Interactions intramoléculaires. XXVII—Etudes structurales en série bicyclo[4.1.0]heptanique (effets d'anisotropie sur les déplacements chimiques du proton; constantes de couplage et équilibres conformationnels)

All the ¹H n.m.r. parameters of the following derivatives of 1,6-dimethylbicyclo[4.1.0]heptane are determined: 3,4-dimethoxycarbonyl (3 diastereoisomers), cis- and trans-3-methoxycarbonyl-2,2,5,5-d₄, cis- and trans-3-methyl-3-methoxycarbonyl; the cis- and trans-1,5,5-trimethylbicyclo[4.1.0]-3-heptanols are studied in the same way. The different chemical shifts are correlated with the aid of a collection of empiral increments. The conformational equilibria are determined from the vicinal coupling constants; the conformational free energies of the COOCH₃ group are evaluated; the part played by gauche interactions is considered.     

Interactions intramoléculaires: XXIII—Constantes de couplage et interactions gauches avec un groupement t-butyle (cyclohexanones disubstituées 3, 4)

The ¹H NMR spectra of a series of cis and trans-3R,4 X-cyclohexanones (-2,2,6,6-d₄) are analysed. By comparison of their ³J coupling constants with those of cyclohexane homologues we obtain information about the chair–chair equilibrium constants for R = CH₃, X = CN, the chair structure of cis isomers with an equatorial t-butyl group, and a conformational heterogeneity with trans (CH₃)₃C and CN groups. This latter situation is analysed by means of a simplified but controlled Karplus relationship, on the basis of a mixture of two conformers; this involves a diequatorial chair and a boat form with a dihedral angle Φ₃₄ of about ?6°.     

Interactions intramoléculaires. XXVI—Constantes de couplage et hétérogénéités conformationnelles dans une série de R-3 et R-5 cyano-4 cyclohexènes deutériés (R=méthyl ou t-butyl)

For trans-3-R- and 5-R-1-acetoxy-4-cyanocyclohexene-6,6-d₂ the molar fractions of diequatorial conformers are 0.83 (3-methyl), 0.68 (5-methyl), 0.57 (3-tert-butyl) and 0.55–0.69 (5-tert-butyl). For the last two compounds the values of the coupling constants are in agreement with the hypothesis of an ee?aa equilibrium. For the cis isomers, the molar fractions of equatorial alkyl conformers are 0.76 (3-methyl and 5-methyl) and 1.0 (3-tert-butyl and 5-tert-butyl). The cis-1-acetoxy-3-tert-butyl-4-methoxycarbonyl-cyclohexene presents a conformational heterogeneity. The conformational free energy of the methyl group in position 4 has been evaluated as ?0.6 kcal mol^?1 (2.5 kJ mol^?1).     

Stereochemistry of alkyl 3-substituted 4-halotetrahydro-2-oxo-3-furancarboxylates: 2—1H and 13C NMR spectra

The ¹H NMR parameters of methyl 3-substituted cis-4-halotetrahydro-2-oxo-3-furancarboxylates are reported, with assignments of the ring protons based on solvent-induced changes in the vicinal trans coupling constants, ³J(H-4, H-5). Preferred conformations, ce with a pseudo-equatorial halogen for the cis isomers and ta with a pseudo-axial halogen for the trans isomers, have been suggested on comparison of the magnitudes of J(trans) and J(gem) in both series. The ³J(¹³CH₃, H-4) values measured for methyl cis-4-bromotetrahydro-3-methyl-3-furancarboxylate, methyl trans-4-bromotetrahydro-3-methyl-3-furancarboxylate and trans-3,4-dibromodihydro-3-methyl-2(3H)-furanone have confirmed the stereochemical assignments.     

Interactions intramoléculaires—XIX: Constantes de couplage vicinales, équilibres conformationnels et interactions gauches (séries cyclohexanique et cyclohexénique)

NMR parameters are determined and identified for the four stereoisomers of 3,4-dimethyl methoxycarbonylcyclohexane (d₃-2,2,3,4,5,5), the two stereoisomers of 2-methyl methoxycarbonylcyclohexane (d₅-2,3,4,5,5) and 3-methyl 4-X cyclohexene (d₃-3,6,6) (X = COOCH₃, CH₂OH, CH₂Cl). For the axial COOCH₃ substituted cyclohexane, the vicinal coupling constants are in agreement with the ring deformation. Different conformational equilibria are estimated and discussed, especially in relation to the inequality of gauche interactions between two cis vicinal substituents.     

Utilisation d'ylides du phosphore non stabilisés en chimie des sucres VI. Sucres ramifiés dérivés des di-O-isopropylidène-1,2:5,6-α-D-ribo-et-α-D-xylo-hexofurannosul-3-oses

The cis and trans isomers of 3-deoxy-1,2:5,6-di-O-isopropylidene-3-C-methylthiomethylene-α-D -xylo- and -α-D -ribo-hexofuranoses have been prepared by treatment of 1,2:5,6-di-O-isopropylidene-α-D -xylo- and -α-D -ribo-hexofuran-3-uloses with methylthiomethylene-triphenylphosphorane. Configurations are assigned by NMR. A new type of ⁴J is described. Hydrogenation-desulfurization of the methylthiovinylic sugars affords 3-deoxy-3-methyl sugars of the D -allo, D -gulo, and D -galacto series. Derivatives of 3-deoxy-3-methyl-D -lyxose and 3-deoxy-3-methyl-D -ribose are prepared by chain-shortening of derivatives of the corresponding 3-deoxy-3-methyl-hexoses.     

cis-trans-and Intramolecular enol-enolic equilibrium of β-ketoaldehydes

Tautomerism of aromatic β-ketoaldehydes p-XPhCOCH₂CHO ( 1 , X = NMe₂, OMe, Me, H, Br, NO₂), aliphatic β-ketoaldehydes and benzoylacetaldehyde RCOCH₂CHO ( 2 , R = Me, i-Bu, t-Bu, Ph), RCOCH(Me)CHO ( 3 , R = Me, Et, i-Pr) and methyl 2-formylpropionate MeOCOCH(Me)CHO ( 4 ) has been studied by the ¹H NMR technique. In basic solvents both cis- and trans-enol forms of these compounds co-exist. trans-Enolisation, which occurs exclusively at the formyl group, is most favoured in compound ( 4 ) and least favoured in compounds ( 1 ) and ( 2 ). The increasing electron-attracting property of the substituent X in the aromatic β-ketoaldehydes ( 1 ), as well as increasing solvent basicity in the series propanediol-1, 2-carbonate, acetone < dimethylformamide < dimethylacetamide < pyridine, also shifts the equilibrium towards the trans-enol form. The trans-enol form is absent in aprotic solvents of low basicity such as CCl₄, C₂HCl₃ and toluene. The thermodynamic parameters of the cis-trans-enol (C ? T) and cis-enol-enolic (C ? C') equilibria have been estimated from the temperature dependences. The transition from the cis-to the trans-enol form is accompanied by an entropy decrease of about 10 cal mol^?1 degree^?1. Nevertheless the trans-enol form is stabilised due to its lower enthalpy. The cis-trans-enol equilibrium is determined by the relative strength of the intramolecular hydrogen bond in the cis-enol form and the intermolecular hydrogen bonds with basic solvent molecules of the trans-enol form. The enthalpy difference of the two cis-enolic forms does not exceed 1.0 kcal/mol, in rough agreement with the data calculated by the CNDO/2 approximation. Polar solvents favour the hydroxymethyleneketone form (C) for both groups of compounds 2 and 3 . The content of the hydroxymethyleneketone form is about the same within series 2 where R = Me, i-Bu, Ph and is a little higher for the t-Bu derivative. A decrease of temperature only slightly shifts the equilibrium of compounds 1 and 2 to the hydroxymethyleneketone form, while in the case of 2-methyl-β-ketoaldehydes (3) this effect is markedly pronounced.     

Stereochemistries of electron impact induced hydrogen abstraction reactions proceeding through 6-membered transition states

The stereochemistries of nine electron-impact induced eliminations proceeding from derivatives of the cis-4-t-butyl system have been determined. The predominant cis elimination observed in every case is consistent with the substantial integrity of the cyclohexyl ring prior to fragmentation, and with a cyclic transition state for hydrogen abstraction. The stereochemistries of electron impact induced eliminations from 11 derivatives of the trans-4-t-butylcyclohexyl system exhibit a dichotomy. The predominatn trans stereochemistry observed in six electron impact induced eliminations, and the nonstereospecific electron impact induced dehydration of trans-4′-t-butylcyclohexyl-ethanol are consistent with nonconcerted elimination from a chair-like cyclohexyl ring. Conversely, the McLafferty rearrangement of trans-4′-t-butyl-cyclohexyl-2-propanone proceeds nonstereospecifically. trans-4-t-Butylcyclohexyl acetaldehyde, 2-methyl-3-(trans-4′-t-butylcyclohexyl)-1-propane and trans-4-t-butylcyclohexyl-S-methyl xanthate exhibit predominant cis McLafferty rearrangement stereochemistry. This result may be due to fragmentation through boat-like conformers in these compounds.     

Synthesis, 1H- and 13C-NMR spectra,crystal structure and ring openings of 1-methyl-6,9-epoxy-9-aryl-5,6,9,10-tetrahydro-1H-imidazo [3,2-e] [2H-1,5] oxazocinium methanesulfonate

The methanesulfonic acid catalyzed reaction of 1-(4-chloro- and 2,4-dichlorophenyl)-2-(1-methyl-2-imida-zolyl)ethanones 1a and 1b with glycerol produced cis- and trans-{2-haloaryl-2-[(1-methyl-2-imidazolyl)methyl]-4-hydroxymethyl}-1,3-dioxolanes 2a and 2b with a 2:1 cis/trans ratio. Besides these five-membered ketals, the reaction of 1a with glycerol afforded a small amount of trans-{2-(4-chlorophenyl)-2-[(1-methyl-2-imidazolyl)methyl]-5-hydroxy}-1,3-dioxane ( 3a , 7%). The reaction of methanesulfonyl chloride with cis-1 formed the corresponding methanesulfonates, cis- 4 , which rapidly cyclized to the title compounds 5 . Base-catalyzed ring opening of 5 furnished 1-methyl-5,6-dihydro-6-hydroxymethyl-8-(4-chloro- and 2,4-dichlorophenyl)-1H-imidazo[3,2-d][1,4]oxazepinium methanesulfonates 7 . Acid-catalyzed hydrolyses of 5 or 7 provided 1-methyl-2-[(4-chloro- and 2,4-dichloro)phenacyl]-3-[(2,3-dihydroxy)-1-propyl]imidazolium salts 12 . Structure proofs were based on extensive ¹H and ¹³C chemical shifts and coupling constants and structures of 3a and 5a were confirmed by single crystal X-ray crystallography.     

Sur la tétrabromo-2, 2, 6, 6 méthyl-4 cyclohexanone: Mise en evidence d'un equilibre conformationnel par RMN à haut champ

High field n.m.r. spectra of 2,2,6,6-tetrabromo-4-methyl- and -4-tert-butylcyclohexanones ( 1 and 2 ) have been computed and simulated. From coupling constants (J_gem, J_ea, J_aa and ⁴J) and chemical shifts it is shown that 1 is in equilibrium in solution. This work supports the conclusions deduced from infrared data of 1 in the scissors vibration region δ(CH₃).     

NMR experiments on acetals—XXXIX: Conformational insights through NMR studies at 300 MHz of 2-methyl-4-halogenomethyl-1,3-dioxolanes

NMR spectra of cis- and trans-2-methyl-4-halogeno-methyl-1,3-dioxolanes have been analysed at 300 MHz. Some of the extracted parameters facilitate easy distinction between these 1,3-dioxolanes and the corresponding structurally isomeric 2-Methyl-5-halogeno-1,3-dioxanes. Criteria enabling configurational assignments to be made for the cis-trans isomers of the dioxolane series are tested. The Me-2 group causes an upfield shift (0·2 to 0·3 ppm) of a trans proton at position 5, but the reversed shift for the corresponding cis proton. This competes with, or even overwhelms the effect of the CH₂X-4 substituent, which by virtue of its pronounced preferential rotameric orientation and in comparison with a simple Me-group, has no large upfield effect on the shift of the syn-adjacent proton. Shift criteria and coupling constants J_{H-4, H-5} in cis- and trans derivatives allow further conformational insights into these 1,3-dioxolanes.     

Die thermische Umlagerung von 2-(Buta-1′,3′-dienyl)-phenolen in 2-Alkyl-2H-chromene; Beispiele für aromatische [1,7a]- und [1,5s]sigmatropische Wasserstoffverschiebungen

2-(1′-cis,3′-cis-)- and 2-(1′-cis,3′-trans-Penta-1′,3′-dienyl)-phenol (cis, cis- 4 and cis, trans- 4 , cf. scheme 1) rearrange thermally at 85–110° via [1,7 a] hydrogen shifts to yield the o-quinomethide 2 (R ? CH₃) which rapidly cyclises to give 2-ethyl-2H-chromene ( 7 ). The trans formation of cis, cis- and cis, trans- 4 into 7 is accompanied by a thermal cis, trans isomerisation of the 3′ double bond in 4. The isomerisation indicates that [1,7 a] hydrogen shifts in 2 compete with the electrocyclic ring closure of 2 . The isomeric phenols, trans, trans- and trans, cis- 4 , are stable at 85–110° but at 190° rearrange also to form 7 . This rearrangement is induced by a thermal cis, trans isomerisation of the 1′ double bond which occurs via [1, 5s] hydrogen shifts. Deuterium labelling experiments show that the chromene 7 is in equilibrium with the o-quinomethide 2 (R ? CH₃), at 210°. Thus, when 2-benzyl-2H-chromene ( 9 ) or 2-(1′-trans,3′-trans,-4′-phenyl-buta1′,3′-dienyl)-phenol (trans, trans- 6 ) is heated in diglyme solution at >200°, an equilibrium mixture of both compounds (～ 55% 9 and 45% 6 ) is obtained.     

Interactions intramoleculaires: XXII—Constantes de couplage, équilibres conformationnels et interactions gauches avec un groupement t-butyle (molécules cyclohexéniques deutériées)

The NMR parameters are determined for a series of disubstituted (R = CH₃, (CH₃)₃C; X = COOCH₃, CN) and specifically deuterated cyclohexenes. The ³ J(HH), ³J(HD), ⁴J(HH) and ⁵ J(HH) coupling constants are used to evaluate the conformational equilibria. Three of the five compounds with an allylic t-butyl substituent, are conformationally heterogeneous; these equilibria, and those between stereoisomers are used for an analysis of this phenomenon, carried out within the framework of the hypothesis of additivity of conformational free energies and gauche interactions.     

Conformation et spectrométrie de R.M.N.: II

The four isomeric 3-dimethylamino-trans-2-decalols-1,1,4,4-d₄ have been synthesised. Examination of PMR spectra of these compounds allows us to confirm the ‘flattened-chair’ conformation for the cis N(CH₃)₂^a OH^e isomer, whereas the remaining three conserve the double chair conformation. The same type of flattening is also observed in the case of the diaxial quaternary ammonium salt and is even more marked in the cis N(CH₃)₃^a OH^e isomer resulting in a ‘twist-chair’ conformation.     

Optisch aktive 4,5-Epoxy-4,5-dihydro-α-ionone und Synthese der stereoisomeren 4,5:4′,5′-Diepoxy-4,5,4′,5′-tetrahydro-ϵ,ϵ-carotine und der sterische Verlauf ihrer Hydrolyse

Optically Active 4,5-Epoxy-4,5-dihydro-α-ionones; Synthesis of the Stereoisomeric 4,5:4′,5′-Diepoxy-4,5,4′,5′-tetrahydro-?,?-carotenes and the Steric Course of their Hydrolysis We prove that epoxidation with peracid of α-ionone, contrary to a recently published statement, predominantly leads to the cis-epoxide. Acid hydrolysis affords a single 4,5-glycol whose structure, established by an X-ray analysis, shows that oxirane opening occurred with inversion at the least substituted position (C(4)). Stable cis-and trans-epoxides are prepared by epoxidation of the C₁₅-phosphonates derived from α-ionone. Both the racemic and optically active form are used for the synthesis of the 4,5:4′,5′-diepoxy-4,5,4′,5′-tetrahydro-?,?-carotenes having the following configuration in the end groups: meso-cis/cis, meso-trans/trans, rac-cis/trans, rac- and (6R, 6′ R)-cis/cis, rac- and (6R, 6′R)-trans/trans, rac- and (6R, 6′R)-cis/trans, and (6R, 6′ R)-cis/?. Acid hydrolysis of the cis/cis-epoxycarotenoids under relatively strong conditions occurs again with inversion at C(4)/C(4′) in case of the cis/cis-epoxycarotenoids, but at C(5)/C(5′) in case of the trans/trans-epoxycarotenoids. An independent synthesis of this 4,5,4′,5′-tetrahydro-?,?-carotene-4,5,4′,5′-tetrol is presented. The irregular results of the oxirane hydrolysis are explained by assumption of neighbouring effects of the lateral chain. 400-Mz-¹H-NMR data are given for each of the stereoisomeric sets. In the visible range of the CD spectra, the (6R, 6R′)-epoxycarotenoids compared with (6R, 6R′)-?,?-carotene exhibit an inversion of the Cotton effects.     

Cyanidverbrückte Koordinationspolymere aus cis‐ oder trans‐[Ru(tBuNC)4(CN)2] und MnCl2: Zum Einfluß unterschiedlicher Topologien auf die magnetischen Eigenschaften von Materialien

Cyanide Bridged Coordination Polymers from cis‐ or trans‐[Ru(^tBuNC)₄(CN)₂] and MnCl₂: About the Influence of Different Topologies on the Magnetic Properties of Materials The reaction of cis‐ or trans‐[Ru(^tBuNC)₄(CN)₂] with MnCl₂ as an additional transition metal fragment yields the one dimensional coordination polymers {cis‐[Ru(CN)₂(^tBuNC)₄] MnCl₂}_n, ( 1 ), and {trans‐[Ru(CN)₂(^tBuNC)₄]MnCl₂}_n, ( 2 ), with a different arrangement of the metal centers caused by the different stereochemistry of the starting compounds. The variation of the Ru‐C‐N‐Mn geometry nevertheless leads to significant differences in the magnetic properties of 1 and 2 . The coordination polymer derived from trans‐[Ru(^tBuNC)₄(CN)₂] shows a more efficient antiferromagnetic intrachain interaction between the manganese centers compared to the cis‐derivative.     

Déplacements Chimiques induits en RMN par un Réactif Lanthanidique: II—Analyse Conformationnelle de Sulfinamates Cycliques: Oxo-2 Oxathiazannes-1,2,3 et Oxo-2 Benzo-5,6 Dihydro-3,4 Oxathiazines-1,2,3

Re-examination of recent results in the literature about 2-r-substituted 5-c-tert-butyl-1,3,2-dioxaphosphorinanes and 3,3-dimethyl-1-oxothiethan made us select, under the indicated conditions, the static model because it is easier to use than the dynamic one. Its application to 17 cyclic sulphinamates belonging to two series—the 2-oxo-1,2,3-oxathiazans (I) and the 5,6-benzo-3,4-dihydro-2-oxo-1,2,3-oxathiazins (II)—confirms, in the presence of Eu(fod)₃, the structures established without the shift reagent, from chemical shifts and coupling constants only, and shows their conformational diversity. For the series (I) the following conformations are found: (i) standard chairs with an axial S?O group (CA) when the molecule is not substituted in the 4 and 6 positions or when the substituents are equatorial (with the exception of 3-tert-butyl-4-t-methyl-2-r-oxo-1,2,3-oxathiazan); the substituents R?Me, iPr or tBu on the nitrogen atom are preferentially axial; (ii) strained chairs with axial Me-4 and S?0 groups (CA); in this conformation R?Ph may be partially conjugated and R?Me or tBu may prefer the more favourable axial orientation; (iii) twist conformations with a 1,4-axis and an axial S?O group (COA) for the two 4-c,6-c- and 4-t,6-c-di-tert-butyl-2-r-oxo-3-phenyl-1,2,3-oxathiazans; (iv) the twist conformation with a 3,6-axis and an axial S?O group (CNA) for trans-3-tert-butyl-4-methyl-2-oxo-1,2,3-oxathiazan because of the 4-methyl—3-tert-butyl 1,2-interaction. For the series (II) half-chair forms with an axial S?O group are proposed.     

Synthesis and structure of stable cis-dimethyl complex of oxotungsten(VI)

Oxotungsten(VI) complex cis-[WO(L^tBu)Me₂] (L^tBu = methylamino-N,N-bis(2-methylene-4-methyl-6-tert-butylphenolate) dianion) was prepared by the transmetallation reaction of [WO(L^tBu)Cl₂] (either cis or trans isomer) with methyl magnesium iodide. This unexpectedly stable dialkyl complex can be activated by Et₂AlCl to catalyze the ring-opening metathesis polymerization of norbornene.     

Synthese von (±)-Diplodialid B und A

Synthesis of (±)-Diplodialide B and A Two steroid hydroxylase inhibitors, diplodialide B (1) and A (2) have been synthesized in the following way: The lithium enolate 5 of S-t-butyl thioacetate (4) was added to (E)-7-(2′-tetrahydropyranoxy)-2-octen-1-al (8) and the newly formed 3-hydroxy group in the product 9 was protected as t-butyl-diphenyl silyl ether followed by selective hydrolysis of the tetrahydropyranyl ether to give 10. Treatment with AgNO₃/H₂O cleaved the S-t-butyl ester group in 10 to give the corresponding hydroxy carboxylic acid which was converted into the S-2-pyridyl thioester by treatment with di(2-pyridyl)disulfide and triphenyl phosphine and cyclized with AgClO₄ to give the (4E,3,9-trans)- and (4E,3,9-cis)-lactone 11 and 12 (R?t-Bu(C₆H₅)₂Si) in 67% yield. Chromatographic separation of 11 and 12 and cleavage of the t-butyl-diphenyl silyl ether with tetrabutyl ammonium fluoride yielded (±)-diplodialide B (1) with (4E,3,9-trans)-configuration and the (4E,3,9-cis)-isomer 12 (R?H). Both isomers could be oxidized to diplodialide A (2) with manganese dioxide. The synthesis described above has also been carried out via the intermediates 10 , 11 and 12 with R?COOCH₂CH₂Si(CH₃)₃.     

High-resolution NMR spectra of the polysulfones of six monolefins

100-MHz NMR spectra are reported for solutions of the 1:1 copolymers of sulfur dioxide with hex-1-ene, cis- and trans-but-2-enes, cyclohexene, cyclopentene, and norbornene, including the deuterated polymers made from hex-1-ene-2-d₁, cis- and trans-but-2-ene-2,3-d₂, and cyclohexene-3,3,6,6-d₄. The resolution of the spectrum of poly-(hex-1-ene sulfone) was very poor in CCl₄ as solvent but good in polar solvents. The main-chain CH₂ protons are nonequivalent, and their chemical shifts show sensitivity to dyad structure; the α-CH₂ protons are also non-equivalent. The spectra of most of the other polymers are discussed in terms of possible preferential modes of addition as well as tacticity effects.