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

2.1 – A new reaction
anticipated that changing to a cis geometry would only affect the diastereoselectivity
of the addition, as found by Meyers (section 1.3.2.c).
The norephedrine-derived oxazoline 110 (entry f) proved better at promoting the
dearomatising addition than Meyers’ oxazoline (104) had, however it was also
accompanied by benzylic lithiation (114).
Ph
Me
Ph
Me
Ph
Me
Ph
Me
Me
O
N
i) i-PrLi (1.5 eq), DMPU (6 eq)
−78 °C, 30 min
ii) MeI
O
N
Me
+
O
N
Me
+
O
N
Me
40% 12% 5%
110 112 113 114
Scheme 2.4 – dearomatising addition to norephedrine-derived oxazoline
Valine-derived oxazolines had been synthetically useful in many asymmetric reactions,
most notably for additions to naphthyloxazolines 37 and (η 6 -arene)Cr(CO) 3 species. 53
However, valine-derived oxazolines 111 (entries g, h) showed no significant reaction
with the organolithium, and a translucent reaction solution was seen as opposed to the
opaque solutions which had become characteristic of a successful reaction.
The high levels of diastereoselectivity, and the potential for use in asymmetric
synthesis was shown by removing the oxazoline moiety, and derivative 115 was shown
to be enantiomerically pure by HPLC analysis. Oxazoline removal is described in
section 3.2.
Ph Ph
(p-BrBz)O
O N
Section 3.2.6
OMe
101b 115
O(p-BrBz)
Scheme 2.5 – determination of enantiomeric purity
58%, 5 steps
>99:1 er
54