RESUMEN

Polystyrene grafted with a chiral zinc-complexing camphor-derived N,N-disubstituted hydroxyamide is proposed as a new type of functional polymer of high reusability for the development of sustainable organozinc-catalyzed asymmetric reactions. The main goal of this new functional polymer is the ease of the hydroxyamide-moiety preparation (cheap chiral ligand obtained straightforwardly from an enantiopure starting material coming from the chiral pool), as well as its chemical robustness when compared with other related zinc-complexing functional groups. The latter allows the polymer to be active after multiple applications, without significant loss of its catalytic activity. This fact is exemplified by the design and preparation of a polymer functionalized with a bis(hydroxyamide) proved previously as active in the homogeneous enantioselective addition of diethylzinc to aldehydes. The result is a cheap functional polymer with a very high reusability (the enantioselectivity and chemical yield are maintained practically constant after 20 applications). Additionally, a methodology for the multicycle use of these functional polymers is presented.

RESUMEN

The screening of the catalytic activity in the diethylzinc reaction of a series of easily accessible (1S)-ketopinic-acid derived hydroxyamides, designed by key structure modifications of a parent highly active related bis(hydroxyamide), has allowed to find the first case of dual stereoselection in highly structurally close ligands of such interesting chemically sustainable typology. The found striking dual stereoselection is explained on the basis of empiric models for the acting zinc catalysts and involved controlling transition states, which are supported by additional specific experimental structure-activity tests.

RESUMEN

Asymmetric bis(hydroxyamide)-based zinc-chelate catalysts are able to promote the enantioselective addition of diethylzinc to benzaldehyde in the absence of titanium with yields and ees comparable, or inclusively superior, to their C(2) -symmetric analogues. This unexpected fact demonstrates that the previously established assumption on the necessity of using C(2) -symmetric bis(hydrdoxyamides) to generate C(2) -symmetric zinc-chelate catalysts can be discarded, which expand the possibilities for designing new ligands based on the interesting hydroxyl-amide functional grouping.

RESUMEN

The electron ionization (EI) mass spectra of a series of bridgehead-substituted 3,3-dimethylnorbornan-2-ones, derived from natural (1R)-(+)-camphor, have been studied and their cleavage mechanisms rationalized on the basis of the substituent shifts as well as on the identification of relevant peaks through accurate mass measurements and collision-induced dissociation (CID) tandem mass spectrometric experiments. The fragmentation patterns are very dependent on both the structural nature and the electronic properties of the bridgehead substituent. The driving force for the main fragmentation pathways are competitive cleavages of the C(1)-C(2) and C(2)-C(3) bonds directed by the bridgehead substituent and either the gem-dimethyl or carbonyl groups. These cleavages lead to distonic ions in which the charge is preferentially located either at the C(1), C(2) or C(3) positions depending on the electronic character and structural nature of the bridgehead substituent. This charge distribution determines the subsequent rearrangements and fragmentations.

RESUMEN

A new set of optically active 2,3,3- and 2,7,7-trimethyl-substituted gamma-aminonorbornan-2-ols have been obtained from 2-methylenenorbornane-1-carbonitriles derived from (+)-camphor and (-)-fenchone and probed as chiral ligands for the enantioselective addition of diethylzinc to benzaldehyde. This has allowed the study of the structural factors influencing the chirality transfer, such as variation of the relative configuration at C(2) and steric hindrance at C(2), C(3), and C(7) positions of norbornane, which result in the observance of the important role played by the gem-dimethyl position in gamma-aminonorbornan-2-exo-ols. An empirical rationalization of the obtained experimental results has been realized on the basis of energetically-favored diastereomeric Noyori-like transition states.

RESUMEN

The study of the stereochemical outcome of the solvolysis of oxaspirocyclopropanated 1-norbornyl triflates is highly interesting since these reactions do not lead to the usual retention or fragmentation products but only synthetically interesting rearranged products are enantiospecifically formed. There is no correlation between the experimental solvolysis rates (ln k) and the B3LYP/6-31G(d)-computed ionization energies (Delta E) of the corresponding bridgehead hydrocarbons in gas phase. However, this work demonstrates the existence of a fair linear correlation between the experimental reaction rates and the PCM//B3LYP/6-31G(d)-computed free ionization energies in solution (Delta G). This theoretically relevant result reveals that the reason for the lack of linearity in gas phase is not the rearrangement of the intermediate carbocations but unspecific solvent effects on the solvolysis rates, accounted for by the PCM model.

RESUMEN

[structure: see text] The activation energy in the gas phase (deltaE(double dagger)) and the free energy of activation (deltaG(double dagger)) in water solution for the hydrolysis of the monohydrates of methyl chloride (MeCl), tert-butyl chloride (t-BuCl), and 1-adamantyl chloride (AdCl) have been computed with the B3LYP/631-G(d) method and the polarizable continuum (PCM) solvation model. There is a fair agreement between the deltaG(double dagger) values computed by us and the experimental data. The mechanistic implications of our computations are in severe contradiction with conventional representations. Thus, the computed nucleophilic solvent assistance (NSA) for the backside attack of a water molecule in the hydrolysis of MeCl is slightly lower than the corresponding NSA for t-BuCl. Hence, the hydrolysis of both MeCl and t-BuCl takes place mainly according to the classical S(N)2 mechanism. The most relevant difference is that deltaG(double dagger) for the frontside attack of water to t-BuCl is disfavored only by ca. 2 kcal/mol with regard to the backside attack but by ca. 23 kcal/mol in the case of MeCl. The higher solvolysis rate in water of t-BuCl in relation to AdCl is not due to steric factors affecting the specific solvation of the corresponding transition states, but to differential bulk solvent effects, which are accounted for by the PCM model.

Asunto(s)

RESUMEN

The valuable chiral sources C(9),C(10)-disubstituted camphors can be enantiospecifically obtained from the corresponding C(9)-substituted camphors by a general and straightforward synthetic method. This method involves the electrophilic treatment of a key 2-methylenenorbornan-1-ol intermediate, followed by a controlled tandem carbon-carbon double-bond addition-Wagner-Meerwein rearrangement of the norbornane framework. Discussion of the results presented suggests possible extensions and limitations of the methodology used. The feasibility of this method has been exemplified by the highly efficient enantiospecific preparation of several interesting C(9)-halogen-, C(10)-halogen, O-, S-, or Se-substituted camphors.

Asunto(s)

RESUMEN

Our interest in the relationship between the hydrogen bonding motifs displayed by monoalcohols and the properties of the solids which contain these motifs has led us to determine the crystal structures of three polycyclic bridgehead monoalcohols. One C10H16O isomer crystallises in the space group P2(1)2(1)2(1) but the three molecules which comprise the asymmetric unit are related approximately by the operations of a 3(1) screw axis. They are linked by hydrogen bonds to form an infinite helix. A second C10H16O isomer forms rings containing four molecules joined by cooperative hydrogen bonds. The chiral space group P4(1)2(1)2 accommodates molecules of the S,S and R,R enantiomers in the molar ratio 92:8 (ee 84%) owing to disorder. A related C9H14O2 keto-alcohol forms infinite chains by C-OH...O = C hydrogen bonding. These hydrogen bond motifs are shown to be typical for 45 tertiary monoalcohols, CmHnOH, present in the Cambridge Structural Database. Tertiary monoalcohols display in a more pronounced form the strong preferences for trigonal and tetragonal space groups and for asymmetric units containing several molecules which are established features of the crystallochemistry of monoalcohols.

RESUMEN

Valuable chiral sources of C(10)-substituted camphors and C(10)-substituted fenchones can be straightforwardly obtained by treatment of an appropriate, easily obtainable, camphor- or fenchone-derived 2-methylenenorbornan-1-ol with an electrophilic reagent. The process takes place via a tandem regioselective carbon-carbon double-bond addition/stereocontrolled Wagner-Meerwein rearrangement. A complete study of the enantiospecificity, scope, and limitations of this process, as well as about the role played by the hydroxyl group attached at the C(1) bridgehead position of the starting 2-methylenenorbornan-1-ols, has been realized. The feasibility of the described methodology has been exemplified by the highly efficient enantiospecific preparation of several interesting C(10)-halogen-, C(10)-O-, C(10)-S-, C(10)-Se-, or C(10)-C-substituted camphors and fenchones.

Asunto(s)

RESUMEN

The effect of a bridgehead methyl group on the hydride ion affinity in the gas phase of bicyclo[1.1.1]pent-1-yl (1+), 1-norbornyl (3+), cubyl (5+), 1-adamantyl (7+), bicyclo[2.2.2]oct-1-yl (9+),and bicyclo[3.1.1]hept-1-yl (11+) cations has been studied using density functional theory and ab initio methods. It is concluded that the methyl group always increases the stability of the substituted cations. The effect of the solvent on the stability of methyl-substituted cations in relation to the unsubstituted cations has been studied using the polarizable continuum model of the self-consistent reaction field theory. In the case of rearranging cations, the nucleophilic assistance of the solvent is determined by means of the interaction energy of the corresponding water complexes. It is concluded that the solvent causes the relative stabilization of the parent cations. As a consequence, most of the methyl-substituted bridgehead derivatives show a lower solvolysis rate than the corresponding unsubstituted compounds. A nonqualitative explanation of the methyl effect on the relative stability of bridgehead cations in both gas phase and solution is given for the first time. The ratios of solvolysis products in the case of rearranging bridgehead cations have also been computed from the relative stability of the intermediate water complexes.

RESUMEN

7',7'-Dimethylspiro[cyclopropane-1,2'-norbornan]-1'-yl triflate (9) was obtained and its solvolysis rates in buffered 60% aqueous ethanol were determined at different temperatures. The solvolytic behavior of 9 and other bridgehead derivatives (13-17, see Table 1) was studied by force-field, semiempirical and ab initio [B3LYP/6-31g(d)] methods. Cation 9(+) is a slightly pyramidal cyclopropylcarbinyl cation in a nearly perpendicular conformation, showing an sp(2)-like hybridization. Its high electron demand provokes an enhancement of the sigma-participation of the C(5)-C(6) and C(4)-C(7) bonds. The introduction of a cyclopropyl group adjacent to the bridgehead cation leads to an increase of the strain energy. This fact has two opposite effects on the solvolysis rate: (a) the strain energy hinders the flattening of the cation and, hence, originates a rate depression, and (b) the strained C-C bonds are prone to stabilize the cation at C(1) by sigma-delocalization, which provokes a rise of the solvolysis rate. Both effects are accounted for only by the B3LYP/6-31g method. The claimed electron-withdrawal effect of the cyclopropyl group as a basis for the small k(17)/k(16) rate ratio is not confirmed by our calculations.