Deuterium bridgehead

An unusual isomerization of perhydro[2.2]paracyclophane 29, an out-in hydrogen transfer process, was observed in triflic acid123 [Eq. (5.53)]. Reaction in CF3SO3D resulted in the incorporation of up to five deuteriums without specific locations. The authors suggested the backside attack of the inside hydrogen (Hj) to the bridgehead... 

Deuterium atom was neatly incorporated at the bridgehead position C-l in ketone 464, the only compound in which the cyclohexane ring is locked in a boat conformation. Examination of molecular models indicates that the cyclohexanone ring can easily adopt a boat form in 460 and 461. It appears to be more difficult with ketone 462 and almost impossible with ketone 463. 

The precise mechanism of these intermolecular reactions is not known. Transient disproportionation processes, although well documented in less acidic media (see below and Section V.A.l), seem unlikely if alkyl cations alone are involved. Two possible explanations for the observed results may be considered. Small amounts of polymeric impurities may be present in the reaction mixture which could serve as a hydride source, catalyzing the intermolecular reaction as indicated in Eq. (16)4°). Alternatively, the intermolecular reactions may result from inefficient mixing during reaction initiation. In this case, unionized alcohols would serve as the hydride source. This latter alternative is consistent with the observation 4°1 that the deuterium in the 1-adamantanol obtained from the rearrangement of 38 is distributed between bridgehead and methylene positions. Unless more than one re-... 

The isomeric homoadamantene, 53 (R=H), should also be isolable, since it is also a tra s-cycloheptene analogue. An attempt to observe bridgehead deuterium incorporation via the corresponding enol (53, R=0 ) during the treatment of 4-homoadamantanone with KOfBu in DO/Bu was not successful, however 103 One must suspect that the conditions were not sufficiently vigorous. 

For strained bicyclic molecules such as bicyclo[2.1.0]pentane calculations suggest a strong preference for protonation at a bridgehead carbonThis prediction seems to be consistent with experimental results in which bicyclo[2.1.0]pentane-endo-5-d is solvolyzed in acetic acid containing p-toluenesulfonic acid to give cyclopentyl acetates and tosylates (as well as some cyclopentene) in which distribution of the deuterium among all possible sites could be quantified. Isotope effects and label distributions were found to be consistent with the initial formation of a C(l)-protonated bicyclo[2.1.0]pentane. 

Most other systems studied have bridgehead halogens, and special attention has been paid to the reactions of the kind shown in Scheme 35. The yields of rearrangement products are uniformly good, and deuterium incorporation results imply that the semibenzilic mechanism operates for the smaller ring... 

On rhodium the intermediate seems to be preferentially cis adsorbed, and on palladium it may be largely trans adsorbed. The amount of exchange is slightly more in the ois-adsorbed state because the bridgehead hydrogen is toward the catalyst. Thus, the deuterium content was higher in the cis-decalin than in the frons-deoalin. Presumably, the isomerized octalin is formed only from the cis-adsorbed state in competition with formation of cia-decalin. 

This explanation is supported by the behaviour of ck-435 and trans-bicyclo-[3,2,0]heptadienols 436 in fluorosulphonic acid. In this case the signal intensity ratio of the protons of bonded and unbonded olefine fragments, and of the bridgehead and bridge protons of the forming 7-norbomadienyl ion is 2 1.5 1.5 1.0, i.e. in 50% of the cases deuterium is in the bridge-head and in the other 50% — in die unbonded olefine fragment. 

Further evidence for the pathways described above comes from labeling studies in which deuterium replaced both hydrogens at the bicyclobutane bridgehead positions, leading to the cyclic dienes with deuteriums at carbons 2 and 3 " This study also included an unsaturated derivative of the tricyclo heptane above as well as measurements of activation parameters for all of the bridged bicyclobutane systems known at that point of time. 

The ring opening reaction is accompanied by an extraordinarily large deuterium kinetic isotope effect at the bridgehead positions. With l,2,4-trideuterio-5,5-dimethylbicyclo[2.1.0]pentene, is 1.85 at 24.6°C. Since the 2-deuterio... 

When the elimination was conducted at — 35°C in the additional presence of tetramethylenediamine and diphenylisobenzofuran, an adduct of 1-dimethylamino-bicyclo[2.2.0]hexa-2,5-diene derived by addition of the deuterated solvent to the butalene was formed. In this reaction all the deuterium was found at the bridgehead position at the level of NMR detection (Scheme 7.3). 

However, this pathway would not give deuterium on the bridgehead position of C9,10. 

Deuterium labeling at the carbons adjacent to the bridgehead carbons revealed that the reaction was formally a concerted 1,3-shift and did not involve a label scrambling biradical. 

There have also appeared very recently the studies of Kokke and Oosterhoff (78,22) These authors have prepared (lR)-[2- 0]-Q -fenchocamphoronequlnone and (ir)-[1-D]-o-fenchocamphoronequlnone. In these molecules thes sole source of asymmetry was either an in the a-diketone function, or a single deuterium atom at a bridgehead. The circular dichroism spectra of these two compounds in the visible are remarkably different. 

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