A mild method for formylating amino esters without using any formulating agent

Article abstract of DOI:10.1055/s-1998-2025

A simple and mild method for the N-formylation of α-amino esters is described via an intermediate oxaziridine. This procedure avoids the necessity of specific formylating agents and yields the N-formyl species in high yield and without racemization.

Full text of DOI:10.1055/s-1998-2025

March 1998
SYNTHESIS
297
A Mild Method for Formylating Amino Esters Without Using any Formylating Agent
Thierry Giard, Didier Bénard, Jean-Christophe Plaquevent*
Laboratoire des Fonctions Azotées et Oxygénées Complexes de l’IRCOF (UPRES-A 6014), F 76821 Mont Saint Aignan, France
Fax +33(2)35522411
Received 19 June 1997; revised 13 October 1997
Abstract: A simple and mild method for the N-formylation of a-
amino esters is described via an intermediate oxaziridine. This pro-
cedure avoids the necessity of specific formylating agents and
yields the N-formyl species in high yield and without racemization.
Key words: formylation, amino esters, oxaziridines, imines,
Möhr’s salt
During our previous work on the chemistry of functional-
ized oxaziridines,1–4 we investigated the synthesis and re-
activity of amino ester and peptide derived oxaziridines.1–8
We were able to observe that Fe(II) ions converted oxazir-
idines to N-formyl derivatives (Scheme 1), when the het-
erocycle bore a tert-butyl group, while the oxaziridine-
amide rearrangement was preferred for other substituents,
such as a phenyl ring. These behaviors were in agreement
with the previous studies reported in the literature.9,10
Scheme 2
In all the cases studied, the overall yield (3 steps) was in
the range of 80–99%. Optical rotations compared well
with the literature data, indicating that no racemization
occurred during the synthetic steps. For unknown com-
pounds (see Table), HPLC or GC analysis on a chiral col-
umn confirmed this result. Some experiments were
carried out using a “one-pot” procedure, yielding the same
N-formyl compounds 4, but with lower yields (Table). In
Scheme 1
addition, the reaction is chemoselective, since primary
amines are preferably formylated with respect to second-
ary ammes.
Since the reaction involves a free-radical induced ring
opening, the special behavior of the tert-butyl group can
be attributed to the relative stability of the tert-butyl radi-
cal, which can easily be removed, thus propagating the re-
action. One of the advantages of this reaction was that all
by-products are gaseous, thus yielding a very pure formy-
lated material. The continuing interest for the N-formyla-
tion of a-amino esters11–18 led us to investigate the
potential of this reaction for this purpose. We expected
that the very mild conditions involved could avoid any ra-
cemization and allow very good yields. Indeed, the a-
amino ester hydrochlorides 1 were easily transformed into
the corresponding imines 2, the oxidation of which by 3-
chloroperoxybenzoic acid (mCPBA) yielded the required
oxaziridinoesters 3. The two steps were very efficient,
with yields up to 99% in some cases. As expected, the ox-
aziridines 3 were obtained as mixtures of diastereoiso-
mers resulting from the newly created stereogenic centers
of the heterocycle. The key reaction, i.e. the action of Fe
(II) ions to give N-formyl a-amino esters 4, was per-
formed using ammonium ferrous sulfate hexahydrate
(Möhr’s salt) at room temperature. Again, yields were as
high as 90–99% (Scheme 2, Table).
In conclusion, the N-formylation of a-amino ester hydro-
chlorides 1 can easily be carried out with very good yields
at room temperature.19 In addition to the synthetic effi-
ciency of the method, an advantage is that it does not re-
quire the use of any formylating agent.20 Only standard
reagents are required and the reactions conditions are
mild. Nevertheless, we recommend that this procedure be
used only for amino esters carrying an unfunctionalized
chain.
NMR spectra were recorded on a Bruker AC 200 apparatus (1H at
200 MHz, 13C at 50 MHz). GC analyses were realized on a Hewlett-
Packard 5890 A apparatus, and HPLC on a Spectra Series P-100 chro-
matograph. HRMS were recorded on a Jeol-AX-500 spectrometer. IR
spectra were recorded on a Perkin-Elmer 16 PC IRFT spectrophotom-
eter. TLC were performed on Merck Kieselgel 60 F-254-0.25 mm
mesh and flash chromatography was carried out using Merck Kiesel-
gel 60 (230–400 mesh ASTM). Melting points were determined using
a Reichert apparatus. Optical rotations were measured at 20°C with a
Perkin-Elmer 341 polarimeter.
CH2Cl2 was dried by distilling over P2O5. Petroleum ether used had
bp 40–60°C.

298
Papers
SYNTHESIS
Table. N-Formylation of a-Amino Esters
Prod-
uct
Amino
Acid
Configu-
ration
R1
R2
Yielda
(%)
[a]D (c, solvent)
1H NMRb
d (CHO)
found
reported
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
ALA
ALA
VAL
VAL
VAL
LEU
LEU
LEU
ILE
norLEU
norLEU
PheGly
PHE
S
S
S
S
S
S
S
S
S
S
S
R
S
S
Me
Me
i-Pr
i-Pr
CH2Ph
Me
CH2Ph
Me
t-Bu
CH2Ph
Me
t-Bu
Me
CH2Ph
Me
Me
Me
t-Bu
87
80
89
91
–18.3 (1, CH2Cl2)c
–34.6 (0.6, EtOH)
–40.1 (2, EtOH)
8.05
8.12
8.15
8.24
8.23
8.14
8.09
8.10
8.16
8.16
8.19
8.14
8.01
8.16
–34.65.15
–40.115
–23.45 (2, EtOH)
–33.33 (2, EtOH)
–13.4 (1, CH2Cl2)d
–43.2 (1, MeOH)
–49.8 (2, EtOH)
–23.2416
–33.3815
i-Pr
90 (73)
82
i-Bu
i-Bu
i-Bu
s-Bu
Bu
Bu
Ph
99 (74)e
90 (73)
99
–43.515
–49.915
–32.521
–32.25 (1, CHC13)
–2.58 (3, CH2Cl2)c
+28.5 (1, CH2Cl2)d
–196 (1, CHCl3)
+84.9 (1, CH2Cl2)
+16.2 (0.7, EtOH)
84
85
90
96 (63)
96 (77)
–20021
+85.115
+16.215
PhCH2
PhCH2
PHE
a Overall yield. Yield given in parenthesis refers to one-pot reaction.
b Recorded in CDCl3/TMS.
d ee determined by GC.
e Identical result was obtained when sarcosine was added to the initial
amino ester hydrochloride.
c ee determined by HPLC.
1H NMR (CDCl3, 200 MHz): d = 1.33 (d, 3 H, J = 7.14 Hz), 4.55–4.70
(m, 1 H), 5.08 (s, 2 H), 7.10–7.20 (m, 1 H), 7.25 (s, 5 H), 8.05 (s, 1 H).
13C NMR (CDCl3, 50MHz): d = 17.86, 46.77, 67.00, 127.97, 128.31,
128.50, 135.23, 161.09, 172.33.
Imines 2; General Procedure:
To a solution of a -amino ester hydrochloride 1 (5.5 mmol) in CH2Cl2
(5 mL) containing molecular sieves (1.1 g), were added Et3N (0.557 g,
5.5 mmol) and then pivalaldehyde (0.52 g, 6.0 mmol) at r.t., under ar-
gon. After stirring for 40 h, anhyd Et2O (15 mL) was added. The mix-
ture was stirred for 20 min, filtered, and the solvents were removed to
give the imine 2; yield: 89–99%.
IR (film): n = 1740, 1666 cm–1.
MS (EI): m/z = 207 (M+.).
HRMS (CI+, 70 eV, i-BuH, 10–5 Torr): m/z found 208.0977 (M+H);
calc. for C11H14NO3 208.0974.
Oxaziridines 3; General Procedure:
To a solution of the imine 2 (2.8 mmol) in CH2Cl2 (7 mL) was added
mCPBA (0.485 g, 2.8 mmol) in portions at 0°C. The mixture was
stirred at 0°C for 20 min, then for 1 h at r.t. The mixture was filtered,
washed with 10% aq Na2SO3 solution (7 mL), then with aq sat.
NaHCO3 solution (7 mL), and finally with H2O (5 mL). The organic
layer was dried (MgSO4) and then concentrated to give the oxaziri-
dine 3; yield: 90–99%.
N-Formyl-L-Alanine Methyl Ester (4b):
The crude oil was purified by chromatography on silica gel (CH2Cl2/
MeOH, 95:5); Rf 0.33; yield: 80%; yellow oil; [a]D –34.6 (c = 0.6,
EtOH).
1H NMR (CDCl3, 200 MHz): d = 1.37 (d, 3 H, J = 7.15 Hz), 3.70 (s,
3 H), 4.55–4.75 (m, 1 H), 6.45–6.70 (m, 1 H), 8.12 (s, 1 H).
13C NMR (CDCl3, 50 MHz): d = 17.77, 46.53, 52.25, 160.98, 173.00.
IR (film): n = 1740, 1664 cm–1.
N-Formyl Amino Esters 4; General Procedure:
MS (EI): m/z = 131 (M+.), 116.
To a solution of the oxaziridine 3 (1.53 mmol) in MeOH (2 mL) and
water (5 mL) was added Möhr’s salt (0.626 g, 1.53 mmol) at r.t. under
argon. The reaction mixture turned green, then to a brown-orange
colour. After adding CH2Cl2 (15 mL), the organic layer was dried
(MgSO4) and concentrated to give the crude product, which was pu-
rified by chromatography on silica gel. Reaction time for methyl and
benzyl valinates was 7 h, and 9 h for tert-butyl esters.
HRMS (EI, 70 eV): m/z found 131.0574; calc. for C5H9NO3 131.0582.
N-Formyl-L-Valine Benzyl Ester (4c):
The crude oil was purified by chromatography on silica gel (CH2Cl2/
petroleum ether, 70:30); Rf 0.3; yield: 89%; yellow oil; [a]D –40.1 (c
= 2, EtOH).
1H NMR (CDCl3, 200 MHz): d = 0.80 (d, 3 H, J = 6 .88 Hz), 0.86 (d,
3 H, J = 6.81Hz), 2.05–2.30 (m, 1 H), 4.62 (dd, 1 H, J = 8.5, 4.8 Hz),
5.00–5.20 (m, 2 H), 6.95 (d, J = 8.5 Hz), 7.27 (s, 5 H), 8.15 (s, 1 H).
13C NMR (CDC13, 50 MHz): d = 17.42, 18.89, 31.00, 55.66, 66.94,
128.34, 135.19, 161.48, 171.48.
N-Formyl Amino Esters 4; One-Pot Procedure:
To a solution of the a-amino ester hydrochloride (2.2 mmol) in
CH2Cl2 (5 mL) containing molecular sieves (0.4 g) were added Et3N
(0.22 g, 2.2 mmol) and then pivalaldehyde (0.21 g, 2.4 mmol) at r.t.
under argon. After stirring for 40 h, mCPBA (0.38 g, 2.2 mmol) was
added. The mixture was stirred for 20 min at 0°C and then for 1 h at
r.t. Then, a solution of Möhr’s salt (0.91 g, 2.2 mmol) was added in
MeOH (2 mL) and H2O (5 mL). The mixture was stirred for 15 h, fil-
tered, and the organic layer was washed with 10% aq Na2SO3, then
with aq sat. NaHCO3 solution (7 mL), and finally with H2O (5 mL).
The organic layer was dried (MgSO4), filtered and the solvents were
removed. The crude product was purified by chromatography on sili-
ca gel to give the N-formyl amino ester 4; yield: 63–77%.
IR (film): n = 1746, 1666 cm–1.
MS (EI): m/z = 235 (M+.), 234, 206.
HRMS(EI, 70eV):m/zfound235.1216;calc. forC13H17NO3 235.1208.
N-Formyl-L-Valine Methyl Ester (4d):
The crude oil was purified by column chromatography on silica gel
(CH2Cl2/petroleum ether, 70:30); Rf 0.3; yield: 91%; yellow oil; [a]D
–23.45 (c = 2, EtOH).
1H NMR (CDCl3, 200 MHz): d = 0.89 (d, 3 H, J = 6.6 Hz), 0.94 (d, 3
H, J = 6.8 Hz), 2.05–2.25 (m, 1 H), 3.74 (s, 3 H), 4.65 (dd, 1 H, J =
9.0, 4.8 Hz), 5.95–6.15 (m, 1 H), 8.24 (s, 1H).
13C NMR (CDCl3, 50 MHz): d = 17.52, 18.84, 31.10, 52.19, 55.49,
160.95, 172.0.
N-Formyl-L-Alanine Benzyl Ester (4a):
The crude oil was purified by chromatography on silica gel (CH2Cl2/
MeOH, 97:3); Rf 0.3 ; yield: 87%; colorless oil; [a]D –18.3 (c = 1,
CH2Cl2).
IR (film): n = 1730, 1660 cm–1.
MS (EI): m/z = 159 (M+.), 115.
Chiral HPLC Analysis: Daicel Chemical Industries, Chiracel OJ, i-
PrOH/hexane, 6:94; flow = lmL/min. Racemic: 30.06¢ and 36.98¢ (S
enantiomer).
HRMS (CI+, 200 eV, i-BuH, 10–5 Torr): m/z found 160.0969 (M+H);
calc. for C7H14NO3 160.0974.

March 1998
SYNTHESIS
299
IR (film): n = 1743, 1666 cm–1.
N-Formyl-L-Valine tert-Butyl Ester (4e):
MS (EI): m/z = 173 (M+.), 142, 129.
The crude oil was purified by column chromatography on silica gel
(EtOAc/petroleum ether, 30:70); Rf 0.3; yield: 90%; white solid; mp
66°C; [a]D –33.33 (c = 2, EtOH).
HRMS (EI, 70 eV): m/z found 173.1038, calc. for C8H15NO3
173.1052.
1H NMR (CDCl3, 200 MHz): d = 0.88 (d, 3 H, J = 6.8 Hz), 0.93 (d, 3
H, J = 6.8 Hz), 1.45 (s, 9 H), 2.10–2.25 (m, 1 H), 4.53 (dd, 1 H, J =
4.6, 8.0 Hz), 6.00–6.10 (m, 1 H), 8.23 (s, 1 H).
13C NMR (CDCl3, 50 MHz): d = 17.36, 18.78, 27.85, 31.25, 55.84,
82.63, 160.99, 171.13.
N-Formyl-L-Norleucine Benzyl Ester (4j):
The crude oil was purified by column chromatography on silica gel
(EtOAc/petroleum ether, 95:5); Rf 0.5; yield: 84%; yellow oil; [a]D
–2.58 (c = 3.1, CH2Cl2).
IR (KBr): n = 1736, 1656 cm–1.
Chiral HPLC Analysis: Daicel Chemical Industries, Chiracel OJ, i-
PrOH/hexane (5:95); flow = 1 mL/min. Racemic: 20.55¢ and 25.10¢ (S
enantiomer).
MS (EI): m/z = 201 (M+.), 200.
HRMS (CI+, 200 eV, i-BuH, 10–5 Torr): m/z found 202.1451 (M+H)
and 146.0811 (C6H12NO3, Mac Lafferty’s rearrangement); calc. for
C10H20NO3 202.1443.
1H NMR (CDCl3, 200 MHz): d = 0.77–0.84 (m, 3 H), 1.13–1.26 (m,
4 H), 1.55–1.93 (m, 2 H), 4.70 (dd, 1 H, J = 9.4, 13.3 Hz), 5.07–5.21
(m, 2 H), 6.30–6.40 (m, 1 H), 7.32 (s, 5 H), 8.16 (s, 1 H).
13C NMR (CDCl3, 50 MHz): d = 13.73, 22.10, 27.08, 31.88, 50.76,
67.05, 128.17, 128.39, 128.51, 135.16, 160.99, 172.05.
IR (film): n = 1751, 1679 cm–1.
N-Formyl-L-Leucine Benzyl Ester (4f):
The crude oil was purified by column chromatography on silica gel
(CH2Cl2/MeOH, 98:2); Rf 0.25; yield: 82%; colorless oil; [a]D –13.4
(c = 1, CH2Cl2).
MS (EI): m/z = 249 (M+.), 142.
HRMS (CI+, 200 eV, i-BuH, 10–5 Torr): m/z found 250.1430 (M+H),
calc for C14H20NO3 250.1443.
Chiral CPG Analysis : b-dexTM 120 permethylated b cyclodextrin
0.25mm ID ´ 0.25 mm df, Tf = 181°C. Condition: 15¢ at 121 °C then
temperature increase of 0.5 °C per min. Racemic: 121.2¢ and 122.3¢ (S
enantiomer).
N-Formyl-L-Norleucine Methyl Ester (4k):
1H NMR (CDCl3, 200 MHz): d = 0.86–0.90 (m, 6 H), 1.52–l.67 (m,
3 H), 4.65–4.80 (m, 1 H), 5.13 (s, 2 H), 6.43 (d, 1 H, J = 8.1 Hz), 7.31
(s, 5 H), 8.14 (s, 1 H).
The crude oil was purified by column chromatography on silica gel
(EtOAc/petroleum ether, 70:30); Rf 0.2; yield: 85%; yellow oil; [a]D
28.5 (c = 1, CH2Cl2).
13C NMR (CDCl3, 50 MHz): d = 21.66, 22.69, 24.65, 41.15, 49.34,
67.02, 128.09, 128.33, 128.50, 135.75, 161.11, 172.49.
IR (film): n = 1742, 1686 cm–1,
Chiral CPG Analysis : b-dexTM 120 permethylated b cyclodextrin
0.25mm ID ´ 0.25 mm df, Tf = 181°C. Condition: 15¢ at 119°C then
temperature increase of 0.5°C per min. Racemic: 22.305¢ and 23.022¢
(S enantiomer).
MS (EI): m/z = 249 (M+.), 114.
HRMS (EI, 70 eV): m/z found 249.1360; calc. for C14H19NO3
249.1365.
1H NMR (CDCl3, 200 MHz): d = 0.80–0.95 (m, 3 H), 1.20–1.35 (m,
4 H), 1.55–1.95 (m, 2 H), 3.73 (s, 3 H), 4.62–4.73 (m, 1 H), 6.10–6.25
(m, 1 H), 8.19 (s, 1 H).
N-Formyl-L-Leucine Methyl Ester (4g):
13C NMR (CDCl3, 50 MHz): d = 13.63, 22.03, 27.15, 31.76, 50.61,
52.20, 161.03, 172.63.
The crude oil was purified by column chromatography on silica gel
(CH2Cl2/MeOH, 96:4); Rf 0.5; yield: 99%; colorless oil; [a]D –43.2
(c = 1, MeOH).
IR (film): n = 1746, 1700 cm–1.
MS (EI): m/z = 173 (M+.), 117.
1H NMR (CDCl3, 200 MHz): d = 0.84 (d, 6 H, J = 6.0 Hz), 1.40–1.70
(m, 3 H), 3.63 (s, 3 H), 4.55–4.80 (m, 1 H), 6.76 (d, 1 H, J = 7.5 Hz),
8.09 (s,1 H).
HRMS (CI+, 200 eV, i-BuH, 10–5 Torr): m/z found 174.1118 (M+H),
calc. for C8H16NO3 174.1130.
13C NMR (CDCl3, 50 MHz): d = 21.42, 22.54, 24.49, 40.82, 49.11,
52.05, 161.28, 172.94.
N-Formyl-D-Phenylglycine Methyl Ester (4l):
IR (film): n = 1744, 1666 cm–1.
The crude oil was purified by column chromatography on silica gel
(CH2Cl2/MeOH, 98:2); Rf 0.25; yield: 90%; white solid; mp 64°C;
[a]D –196 (c = 1, CHCl3).
MS (EI): m/z = 173 (M+.), 142.
HRMS (CI+, 200 eV, i-BuH, 10–5 Torr): m/z found 174.1137 (M+H),
calc. for C8H16NO3 174.1130.
1H NMR (CDCl3. 200 MHz): d = 3.68 (s, 3 H), 5.61 (d, 1 H, J =
7.4 Hz), 7.04–7.10 (m, 1 H), 7.31 (s, 5 H), 8.14 (s, 1 H).
13C NMR (CDCl3, 50 MHz): d = 52.81, 54.95, 127.12, 128.55,
128.90, 135.95, 160.38, 171.33.
N-Formyl-L-Leucine tert-Butyl Ester (4h):
The crude oil was purified by column chromatography on silica gel
(EtOAc/petroleum ether, 30:70); Rf 0.25; yield: 90%; yellow oil;
[a]D –49.8 (c = 2, EtOH).
IR (KBr): n = 1744, 1666 cm–1.
MS (EI): m/z = 193 (M+.), 162.
1H NMR (CDCl3, 200 MHz): d = 0.85 (d, 6 H, J = 6.0 Hz), 1.37 (s,
9 H), 1.41–1.63 (m, 3 H), 4.45–4.56 (m, 1 H), 6.62 (d, 1 H, J = 7.4
Hz), 8.10 (s, 1 H).
HRMS (EI): m/z found 193.0683, calc. for C10H11NO3 193.0739.
N-Formyl-L-Phenylalanine Methyl Ester (4m):
The crude oil was purified by column chromatography on silica gel
(CH2Cl2/MeOH, 97:3); Rf 0.33; yield: 96%; yellow oil; [a]D 84.9 (c
= 1, CH2Cl2).
13C NMR (CDCl3, 50 MHz): d = 21.75, 22.61, 24.64, 27.75, 41.44,
49.75, 81.82, 160.91, 172.25.
IR (film): n = 1734, 1670 cm–1.
1H NMR (CDCl3, 200 MHz): d = 2.95–3.15 (m, 2 H), 3.65 (s, 3 H),
4.80–4.95 (m, 1 H), 6.65 (d, 1 H, J =7.4 Hz), 7.03–7.08 (m, 2 H),
7.15–7.30 (m, 3 H), 8.01 (s, 1 H).
MS (EI): m/z = 215 (M+.), 214.
HRMS (CI+, 200 eV, i-BuH, 10–5 Torr): m/z found 216.1601 (M+H)
and 160.0959 (C7H14NO3, Mac Lafferty’s rearrangement), calc. for
C11H22NO3 216.1600.
13C NMR (CDCl3, 50 MHz): d = 37.62, 51.78, 52.59, 127.09, 128.48,
129.17, 135.55, 160.78, 171.81.
IR (film): n = 1744, 1690 cm–1.
N-Formyl-L-Isoleucine Methyl Ester (4i):
MS (EI): m/z = 207 (M+.), 130, 116.
The crude oil was purified by column chromatography on silica gel
(CH2Cl2/MeOH, 99:1); Rf 0.3; yield: 99%; yellow oil; [a]D –32.25 (c
= 1, CHCl3).
HRMS (CI+, 200 eV, i-BuH, 10–5 Torr): m/z found 208.0963 (M+H),
calc. for C11H14NO3 208.0974.
1H NMR (CDCl3, 200 MHz): d = 0.81–0.89 (m, 6 H), 1.02–1.22 (m,
1 H), 1.27–1.45 (m, 1 H), 1.75–1.82 (m, 1 H), 3.67 (s, 3 H), 4.61 (dd,
1H, J = 4.8, 9.1 Hz), 6.50–6.65 (m, 1 H), 8.16 (s, 1 H).
13C NMR (CDCl3, 50 MHz): d = 11.30, 15.24, 24.85, 37.58, 51.98,
54.88, 161.11, 172.03.
N-Formyl-L-Phenylalanine tert-Butyl Ester (4n):
The crude oil was purified by column chromatography on silica gel
(EtOAc/petroleum ether, 30:70); Rf 0.25; yield: 96%; colorless oil.
[a]D 16.2 (c = 0.7, EtOH).

300
Papers
SYNTHESIS
1H NMR (200 MHz, CDCl3): d = 1.40 (s, 9 H), 3. 11 (d, 2 H, J =
6.0 Hz), 4.77–4.87 (m, 1 H), 6.00–6.10 (m, 1 H), 7.11–7.16 (m, 2 H),
7.21–7.30 (m, 3 H), 8.16 (s, 1 H).
(5) Yijima, C.; Hino, F.; Suda, K. Tetrahedron Lett. 1980, 21, 4725.
(6) Grundke, G.; Keese, W.; Rimpler, M. Synthesis 1987, 1115.
(7) Marchand-Brynaert, J.; Bounkhala-Khrouz, Z.; Vanlierde, H.;
Ghosez, L. Heterocycles 1990, 30, 971.
(8) Wolfe, M. S.; Dutta, D.; Aube, J. J, Org. Chem. 1997, 62, 654.
(9) Emmons, W. D. J. Am. Chem. Soc. 1957, 79, 5739.
(10) For a recent review, see: Davis, D. A.; Reddy, R. T. In Compre-
hensive Heterocyclic Chemistry II; Katritzky,A. R.; Rees, C. W.;
Scriven, E. F. V., Eds; Pergamon: London, 1996, Vol 1A, p 135.
(11) Chen, F. M. F.; Benoiton, N. L. Synthesis 1979, 709.
(12) Kisfaludy, L.; Ötvös, L. Synthesis 1987, 510.
13C NMR (CDCl3, 50 MHz): d = 27.79, 37.87, 52.24, 83.34, 126.85,
128.23, 129.37, 135.92, 160.75, 170.35.
IR (film): n = 1730, 1688 cm–1.
MS (EI): m/z = 249 (M+.), 158.
HRMS (CI+, 200 eV, i-BuH, 10–5 Torr): m/z found 250.1450 (M+H)
and 194.0855 (C10H12NO3, McLafferty’s rearrangement), calc. for
C14H20NO3 250.1443.
(13) Giesemann, G.; Ugi, I. Synthesis 1983, 788.
(14) Waki, M.; Meienhofer, J. J. Org. Chem. 1977, 42, 2019.
(15) Duczek, W.; Deutsch, J.; Vieth, S.; Niclas, H. J. Synthesis 1996,
37.
(16) Chancellor, T.; Morton, C. Synthesis 1994, 1023.
(17) Vlietstra, E. J.; Zwikker, J. W.; Nolte, R. J. M.; Drenth, W.
J. Royal Neth. Chem. Soc. 1982, 101, 460.
The authors wish to thank A. Marcualfor recording the mass spec-
tra; Dr D. Danvy (Bioprojet) is gratefully acknowledged for provid-
ing some samples of optically pure a-amino esters as well as for
helpful discussions on the use of HPLC on chiral columns.
(18) Martinez, J.; Laur, J. Synthesis 1982, 979.
(1) Bénard, D.Ph.D, Thesis, University of Rouen, France, 1986.
(2) Duhamel, P.; Bénard, D.; Plaquevent, J. C. Tetrahedron Lett.
1985, 26, 6065.
(19) Ionic rearrangement of imines to formamides under acidic con-
ditions has also been recently reported: Nongkunsarn, P.; Rams-
den, C. A. Tetrahedron 1997, 53, 3805.
(3) Duhamel, P.; Goument, B.; Plaquevent, J. C. Tetrahedron Lett.
1987, 28, 2595.
(4) Plaquevent, J. C.; Bénard, D.; Goument, B. New J. Chem. 1991,
15, 579.
(20) For a review regarding formylating agents, see: Olah, G. A.;
Ohannesian, L.; Arvanaghi, M. Chem. Rev. 1987, 87, 671.
(21) Karim, A.; Mortreux, A.; Petit, F.; Buono, G.; Peiffer, G.;
Siv, C. J. Organometal. Chem. 1986, 317, 93.