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

Chapter 1: Introduction
chiral oxazolines, 25 initial development focused on racemic 1-naphthyloxazoline 34. 26
No mention of the dearomatisation of naphthyloxazolines by Grignard reagents has
been found.
O
N
NuLi
O
NLi
Nu
MeI
O
N
Me
Nu
34 35 trans-36
entry NuLi T / °C Yield / % trans : cis-36
a MeLi –20 65 >99 : 1
b n-BuLi –45 90 >99 : 1
c s-BuLi –45 94 >99 : 1
d t-BuLi –45 99 >99 : 1
e Li –80
95 >99 : 1
f allyl-Li –80 85 >62 : 38
g PhCH 2 Li –80 91 >99 : 1
h Ph-C≡CCH 2 Li –40 90 70 : 30
i
THPO Li –40 74 84 : 16
j NC-CH 2 Li –80 to –10 0 –
k n-Pr-C≡CLi –80 to –10 0 –
l 27
Li
OEt
–10 66 * –
* including 16% ketone
26
Table 1.5 – addition of nucleophiles to 1-naphthyloxazolines
The addition proceeds with high trans selectivity, induced by attack on the less
hindered face of azaenolate 35. Protonation of the azaenolate with weak acids such as
alcohols favoured the products of apparent syn addition, believed to be due to
epimerisation to the more stable trans adduct (vide infra). Initial studies showed that
the addition of HMPA as deaggregating agent made no difference to selectivity or
yields, whilst freshly prepared organolithium gave improved conversion of starting
material. 28
27