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

Chapter 1: Introduction
O
i) ATPH, −78 °C
PhMe/THF
then t-BuLi (2 eq)
O
ii) HCl (conc.)
t-Bu
89%
O
Cl
i) ATPH, −78 °C
PhMe
then MeLi (3 eq)
CO 2 H
CO 2 H
69
ii) HCl (conc.)
70
22% 38%
71
Scheme 1.18 – addition to functionalised aromatic systems
Some degree of aromatic functionalisation is tolerated by the reaction, but only methyl
substituents have been studied and have a significant effect of the regioselectivity of
addition (Scheme 1.18). Dearomatising addition of MeLi to dimethylbenzoyl chloride
69, favours 1,4-addition over 1,6-addition (entry l, Table 1.12) and shows poor
regioselectivity in light of the ‘pocket’ found in the crystal structure of the ATPHcomplex
(vide supra). 43 Equally interesting is that no benzylic lithiation is reported for
these reactions; even addition of t-BuLi to 69 only gives 1,6-addition without any
reported lithiation.
The only attempt to induce asymmetry in the reaction is the use of an O-(+)-menthyl
enolate, with gave the dearomatised adduct with 3% d.e. in 77% yield. 45 There has
been no reported use of any chiral analogues of ATPH, this is possibly because
Yamamoto has found the complexes to be quite labile. 43
39