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

Chapter 3 – Oxazoline synthesis & removal
Ph
O
N
c-Hex
Ph
H 2 / cat.
O
H
N
c-Hex
Ph
Ph
c-Hex
101m 204
205
Entry Catalyst H 2 pressure / T Solvent 204:205*
a Pd/C 50 bar / 50 ºC MeOH 100:0
b Pd/C 50 bar / 50 ºC MeOH:AcOH (9:1) 100:0
c Pd/C 50 bar / 30 ºC EtOAc 100:0
d Ru/Al 2 O 3 50 bar / rt MeOH 100:0
e RaNi 50 bar / rt MeOH 100:0
f Pd(OH) 2 /C 50 bar / 50 ºC MeOH:AcOH (9:1) 98:2
g
H-Cube
Pd(OH) 2 /C 80 bar / 50 ºC AcOH 94:6
h Pd(OH) 2 /C 80 bar / rt AcOH 66:22
i Pd(OH) 2 /C 70 bar / rt EtOAc 85:15
j Pd(OH) 2 /C 80 bar / rt TFA, MeOH/H 2 O 80:20
k
Bomb **
Pd(OH) 2 /C 70 bar / rt TFA, MeOH (pre-stir) 80:20
* Crude 1H NMR ratio ** overnight reactions, c. 14 hr
Table 3.7 – hydrogenation of oxazoline
Unfortunately none of the desired primary amide 203 was formed, only secondary
amides 204 and 205. Aprotic solvent was used in an attempt to minimise tautomerism
of 202 hoping that the aza-allylic intermediate might hydrogenolyse (entries c, i),
however this is unlikely to have worked since the palladium contains up to 50% water.
Bound water is also thought to be responsible for the formation of hydroxyamide 205
(entries f-k), whose stereochemistry is assigned by comparison with a known sample
(vide infra). TFA was added (entries j, k) in an attempt to form the trifluoroacetate salt
of either the oxazoline or ester, again without success.
+
O
H
N
Ph
OH
Ph
115