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Scheme 2.3 Claisen rearrangement via an oxazole.
BzHN
R 2
R 1
51
O
O
R 2
R
N
O
O
1
P2O5 or COCl2 [3,3]
Ph
R 2
R 1
N O
Ph
52 53
Interest in preparing allenic amino acid derivatives was spurred by their potential to act as
specific inhibitors of vitamin B6-linked decarboxylases. 59 Krantz and Castelhano reported that a
combination of PPh3, CCl4 and Et3N provides a milder and robust protocol for effecting the same
transformation of propargyl esters (45 to 47, Scheme 2.2). 56 It was established, however, that the
benzamide protecting group is essential for reaction to proceed, which is attributed to a
stabilizing effect of the phenyl group on the oxazole intermediate. The use of other protecting
groups including trifluoroacetamide, Boc and Cbz groups was unsuccessful.
Using this protocol, the phenylalanine-derived allene 58a was prepared as outlined in
Scheme 2.4. Esterification of N-benzoyl phenylalanine 54a with 3-butyne-2-ol by using DCC
and DMAP gave ester 56a in 78% yield. The reaction proceeds via the intermediacy of
oxazolone 55a which is then subject to nucleophilic attack by the alcohol. Treatment of ester 56a
with CCl4, PPh3 and Et3N in acetonitrile affords the 4-allenyl-2-oxazolin-5-one 57a, which is
treated with MeOH/HCl to give allene 58a in 74% yield as a 1.7 : 1 mixture of diastereomers (as
previously reported by Krantz). 56
Scheme 2.4 Synthesis of phenylalanine-derived allene 58a.
BzHN
Bn
O
OH
OH
DCC, DMAP
CH 2Cl 2, rt, 78%
Bn
N
Ph
O
O
BzHN
Bn
O
O
PPh 3, CCl 4, Et 3N
Bn
N O
Ph
•
O
O
H
MeOH, HCl, rt
74% (2 steps)
MeO 2C
54a 55a
56a 57a 58a
18
MeCN
•
H
Bn
NHBz