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as an isobutyl-amide 155b was prepared using the same protocol in 41% yield over three steps.
To our knowledge, oxazolidinones with this substitution pattern have not been reported. 103
Scheme 3.27 Synthesis of novel imino-oxazolidinone trienes 155a and 155b.
HN
MeO2C Bn
O
146a
1. LiOH, THF/H 2O, rt.
2. RCH 2NH 2, EDCI, DMAP
HOBt, CH 2Cl 2, rt.
R
O
HN
H
N
Bn
O
154a, R = -CO 2Me
154b, R = i-Pr
phosgene, Et 3N
CH 2Cl 2, -10 o C.
O
O
N
O
N
Bn
R
155a, R = -CO2Me 55% yield (3 steps)
155b, R = i-Pr
41% yield (3 steps)
MeO 2C
O
N
O
N
Bn
O
147a or 147b
not observed
It was rationalized that the imino-oxazolidinone 155a resulting from O-acylation of the
appending amide is a kinetic product of the reaction, and a consequence of the preferred
conformation of the amide side chain in 154a. To confirm this, computational modeling of 154a
was performed using Cache. The energy minimized model placed the appending amide oxygen
O2 and lactam nitrogen N1 of 154a in the same direction, confirming the observed reactivity
(Figure 3.1). f Finally, it should be noted that the newly obtained imino-oxazolidinone ring in
155a and 155b proved relatively sensitive to silica gel, since prolonged chromatographing led to
opening to the parent diamides 154a and 154b, respectively.
f Energy minimization was performed with Cache Worksystem Pro. version 6.1.10. First, global minimum search
was performed using MM3 parameters, followed by optimization of the side chain conformation with AM1
parameters. Then, energy minimization of the sample was performed using AM1 parameters.
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