Interaction between Exocyclic s-cis-Butadiene and Homoconjugated Functions. Preparation and Diels-Alder Reactivity of Remotely Substituted 2,3-Dimethylidenebicyclo[2.2.2]octanes

The preparations of 5,6-dimethylidene-2exo-bicyclo[2.2.2]octanol ( 8 ), its endo isomer 9 , 5,6-dimethylidene-2-bicyclo[2.2.2]octanone ( 10 ) and 2 exo, 3 exo-epoxy-5,6dimethylidenebicyclo[2.2.2]octane ( 11 ) are described. The kinetics of their cycloaddition to tetracyanoethylene has been measured in toluene at 25° together with those of 2,3-dimethylidenebicyclo[2.2.2]octane ( 7 ) and 5,6-dimethylidenebicyclo[2.2.2]oct-2-ene (12). The effects of remote substitution on the Diels-Alder reactivity of 2,3-dimethyl idenebicyclo[2.2.2]octanes are compared with those observed in the 2,3-dimethylidenenorbornane series ( 1–6 ).     

1H and 13C NMR study of the effects exerted by an oxirane ring in the epoxybicyclo-[2.2.2]octane series

The ¹H and ¹³C NMR spectra of 2,3-disubstituted exo-5,6- and endo-5,6-bicyclo[2.2.2]octanes, and the corresponding alkanes, have been investigated to determine the effects exerted by an oxirane ring. The ¹H NMR study showed that the anti protons, H-7a and H-8a, are significantly shielded and the syn protons, H-7s and H-8s, are deshielded, although to a smaller extent, by the exo-oxirane. An endo-oxirane has practically no effect on the same protons. The stereochemistry of epoxybicyclo[2.2.2]octanes is, thus, easily deduced from ¹H NMR data. The ¹³C NMR study of the epoxy compounds provided an estimate of the value of α, β, γ syn and γ anti effects (to the epoxide oxygen) of an oxirane ring. In these rigid bicyclic molecules, of known geometry, the γ syn and the γ anti effects are of the same value, even though the dihedral angles are very different (0° and 120°).     

The Synthesis and Chemistry of 1,3‐Bridged Polycyclic Cyclopropenes: 8‐Oxatricyclo[3.2.1.02,4]octa‐2,6‐dienes

Three 1,3‐bridged polycyclic cyclopropenes, exo‐8‐oxatricyclo[3.2.1.0^2,4]octa‐2,6‐diene ( 10 ), endo‐8‐oxatricyclo[3.2.1.0^2,4]octa‐2,6‐diene ( 11 ), and exo‐6,7‐benzo‐1,5‐diphenyl‐8‐oxatricyclo[3.2.1.0^2,4]octa‐2,6‐diene ( 12 ), have been synthesized by elimination of 2‐chloro‐3‐trimethylsilyl‐8‐oxatricyclo[3.2.1.0^2,4]‐oct‐6‐enes, 17 , 18 and 30 , which were generated from 1‐chloro‐3‐trimethylsilylcyclopropene with furan and diphenylisobenzofuran. We have demonstrated a facile route to synthesize the highly strained 1,3‐fused polycyclic cyclopropenes, 10 , 11 , and 12 . The stereochemistry of the Diels‐Alder reactions of cyclopropene 16 with furan and DPIBF are different. Cyclopropene 16 was treated with furan to form exo‐exo and endo‐exo adducts (5:2) and treated with DPIBF to generate an exo‐exo adduct. Compounds 10 , 11 and 12 undergo isomerization reactions to form benzaldehyde and phenyl 4‐phenyl‐[1]naphthyl ketone to release strain energies via diradical mechanisms.     

13C-NMR-Spektren von Tetracyclo[4.1.0.02,4.03,5]heptanen,Tetracyclo[5.1.0.02,4.03,5]octanen und Tricyclo[4.1.0.02,7]hept-3-enen. Ungewöhnliche δ- und γ-Substituenteneffekte

Carbon-13 NMR spectroscopic data of eleven tetracyclo[4.1.0.0^2,4.0^3,5]heptanes, two tetracyclo-[5.1.0.0^2,4.0^3,5]octanes and twelve tricyclo[4.1.0.0^2,7]hept-3-enes are reported. In the tetracycloheptanes, halogens located at the 7-position cause large δ substituent effects. endo-Halogens shift the C-4 signal to lower field by about 6 ppm, while exo-haolgens produce upfield shifts of the C-3 signal, which are dependent on the nature of the halogen and reach a maximum of 9.1 ppm in the case of fluorine. An orbital model is proposed to explain the δ upfield shifts. The compounds containing fluorine reveal a connection between the δ substituent effects and the corresponding ¹³C? ¹⁹F coupling constants. Substituents in the 5 position of tricycloheptenes are γ-substituents of C-1, C-3 and C-7 and produce downfield shifts of the absorptions of these nuclei. Their dependence on the nature of the substituent follows approximately those in 1-substituted adamentanes; in the case of C-7, however, their magnitude by far exceeds the adamantane values, bromine (15.5 ppm) being most effective.     

Five bicyclo[3.3.0]octa‐2,6‐dienes

A series of five compounds containing the bicyclo[3.3.0]octa‐2,6‐diene skeleton are described, namely tetramethyl cis,cis‐3,7‐dihydroxybicyclo[3.3.0]octa‐2,6‐diene‐2,4‐exo,6,8‐exo‐tetracarboxylate, C₁₆H₁₈O₁₀, (I), tetramethyl cis,cis‐3,7‐dihydroxy‐1,5‐dimethylbicyclo[3.3.0]octa‐2,6‐diene‐2,4‐exo,6,8‐exo‐tetracarboxylate, C₁₈H₂₂O₁₀, (II), tetramethyl cis,cis‐3,7‐dimethoxybicyclo[3.3.0]octa‐2,6‐diene‐2,4‐exo,6,8‐exo‐tetracarboxylate, C₁₈H₂₂O₁₀, (III), tetramethyl cis,cis‐3,7‐dimethoxy‐1,5‐dimethylbicyclo[3.3.0]octa‐2,6‐diene‐2,4‐exo,6,8‐exo‐tetracarboxylate, C₂₀H₂₆O₁₀, (IV), and tetramethyl cis,cis‐3,7‐diacetoxybicyclo[3.3.0]octa‐2,6‐diene‐2,4‐exo,6,8‐exo‐tetracarboxylate, C₂₀H₂₂O₁₂, (V). The bicyclic core is substituted in all cases at positions 2, 4, 6 and 8 with methoxycarbonyl groups and additionally at positions 3 and 7 with hydroxy [in (I) and (II)], methoxy [in (III) and (IV)] or acetoxy [in (V)] groups. The conformations of the methoxycarbonyl groups at positions 2 and 4 are exo for all five compounds. Each C₅ ring of the bicyclic skeleton is almost planar, but the rings are not coplanar, with dihedral angles of 54.93 (7), 69.85 (5), 64.07 (4), 80.74 (5) and 66.91 (7)° for (I)–(V), respectively, and the bicyclooctadiene system adopts a butterfly‐like conformation. Strong intramolecular hydrogen bonds exist between the –OH and C=O groups in (I) and (II), with O...O distances of 2.660 (2) and 2.672 (2) Å in (I), and 2.653 (2) and 2.635 (2) Å in (II). The molecular packing is stabilized by weaker C—H...O(=C) interactions, leading to dimers in (I)–(III) and to a chain structure in (V). The structure series presented in this article shows how the geometry of the cycloocta‐2,6‐diene skeleton changes upon substitution in different positions and, consequently, how the packing is modified, although the intermolecular interactions are basically the same across the series.     

An Improved General Procedure for the Synthesis of Aryloxysulfonyl Azides

In 1975, we have described the first synthesis of the aryloxysulfonyl azides (aryl azidosulfates),¹ the interest of which is confirmed to be varied, especially about the elaboration of molecules such that sulfamates² (Ar-O-SO₂-NH₂), not easily accessible by other methods and endowed with very important biological properties.^3–5 Their cycloaddition on bicyclic olefinic systems gives a new family of N-substituted aziridines, the N-aryloxy-3-aza-tricyclo[3,2,1,0^{2,4 exo}]octanes.⁶ They react with trivalent phosphorus compounds to afford some very interesting phosphine-imides.⁷     

Synthesis of fluorinated 2,6-heptanediones and 2-oxa-6- azabicyclo[2.2.2]octanes from 1,4-dihydropyridines

Electrophilic fluorination of Hantzsch-type 1,4-dihydropyridines with Selectfluor^® led to the formation of new fluorinated 2,6-heptanediones - dialkyl 2,4-diacetyl-2,4-difluoro-3-phenylpentanedioates. Novel 2,6-heptanedione derivatives in reaction with hydrazine hydrate easily form 6-amino-4,7-difluoro-3-hydroxy-1,3-dimethyl-5-oxo-8-phenyl-2-oxa-6-azabicyclo[2.2.2]octanes instead of the corresponding diazepine derivatives. The obtained 2-оxa-6-azabicyclo[2,2,2]octanes are thermally stable at the temperatures below 50°С. At higher temperatures rearrangement of 2-oxa-6-azabicyclo[2,2,2]octanes offers new fluorine-containing pyrazolinone derivatives - alkyl esters of 2-fluoro-2-((4-fluoro-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)(phenyl)methyl)-3-oxobutanoates.     

Carbon-13 nuclear magnetic resonance spectra of exo- and endo-2-norbornyltrimethyl-stannanes: Corrected assignments

The ¹³C NMR spectra of pure exo-2-norbornyltrimethylstannane and a mixture of the exo- and endo-isomers have been recorded. ¹H–¹³C polarization transfer spectra have been obtained and require the previously reported assignments for C-3 and C-4 in the exo-isomer to be reversed. The reported assignments for the endo-isomer are correct. The new assignment for C-4-exo [with J(¹¹⁹Sn,¹³C) vic=12 Hz, instead of the previously assigned J(vic)=23 Hz], has a very minor effect on the nature of the Karplus curve [for ³J(¹¹⁹Sn,¹³C)] generated previously.     

Diastereochemical differentiation of bicyclic diols using metal complexation and collision‐induced dissociation mass spectrometry

Metal complex formation was investigated for di‐exo‐, di‐endo‐ and trans‐2,3‐ and 2,5‐disubstituted trinorbornanediols, and di‐exo‐ and di‐endo‐ 2,3‐disubstituted camphanediols using different divalent transition metals (Co²⁺, Ni²⁺, Cu²⁺) and electrospray ionization quadrupole ion trap mass spectrometry. Many metal‐coordinated complex ions were formed for cobalt and nickel: [2M+Met]²⁺, [3M+Met]²⁺, [M–H+Met]⁺, [2M–H+Met]⁺, [M+MetX]⁺, [2M+MetX]⁺ and [3M–H+Co]⁺, where M is the diol, Met is the metal used and X is the counter ion (acetate, chloride, nitrate). Copper showed the weakest formation of metal complexes with di‐exo‐2,3‐disubstituted trinorbornanediol yielding only the minor singly charged ions [M–H+Cu]⁺, [2M–H+Cu]⁺ and [2M+CuX]⁺. No clear differences were noted for cobalt complex formation, especially for cis‐2,3‐disubstituted isomers. However, 2,5‐disubstituted trinorbornanediols showed moderate diastereomeric differentiation because of the unidentate nature of the sterically more hindered exo‐isomer. trans‐Isomers gave rise to abundant [3M–H+Co]⁺ ion products, which may be considered a characteristic ion for bicyclo[221]heptane trans‐2,3‐ and trans‐2,5‐diols. To differentiate cis‐2,3‐isomers, the collision‐induced dissociation (CID) products for [3M+Co]²⁺, [M+CoOAc]⁺, [2M–H+Co]⁺ and [2M+CoOAc]⁺ cobalt complexes were investigated. The results of the CID of the monomeric and dimeric metal adduct complexes [M+CoOAc]⁺ and [2M–H+Co]⁺ were stereochemically controlled and could be used for stereochemical differentiation of the compounds investigated. In addition, the structures and relative energies of some complex ions were studied using hybrid density functional theory calculations. Copyright © 2009 John Wiley & Sons, Ltd.     

Substituierte 9-Oxabicyclo[4.2.1]- und 9-Oxabicyclo[3.3.1]nonane IV. endo,endo-2,5-Dihydroxy-9-oxabicyclo[4.2.1]nonan,endo, endo-, endo,exo- und exo,exo-2,6-Dihydroxy sowie endo,exo-2,7-Dihydroxy-9-oxabicyclo[3.3.1]nonan; Darstellung und Umwandlungsprodukte

The synthesis of the following compounds and reaction products thereof are described: endo, endo-2,5-dihydroxy-9-oxabicyclo[4.2.1]nonane ( 3–5 ), epimeric 2,6-dihydroxy-9-oxabicyclo[3.3.1]nonanes (endo, endo: 6–8 , exo, exo: 29–32 , and endo, exo: 43–45 ), and endo, exo 2,7-dihydroxy-9-oxabicyclo[3.3.1]nonane ( 46–50 ).     

Stereochemistry of Seven-Membered Heterocycles: XLIII. Steric Structure of Diastereoisomeric 8,8-Dichloro(dibromo)-4-R-3,5-dioxabicyclo[5.1.0]octanes

Dichloro- and dibromocyclopropanation of 2-substituted 1,3-dioxacyclohept-5-enes according to Makosza resulted in formation of the corresponding 4-substituted 8,8-dichloro(dibromo)-3,5-dioxabicyclo[5.1.0]octanes in good yields. Ultrasonic activation of the process considerably shortened the reaction time. According to the ^{1 3}C NMR spectra, the chair-twist equilibrium is essentially displaced toward the chair conformer for the exo isomers and toward the twist conformer for the endo structures. Similar results were obtained by AM1 semiempirical calculations which indicated that the CCl···O interaction largely determines the conformational equilibrium. The state of the diastereoisomer epimerization equilibrium depends on the size of the substituent at the acetal carbon atom.     

1H NMR studies of 3,8-dioxatricyclo-[3.2.1.02,4]octane derivatives

A series of 6-X-3,8-dioxatricyclo[3.2.1.0^2,4]octanes (X?CO₂CH₃, CN, Cl and CN) are studied by NMR, after their syntheses by epoxidation of the corresponding 7-oxabicyclo[2.2.1]heptenes. The NMR parameters (J, δ) are determined, and also the anisotropy effects of methyl groups at the 1,5 bridgehead positions. The results allow an unambiguous identification of the diastereo-isomers having a gem-chlorocyano group in the 6 position.     

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     

Synthesis of Bridged Bicyclic Molecules using Halocarbenes. Derivatives of bicyclo[4.2.1]nonane

The addition of dichlorocarbene (generated by the interaction of sodium methoxide and ethyl trichloroacetate) to bicyclo[3.2.1]oct-2-ene, its 3-chloro and exo-3,4-dichloro derivatives gives the exo 1 : 1 adducts in yields of 94, 89 and 48%. By suitable chemical reactions of these adducts, convenient syntheses of bicyclo[4.2.1]nona-2,4-diene and bicyclo[4.2.1]non-3-ene, together with their monochloro, dichloro and trichloro derivatives are obtained. Bicyclo[4.2.1]-nonan-3-one is also obtained from bicyclo[4.2.1]non-3-ene in a synthesis starting from the readily available 5-hydroxymethylnorborn-2-ene in an overall yield of 20%.     

The Reaction of Dihalocarbenes with Quadricyclane

The reactions of difluoro-, dichloro- and dibromocarbene with quadricyclane ( 2 ) were examined. In all cases, conversions were low (4–15%), but three distinct reaction courses were observed: cleavage, 1,2-addition, and 1,4-addition. Difluorocarbene gave mainly 6-endo-(2,2-difluorovinyl)-cis-bicyclo[3.1.0]hex-2-ene ( 8 ; 52–89% relative yield), together with minor amounts of exo-3,3-difluorotricyclo[3.2.1.0^2,4]oct-6-ene (7; 13–17%), and 4,4-difluorotetracyclo[3.3.0.0^2,8.0^3,6]octane ( 5 ; 2–4%). Dichlorocarbene gave analogous products, but in relative yields of 35 ( 17 ), 51 ( 11 ), and 12% ( 16 ). The product 11 of 1,2-endo addition underwent further rearrangement to its allylic derivative 12 . A small amount of 1,2-endo addition also occurred (2% of 14 / 15 ). Dibromocarbene gave predominantly products derived from rearrangement of the 1,2-exo (61% of 20 / 21 ) and 1,2-endo adducts (10% of 23 / 24 ). In addition, a significant amount of 4,4-dibromotetracyclo[3.3.0.0^2,8.0^3,6]octane ( 25 ; 21%) was formed. The cleavage product, 6-endo-(2,2-dibromovinyl)-cis-bicyclo[3.1.0]hex-2-ene ( 26 ) was also observed (7%). The yields and product compositions were compared to those obtained from norbornadiene ( 1 ) and found to be entirely different (Table 1), for example no cleavage occurred with difluorocarbene.     

The conformation of (1R,2S,4R,5S)-2,4-dimethoxybicyclo[3.3.1]nonan-9-one and some related compounds

A mixture of stereoisomers of 2,4-dimethoxybicyclo[3.3.1]nonan-9-one was prepared, separated by column chromatography and characterized by 60 MHz ¹H NMR spectroscopy using Eu(fod)₃. A double chair conformation with axial methoxyl groups is established for (1R,2S,4R,5S)-2,4-dimethoxybicyclo[3.3.1]-nonan-9-one on the basis of the J(12), J(2,H-3 exo) and J(2,3 endo) values and the chemical shifts for H-2(4). The conformation of some related compounds is subsequently inferred.     

Mannich Condensation of exo-2,exo-6-Tricyclo[5.2.1.02,6]decan-8-one

Mannich condensation of exo-2,exo-6-tricyclo[5.2.1.02,6]decan-8-one with paraformaldehyde and dimethylamine hydrochloride results in the addition of dimethylaminomethyl fragment at the C⁹ atom to give the exo-9-isomer. The reaction of exo-9-dimethylaminomethyl-exo-2,exo-6-tricyclo[5.2.1.02,6]decan-8-one with hydroxylamine hydrochloride in alcoholic alkali yields the corresponding Z-oxime which undergoes selective rearrangement into exo-10-dimethylaminomethyl-9-aza-exo-2,exo-6-tricyclo[5.3.1.02,6]undecan-8-one by the action of sulfuric acid in acetonitrile.     

1H-NMR Spectra of Cyclohexa-1,4-dienes and Cyclohexenes Annellated to Bicyclo[2.2.1]hept-2-enes. The Inter-Ring Homoallylic H,H Coupling Constants as Stereochemical Probes

The 360-MHz-¹H-NMR spectra of cyclohexa-1,4-dienes and cyclohexenes annellated to bicyclo[2.2.1]hept-2-enes and 7-oxabicyclo[2.2.1]hept-2-enes show inter-ring homoallylic coupling constants between the bridgehead protons of the bicyclo[2.2.1]heptenes and the exo-protons of the allylic methylene groups (0.8 ± 0.15 Hz for bicyclo[2.2.1]hept-2-enes; 0.8–1.4 Hz for 7-oxabicyclo[2.2.1]hept-2-enes). Contrastingly, the corresponding coupling between the bridgehead protons and the endo-protons is absent. The observed values are compared with those calculated by the INDO and CNDO/2 methods and discussed in the light of the bicyclo[2.2.1]hept-2-ene bond π-anisotropy. Vicinal as well as intra-ring homoallylic coupling constants are consistent with a small puckering of the cyclohexa-1,4-diene rings toward the endo-face. The allylic exo-methylene protons are more deshielded than the endo-protons independent of the nature of the substituents, the nature of the bridges, and the degree of unsaturation of the annellated systems. These results constitute a probe for the configuration of cyclohexa-1,4-dienes and cyclohexenes annellated to these bicyclic skeletons.     

Solution conformation and dynamics of L-6-methylperhydroimidazo[1,5-c]thiazole-5,7-dione (γ-thiaprolinehydantoin). A 1H and 13C NMR study

The solution conformation of L-6-methylperhydroimidazo[1,5-c]thiazole-5,7-dione (γ-thiaprolinehydantoin) has been determined from an extensive ¹H and ¹³C NMR study, allowing the extraction of vicinal inter-proton and carbon-hydrogen coupling constants. The major conformation of the thiazolidine ring is an envelope with C-δ as the flap exo (δ^?). In solution the preferred solid state (twist) conformer with C-α exo and C-β endo (_α^βT) is only a minor contributor. ¹³C spin–lattice relaxation data reveal the flexibility of the thiazolidine ring.     

Photochemische Umwandlungen. XV [1] Photochemische Isomerisierung des exo-Tricyclo[4.2.1.02′5]nona-3,7-dien-Systems. Vorläufige Mitteilung

The acetone sensitized isomerization of two exo-tricyclo[4.2.1.0^2,5]nonadiene derivatives, of the corresponding tricyclo[4.3.0.0^2,5]nonadienes, and the photoisomerization of two bicyclo[4.3.0]nonatrienes by direct excitation are described.