Abstract: First described in the late 1960s, N-alkylsulfonylimines are heterocumulenes that participate in reactions with a range of 1,3-dipoles to afford interesting 3-, 4-, 5-, and 6-membered heterocycles. The distribution of adducts obtained suggests that multistage, stepwise mechanistic pathways rather than a concerted process are in operation.
Abstract: A small library of amphiphilic compounds was synthesized in an array using the Huisgen 1,3-dipolar cycloaddition of terminal alkynes with azides (CuAAC or click reaction). The self-assembling properties of these compounds were evaluated by polarizing microscopy and synchrotron small-angle X-ray scattering analysis.
Abstract: The first total synthesis of the low-abundance natural product 2?,5?-diepisilvestrol (4) is described. The key step involved a Mitsunobu coupling between cyclopenta[b]benzofuran phenol 7 and dioxane lactol 6. Deprotection then gave a 1:2.6 ratio of natural product 2?,5?-diepisilvestrol (4) and its C1 epimer 1?,2?,5?-triepisilvestrol (15) in 50% overall yield. An in vitro protein translation inhibition assay showed that 2?,5?-diepisilvestrol (4) was considerably less active than episilvestrol (2), while the unnatural isomer 1?,2?,5?-triepisilvestrol (15) was essentially inactive, showing that the configuration at C1? and C2? has a large effect on the biological activity.
The first total synthesis of the low-abundance natural product 2?,5?-diepisilvestrol (4) is described. The key step involved a Mitsunobu coupling between cyclopenta[b]benzofuran phenol 7 and dioxane lactol 6. Deprotection then gave a 1:2.6 ratio of natural product 2?,5?-diepisilvestrol (4) and its C1 epimer 1?,2?,5?-triepisilvestrol (15) in 50% overall yield. An in vitro protein translation inhibition assay showed that 2?,5?-diepisilvestrol (4) was considerably less active than episilvestrol (2), while the unnatural isomer 1?,2?,5?-triepisilvestrol (15) was essentially inactive, showing that the configuration at C1? and C2? has a large effect on the biological activity.
Abstract: Recently, a novel chiral cubane-based Schiff base ligand was reported to yield modest enantioselectivity in the Henry reaction. To further explore the utility of this ligand in other asymmetric organic transformations, we evaluated its stereoselectivity in cyclopropanation and Michael addition reactions. Although there was no increase in stereocontrol, upon computational evaluation using both M06L and B3LYP calculations, it was revealed that a pseudo six-membered ring exists, through H-bonding of a cubyl hydrogen to the copper core. This decreases the steric bulk above the copper center and limits the asymmetric control with this ligand.
Abstract: A fragment-based screen against human immunodeficiency virus type 1 (HIV) integrase led to a number of compounds that bound to the lens epithelium derived growth factor (LEDGF) binding site of the integrase catalytic core domain. We determined the crystallographic structures of complexes of the HIV integrase catalytic core domain for 10 of these compounds and quantitated the binding by surface plasmon resonance. We demonstrate that the compounds inhibit the interaction of LEDGF with HIV integrase in a proximity AlphaScreen assay, an assay for the LEDGF enhancement of HIV integrase strand transfer and in a cell based assay. The compounds identified represent a potential framework for the development of a new series of HIV integrase inhibitors that do not bind to the catalytic site of the enzyme.
Abstract: The formation of functional liposomes by the self assembly of a peptide–amphiphile that comprises the neuroprotective tripeptide motif glycyl-prolyl-glutamic acid linked to a hydrophobic moiety is reported. The self-assembled peptide–lipid conjugate displays long range order and can be dispersed as nanometre sized particles.
Abstract: An aryl substrate with dual functionality consisting of a nitrile oxide and a pinacolyl boronate ester was prepared by mild hypervalent iodine oxidation (diacetoxyiodobenzene) of the corresponding aldoxime, without decomposition of the boronate functionality. The nitrile oxide was trapped in situ with a variety of dipolarophiles to yield aryl isoxazolines with the boronate ester function intact and available for subsequent reaction.
Abstract: N-Aryl 4-methylene-2-oxazolidinones, preparedviathe corresponding O-propargyl carbamates, underwent nitrile oxide cycloaddition with benzonitrile oxide to give 5-spiro isoxazoline adducts with complete regioselectivity. Steric hindrance by atropisomerism around theN-aryl bond induced facial selectivity in these cycloadditions.
Abstract: Background: HIV-1 integrase is a clinically validated therapeutic target for the treatment of HIV-1 infection, with one approved therapeutic currently on the market. This enzyme represents an attractive target for the development of new inhibitors to HIV-1 that are effective against the current resistance mutations.
Methods: A fragment-based screening method employing surface plasmon resonance and NMR was initially used to detect interactions between integrase and fragments. The binding sites of the fragments were elucidated by crystallography and the structural information used to design and synthesize improved ligands.
Results: The location of binding of fragments to the catalytic core of integrase was found to be in a previously undescribed binding site, adjacent to the mobile loop. Enzyme assays confirmed that formation of enzyme–fragment complexes inhibits the catalytic activity of integrase and the structural data was utilized to further develop these fragments into more potent novel enzyme inhibitors.
Conclusions: We have defined a new site in integrase as a valid region for the structure-based design of allosteric integrase inhibitors. Using a structure-based design process we have improved the activity of the initial fragments 45-fold.
Abstract: When used as solvent, chloroform was found to act as a hydrogen atom donor in Barton reductive decarboxylation reactions. Chloroform offers a substantial practical advantage over pre-existing hydrogen atom donors.
Abstract: Aliphatic nitrile oxides were generated in situ, by dehydration of terminal nitro compounds, and reacted with dipolarophiles using continuous flow techniques to afford substituted isoxazolines. The yields of cycloadducts were comparable with traditional flask-based reactions but reaction times were much shorter. In-line scavenger cartridges conveniently removed by-products and unreacted reagents to give almost pure crude products. The process was demonstrated up to gram scale.
Abstract: A high yielding practical three-step procedure, which relies on an extractive work-up procedure, has been developed to convert N-phenylsulfonyl-trans -4-hydroxy-L -proline to N-phenylsulfonyl- cis -4-hydroxy-L -proline methyl ester in 82 % yield over three steps.
Abstract: Cubane is a highly strained unsaturated molecule that was first synthesized in 1964 by Philip E. Eaton. Since cubane’s discovery, it has been researched in pharmaceuticals, explosives, and polymers. Due to its range of uses, we have explored the thermo-stability of a number of cubane derivatives. Some derivatives have revealed its propensity to undergo cage opening/rearrangement. In examining 1-iodocubane-4-carboxaldehyde, we observed that benzoic acid, benzaldehyde, benzyl alcohol, and benzyl benzoate were surprisingly formed in this thermo-decay.
Abstract: A sequence of Sonogashira coupling, Pd(II)-catalyzed carbonylative annulation, and benzofuran reduction (Mg, MeOH, NH4Cl) provides a convergent and modular synthetic route to trans-2-aryl-2,3-dihydrobenzo[b]furan-3-carboxylates, which are a structural feature of numerous biologically active natural products. This versatile strategy was applied to the formal total synthesis of the anti-HIV natural product (+)-lithospermic acid.
Abstract: N-Aryl 5-methylenehydantoins underwent nitrile oxide cycloaddition with benzonitrile oxide to give 5-spiro isoxazoline adducts with complete regioselectivity. Atropisomerism around the N-aryl bond also led to facial selectivity in these cycloadditions.
Abstract: The first reported cubane-based chiral Schiff base ligand has been successfully synthesized. This ligand has been evaluated on the nitro-aldol (Henry) reaction. The reactions were performed in the presence of four different copper salts, using eight different solvents, and five different temperatures. The highest enantioselectivity obtained for this novel ligand was ˜39% ee.
Abstract: Since the initial synthesis of cubane, numerous derivatives have been made with a diverse range of physical, chemical, and biological properties. Some iodinated cubane derivatives have been reported to be thermolytically unstable and/or rearrange in situ. An iodinated cubane-containing, norbornene-based polymer showed rapid thermo-decomposition during TGA studies. Bis-(4-iodocubylmethyl)-dialkoxy disulfide undergoes fragmentation more easily than its non-iodinated counterpart. The synthesis and thermal behaviour of a library of iodinated cubane compounds are herein reported. Most of the iodinated cubane derivatives showed melting/decomposition with no exotherm upon cooling. 4-Iodo-1-vinylcubane was observed to rearrange to 4-vinyl-trans-β-iodostyrene and its cyclooctatetraene intermediate during DSC analysis. TGA studies on 1-iodo-4-(hydroxymethyl)-cubane suggest that this particular iodinated cubane scaffold is mostly prone to rapid thermo-decomposition.
Abstract: Cubane can be considered the ideal internal standard for reactions observed by NMR, due to an almost complete benign reactivity and uniquely reliable 1H and 13C NMR resonances, in wide variety of deuterated solvents.
Abstract: The 1,3-dipolar cycloaddition reaction of nitrile oxides with carbon dipolarophiles is a versatile and powerful synthetic method to prepare isoxazolines. In particular nitrile oxide cycloaddition reactions with exocyclic methylene or alkylidene compounds generally proceed regioselectively leading to spiro heterocyclic compounds. This review deals with progress in the field of nitrile oxide cycloaddition chemistry for the synthesis of spiro isoxazolines.
Abstract: Substituted 5-methylene-1H-pyrrol-2(5H)-ones underwent a 1,3-dipolar cycloaddition reaction with nitrile oxides to give the corresponding spiro heterocycles. Critical to this reaction was the development of a biphasic system for base-induced dehydrohalogenation of hydroximoyl chlorides, to give nitrile oxides, in the presence of a base-sensitive dipolarophile. A substituted N-tolyl 5-methylene-1H-pyrrol-2(5H)-one exhibited atropisomerism, which in turn led to a 4:1 facial selectivity during cycloaddition.
Abstract: Total synthesis of the anticancer 1,4-dioxane containing natural products silvestrol (1) and episilvestrol (2) is described by an approach based on the proposed biosynthesis of these novel compounds. The key steps included an oxidative rearrangement of the protected d-glucose derivative 11 to afford the 1,4-dioxane 12, which could be elaborated to the coupling partner 5 and a photochemical [3 + 2]-cycloadditon between the 3-hydroxyflavone 27 and methyl cinnamate followed by base-induced α-ketol rearrangement and reduction to give the cyclopentabenzofuran core 33. The core (−)-6 and 1,4-dioxane fragment 5 were united by a highly stereoselective Mitsunobu coupling with the modified azodicarboxylate DMEAD to afford the axial coupled product 36. Deprotection then gave episilvestrol (2). Silvestrol (1) was synthesized by a coupling between core (−)-6 and the dioxane 44 followed by deprotection. Compound 1 was also synthesized from episilvestrol (2) by a Mitsunobu inversion. In addition, the analogue 4′-desmethoxyepisilvestrol (46) was synthesized via the same route. It was found that 46 and episilvestrol 2 displayed an unexpected concentration-dependent chemical shift variation for the nonexchangeable dioxane protons. Synthetic compounds 1, 2, 38, 46, and 54 were tested against cancer cells lines, and it was found that the stereochemistry of the core was critical for activity. Synthetic analogue 4′-desmethoxyepisilvestrol (46) was also active against lung and colon cancer cell lines.
Abstract: A pendant cubane substituent has been incorporated into an acrylate polymer side chain to give poly[methyl 4-(acryloyloxymethyl)cubane carboxylate]. Treating this polymer with a rhodium(I) salt triggers a catalytic, ring-opening rearrangement of the cubane substructure to cyclooctatetraene, with a concomitant expansion in molecular volume. This system offers a unique opportunity to reverse the shrinkage associated with polymerization
Abstract: Substituted 4-methylene-2-oxazolidinones were prepared in two steps by cyclizing O-propargyl carbamates, which in turn were prepared from propargyl alcohols and phenyl isocyanate. The 4-methylene-2-oxazolidinones underwent a 1,3-dipolar cycloaddition reaction with benzonitrile oxide to give the corresponding spiro heterocycles.Where the substitution pattern on the oxazolidinone engendered facial asymmetry, the cycloadditon reaction proceeded with 5:1 selectivity for the less hindered face of the dipolarophile.
Abstract: Four spiroisoxazolines have been prepared, by cycloaddition of aceto-, pivalo-, benzo- and mesito-nitrile oxide with 3-methylenequinuclidine. The reactions were completely regioselective, within the limits of detection. None of the isoxazolines showed significant inhibition of acetylcholinesterase.
Abstract: The title natural product (-)-aiphanol has been prepared by total synthesis. A key step involved the asymmetric dihydroxylation of (E)-3,5-dimethoxy-4-(methoxymethoxy)cinnamyl alcohol with the AD-mix-beta to give triol (1R,2R)-1-(3',5'-dimethoxy-4'-methoxymethoxyphenyl)-2,3-dihydroxypropano l, the absolute stereochemistry of which was confirmed by single-crystal X-ray analysis of a readily available bromo-derivative. These Studies have established that the naturally occurring enantiomer of aiphanol possesses the (S)-configuration at each of C-2' and C-3'. (C) 2005 Elsevier Ltd. All rights reserved.
Abstract: Bicyclic analogues of methyllycaconitine (MLA), such as 12, have been synthesised that incorporate the C1-OMe substituent present in the natural product. Electrophysiology experiments using Xenopus oocytes expressing nicotinic acetylcholine receptors (nAChRs) were conducted on these analogues and a related tricyclic analogue 2. The most potent compound, 2, was an antagonist at all receptors studied but displayed different antagonist effects at each receptor subtype. This study more clearly defines the biological effects of MLA analogues at nAChRs and demonstrates that these analogues are not selective ligands for the alpha 7 nAChR subtype. (c) 2005 Elsevier Ltd. All rights reserved.
Abstract: The relatively hindered 2,2-bis(benzotriazol-1-yl)acetonitrile oxide was prepared in situ from the precursor hydroximinoyl chloride, and was allowed to react with dipolarophiles to give rise to several isoxazoles. The benzotriazole substituents acted as steric auxiliaries to prevent unwanted dimerization of the nitrile oxide to the furoxan by-product.
Abstract: The synthesis of several ABE tricyclic analogues of the alkaloid methyllycaconitine 1 is reported. The analogues contain two key pharmacophores: a homocholine motif formed from a tertiary N-ethyl amine in a 3-azabicyclo-[3.3.1]nonane ring system and a 2-(3-methyl-2,5-dioxopyrrolidin-1-ly)benzoate ester. The synthesis of the ABE tricyclic analogues of MLA 1 began with selective allylation at C-3 of 3 to produce allyl beta-keto ester 4. Double Mannich reaction of 4 with ethylamine and formaldehyde produced bicyclic amine 5. The C-9 ketone of bicyclic amine 5 was selectively reduced to form bicyclic alcohols 6 and 7 which were subsequently allylated to form dienes 8 and 9. Ring closing metathesis of dienes 8 and 9 afforded tricyclic ethers 11 and 12, respectively, the C-8 ester of which was reduced to a hydroxymethyl group to form ABE tricyclic analogues 13 and 14. Addition of allylmagnesium bromide to the C-9 ketone of 20 afforded dienes 21 and 22, which underwent ring closing metathesis to form tricyclic esters 23 and 24, respectively. Reduction of the C-8 ethyl ester of 23 and 24 to a hydroxymethyl group afforded diols 25 and 26 respectively. The 2-(3-methyl-2,5-dioxopyrrolin-1-ly)benzoate ester was introduced by conversion of alcohols 13, 14, 25 and 26, to the anthranilate esters 16, 17, 27 and 28 using N-(trifluoroacetyl)anthranilic acid 15 followed by fusion with methylsuccinic anhydride to afford the substituted anthranilates 18, 19, 29 and 30 containing the key 2-(3-methyl-2,5-dioxopyrrolidin-1-ly)benzoate ester pharmacophore.
Abstract: Treatment of an equimolar mixture of stilbene 7 and cinnamyl alcohol 8 with silver carbonate in acetone-benzene afforded a ca. 2 : 1 : 2 : 1 mixture of the stilbenolignan (+/-)-aiphanol (1) and congeners 2-4 each of which show significant anti-angiogenic and COX-2 inhibitory properties.
Abstract: The synthesis of four novel ABE ring analogues of methyllycaconitine (MLA) is reported, employing olefin metathesis as the key step for appending the seven-membered B ring onto an AE bicyclic ring system. This strategy allows the stereodivergent synthesis of ABE ring analogues in which the stereochemistry of the AB ring junction is well defined. The compounds are designed as ligands to study binding and function of the alpha7-nAChR. (C) 2002 Elsevier Science Ltd. All rights reserved.
Abstract: The synthesis of ABE tricyclic analogues 18 of the alkaloid methyllycaconitine 1 is described. The analogues contain the key pharmacophore reputed to be responsible for the biological activity of methyllycaconitine 1, namely, a homocholine motif formed from a tertiary N-ethylamine in a 3-azabicyclo[ 3.3.1] nonane ring system and a 2-(3-methyl-2,5-dioxopyrrolin-1-yl) benzoate ester side chain. The 3-azabicyclo[3.3.1] nonane ring system 10 was assembled via a double Mannich reaction of ethyl 3-(but-3'- enyl)-2-oxocyclohexane-1-carboxylate 9 with ethylamine and formaldehyde. Attempts to append a B ring to this AE ring system via McMurray coupling of dialdehyde 5 were hampered by the inability to effect conversion of the C-9 ketone 10 to vinyl ether 6. Wittig methylenation of ketone 10 afforded diene 7, however, subsequent attempts to effect double hydroboration-oxidation of diene 7 failed to realise diol 11 en route to the key dialdehyde precursor 5 required for the McMurray coupling. Wacker oxidation of the homoallyl group of 10 afforded methyl ketone 12 which underwent intramolecular aldol condensation to form enone 13. After selective reduction of the ketone and methylation, the resultant methyl ethers 15 underwent reduction of the ester sidechain affording neopentyl substituted alcohols 16. Finally, the 2-(3-methyl-2,5-dioxopyrrolin-1-yl) benzoate ester sidechain was appended by treatment of alcohols 16 with N-(trifluoroacetyl) anthranilic acid followed by fusion of the resultant anthranilates 17 with methylsuccinic anhydride.
Abstract: A high yielding and operationally simple synthesis of anthranilate esters derived from primary, secondary and tertiary alcohols is reported. Esterification of the alcohol with N-(trifluoroacetyl)anthranilic acid under Steglich conditions, followed by sodium borohydride mediated cleavage of the trifluoroacetyl group affords the anthranilate ester. This new method has application in the synthesis of the ester sidechains of the commonly occurring Delphinium and Aconitum alkaloids and their analogues. (C) 2001 Elsevier Science Ltd. All rights reserved.
Abstract: Isoxazoles substituted with an electron-withdrawing group at the 4-position undergo electrochemical and yeast-catalysed N-O bond cleavage. The electrolysis is much more efficient and, with acyl- and alkoxycarbonyl-substituted isoxazoles, it affords the enolised dicarbonylimine functionality characteristic of the herbicide Grasp (R). Regioisomeric 4- and 5-substituted isoxazoles are accessible through nitrile oxide cycloaddition chemistry, using halogen as a steric auxiliary to control the regiochemistry of reaction. Crystal data for compounds 11 and 19b are presented.
Abstract: A series of gamma-substituted alpha-methylidene-gamma-butyrolactone derivatives underwent regiospecific 1,3-dipolar cycloaddition with N-methyl-C-phenylnitrilimine. These reactions proceeded regiospecifically and with high diastereoselectivity, generally favouring the anti diastereomer as determined by n.m.r. spectroscopy and semiempirical molecular orbital calculations. The assignment for one product was confirmed by X-ray crystallography. N-Methyl-C-phenylnitrilimine underwent regiospecific cycloaddition with a range of C=S-containing dipolarophiles. Substituted thioureas were generally unreactive as dipolarophiles, while 5-thio-substituted 1,3,4-thiadiazole-2(3H)-thiones underwent ready reaction to produce, rather than the expected cycloadducts, complex rearrangement products. The structure of one of these unusual products has been confirmed by X-ray crystallography. A series of disubstituted nitrilimines underwent regiospecific cycloaddition with thiobenzophenone; the structures of the products were confirmed by X-ray crystallography.
Abstract: The 1,3-dithiane of 2-oxopropanenitrile oxide is less prone to dimerization than the parent compound and, as a consequence, it undergoes more efficient cycloaddition reactions with a range of mono- and 1,1- and 1,2-di-substituted alkenes. (C) 1997 Elsevier Science Ltd.
Abstract: Fused isoxazoles underwent reductive ring-opening in the presence of molybdenum hexacarbonyl to give the corresponding beta-disubstituted compounds. 3,6,6-Trimethyl-6,7-dihydro-1,2-benzisoxazol-4(5H)-one oxime underwent reductive ring-opening in the presence of molybdenum hexacarbonyl to give 3,6,6-trimethyl-6,7-dihydro-1H-indazol-4(5H)-one. A mechanism is proposed.
Abstract: Perfluorohexane is shown to be a good alternative to carbon tetrachloride as a non-toxic, non-ozone-depleting, inert reaction medium for bromination reactions. Yields of brominated products were nearly quantitative and the reaction work-up was easier.
Abstract: Contrary to recent reports, baker's yeast is not required for reactions of nitrile oxides with either ethyl cinnamate or 4-vinylpyridine to give isoxazolines. beta-Cyclodextrin may alter the ratio of isomers isolated from the reactions of the cinnamate but only at concentrations of reactants much lower than those reported, and this effect is most likely due to selective product complexation rather than selective product formation.
Abstract: A series of substituted 2,2'-bipyridine derivatives was prepared using the Krohnke reaction and alkylation of 4,4'-dimethyl-2,2'-bipyridine. These compounds were screened for fungicidal activity against 9 plant diseases. 5-Phenyl-2,2'-bipyridine exhibited strong preventative and curative fungicidal activity against wheat powdery mildew (Erisyple graminis) and wheat leaf rust (Puccinia recondita).
Abstract: The title compound, C7H11NOS, an analogue of biotin, was prepared in order to further investigate the binding characteristics of biotin. The bicyclic ring system has pseudo-mirror symmetry with the tetrahydrothieno ring in an S5 beta-envelope form with the methyl substituent in an equatorial position. The cis-fused pyrrolidone system is planar [non-H atoms coplanar within 0.03 (1) A] and the dihedral angle between it and the four coplanar C atoms of the tetrahydrothieno ring is 119.0 (2)degrees. The C-S bond lengths are 1.808 (4) and 1.803 (4)Angstrom, and the C-S-C angle is 88.8 (2)degrees.
Abstract: (3a alpha,6 beta,6a alpha)-6-Methyltetrahydro-1H-thieno[3,4-b]pyrrol-2(3H)-one (2) was prepared as a crippled analogue of biotin. The key synthetic step involved hydrogenation of 6-methyl-1H- thieno[3,4-bipyrrol-2(3H)-one on palladium to introduce the necessary ali-cis configuration. Both compounds were weak inhibitors of the biotin-dependent wheat acetyl-CoA carboxylase compared to substrates or the potent herbicidal inhibitors of this enzyme, but were more potent than biotin or imidazolidone. Neither compound inhibited the biotin-dependent transcarboxylase component of bacterial acetyl-CoA carboxylase, nor did they significantly inhibit the growth of Arabidopsis thaliana.
Abstract: Pyridin-2-nitrile oxide was generated in situ and reacted with 2-substituted but-1-ene-4-ols to give 5-substituted 5-(2-hydroxyethyl)-3-(pyrid-2-yl)-Delta(2)-isoxazolines. The isoxazolines were reductively ring-opened with LiAlH4 to give 2-(3-substituted-1-amino-3,5-dibydroxypentyl)-pyridines, which were subjected to Dess-Martin oxidation with concomitant dehydration to give 4-substituted 2,2'-bipyridines.
Abstract: The title compound, C15H13Cl2NO2, resulted from a 1,3-dipolar cycloaddition (a class of reactions of significant importance in heterocyclic chemistry). The isoxazole ring atoms are coplanar to within 0.05 (1) Angstrom and the cyclohexanone ring of the norbornanone moiety adopts the expected boat form with the two five-membered rings in envelope conformations. The orientation of the isoxaxole ring to the cyclohexanone ring is given by the torsion angles O1'-C2-C3-O3 71.7 (4) and C4'-C2-C1-C6 -64.0 (4)degrees. The dihedral angle between the isoxazole and 2,6-dichlorophenyl rings is 73.3 (3)degrees.
Abstract: The anion derived from 2-methylpropyl 3-(2-methylpropoxy)-5-oxocyclohex-3-ene-1-carboxylate was reacted with methyl iodide to give cis and trans isomers of 2-methylpropyl 6-methyl-3-(2-methylpropoxy)-5-oxocyclohex-3-ene-1-carboxylate. The reaction proceeded with high regioselectivity. A combination of n.m.r. experiments was used to determine that the major diastereoisomer was in a trans configuration. The dianion derived from 2-methylpropyl 3-(2-methylpropoxy)-5-oxocyclohex-3-ene-1-carboxylate methylated at C 1 and C 6 with a roughly equal proportion of cis and trans isomers. When treated with 1 equiv. of 1-bromo-3-chloropropane the same dianion alkylates at C 1 to give 2-methylpropyl 1-(3-chloropropyl)-3-(2-methylpropoxy)-5-oxocyclohex-3-ene-1-carboxylate .
Abstract: The isoxazolines 2a, 2b and 8 obtained from nitrile oxide cycloadditions to cyclohex-2-enone 1a and its analogues 1b and 7 reacted with nickel peroxide to give the isoxazoles 3a, 3b and 9. In contrast, the corresponding 2-bromocyclohex-2-enones 4a, 4b and 10, prepared by bromination of the corresponding alkenes la, Ib and 7, underwent nitrile oxide cycloadditions to afford the regioisomeric isoxazoles 6a, 6b and 12, respectively.
Abstract: (2R)-4-Methylene-2-phenyl-3-propionyloxazolidin-5-one underwent 1,3-dipolar cycloaddition with 2,6-dichlorobenzonitrile oxide to give (5S,7R)-3(2,6-diphenyl)-7-phenyl-6-propionyl-2,6-propionyl-2,6-diaza-1,8 -dioxaspiro[4.4]non-2-en-9-one, a protected isoxazoline amino acid. The reaction proceeded regiospecifically and with high stereoselectivity. The anti addition product predominated. The regiochemistry of addition was determined by nmr and the stereochemistry of addition was determined by X-ray analysis. The transition state energies for syn and anti addition were calculated using the semi-empirical AM1 method in the MOPAC package.
Abstract: The phase behaviour, liquid crystal structures and head group hydration of two 4-n-alkylpyridine-N-oxide surfactants have been studied using optical microscopy, DSC and H-2 NMR spectroscopy. Only a limited swelling of the surfactant phase occurs in water, so that no micellar solution phase (L1) occurs. The lamellar phase is the only mesophase observed. Water (H-2) quadrupole splittings indicate that the head group binds c. 6 water molecules.
Abstract: A number of gamma-substituted alpha-methylene-gamma-butyrolactone derivatives underwent 1,3-dipolar cycloaddition with propionitrile oxide to give spiro DELTA2-isoxazolines. The reaction proceeded regiospecifically and with high diastereoselectivity. The products of anti addition predominated. The regiochemistry of addition and relative stereochemistry of the products were determined by a combination of n.O.e., HETCOR and DOUBTFUL n.m.r. experiments. The assignment was confirmed in one case by X-ray crystallography.
Abstract: Anions derived from t-butyl-substituted pyrimidin-4-ols were methylated with iodomethane. The site of methylation was determined by proton-coupled C-13 n.m.r. and the relative proportions of isomers were determined by H-1 n.m.r. A t-butyl substituent ortho to a ring nitrogen markedly reduced the propensity for methylation at that nitrogen to the point where O-methylation, uncommon under these conditions, was observed.
Abstract: Thresholds for the appearance of fragment ions allowed the estimation of threshold fragmentation energies (TFE) for the collisionally activated dissociation (CAD) in the gas phase of laser-desorbed pyridine-ring substituted N-benzylpyridinium cations to form pyridine and a carbocation. p-Methylbenzylpyridinium cation underwent an alternative CAD into pyridinium cation and the p-quinodimethane. The TFE are discussed in comparison with the energy differences (DELTADELTAH(f) = DELTAH(f)(Py) + DELTAH(f)(R+) - DELTAH(f)(Py+R)) calculated by the AMI method to provide strong evidence for benzyl to tropylium cation rearrangement in an ion-molecule pair.
Abstract: The preparations are described of 10-dodecyl- and 10-tetradecylbenzo[a]acridines, 9-tetradecylbenzo[c]acridine, and some 8-tetradecylbenzo[a]carbazoles and 10-tetradecylbenzo[c]carbazoles.
Abstract: Six organic compounds were spray-coated onto surface acoustic wave devices which were then exposed to vapors of acetone, diethyl ether, dichloromethane, chlorobenzene, benzene, and acetonitrile. Changes in the resonant frequency of the device or in the resistance of the coating were collected by computer-controlled data acquisition. Different patterns of response to the six vapors were observed for each of the coatings.
Abstract: A gem-diazide has been prepared from bis(benzotriazol-1-yl)methane and further elaborated through Staudinger phosphorylation, Grignard reactions, and treatment with 1,2-diketones to give a new route to 2,2-disubstituted 4,5-diphenylimidazoles.
Abstract: A review of nitrile oxide cycloaddition chemistry, with 350 references, which covers the literature between 1985 and 1992. Earlier work is covered where it is required to put recent developments into context. Particular attention is given to dramatic improvements in the degree of stereochemical control that has been obtained in intermolecular nitrile oxide cycloaddition reactions.
