John S. Lomas

Hydrogen bonding and solvent effects in heteroaryldi(1-adamantyl)methanols: an NMR and IR spectroscopic study

Reaction of the organolithium derivatives of certain heteroaromatics [2-furanyl, 2-thienyl, 2-thiazolyl, 2-pyridyl and 2-(3-methylpyridyl)] with di(1-adamantyl) ketone gives potentially rotameric tertiary alcohols. With 2-pyridyl- and 2-(3-methylpyridyl)lithium only the syn isomer is obtained. The syn isomer makes up 85–100% of (2-furanyl)diadamantylmethanol and 80–90% of the 2-thienyl derivative, depending on the NMR solvent. In chloroform or benzene the 2-thiazolyl derivative is a 2∶1 mixture, the isomer with the sulfur atom syn to the OH group predominating; in DMSO or in the solid state this is the sole species. The IR absorption frequency for OH stretching correlates with the corresponding proton NMR shift in chloroform and with its temperature dependence, Δδ/ΔT. In pyridine Δδ/ΔT is either large (–20 ppb/°C) or small (–1 to –2 ppb/°C) for intermolecular and intramolecular hydrogen-bonded species, respectively. Semi-empirical calculations (AM1 and PM3) suggest that the anti alcohols should be the more stable in the gas phase, but solvent effects and hydrogen bonding, in the case of the pyridyl derivatives, appear to reverse this situation, making the isomer with OH syn to the heteroatom the principal, and sometimes the only, species observed in solution.

Heteroaromatic organolithium addition to a congested ketone: conformational isomerism in (N-alkylpyrrol-2-yl)di(1-adamantyl)methanols

Tertiary alcohols have been prepared by reaction of 2-lithio-N-methylpyrrole and 2-lithio-N-ethylpyrrole with di(1-adamantyl)ketone. The conformations of the N-methyl derivatives have been determined by single crystal X-ray diffraction studies. The N-alkylpyrrol-2-yl derivatives are synthesized as the anti isomers which upon heating undergo rotation about the sp2–sp3 C–C bond to give the more stable, syn isomers with activation energies in benzene of 31.0 (Me) and 30.7 (Et) kcal mol–1. Semi-empirical (AM1) and ab initio (3-21G*//AM1) calculations indicate that the energy difference between the two rotamers is of the order of 5 kcal mol–1. Ionic hydrogenation of anti-(N-methylpyrrol-2-yl)diadamantylmethanol in dichloromethane–TFA–triethylsilane gives the anti isomer of (N-methylpyrrol-2-yl)diadamantylmethane, accompanied by substantial amounts of diadamantylketone. The barrier to anti→syn rotation in the deoxygenation product is about 4 kcal mol–1 higher than for the corresponding alcohol.

Thermal fragmentation of 1-substituted spiro[adamantane-2,2′-adamantane] derivatives

Thermolysis of 1-hydroxy- or 1-acetoxy[1]diadamantane gives mixtures of 3-(adamantylidene)-bicyclo[3.3.1]non-6-ene,3, 3-(2-adamantyl)bicyclo[3.3.1]nova-2,6- and -2,7-dienes, 4, and 2-(3-noradamantyl)-2,4-dehydroadamantane, 7. At low conversion 3 and 7 are the major products, while one isomer of 4, the 2,6-diene, predominates in the equilibrium mixture. Pd/C-catalysed hydrogenation of the dienes in ethanol gives first 3-(2-adamantyl)bicyclo[3.3.1]non-2-ene, 5, and then endo-3-(2-adamantyl)bicyclo[3.3.1]nonane, 6. Hydrocarbon 7 is not hydrogenated under these conditions; it is converted into a mixture of 3 and 4(2,6) upon heating. Mechanisms for the fragmentation of the 1-[1]diadamantyl carbocation are discussed. While a 1,4-hydride shift may contribute to the reactions of the [1]diadamantane system, molecular mechanics calculations suggest that the ready formation of an olefin from 1-hydroxyspiro [adamantane-2,9′-bicyclo[3.3.1]nonane] is best interpreted in terms of a 1,5-hydride shift involving the chair-boat conformation of the bicyclononane system.

Thermal rearrangement of 1-substituted spiro[adamantane-2,2′-adamantane] derivatives

Tertiary 1-halospiro[adamantane-2,2′-adamantane] derivatives (1-halo[1]diadamantanes) have been synthesised by reaction of the 1-[1] diadamantyl cation with appropriate nucleophiles. Thermolysis of 1-chloro- or 1-bromo-[1]diadamantane, but not the 1-fluoro derivative, gives the corresponding secondary 4-halo derivative in good yield. By 1H and 13C NMR spectroscopy and by X-ray crystallography it has been established that the 4-bromo [1]diadamantane isolated is the anti isomer, with the Br–C–C–Cspiro torsion angle close to 170°, this being the less strained of the two possible 4-substituted isomers, according to molecular mechanics calculations. Possible mechanisms for the rearrangement are discussed.

Ring opening of a formal cyclopentylmethyl radical in the thermolysis of di(tert-alkyl)(1-norbornyl)methanols

In the thermolysis of di(1-adamantyl)(1-norbonyl)methanol, Ad2NorCOH, 1a, in toluene at 220–265 °C, C–C bond cleavage within the norbornyl group of the first-formed (1-adamantyl)(1-norbornyl)ketyl radical (by loss of Ad˙) leads to ring-opened ketones and several ketonic cross-products. These are isomeric with the secondary alcohol, AdNorCHOH, and with the regular cross-product, AdNorSCOH (S = benzyl), respectively, also present in the product mixture. Formation of the ring-opened thermolysis products is particularly favoured by high temperature and the use of deuteriated solvent, which slows hydrogen transfer from the solvent to the intermediate ketyl radical. The new products are cyclopentane derivatives, formed by cleavage of the norbornyl C(1)–C(2) bond, in agreement with MM2 calculations on the transition states. Self-consistent values for the cage effect have been determined by measuring the extent of 1-[2H] labelling of the adamantane formed in [2H8] toluene and by scavenging the ketyl radical with benzenethiol in [1H8] toluene. The product composition of the scavenger-free reaction in [1H8] or [2H8] toluene has been interpreted by kinetic simulation based on the steady state approximation, a Simplex procedure being used to optimise several rate constants, in particular those for hydrogen transfer from toluene to the ketyl radical and ring opening of the latter. The Arrhenius pre-exponential factor and activation energy are both much greater for ring opening than for hydrogen transfer.

Competing intermolecular and intramolecular hydride transfers in the ionic hydrogenation of (2-alkoxyphenyl)di(1-adamantyl)methanols†

ortho-Lithiation of anisole followed by reaction with di(1-adamantyl) ketone gives syn-(2-anisyl)di(1-adamantyl)methanol with the C–OH proton intramolecularly hydrogen-bonded to the methoxy group. Reaction of the alcohol with trifluoroacetic acid (TFA) in dichloromethane leads to a trifluoroacetate and a substituted phenol. These are formed via a carboxonium ion, resulting from an intramolecular 1,5-hydride shift of the initially formed carbocation. Ionic hydrogenation of the alcohol with TFA and a hydrosilane in dichloromethane results in the expected anti and syn deoxygenation products as well as the trifluoroacetate and the phenol. anti-(2-Anisyl)diadamantylmethane (benzylic hydrogen remote from methoxy, confirmed by a single crystal X-ray diffraction study) is formed directly from the carbocation while the syn isomer results from reduction of the carboxonium ion. Reduction of the carbonium ion is more hydrosilane-selective than that of the carboxonium ion. Kinetic isotope effects (kH/kD) on the reaction of the carbocation at room temperature average 1.50 for triethylsilane and dimethylphenylsilane. Analogous reaction of the (2-ethoxyphenyl) derivative gives only syn-(2-ethoxyphenyl)diadamantylmethane and the substituted phenol. Kinetic isotope effects on the reduction of the corresponding carboxonium ion average 1.34 for the same hydrosilanes.

An unusually large kinetic Br/Cl leaving group effect for the solvolysis of1-halospiro[adamantane-2,2′-adamantane]

The very large kBr/kCl leaving group effects of 2300–4500 for solvolysis of 1-halospiro[adamantane-2,2′-adamantane] compounds in slightly ethanolic or aqueous acetone are consistent with the occurrence of F-strain.

1,4-Hydride shifts in ortho-alkyl-substituted di(1-adamantyl)benzyl cations: an NMR spectroscopic and X-ray crystallographic study

When carbocations are formed from ortho-alkyl-substituted phenyldi(1-adamantyl)-methanols in the anti conformation, the alkyl group being isopropyl or ethyl, rapid 1,4-hydride transfer from the alkyl group to the charged carbon occurs, giving either styrene (o-isopropyl) or secondary (o-ethyl) derivatives. 13C and 1H NMR spectroscopy and, in one case, single crystal X-ray crystallography show that all products are the syn rotamers, with the benzylic hydrogen of the diadamantylmethyl group oriented towards the ortho substituent. Even in the presence of triethylsilane no anti isomer is formed; instead, the rearranged carbocation is wholly or partially reduced by hydride transfer from the silane.

13 C NMR spectroscopic comparison of sterically stabilized meta- and para-substituted o-tolyldi(adamant-1-yl)methyl cations with conjugatively stabilized benzyl cations

A series of meta- and para-substituted anti-o-tolyldi(adamant-1-yl)methyl cations has been generated by reaction of anti-o-tolyldi(adamant-1-yl)methanols with trifluoroacetic acid in chloroform. 13C NMR spectroscopy indicates small but significant variations in the chemical shifts of the charged carbon and its nearest neighbours on the adamantyl groups, and departures from additivity of substituent effects on the shifts of the aromatic carbons. Previous work on the closely related di(adamant-1-yl)benzyl cations is discussed. Comparison with data on aryl-substituted carbocations in superacid media reveals marked differences in the aromatic carbon shifts in the two types of carbocation. The dihedral angle between aryl and carbocation planes in aryldi(adamant-1-yl)methyl cations is estimated to be about 60°.

Thermolysis of highly congested tri-tert-alkylmethanes. Rearrangement of a 3-noradamantylmethyl radical

Activation energies for C–Ad fission in the thermolysis of di-1-adamantyl-tert-alkylmethanes and 1-adamantyl-di-1-bicyclo[2.2.2]octylmethane, AdR1R2CH, in toluene are best correlated with the strain energy difference (MMP2 force field) between the methane and the corresponding radical, R1R2C·H; difficulties were encountered in the application of MM3 to certain of these trialkylmethanes. Normally, the major thermolysis product is the di-tert-alkylmethane, R1R2CH2, but when a 3-noradamantyl group is present (1d) the initially formed radical ring opens to give 1,2′-biadamantyl in amounts which depend on the temperature and the solvent (normal or octadeuteriated). This rearrangement is readily explained by MMP2 calculations. Since the crossproduct yield is low (less than 3%, even in deuteriated solvent at the highest temperature) the thermodynamic parameters for the hydrogen transfer and ring opening reactions of the 1adamantyl-3-noradamantylmethyl radical can be compared directly. Both the activation enthalpy and entropy are much greater for ring opening than for hydrogen abstraction from the solvent. Isotope effects on hydrogen abstraction are high and satisfy certain criteria for tunnelling, as do data on the analogous reaction of Ad2C·H. A more sophisticated treatment of the product composition for 1d thermolysis, using kinetic simulation, leads to essentially the same conclusions as the simpler treatment.