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

1.3 – Nucleophilic dearomatisation
1.3.1 Favourable electron withdrawing groups
1.3.1.a Nitro group
Perhaps one of the most widely explored electron withdrawing groups in aromatic
chemistry is the relatively inert and strongly π-withdrawing nitro group. In light of the
significant body of work performed with respect to Meisenheimer complexes, it is
perhaps surprising that the dearomatisation of nitrobenzenes has only been generally
achieved by borohydride species, which is beyond the scope of this discussion. 1
However, Bartoli and co-workers were able to achieve the dearomatisation of
dinitrobenzene by Grignard reagents.
O 2 N
17
NO 2
i) RMgX (2 eq)
THF, −70 °C 10 min
ii) NaOCl
O 2 N
R
18
NO 2
R
+ 17
entry R 18 / % 17 / %
a Me 56 31
b Et 30 37
c Me 3 SiCH 2 18 50
d Bn 20 53
e PhCH 2 CH 2 34 38
f CH 2 =CH(CH 2 ) 2 36 37
13
Table 1.1 – dearomatisation of dinitrobenzene
Dearomatisation of dinitrobenzene with Grignard reagents (Table 1.1) suffers from
competing reduction of the nitro group, which upon an oxidative workup returns
starting material 17. It was possible to minimise reduction by performing the reaction
at low temperature. Interestingly, only trace amounts of the mono-alkylated adduct
were obtained when using a single equivalent of the organometallic, presumably
because the intermediate nitroalkene is significantly more electrophilic than the
nitroarene.
It is proposed that the decrease in dearomatisation with increasing bulk (entries a-c) is
indicative of a single electron transfer (SET) mechanism since a bulky radical would
20