Abstract: A series of dendrimeric compounds bearing pyrene units were synthesized to afford light-harvesting antennae based on the formation of intramolecular excimers. The synthetic plan profited front the efficiency of the Huisgen reaction, the 1,3-dipolar cycloaddition of azides and terminal alkynes, which allowed ready assembly of the different building blocks. The three molecular antennae obtained, of increasing generation, revealed efficient energy transfer both in solution and in the solid state.
Abstract: A new organogelating moiety, 1, is proposed as a suitable and versatile building block for the production of other gelling compounds. Linking 1 with several different molecular fragments afforded new gels with different properties. A detailed investigation of the ferrocene substituted gelator is reported in this study.
Abstract: A series of 3-spirocyclopropanedihydro- and -tetrahydropyrid-4-ones have been synthesized by nitrone cycloaddition to 1,1â-bicyclopropylidene (BCP), chemoselective reduction of the N-O bond of the isoxazolidine ring, and Pd-II-catalyzed cascade rearrangement of the beta-anunocyclopropanol derivatives into the final products. The new tetrahydropyridone derivatives were also prepared by thermal rearrangement of the isoxazolidines.
Abstract: The synthesis of new organogelators based on a triazine nucleus is described together with the analysis of the properties of the main compound 15. This compound revealed an efficient organogelator in both polar and apolar solvents and represents a promising precursor of other functionalized organogelators. (c) 2008 Elsevier Ltd. All rights reserved.
Abstract: A protocol for the formal mixed addition of two different C-nucleophiles at C1 and C1âof N-glycosylnitrones has been developed. Addition of Grignard reagents to N-erythrosyl-N-benzylhydroxylamine I affords hydroxylamines 6 almost quantitatively with high diastereoselectivity. These compounds undergo regioselective oxidation to the corresponding C-phenyl nitrones 7, which in turn add a second Grignard reagent to give hydroxylamines 5. Synthetic usefulness of mixed bisadduct 5d has been proved by its enyne ring-closing metathesis to afford the densely functionalized unsaturated piperidine derivative 8.
Abstract: This work presents an experimental and computational study of the intramolecular electronic energy transfer process occurring in two newly synthesized bichromophoric species: N-(7-nitro-2,1,3-benzoxadiazol-4-yl)amino-bis-ethyl-2-[(4-chloro-1-nap hthyl)oxy]acetate (f-Bi) and N-(7-nitrobenzo[c][1,2,5]oxadiazole-4-yl)-(3S, 4S)-pyrrolidin-3,4-bis-yl-2-[(4-chloro-1-naphthyl)oxy]acetate (r-Bi). In both f-Bi and r-Bi the donor chromophore is the [(4-chloro-1-naphthyl)oxy]acetate moiety, whereas the acceptor units belong to the family of the 4-dialkylaminonitrobenzoxadiazoles, well-known fluorescent probes. The two bichromophores differ in the structural flexibility. In f-Bi, acceptor and donors are linked by a diethanolamine moiety, whereas in r-Bi through a (3S, 4S)3,4-dihydroxypyrrolidine ring. By means of steady-state and time-resolved UV-vis spectroscopies we carried out a detailed analysis of the photo-response of donor and acceptor chromophores as individual molecules and when covalently linked in f-Bi and r-Bi. The intramolecular energy transfer process occurs very efficiently in both the bichromophores. The rate constant and the quantum efficiency of the process are k(ET) = (2.86 +/- 0.16) x 10(11) s(-1) and Q = 0.998 in f-Bi, and k(ET) = (1.25+/-0.08) x 10(11) s(-1) and Q = 0.996 in r-Bi. Semiempirical calculations were utilized to identify the energy and the nature of the electronic states in the isolated chromophores. Molecular mechanics calculations have been performed to identify the most stable structures of the bichromophoric compounds. The predictions of Forster theory are consistent with the experimental results and provide a suitable way to evaluate the structural differences between the two compounds. (C) 2006 Elsevier B.V. All rights reserved.
Abstract: The synthesis of enantiopure cyclic nitrones has become a frequently addressed topic in discussions of their usefulness in the production of natural products and biologically active compounds. This emphasis has stimulated the development of a variety of synthetic approaches that are described in this review, organized on the basis of the size of the nitrone ring.
Abstract: The title compound, C29H49N3O4, is a model compound synthesized to obtain information on the intermomecular forces that drive the self-assembly of a similar compound bearing longer aliphatic chains. In the crystal, molecules are arranged in columns due to the formation of two antiparallel strong hydrogen-bonded chains by the carbamate units. The two long aliphatic chains are trans.
Abstract: Background: Indolizidine alkaloids widely occur in nature and display interesting biological activity. This is the reason for which their total synthesis as well as the synthesis of non-natural analogues still attracts the attention of many research groups. To establish new straightforward accesses to these molecules is therefore highly desirable. Results: The ring closing metathesis (RCM) of enantiopure hydroxylamines bearing suitable unsaturated groups cleanly afforded piperidine derivatives in good yields. Further cyclization and deprotection of the hydroxy groups gave novel highly functionalized indolizidines. The synthesis of a pyrroloazepine analogue is also described. Conclusion: We have developed a new straightforward methodology for the synthesis of densely functionalized indolizidines and pyrroloazepine analogues in 6 steps and 30-60% overall yields from enantiopure hydroxylamines obtained straightforwardly from carbohydrate-derived nitrones.
Abstract: The synthesis and the properties of a new chiral organogelator based on a C-2 symmetric pyrrolidine, are described together with its use for the synthesis of other functionalised organogelators.
Abstract: A new straightforward and inexpensive one-pot procedure is described for the preparation of enantiopure five-membered cyclic nitrones starting from the corresponding lactols. Its efficiency relies on the condensation of unprotected hydroxylamine with readily available lactols and on the chemoselectivity of the subsequent esterification with methanesulfonyl chloride. The targeted enantiomerically pure pyrroline N-oxides are versatile synthetic intermediates: one of the nitrones so-obtained has been converted into new polyhydroxypyrrolizidines, analogues of the alkaloids rosmarinecine and crotanecine, which were assayed for their inhibitory activities toward 22 commercially available glycosidase enzymes. One of them ((-)-7a-epi-crotanecine) is a potent and selective inhibitor of alpha-mannosidases from jack beans and almonds.
Abstract: 2-Chloro-2-cyclopropylideneacetates (1-Me and 1-Et) and their spiropentane analogues 2 cycloadd enantiopure five-membered cyclic nitrones to give the corresponding adducts (quantitatively, four examples), which undergo cascade ring enlargements to yield indolizinone derivatives (53-70%, four examples). The ring enlargement process is triggered by the abstraction of a bridgehead proton induced by a base and can be suppressed by the presence of a bulky substituent nearby, such as a (triisopropylsilyl)-oxy group.
Abstract: C-Pheynl-N-erythrosylnitrone 3 behaves as a C1,C1â bis-electrophile, undergoing a double addition of Grignard reagents in a domino fashion to afford acyclic hydroxylamines 4. The reaction proceeds at 0 degreesC with variable degrees of diastereoselectivity, from moderate to good. mainly depending on the organomagnesium reagent used. The usefulness of compounds 4 has been exemplified with the synthesis of pyrroloazepine 12 through a ring closing metathesis key step.
Abstract: The two-step metal-catalyzed overall transformation of isoxazolidine-5-spirocyclopropanes into the corresponding dihydro- and tetrahydropyridones is described. The first step is the chemoselective reduction of the N-O bond of the isoxazolidine ring preserving the fragile cyclopropanol moiety while the second transformation is the Pd(II) or Pd(O) conversion of the beta-aminocyclopropanol derivatives into the final compounds. The scope and limitations of this strategy are described.
Abstract: A practical synthesis of 2-aminomethyl- and 2-hydroxymethyl-3,4-dihydroxypyrrolidines via stereocontrolled addition of TMSCN and LiCH2OMOM to chiral 3,4 dihydro-2H-pyrroline N-oxides is reported. (C) 2004 Elsevier Ltd. All rights reserved.
Abstract: A new total synthesis of (2S,3R)-3-hydroxy-3-methylproline has been performed via a key intermediate chiral pyrroline N-oxide, obtained from (R)-citramalic acid. This nitrone underwent nucleophilic addn. of furyllithium with complete stereoselectivity through a preferential attack anti to the methoxymethoxy group. The correct stereochem. was established through an oxidn.-redn. sequence, which allowed inversion of configuration at C-2. [on SciFinder(R)]
Abstract: SmI2 was used as reducing agent for the N-O bond cleavage in isoxazolidines. The procedure revealed is general and particularly useful for the transformation of 5-spirocyclopropane isoxazolidines to the corresponding beta-aminocyclopropanols, a troublesome transformation with other known reagents. (C) 2004 Elsevier Ltd. All rights reserved.
Abstract: beta-Aminocyclopropanols were transformed, in a domino process catalyzed by Pd(II) salts, into the corresponding 2,3-dihydro-1H-pyridin-4-ones. Conversely the use of a Pd(0) derivative, Pd(dba)(2), afforded the corresponding tetrahydropyrid-4-ones. The saturated derivatives were also obtained, in better yields, using Pd(II) and Cu(OAc)(2) as stoichiometric oxidant.
Abstract: N-benzyl- and N-methyl-N-glycosylhydroxylamines 3a-i were conveniently obtained by reaction of sugars with N-substituted hydroxylamines according to a novel procedure. Subsequent oxidation occurred at the alkyl group, selectively affording the corresponding C-phenyl- and C-unsubstituted N-glycosylnitrones. C-phenyl-N-glycosylnitrones 10 and 13 under-went highly stereoselective 1,3-dipolar cycloaddition with dimethyl maleate, with the sugar moiety acting as a chiral auxiliary. Final removal of the glycosyl moiety afforded enantiopure enantiomeric isoxazolidines 17 and ent-17 which are oxa-analogues of proline diester derivatives. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).
Abstract: Iteration of organometallic addition to chiral hydroxylated pyrroline N-oxides through an addition-oxidation-addition synthetic sequence allowed highly stereoselective double alkylation of pyrrolidine at C-2 or at C-2 and C-5 depending on the regioselectivity of the oxidation step. Application of this methodology has been exemplified by the synthesis of the all-substituted pyrrolidine alkaloid (-)-codonopsinine and of proline-type amino acid precursors possessing a quaternary stereogenic center, whose configuration can be controlled.
Abstract: A highly diastereoselective addition of lithiated methoxyallene 3 to chiral cyclic nitrones 1 and 2 provided N-hydroxy pyrrolidines 4 and 5, respectively, which cyclized to bicyclic 1,2-oxazines 6 and 7 by simple stirring in dilute CH22Cl solution. Storage of 4 in a more concentrated solution led to formation of a 60:40 mixture of 1,2-oxazine 6 and amine oxide 8. Hydroboration of 7 furnished the hydroxy-substituted bicyclic 1,2-oxazine 9 with excellent diastereoselectivity. Hydrogenolysis of 6 provided the substituted pyrrolidine derivative 10. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).
Abstract: The mild cyanating agent trimethylsilyl cyanide adds with total stereo selectivity to alpha-alkoxy cyclic nitrones to afford the corresponding trans-hydroxyaminonitriles. The addition of Lewis acids to precomplexing the nitrones does not affect the stereoselectivity of these additions significantly. In all of the cases examined, excellent yields of diastereomerically homogeneous products were obtained. On the other hand, the use of diethylaluminum cyanide as cyanating agent leads to low diastereoselectivities. Both NMR studies and theoretical calculations show that whereas the addition of trimethylsilyl cyanide takes place through a concerted mechanism, in the addition of diethylaluminum cyanide, a complex is formed prior to the intramolecular delivery of the cyanide ion. (C) 2003 Elsevier Science Ltd. All rights reserved.
Abstract: The synthesis of two new bicyclic nucleoside analogues is reported. These compounds are iso-homonucleoside and are synthesised through a 1,3-dipolar cycloaddition of an enantiopure cyclic nitrone to protected allyl acohol and subsequent introduction of thymine by a Mitsunobu reaction. (C) 2003 Elsevier Science Ltd. All rights reserved.
Abstract: The synthesis of a new pseudopeptide material based on a chiral pyrrolidine skeleton is described. One of these new compounds interacts, in chloroform solution, selectively with amines.
Abstract: [GRAPHICS] A novel and simple procedure for reduction of hyproxylamines to the corresponding amines by means of indium powder in aqueous media is reported. Applicability to one-pot reactions and isoxazolidine N-O bond reduction is also demonstrated. A catalytic version of the process using 2-5% In in the presence of other metals (Zn, Al) has been successfully developed.
Abstract: The enantiomerically pure nitrone 3, a valuable precursor of mono- and bicyclic azaheterocycles, has been synthesized in 57% yield by a novel âone-potâ process starting from lactol 1, in turn readily available from D-arabinose. The same process, consisting of reaction with a O-silyl-protected hydroxylamine followed by mesylation in pyridine. furnished ent-3 in 55% yield when applied to L-arabinose.
Abstract: The authors were able to observe that the conjugation of a glycosyl moiety to an Asn (N-glycosidic linkage) in the glycopeptide CSF114(Glc) allowed the detection of specific antibodies in sera of patients with multiple sclerosis (MS). Data showed the relevance of the presence of a sugar moiety, favorably presented by a ò-hairpin structure to a glycosylated epitope, for antibody recognition in MS. We synthesized a new Fmoc-protected amino acid bearing dihydroxypyrrolidine azasugar and introduced it into the CSF114 sequence. [on SciFinder(R)]
Abstract: The oxidation of a C-2 symmetric piperidine, obtained through a ring enlargement process of the enantiopure protected (4R)-hydroxy-(2S)-hydroxymethyl pyrrolidine, is reported. Oxidation with C-phenyl-N-phenylsulfonyloxaziridine afforded the corresponding nitrone that is too unstable for isolation and which reacted in situ with dimethyl maleate. The major adduct was transformed to the corresponding protected dihydroxyindolizidinone. (C) 2002 Elsevier Science Ltd. All rights reserved.
Abstract: Unprotected pyrimidine bases were used in Mitsunobu reaction to afford in high yield new substituted pyrrolidines. The reaction is chemo-, regio- and stereoselective affording exclusively N-1 alkylated derivatives of (3S)-N-benzyl-3-hydroxy-pyrrolidine and (3S,4S)-N-benzyl-3,4-dihydroxypyrrolidine. (C) 2002 Elsevier Science Ltd. All rights reserved.
Abstract: A practical synthesis of N-benzyl-N-glycosylhydroxylamines 3 (R = CH2Ph) is reported. The ability of these compounds to act as versatile synthetic intermediates is demonstrated by their oxidation followed by cycloaddition to N-glcosyl isoxazolidines and by the novel direct cycloaddition as masked acyclic. highly functionalized chiral nitrones. (C) 2002 Elsevier Science Ltd. All rights reserved.
Abstract: Several alpha -spirocyclopropanated heterocyclic ketones were converted to the corresponding cyclopentene-anellated heterocycles in moderate to good yields (overall 31-60%) by Wadsworth-Emmons olefination followed by thermal rearrangement of the formed vinylcyclopropanes. In this sequence, the phosphonoacetonitrile was found to be superior to phosphonoacetate in the Wadsworth-Emmons olefinations of tetrahydropyridones.
Abstract: Cyclobutylidenecyclopropane (7) was prepared in multigram quantities by a new three-step sequence starting from ethyl cyclobutanecarboxylate (4) (39% overall yield), 1,3-Dipolar cycloadditions of phenyl- (9), pyridyl- (10), and the newly prepared (four steps, 43% overall yield) spirocyclic nitrone 11 onto 7 resulted in the regioselective formation of the corresponding adducts 15-17, with the spirobutane moieties adjacent to the oxygen atom in the oxazolidine rings, in 52, 84, and 48% yields, respectively. Under flash vacuum pyrolysis conditions, the cycloadducts 15-17 underwent thermal rearrangement with opening of the four-membered ring, to afford the spirocyclopropanated azepinones 21-23 in 32, 30, and 19% yields, respectively. In the case of 17, the indolizidinone 25 was also isolated (13% yield). Mechanistically this rearrangement is interpreted in terms of a cyclobutylmethyl-to-penten-5-yl radical rearrangement.
Abstract: Several structurally differentiated N,N-dialkylhydroxylamines were oxidised to the corresponding nitrones using MnO2. Manganese dioxide revealed an efficient and mild reagent for oxidation of hydroxylamines, showing a level of regioselectivity comparable to HgO. Its non-toxicity makes MnO2 the reagent of choice for replacing HgO in this oxidation. (C) 2001 Elsevier Science Ltd. All rights reserved.
Abstract: The synthesis of new five-membered enantiopure cyclic nitrones bearing protected cis vicinal amino and hydroxy functionalities is reported. The key step was a Mitsunobu reaction, which allowed placement of an azido group, with inversion of configuration, at the reacting centre. Cycloaddition of the novel nitrones to but-3-en-1-ol followed by simple elaboration of the adducts readily afforded protected amino dihydroxy indolizidines. (C) 2000 Elsevier Science Ltd. All rights reserved.
Abstract: The cycloaddition reactions of dimethyl maleate to three functionalized enantiopure pyrroline N-oxides and one related racemic nitrone are reported. The study of the diastereoselectivity in the cycloaddition has been carried out by ample variation of the substituents at both the dipole and dipolarophile counterparts. The major cycloadducts, derived from the preferred exo-anti transition states and formed with 62-90% diastereoselectivity, have been subjected to Mo(CO)G-induced reductive ring-opening to afford directly highly functionalized enantiopure pyrrolizinone derivatives, valuable as synthetic intermediates. Applications of this strategy to a straightforward formal synthesis of (-)-hastanecine and to the total synthesis of the novel 7-epi-croalbinecine and of (-)-croalbinecine are reported.
Abstract: A review with 39 refs., on synthetic methods, properties, and applications of dendrimers and dendritic polymers. Synthetic methods (convergent and divergent routes), catalysts, and selection of core species are discussed. Characteristics of metallo-dendrimers, supramol. structure, and applications of dendrimers in catalysis, encapsulation, and mol. recognition are described. [on SciFinder(R)]
Abstract: The total synthesis of natural products requires selective methods to adapt to the structural complexity the nature has introduced in natural compds. From this challenge derives the impetus to find new reactions, new reagents and new catalysts to run reactions in a chemoselective, regioselective and stereoselective way. Recently, domino or multicomponent, combinatorial or enzymic processes, have expanded the synthetic tools available to researchers, and topics like atom economy and environmentally friendly syntheses became the concern of org. chemists. Having in mind all these points we approached the synthesis of natural products like glycosidase inhibitors, belonging to the classes of indolizine and pyrrolizine alkaloids, which are attracting growing interest from synthetic chemists for their various and essential biol. activities. [on SciFinder(R)]
Abstract: Oxidation of N,N-disubstituted hydroxylamines to nitrones catalyzed by the Jacobsen catalyst occurs cleanly in the presence of hydrogen peroxide, sodium hypochlorite or iodosylbenzene as the stoichiometric oxidant. Meso 3,4-cis-isopropylidenedioxy-1-hydroxypyrrolidine gave the corresponding protected 3,4-cis-dihydroxypyrroline N-oxide in an enantioenriched fashion for the first time (up to 36% e.e.). (C) 1999 Elsevier Science Ltd. All rights reserved.
Abstract: The symposium proceedings from 14th conference on phosphorus chem. is reviewed with 12 refs. Enantiopure five-membered ring nitrones derived from L-tartaric acid and from L-malic acid undergo highly regio- and stereoselective cycloaddn. reactions with an excess of racemic 2,3-dihydro-1-phenyl-1H-phospholes producing two readily separable tricyclic cycloadducts and concomitantly effecting kinetic resoln. of the dihydrophosphole deriv. Stereochem. of the cycloaddn. process and scope of the kinetic resoln. process have been established in details and adjusted to produce dihydrophosphole derivs. in good yields and in very high optical purity. To effect syntheses of single cycloadducts of 100% ee the techniques of doubly asym. synthesis and parallel kinetic resolns. have been employed. The resulting tricyclic cycloadducts feature 2,2â-connection of pyrrolidine and phospholane rings and five to seven contiguous stereogenic centers of which three have been induced and one or two kinetically resolved during the cycloaddn. process. [on SciFinder(R)]
Abstract: Enantiomerically pure, five membered cyclic nitrones, easily obtained in large amounts from protected hydroxyacids and aminoacids such as D- and L-tartaric, L-malic, and L-aspartic acids, give cycloaddition reactions with a good diastereocontrol. The adducts of L-malic and L-aspartic acids derived from addition of nitrones to dimethyl maleate and gamma-crotonolactone were easily converted into enantiopure pyrrolizidinones, which can be transformed into polyhydroxypyrrolidines or polyhydroxypyrrolizidines, both interesting compounds as potential glycosidase inhibitors. The method is suitable for natural products synthesis as exemplified by a straightforward and convenient access to the pyrrolizidine alkaloid necine base (-)-hastanecine, as well as to indolizidine alkaloids, i.e. (+)-lentiginosine.
Abstract: A review with 17 refs. in which hydroxylated pyrroline-N-oxides provide a general entry to the synthesis of polhydroxylated pyrrolizidine and indolizidine alkaloids. [on SciFinder(R)]
Abstract: (3S,4S)-N-Benzyl-3,4-dihydroxypyrrolidine 1 has been used as a building block for new enantiopure macrocyclic polyesters, Two different synthetic approaches are presented leading to complementary results, The structure of the macrocycles synthesized has been confirmed by NMR spectroscopy and FAB mass spectrometry, and that for dimer 8 has been confirmed by X-ray analysis.
Abstract: A protocol is presented for a completely enantioselective format desymmetrization of C-s-symmetric diols by monoprotection of the corresponding enantiopure C-2 diols, followed by an inversion of configuration by a Mitsunobu reaction (âMitsunobu trickâ). Its application to the unprecedented synthesis of enantiopure cis-3,4-dihydroxypyrroline N-oxides, employed in the enantiodivergent synthesis of two selectively protected 1,2,7-trihydroxyindolizidines, is also reported.
Abstract: The synthesis of the first and second generation of enantiopure dendrimers based on a chiral trans-3,4-dihydroxypyrrolidine is reported. Benzenepolycarboxylic acids were used as central nucleus to afford linear and radial growth, and terephthalic acid was used as spacer between the pyrrolidine nuclei. The analysis of the chiroptical properties ([alpha](D), circular dichroism) of these new dendrimers suggests that those with radial growth present a self organisation of chiral units.
Abstract: The syntheses of four new, differently O-substituted 3-hydroxypyrroline N-oxides and the first 3-amino analogue have been performed by the use of a strategy involving double nucleophilic displacement of the corresponding dimesylates by hydroxylamine and oxidation of the resulting 1-hydroxypyrrolidines. The regioselectivity data of the oxidation reactions nicely confirm the mechanistic hypothesis, which explains the dependence on the electronic nature of the substituent. The trend of the regioselectivity ratio has useful predictive value. Practical complete regioselection has been obtained by substitution with a benzoyloxy functionality. The O-allyl-substituted nitrone is not stable in the reaction conditions, undergoing immediately an intramolecular cycloaddition reaction with complete stereocontrol and inversion of regio- and stereoselectivity with respect to the intermolecular case.
Abstract: The straightforward synthesis of new enantiopure gamma-aminoalcohols through 1,3-dipolar cycloadditon to a chiral cyclic nitrone derived from L-malic acid is described. Results of the application of these compounds as chiral catalysts in the alkylation of benzaldehyde with diethylzinc are also reported. (C) 1997 Elsevier Science Ltd.
Abstract: Hexahydro-, 5b-1 and 6a,f,l and tetrahydropho spholo[2,3-d]isoxazoles 8, 9 and 10 were synthesized by 1,3-dipolar cycloaddition of nitrones 3b-1 and benzonitrile oxide (4) to 2,3-dihydro-1-phenyl-1H-phosphole 1-oxide (1) and 2,3-dihydro-1-ethoxy-1H-phosphole 1-oxide (2). The structural assignment to the compounds was confirmed by an X-ray study of two compounds of the series 5a and 5m. The compounds show a good activity as fungicides against Plasmopara viticola on vines and against Botrytis cinerea on apples. Compounds 5a-d showed weak to moderate activity as herbicides.
Abstract: A pi-acidic, totally synthetic HPLC chiral stationary phase is used to separate the enantiomers of a wide range of unsaturated P-chiral phosphine oxides. If allows for fast, sensitive and accurate e.e. determinations and secures easy access to opfically pure enantiomers by chromatography on preparative columns.
Abstract: The chiral optically pure five-membered 3-tert-butoxy-1-pyrroline N-oxide (1) was synthesized by a convenient five-step procedure from diethyl L-malate. The key step is the regioselective HgO dehydrogenation of the N-hydroxypyrrolidine 6 obtained by double-nucleophilic displacement of a (bis)mesylate with hydroxylamine. A rationalization of the observed regioselectivity of the oxidation by studying the oxidation of a deuterated N-hydroxypyrrolidine 20 is reported. Nitrone 1 has been applied to the synthesis of a new (1S,7S,8aR)-1,7-dihydroxyindolizidine (28) via 1,3-dipolar cycloaddition strategies.
Abstract: A new approach to the synthesis of chiral P,N-ligands containing a stereogenic phosphorus atom is reported; the synthesis, characterization and coordination properties of (PR, 2R, 3R, 2âR, 3âS, 4âS) 2[2â(3â,4â-di-tert-butoxy-1â-methyltetrahydropyrrolyl)]-3-methoxy-1-ph enyltetrahydrophosphole (P*-N-1), which contains a stereogenic phosphorus in addition to five contiguous stereocentres in the ligand backbone; compound P*-N-1 represents the first example of a new class of chiral P,N-ligands with the heteroatoms incorporated in two 2,2â-coupled pyrrolidine-phospholane rings.
Abstract: The structure and abs. configuration of natural (+)-lentiginosine (I) isolated from plant sources was detd. to be (1S,2S,8aS)-1,2-dihydroxyindolizidine on the basis of synthesis of both enantiomers and their inhibition of amyloglucosidases. (+)-I was derived from (L)-(+)-tartaric acid via a highly stereo- and regioselective 1,3-dipolar cycloaddn. of (3S,4S)-3,4-bis[(tert-butyldiphenylsilyl)oxy]-1-pyrroline N-oxide to methylenecyclopropane, followed by thermal rearrangement of the adduct into (1S,2S,8aS)-1,2-[(tert-butyldiphenylsilyl)oxy]octahydroindolizin-7-one. (-)-I was derived in the same way from (D)-(-)-tartaric acid. Both (+)-I and (-)-I displayed inhibition specificity for amyloglucosidases, being inactive toward 17 other glycosidases. With amyloglucosidase from Aspergillus niger, (+)-I displayed inhibition (Ki = 2 ÃÅM) 5 times stronger than that reported for natural lentiginosine, 35 times that measured for (-)-I, and twice that of castanospermine. (+)-I is thus the most potent and specific competitive inhibitor of amyloglucosidases among azasugars and their analogs. [on SciFinder(R)]
Abstract: The structure and abs. configuration of the predominant I of the two diastereomeric 7,8-di-tert-butoxy-1-phenyloctahydro-1H-pyrrolo[1,2-b]phospholo[2,3-d]isoxazole 1-sulfides obtained in the kinetic resoln. expt. involving cycloaddn. reaction of (S,S)-3,4-di-tert-butoxy-3,4-dihydro-2H-pyrrole 1-oxide (1) with an excess of racemic 2,3-dihydro-1-phenyl-1H-phosphole 1-sulfide (2), was detd. by a single-crystal x-ray diffraction technique. C22H34O3NPS, trigonal, space group P31, a = b 11.831(1), c 14.761(2) ÃÂ, ñ = ò 90, ó = 120.ð, Z = 3. The structure was solved by direct methods and was refined by full matrix least-squares calcns. to R = 0.031 and Rw = 0.036 using 3737 unique reflections with I > 3ÃÂ(I). The abs. configuration of the studied mol. was detd. by calcn. of the ETA (÷) parameter and is 1S, 3aR, 7S, 8S, 8aR, 8bR. This finding assigns unequivocally the S configuration to the faster reacting enantiomer of 2 and correspondingly the R configuration to the isolated slower reacting (-)-2. It also confirms fully the notion that in the cycloaddn. transition state 1 and 2 prefer to approach each other in the exo mode and from the ring faces opposite to P-Ph and C3-O-t-Bu substituents, resp. [on SciFinder(R)]
Abstract: The structure and absolute configuration of the predominant of the two diastereomeric 7,8-di-tert-butoxy-1-phenyloctahydro-1H-pyrrolo[1,2-b]phospholo[2,3- d]isoxazole 1-sulfides obtained in the kinetic resolution experiment involving cycloaddition reaction of (S,S)-3,4-di-tert-butoxy-3,4-dihydro-2H-pyrrole 1-oxide (I) with an excess of racemic 2,3-dihydro-1-phenyl-1H-phosphole I-sulfide (2), was determined by a single-crystal X-ray diffraction technique. C22H34O3NPS, trigonal, space group P3(1), a = b = 11.831(1), c = 14.761(2) Angstrom, alpha = beta = 90 degrees, gamma = 120 degrees, V = 1789(4) Angstrom(3), Z = 3. The structure was solved by direct methods and was refined by full matrix least-squares calculations to R = 0.031 and R(w) = 0.036 using 3737 unique reflections with I > 3 sigma(I). The absolute configuration of the studied molecule was determined by calculation of the ETA (eta) parameter and was found to be 1S, 3aR, 7S, 8S, 8aR, 8bR. This finding assigns unequivocally the S configuration to the faster reacting enantiomer of 2 and correspondingly the R configuration to the isolated slower reacting (-)-2. It also confirms fully the notion that in the cycloaddition transition state 1 and 2 prefer to approach each other in the exo mode and from the ring faces opposite to P-Ph and C3-O-t-Bu substituents, respectively.
Abstract: The total synthesis of Lentiginosine (3) is reported. The strategy is based on the 1,3-dipolar cycloaddition of a TBDPS protected 3,4-dihydroxypyrroline N-oxide to methylenecyclopropane followed by the thermal rearrangement of the resulting spirocyclopropaneisoxazolidine to give the functionalised indolizidine skeleton. The compound shows an [alpha](D) value identical, but opposite in sign, with that reported for the natural isomer which has been assigned the same absolute configuration.
Abstract: Enantiomerically pure five-membered ring nitrones derived from L-tartaric acid via C2-symmetric O,Oâ-protected 3,4-dihydroxy pyrrolidines undergo highly regio- and stereoselective cycloaddition reactions with racemic 2,3-dihydro-1-phenyl-1H-phosphole 1-oxide and 1-sulfide. In all cases formation of only two diastereomeric cycloadducts is observed and their ratio (up to 10:1) is dependent on the size of the protecting groups in the nitrone and on the extent of conversion. The tricyclic cycloadducts feature 2,2â-connection of pyrrolidine and phospholane rings and six contiguous stereogenic centers of which three are created and the one at phosphorus is kinetically resolved during the cycloaddition process. It is established that in the studied kinetic resolutions the stereoselectivity factor 8 = k(S)/k(R) exceeds the value of 10 (up to 14) in the most favorable cases. In a properly tuned reaction both the diastereomeric cycloadducts and the enantiomerically enriched dihydrophosphole derivative can be simultaneously obtained in satisfactory chemical and optical yields.
Abstract: The 1,3-dipolar cycloaddition of nitrones with chiral vinylphosphine oxides or sulfides provides 5-phosphinyl substituted isoxazolidines with selectivity up to 99:1. Use of chiral nitrones allows a more generalized stereoselective synthesis of these compounds, also by means of a double asymmetric induction. With a racemic phospholene oxide, the high diastereofacial selectivity of the cycloaddition gives rise to a single 4-phosphinyl substituted isoxazolidine from each enantiomer. Moreover, a certain degree of enantiomeric discrimination permits a partial kinetic resolution of the phospholene oxide.
Abstract: The 1,3-dipolar cycloaddition of nitrones to vinylphosphine derivatives gives valuable new phosphinyl- and phosphino-substituted isoxazolidines also in optically pure form. A complete study of the regioselectivity and stereoselectivity of the cycloaddition is reported. Cycloaddition to chiral vinylphosphine derivatives allow the postulation of a transition state geometry able to explain the diastereoface control of the allylic phosphorus stereocentre.
Abstract: Carbon centered radicals derived from reactions of halides 3-5 with Bu3SnH in the presence of AIBN have been trapped by diphenylvinylphosphine oxide 2 giving the addition products 6-8 in high yields. Free radical addition to 2 employing the Barton methodology gave lower yields. The use of chiral (racemic) vinylphosphine oxides allowed a stereoselective radical addition with a diastereomeric ratio as high as 9:1 for mesitylmethylvinylphosphine oxide 1.
Abstract: The asymmetric 1,3-dipolar cycloadditions of the chiral alpha,beta-dialkoxynitrones (4S)-(Z)-N-(2,2-dimethyl-1,3-dioxolan-4-yl)methylenebenzylamineN-oxide 3 and (4S,5S)-(Z)-N-(2,2,5-trimethyl-1,3-dioxolan-4-yl) methylenebenzylamine N-oxide 4a to diphenylvinylphosphine oxide 2 give, besides complex mixtures of all the possible regio- and diastereoisomers, one major isomer, 5a and 8a respectively, consisting of 65% of the total isomeric amount. This compounds have been assigned the erythro C(3)-C(4â) configurations deriving from the most reactive conformation A or B through an endo transition state. The cycloaddition of the same nitrones with racemic and enantiomerically pure (-)-S-methylphenylvinylphosphine oxide (1) allowed the study of the double asymmetric induction. The selectivity towards the erythro compounds increases remarkably to ca. 40:1 for the endo approach, indicating that (2S)-nitrones 3 or 4a and (S)-phosphine oxide 1 constitute a matched pair of reactants. The synthesized phosphinylisoxazolidines can be conveniently transformed into selectively protected C-phosphinyl-aminotriols. An illustrative example of the synthesis of the novel fully and selectively protected 1-phosphinyl-seco-daunosamine 22 is reported.
Abstract: Meaningful diastereofacial selectivity in cycloaddition of 2,2-dimethyl-3,4-pyrroline N-oxide (DMPO) to 12 structurally diversified vinylphosphine derivatives 1-12 has been achieved by proper choice of the polar substituent on phosphorus combined with effective steric differentiation of the remaining substituents. The unique sense of induction in all these reactions is consistent with the assumption that vinylphosphorus dipolarophiles prefer an s-cisoid array of C = C - P = X fragments in their reactive conformations. Use of divinylphosphine derivatives in such reactions exemplifies the possibility of synthesizing chiral phosphine oxides and sulfides from prochiral precursors in a highly selective and stereochemically predictable manner. An observation that in P-31 NMR spectra the adducts of type I are uniformly found at lower field than adducts of type II facilitates the stereochemical assignments.
Abstract: The 1,3-dipolar cycloaddition reaction of N-alkyl nitrones with diphenylvinylphosphines affords directly isoxazolidinylphosphines in satisfactory yields and in regio- and stereoselective manner. The parent diphenylvinylphosphine was found to favor the formation of 5-phosphinoisoxazolidines whereas diphenylpropenylphosphine gave instead the 4-phosphinoisoxazolidine regioisomer. However, in reactions utilizing an alkylarylvinylphosphine and/or N-arylnitrone, oxidation of the phosphine by the nitrone reagent was found to precede the cycloaddition. An attempted conversion of the bicyclic isoxazolidine derived from 2,2-dimethyl-dihydro-2H-pyrrole 1-oxide and diphenylvinylphosphine to the perhydropyrrolo[1,2-c] [1,3,2]oxaza-phosphorine ring system was accomplished through the use of the corresponding phosphine oxide derivative and provided a single diastereoisomer of the desired pyrrolooxazaphosphorinane characterized ultimately in the form of its dioxide hydrate by the X-ray diffraction technique.
Abstract: The structure of the major product of the cycloaddition of 2,2-dimethyl-3,4-dihydro-2H-pyrrole N-oxide to tert-butyldivinylphosphine sulfide was analyzed by means of single-crystal X-ray diffraction technique. The analysis revealed two crystallographically independent molecules that differed in conformation of the fused five-membered heterocyclic rings. These rings were found to be two envelopes in one molecule and two half-chairs in the other. The studied compound was identified as an exo adduct of the expected erythro configuration and was found to favor a conformation in which the P = S and ring C-O bonds were anti and the C = C = P = S moiety was in the s-cis array. C14H26NOPS, space group P1BAR, a = 10.6004(7) angstrom, b = 12.3225(6) angstrom, c = 13.4404(7) angstrom, alpha = 104.073(4)-degrees, beta = 92.758(4)-degrees, gamma = 95.968(5)-degrees, V = 1688.802(4) angstrom3, Z = 4.
Abstract: The cycloadditions of nitrones with 2,3-dihydro-1-phenyl-1H-phosphole 1-oxide give a single cycloadduct deriving from a highly diastereoselective approach of the nitrone anti to the phenyl ring of phospholene oxide. When the chiral gliceraldehyde derived nitrone is used, only two diastereoisomers are produced in 1.7:1 ratio. The structural assignment based on NMR data and X-ray analysis of the major isomer established a trans C3-C4 stereochemistry (derived from endo TS with respect to nitrone) and a C3-C4â relative stereochemistry of threo type in the major isomer and erythro in the minor one. Therefore, each enantiomer of phospholene oxide 6 gives exclusively one cycloadduct with five contiguous stereogenic centres in an established and predictable absolute configuration. The difference of reactivity of the two enantiomers allowed a partial kinetic resolution of the racemic phospholene oxide, affording (+)-(S) enantiomer with 90% enantiomeric excess.
Abstract: A review on five-membered ring systems with O and N atoms. This review covers recent progress in transition metal-catalyzed cross-coupling reactions using isoxazoles. [on SciFinder(R)]
Abstract: A review of the prepn. and synthetic applications of of imidic acid derivs. featuring C-heteroatom-substituted nitrones and other dipoles. [on SciFinder(R)]
Abstract: A review on total syntheses of natural products published in the most important journals of org. chem. (listed) during the year 2003 (partial and formal syntheses as well as syntheses of structural analogs are excluded; also syntheses of nucleotides, nucleic acids, polypeptides, and polysaccharides are not referred). The total syntheses of (-)-tetrodotoxin and (+)-discodermolide are discussed in detail. [on SciFinder(R)]
Abstract: A review on the current advances in the chem. of five-membered ring systems with O and N atoms, particularly isoxazoles, isoxazolines, isoxazolidines, oxazoles, oxazolines, oxazolidines, and oxadiazoles. [on SciFinder(R)]
Abstract: A review discusses the reaction mechanism, synthesis, structure and properties of various oxygen and nitrogen heteroatoms, such as isoxazoles, isoxazolines, isoxazolidines, oxazoles, oxazolines oxazolidines, and oxadiazoles. [on SciFinder(R)]
Abstract: A review on the synthesis of five-membered heterocycles contg. oxygen or nitrogen atoms. Examples of compds. prepd. include isoxazoles, isoxazolines, isoxazolidines, oxazoles, oxazolines, oxazolidines, and oxadiazoles. [on SciFinder(R)]
