Enhanced reactivity in radical cyclizations of hydrazones using the silicon-tethered 1-bromovinyl group

A silicon-tethered 1-bromovinyl group was shown to function as a radical precursor for tin-mediated vinyl additions to chiral α- or β-hydroxyhydrazone. In contrast to related thiyl-mediated methods, these vinyl bromides were not limited to the 5-exo cyclization mode. A series of Si-tethered 5-exo and 6-exo cyclizations formed the corresponding five- and six-membered exo-methylene-substituted oxasilacycles. Treatment with fluoride cleaved the Si-C and Si-O bonds to afford the corresponding allylic hydrazines. Diastereoselectivities ranged from 2:1 to 25:1 (anti:syn) for the 5-exo cyclizations, depending on the size of the exocyclic substituent, but 6-exo cyclization was not diastereoselective. A variant involving Tamao oxidation of the exo-methylene oxasilacyclopentane intermediate afforded a methyl ketone, a net process corresponding to addition of a radical acyl anion equivalent.     

Efficient access to disubstituted exo-glycals. Application to the preparation of C-glycosyl compounds

Efficient methods of preparation of disubstituted exo-glycals by palladium cross-coupling reaction on the readily available dibromo exo-glycal and methoxycarbonyl exo-glycal have been developed. Hydrogenation of these new monosubstituted and disubstituted exo-glycals proceeded with a high stereocontrol and led to original C-glycosyl compounds.     

Conversion of arenes to cyclohexa-1,3-dienes via (exo-5-dialkylphosphonoexo-6-R-η4-cyclohexadiene) manganese dicarbonylnitrosyl compounds

(exo-5-Dialkylphosphono-exo-6-R-η⁴-cyclohexadiene)Mn(CO)₂NO compounds were prepared by the reaction of (exo-6-R-η⁵-cyclohexadienyl)Mn(CO)₂ NO⁺ with an excess of P(OMe)₃. When (exo-5-dialkylphosphono-exo-6-η⁶-R-cyclohexadiene) Mn(CO)₂NO compounds are refluxed with Me₃NO in benzene, two kinds of cyclohexadiene compounds are formed depending upon the R group.     

Stereoselective synthesis of substituted exo-glycals from 1-exo-methylene pyranoses

Halo-exo-glycals of the gluco-, manno- and galacto- series, readily prepared by reaction of 1-exo-methylene pyranoses with iodonium dicollidinium triflate (IDCT), undergo Suzuki or B-alkyl Suzuki cross-coupling reactions with boronic acids or alkyl boranes to yield, in a stereoselective manner, functionalized exo-glycals.     

Experimental and DFT study of the aza-Diels-Alder reaction between cyclopentadiene and protonated benzylimine derivated from glyoxylates

The Diels-Alder reaction of protonated N-benzyl imine of methyl glyoxylate with cyclopentadiene in different solvents gave mixtures of exo/endo adducts. The exo/endo selectivity of the reaction was elucidated by NMR experiments. Theoretical calculations by means of density functional theory (DFT) at the B3LYP/6-31G(d) level have also been performed to elucidate the molecular mechanism of this reaction. The DFT results suggest a highly asynchronous concerted mechanism, which in turn can explain the preferred exo stereoselectivity of the reaction. Inclusion of solvent effects enhances the exo selectivity, and this effect increases with the polarity of the solvent, in good agreement with the experimental findings.     

Stereochemistry of the tin—carbon bond: II. Brominolysis of a series of exo- and endo-2-triorganostannylnorbornanes

The brominolysis of a series of exo- and endo-2-triorganostannylnorbornanes with methyl, isopropyl, neopentyl and cyclohexyl as substituents on tin, proceeds with inversion of configuration for the endo-carbon—tin bond and with retention of configuration for the exo-carbon—tin bond. The norbornyl system seems to favour the exo-approach of the electrophile.     

Synthesis of (−)-aphanorphine using a sulfur-directed aryl radical cyclization

Treatment of radical precursor 15a having a vinyl sulfide moiety with Bu₃SnH in the presence of AIBN in boiling benzene afforded exclusively the 6-exo cyclization product 16a, whereas similar treatment of the exo-methylene compound 15b gave a mixture of the 6-exo cyclization product 16b and the endo-olefin product 17 formed by a 1,5-hydrogen shift. Based on these findings, the synthesis of (−)-aphanorphine was achieved using a sulfur-directed 6-exo-selective aryl radical cyclization of 22.     

Synthesis of exo-glycals and their biochemical applications

exo-Glycals are both valuable synthetic tools and biologically relevant structures. This article reviews the novel synthetic approaches that have been reported to synthesize sugar based tri- or tetrasubstituted exocyclic enol ethers. Among those, the Julia modified olefinations as well as the transition metal catalyzed cross-couplings have been extensively developed. The synthesis of unprecedented fluorinated and sulfonylated phosphono-exo-glycals are also described. An overview of the biological applications in which exo-glycals acts as inhibitors or inactivator of relevant enzymes is finally presented.     

Substituent control in the diastereoselectivity of dipolar cycloadditions of nitrones and their Zn(II) complexes with N-arylmaleimides

The π-π stacking interactions between maleimide's and nitrone's aromatic rings during the 1,3-dipolar cycloaddition were assumed to control the exo-endo selectivity of the reaction. The exo-endo ratios change during the reactions until they reach a constant value, which depends on the substituent. Electron-withdrawing groups favour the exo adduct while electron-donating groups favour the endo adduct. The nitrone ZnBr₂ complexes react much more slowly than the free nitrone and the cycloaddition is exo selective in all cases independent of the substituents on the maleimide's aromatic ring. Thermal retrocycloaddition of the cycloadducts produce the corresponding nitrones. The ring opening in the presence of secondary amines did not induce imine formation. endo Adducts were shown for the first time to be the stable paramagnetic compounds.     

Azabrendanes IV. Synthesis and characterization of N-(alkyl- and benzylsulfonyl)-exo-2-hydroxy-4-azatricyclo[4.2.1.0]nonanes

exo- and endo-5-Aminomethylbicyclo[2.2.1]hept-2-enes have been obtained from stereoisomeric exo- and endo-5-cyanobicyclo[2.2.1]hept-2-enes and the corresponding sulfonamides were obtained through reaction of amines with methyl-, n-propyl-, n-butyl-, benzyl-, and cyclohexylsulfonyl chlorides. From the stereoisomeric sulfonamides with peroxy acids, various products were obtained: exo-sulfonamides were transformed into epoxy derivatives, and, in contrast, most of the endo-stereoisomers underwent heterocyclization resulting in substituted exo-2-hydroxy-4-azatricyclo[4.2.1.0^3,7]nonanes. The type of the products obtained did not depend on the type of peroxy acid used (peroxyacetic, peroxyphthalic, and m-chloroperoxybenzoic one). In contrast to other endo-sulfonamides, N-(cyclohexylsulfonyl)-endo-5-aminomethylbicyclo[2.2.1]hept-2-ene in reaction with peroxyacetic acid did not undergo heterocyclization, probably, due to steric factors. The structure and stereochemical homogeneity of the sulfonamides and the structure of the products of their oxidation with peroxy acids were confirmed by spectroscopic methods. The molecular structure of N-(cyclohexylsulfonyl)-endo-5-aminomethyl-exo-2,3-epoxybicyclo[2.2.1]heptane was determined by X-ray diffraction analysis. The mechanism of the intramolecular heterocyclization reaction of N-substituted endo-5-aminomethyl-exo-2,3-epoxybicyclo[2.2.1]heptanes was studied at the BHandHLYP/6-31G(d) level of theory.     

The Beckmann fragmentation of quadricyclanone oxime

The attempted O-tosylation of tetracyclo[3.2.0.0^2,7.0^4,6]heptan-3-one (quadricyclanone) oxime with p-toluenesulfonyl chloride in dichloromethane in the presence of triethylamine/DMAP or pyridine resulted in the Beckmann fragmentation to give a mixture of 4-exo-/4-endo-tosyloxy- and 4-exo-/4-endo-chlorobicyclo[3.1.0]hex-2-ene-6-endo-carbonitriles in 90% overall yield. Solvolysis of all four products in 2,2,2-trifluoroethanol afforded the corresponding 4-exo-trifluoroethoxy derivative as the sole product. Quadricyclanone itself undergoes the fragmentation reaction with hydroxylamine-O-sulfonic acid, selectively affording the 4-exo-hydroxy-6-endo-nitrile in 90% isolated yield.     

Orbital control of stereochemistry in acid-catalysed addition reactions of endo -tricyclo[3.2.1.02,4]0ct-6-ene

The reaction of endo-tricyclo[3.2.1.0^2,4]oct-6-ene 1 with methanol in the presence of catalytic amounts of toluene-p-sulphonic acid has been shown to give 2-exo- and endo-methoxybicyclo[3.2.1]oct-3-ene (2c) and (2d) and 2-endo-methoxybicyclo[3.2.1]oct-6-ene (13). The formation of 2-exo- methoxybicyclo[3.2.1]oct-3-ene (2c), the major product of reaction, has been probed by deuterium labelling experiments and a series of 6-exo-7-exo- dideuterobicyclo[3.2.1]oct-3-enes synthesised for ²H, ¹H and ¹³C NMR spectral analysis in order unambiguously to determine the stereochemistry of proton attack on endo-tricyclo[3.2.1 0^2,4]oct-6-ene (1). The formation of 2-exo-methoxybicyclo[3.2.1]oct-3-ene (2c) has been determined to involve corner protonation of the cyclopropyl moiety and skeletal rearrangement to an allylic cation with a small but measurable memory effect     

Oxanorbornenes: promising new single addition monomers for the metathesis polymerization

Higher ring-opening metathesis propagation rates of exo-norbornene derivatives over endo derivatives are well established in the literature. Here, we report for the first time that endo-isomers of oxanorbornene derivatives show higher reactivity towards ring-opening metathesis with Grubbs'' 3rd generation catalyst (G3) than the corresponding exo-isomers. A very high selectivity for the reaction of G3 with endo over the exo-isomers could be shown. Furthermore, single molecular addition of the endo-isomers with G3 was observed. On the other hand, pure exo-monomers could successfully be homopolymerized. Mixtures of exo- and endo- monomers, however, prevented the homopolymerization of the exo-monomer. Such mixtures could successfully be copolymerized with cycloalkenes, resulting in alternating copolymers. An oxanorbornadiene derivative could be shown to undergo single addition reactions, exploited in the preparation of mono-end functional ROMP polymers. These could be selectively derivatized via endgroup selective thiol-ene click reactions. A thiol and alcohol end functional ROMP polymer was synthesized, and the efficient end functionalization was confirmed by ¹H NMR spectroscopy and MALDI-ToF spectrometry.

Bridgehead revisited: endo-7-oxa norborneneimide derivatives (green) initiate faster but propagate more slowly than the analogous exo-derivatives (red) in ring-opening metathesis allowing the synthesis of alternating and end functional polymers.     

Rhodium(I) catalysis of cycloprop[a]acenaphthylene isomerizations

Cycloprop [a] acenaphthylene was found to rearrange to phenalene in the presence of rhodium dicarbonyl chloride dimer. Deuterium labeling of this molecule at C(7) (both exo and endo), at C(8), at C(7) (exo) and C(8) and at C(7) (exo), C(8), and C(8') indicated that the C(7) (exo) deuterium was migrating stereospecifically. Furthermore, all of the isotopic label present in the cycloprop[a]acenaphthylene was found statistically distributed over positions 1, 3, 4, 6, 7, and 9 of the phenalene product. Control experiments established the need of the catalyst, the inability to achieve rearrangement of the exo-7-methyl derivative, and the susceptibility of a monodeuterated phenalene for extensive isotopic scrambling in its own right when exposed to rhodium(I). These results have been interpreted on the basis of oxidative addition by rhodium(I) into the central bond of cycloprop[a]acenaphthylene from above the “flap”, followed by shifting of the C(7) (exo) hydrogen (or deuterium) to give a η³-allylrhodim-(III) complex. The experimental data further support a mechanism involving subsequent rearrangement of this intermediate around the periphery of the phenalene ring. This process which is otherwise degenerate is thought to be facilitated by the special electronic features of the phenalenyl system.     

New exo/endo selectivity observed in monohydrolysis of dialkyl bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylates

New monohydrolysis reactions of several exo or endo dimethyl or diethyl bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylates showed higher selectivity toward monohydrolyses of exo-carboalkoxy groups, although the reaction centers are located away from the norbornene rings.     

Photocrosslinkable polynorbornene-based block copolymers with enhanced dielectric and thermal properties

Block copolymers poly(endo-N-3,5-bis(trifluoromethyl)biphenyl-norbornene-pyrrolidine)-block-poly(exo-N-(cinnamoyloxyethyl)-7-oxanorborn-5-ene-2,3-dicarboximide) (endo-PTNP-b-exo-PCONBI) and poly(exo-N-3,5-bis(trifluoromethyl)biphenyl-norbornene-pyrrolidine)-block-poly(exo-N-(cinnamoyloxyethyl)-7-oxanorborn-5-ene-2,3-dicarboximide) (exo-PTNP-b-exo-PCONBI) were synthesized by ring-opening metathesis polymerization. The endo- or exo-PTNP served as the high dielectric functional chain, and exo-PCONBI acted as the crosslinking segment. The endo-PTNP-b-exo-PCONBI, in which endo-PTNP has a high content of trans double bond and adopts isotactic configuration, shows a dielectric constant (ε) of 15.5, whereas exo-PTNP-b-exo-PCONBI, in which exo-PTNP has 67% trans double bonds and atactic microstructure, displays relatively low ε of 7.1. The cinnamate groups in exo-PCONBI were crosslinked to form three-dimensional network by cycloaddition reaction under UV irradiation. Exposed to UV-light for 10 min, the cinnamate group in polymer films has a crosslinking conversion of 36%, as determined by UV-Vis absorption measurements. By photocrosslinking, the polymer film has an increased ε of 16.6, a dielectric loss of 0.03, an elevated glass-transition temperature of 137 °C, and an enhanced decomposition temperature of 405 °C, compared to those of polymer films without irradiation.     

Metal-catalyzed cyclopropanation on the 8-oxabicyclo[3.2.1]oct-6-ene template

Cyclopropanations of an 8-oxabicyclo[3.2.1]octene substrate using diazocarbonyl compounds provided exo, exo-cyclopropanated products as the sole or major diastereomeric oxatricyclic products. Reductive cleavage of a meso-oxatricyclic ketone by samarium iodide resulted in desymmetrization without concomitant oxygen bridge cleavage.     

The synthesis and decomposition of 3-p-nitrophenyl-3,4,5-triazatricyclo(5.2.1.02,6endo)dec-4-ene : Triazoline thermolyses

A stereospecific synthesis of the endo triazoline 20 has been accomplished by the sequential conversion of norbornylene to the oxime of 3-exo-chloronorbornanone followed by reduction of its acetate or p-nitrobenzoate with diborane to give 2-endo-amino-3-exo chloronorbornane, then coupling of the latter with p-nitrobenzene diazonium chloride to give diazoamine 19, which was cyclized with ethanolic sodium ethoxide in the presence of silver nitrate. Photolysis of endo triazoline 20 gave exclusively endo aziridine 3 (R = p-NO₂C₆H₄), while on pyrolysis in decalin at 165–170° there was obtained endo aziridine 3, exo axiridine 2, imine 4 and a large amount of polymer. Under identical conditions, the isomeric exo triazoline 1 (R = p-NO₂C₆H₄) gave exo aziridine 2, endo aziridine 3, imine 4 and no polymer. The “triazoline-aziridine inversion” is presumed to occur via the diazoimine intermediate 7. While photolysis of exo triazolines 23 and 24 and pyrolysis of 23 gave, as expected, the corresponding exo aziridines 25 and 26, pyrolysis of 24 appears to have given the isoxazoline 28. Evidence for the intermediacy of the diazoimine 27 in the formation of 28 is presented.     

Convergent stereocontrolled synthesis of substituted exo-glycals by Stille cross-coupling of halo-exo-glycals and stannanes

(Z)-exo-Glycals can be conveniently prepared in a convergent manner by Stille cross-coupling of (Z)-halo(Br,I)-exo-glycals and aryl or alkenyl stannanes, the latter are readily obtained by addition of tributylstannyl radicals to terminal alkynes.