Search

Camphor- and fenchone-based bridgehead-substituted norbornan-2-ones constitute an interesting class of chiral synthons with applications in stereoselective synthesis, due to the wide variety of stereocontrolled transformations which they can undergo. Despite their synthetic value, few mass spectral studies have been realized for these compounds due to the lack of general procedures for their preparation. In this paper we have carried out an electron ionization (EI) mass spectral study of a series of heteroatomically bridgehead-substituted 7,7-dimethylnorbornan-2-ones. Their cleavage mechanisms have been 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 driving force for the main fragmentation pathways of C(1)- O - and C(1)- N -substituted 7,7-dimethylnorbornan-2-ones is the α-cleavage of the C(1) C(2) bond directed by the bridgehead substituent. Further rearrangements and fragmentations of the distonic ions initially formed lead to the major ions in the spectra of all the compounds. A comparison with the known behaviour of their isomeric 3,3-dimethylnorbornan-2-ones reveals that the key bridgehead heteroatom effect controlling the fragmentation pathways can be modulated by the position of the gem -dimethyl group. As a consequence, the corresponding fragmentation patterns of both isomeric series are very different. In contrast, the fragmentation patterns of 7,7-dimethyl-2-oxo-1-norbornanesulphonamides, whose main fragmentation pathway involves homolytic S N bond cleavage, are almost identical to those displayed by their 3,3-dimethylated isomers.

The reaction rates of the water-trapping of unstable 1-norbornyl cations in relation to the rates of their rearrangement (ring contraction) have been experimentally determined. The activation barrier of the rearrangement reactions was calculated with the QST2 method, whereas the Marcus theory was applied to predict the activation barrier of the trapping reaction. All computations in gas phase were performed with the DFT B3LYP/6-31G(d) method, while the PCM model was used for the computation of unspecific solvent effects. The established methodology was able to predict the major product formed in the solvolysis of the corresponding triflate precursors of the studied carbocations. The agreement between experiment and theory supports, for the first time, the interesting conclusion that the very exergonic trapping-reaction of unstable 1-norbornyl cations takes place with relatively high barriers of activation and, hence, into the Marcus inverted region. Additionally, a noteworthy relationship between the free energy of activation for the carbocation rearrangement in gas phase and the length of the rearranging bond in the ground state is reported.

Interesting norbornane-fused tetrahydrofurans, with an additional synthetically-valuable vicinal dioxy-substitution in the norbornane skeleton, are enantiospecifically obtained in high yield from epimeric camphor-derived 3-endo-bromomethyl-substituted spiroepoxidic 1-norbornyl triflates. The process takes place via a domino reaction stereoelectronically controlled by the bromine atom. The described process has synthetic value, since it opens the way for a future enantiospecific preparation of 2,3-disubstituted tetrahydrofurans from camphor.

A highly-functionalized eight-membered cyclic ether, with an additional interesting trans-fusion to a cyclobutane ring, is enantiospecifically obtained in high yield from a camphor-derived di(spiroepoxide)-substituted 1-norbornyl triflate, via a regio- and stereocontrolled domino process. The described process could constitute a novel model procedure for the preparation of eight-membered cyclic ethers from α,α′-bis(spiroepoxide) cyclopentyl derivatives.

An easy two-step route for the stereoselective synthesis of novel bridgehead-fused norbornanethiazolines from readily available natural camphor and fenchone is described. The key step of the synthetic route is the highly stereoselective trapping of 1-(trifluoromethylsulfonylthio)-2-norbornyl cations by nitriles followed by intramolecular cyclization, which constitutes a new modification of the Ritter reaction.

The synthesis of chiral, rigid analogues of glycerol and cyclitols has been achieved by means of the stereocontrolled reduction of chiral bridgehead-substituted camphorquinones. This simple and easy procedure exclusively affords dihydroxy derivatives with a 2,3-cis-exo-configuration. The employment of different hydrides has also allowed the synthesis of enantiopure 2,3-dihydroxy carboxylic acids with high diastereoselectivity.

The electron ionization (EI) mass spectra of some new bridgehead 7,7-dimethylnorbornane-based β-amino alcohols have been studied and their fragmentation patterns compared with those of isomeric 3,3-dimethyl derivatives described by us previously. The dimethyl substitution at C7 results in a significant complication of the spectra, although all compounds show a C1–C2 bond cleavage with charge location at the nitrogen atom that leads to the base peak. Thus, two main fragmentation patterns dominated by cyclopentenylimmonium or methyleneimmonium ions are described depending on the position of the amino group in the norbornane framework (C1 or C2, respectively), as well as other secondary routes that can explain the appearance of the less noticeable fragments. Copyright © 2005 John Wiley & Sons, Ltd.

An empiric first approach to the knowledge about the structural factors influencing the catalytic behavior of conformationally flexible δ-amino-alcohol-based ligands, for the enantioselective addition of dialkylzincs to prochiral carbonyl groups, has been applied using the 1-(2-aminoethyl)norbornan-2-ol moiety as the model chiral system, and the asymmetrically catalyzed addition of diethylzinc to benzaldehyde as the test reaction. For this purpose, a selected small library of seven norbornane-based chiral ligands, bearing well-defined structural variations to allow a comparative study, that is, variation of the relative configuration and steric hindrance at the C(2), C(3) and/or C(7) norbornane positions, has been synthesized and probed in the mentioned test reaction. The experimental results obtained have been rationalized empirically using diastereomeric Noyori-like transition states, demonstrating that the conformational flexibility of the δ-amino-alcohol ligands, contrary to the more studied and rigid β-amino-alcohols, plays a crucial role on the catalytic behavior of such ligands (stereochemical sense and degree of the stereodifferentiation in the asymmetric process), which makes such structural factors, important for the improved design of new related chiral catalysts. In this sense, a robust crude empirical model for the prediction of the catalytic behavior of such δ-amino-alcohol-based ligands is proposed.

The competitive pathway timing for the previously described unexpected bromo-assisted Beckmann fragmentation of 7-anti-bromo-3,3-dimethyl-2-oxonorbornane-1-carboxamide has been investigated. It is concluded that this unusual process is activated by a synergic effect exerted by both the C(7)-anti-bromo and C(1)-aminocarbonyl groups. The effect consists in a specific intramolecular activation of the bromo-assistance by the bridgehead aminocarbonyl group.

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.

Enantiopure 1-[2-(dimethylamino)ethy]-2,3,3-trimethylnorbornan-2-endo-ol, a new norbornane-based δ-amino alcohol, has been straightforwardly prepared from fenchone. The described route constitutes a model procedure for the preparation of other related C(2)-substituted δ-amino 2-endo-norbornanol ligands. The catalytic activity of the obtained δ-amino 2-endo-norbornanol (for the enantioselective addition of diethylzinc to benzaldehyde) has been compared with that previously described for the corresponding C(2)-epimer, which allows us to study about the role played by the configuration of the hydroxyl-bearing C(2) atom on the catalytic activity. Catalyst models and transition-state models for explaining such a role are proposed and discussed.

A short and convenient procedure for the stereoselective synthesis of novel optically active 2-hydroxy-1-norbornanesulfonamides starting from commercially available natural camphor and fenchone is reported. The synthetic route involves a nucleophilic substitution at the sulfenyl sulfur atom of 2-methylene-1-norbornylthiotriflates followed by oxidation of the intermediate sulfenamides and highly diastereoselective reduction of the carbonyl group of the parent 2-oxo-1-norbornanesulfonamides.

Five enantiopure C(2)-substituted 10-[(dimethylamino)methyl]isoborneols has been prepared by a novel straightforward camphor-based route, and probed as δ-amino-alcohol ligands for the enantioselective addition of diethylzinc to benzaldehyde. The established route constitutes a divergent model procedure for this class of δ-amino-isoborneol ligands, allowing different substitutions, not only at the nitrogen atom, but also at the more interesting hydroxyl-bearing C(2)–norbornane position. This last synthetic possibility has made possible a study of the role played by the group located at the C(2)–norbornane position on the catalytic activity. New catalyst models and transition-state models for explaining such a role are also proposed and discussed.

The mechanism of the Leuckart reaction of 3,3- and 7,7-dimethyl-2-oxo-1-norbornyl triflates and triflamides, synthesised by us starting from (1R)-camphor and (1R)-fenchone, has been studied. Strikingly, the electron-withdrawing capacity of the bridgehead substituents has demonstrated not to be enough to control the Wagner–Meerwein rearrangement during the course of the reaction, so that only both enantiomers of a 3,3-dimethylnorbornanediamine derivative have been obtained as final products. As a result, the total synthesis of these interesting chiral compounds has been optimised and shortened until three overall steps starting from (1R)-fenchone.

An easy three-step route for the enantiospecific synthesis of novel 1-norbornyl thioethers and thiocyanates from readily available natural fenchone and camphor is described. The key step of the synthetic route is the nucleophilic substitution over the sulfenyl sulfur atom of the intermediate thiotriflates by the corresponding C-nucleophiles.

The enantioselective addition of diethylzinc to benzaldehyde has been used as standard procedure to test a series of new chiral catalysts derived from norbornane framework. The new ligands are β-amino alcohols possessing both heteroatomic substituents attached to the C(1) and C(2)-endo positions (novel non-coplanar disposition) of a 3,3-dimethylsubstituted norbornane. The results obtained, compared with other previously reported on the related C(2)-exo-7,7-dimethyl series, demonstrate that the relative disposition of the amino, hydroxy and gem-dimethyl groups, as well as the N-alkyl substituents, play an important role on the catalytic activity. Interesting transition-state models have been also proposed in order to explain the observed experimental results.

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 ...

The cis/trans ratio of N-methylformamide (NMF), N-methylacetamide (NMA), and N-(2-endo-norbornyl)formamide (NNF) in dilute solutions in chloroform, methanol, and water have been experimentally measured by 1H NMR. Unlike NMA and NMF, the cis/trans ratio of NNF is sensitive to the solvent environment. To understand the anomalous behavior of NNF, we have performed calculations of ΔG and other observables between the cis and trans isomers of NMA, NMF, and NNF both in gas phase and in solution using several ab initio and DFT methods and SCRF models. The strikingly predominance of the trans isomers of N-alkyl substituted formamides can be rationalized in terms of close contact interactions between the formyl group and the C−H bond of the N-alkyl group. The molecular geometries and dipole moments of the studied amides using the RHF and B3LYP theoretical levels and split valence sets are in good accordance with the experimental values. The rotational barriers (ca. 7.0 kcal/mol) around the C2−N bond of cis- and tr...

Five new optically active bridgehead-norbornane-derived β-amino alcohols with different substitution patterns have been obtained using a straightforward procedure from commercial (+)-camphor or (−)-fenchone, and tested as chiral catalysts in the enantioselective diethylzinc-addition to benzaldehyde. The obtained results show that chirality transfer is mainly governed by the hydroxyl group and, therefore, by the surroundings of the CO stereocenter. On the other hand, the N- alkyl substitution play an important role by modulating the degree of enantioselectivity.

The preparation of two new spiro[oxirane-2,2′-norborn]-1′-yl triflates as well as the study on the behavior of such triflates under nucleophile treatment is reported. Three different nucleophile reagents have been chosen for this study: aqueous ethanol (a weak hard-base nucleophile), sodium hydroxide (a strong hard-base nucleophile) and lithium aluminum hydride (a strong soft-base nucleophile). It is concluded that the described norbornane-derived bridgehead triflates react chemoselectively with these nucleophiles following one of three possible reaction pathways, according to the character (strong or weak nucleophile, hard or soft base) of the reagent. For strong nucleophiles the HSAB principle is fulfilled.

The preparation of enantiopure (1R,2S)-2-chloromethyl-3-oxocyclopentanecarboxylic acid 9, an interesting possible precursor of the antitumor agent sarkomycin, from a camphor-derived 3-hydroxymethylnorbornan-2-one is reported. The described procedure constitutes the first stereocontrolled approach to sarkomycin starting from commercially available natural camphor. The procedure takes place in only six steps with a high overall yield (59%). The key-step of the described procedure is the stereocontrolled ring opening of a conveniently functionalized 3-oxonorborn-1-yl triflate under a straightforward basic hydrolysis. The described route constitutes a model procedure for the preparation of other enantiopure C2-substituted 3-oxocyclopentanecarboxylic acids; which are related with the sarkomycin family of antitumor agents.

The enantiospecific preparation of the interesting chiral source 10-hydroxycamphor from commercially available camphor is described. The synthetic procedure takes place straightforwardly in only three synthetic steps with a high overall yield. The key step of the described route is based on the ability of a 2-methylenenorbornane intermediate to undergo an enantiospecific Wagner–Meerwein rearrangement under electrophilic treatment with m -CPBA.

A new enantiospecific synthetic route to the interesting chiral synthetic intermediate 10-bromocamphor starting from readily available camphor is described. The procedure takes place straightforwardly in only three synthetic steps with high overall yield. Mechanistically, two interesting enantiospecific Wagner–Meerwein rearrangements involving 2-norbornyl carbocations take place during the process.

New homochiral 1-norbornanesulfenic and sulfonic acid derivatives 2 – 7 , as well as the sulfonic acids 8 , are easily synthesised starting from 2-methylene-1-norbornylthiotriflates 1 . This new class of homochiral bridgehead thiosulfonates was prepared by us from naturally occurring (+)-camphor and (−)-fenchone. Nucleophilic substitution at the sulfenyl sulfur atom is the key step for this synthetic strategy.

The electron impact mass spectra of several 3,3-dimethyl-1, 2-norbornanediols, diamines, amino alcohols and related derivatives have been studied and their fragmentation pathways discussed. Different fragmentation patterns were observed, depending not only on the nature of the substituents, but also on their relative positions on the norbornane framework. In general, the dominant peaks in the spectra of these compounds originate from initial C1-C2 bond cleavage (alpha-cleavage) with charge retention on the heteroatom (oxygen or nitrogen) attached at the bridgehead position, followed by hydride shift and loss of the C2-C3 fragment by homolytic cleavage of the C3-C4 bond. This fragmentation pathway leads to a highly stabilized cyclopentenylimmonium or cyclopentenyloxonium ion, which constitutes the base peak in the spectra in most of the studied compounds. Copyright 1999 John Wiley & Sons, Ltd.

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.

Two different 1-amino-3,3-dimethyl-2-methylenenorbornane hydrochlorides, a primary ammonium chloride and a tertiary one, react unexpectedly with m-CPBA (meta-chloroperbenzoic acid) according to two different paths. The primary ammonium chloride gives place to a diastereomeric mixture of the corresponding spiranic 1-nitronorbornane-based epoxides, whereas the tertiary derivative undergoes a skeleton rearrangement giving 10-chlorocamphor. The results are interpreted in terms of competitive reaction pathways controlled by the nitrogenated group located at the C1 norbornane position.

One of the most important features of the synthesis of camphor-derived compounds is the control of the stereochemistry at the C2 position. According to this, reduction of bridgehead-substituted 2-norbornanones 1 and 2-norbornanoximes 3 has been considered by us as a very convenient method for the preparation of different classes of enantiomerically pure 1,2- and 1,3-difunctionalised norbornane derivatives. Factors controlling the stereoselectivity in these reductions, as well as the role played by the nature of the bridgehead functional groups are discussed.

The reaction of different substituted 2-norbornanones 1 with triflic anhydride in the presence of nitriles 6 is carried out in order to study the factors that influence on the different reaction possibilities of 2-norbornyl carbocations. The syntheses of interesting annulated pyrimidine derivatives 10 and conformationally rigid 1,3 disubstituted products are described.

New homochiral 1-norbornylthiotriflates 6 and 7 and 1-norbornanethiols 8 and 9 are easily prepared starting from naturally occurring 2-norbornanones 1 . The key step is the reaction of chiral 2-norbornanethiones 2 with Tf 2 O under mild conditions.

7,7-Dimethyl-2-methylenenorbornan-1-ol, a fenchone-derived strained allylic bicycloalkan-1-ol, undergoes an unexpected new type of anomalous ozonolysis to yield a mixture of a rearranged β-hydroxyketone and a fragmented carboxylic acid. The proposed mechanisms involves two unusual different trappings for two different key Criegee’s intermediates.

A general and straightforward enantiospecific access to synthetically valuable 10-N-substituted camphors (amines and secondary amides) has been developed. The synthetic method uses camphor as the starting enantiopure material and takes place in five individual steps with a high overall yield. The process involves a stereocontrolled double-Wagner–Meerwein-rearrangement strategy to generate key-intermediate 10-(triflyloxy)camphor, a peculiar and highly-reactive primary triflate, which is able to alkylate soft N-nucleophiles, such as amines and nitriles, easily and without producing Grob-like fragmentation of the β-(triflyloxy)ketone-based norbornane system.

The solvolysis of 3,3-dimethyl-2-oxo- and 2,2-dimethyl-3-oxo-1-norbornyl triflates (6 and 8) takes place with formation of ring contracted and fragmented products respectively. The effect of the substituents on the solvolysis rates is explained taking into account n- and σ-participation. This n,σ-participation causes changes in the structure and stability of the intermediate carbocations, which can be detected by the AM1 method.

A new, general and straightforward method for the enantiospecific synthesis of 9,10-dihalocamphors (including mixed derivatives) is reported and exemplified for the preparation of (+)-9,10-dibromocamphor (a well-known chiral intermediate) as well as (+)-9-bromo-10-chlorocamphor and (+)-9-bromo-10-iodocamphor (novel mixed dihalides). Our approach is based on a key stereocontrolled tandem electrophilic addition - Wagner-Meerwein rearrangement of optically pure 3-endo-(halomethyl)-3-methyl-2-methylenenorbornan-1-ols, which are easily obtained from readily accessible 9-halocamphors.

A valuable route for the preparation of enantiopure C(7)- anti -substituted fenchones, a new interesting type of the C(7)-substituted-norbornane-based chiral-sources, has been established. The procedure takes place diastereoselectively in just three easy individual synthetic steps starting from readily available fenchone. The established route constitutes a model procedure for the preparation of other interesting C(7)-substituted fenchone-based chirality transfers [e.g. C(2)C(7)-bidentate norbornane-based ligands] from the chiral pool.

The main fragmentation pathway of vinyl triflates in mass spectra involves the loss of CF3SO, followed by the loss of olefin and/or CO. The loss of TfOH takes place with fragmentation of a vinylic CH bond. TfOH ions are formed via regiospecific double hydrogen transfer from five- and six-membered cyclic triflates.

Camphor-derived 3,3-dimethyl-2,7-dioxonorborn-1-yl triflate, a new C(7)-substituted 2-oxonorborn-1-yl triflate, reacts readily with water to give an interesting bicyclo[2.2.2]octane-derived lactone, which results from an expansion of the norbornane ring by the methano bridge. This unusual reactivity constitutes the first example in which a 2-oxonorborn-1-yl triflate undergoes hydrolysis with norbornane-ring expansion instead of the expected norbornane-ring contraction (formation of a bicyclo[2.1.1]hexane-1-carboxylic acid). Mechanistically the process takes place through a stereocontrolled tandem bicycle-ring opening−bicycle-ring closing, which is activated by the oxo group located at the C(7)-norbornane position. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Enantiopure 7-anti-bromo-3,3-dimethyl-2-oxonorbornan-1-carboxamide, which is easily obtained from commercially available 3-endo-bromocamphor, undergoes an unexpected stereocontrolled Beckmann fragmentation in situ upon treatment with hydroxylamine. This reaction constitutes the first example in which a C1-electron-acceptor substituted 3,3-dimethylnorbornan-2-one undergoes: a) an in situ Beckmann fragmentation upon reaction with hydroxylamine, and b) a Beckmann fragmentation of the C1−C2 norbornane bond instead of the C2−C3 bond. Both facts can be attributed to the effect exerted by the bromine substituent located at the C7-norbornane position. Since the described stereocontrolled bromine-promoted fragmentation leads to an enantiopure 1,3-disubstituted five-membered carbocycle, it could constitute a model procedure for the synthesis of other interesting enantiopure cyclopentanoids.

A new straightforward enantiospecific synthetic procedure to both 10-methylenecamphor and 10-methylenefenchone, from (+)-camphor and (−)-fenchone, respectively, is described. 10-Methylenecamphor is the key intermediate in Paquette's approach to taxol and taxusin, whereas 10-methylenefenchone could be a convenient intermediate to a new family of potentially interesting taxoids. The key steps of the described procedure are: (a) stereocontrolled tandem electrophilic carboncarbon double-bond addition-Wagner–Meerwein rearrangement of a camphor- or fenchone-derived 2-methylenenorbornan-1-ol under Eschenmoser's salt treatment, and (b) Cope elimination for generation of the vinyl group at the bridgehead norbornane position.

Enantiopure 3,3-dimethyl-2-methylenenorbornan-1-ol, readily obtained from commercially available camphor, is able to react with Eschenmoser's salt under very soft reaction conditions. This reaction constitutes the first example in which a non-mesomerically activated olefin easily adds the Eschenmoser's salt. The addition takes place regiospecifically and it is followed by an enantiospecific Wagner–Meerwein rearrangement of the norbornane skeleton to afford enantiopure 10-dimethylaminomethylcamphor, an interesting chiral δ-amino ketone, with excellent yield. The obtained amino ketone is a key intermediate to new valuable C10 C-substituted camphor-derived chiral sources.

A novel, highly efficient enantiospecific preparation of 10-hydroxyfenchone from commercially available fenchone is described. The three-step synthetic route is based on two consecutive Wagner–Meerwein rearrangements of the fenchone skeleton, taking place with a high overall yield. This straightforward access to optically active 10-hydroxyfenchone, together with the scope for further functionalisation of the hydroxyl group, makes 10-hydroxyfenchone a convenient key intermediate to other optically active C(10)- O -substituted fenchones, which are analogues of well-known C(10)- O -substituted camphor-derived chiral sources.

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.

The enantiospecific preparation of two novel C10-S(II)- and C10-Se(II)-substituted camphor derivatives (arylsulfide and arylselenide) from readily available camphor is described. The established three-step route constitutes a model procedure for the straightforward preparation of interesting enantiopure C10-S- and C10-Se-substituted camphor-derived chiral sources. The key-step of the described route is an enantiospecific Wagner–Meerwein rearrangement of 3,3-dimethyl-2-methylenenorbornan-1-ol 6 under electrophilic treatment with an arylsulfenyl (or arylselenyl) chloride.

A novel four-step synthetic route to enantiopure cyclopentene carboxylic acids starting from commercially available 3-endo-bromocamphor is described. The synthesis is straightforward and practical. The key transformations involve firstly, an enantiospecific Wagner–Meerwein rearrangement of a bromocamphor derived cyanohydrin, and secondly the regiospecific C-(1)C-(2) bond scission of a 7-bromonorbornan-2-one.

The preparation of two new spiro[oxirane-2,2′-norborn]-1′-yl triflates as well as the study on the behavior of such triflates under nucleophile treatment is reported. Three different nucleophile reagents have been chosen for this study: aqueous ethanol (a weak hard-base nucleophile), sodium hydroxide (a strong hard-base nucleophile) and lithium aluminum hydride (a strong soft-base nucleophile). It is concluded that the described norbornane-derived bridgehead triflates react chemoselectively with these nucleophiles following one of three possible reaction pathways, according to the character (strong or weak nucleophile, hard or soft base) of the reagent. For strong nucleophiles the HSAB principle is fulfilled.

The reaction of 2-norbornanones bearing an amine derivative in the bridgehead position with formamide and formic acid yields enantiomerically pure 1,2-norbornane diamides. These compounds are excellent precursors of chiral vicinal diamines, which have been increasingly used due to their numerous applications in medicinal chemistry and asymmetric synthesis. The rigid structure of the norbornane framework allows the study of conformational equilibrium in the formamide groups and its dependence on other substituents in the molecule.