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

1.3 – Nucleophilic dearomatisation
Later studies of amino acid-derived oxazolines, which only have one Lewis basic
centre and would not be able to form the bidentate chelates, gave some interesting
results.
R
O
N
R'
i) NuLi
ii) MeI
R
O
R'
N
E
Nu
i) MeOTf
then NaBH 4
ii) H +
OHC
E
Nu
52
53
Entry Nu R R’ T / °C 53 / % d.r. e.e. / %
a n-Bu Ph CH 2 OMe –78 97 96 : 4 90
b Ph Ph CH 2 OMe –40 86 83 : 17 78
c n-Bu H i-Pr –78 97 97 : 3 90
d Ph H i-Pr –40 87 87 : 13 74
e n-Bu H t-Bu –78 99 99 : 1 98
f Ph H t-Bu –40 81 95 : 5 90
Table 1.8 – non-chelating vs chelating oxazoline substituents 37
The diastereoselectivity of addition to the chelating oxazoline (entries a, b) are
comparable to those of the oxazoline derived from valine (entries c & d), whilst that of
the oxazoline derived from tert-leucine (entries e & f) is significantly better. Meyers
proposed a new rationale for these monodentate auxiliaries. 37
R
Li
54
Scheme 1.15 – Meyers’ stereochemical rational for “monodentate” oxazolines
In this description, the nitrogen lone pair lies in the plane of the oxazoline and the
bulky C4 substituent favours attack from the opposite face. Complexation with
nitrogen is consistent with the complex-induced proximity effect (CIPE) of Meyers
and Beak, 38 although Meyers does not seem to acknowledge this. This simple
explanation could be applied for Meyers’ earlier chiral auxiliary, but until recently
monodentate and bidentate oxazolines were described as having different mechanisms.
O
N
32