidence is provided which indicates that the complexes [FeC5H6]+, [FeC7H8]+, and [FeC6H6]+ originate from an Fe(norbornene)+ intermediate which itself is formed by elimination of H2O from the [FeO(norbornane)]+ encounter complex. Although the reactions are preceded and/or accompanied by partial H/D exchange, the isotope distribution in the productions clearly points to a preferential endo‐attack of bare FeO+, with an endo/exo‐ratio of ca. 10.3 and kinetic isotope effects kH/kD for the endo‐abstraction of 2.4 and of 7.7 for approaching an exo‐CH bond. The preferred endo‐approach of bicyclo[2.2.1]heptane by ‘bare’ FeO+ is in distinct contrast to the P‐450‐mediated or the iron(III)porphyrin‐catalyzed hydroxylation of this substrate which favor reactions at the exo‐face.
Erstes Beispiel einer H‐Verschiebung in ‘Thiocarbonyl‐aminiden’ (N‐(Alkylidensulfonio)aminiden)
Authors: Mlostoń Grzegorz , Romański Jaroslaw , Linden Anthony , Heimgartner Heinz 
Published: December 2004

First Example of an H‐Shift in ‘Thiocarbonyl Aminides’ (N‐(Alkylidenesulfonio)aminides)Reaction of benzyl azide (15a) with the sterically hindered CS group of 4,4‐dimethyl‐1,3‐thiazole‐5(4H)‐thiones 14 (Scheme 3) and 1,1,3,3‐tetramethylindane‐2‐thione (17, Scheme 4) at 80° leads to the corresponding imines in high yield, without formation of any by‐product. In contrast, 15a and 2,2,4,4‐tetramethyl‐3‐thioxocyclobutanone (7) under the same conditions yielded, in addition to imine 19, products 20a and 21 (Scheme 5). For the formation of 20a, a reaction mechanism via [1,4]‐H shift in the intermediate ‘thiocarbonyl aminides’ 23 is proposed (Scheme 6). Product 21 as well as the dithiazole derivative 22, which is formed only in the reaction with 4‐nitrobenzyl azide (15c), are formal adducts of the dipole 23. Whereas precedents are known for the formation of cycloadducts of type 22, the pathway to 21 is not known. Two possible mechanisms of its formation are proposed in Schemes 8 and 9.
Solid‐State Photocyclodimerization of 1‐Thiocoumarin (= 2H‐1‐Benzothiopyran‐2‐one)
Authors: Klaus Christian P. , Thiemann Carolin , Kopf Jürgen , Margaretha Paul 
Published: December 2004

AbstractIrradiation (λ > 390 nm) of 2H‐1‐benzothiopyran‐2‐one (1) in the solid state affords selectively 6aα,6bα,12bα,12cα ‐tetrahydrocyclobuta[1,2‐c:4,3‐c′]bis[1]benzothiopyran ‐6,7‐dione (2), the head‐to‐head (HH) cis‐cisoid‐cis‐dimer, while irradiation of 1 in the solid state using shorter wavelengths (λ > 340 nm) affords a mixture of all four cis‐fused tricyclic dimers 2–5. These results represent a novel wavelength effect in solid‐state photochemistry.
Synthesis and First Applications of a New Chiral Auxiliary (tert‐butyl 2‐(tert‐butyl)‐5,5‐dimethyl‐4‐oxoimidazolidine‐1‐carboxylate)
Authors: Studer Armido , Hintermann Tobias , Seebach Dieter 
Published: December 2004

AbstractBoth enantiomers of tert‐butyl 2‐(tert‐butyl)‐5,5‐dimethyl‐4‐oxoimidazolidine‐1‐carboxylate (11; Bbdmoic) were prepared from L‐alanine (Schemes 1 and 2). The parent heterocycle, 2‐tert‐butyl‐5,5‐dimethylimidazolidin‐4‐one (12; from 2‐aminoisobutyramide, H‐Aib‐NH2, and pivalaldehyde) was also available in both enantiomeric forms by resolution with O,O′‐dibenzoyltartaric acid. The compound (R)‐ or (S)‐11 was used as an auxiliary, but also as a chiral Aib building block in a dipeptide synthesis. The 3‐propanoyl derivative 13 of (R)‐11 was used for the preparation of enantiomerically pure 2‐methyl‐3‐phenylpropanoic acid (enantiomer ratio (e.r.) 99.5:0.5), by benzylation of the Zn‐enolate (→ 14; Scheme 3). Oxidative coupling of the bis‐enolate derived from heptanedioic acid and (S)‐11 (→ 23) and methanolysis of the auxiliary gave dimethyl trans‐cyclopentane‐1,2‐dicarboxylate (26) with an e.r. of 93:7 (Scheme 5, Fig. 5). The 3‐(Boc‐Gly)‐Bbdmoic derivative 29 was doubly deprotonated and, after addition of ZnBr2 alkylated with alkyl, benzyl, or allyl halides to give the higher amino‐acid derivatives with excellent selectivities (e.r. > 99.5:0.5, Schemes 6 and 7). Michael additions of cuprates to [(E)‐MeCHCHCO]‐Bbdmoic 36 occurred in high yields, but high diastereoselectivities were only observed with aryl cuprates (diastereoisomer ratio (d.r.) 99:1 for R = Ph, Scheme 8). Finally, 3‐(Boc‐CH2)‐Bbdmoic 17 was alkylated through the ester Li‐enolate with primary and secondary alkyl, allyl, and benzyl halides with diastereoselectivities (ds) ranging from 91 to 98%, giving acetals of Boc‐Aib‐Xxx‐O(t‐Bu) dipeptides (Scheme 4). The effectiveness of Bbdmoic is compared with that of other chiral auxiliaries previously used for the same types of transformations.
Formation of Heptaleno[1,2‐c]furans and Heptaleno[1,2‐c]furanones
Authors: Uebelhart Peter , Mohler Peter , Fallahpour Reza‐Ali , Hansen Hans‐Jürgen 
Published: December 2004

AbstractThe dehydrogenation reaction of the heptalene‐4,5‐dimethanols 4a and 4d, which do not undergo the double‐bond‐shift (DBS) process at ambient temperature, with basic MnO2 in CH2Cl2 at room temperature, leads to the formation of the corresponding heptaleno[1,2‐c]furans 6a and 6d, respectively, as well as to the corresponding heptaleno[1,2‐c]furan‐3‐ones 7a and 7d, respectively (cf. Scheme 2 and 8). The formation of both product types necessarily involves a DBS process (cf. Scheme 7). The dehydrogenation reaction of the DBS isomer of 4a, i.e., 5a, with MnO2 in CH2Cl2 at room temperature results, in addition to 6a and 7a, in the formation of the heptaleno[1,2‐c]‐furan‐1‐one 8a and, in small amounts, of the heptalene‐4,5‐dicarbaldehyde 9a (cf. Scheme 3). The benzo[a]heptalene‐6,7‐dimethanol 4c with a fixed position of the CC bonds of the heptalene skeleton, on dehydrogenation with MnO2 in CH2Cl2, gives only the corresponding furanone 11b (Scheme 4). By [2H2]‐labelling of the methanol function at C(7), it could be shown that the furanone formation takes place at the stage of the corresponding lactol [3‐2H2]‐15b (cf. Scheme 6). Heptalene‐1,2‐dimethanols 4c and 4e, which are, at room temperature, in thermal equilibrium with their corresponding DBS forms 5c and 5e, respectively, are dehydrogenated by MnO2 in CH2Cl2 to give the corresponding heptaleno[1,2‐c]furans 6c and 6e as well as the heptaleno[1,2‐c]furan‐3‐ones 7c and 7e and, again, in small amounts, the heptaleno[1,2‐c]furan‐1‐ones 8c and 8e, respectively (cf. Scheme 8). Therefore, it seems that the heptalene‐1,2‐dimethanols are responsible for the formation of the furan‐1‐ones (cf. Scheme 7). The methylenation of the furan‐3‐ones 7a and 7e with Tebbe's reagent leads to the formation of the 3‐methyl‐substituted heptaleno[1,2‐c]furans 23a and 23e, respectively (cf. Scheme 9). The heptaleno[1,2‐c]furans 6a, 6d, and 23a can be resolved into their antipodes on a Chiralcel OD column. The (P)‐configuration is assigned to the heptaleno[1,2‐c]furans showing a negative Cotton effect at ca. 320 nm in the CD spectrum in hexane (cf. Figs. 3–5 as well as Table 7). The (P)‐configuration of (–)‐6a is correlated with the established (P)‐configuration of the dimethanol (–)‐5a via dehydrogenation with MnO2. The degree of twisting of the heptalene skeleton of 6 and 23 is determined by the Me‐substitution pattern (cf. Table 9). The larger the heptalene gauche torsion angles are, the more hypsochromically shifted is the heptalene absorption band above 300 nm (cf. Table 7 and 8, as well as Figs. 6–9).
On the Funicolides, Briaranes of the Pennatulacean Coral Funiculina quadrangularis from the Tuscan Archipelago: Conformational preferences in this class of diterpenes
Authors: Chiasera Giuseppe , Guerriero Antonio , D'Ambrosio Michele , Pietra Francesco 
Published: December 2004

AbstractKinetic and equilibrium NMR studies of briarane diterpenes isolated from the pennatulacean coral Funiculina quadrangularis showed that funicolide A (1), funicolide D (5), and brianthein W (6), with R2 = Hβ, undergo slow flipping by rotation of the C(1)C(2)C(3)C(4) dihedral angle, giving rise to two observable conformers in a 4:96 population ratio, both having an axial AcOC(14) and C(16) pointing ‘downwards’, but differing for pseudoaxial or pseudoequatorial position of R1O, respectively. δ(C) for the minor conformers could be quickly assigned by an original emulation methodology. Similar studies revealed that funicolide B (2), 7‐epifunicolide A (4), funicolide E (7), and unnatural epibrianthein W (8) undergo similar motions, where, however, the nature of the α‐positioned substituent R2 determines which conformer predominates: axial R1O for R2 = Hβ (4 and 8) or equatorial R1O for R2 α‐OH, (2 and 7). In contrast, funicolide C (3) proved to undergo slow conformational motions that involve also the cyclohexene ring, resulting in two observable conformers characterized by either an equatorial AcOC(14) and trans‐diaxial C(2)/C(9) or an axial AcOC(14) and trans‐diequatorial C(2)/C(9) in a 9:1 population ratio, respectively. These observations, and molecular‐mechanics calculations for briaranes known to exhibit broad NMR signals, lead to general views on the conformational preferences of diterpenes of this class.
4‐Amino‐1,5‐dihydro‐2H‐pyrrol‐2‐one aus Bortrifluorid‐katalysierten Umsetzungen von 3‐Amino‐2H‐azirinen mit Carbonsäure‐Derivaten
Authors: Hugener Martin , Heimgartner Heinz 
Published: December 2004

4‐Amino‐1,5‐dihydro‐2H‐pyrrol‐2‐ones from Boron Trifluoride Catalyzed Reactions of 3‐Amino‐2H‐azirines with Carboxylic Acid DerivativesReaction of 3‐amino‐2H‐azirines 1 with ethyl 2‐nitroacetate (6a) in refluxing MeCN affords 4‐amino‐1,5‐dihydro‐2H‐pyrrol‐2‐ones 7 and 3,6‐diamino‐2,5‐dihydropyrazines 8, the dimerization product of 1 (Scheme 2). Thus, 6a reacts with 1 as a CH‐acidic compound by CC bond formation via C‐nucleophilic attack of deprotonated 6a onto the amidinium‐C‐atom of protonated 1 (Scheme 5). The scope of this reaction seems to be rather limited as 1 and 2‐substituted 2‐nitroacetates do not give any products besides the azirine dimer 8 (see Table 1). Sodium enolates of carboxylic esters and carboxamides 11 react with 1 under BF3 catalysis to give 4‐amino‐1,5‐dihydro‐2H‐pyrrol‐2‐ones 12 in 50–80% yield (Scheme 3, Table 2). In an analogous reaction, 3‐amino‐2H‐pyrrole 13 is formed from 1c and the Li‐enolate of acetophenone (Scheme 4). A reaction mechanism for the ring enlargement of 1 involving BF3 catalysis is proposed in Scheme 6.
Preparation, Structure, and Properties of All Possible Cyclic Dimers (Diolides) of 3‐Hydroxybutanoic Acid
Authors: Seebach Dieter , Hoffmann Torsten , Kühnle Florian N. M. , Kinkel Joachim N. , Schulte Michael 
Published: December 2004

AbstractIn connection with the proposed structure of a trans‐membrane cellular ion channel consisting of a complex between poly[(R)‐3‐hydroxy butanoate] (P(3‐HB)) and calcium polyphosphate, CaPPi (ca. 150 units each), which is supposed to contain s‐cis‐bonds or even more highly strained ester conformations, we have prepared and studied the properties of the cyclic dimer of 3‐HB, the diolide 1. All possible forms of 1, the rac‐, the meso‐, and the enantiomerically pure (R,R)‐ and (S,S)‐compounds were prepared, purified, and characterized. The synthesis (Scheme 1) started from dimethyl succinate with the key step being the Baeyer‐Villiger oxidation of the rac‐ and meso‐2,5‐dimethylcyclohexane‐1,4‐diones 5. The rac‐diolide 1 was resolved by preparative chromatography on a Chiralcel OD column (Fig.1). The crystal structures of rac‐ 1 (Fig.3) and of meso‐ 1 (Fig.5) were determined by X‐ray diffraction: the diolides 1 contain s‐cis‐ester bonds and an ester group with a conformation half way to the transition state of rotation (Fig.2). Strain energies for the diolides 1 of up to 17.8 kcal/mol are suggested. Accordingly, these compounds show reactivities similar to those of carboxylic‐acid anhydrides or even acid chlorides. They cannot be chromatographed on silica gel, and they react with primary, secondary, and tertiary alcohols, and with amines to form derivatives of open chain 3‐HB ‘dimers’, hydroxy acids 6, esters 7, and amides 8 (Scheme 2). The rate of acid‐catalyzed ring opening of the diolides 1 with alcohols has been measured (Fig.6 and 7). From the results described, we conclude that it is unlikely for strained and reactive ester conformations to occur as part of ion channels through phospholipid bilayers of cells.