Norbornane derivatives

Bicyclo[2.2.1]hepten-7-one is a useful intermediate in the synthesis of a variety of norbornane derivatives. The present procedure involves a four-step synthesis from hexachlorocyclo-pentadiene with a 39% overall yield. The next best method3 involves a four-step synthesis from norbornadiene with a 15% overall yield. 

All difficulties arising from an uncritical use of van t Hoff s concept are due to the treatment of the chirality of compounds with rigid polycentric skeletons on the basis of asymmetric C-atoms. For example, the chirality of the norbornane derivatives, i.e., 13, has been attributed to its asymmetric bridgehead C-atoms 20c>23). 

Substituted norbornane derivatives have been synthesized by the reaction of norbornenes with carbonyl ylides derived from a-diazoketones by a 1,3-dipolar cycloaddition route (Equation 97) <2002TL5981>. These reactions occur in high yields and with excellent o o-selectivity (Table 8). 

Two molecules of norbornene 116 are incorporated in its coupling with / -bromostyrene to yield the bisnorbornane-annelated methylenecyclopentane derivative 120. But under different conditions, the reaction proceeds with the reverse 2 1 stoichiometry to give the cyclohexadiene-annelated norbornane derivative 121 (Scheme 32). ... 

Treatment of em/ -2-methylbicyclo[3.2.0]heptan-<3.x n-2-ol with 0.25 M sulfuric acid in acetic acid, followed by reduction of the resulting acetate with lithium aluminum hydride, gave l-methylbicyclo[2.2.1]heptan-7-ol (10) in almost quantitative yield and with greater than 95% purity.10 The virtually exclusive formation of the norbornane derivative under thermodynamic control is commensurate with the lower strain energy of the bicyclo[2.2.1]heptane skeleton (62.8 kJ mol ), as compared to that of bicyclo[3.2.0]heptane (138.2 kJ mol- l.10... 

Similarly, norbornane derivatives with considerable complexity were also obtained via a cy-clobutylmethyl cation to cyclopentyl cation rearrangement. Acid hydrolysis of tricy-elo[5.4.0.02 5]undecan-1-ol 11 with trifluoroacetic acid and subsequent saponification of the resulting trifluoroacetate gave cis-syn-ol 12 in 90% yield, together with trans-syn-ol 13 (3%).13 Most remarkably. 12 was the major product. 

Rule 2, Adopt bicyclo plan enumeration for the complete ring carbon skeleton (Chart 9) and for the structures named as norbornane derivatives. Adopt a fixed numbering for the complete carbon skeleton of the larger parent compound (Chart 8). Thus ... 

Rule 7. If a double bond attaches a substituent to the nor- ring, its presence is denoted by the name of the substituent group preceded by the proper ring position number, and the structure is named as a norbornane derivative - e.g., 2-methylene-norbornane. 

The EIZ equilibrium of the open-chain tautomers may exert an influence on the ring-chain equilibria just discussed, but this problem has not been studied. In order to obtain the best comparable results for the whole series of systems 13-30, the ring-chain equilibrium constants for the norbornane derivatives 26 and 27 were calculated as KT = [B + B ]/[A- ], i.e., those involving only the E isomer of the open-chain form (91T403I). 

Fig. 2.28. Stereoselectivity by neighboring group participation in the acetolysis of norbornane derivatives 2e, 3c, two-electron, three-center.

The 2-methylcyclohexane derivative X, the norbornane derivative XV, the tert.leucine (I) and the N-trimethylglycine (XVI) provide information about the structural preconditions for sweet taste in the vicinity of ammonium and carboxylate groups (cf. Fig. 4 and 5). 

Even PhLi can be used to transmetallate a primary alkyl iodide if the product organolithium is consumed by a subsequent reaction. For example, the norbornane derivative 8 forms in good yield on treatment of 7 with PhLi, despite the thermodynamic unfavourability of the transmetallation step.13... 

Ail carbcne rearrangements (as well as carbenium ion rearrangements, such as pinacol type isomerisations) require that the o-bond of the migrating group and the empty orbital of the carbene should be parallel. TNs has been dcmunstiated, for example, by the isotope labeling of hydrogens in norbornane derivatives (33] ... 

The spiro-triazoline (380) can be converted into both the ketenimine (381) and the cyclobutanimine (382) (74JOC63). Triazolines formed by cycloaddition of azides to norbor-nene lead to munerous interesting norbornane derivatives (of. 78bsf(2)48s). 5-Hydroxytriazo-lines (383) afford the ring-contracted amide (384) by thermal dehydration (67mi411oo). 

The H-H bonding interaction is ubiquitous and has been found in a number of systems. The earliest experimental account I am aware of reporting unusually short intramolecular H- H distances is that of Ernier and Mason [42]. These authors find H- -H distances as short as 1.754(4) A and 1.713(3) A between neighbouring bridgehead hydrogen atoms in fused norbomenes based on low temperature neutron diffraction experiments [42]. Even shorter H- -H distances were suggested in another norbornene derivative on the basis of an X-ray diffraction determination (Jr h = 1-62 A) [49]. While the latter result awaits confirmation by neutron diffraction, it still indicates that norbornene or norbornane derivatives are candidates for very short, perhaps the shortest, intramolecular H- H distances. The molecular graph of the parent compound in this series (exo, exo-tetracyclo[6.2.1.1 .0 ]dodecane) obtained at the... 

Since the 1950 s, an enormous amount of work has been carried out on other nucleophilic substitutions of norbornane derivatives and related compounds. This was particularly due to the alternative mechanistic explanation proposed by H. C. Brown in 1962 (see also Brown, 1966, 1976, 1977). He postulated that instead of the nonclassical intermediate 7.97, the expected classical carbocation 7.100 is formed in a rapid equilibrium with the ion 7.101. In his opinion, 7.97 is not an intermediate, but corresponds to the transition state in the equilibrium 7.100 7.101 (Scheme 7-33). Arguments for and against Winstein s and Brown s proposals by other researchers can be found first of all in Bartlett s anthology (1965) and in the literature until the present day (see some 30 references in the period 1977-1988 in March s book, 1992, p. 321) ... 

Particularly in the first half of the more than forty years since Winstein and Trifan s proposal, the contributions concentrated mainly on kinetics and product ratios of 2-norbornane derivatives Olah s development of superacid media ( magic acid , see review of Olah et al., 1985d) allowed preparation of stable solutions of aliphatic carbocations. As a result, direct spectroscopic investigation with UV, IR, NMR, etc., became feasible for carbocations in general and for the 2-norbornyl cation in particular (NMR in liquid phase Olah et al., 1982 NMR in solid phase Yan-noni et al., 1982 IR Koch et al., 1989, 1990). 

After this general discussion of the nucleophilic substitution of norbornane derivatives, we will concentrate on the deamination of exo- and eAzrfo-2-norbornyl-amine. The acetolysis of norbornanediazonium ions was first studied by Corey et al. (1963) and by Berson and Remanick (1964). Their results could not be interpreted easily either by Winstein s or by Brown s hypothesis, as seen, for example, in Bartlett s annotated reprint collection (1965), in which he emphasized the need for fully resolved reagents and for better separation methods. 

Table 4. Reactivity of 7-Thia- and 7-Oxa-norbornane Derivatives in Solvolysis...

Polyhydrojgrlated norbomanes and derivatives. To more closely mimic the B conformation, the norbornane derivative 19 and the oxygenated... 

A series of phosphonylated bicyclic nucleosides (locked in a South conformation, no o>ygen atom in the rings) was synthesised by Nencka and co-workers. The synthesis begun with norbornane derivative 34 (Scheme 10), which, in a multistep process was converted into the bicyclic nucleoside 35 bearing 6-chloropurine or 2-amino-6-chloropurine. The chlorine atom was then replaced with several other substituents. Finally, a methylphosphonate group was attached at the hydroxyl group... 

If additional side chains (other than methyl or methylene groups) are present naming is based on the respective trivial names. Other substitution products of these skeletons are treated as norcarane, norpinane, and norbornane derivatives. 

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