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

Chapter 3 – Oxazoline synthesis & removal
3.1.1.c Activated carbonyl
Whilst the amide methods form the C–O bond of the oxazoline with inversion,
condensation of the amino alcohol with an activated carbonyl proceeds with retention
at the C5 stereocentre. These methods would therefore allow the same amine to be
used to make epimeric oxazolines.
O
NH 2
i) (Et 3 O)BF 4 , CH 2 Cl 2
Ph
O
N
OMe
R
ii)
Ph
HO
OMe
NH 2 Δ
38
R
83-94%
3 examples
Scheme 3.7 – oxazolines from primary amides 32
Although Meyers published a number of ways to make oxazolines, his preferred
method for making chiral oxazolines 38 was via an imidate formed in situ before
addition of the desired amino alcohol. 32 This method has been used for a wide range
of naphthalenes, and since it is a retentive reaction, the stereochemistry and optical
purity of the product depends on the amino alcohol used.
MeO
OMe
OMe
Ph
173
R
HO
R'
NH 2
TFA, DCE
Δ 4 hr
R
O
Ph
N
R
88-97%
3 examples
124
Scheme 3.8 – oxazolines from ortho esters
An analogous method published more recently by Meyers uses aryl ortho esters 173 to
give a small selection of aryl oxazolines in good yield. 124
Since ortho esters can be
made by methanolysis of nitriles, this would offer another route to their synthesis. The
zinc chloride catalysed condensation of aromatic nitriles with amino alcohols under
reflux has also been used to synthesise 2-aryl oxazolines, but has only been used to
make a small range of compounds. 125
99