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

1.3 – Nucleophilic dearomatisation
1.3.1.d Bulky esters
When studying S N Ar reactions of aromatic esters, Miyano found that BHA benzoate
25 underwent conjugative addition to the aromatic ring for a range of organolithiums
and Grignard reagents.
OMe
i) RM, THF
OMe
OMe
R
COBHA −78 °C
COBHA
COBHA
ii) NH 4 Cl
+ +
iii) DDQ
R R
25 26 27 28
entry RM 26 / % 27 / % 28 / %
a t-BuMgBr * 74 – –
b BnMgBr * 76 – –
c BnLi 71 – –
d n-BuLi – – 70
e n-BuLi ‡ 6 29 42
f i-PrLi 14 57 –
g t-BuLi 33 – 50
h t-BuLi ‡ 45 – 16
i allyl-Li 73 – –
j Me 3 SiLi ‡ 85 – –
k PhLi – – 85
l n-BuMgBr * – – 93
m i-PrMgBr * – – 92
* reactions in diethyl ether at rt ‡ THF-HMPA solvent (4:1)
19
Table 1.3 – dearomatisation-oxidation of aryl esters
COBHA
Whilst exclusive substitution (S N Ar) of the methoxy group was observed in a number
of instances (entries k-m) the bulky ester both resists direct addition and promotes 1,4-
and occasionally 1,6-addition to the unsaturated system. The dearomatised compounds
could not be isolated since they were unstable to chromatography, and were instead
oxidised and characterised as rearomatised adducts 26 and 27. It seems that the
reaction is sensitive to both the nature of the organometallic and the reaction
24