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

3.1 – Oxazoline synthesis
Ph
Ph
Ph
Ph
O
OH
OH
HN
Ph
173
Ph
EDC.HCl
SiO 2 , CH 2 Cl 2
rt, 30 hr
O
N
101k
AllylBr, K 2 CO 3
DMF, NaI
OH
57%
(80% conv.)
O
N
101j
O
38%
3.1.4.c Method C: benzyl imidate
Scheme 3.13 – synthesis of O-allyl oxazoline
O NH 2
i) (Et 3 O)BF 4 (1.1 eq)
CH 2 Cl 2 , rt 16 hr
ii)
1.2 eq
R 1
R 1
O
N
R 2
R
HO
Δ
16 hr
R 2
NH 2
R
Entry R R 1 (R/S) R 2 (R/S) Yield / % Compound
a 4-OMe Ph (S) OMe (S) 72 104b
b H H i-Pr (S) 82 111a
c 4-OMe H i-Pr (S) 58 111b
d H Ph (S) Ph (R) 70 109a
e 4-OMe Ph (S) Ph (R) 66 109b
f H Ph (RS) Ph (RS) 85 ±101a
g 4-OMe Ph (RS) Ph (RS) 86 ±101b
h 3-F Ph (RS) Ph (RS) 82 ±101d
i 4-NO 2 Ph (RS) Ph (RS) 55 ±101h
j c-Hex Ph (RS) Ph (RS) 93 ±101m
Table 3.5 – synthesis of oxazolines via imidate (Route C)
Although relatively slow, the one-pot imidate method favoured by Meyers proved to
be the most reproducible and highest yielding method used. Whilst an excess of the
amino alcohol is used, the previous amide condensations used a similar excess.
Unfortunately oxazolines 101 can only be made racemically since it had not been
possible to attain optically pure amino alcohol 175; however this would be possible if
the oxazoline could be cleaved to return the optically pure amino alcohol. Recently,
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