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Scheme 3.25 Amide bond rotamers of 145a.
NH
O
MeO2C Bn
•
145a
trans-amide
favored
H
HN
MeO 2C
O O
Bn
•
145a
cis-amide
disfavored
H
Rh(I), 90 o C
HN
MeO 2C
Bn
To confirm this, allenyne 145e with benzamide protection on the amide nitrogen was synthesized
in 69% yield by treatment of 145a with BzCl at 70 °C (Scheme 3.26). Indeed, reaction of this
precursor using 10 mol% of [Rh(CO)2Cl]2 occurred in less than 1h at rt, affording cross-
conjugated triene 146e in 75% yield.
Scheme 3.26 Preparation and cycloisomerization of 145e.
O O
HN
MeO2C •
Bn
H
BzCl, Et3N, DMAP
molecular sieves
DCE, 70
MeO2C N
Bn
o O
Ph
145a
C, 1h
69%
Ph
N
O
MeO2C •
Bn
145e
10 mol% [Rh(CO) 2Cl] 2
toluene (0.03M), rt, 1h
H 75%
O
146e
With a synthetic route to lactam triene 146a, a facially differentiated precursor for the
Diels-Alder reaction was next prepared. Saponification of the methyl ester occurred within 5 min
upon treatment of 146a with LiOH. After aqueous work-up, the acid was obtained in sufficient
purity (by 1 H NMR) and was immediately coupled with glycine-methyl ester using EDCI, HOBt
and DMAP to give diamide 154a (Scheme 3.27). In order to complete the synthesis of hydantoin
147a, amide 154a was reacted with phosgene (COCl2). Interestingly, the exclusive product of the
reaction was the unexpected imino-oxazolidinone 155a in 55% yield for three steps (this
structural assignment was made later based on an X-ray crystal structure of the Diels-Alder
product 156a, vide infra). Nevertheless, imino-oxazolidinone 155a should provide the same
steric and electronic control elements as hydantoin 147a. An additional substrate functionalized
54
146a