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

Chapter 2 – Dearomatising additions to aryl oxazolines
Addition to para-cyano 210g resulted in complete consumption of starting material,
with no products isolated. Nitriles are very susceptible to nucleophilic attack, and
lithiation of cyanobenzenes usually requires non-nucleophilic bases such as LDA. 73
The lack of reaction with the para-nitro 101h was disappointing since by lowering the
energy of the LUMO it should make the aromatic ring more susceptible to attack. The
complete absence of reaction is also surprising since Köbrich found that aromatic nitro
groups are readily reduced even when competing with the rapid halogen-lithium
exchange, indeed reduction still dominated at –100 °C. 74 The meta isomers of both
these oxazolines would be better predisposed to dearomatising addition by cumulative
electron withdrawal.
Scheme 2.14 – reaction solution of 101i (p-NO 2 )
ortho-Anisole 101i underwent S N Ar (entry i) which was also observed by Baker for the
2,4-dimethoxyoxazoline; 72 nucleophilic aromatic substitution was also observed by
Meyers for similar compounds. 75 Treatment of ortho-alkylated 103b (entry j, Scheme
2.15) led to benzylic lithiation, reaffirming that the organolithium is still highly basic
under the reaction conditions. Analysis of the crude reaction mixture showed small
quantities of another lithiation product, as well as traces of dearomatisation; a
disappointing outcome in light of Yamamoto’s ATPH-promoted dearomatisation of
similar methyl benzenes by organolithiums (section 1.3.3).
Ox*
i) i-PrLi (3 eq)
THF, DMPU (6 eq)
−78 °C
ii) MeI
Ox*
OMe OMe 65%
103b 120
Scheme 2.15 – reaction of ortho-alkylated oxazoline
69