Lewis acid catalyzed intramolecular allylic substitution of bis(trichloroacetimidates): A versatile approach to racemic unsaturated amino acids

Article abstract of DOI:10.1002/ejoc.201100060

Lewis acid catalyzed cyclization of trichloroacetimidates derived from 1,4-butenediols and 1,5-butenediols was achieved to give 4-vinyl oxazolines and 4-vinyloxazines in good to excellent yields. The cyclization products were transformed to protected unsaturated α- and β-amino acids, thus demonstrating the novel approach to access these important classes of compounds. Lewis acid catalyzed cyclization of allylic bis(trichloroacetimidates) (n = 1, 2) provides 4-vinyloxazolines and 4-vinyloxazines. The products of cyclization weredemonstrated to be versatile intermediates for the synthesis of unsaturated α- and β-amino acids. Copyright

Full text of DOI:10.1002/ejoc.201100060

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201100060
Lewis Acid Catalyzed Intramolecular Allylic Substitution of
Bis(trichloroacetimidates): A Versatile Approach to Racemic Unsaturated
Amino Acids
Liene Grigorjeva[a] and Aigars Jirgensons*[a]
Keywords: Amino acids / Lewis acids / Cyclization / Diols
Lewis acid catalyzed cyclization of trichloroacetimidates de-
rived from 1,4-butenediols and 1,5-butenediols was achieved
to give 4-vinyl oxazolines and 4-vinyloxazines in good to ex-
cellent yields. The cyclization products were transformed to
protected unsaturated α- and β-amino acids, thus demon-
strating the novel approach to access these important classes
of compounds.
acid promoted cyclization of bis(imidates) has not been re-
ported in acyclic systems. Close analogue of such reaction
type in acyclic systems is recently reported FeCl3·6H2O-cat-
alyzed intramolecular O- and N-allylation with allylic
alcohols leading to vinyl-tetrahydropyran and piperidine
derivatives.[12] Cyclization of allylic bis(imidates) 1, 2 could
lead, among several potential products, to 4-vinyloxazolines
3 and 4-vinyloxazines 4 that are precursors of unsaturated
amino acids 5 and 6, respectively (Scheme 1). Thus, the aim
of the investigation presented in this communication was to
study the efficiency of Lewis acid catalyzed cyclization of
acyclic imidates 1 and 2.
Introduction
Oxazolines and oxazines are versatile precursors of
amino alcohols and amino acids that have prompted the
development of methods for their synthesis.[1] The major
focus has been on cyclization reactions of trichloroacetimid-
ates that are relatively stable intermediates, readily avail-
able from the corresponding alcohols and provide unsubsti-
tuted imino group as a nitrogen nucleophile.[2] Commonly
used cyclization reactions of trichloroacetimidates are ring-
opening of epoxides,[1a,1b,3] intramolecular haloamination
of olefins,[1c,1d,4] alkylation[5] and allylic substitution,[6] aza-
Michael reaction.[1d,7a,7b] as well as AuI-promoted hydro-
amination of alkynes.[8] Complementary to these methods,
we recently reported PdII catalyzed cyclization of δ-acetoxy-
allylic and homoallylic trichloroacetimidates leading to 4-
vinyloxazolines and 4-vinyloxazines.[9] These cyclic imidate
derivatives could be transformed to unsaturated α- and β-
amino acids – classes of compounds that are important syn-
thetic intermediates and exhibit biological activity.[10a–10e]
This inspired us to develop alternative methods for the syn-
thesis of 4-vinyloxazolines and 4-vinyloxazines that would
offer the benefits in terms of shorter synthetic route and
eco-friendliness.
Scheme 1. Synthesis of cyclic imidates and unsaturated amino acid
derivatives based on Lewis acid (LA) catalyzed cyclization of bis-
(imidates) 1 and 2.
Results/Discussion
Allylic trichloroacetimidates are well known reagents for
Lewis acid catalyzed allylation of nucleophiles.[11] There are
a few examples known in the literature where one imidate
group in bis(trichloroacetimidates) serve as a leaving group
and the another as N-nucleophile. However, these examples
are limited to BF3 promoted imidate allylic substitution of
cyclic bis(imidates).[6] To the best of our knowledge, Lewis
1,4-Butenediols E,Z-7a–e and 1,5-butenediols E,Z-8a,b
(Scheme 2) were readily available by two step synthesis
starting from the corresponding aldehydes, that were sub-
[a] Latvian Institute of Organic Synthesis,
Aizkraukles 21, Riga 1006, Latvia
Fax: +371-7541408
E-mail: aigars@osi.lv
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100060.
Scheme 2. Synthesis of bis(imidates) 1, 2 and their cyclization to
vinyloxazolines 3 and vinyloxazines 4.
Eur. J. Org. Chem. 2011, 2421–2425
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2421

L. Grigorjeva, A. Jirgensons
SHORT COMMUNICATION
sequently transformed to the corresponding bis(imidates) 1
The exception to the general Scheme 2 were preparation
and 2 in good yields (see Supporting Information). These of imidates E-1d,e, Z-1e and E-2b, Z-2b which turned out
imidates were exposed to catalytic amounts of Lewis acids to be unstable during the conditions of their synthesis and
such as FeCl3, AlCl3, BF3·Et2O and Me3SiOTf that pro- gave considerable amount of cyclization products 3d,e and
moted the cyclization of bis(imidates) E-1a–c, Z-1a–d and 4b. These compounds were isolated in medium yield after
E-2a, Z-2a providing vinyloxazolines 3a–d and vinyloxazine prolonged stirring (Table 1, Entries 27, 32, 33, 42, 43).
4a in good to excellent yields in a very short reaction time.
Noteworthy, in all cases cyclization of imidates 1 and 2
Brønsted acid such as TsOH·H2O also catalyzed the cycliza- led exclusively to vinyloxazolines 3 and oxazines 4 bearing
tion of imidates E-1b and Z-1b (Table 1, Entries 13, 18), E-configuration double bond. In addition, no other poten-
although the reaction time was considerably longer. Work- tial cyclization products were detected. Selective formation
up involved purification by flash chromatography on a of cyclic imidates 3 and 4 could be explained by SN1Ј type
short silica gel column to separate from trichloroacetamide reaction that involves formation of most stable secondary
by-product providing the product in 90–99% purity accord- allylic carbenium ion which is intramolecularly trapped by
ing to GC/MS analysis.
imidate of primary alcohol (Scheme 3). In the case of imid-
ates 1d,e and 2b formation of secondary carbenium ion is
relieved because of additional stabilization by adjacent aryl
group that may account for cyclization to imidates 3d,e and
4b without assistance of Lewis acid. Nevertheless, without
detailed mechanistic studies, one should not to exclude
SN2Ј-type reaction involving complexed imidate as a leaving
group.
Table 1. Catalysts and reaction time for cyclization of imidates 1,
2 and yields of the products 3, 4.
Entry Imidate
R
n
Catalyst
Time
3, 4
% yield
E/Z[a]
1
2
3
4
5
6
7
8
E-1a
Z-1a
E-1b
nPent, E
nPent, Z
iPr, E
1
FeCl3
AlCl3
BF3·Et2O
Me3SiOTf 1 min
FeCl3
AlCl3
BF3·Et2O
Me3SiOTf 1 min
FeCl3
AlCl3
BF3·Et2O
Me3SiOTf 1 min
TsOH·H2O 4.5 h
FeCl3
AlCl3
BF3·Et2O
Me3SiOTf 1 min
TsOH·H2O 16 h
FeCl3
AlCl3
BF3·Et2O
Me3SiOTf 1 min
FeCl3
AlCl3
BF3·Et2O
Me3SiOTf 1 min
none
FeCl3
AlCl3
BF3·Et2O
Me3SiOTf 1 min
none
20 min
15 min
2 min
96
98
94
90
88
96
94
96
98
93
84
93
92
92
94
93
92
90
94
91
91
94
89
94
95
90
58
91
94
90
90
69
68
97
99
93
93
98
95
89
97
55
57
1
1
10 min
10 min
2 min
9
10 min
10 min
2 min
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
Scheme 3. Proposed reaction mechanism for the cyclization of
bis(imidates) 1 and 2.
Oxazolines 3 and oxazines 4 can be readily transformed
to protected α-amino acids and β-amino acids, respectively
(Scheme 4, Table 2). Hydrolysis of cyclic imidates 3a–d and
4a,b followed by N-protection gave unsaturated amino
alcohol derivatives 5a–d and 6a,b.[1e] Oxidation of amino
alcohol derivatives 5a–d, 6a,b[13] provided amino acids that
Z-1b
iPr, Z
1
10 min
10 min
2 min
E-1c
Z-1c
BnOCH2, E
1
1
5 min
12 min
1 min
BnOCH2,
Z
5 min
5 min
1 min
E-1d
Z-1d
Ph, E
Ph, Z
1
1
1.5 h
2 min
2 min
1 min
Scheme 4. The synthesis of protected amino acids 5, 6 from oxazol-
ines 3 and oxazines 4.
E-1e
Z-1e
E-2a
Anthr,[b]
Anthr,[b]
iPr, E
E
Z
1
1
2
1.5 h
2 h
3 min
2 min
2 min
none
FeCl3
AlCl3
BF3·Et2O
Me3SiOTf 1 min
FeCl3
AlCl3
BF3·Et2O
Me3SiOTf 1 min
none
none
Table 2. Yields in the synthesis of amino alcohols 9, 10 and amino
acid methyl esters 5, 6.
Entry
R
9 or 10, yield[a]
5 or 6, yield[a]
Z-2a
iPr, Z
2
4 min
3 min
2 min
1
2
3
4
5
6
nPent
iPr
BnOCH2
Ph
iPr
Ph
9a, 81%
9b, 71%
9c, 71%
9d, 77%
10a, 80%
10b, 73%
5a, 54%
5b, 53%
5c, 75%
5d, 54%
6a, 63%
6b, 67%
E-2b
Z-2b
Ph, E
Ph, Z
2
2
6 h
20 h
[a] Configuration of the double bond in bis(imidates) 1 and 2. [b]
9-Anthracenyl.
[a] Total yield in two steps.
2422
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2421–2425

Versatile Approach to Racemic Unsaturated Amino Acids
General Procedure for Synthesis of Amino Alcohols 9 and 10: 6 m
aq. HCl (2 mL) was added to a solution of oxazoline 3 or oxazine
4 (1 mmol) in EtOH (2 mL) at room temp., and the reaction mix-
ture was stirred at room temp. for 1–2 h, then refluxed for 10 h.
Resulting dark brown solution was cooled to room temperature
and concentrated in vacuo. The residue was dissolved in a mixture
of saturated aq. NaHCO3 (10 mL) and EtOAc (10 mL). Boc2O
(1.2 mmol, 1.2 equiv.) was added to the resulting biphasic mixture
and vigorous stirring was continued overnight. Organic phase was
separated and washed with water and brine, dried with Na2SO4
were transformed to their methyl esters 7a–d, 8a,b in order
to facilitate the purification and characterization.
Compared to our previously reported method that in-
volved PdII catalysis,[9] the synthesis of cyclic imidates 3, 4
by Lewis acid catalysed cyclization of bis(trichloroacetimid-
ates) 1, 2 offers shorter synthetic route and permits efficient
use of substrates having both E- and Z-configuration. In
addition, the method presented in this communication in-
volves non-expensive and less toxic catalysts. The limitation
is the lack of chirality transfer[14] that, in turn, was very and concentrated in vacuo. The residue was purified by column
high in PdII-catalysed cyclization of δ-acetoxy-allylic tri-
chromatography on silica gel eluting with a mixture of hexane and
ethyl acetate (gradient 4:1 to 1:1) to afford pure product 9 and 10.
chloroacetimidates.[9]
Compound 9d has been described previously in the literature.[15]
(E)-2-[(tert-Butoxycarbonyl)amino]non-3-en-1-ol (9a): 1H NMR
(400 MHz, CDCl3): δH = 5.68 (dt, J = 15.3, 6.7 Hz, 1 H, -CH=CH-
Conclusion
CH-CH2OH), 5.36 (dd, J = 15.3, 6.3 Hz, 1 H, -CH=CH-CH-
CH2OH), 4.79 (br. s, 1 H, -NH), 4.17–4.15 (m, 1 H, -CH-CH=
4-Vinyloxazolines 3 and 4-vinyloxazines 4 can be ef-
ficiently prepared by Lewis acid catalyzed cyclization of
CH-), 3.68–3.55 (m, 2 H, -CH2OH), 2.42 (br. s, 1 H, -OH), 2.02
bis(trichloroacetimidates) 1 and 2. We have demonstrated
(q, J = 7.0 Hz, 2 H, -CH=CH-CH2CH2-), 1.44 [s, 9 H, -C(CH3)3],
an application of this reaction for efficient synthesis of race-
1.39–1.99 (m, 6 H, -CH2CH2CH2CH3) and 0.89–0.84 (m, 3 H,
mic unsaturated amino acids 5 and 6. Further research to
expand the utility of imidate cyclization, as well as mechan-
istic investigations are ongoing.
-CH2CH3) ppm. 13C NMR (100 MHz, CDCl3): δC = 156.08,
133.71, 126.53, 79.72, 65.96, 54.42, 32.30, 32.31, 28.75, 28.34, 22.45
and 13.99 ppm. HRMS (EI) [M + Na]+: calcd. for C14H27NO3Na
280.1889, found 280.1881.
(E)-[(tert-Butoxycarbonyl)amino]-5-methylhex-3-en-1-ol (9b): 1H
NMR (400 MHz, CDCl3): δH = 5.66 (dd, J = 15.7, 6.3 Hz, 1 H,
-CH=CH-CH-CH2OH), 5.31 (dd, J = 15.7, 5.9 Hz, 1 H, -CH=CH-
CH-CH2OH), 4.74 (br. s, 1 H, -NH), 4.23–4.15 (m, 1 H, -CH-
CH=CH-), 3.66 (dd, J = 11.0, 4.3 Hz, 1 H, -CH2OH), 3.59 (dd, J
= 11.0, 6.3 Hz, 1 H, -CH2OH), 2.29 [octet, J = 6.7 Hz, 1 H,
-CH(CH3)2], 1.49 [s, 9 H, -C(CH3)3] and 0.98 [d, J = 6.7 Hz, 6 H,
-CH(CH3)2] ppm. 13C NMR (100 MHz, CDCl3): δC = 156.11,
140.61, 123.57, 79.79, 66.19, 54.41, 30.86, 28.35 and 22.24 ppm.
HRMS (EI) [M]+: calcd. for C12H24NO3 230.1756, found 230.1748.
Experimental Section
General: Reagents and starting materials were obtained from com-
mercial sources and used as received. The solvents were purified
and dried by standard procedures prior to use; petroleum ether of
boiling range 60–80 °C was used. All reactions were performed un-
der an argon atmosphere. Flash chromatography was carried out
using Merck Kieselgel (230–400 mesh). Thin-layer chromatography
was performed on silica gel, spots were visualized by staining with
KMnO4. NMR spectra were recorded on Varian Mercury spec-
trometer (400 MHz) with chemical shifts values (δ) in ppm relative
to TMS using the residual chloroform signal as internal standard.
Gas chromatographic analyses were performed using HP 6890 gas
chromatographic system with HP 5972 MSD detector. HRMS were
obtained using Q-TOF micro high resolution mass spectrometer
with ESI (ESI+/ESI–) 3.
(E)-5-(Benzyloxy)-2-[(tert-butoxycarbonyl)amino]pent-3-en-1-ol (9c):
1H NMR (400 MHz, CDCl3): δH = 7.37–7.27 (m, 5 H, Ph), 5.81
(dt, J = 15.7, 5.5 Hz, 1 H, -CH=CH-CH2O-), 5.70 (dd, J = 15.7,
5.1 Hz, 1 H, -CH=CH-CH2O-), 4.88 (d, J = 6.7 Hz, 1 H,
-NH), 4.51 (s, 2 H, -OCH2Ph), 4.29–4.20 (m, 1 H, -CH-CH=
CH-), 4.03 (d, J = 5.5 Hz, 2 H, -CH2OBn), 3.69–3.60 (m, 2 H,
-CH2OH), 2.42 (br. s, 1 H, -OH) and 1.44 [s, 9 H, -C(CH3)3] ppm.
13C NMR (100 MHz, CDCl3): δC = 158.87, 138.01, 130.07, 128.72,
128.39, 127.77, 127.68, 79.79, 72.39, 69.99, 65.36, 53.78 and 28.33
ppm. HRMS (EI) [M + Na]+: calcd. for C17H25NNaO4 330.1681,
found 330.1661.
General Procedure for Cyclization of Bis(imidates) 1 and 2. Synthesis
of Oxazolines 3 and Oxazines 4: Molecular sieves (4 Å) and Lewis
acid catalyst (0.05 mmol, 10 mol-%) were added to a stirred solu-
tion of bis(imidate) 1 or 2 (0.50 mmol) in DCM (10 mL) at room
temp. After reaction was complete (TLC control in the first minute
of the reaction), TEA (50 mol-%) was added to the reaction mix-
ture and then the solvent was removed under reduced pressure. The
residue was purified by chromatography on a short silica gel col-
umn eluting with a mixture of light petroleum ether and ethyl acet-
ate (8:1) to afford the product 3 or 4.
(E)-3-[(tert-Butoxycarbonyl)amino]-6-methylhept-4-en-1-ol
(10a):
1H NMR (400 MHz, CDCl3): δH = 5.59 (dd, J = 15.7, 6.7 Hz, 1
H, iPrCH=CH-), 5.35 (dd, J = 15.7, 5.5 Hz, 1 H, iPr–CH=CH-),
4.52 (d, J = 7.4 Hz, 1 H, -NH), 4.34–4.24 (m, 1 H, -CH2-CH-
CH=CH-), 3.71–3.58 (m, 2 H, -CH2OH), 3.21 (br. s, 1 H, -OH),
2.27 [octet, J = 6.7 Hz, 1 H, -CH(CH3)2], 1.91–1.81 (m, 1 H,
-CH2CH2OH), 1.50–1.40 (m, 1 H, -CH2CH2OH), 1.45 [s, 9 H,
-C(CH3)3] and 0.97 [d, J = 7.0 Hz, 6 H, -CH(CH3)2] ppm. 13C
NMR (100 MHz, CDCl3): δC = 156.56, 138.48, 126.88, 79.83,
58.75, 48.40, 38.84, 30.79, 28.32 and 22.28 ppm. HRMS (EI)
[M]+: calcd. for C13H26NO3 244.1913, found 244.1895.
Compounds 3a–e, 4a have been described previously in the litera-
ture.[9]
4-[(E)-Styryl]-2-trichloromethyl-5,6-dihydro-4H-1,3-oxazine
(4b):
1H NMR (400 MHz, CDCl3): δH = 7.41–7.23 (m, 5 H, Ph), 6.56
(d, J = 15.7 Hz, 1 H, -CH=CH-Ph), 6.27 (dd, J = 15.7, 5.1 Hz, 1
H, -CH=CH-Ph), 4.48–4.41 (m, 3 H, -N-CHCH2CH2O-), 2.22–
2.15 and 1.91–1.83 (m, 2 H, -N-CHCH2CH2O-) ppm. 13C NMR (E)-3-[(tert-Butoxycarbonyl)amino]-5-phenylpent-4-en-1-ol (10b): 1H
(100 MHz, CDCl3): δC = 153.85, 136.59, 131.38, 129.50, 128.51, NMR (400 MHz, CDCl3): δH = 7.37–7.22 (m, 5 H, Ph), 6.55 (d, J
127.64, 126.43, 92.40, 65.23, 53.14 and 26.58. GC-MS: m/z (EI):
= 16.0 Hz, 1 H, -CH=CH-Ph), 6.16 (dd, J = 16.0, 5.9 Hz,
1 H, -CH=CH-Ph), 4.74 (d, J = 8.6 Hz, 1 H, -NH), 4.58–4.48 (m,
304 (M+).
Eur. J. Org. Chem. 2011, 2421–2425
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2423

L. Grigorjeva, A. Jirgensons
SHORT COMMUNICATION
1 H, -CH-CH=CH-), 3.73–3.69 (m, 2 H, -CH2OH), 3.10 (br. s, 1
5.5 Hz, -CH2COO-), 2.25 [1 H, octet, J = 7.0 Hz, -CH(CH3)2], 1.43
H, -OH), 2.03–1.96 (m, 1 H, -CH2CH2OH), 1.63–1.56 (m, 1 H, [s, 9 H, -C(CH3)3] and 0.95 [d, 6 H, J = 6.7 Hz, -CH(CH3)2]. 13C-
-CH2CH2OH), 1.47 [s, 9 H, -C(CH3)3] and 0.97 [d, J = 7.0 Hz, 6 NMR δC (100 MHz, CDCl3): 171.66, 155.00, 139.11, 125.68, 79.37,
H, -CH(CH3)2] ppm. 13C NMR (100 MHz, CDCl3): δC = 156.42,
51.57, 48.91, 39.80, 30.67, 28.35 and 22.23. HRMS (EI) [M +
136.53, 130.27, 129.66, 128.57, 127.67, 126.33, 80.04, 58.80, 48.92, Na]+: calcd. for C14H25NNaO4 294.1681, found 249.1711.
38.47 and 28.34 ppm. HRMS (EI) [M + Na]+: calcd. for
Supporting Information (see footnote on the first page of this arti-
C16H23NNaO3 300.1576, found 300.1573.
cle): Syntheses of diols 7, 8 and imidates 1, 2, and copies of 1H
NMR, 13C NMR and IR spectra of novel compounds.
General Procedure for Synthesis of Protected Amino Acids 5 and 6:
Amino alcohol 9 or 10 (0.7–0.8 mmol) was dissolved in dry acetone
(5–10 mL) and the solution was cooled in an ice bath. Excess of
Jones reagent was added dropwise to the solution and the stirring
was continued while cooling until complete conversion of starting
material as judged by TLC (1–2 h). The excess of Jones reagent
was quenched with iPrOH. Solvent was removed under reduced
pressure, and the residue was partitioned between water (10–
20 mL) and EtOAc (10–20 mL). Organic phase was separated, and
extracted with saturated aqueous NaHCO3 (20 mL). Aqueous
phase was acidified with 6 m aq. HCl to pH ≈ 3 and extracted with
EtOAc. Organic phase was separated, dried with Na2SO4, filtered,
and concentrated in vacuo. The residue was dissolved in THF (10–
20 mL), and the solution was cooled in an ice bath. Then CH2N2
(solution in Et2O) was added in excess. After the reaction was com-
plete, the excess CH2N2 was removed with argon flow. The reaction
mixture was concentrated in vacuo, and the residue was purified
by column chromatography on silica gel eluting with a mixture of
hexane and ethyl acetate (4:1) to afford pure product 5 and 6.
Acknowledgments
Funding by the European Union (European Social Fund, grant
number 2009/0203/1DP/1.1.1.2.0/09/APIA/VIAA/023) is gratefully
acknowledged.
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[10] Selected references: a) N. G. W. Rose, M. A. Blaskovich, A.
Wong, G. A. Lajoie, Tetrahedron 2001, 57, 1497–1507; b) J.
Hang, L. Deng, Bioorg. Med. Chem. Lett. 2009, 19, 3856–3858;
c) P. A. Alexander, S. P. Marsden, D. M. M. Subtil, J. C.
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Chem. 1984, 49, 2632–2634; e) A. E. Lurain, P. J. Walsh, J. Am.
Chem. Soc. 2003, 125, 10677–10683 and references cited
therein.
[11] a) H.-P. Wessel, T. Iversen, D. R. Bundle, J. Chem. Soc. Perkin
Trans. 1 1985, 2247–2250; b) G. Kokotos, A. Chioum, Synthe-
sis 1997, 168–170; c) H. Abdel-Rahman, G. Winterfeld, M.
Takhi, R. Schmidt, Eur. J. Org. Chem. 2002, 713–717.
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Reymond, J. Cossy, Org. Lett. 2010, 12, 1808–1811.
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56, 4196–4204.
Compounds 5a[16] and 6b[17] have been described previously in the
literature.
Methyl
(E)-2-[(tert-Butoxycarbonyl)amino]-5-methylhex-3-enoate
(5b): 1H NMR (400 MHz, CDCl3): δH = 5.73 (dd, J = 15.7, 6.7 Hz,
1 H, -CH=CH-CHCOOCH3), 5.40 (dd, J = 15.3, 5.9 Hz, 1 H,
-CH=CHCHCOOCH3), 5.08 (br. s, 1 H, -NH), 4.79–4.75 (m, 1 H,
CH3COOCH-CH=CH-), 3.75 (s, 3 H, -OCH3), 2.29 [octet, J =
6.7 Hz, 1 H, -CH(CH3)2], 1.44 [s, 9 H, -C(CH3)3] and 0.97 [d, J =
6.7 Hz, 6 H, -CH(CH3)2] ppm. 13C NMR (100 MHz, CDCl3): δC
= 172.03, 154.96, 141.39, 121.31, 79.96, 55.26, 52.43, 30.74, 28.28
and 21.93 ppm. HRMS (EI) [M + Na]+: calcd. for C13H23NNaO4
280.1525, found 280.1612.
Methyl (E)-5-(Benzyloxy)-2-[(tert-butoxycarbonyl)amino]pent-3-en-
oate (5c): 1H NMR (400 MHz, CDCl3): δH = 7.37–7.27 (m, 5 H,
Ph), 5.89 (dt, J = 15.7, 5.1 Hz, 1 H, -CH=CH-CH2-), 5.80 (dd, J
= 15.7, 5.1 Hz, 1 H, -CH=CH-CH2-), 5.17 (br. s, 1 H, -NH), 4.91–
4.87 (m, 1 H, -CH-CH=CH-), 4.51 (s, 2 H, CH2Ph), 4.04 (d, J =
5.1 Hz, 2 H, BnOCH2-), 3.76 (s, 3 H, -OCH3) and 1.45 [s, 9 H,
-C(CH3)3] ppm. 13C NMR (100 MHz, CDCl3): δC = 171.27, 154.90,
137.96, 129.87, 128.38, 127.73, 127.67, 126.85, 73.34, 72.34, 69.81,
54.87, 52.59 and 28.27 ppm. HRMS (EI) [M + Na]+: calcd. for
C18H25NO5Na 358.1630, found 358.1638.
Methyl
(E)-2-[(tert-Butoxycarbonyl)amino]-4-phenylbut-3-enoate
1
(5d): H NMR (400 MHz, CDCl3): δH = 7.38–7.23 (m, 5 H, Ph),
6.66 (d, J = 16.0 Hz, 1 H, -CH=CH-Ph), 5.40 (dd, J = 16.0, 6.7 Hz,
1 H, -CH=CH-Ph), 5.31 (br. s, 1 H, -NH), 5.06–4.06 (m, 1 H,
-CH-CH=CH-), 3.78 (s, 3 H, -OCH3) and 1.44 [s, 9 H, -C(CH3)3],
ppm. 13C NMR (100 MHz, CDCl3): δC = 171.43, 154.89, 135.90,
132.83, 128.57, 128.11, 126.62, 123.81, 80.18, 55.45, 52.69 and
28.29 ppm.
Methyl (E)-3-[(tert-Butoxycarbonyl)amino]-6-methylhept-4-enoate
(6a): 1H-NMR δH (400 MHz, CDCl3): 5.58 (dd, 1 H, J = 15.7,
6.7 Hz, -CH=CH-CH-NH-) 5.36 (dd, 1 H, J = 15.7, 5.9 Hz,
-CH=CH-CH-NH-), 5.04 (br. s, 1 H, -NH), 4.48–4.38 (m, 1 H,
-HN-CH-CH=CH-), 3.66 (s, 3 H, -OCH3), 2.57 (d, 1 H, J =
2424
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2421–2425

Versatile Approach to Racemic Unsaturated Amino Acids
[14] Enantiomerically enriched imidates E-1b and Z-1b gave vinyl-
oxazoline 3b enantiomer[9] in a very poor enantiomeric excess
(ee 4–16%) when exposed to FeCl3, AlCl3, BF3·Et2O and
Me3SiOTf catalysts according to GC analysis on a chiral sta-
cionary phase (6-TBDMS-2,3-Me-β-CD 50%).
[15] M. P. Sibi, D. Rutherford, P. A. Renhowe, B. Li, J. Am. Chem.
Soc. 1999, 121, 7509–7516.
[16] T. Ibuka, K. Suzuki, H. Habashita, A. Otaka, H. Tamamura,
N. Mimura, Y. Miwa, T. Taga, N. Fujii, J. Chem. Soc., Chem.
Commun. 1994, 2151–2152.
[17] M. E. O’Donnell, J. Sanvoisin, D. Gani, J. Chem. Soc. Perkin
Trans. 1 2001, 1696–1708.
Received: January 15, 2011
Published Online: March 8, 2011
Eur. J. Org. Chem. 2011, 2421–2425
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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