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

Chapter 3 – Oxazoline synthesis & removal
Since neither the aza-allylic nor amide N-benzyl bonds were apparently susceptible to
hydrogenolysis, it was hoped that this bond in the corresponding secondary amine
would be. This could be made by reduction of the amide or by treating oxazolines
directly with DIBAlH (section 3.2.1.c).
3.2.3.b DIBAlH reduction
Ph
O
N
Ph
DIBAlH
solvent,
0 °C
H
N
Ph
OH
Ph
101m 210 205
O
H
N
Ph
OH
Ph
solvent 210/% 205/%
THF (wet) 40 20
THF 60 20
Toluene 80 10
Table 3.8 – DIBAlH reduction of oxazolines
Whilst the procedure 137 did not specify whether wet or dry solvent should be used the
reduction worked well on test substrate 101m using dry THF. The structure of amine
210 was confirmed by synthesis from benzaldehyde and amino alcohol 175.
Catalyst bar / ° C solvent
Pd/C 80 / 50
AcOH in MeOH
(10% to 100%)
Pd(OH) 2 /C 70 / rt AcOH
H
N
Ph
OH
Ph
H 2
Conditions
nr
Pd(OH) 2 /C 70 / rt TFA/MeOH
210
Table 3.9 – hydrogenolysis of secondary amine 210
The benzylic C–N bond of amine 210 was resistant to hydrogenolysis under a similar
range of conditions as the parent compound. Whilst hydrogenation was only
conducted under acid conditions, it is not thought this jeopardised the reaction since
similar N-debenzylations have been conducted in TFA-MeOH. 140 Recently Li has
shown that an equimolar mixture of Pd and Pd(OH) 2 catalysts on carbon can be more
active than either individual catalyst, 141 but this, nor transfer hydrogenation are thought
likely to prove more productive than the methods already attempted.
117