A Route to Carbasugar Analogues - Jonathan Clayden - The ...

2.4 – Mechanistic discussion
Yamataka developed these approaches to monitor nucleophilic attacks since there is
normally no free radical intermediate to intercept with a tethered probe. Yamataka’s
use of 14 C labelling at the site of attack works on the assumption that the transfer of an
electron will not perturb the hybridisation or geometry, whilst a polar reaction, or a
rate determining RC clearly would. The rational for a small ρ-value for an ET rate
determining step is not so well understood, but is taken to be characteristic since a Pl
anionic processes would clearly be assisted by removing electron density. The data
presented in Table 2.10 indicate that Yamataka and co-workers have found a method
for distinguishing the three rate determining steps; they even seem able to differentiate
a change in RDS of Grignard addition (entries h-k). This change from an ET to a RC
rate determining step is reported to reflect how finely balanced SET reaction is.
In a similar manner, Gajewski measured secondary deuterium KIEs of some of these
additions by “α-deuteration” of benzaldehyde. 105 ortho-Deuteration of oxazolines
would allow α-deuteration studies to be undertaken and would be significantly easier
than 14 C. Surprisingly, the ortho-lithiation of oxazolines 101a and 101b was
unsuccessful, however meta-anisole 101c should be particularly amenable to orthodeuteration
and kinetic study of the resulting d-101c (Scheme 2.32). Whilst
unexpected, Meyers reports that ortho-lithiation can be slow when studying the
deuteration of phenyl oxazolines. 106
Ox*
D
Ox*
Ox*
OMe
d-101c
α-deuteration
KIE
R
150
linear free-energy
relationship
t-Bu
151
radical isomerisation
Scheme 2.32 – possible mechanistic probes
Whilst it may not be strictly valid, a Hammett linear free energy study might provide
some insight, possibly through the study of para-aryl oxazolines 150; since reaction
occurs at the aromatic ring, kinetic data could not be collected for substituents on that
ring since they would have both a direct electronic and steric interaction with the
reacting centres. Fortunately a wealth of Hammett substituent constants are available
86