2
084
S. K. Chattopadhyay et al.
LETTER
for various reasons. Furanylglycine derivatives have also
1
5
n
ii
n
n
i
been prepared through a creative application of enzym-
atic resolution. Althouh separate aromatization of the di-
hydrofuran derivatives 7–12 at any stage would lead to the
corresponding aromatic compounds, a one-pot ring-clos-
ing metathesis and aromatization protocol was developed
O
O
N
O
O
N
OH
N
O
Boc
Boc
Boc
1
2
6, n = 1
2, n = 2
17, n = 1
23, n = 2
18, n = 1
24, n = 2
1
6
following our related work. Thus, treatment of the mix-
ture of the epimeric ethers 4 and 5 with Grubbs’ catalyst 6
and then with DDQ in a one-pot manner directly provided
the furanylglycine derivative 13 in 56% yield (Scheme 2).
Deprotection of the oxazolidine unit in the latter neatly
provided the amino alcohol 14, which on oxidation pro-
vided the protected furanylglycine derivative 15.
n
HOH2C
iii
iv
n
v
O
O
O
N
NHBoc
Boc
1
9, n = 1
25, n = 2
20, n = 1
26, n = 2
HO2C
n
O
NHBoc
2
2
1, n = 1
7, n = 2
O
O
Scheme 3 Reagents and conditions: (i) vinylmagnesium bromide,
–78 °C to –20 °C, 1.5 h, 17, 78%; 23, 92%; (ii) allyl bromide, t-
BuOK, DMF, 0 °C to r.t., 18 h, 18, 52%; 24, 57%; (iii) Grubbs’ cata-
lyst 6 (5 mol%), CH Cl , r.t., 4 h, then DDQ, benzene, reflux, 16 h,
R
i
ii
O
4
+ 5
N
NHBoc
Boc
2
2
13
14, R = CH2OH
1
iii
19, 54%; 25, 57%; (iv) MeOH–HCl (5%), 0 °C, 0.5 h, 20, 82%; 26,
8%; (v) H CrO , Et O–H O, r.t., 2 h, 21, 46%; 27, 49%
5, R = CO2H
7
2
4
2
2
Scheme 2 Reagents and conditions: (i) Grubbs’ catalyst 6 (5
mol%), CH Cl , r.t., 4 h, then DDQ, benzene, reflux, 16 h, 56% over
2
2
two steps (ii) MeOH–HCl (5%), 0 °C, 0.5 h, 82%; (iii) H CrO , Et O–
2
4
2
H O, r.t., 2 h, 49%
Acknowledgment
2
Financial assistance from DST, Govt. of India (Grant No. SR/S1/
The aspartic acid derived chiral aldehyde 16 (Scheme 3), OC-24) is gratefully acknowledged. One of us (KS) is thankful to
prepared following the established methodology,17 on University of Kalyani for a fellowship.
treatment with vinylmagnesium bromide furnished a mix-
ture (ca. 1:1) of the epimeric allylic alcohols 17 which
were not separated. The lack of stereocontrol in the vinyl-
References
(
1) (a) Williams, R. M. Synthesis of Optically Active a-Amino
Acids, Vol. 7; Baldwin, J. E.; Magnus, P. D., Eds.; Organic
Chemistry Series, Pergamon Press: Oxford, 1989.
ation is not important as subsequent aromatization re-
moves the stereocenter. This mixture was then alkylated
with allyl bromide to provide the corresponding ethers 18
which when subjected to the developed one-pot RCM–
aromatization sequence provided the protected furanyl-
alanine derivative 19, [a] +6.5 (c 0.75, CH Cl ). Depro-
(
3
b) Barrett, G. C. Amino Acids, Peptides and Proteins, Vol.
2; The Chemical Society: London, 2001.
(
2) (a) Cativiela, C.; Diaz-de-Villegas, M. D. Tetrahedron:
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D
2
2
tection of the latter to the aminoalcohol 20 followed by its
oxidation led to the N-Boc-furanylalanine 21.
4197. (c) Desrosiers, J.-N.; Cote, A.; Charette, A. B.
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Similarly, the glutamic acid derived aldehyde 22, pre-
pared analogously, when subjected to the same sequence
of reactions viz. vinylation to the epimeric allyl alcohols
(
(
4) (a) Jackson, R. F. W.; Wishart, N.; Wood, A.; James, K.;
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2
3, etherification of the latter to the mixture of the epi-
meric allyl ethers 24, one-pot ring-closing metathesis–
aromatization to the furan derivative 25 followed by its
sequential deprotection (leading to 26) and oxidation led
to the N-protected homo-furanylalanine 27 in an overall
3
401. (c) Harwood, L. M.; Manage, A. C.; Robin, S.; Hoes,
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(
1
8
yield of 10.7% over five steps.
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Tetrahedron Symposium-in-Print, Number 33 1988, 44,
In short, we have demonstrated that optically pure di-
hydrofuranylglycine, furanylglycine, furanylalanine and
homo-furanylalanine derivatives could be conveniently
prepared from enantiomerically pure aldehydes derived
from serine, aspartic acid and glutamic acid using a novel
one-pot RCM–aromatization reaction as the key step. The
prepared compounds may find application in chemistry
and biology.
5253–5605.
(
(
5) Garner, P.; Park, J. M. Org. Synth. 1992, 70, 18.
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(7) (a) Strekowski, L.; Wydra, R. L.; Cegla, M. T.; Czarny, A.;
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Synlett 2005, No. 13, 2083–2085 © Thieme Stuttgart · New York