Bridgehead carbocations

Certain aliphatic diazonium species such as bridgehead diazonium ions and cyclo-propanediazonium ions, where the usual loss of N2 would lead to very unstable carbocations, have been coupled to aromatic substrates. ... 

Since the central carbon of tricoordinated carbocations has only three bonds and no other valence electrons, the bonds are sp and should be planar. Raman, IR, and NMR spectroscopic data on simple alkyl cations show this to be so. In methylcycohexyl cations there are two chair conformations where the carbon bearing the positive charge is planar (9 and 10), and there is evidence that difference is hyperconjugation make 10 more stable. Other evidence is that carbocations are difficult to form at bridgehead atoms in [2.2.1] systems, where they cannot be planar (see p. 397). ° Bridgehead carbocations are known, however, as in [2.1.1]... 

Certain nucleophilic substitution reactions that normally involve carbocations can take place at norbomyl bridgeheads (though it is not certain that carbocations are actually involved in all cases) if the leaving group used is of the type that cannot function as a nucleophile (and thus come back) once it has gone, for example. 

The SnI reactions do not proceed at bridgehead carbons in [2.2.1] bicyclic systems (p. 397) because planar carbocations cannot form at these carbons. However, carbanions not stabilized by resonance are probably not planar SeI reactions should readily occur with this type of substrate. This is the case. Indeed, the question of carbanion stracture is intimately tied into the problem of the stereochemistry of the SeI reaction. If a carbanion is planar, racemization should occur. If it is pyramidal and can hold its structure, the result should be retention of configuration. On the other hand, even a pyramidal carbanion will give racemization if it cannot hold its structure, that is, if there is pyramidal inversion as with amines (p. 129). Unfortunately, the only carbanions that can be studied easily are those stabilized by resonance, which makes them planar, as expected (p. 233). For simple alkyl carbanions, the main approach to determining structure has been to study the stereochemistry of SeI reactions rather than the other way around. What is found is almost always racemization. Whether this is caused by planar carbanions or by oscillating pyramidal carbanions is not known. In either case, racemization occurs whenever a carbanion is completely free or is symmetrically solvated. 

In 2003, Williams and Mander reported a method designed to access the hetisine alkaloids (Scheme 1.3) [27]. This approach, based upon a previously disclosed strategy by Shimizu et al. [28], relied on arylation of a bridgehead carbon via a carbocation intermediate in the key step. Beginning with (1-keto ester 46, double Mannich reaction provided piperidine 47. Following a straightforward sequence, piperidine 47 was transformed to the pivotal bromide intermediate 48. In the key step, bromide 48 was treated with silver (I) 2,4,6-trinitrobenzenesulfonate in nitro-methane (optimized conditions) to provide 49 as the most advanced intermediate of the study, in 54 % yield. 

C. The smaller retarding effect of the thioxo group when introduced into the more flexible system supports the applicability of the authors methodology to change the conjugative ability of bridgehead carbocations. 

Further evidence for the SnI mechanism is that reactions run under SnI conditions fail or proceed very slowly at the bridgehead positions10 of [2.2.1] (norbornyl) systems25 (e.g. 1-chloroapocamphane, 8). If SnI reactions require carbocations and if carbocations must... 

For a review of organic synthesis using bridgehead carbocations, sec Kraus Hon Thomas Laramay Liras Hanson Chem. Rev. 1999, 89, 1591-1598. 

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