Polar effects in the solvolysis of 6-exo-substituted endo-2-norbornyl p-toluenesulfonates

The solvolysis rates of endo-2-norbornyl p-toluenesulfonates $\text{1}$ are affected far less by 6-exo-substituents than are the rates of the corresponding exo-2-norbornyl p-toluenesulfonates $\text{2}$¹.     

Verbrückte und unverbrückte norbornyl-kationen in der gasphase. Berechnungen zur stabilität isomerer norbornyl-kationen mit hilfe quantenmechanischer verfahren

The geometry and the relative stability of bicyclic compounds 1–20 have been calculated by standard quantum mechanics methods.MINDO/3 yields the following stability order of isomeric norbornyl cations (relative energies in $\text{kcal}\text{mole}$): 1-norbornyl cation 9 (0.0); 1.7 σ-bridged cation 6 (0.7); 7-norbornyl cation (nonplanar) 7 (1.1); 2-norbornyl cation (classical) 2 (4.2); 7-norbornyl cation (planar) 8 (4.3); 2-norbornyl cation (bridged) 1 (6.1). The stability of the same ions calculated by ab initio methods (STO-3G, MINDO/3-geometry) leads to an order more nearly consistent with experimental results: 2-norbornyl cation (classical) 2 (0.0); 2-norbornyl cation (bridged) 1 (5.9); 7-norbornyl cation (planar) 8 (11.1); 1-norbornyl cation 9 (14.6); 7-norbornyl cation (nonplanar) 7 (21.2). For the secondary 7-norbornyl cation, MINDO/3 gives a pyramidal configuration, 3.2 $\text{kcal}\text{mole}$ more stable than the planar form. In contrast, the ab initio results (complete optimization of all geometrical parameters) indicate the planar cation to be the most stable form. The bridged structure of 2-norbornyl cation 1 is calculated (STO-3G, partly optimized) to be 4.3 $\text{kcal}\text{mole}$ less stable than the classical counterpart, 2. For the lower homologues 12 and 13 (STO-3G, complete geometry optimization), this difference is 6.4 $\text{kcal}\text{mole}$. However, more extended basis sets should favour the bridged structures. The hydrogen bridged norbornyl cations 3, 4, and 5 have been calculated (STO-3G, partly optimized) to be 14.4, 23.6 and 29.9 $\text{kcal}\text{mole}$ less stable than 2. The stability differences between the corresponding tertiary bicyclic ions 10 vs 11, and 14 vs 15 are calculated (ab initio) to be 15.3 and 19.0 kcal/mole, respectively, in favour of classical structures. The influence of methyl substitution at positions C₁ and C₆ (exo) on bridged and unbridged structure of 2-norbornyl cation is calculated. Pyramidal secondary and tertiary 2-norbornyl cations 19 (a; R=H, b; R=CH₃) and 20 (a; R=H, b; r=CH₃) have been used to model the electrical effects in the solvolysis transition states of epimeric 2-norbornyl esters. Due to more efficient hyperconjugation the pyramidal exo cation is stabilized more than the endo cation by 5.2 $\text{kcal}\text{mole}$ for the secondary series and 3.5 $\text{kcal}\text{mole}$ for the tertiary series. Bonding of endo cation 20 with a nucleophile should be stronger than bonding of exo cation 19 due to more efficient HOMO-LUMO interaction.     

Exo/emdo soltolysis rate ratios in constrained 2-norbornyl systems

Tetracyclol[6.2.1.0^2,6.0^5,10]undec-3-yl derivatives ($\text{6}$ - $\text{8}$) show typically high tertiary exo/endo solvolysis rate ratios, but the ratios for secondary reactants are suppressed. The rate and product data support the theory of anchimeric assistance in the parent $\text{exo}$-2-norbornyl solvolysis.     

Solvolysis of 2-aryl-exo-5,6-trimethylene-2-norbornyl p-nitrobenzoates as a reference of 2-aryl-2-norbornyl p-nitrobenzoates solvolysis: Further evidence for the unimportance of σ-participation in the solvolysis of 2-aryl-2-norbornyl derivatives

The rates of solvolysis of 2 - aryl - exo - 5,6 - trimethylene - exo - and endo - 2 - norbornyl p-nitrobenzoates (7 and 8, respectively) with representative substituents [p-CH₃O, p-CH₃, H, m-CF₃, p-CF₃, and 3,5-(CF₃)₂] were determined in 80% aqueous acetone and compared with those of the parent 2-aryl-exo- and endo-2-norbornyl p-nitrobenzoates (5 and 6, respectively). The rate ratios for the endo-p-nitrobenzoates ($\text{6}\text{8}$) are essentially constant and close to unity for these substituents, indicating that the perturbation of the trimethylene bridge toward the C₂-position is virtually negligilbe. The rate ratios for the exo-p-nitrobenzoates ($\text{5}\text{7}$) can also be regarded as invariant over the reactivity range studied. The exo/endo rate ratios ($\text{7}\text{8}$) are 246 (p-CH₃O), 196 (P-CH₃), 129 (H), 80 (m-CF₃), 90 (p-CF₃), and 89 [3,5-(CF₃)₂], being similar to the corresponding $\text{5}\text{6}$ rate ratios. The solvolyses of these p-nitrobenzoates (7 and 8) afford predominantly ( > 97%) exo-alcohols. Since the secondary exo-5,6-trimethylene-2-norbornyl system, with its low exo/endo rate ratio, 11.2, is known to solvolyse without significant σ-participation, the tertiary derivatives should also undergo solvolysis without σ-participation. Consequently, the similarities in the solvolytic behaviors between the two systems (5 vs 7; 6 vs 8) strongly support the previous conclusion that σ-participation is unimportant in the solvolysis of 5.     

Solvent Dependence of Inductivity in the Solvolyses of Substituted Norbornyl p-Toluenesulfonates. Norbornanes,Part 14

A comparison of the solvolysis rates of the substituted 2-exo- and 2-endo -norbornyl p-toluenesulfonates 1, 2, 3 and 4 and the substituted 1- and 2-adamantyl sulfonates 9 and 10 , respectively, in 80% ethanol and 97% trifluoroethanol has shown that the sensitivity of rates to the I-effect of substituents, i.e. the inductivity of these compounds, varies strongly with structure, configuration and solvent. In 97% trifluoro-ethanol, a solvent of low nucleophilicity and high ionizing power, the inductivities of the 2-endo-norbornyl p-toluenesulfonates 2 and 4 as well as the inductivities of the adamantyl derivatives 9 and 10 were larger than in 80% ethanol. In contrast, the inductivity of the 2-exo-norbornyl p-toluenesulfonates 1 was practically unchanged. It was, therefore, concluded that the transition states for the former compounds are not, or only weakly, bridged, whereas the transition states for the 2-exo-norbornyl p-tolu-enesulfonates 1 involve graded bridging by C (6). These results confirm that, due to differential bridging strain, 2-norbornyl cations are anisotropic to polar effects.     

Carbon Participation in the Solvolysis of 6- and 7-Substituted 2-Norbornyl p-Toluenesulfonates. Norbornanes,Part 11

The solvolysis rates and products of several 7-anti-substituted 2-endo-norbornyl p-toluenesulfonates 11 have been determined and compared with those of the previously reported 6-exo-substituted 2-exo-norbornyl p-toluenesulfonates 1. Although the number of bonds between the substituent and the reaction site is the same in the two series, the inductive effect of the substitutents is transmitted far more strongly in the 6-exo-2-exo-series 1 than in the 7-anti-2-endo-series 11 ; i.e. their inductivities differ widely. It is concluded that through space induction involves graded bridging of the substituent-bearing C-atom to the incipient cationic center at C(2) and that this involves differential bridging strain. The different reactivities of unsubstituted 2-exo- and 2-endo-norbornyl derivatives can then be ascribed to a stereoelectronic effect.     

Conformation and rotational barriers of 2-substituted 1,3-diphenylallyl anions

The conformations and the rotational barriers of the 2-substituted 1,3-diphenylallylanions $\text{1b}$–$\text{g}$ (Tab. 2) have been determined. Increasing size of the substituents leads to more $\text{exo}$,$\text{endo}$- and $\text{endo}$,$\text{endo}$-conformers at the cost of the $\text{exo}$,$\text{exo}$-species. This trend is connected with decreasing ΔG³-value sof the rotational barriers; the barriers are essentially not affected by ion pair effects, which is in contrast to the parent “allyl anion”.     

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.     

Norbornanes. Part 10. Solvolysis of the Stereoisomeric 6-Cyano-2-norbornyl p-Toluenesulfonates. A Correction

The solvolysis products of the stereoisomeric 6-cyano-2-norbornyl p-toluene sulfonates 1 - 4 (R ? CN) in dioxane/water 7 : 3 have been determined. In contrast to an earlier report the 6exo-cyano-2exo-norbornyl p-toluenesulfonate ( 1 ; R?CN) yields 30% of the 2endo-alcohol 9 (R?CN) beside the 2exo-alcohol 10 and the norbornenes 12 and 13. The results confirm that - I substituents at C(6) reduce 1,3-bridging in the intermediate norbornyl cation and hence its rate of rearrangement. The relatively high rate constants for some 6-fluoro- and 6-cyano-2exo norbornyl p-toluenesulfonates are ascribed to C, C-hyperconjugation assisted by the conjugative effects of the 6-fluoro and cyano substituents.     

Polar substituent effects in the solvolysis of 2-methyl-2-endo-norbonyl 2,4-dinitrophenyl ethers

The solvolysis rates of tertiary 2-endo-norbonyl derivatives $\text{2}$ are less strongly controlled by the polar effects of substituents at C(6) than the rates of the secondary analogues $\text{1}$.     

Comparison of cationic rhodium and iridium complexes in directed homogeneous hydrogenation

The hydrogenation of $\text{endo}$-6-methylenebicyclo[2,2,2]octan-2-ol catalysed by a range of rhodium and iridium complexes has been investigated. Unlike the corresponding $\text{exo}$-alcohol, reduction is highly stereoselective leading to 95 – 99.7% of $\text{endo}$-exo-6-methylbicyclo[2,2,2]octan-2-ol. Selectivity is much less pronounced for the corresponding methyl ether. Rhodium catalysts promote a competitive isomerisation of the double bond to $\text{endo}$-6-methyl-bicyclo[2,2,2]oct-5-en-2-ol, of which an authentic sample was reduced in high yield to pure $\text{exo}$-$\text{endo}$ product. Reduction of both $\text{endo}$-hydroxy substrates by iridium complexes is rapid and highly selective.NMR studies employing europium shift reagents played a central part in defining the stereochemical interrelationships of 2,6-disubstituted bicyclo[2,2,2]octanes.     

Norbornanes. Part 19. The Inductive Model for Norbornyl Cation Formation

Two CH₃ groups at C(6) of 2-exo- ( 10a ) and 2-endo-norbornyl p-toluenesulfonate 11a lower their solvolysis rates in 80% EtOH by factors of 28 and 16, respectively. A spirocyclopropyl group including C(6), as in 21a and 22a , reduces the rate of exo- and endo-ionization by factors of 250 and 8, respectively. The geminally dimethyl-substituted tosylates 10a and 11a yield the 2-exo-alcohol 10b , whereas the spirocyclopropyl-substituted tosylates 21a and 22a furnish rearranged 3-brendanol 23 . These findings are readily rationalized by the inductive model, according to which norbornyl cation formation is controlled by the inductive effect of dorsal substituents.     

Polar versus steric effects in the solvolysis of 6endo-substituted 2endo-norbornyl p-toluenesulfonates. Norbornanes,Part 8

The solvolysis rates and products of the 6endo-R-substituted 2endo-norbornyl toluenesulfonates 6a – 6i have been determined. The rates of 6a – 6g correlate with the inductive constants σ the 6endo-substituents and are not related to the size of the latter. It is therefore concluded that polar rather than steric effects control the exo/endo-rate ratios of norbornyl sulfonates. Products are derived mainly from rearranged 6exo-R-norbornyl cations when the substituent is an electron donor and from unrearranged 6endo-R-substituted cations when the substituent is an electron acceptor.     

Bridged and unbridged norbornyl cations

The solvolysis rates and products of 6-substituted 2-norbornyl-p-toluene-sulfonates $\text{1}$ and $\text{5}$ are controlled by 1,3-bridging, i.e. by the degree of bonding between C(6) and C(2) in the intermediate norbornyl cations.     

The effect of ultrasound on the solvolysis of 2-chloro-2-methylpropane in aqueous alcoholic media

The effect of ultrasonic irradiation (45KHz at 25°C) on the solvolysis of $\text{t}$-butyl chloride in aqueous ethanol, $\text{i}$-propanol and $\text{t}$-butanol is (1) to increase the rate constants in the more alcoholic media and (2) to reduce the m values of these reactions.     

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, $\text{7}$.     

A mass-spectral study of exo- and endo-2-norbornyl bromide and exo and endo-8-bromobicyclo[3.2.1]octane by photoionization

The photoionization, as well as the electron-impact, mass spectra of exo-and endo-norbornyl bromide and of exo-and endo-8-bromobicyclo[3.2.1]octane show that exo-Br loss is more facile than endo-Br loss in formation of C₇H₁₁^⊕ and C₈H₁₃^⊕, respectively. The relative intensity values are compared with solvolysis data from the same systems.     

The synthesis of a 3-diazobicyclo[2.2.1]Heptan-2-one inhibitor of thromboxane a2 synthetase

The synthesis of a PGH₂ analog 5-$\text{endo}$(2(Z), 6-$\text{exo}$(1E)-3-diazo-5-(7-hydroxy-2-heptenyl)-6-(3-hydroxy-1-octenyl)bicyclo[2.2.1]heptan-2-one 2 is described.     

The stereochemistry of the reaction of 2-norbornylmagnesium bromide with formaldehyde

Diastereomeric $\text{endo}$-2-norbornylmagnesium bromide and mixtures of $\text{endo}$- and $\text{exo}$-2-norbornylmagnesium bromide react stereospecifically with retention of configuration at the carbon-magnesium bond with formaldehyde to form the expected primary alcohol. This stereochemical result, which is comparable to that observed previously in electrophilic substitutions of stereoisomeric organomagnesium reagents, is observed even when 5 mole % ferric chloride is added. The stereospecificity observed both with and without added metal salts suggests that single electron transfer is not important in 1,2 addition of $\text{sec}$-alkylmagnesium reagents to simple aliphatic aldehydes.