Showing papers on "Intramolecular reaction published in 1996"

Olefin Metathesis in Cyclic Ether Formation. Direct Conversion of Olefinic Esters to Cyclic Enol Ethers with Tebbe-Type Reagents

Abstract: Department of Chemistry, The Scripps Research Institute 10666 North Torrey Pines Road, La Jolla, California 92037 Department of Chemistry and Biochemistry UniVersity of California, San Diego 9500 Gilman DriVe, La Jolla, California 92093 ReceiVed October 17, 1995 The olefin metathesis reaction1 is rapidly emerging as a powerful tool in organic synthesis.2 Of particular interest are ring forming metathesis reactions catalyzed by transition metal complexes, several elegant examples of which have recently appeared.3 Despite the successes of this general approach to ring construction, much remains to be improved in terms of scope, convenience, and generality. In this communication we report a new strategy, based on the olefin metathesis reaction, for the generation of cyclic enol ethers directly from olefin esters4 using the Tebbe5 or the Petasis reagents.6 Scheme 1 shows the general concept7 for the envisioned Tebbe-reagent-mediated transformation of olefinic esters of type I to cyclic enol ethers of type VI. Thus it was anticipated that the initially formed enol ether II would react with a second molecule of the Tebbe reagent to afford the titanacyclobutane III, fragmentation of which would then lead to titanium alkylidene IV. Intramolecular reaction of IV was then expected to lead to titanacyclobutane V, whose regioselective fragmentation as shown should allow an entry to the desired cyclic enol ethers VI via olefin metathesis. Implementation of this strategy using olefinic ester 1 leads to the formation of cyclic enol ether 3 via the initially formed methylenation product 2 in 71% overall yield (Scheme 2). The intermediacy of compound 2 was proven by isolation and full spectral characterization followed by conversion to 3 under the influence of the Tebbe reagent. The generality and scope of this new process was investigated by employing a variety of substrates. As illustrated in Table 1, the reaction can deliver a series of sixand seven-membered cyclic enol ethers in good yields (entries 1-3 and 10-12, respectively). In addition to these findings, the important observation of the open-chain products shown in entries 6-9 (Table 1) was made. These hydroxy exomethylenic compounds are presumably obtained by sequential hydrolysis and olefination of the initially formed cyclic enol ethers.8 Apparently the lability of the enol ether products depends on their precise environment and the reaction conditions, a circumstance that

Divergent Pathways in the Intramolecular Reactions between Rhodium-Stabilized Vinylcarbenoids and Pyrroles: Construction of Fused Tropanes and 7-Azabicyclo[4.2.0]octadienes

Abstract: The rhodium(II)-catalyzed intramolecular reaction between vinyldiazomethanes and pyrroles leads to a novel synthesis of fused tropanes. The reaction occurs by a stepwise 3 + 4 annulation mechanism between a rhodium-stabilized vinylcarbenoid intermediate and the pyrrole rather than by the typical tandem cyclopropanation/Cope rearrangement sequence. The outcome of the reaction is very sensitive to the vinylcarbenoid structure. In particular, the presence of a 2-siloxy substituent on the vinylcarbenoid strongly favors the formation of fused tropanes. In the absence of such functionality, the formation of fused 7-azabicyclo[4.2.0]octadienes becomes the dominant reaction pathway.

Measurement of Internal Acyl Migration Reaction Kinetics Using Directly Coupled HPLC−NMR: Application for the Positional Isomers of Synthetic (2-Fluorobenzoyl)-d-glucopyranuronic Acid

Abstract: Ester glucuronides (1-O-acyl-β-d-glucopyranuronates) of many drugs may undergo internal acyl migration reactions, resulting in the formation of new positional isomers with both α- and β-anomers. We...

Synthesis of 4-Alkyl-4-alkoxybutenolides Having Unsaturated Side Chains via Chromium Carbene Complex Photochemistry: (+)-Cerulenin.

Abstract: The photochemical reaction between optically active ene carbamates and chromium alkoxycarbene complexes containing unsaturated aliphatic side chains was further developed. Although remote olefinic groups, including conjugated dienes, were tolerated, a homoallylic side chain underwent intramolecular reaction to give a strained cyclobutanone. (+)-Cerulenin was synthesized utilizing the photochemical reaction of an alkynylcarbene complex with an optically active ene carbamate and the bis(π-crotyl)nickel halide alkylation of a vinyl bromide as key steps.

Intramolecular condensation reactions of {alpha},{omega}-bis(triethoxysilyl)alkanes. Formation of cyclic disilsesquioxanes

Abstract: In this paper, we used mass spectrometry and {sup 29}Si NMR spectroscopy to discover that the length of the alkylene-bridging groups had a pronounced effect on the competition between cyclization and polymerization of {alpha},{omega}-bis(triethoxysilyl)alkanes and on the formation of polymeric gels. While the intramolecular reaction clearly slows gelation, the cyclic disilsesquioxanes are still tetrafunctional monomers theoretically capable of forming polymeric gels. If the ring structures, which bear a striking resemblence to carbohydrates, are preserved through the polymerization, the resulting poly(cyclic disilsesquioxane) gels may have structural similarities to branched or cross-linked carbohydrates, such as cellulose or chitosan. Under base-catalyzed sol-gel polymerization conditions, 3 and 4 (six- and seven-membered cyclic disilsesquioxanes, respectively) quickly reacted to give gels with significant ring opening as determined from the {sup 29}Si chemical shifts in solid-state (CP MAS) NMR spectra. However, gels prepared under acidic conditions reveal some or all of the cyclic disilsesquioxane functionality was preserved in the polymers. 13 refs., 1 fig.

Preparation of Alkyl-Substituted Indoles in the Benzene Portion. Part 14. Synthesis of (.+-.)-Duocarmycin SA, Natural (+)-Duocarmycin SA and Non-natural (-)-Duocarmycin SA.

Abstract: Total synthesis of duocarmycin SA (1), an extremely potent cytotoxic antibiotic, was achieved in the racemic form at first by effectively utilizing two reactions as key steps, (i) an intramolecular Heck reaction of the benzyl ether 21a, derived from a dihydropyridine 13a and a pyrrole derivative 11, to form tricyclic compounds 25a and 26a, and (ii) a modified Mitsunobu reaction on the diol derivative 40 for the construction of compound 41 having the pivotal pharmacophore of a cyclopropanoindolinone partial structure, which is critical for the high biological activities of 1. Next, optical resolution of an intermediary racemic secondary alcohol 50 was cleanly attained by derivatizing it to (R)-O-methylmandelates 52 and 53, and the resulting chiral alcohols (+)-50 and (-)-50 were respectively transformed into unnatural (-)-1 and natural (+)-1. Finally inversion of the secondary alcohol (+)-50 to the enantiomer (-)-50 was effected by using the Mitsunobu reaction. This constitutes an enantio-convergent total synthesis of natural duocarmycin SA (1) starting from a racemic compound.

Intramolecular and intermolecular photoinduced electron transfer in isomeric mesoporphyrin nitrobenzyl esters: structure and solvent effects

Abstract: Photoinduced intramolecular electron transfer was studied in a series of flexible dyads consisting of the isomeric ortho-, meta- and para- nitrobenzyl monoesters and diesters of mesoporphyrin existing preferentially in folded conformations. This process was compared with the intermolecular electron transfer between mesoporphyrin dimethyl ester and the 2-, 3- and 4-nitrobenzyl acetates. In both cases, electron transfer occurs from the porphyrin first excited singlet state, and the rate constant is lower in the ortho isomer, although intermolecular electron transfer is less isomer selective. The selectivity in the intermolecular case can be related to the isomer redox potentials, but in the dyads an ortho effect must also be taken into account; this effect produces a deviation from coplanarity between the nitro group and the phenyl ring. Electron paramagnetic resonance (EPR) in a low temperature matrix permits the charge transfer product to be detected. The process does not lead to the production of long-lived species, as shown by optoacoustic calorimetry. The efficiency of photoinduced electron transfer strongly depends on the ability of the solvent to stabilize the radical ion pair; this process occurs in CH 3 OH, CH 3 CN and CH 2 Cl 2 , but is inhibited in toluene and benzene. In the last two solvents, singlet oxygen is formed instead via energy transfer from the triplet state, with the same quantum yield as for the nitrobenzyl-free porphyrin.

Chemistry of Oxo-Sugars. III. Transformations of 2- and 3-Oxoglycosides in a Pyridine Solution

Abstract: Methyl arabino-hexopyranosid-2-uloses rearranged, in pyridine, into arabino-hexopyranosid-3-uloses through an intramolecular hydride shift. The product further isomerized, through enolization, to the most stable ribo-hexopyranosid-3-uloses, which, on prolonged standing in the same solvent, gradually liberated methanol giving rise to dioxo derivatives. The last change was particularly evident for 3-oxoglycosides carrying a 4-axial hydroxyl group.

Absence of Noncyclic Imide Formation in PMDA−ODA Polyimide

Abstract: The FT-Raman spectra of two aromatic non-cyclic model compounds, N,N-dibenzoylaniline and N,N-dibenzoyl-4-phenoxyaniline were obtained and compared with the spectra of thermally cured PMDA-ODA polyimides. The results indicate that there is no evidence for non cyclic imide crosslinking in the FT-Raman spectra of PMDA-ODA

Formation of macrocyclic polymers by intramolecular coupling of α,ω‐difunctional precursors. Numerical evaluations

Abstract: The end-to-end cyclization reaction of living monodisperse α,ω-dianion precursors with difunctional electrophiles (EX 2 ) in the presence of partial anion termination is described. A computer simulation was developed to establish the relationship among the initial concentration, the molecular weight of the dianion precursor, the extent of anion termination, and the yield distribution for all of the cyclic and linear polymer species. A master curve is calculated allowing the determination of the macrocycle yield as a function of MW and concentration of the dianion precursor, and degree of anion termination.

Diastereoselectivity in the SE2″ reaction of chiral pentadienylsilanes: a test for the relative importance of steric and electronic effects

Abstract: The homochiral pentadienylsilanes (3Z,5E)-(hepta-3,5-dien-2-yl)dimethyl(phenyl)silane 9, (3Z,5E)-(hepta-3,5-dien-2-yl)trimethylsilane 13, (4Z,6E)-(2-methylocta-4,6-dien-3-yl)dimethyl(phenyl)silane 14 and (4Z,6E)-(2-methylocata-4,6-dien-3-yl)trimethylsilane 17 undergo Lewis acid catalysed reactions with isobutyraldehyde and its dimethyl acetal stereospecifically anti with surprisingly high levels of stereoselectivity, ca. 90:10. The pentadienylsilanes (3Z)-hexa-3,5-dien-2-yldimethyl(phenyl)silane 20aa, (4Z)-(2-methylhepta-4,6-dien-3-yl)dimethyl(phenyl)silane 20ab, (3Z)-(hexa-3,5-dien-2-yl)-trimethylsilane 20ba and (2Z)-(1-phenylpenta-2,4-dienyl)trimethylsilane 20bc undergo dipolar cycloadditions to 2,2-dimethylpropanenitrile oxide regioselectively at the terminal double bond and stereoselectively anti to the silyl group to a somewhat lower extent, ca. 70:30. The pentadienylsilane (3Z,5E)-(6-cyclohexylhexa-3,5-dien-2-yl)trimethylsilane 25 undergoes deuteriodesilylation stereospecifically anti to a lower extent still, ca. 55:45. The pentadienylsilane (3Z,5E)-(8-methyl-8-methoxyethoxymethoxynona-3,5-dien-2-yl)trimethylsilane 34 undergoes an intramolecular reaction stereospecifically anti again to the extent of about 60:40, whereas the reaction of the corresponding allylsilane (3Z)-(6-methyl-6-methoxyethoxymethoxyhept-3-en-2-yl)trimethylsilane 32 is essentially completely anti. These results show that SE2″ reactions can be highly stereoselective in the anti sense, that the high level is probably best accounted for by the steric effect of the silyl group, and that when the steric effect is minimised, the stereospecificity is low, but still measurable. The pentadienylsilanes were prepared by aldol reactions between β-silyl esters and the appropriate α,β-unsaturated aldehyde, followed by decarboxylative elimination. The products of the SE2″ reactions were identified and their stereochemistry determined by comparison with authentic materials or by degradation and synthesis, using chiral auxiliaries to determine the enantiomeric purity. The products of two of the dipolar cycloadditions were identified by degradation and stereospecific vinylogous Peterson elimination, but the vinylogous Peterson elimination taking place with (1RS,2Z,4SR,6SR)-(4,6-dihydroxy-7,7-dimethyl-1-phenyloct-2-enyl)trimethylsilane 67bc and its (1SR) diastereoisomer 68bc was not stereospecific, giving (5E,7E)-2,2-dimethyl-8-phenylocta-5,7-dien-3-ol 73 from both isomers. The stereochemistries of all the reactions are summarised.

Chemistry of Oxo-Sugars. IV. Isomerization of 4-Oxoglycosides in a Pyridine Solution

Abstract: 4-Oxoglycosides of xylo-configuration (1a, 1b) rearranged in pyridine-d5 to give exclusively 3-oxoglycosides of ribo-configuration through enediol intermediates. On the other hand, 4-oxoglycosides of lyxo- and arabino-configuration (5, 6) gave an epimeric mixture of both isomers. The reason for this difference was discussed on the basis of AM1 calculations.

Reaction of vinylmagnesium bromide with hexacyclo[10.2.1.02,11.04,9.04,14.09,13]pentadeca-5,7-diene-3,10-dione: Transannular hemiketal formation

Abstract: Reaction between vinylmagnesium bromide and the cage dione leads to attack of only one equivalent of Grignard and intramolecular nucleophilic attack on the second ketone. The product compound crystallizes in the monoclinic space group, P21/a, witha=9.509(1),b=11.071(2),c=12.492(4) A, β=104.32(2)°, andZ=4.

Stereoselective synthesis of γ- butyrolactones by intramolecular Michael addition

Abstract: The intramolecular Michael addition of enantiomerically enriched γ-[(phenylthio)acyl]oxy, β-unsaturated esters opens a way to the synthesis of saturated γ-lactones,α-methylene butyrolactones and butenolides of high enantiomerical purity. The method is complemented by the alkylation of the obtained α-benzenesulfonyl-γ-lactones which with an unusual stereoselectivity leads tto a new methodology to obtain polysubstituted carbocycles of different size.

Photoreactive polyarylenevinylenes: Synthesis, characterization and photochemistry

Abstract: The substitution of every second phenylene subunit in the well-known poly(p-phenylenevinylene) (PPV) by o,o′-bridged biphenyl moieties leads to the novel poly(1,4-phenylenevinylene-2,2′-biphenylylenevinylene) (PPVBV, 5) which can be prepared by palladium-catalyzed aryl-olefin coupling (Heck reaction). PPVBV possesses a high solubility in common organic solvents and good filmforming capabilities. It exhibits a thermochemical and photochemical reactivity comparable to that of the monomeric model compound 2,2′-distyrylbiphenyl (3), which undergoes a [2+2]cycloaddition upon heating or irradiation.

Halogenovinyl sulfones 51. synthesis of a dibenzopyran derivative from an intramolecular diels-alder reaction

Abstract: Reaction of o-(1,3-pentadienyl)-phenol 3 with 1,3-dichloro-2-phenylsulfonylpropane 2 in the presence of triethylamine gave o-(1,3-pentadienyl)-phenyl (2-phenylsulfonyl)-2-propenyl ether 4 in 91–100% yields, which underwent intramolecular Diels-Alder reactions to dord dibenzopyran derivatives.

Olefin Metathesis in Cyclic Ether Formation. Direct Conversion of Olefinic Esters to Cyclic Enol Ethers with Tebbe-Type Reagents.

Abstract: Department of Chemistry, The Scripps Research Institute 10666 North Torrey Pines Road, La Jolla, California 92037 Department of Chemistry and Biochemistry UniVersity of California, San Diego 9500 Gilman DriVe, La Jolla, California 92093 ReceiVed October 17, 1995 The olefin metathesis reaction1 is rapidly emerging as a powerful tool in organic synthesis.2 Of particular interest are ring forming metathesis reactions catalyzed by transition metal complexes, several elegant examples of which have recently appeared.3 Despite the successes of this general approach to ring construction, much remains to be improved in terms of scope, convenience, and generality. In this communication we report a new strategy, based on the olefin metathesis reaction, for the generation of cyclic enol ethers directly from olefin esters4 using the Tebbe5 or the Petasis reagents.6 Scheme 1 shows the general concept7 for the envisioned Tebbe-reagent-mediated transformation of olefinic esters of type I to cyclic enol ethers of type VI. Thus it was anticipated that the initially formed enol ether II would react with a second molecule of the Tebbe reagent to afford the titanacyclobutane III, fragmentation of which would then lead to titanium alkylidene IV. Intramolecular reaction of IV was then expected to lead to titanacyclobutane V, whose regioselective fragmentation as shown should allow an entry to the desired cyclic enol ethers VI via olefin metathesis. Implementation of this strategy using olefinic ester 1 leads to the formation of cyclic enol ether 3 via the initially formed methylenation product 2 in 71% overall yield (Scheme 2). The intermediacy of compound 2 was proven by isolation and full spectral characterization followed by conversion to 3 under the influence of the Tebbe reagent. The generality and scope of this new process was investigated by employing a variety of substrates. As illustrated in Table 1, the reaction can deliver a series of sixand seven-membered cyclic enol ethers in good yields (entries 1-3 and 10-12, respectively). In addition to these findings, the important observation of the open-chain products shown in entries 6-9 (Table 1) was made. These hydroxy exomethylenic compounds are presumably obtained by sequential hydrolysis and olefination of the initially formed cyclic enol ethers.8 Apparently the lability of the enol ether products depends on their precise environment and the reaction conditions, a circumstance that

Vilsmeier-Haack Reaction of Methyl Lambertianate and Non-Sensitized Photocyclization of the Resulting Product.

Abstract: Vilsmeier—Haack formylation of methyl lambertianate results in its 16-formyl derivative as the predominant product, which readily enters the intramolecular reaction of photochemical [2+2]-cycloaddition in the absence of a sensitizer.