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

1.3 – Nucleophilic dearomatisation
toluene alone. In particular, degassed solvent was found to be essential, and the use of
aqueous solutions of acid was detrimental to the successful isolation of diene; failure to
observe these measures leads to near quantitative rearomatisation. 42 Regioselectivity
of addition is generally very good, but slightly diminished for acid chlorides, this is
rationalised by comparison of the crystal structures of ATPH-PhCHO and ATPH-
PhCOCl which show one of the ortho-carbons to be exposed in the latter complex.
Interestingly a number of other differences are observed between the acid chloride and
simple carbonyl complexes; the IR carbonyl stretch for ATPH-PhCOCl is 42 cm -1
lower than the free acid chloride, whereas little difference is reported for the ATPH-
PhCHO complex. 43 This is consistent with the crystal data which shows the C=O in
the ATPH-PhCOCl complex to be almost 0.1 Å shorter than the benzaldehyde
complex. Indeed, additions to benzoyl chloride seem to tolerate a larger range of
nucleophiles, including Grignard reagents which do not react with the other systems
studied.
O
i) ATPH, −78 °C
PhMe/THF
then t-BuLi (2 eq)
O
ii) MeOTf
t-Bu
66
68%
d.r. 1:1
O
OMe
i) ATPH, −78 °C
PhMe/THF
then PhMe 2 SiLi (2 eq)
O
OMe
ii) MeOTf
Me 2 PhSi
67
51%
d.r. >95:5
Scheme 1.17 – alkylation of dearomatised ATPH complexes
Whilst the vast majority of the dearomatising additions were γ-protonated with
concentrated acid, methylation with methyl triflate (Scheme 1.17) was highly
regioselective for α-addition. No stereochemical preference was seen for addition of t-
BuLi/MeOTf to acetophenone (66), 42 but addition of the bulky dimethylphenylsilyl
group engendered high diastereoselectivity in the subsequent alkylation, giving silane
67. 44 This is consistent with the observations of 1,6-additions to benzonitriles by
Ortiz, who also found that bulky reagents increased facial selectivity in the distal
addition-alkylation (Scheme 1.7).
38