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

1.3 – Nucleophilic dearomatisation
diastereoselectivity, whilst DMPU was also found to be moderately effective.
Although addition was successful for a number of lithium amides, an equal number did
not show any dearomatisation; including diethylamide, diallylamide and allylamide. It
appears that β-substitution in the lithium amide disfavours addition, as does an
adjacent π-system.
O
N
i) NuLi (3 eq)
HMPA (1.4 eq)
−78 to −50 °C
ii) EX
58 59
O
N
E
Nu
>99:1 dr
entry NuLi EX Yield / %
a Me 2 NLi MeI 93 *
b n-BuN(Me)Li MeI 93
c n-C 5 H 11 N(Me)Li MeI 93
d Li-piperidide MeI 95
e Li-piperidide allyl-Br 92
f Li-piperidide BnBr 67
g Li-piperidide CO(OEt) 2 0
h
O
O
NLi
MeI 96
* + 1% 1,6-adduct
40
Table 1.10 – 1,4-addition of lithium amides to 1-naphthyloxazolines
One particularly surprising result was that upon quenching with diethyl carbonate no
dearomatisation was observed. This led the authors to investigate whether the addition
might be reversible, which was confirmed by the sequential addition of lithium
piperidide and n-butyllithium, which gave only butylated product. That any
dearomatising reaction is under thermodynamic control seems remarkable.
34