The adamantane rearrangement of 1,2-trimethylenenorbornanes. Part V. Rearrangements of 1,2-trimethylenenorbornanes initiated by regioselective formation of carbocation centers at C(2) and C(6)

The behaviour of the regioselectively generated carbocation centers at C(2) and C(6) in 1,2-trimethylenenorbornanes was investigated in order to study the occurrence or absence of a degenerate rearrangement E⇄M in the adamantane rearrangement of both 1,2-endo- ( 1 ) and 1,2-exo-trimethylenenorbornane ( 2 ) to 2-endo,6-endo-trimethylenenorbornane ( 3 ). A degenerate rearrangement E⇄M is inevitably involved inasmuch as a 1,2-trimethylenenorborn-2-yl cation E not only is formed directly as manifested by the conversions of the reactants 4 (C(2), C(3)-olefin) and 6 (C(2), C(3′)-olefin), but also indirectly (via F→E ) if the leaving group at C(6) to be ionized occupies the endo-position (6-endo-alcohol 8 ). No degenerate rearrangement E⇄M is operative starting from reactants that lead directly to a 2,6-trimethylenenorborn-2-yl cation G ; this is the case with both the ionization of the 6-exo-alcohol 10 having the leaving OH-group in a stereoelectronically favoured configuration to undergo simultaneous C(1), C(2)-bond migration (→ G ) as well as the protonation of the olefin 13 which is followed by same reaction pathway.     

The Adamantane Rearrangement of 1,2endo-Trimethylenenorbornane. Preliminary communication

1,2endo-Trimethylenenorbornane (1) in the presence of aluminium bromide in carbon disulfide at ?60° isomerizes at a much higher rate than its 2exo-isomer 2 to 2endo, 6endo-trimethylenenorbornane (3) as the sole product. By consequence, the hydrocarbon 2 being the next intermediate in the sequence of the adamantane rearrangement of 1 seems to be very unlikely.     

Norbornanes. Part 18. Inductive Charge Dispersal in the Solvolyses of 4- and 5-Substituted 2-Norbornyl p-Toluenesulfonates

The solvolysis rates and products of 4- and 5-exo-substituted 2-exo- and 2-endo-norbornyl tosylates 9 and 10 , respectively, are reported. The logarithms of the rate constants (log k) correlate linearly with the inductive constants σ for the substituents. A comparison of the reaction constants p₁ for the 4-, 5-, 6-, and 7-substituted 2-exo- and 2-endo-tosylates 9 , 10 , 1 , and 2 respectively, indicates that inductivity is higher for 2-exo-ionization than for 2-endo-ionization in all series. This observation is attributed to the more favorable alignment of neighbouring C-atoms for dorsal participation in exo-ionization, especially, in the case of C(6).     

1,2endo-Trimethylenenorbornane. A novel isomer of adamantane

An easy approach to the novel adamantane isomer 1,2endo-trimethylenenorbornane (2) is described. Starting from a mixture of pent-4-ynylcyclopentadienes 3 the tricyclic monosaturated key intermediate 5 was prepared by intramolecular cycloaddition (→ 4 ) and subsequent regioselective reduction of the C(5), C(6) double bond. The title hydrocarbon 2 was obtained from 5 upon stereoselective hydrogenation by diimide. In addition specifically deuteriated analogues of 2 were prepared applying dideuteriodiimide. Compound 2 rearranged to 2endo, 6endo-trimethylenenorbornane (4-homobrendane, 10 ) in sulfuric acid as well as with aluminium bromide in carbon disulfide.     

Stereoselective Synthesis of 2,4,6-Trimethylcyclohex-4-ene-1,3-diol Derivatives and of polypropionate fragments with four contiguous stereogenic centers

The Diels-Alder adduct (±)- 3 of 2,4-dimethylfuran and 1-cyanovinyl acetate was converted stereoselectively into benzyl 6-(4-chlorophenylsulfonyl)-1,3-exo,5-trimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-exo-yl ( 26 ) and -2-endo-yl ether ( 36 ). Addition of LiAlH₄ to the latter led to the 3-O-benzyl derivatives 28 and 37 of (1RS,2SR,3SR,6SR)- and (1RS,2SR,3RS,6SR)-5-(4-chlorophenylsulfonyl)-2,4,6-trimethylcyclohex-4-ene-1,3-diol, respectively. Methylenation of 6-exo-(4-chlorophenylthio)-1-methyl-5-methylidene-7-oxabicyclo[2.2.1]heptan-2-one ( 16 ), obtained by reaction of (±)- 3 with 4-Cl-C₆H₄SCl and saponification gave, 6-exo-(4-chlorophenylthio)-1-methyl-3,5-dimethylidene-7-oxabicyclo [2.2.1]heptan-2-one ( 43 ), the reduction of which with K-Selectride afforded 6-exo-(4-chlorophenylthio)-1,3-endo-dimethyl-5-methylidene-7-oxabicyclo[2.2.1]heptan-2-endo-ol ( 44 ). The 3-O-benzyl derivative 48 of (1RS,2RS,3RS,6SR)-5-(4-chlorophenylsulfonyl)- 2,4,6-trimethylcyclohex-4-ene-1,3-diol was derived from 44 via based-induced oxa-ring opening of benzyl 6-endo-(4-chlorophenylsulfonyl)-1,3-endo-5-endo-trimethyl-7-oxabicyclo[2.2.1]hept-2-endo-yl ether ( 49 ). Benzylation of 28 , followed by reductive desulfonylation and oxidative cleavage of the cyclohexene moiety afforded (2RS,3SR,4RS,5RS)-3,5-bis(benzyloxy)-2,4-dimethyl-6-oxoheptanal ( 32 ).     

Synthese und Hydrolyse von 6-exo-substituierten 2-Methyl-2-exo-norbornyl und 2-Methyl-2-endo-norbornyl-(2,4-dinitrophenyl)äthern Norbornane. 16. Mitteilung

The Synthesis and Hydrolysis of 6-exo-Substituted 2-Methyl-2-exo-norbornyl and 2-Methyl-2-endo-norbornyl 2,4-Dinitrophenyl Ethers The synthesis of the title compounds and their hydrolysis products in aqueous dioxane are described. Upon hydrolysis, the 2-exo-ethers 1 (X=N₂phO) as well as the 2-endo-ethers 2 (X=N₂phO) yield the corresponding 2-methyl-2-exo-norbornanols 3 only. Therefore, the 2-exo-ethers react with retention of configuration at C(2), the 2-endo-ethers 2 with inversion at C(2).     

Carbon Participation in the Solvolysis of 6-exo-substituted 2-exo- and 2-endo-Norbornyl p-Toluenesulfonates. Norbornanes part 5

The solvolysis rates and products of the 6-exo-substituted 2-exo- 1a - 1u , and 2-endo-norbornyl p-toluenesulfonates 2a - 2u , have been determined. In general, the rate constants for 1 and 2 (log k) correlate well with the inductive constants σ of the substitutents at C(6); however, their sensitivity to σ is much larger in the 2-exo-series 1 than in the 2-endo-series 2 . This differential transmission of polar effects is the cause of decreasing 2-exo/2-endo rate ratios from 2388 for R = t-C₄H₉ to 0.37 for R = Br, i. e. with increasing electron attraction by the substituent. The high sensitivity of the rate constants for the 2-exo-p-toluenesulfonates 1 to σ indicates an unusually strong inductive interaction between C(6) and the incipient cationic center at C(2). This interaction is ascribed to the participation of the pentacoordinate C(6)-atom, i. e. to 1,3-bridging, a consequence of steric hindrance of nucleophilic solvent participation in norbornanes. Donor substituents enhance 1,3-bridging, lead to faster reactions and to the formation of 2-exo substitution products. Conversely, acceptor substituents reduce 1,3-bridging, decrease rates and facilitate the formation of 2-endo substitution products. Graded 1,3-bridging is discussed in the light of Winstein's nonclassical ion concept.     

Adamantane rearrangement mechanisms. 1,2-trimethylenenorbornanes

Unexpected differences in the aluminium bromide-catalyzed rearrangement behaviour of 1,2-$\text{endo}$-trimethylenenorbornane ($\text{1}$) and its 1,2-$\text{exo}$-isomer ($\text{2}$) are interpreted. Isotopic labelling studies indicate that reversible abstraction of the tertiary 2-$\text{endo}$ hydride in $\text{2}$ does not occur. Instead, rearrangement to $\text{6}$ is favored. The label scrambling in the final product, adamantane ($\text{8}$), is attributed to degenerate isomerization in the proto-adamantyl precursor, $\text{7}$.     

Carbon Participation in the Solvolysis of Tertiary Norbornyl Derivatives Norbornanes. Part 15. 6-substituted 2-methylnorbornyl 2-exo- and 2-endo-2,4-dinitrophenyl ethers

The solvolysis rates and products of the tertiary 2-methyl-2-exo- and -2-endo-norbornyl 2,4-dinitrophenyl ethers 1 and 2 , (X = 2,4-(NO₂)₂₂C₆H₃O) have been determined. The different sensitivities of the rates of these ethers to the inductive effect of substituents at C(6) indicate that graded bridging of C(2) by C(6) occurs in the ionization of the exo-ethers 1 , not, however, in the ionization of the endo-ethers 2. In both cases hydrolysis leads to 2-methyl-2-exo-norbornanols only. Consequently, substitution takes place with retention at C(2) in the exo-series 1 and with inversion at C(2) in the endo-series 2. It is concluded that stereoelectronic and polar effects, rather than steric bulk effects, determine the high exo/endo rate ratios of the parent norbornyl derivatives 1a and 2a .     

Selective Hydrogen Chloride Elimination from Primary Chlorides Induced by the Fluoride Anion. Anchimeric participation of the chloromethyl group in the heterolytic opening of an epoxide. Stereospecific syntheses of 5,6-bis (methylidene)-syn-2-norbornen-7-ol and 5,6-bis (methylidene)-endo-3-chloro-exo-2-norbornanol

Syntheses of the alcohols 10 and 18 , and the corresponding ketones 11 and 19 are presented. Endo-5, exo-6-bis (chloromethyl)-endo-3-chloro-exo-2-norbornanol ( 16 ) and endo-5-(bromomethyl)-exo-6-(chloromethyl)-endo-3-chloro-exo-2-norbornanol ( 17 ) were obtained by HCl- and, respectively, HBr-addition to endo-5, exo-6-bis (chloromethyl)-exo-2, 3-epoxynorbornane ( 5 ). The Wagner-Meerwein rearrangement was precluded in these reactions probably because of the formation of a relatively stable chloronium ion 15 arising from the participation of the 1,4-chlorine atom of the endo-5-chloromethyl group in the heterolytic ring opening of the epoxide 5 . The ‘naked’ fluoride anion (excess CsF in DMF or KF in DMF with 18-crown-6-ether) permitted the selective elimination of 2 equivalents of HCl from 16 and yielded the chlorohydrin-diene 18 .     

Carbon Participation in the Solvolysis of 6-endo-Substituted 2-exo-Norbornyl Toluenesulfonates. Norbornanes part 6

The solvolysis rate constants k for the 6-endo-substituted 2-exo-norbornyl toluenesulfonates 7 have been determined. Values of logk correlate well with the respective inductive constants of the substitutents except when the latter are nucleophilic and therefore lead to endo-cyclization, or when they are n-electron donors and cause concerted fragmentation. In general 6-endo-substituted tosylates 7 react somewhat more slowly than their 6-exo-epimers. Identical or different mixtures were obtained from the C(6)-epimers 7 and 1 depending on whether the substituent was an electron donor or acceptor. It is concluded that donor substituents at C(6) enhance 1,3-bridging in the intermediate epimeric cations and lead to their rapid and complete equilibration, and that electron acceptors reduce bridging and hence their equilibration rates.     

π-Participation in Diazoketone Hydrolysis II; Exo-endo Cyclization Ratio in the Hydrolyses of 7-syn- and 5-endo-Diazoacetyl-2-norbornene

The rate of the acid-catalysed hydrosis of 7-syn-diazoacetyl-2-norbornene ( 1a ) is enhanced relative to that of the saturated analogue 5a by a factor of 835. In contrast to the behaviour of other primary diazoketones, the substitution step is no longer rate-determining (mechanism A-2), but so much accelerated that the preceding proton transfer becomes the slow step (mechanism A-S_E2, demonstrated by a solvent isotope effect k_H/k_D = 1.76). Product analysis shows 100% cyclization; the product formation is explained in terms of brexyl and brendyl type carbenium ions (or ion pairs). - 5-endo-Diazoacetyl-2-norbornene ( 3a ) shows very slight acceleration, and forms only 27% cyclization products (identical to those formed from 1a). Thus, in spite of the absence of steric hindrance by hydrogen atoms, the exo-endo rate ratio for anchimeric assistance is ≥ 10³.     

Zur Konfiguration der 2,4,6,8-Tetrabrom-cyclooctan-1,5-dione Reduktion des β-Isomers durch Natrium-borhydrid

Of the two previously described 2,4,6,8-tetrabromo-cyclooctane-1,5-diones, the higher melting β-isomer, mp. 226°, was treated with sodium borohydride to give: (1) by a double reduction and an intramolecular S_N2-reaction two epimeric alcohols, namely the 2-exo-hydroxy- ( 6 ) and 2-endo-hydroxy- ( 7 ) isomers of 3-exo,5-exo,7-endo-tribromo-9-oxa-bicyclo[4.2.1]nonane, and (2) by a single step reduction a hemiketal, 1-hydroxy-2-exo,4-exo,6-endo,8-endo-tetrabromo-9-oxa-bicyclo[3.3.1]nonane ( 8 ). The structures of these three hydroxy-compounds ( 6, 7 and 8 ) were derived from their properties, especially from complete analyses of their NMR.-spectra, which led to deductions of all configurations and conformations. Of special interest is the preferred existence of the 9-oxa-bicyclo[3.3.1]norane derivative 8 in a chair-chair conformation. The derivation of the configurations of the three hydroxy-compounds 6, 7 and 8 is tantamount to establishing the 2,4-cis, 4,6-trans, 6,8-cis-configuration ( 5 ) of the β-isomer of 2,4,6,8-tetrabromocyclooctane-1,5-dione, mp. 226°.     

Inductivity and Bridging in 2-Bicyclo[2.2.2]octyl Cations. Polar Effects,Part 11

The solvolysis rates and products of several 6-substituted 2-exo- and 2-endo-Bicyclo[2.2.2]octyl p-toluenesulfonates, 12 and 13 , respectively, are reported. Inductivity, as measured by the reaction constants ρ_I, is considerably less in the exo-series 12 (ρ_I = ?1.50) than in the corresponding 2-exo-norbornyl p-toluenesulfonates 1 (ρ_I= ?2.0). It is proposed that, for geometrical reasons, bridging of the cationic center C(2) by C(6) is not as strong in the bicyclooctane series 12 as it is in the norbornane series 1 . On the other hand, inductivity is higher in the 2-endo-bicyclooctane series 13 (ρ_I= ?1.0) than in the corresponding 2-endo-norbornane series 3 (ρ_I = 0.78), probably, because in the former case bridging of C(6) is less hindered by the departing anion. The relative yields of exo- and endo-substitution products from the series 12 and 13 , are in accord with graded bridging of C(6) in the incipient bicyclooctyl cations. But almost constant bridging of C(2) by C(7) is indicated in the ionization of the 2-endo-bicyclooctane series 13 . Consequently, in the free unsubstituted bicyclooctane cation C(2) is bridged symmetrically by C(6) and C(7), in contrast to the current concept of ‘non-classical’ two-electron-three-center bonding.     

Norbornanes. Part 20. Inductivity and bridging in 2-norbornyl cations

The solvolysis rates and products of several 1-substituted 2exo- and 2-endo-norbornyl p-toluenesulfonates 7 and 8 , respectively, have been determined. Hydrolyses of these epimeric tosylates yielded rearranged products in varying amounts, except when the substituent was COOCH₃ or CN. The logarithms of the rate constants (log k) for the endo-series 8 correlated linearly with the corresponding inductive constants σ with a reaction constant ρ_I of ?1.24. On the other hand, log k values for the exo-series 7 appear to fit two regression lines, the first line (ρ_I = ?1.90) defined by the tosylates that ionize, with rearrangement, to the tertiary cations 11 , the second (ρ_I = ?1.86) by the tosylates 7 (R = H, COOCH³, and CN) that ionize to an asymmetrically bridged secondary cation 19 . These results confirm the unique participation of C(6) with a ρ_I of ?2.00 in the ionization of 2-exo-nor-bornyl tosylate.     

The 1H NMR spectra of some norbornene derivatives,a LIS study

The ¹H NMR spectra of 2-exo-hydroxymethyl-3-endo-methylnorbornene and the corresponding 2-endo-3-exo isomer have been completely assigned with the aid of lanthanide reagents. This enabled a full analysis of the unusual spectrum of 2-exo-hydroxy-methyl-3-endo-methylnorbornene to be undertaken, confirming the proposed structure. The ΔEu values for 2-exo-hydroxymethyl-3-endo-methylnorbornene and the 2-endo-3-exo-isomer have been used to test the effect of rotational averaging on the calculated pseudo contact shifts. Good agreement is obtained for a dynamic model in which the Eu atom exchanges between two sites on the oxygen atom of the OH bond, and in which the rotational equilibrium about the CH? CH₂OH bond is explicitly considered.     

The Homoconjugated Electron-Releasing Carbonyl Group of 1-Methylbicyclo[2.2.1]hept-5-en-2-one. Regioselective syntheses of 5-chloro- and 6-chloro-1-methylbicyclo[2.2.1]hept-5-en-2-one

Syntheses of (±)-2-exo-cyano-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl acetate ( 1 ) and of (±)-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 2 ) are reported. The additon of PhSeCl to 1 afforded (±)-5-endo-chloro-2-exo-cyano-1-methyl-6-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]hept-2-endo-yl acetate ( 6 ), whereas 2 added to PhSeCl with the opposite regioselectivity giving (±)-6-endo-chloro-1-methyl-5-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]heptan-2-one ( 7 ). These adducts were converted into 5-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 9 ) and 6-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 10 ), respectively.     

Zur Photodimerisierung von 3-Phenyl-2H-azirinen. Vorläufige Mitteilung

Irradiation of 3-phenyl-2H-azirine ( 2 ) in benzene solution with a high-pressure mercury lamp yields 4,5-diphenyl-1,3-diazabicyclo[3,1,0]hex-3-ene ( 4 ) and not 3-phenylimino-4-phenyl-1-azabicyclo[2,1,0]pentane ( 1 ), as had been reported previously by others [2]. 2-Methyl-3-phenyl-2H-azirine ( 3 ) yields on irradiation a 2:1 mixture of 2-exo, 6-exo- and 2-exdo, 6-exo-dimethyl-4,5-diphenyl-1,3-diazabicyclo[3,1,0]hex-3-ene (2-exo,6-exo- and 2-endo, 6-exo- 5 ). Irradiation of 2,3-diphenyl-2H-azirine ( 8 ) leads to the formation of 2,4,5-triphenyl-imidazole ( 9 ) and tetra-phenylpyrazine ( 10 ). The suggested reaction path for the generation of 9 and 10 is shown in Scheme 2.     

Reductive Radical Cyclisations of Bromo Acetals and (Bromomethyl)silyl Ethers of Terpenoid Alcohols

The tin hydride promoted and the reductive vitamin B₁₂ catalysed radical cyclisation of mixed 2-bromo-acetaldehyde acetals and of (2-bromomethyl)dimethylsilyl ethers of allylic terpenoid alcohols has been investigated: 3-oxadeca-5,9-dien-l-yl radicals undergo 5-‘exo’ cyclisation to oxolanes (Scheme 4), 3-oxa-2-siladeca-5,9-dien-1-yl radicals sequential 6-‘endo’→5-‘exo’ tandem cyclisation to cis-3-oxa-4-silabicyclo[4.3.0]nonanes (Scheme 5), and 3-oxa-2-silatetradeca-5,9,13-trien-l-yl radicals sequential 6-‘endo’→6-‘endo’→5-‘exo’ triple cyclisation to trans-transoid-trans- 12-oxa-11-silatricyclo[7.4.0.0^2,6] tridecanes (Scheme 6).     

The Diels-Alder Reactivity of 2,2′-Ethylidenebis[3,5-dimethylfuran] and Exploratory Chemistry of the Mono-adducts

In the presence of Me₃Al, 1-cyanovinyl acetate added to 2,2′-ethylidenebis[3,5-dimethylfuran] ( 1 ) to give a 20:10:1:1 mixture of mono-adducts 4,5,6 , and 7 resulting from the same regiocontrol (‘para’ orienting effect of the 5-methyl substituent in 1 ). The additions of a second equiv. of dienophile to 4–7 were very slow reactions. The major mono-adducts 4 (solid) and 5 (liquid) have 2-exo-carbonitrile groups. The molecular structure of 4 (1RS,1′RS,2SR,4SR)-2-exo-cyano-4-[1-(3,5-dimethylfuran-2-yl)ethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl acetate) was determined by X-ray single-crystal radiocrystallography. Mono-adducts 4 and 5 were saponified into the corresponding 7-oxanorbornenones 8 and 9 which were converted with high stereoselectivity into (1RS,1′SR,4RS,5RS,6RS)-4-[1-(3,5-dimethyl furan-2-yl)ethyl]-6-exo-methoxy-1,5-endo-dimethyl-7-oxabicyclo [2.2.1]heptan-2-one dimethyl acetal ( 12 ) and its (1′RS-stereoisomer 12a , respectively. Acetal hydrolysis of 12a followed by treatment with (t-Bu)Me₂SiOSO₂CF₃ led to silylation and pinacol rearrangement with the formation of (1RS,1′RS,5RS,6RS)-4-[(tert-butyl)dimethy lsilyloxy]-1-(3,5-dimethylfuran-2-yl)ethyl]-5-methoxy-6-methyl-3-methylidene- 2-oxabicyclo[2.2.1]heptane ( 16 ). In the presence of Me₃Al, dimethyl acetylenedicarboxylate added to 12 giving a major adduct 19 which was hydroborated and oxidized into (1RS,1′RS,2″RS,3″RS,4SR,4″RS,5 SR,6SR)-dimethyl 5-exo-hydroxy-4,6-endo-dimethyl-1-[1-(3-exo,5,5-trimeth oxy-2-endo,4-dimethyl-7-oxabicyclo[2.2.1]hept-2-yl)ethyl]-7-oxabicyclo [2.2.1]hept-2-ene-2,3-dicarboxylate ( 20 ). Acetylation of alcohol 20 followed by C?C bond cleavage afforded (1′RS,1″SR,2RS,2′″SR,3RS, 3″SR,4RS,4″SR,5RS)-dimethyl {3-acetoxy-2,3,4,5-tetrahydro-2,4-dimethyl-5-[1-(3-exo,5,5-trimethoxy ?2-endo,4-dimethyl-7-oxabicyclo[2.2.1]hept-1-yl)-ethyl]furan-2,5-diyl} bis[glyoxylate] ( 24 ).