Deuterium scrambling

Two serious drawbacks of this method are the extensive deuterium scrambling around the reaction site and the occasional formation of olefinic side products, which are hard to separate by conventional means. The extent of olefin formation may depend on the nature of the Raney nickel since it is known that desulfurization with deactivated Raney nickel can yield olefins. Best results are obtained when the deuterated Raney nickel is prepared very rapidly and used immediately after preparation. 

Three different methods have been discussed previously (sections III-C,III-D and IV-A) for the replacement of a carbonyl oxygen by two deuteriums. However, in the conversion of a 3-keto steroid into the corresponding 3,3-d2 labeled analog, two of the three methods, electrochemical reduction (section ni-C) and Raney nickel desulfurization of mercaptal derivatives (section IV-A), lead to extensive deuterium scrambling and the third method, Clemmensen reduction (section III-D), yields a 2,2,3,3,4,4-dg derivative. 

An N-benzyl-N-methyl carbonate in EtOH was hydrogenated on 10% Pd/C under 60 psi hydrogen for 20 hours. NMR analysis indicated that no deuterium scrambling had occurred during debenzylation (Scheme 4.81).328... 

Typical examples of circumambulatory rearrangements of bicyclo[3.1. Ojhexenyl cations are shown in Schemes 19 and 20. Swatton and Hart reported the isomerization shown in Scheme 19 in 1967 and proposed that the observed deuterium scrambling could be accounted for on the basis of a cyclopropyl walk reaction153. This circumambulation is comparable to that proposed by Zimmerman and Schuster as part of the sequence of reactions involved in the type A photorearrangement of 2,5-cyclohexadienones. ... 

This result coupled with the observation of small amounts of free butadiene in the reaction mixture supports a mechanism involving dehydrocyanation of 2M3BN back to butadiene and HCN [Eq. (22)], though decomplexation of butadiene is not required. An alternative mechanism, involving allylic CN transfer [Eq. (23)], may play a role in the isomerization, but cannot by itself account for the deuterium scrambling. 

It is also apparently possible, despite what would seem to be considerable steric difficulty, for a [1,3]-reaction to be antarafacial on the n component. Measurements of rates of racemization and of deuterium scrambling show that at least part of the rearrangement in Equation 12.78 proceeds by the path illustrated in Equation 12.79.130... 

Fig. 7. Mechanism for deuterium scrambling in reaction of PhMeSiD2 with Cp2ZrCl2/2 1BuLi.50...

The isomeric structures ii and iii do not correspond to minimum structures of the C6 Lj potential energy surface, but are critical points of first and second rank, respectively. The transition structure, represented by ii, corresponds to a 1,2-proton shift, 35 kj mol-1 higher in energy than 1, and it provides a mechanism for the fast proton/deuterium scrambling observed in the gas phase and in acidic solution. Structure iii would correspond to a 71 complex between a proton and benzene. On the basis of the quantum chemical calculations it is clear that this is not a stable structure, and it is 199 kj mol-1 above 1. 

The differences in the gas-phase chemistry of the Cp complexes 5-8 and the Cp analogs 9-12 are confined to two areas. While the Cp-substituted complexes added to pentane, cyclohexane, or benzene, the Cp -substituted analogs reacted with pentane or benzene only. No cyclohexane adducts were observed in the gas-phase reactions of [Cp Ir(PMe3)(CH3)]+ or [Cp Ir(j]2-CH2PMe2)]+. Second, in the CID of the two phenyl-substituted complexes 8 and 12 (R=Ph), there was complete deuterium scrambling in 12, but only partial scrambling in 8. 

It is possible to detect thermally induced circumambulations in certain substituted homotropenylium ions. Hehre in his theoretical study (HF/STO-3G) of 11 suggested that the placement of methyl substituent at C(8) of the homotropenylium ions should reduce the barrier to the thermally induced circumambulation" . The correctness of this prediction was confirmed by Childs and Varadarajan who reported the generation of the deuterium labelled cation 67 and the measurement of the rate of deuterium scrambling associated with circumambulation of C(8) around the seven-membered ring (Scheme 24) 58 barrier for this circumambulation was found to be 14.5 kcalmoT. Scott and Brunsvold have also reported the occurrence of a circumambulation in a bridged homotropylium ion, 68 (Scheme 25). ... 

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