Synthesis and ring opening of methyl 2-alkyl-3-(alkyl/aryl)-1- benzoylaziridine-2-carboxylates: Synthesis of polysubstituted amino acids

Article abstract of DOI:10.1002/(sici)1099-0690(200004)2000:8<1569::aid-ejoc1569>3.0.co;2-x

A new method for the preparation of 2,2,3-trisubstituted methyl 1- benzoylaziridine-2-carboxylates is reported. These compounds have been obtained starting from α-alkyl β-amino acids by formation of the lithium dianion and reaction with iodine. The aziridines undergo ring expansion or ring opening, depending on the substituents of the aziridine ring and on the reaction conditions. Following these methods, both α-substituted α-hydroxy β-amino acids and α-substituted β-hydroxy α-amino acids have been synthesised.

Full text of DOI:10.1002/(sici)1099-0690(200004)2000:8<1569::aid-ejoc1569>3.0.co;2-x

FULL PAPER
Synthesis and Ring Opening of Methyl 2-Alkyl-3-(alkyl/aryl)-1-
benzoylaziridine-2-carboxylates: Synthesis of Polysubstituted Amino Acids
Carmela Papa[a] and Claudia Tomasini*[a]
Keywords: Aziridines / Oxazolines / Ring expansion reactions / α-Hydroxy β-amino acids / β-Hydroxy α-amino acids
A new method for the preparation of 2,2,3-trisubstituted me-
thyl 1-benzoylaziridine-2-carboxylates is reported. These
compounds have been obtained starting from α-alkyl β-
amino acids by formation of the lithium dianion and reaction
with iodine. The aziridines undergo ring expansion or ring
opening, depending on the substituents of the aziridine ring
and on the reaction conditions. Following these methods,
both α-substituted α-hydroxy β-amino acids and α-substi-
tuted β-hydroxy α-amino acids have been synthesised.
Introduction
been used in the racemic form, it is well known that β-
amino acids can be obtained in the enantiomerically pure
Non-proteogenic amino acids are constituents of biolo- form by kinetic resolution of the corresponding phenyl-
gically active compounds.[1] Among them, α-alkyl β-hy- acetylamides by reaction with enzyme PGA, which select-
droxy α-amino acids are part of molecules such as neuro- ively hydrolyse amides of α- and β-amino acids of the 
tropic lactacystin[2] and the immunosuppressive agent myri- series.[11]
ocin.[3] Furthermore, if these molecules are inserted in a
The alkylation was performed in dry THF, by formation
polypeptide structure, they have a marked effect both on of the lithium dianion of rac-1a and rac-1b with 2 equiva-
the peptide conformation and on its biological activity.[4]
lents of LiHMDS and subsequent addition of the alkylating
The synthetic methods for the preparation of α-alkyl β- agent (Scheme 1, Table 1). The reaction temperature was
hydroxy α-amino acids are still few,[5] usually utilising pro- critical in order to obtain a good chemical yield (–30 °C for
teogenic amino acids, such as alanine[6] or threonine[7] as rac-1a and –15 °C for rac-1b) and a complete anti selectiv-
starting material. We describe here a new and stereoselec- ity:[12] when the reaction was carried out at lower or higher
tive synthesis of α-alkyl β-hydroxy α-amino acids starting temperatures (i.e. –78 °C or room temperature), low yields
from α-alkyl β-amino acids, by the intermediate formation were obtained.
and ring opening of 2,2,3-trisubstituted N-benzoyl-2-(me-
thoxycarbonyl)aziridines (methyl 1-benzoylaziridine-2-
carboxylates), which have never been prepared in the past.[8]
These compounds have been obtained starting from α-alkyl
β-amino acids, by formation of the lithium dianion and re-
action with iodine. They underwent ring expansion or ring
opening, depending on the substituents of the aziridine ring
and on the reaction conditions.
Scheme 1
Results and Discussion
Table 1. Alkylation reaction of β-benzamido methyl esters 1a–b
i. Synthesis of Methyl 2-Alkyl-3-(alkyl/aryl)-1-
benzoylaziridine-2-carboxylates
Entry Substrate Product
R
RЈ
anti/syn ratio Yield (%)
1
2
3
4
5
6
7
1a
1a
1a
1a
1b
1b
1b
2a
2b
2c
2d
2e
2f
Me Me
Me Et
Ͼ 99:1
Ͼ 99:1
Ͼ 99:1
71
86
63
61
61
70
80
The anti α-alkyl β-amino acids rac-2a–g have been syn-
thesised starting from fully protected β-amino acids rac-1a
and rac-1b. These compounds have been easily obtained
from commercially available 3-aminobutanoic acid and
from 3-amino-3-phenylpropanoic acid,[9] by protection of
the amino group by Schotten–Baumann reaction and ester-
ification of the carboxy group by reaction with thionyl
chloride and methanol.[10] Although these compounds have
Me Allyl
Me Benzyl Ͼ 99:1
Ph Me
Ͼ 99:1
Ͼ 99:1
Ph Allyl
2g
Ph Benzyl Ͼ 99:1
The next step was the formation of three membered rings
starting from α-alkyl β-benzamido methyl esters rac-2a–g
by the intermediate formation of the lithium enolate of the
α-alkyl α-iodo β-benzamido derivative which spontaneously
afforded the aziridine (Equation 1).
[a]
Dipartimento di Chimica ‘‘G. Ciamician’’ –
`
Universita di Bologna
Via Selmi 2, 40126 Bologna, Italy
E-mail: tomasini@ciam.unibo.it
Eur. J. Org. Chem. 2000, 1569Ϫ1576
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0408Ϫ1569 $ 17.50ϩ.50/0
1569

C. Papa, C. Tomasini
FULL PAPER
substituents at C2 and C3 (a phenyl group and a benzyl
group, respectively) of the starting rac-2g.
The stereochemistry of cis- and trans-aziridines was es-
tablished by NOEDIFF experiments on rac-3d, rac-4a, and
rac-3f (Figure 1). Methyl trans-1-benzoyl-2-benzyl-3-
methylaziridine-2-carboxylate rac-3d showed a strong en-
hancement of the C2 benzylic hydrogens, by irradiating the
C3 methyl group, thus showing a cis relationship between
the methyl and the benzyl groups. On the other hand, rac-
4a shows an enhancement of the 2-methyl group, by irradi-
ating the C3 hydrogen, thus showing a cis relationship be-
tween the C3 hydrogen and the C2 methyl group. On the
contrary, the irradiation of signals of rac-3f showed no
NOEDIFF effects, owing to the trans relationship between
the C3 hydrogen and the C2 allylic group. The other sub-
stituents (phenyl and methoxycarbonyl groups) showed no
NOEDIFF effect, owing to their structure. On the basis of
these results, the stereochemistry of the other compounds
has been attributed by comparison of their 1H-NMR chem-
ical shifts.
The lithium dianion was obtained by reaction of rac-2a–
g with 2.2 equivalents of LiHMDS in dry THF at room
temperature. When the metalation was performed at lower
temperature (such as 0 °C or less) the reaction did not oc-
cur, probably owing to the steric hindrance at C2. The reac-
tion proceeded by the intermediate formation of the N-li-
thium anion of the 2-iodo derivative, which spontaneously
afforded the ring closure product: after reaction workup
only starting material and aziridines were obtained, without
any traces of the intermediate 2-iodo derivative. The lithium
dianion was originally treated with iodine (2.5 equiv.) at low
temperature (–15 °C to –30 °C), with the idea of syn-
thesising 2,4,4,5-tetrasubstituted oxazolines, as we previ-
ously obtained in the cyclisation of methyl 3-benzoylamino-
butanoate[10a] or methyl 3-benzoylamino-3-phenylpro-
panoate.[10b] No oxazolines were obtained in any of the re-
actions. On the contrary, the corresponding N-
benzoylaziridines rac-3a–g and rac-4a–g were synthesised in
good yields and high diastereomeric ratios (Scheme 2 and
Table 2).
Moreover, when NaHMDS was utilised instead of
LiHMDS, completely different results were obtained: in this
case the direct formation of syn-α-alkyl-α-hydroxy-β-
benzoylamino acids was observed,[13] probably by means of
the intermediate formation of 2,4,4,5-tetrasubstituted ox-
azolines, which hydrolysed during the workup.
The stereochemical outcome of the aziridine formation
was quite satisfactory: indeed the trans/cis diastereomeric
ratios ranged from 78:22 to 99:1 and the yields were always
high: a low yield was obtained only in the formation of rac-
3g (Entry 7), probably owing to the steric hindrance of both
Figure 1. Determination of the stereochemistry of aziridines 3 and
4 by means of NOEDIFF experiments performed on 3d and 4a
ii. Ring Opening of Methyl trans-2-Alkyl-1-benzoyl-3-
methylaziridine-2-carboxylates rac-3a–d
Aziridine-2-carboxylic acids are common intermediates
for the synthesis of α- and β-amino acids,[14] thus their ring
opening can afford both β-functionalised α-amino acids
and α-functionalised β-amino acids, which are all important
classes of compounds. From the opening of methyl 2-alkyl-
3-(alkyl/aryl)-1-benzoylaziridine-2-carboxylates we can ob-
tain polysubstituted α- or β-amino acids. These molecules
are part of biologically active compounds and can be intro-
duced in a polypeptide, in order to enhance their rigidity
and their resistance towards peptide hydrolysis.
N-Benzoylaziridines rac-3 and rac-4 may furnish, upon
ring opening, both α- or β-amino acids, simply by changing
the reaction conditions. Furthermore the substituents of the
aziridine ring play an importance role in the steric and regi-
Scheme 2
Table 2. Cyclisation reaction of α-alkyl β-benzamido methyl esters 2a–g, by reaction with iodine
R
Entry
RЈ
LiHMDS: t (h), T (°C)
I2: t (h), T (°C)
3/4 ratio
Yield (%)
Me
Me
Me
Me
Ph
1
2
3
4
5
6
7
Me
5, 20
5, 20
5, 20
5, 20
5, 20
5, 20
5, 20
16, –30
16, –30
16, –30
16, –30
16, –15
16, –15
16, –15
80:20
78:22
82:18
99:1
90
59
80
82
60
70
40
Et
Allyl
Benzyl
Me
Allyl
Benzyl
85:15
94:6
Ph
Ph
99:1
1570
Eur. J. Org. Chem. 2000, 1569Ϫ1576

Synthesis of Polysubstituted Amino Acids
FULL PAPER
ochemical outcome. Zwanenburg and co-workers have DMF, and acetonitrile. While the reaction in THF afforded
extensively studied the ring opening of 3-substituted azirid- only the starting material, opposite results were obtained in
ine-2-carboxylic acid esters both when the substituent is an dichloromethane and DMF (Scheme 4).
aliphatic chain[15] or an aromatic ring.[16] They have demon-
strated that aliphatically substituted aziridinecarboxylates
are much more reluctant to undergo ring opening reactions
than the corresponding 3-aryl compounds. Thus for ali-
phatically substituted aziridine-2-carboxylates, N-activation
by acylation or tosylation is a prerequisite for successful
ring opening reactions, while 3-aryl-substituted aziridine-2-
carboxylates can easily be opened as free aziridines, owing
to the presence of the phenyl group which can stabilise an
incipient carbocation. Following this behaviour, our methyl
2,3-(dialkyl/aryl)-1-benzoylaziridine-2-carboxylates afford
two different results, whether the 3-substituent was a methyl
group (a–d) or a phenyl group (e–g).
Scheme 4
When N-benzoylaziridines rac-3a–d were treated with
BF3 Et2O in chloroform, ring opening was observed
(Scheme 3): owing to BF3 catalysis, the small amount of
ethanol, which is present in commercially available chloro-
form as a stabilising agent (about 1%), reacted as a nucle-
ophile with the aziridine ring, affording an anti-α-alkyl-α-
amino-β-ethoxy methyl ester in quantitative yield.
In both reactions, water acted efficiently as an external
nucleophile, affording a single product, but the opposite re-
giochemistry was obtained. Thus in dichloromethane the β-
hydroxy α-amino acid derivative rac-6a was obtained in
good yield, while in DMF the reaction afforded the α-hy-
droxy β-amino acid derivative rac-7a in lower yield (5 equiv.
of BF3 2 H2O was needed).[20] The stereo- and regiochem-
ical outcome were confirmed by comparison of the data
with those reported in the literature.[10b,21]
On the other hand, when the ring opening of rac-3a was
performed with BF3 H2O in acetonitrile, a complex mix-
ture was obtained, as both the acetonitrile and the water
behaved as nucleophiles. Hence, when the reaction was per-
formed in the absence of water, i.e. with BF3 Et2O in ace-
tonitrile, a 89:11 regioisomeric mixture of the cis-4,5-dihy-
dro-1H-imidazoles rac-8a and rac-8b was achieved
(Scheme 5). The cis relationship among the substituents of
rac-8a and rac-8b was demonstrated by NOEDIFF experi-
ments (Figure 2). Both compounds showed a strong en-
hancement of the C3 hydrogen, by irradiating the C2 methyl
group, thus showing a cis relationship. The regiochemistry
was assigned by comparison of the chemical shifts of the
dihydroimidazole substituents: both substituents at C5 were
more shielded in rac-8a [δ ϭ 1.29 (d, 3 H), 4.50 (q, 1 H)]
than the substituents at C4 of rac-8b [δ ϭ 1.18 (d, 3 H), 4.28
(q, 1 H)], owing to the deshielding effect of the carbonyl of
the benzamido group. The methyl α to the methoxycarbonyl
group showed the opposite behaviour [rac-8a: δ ϭ 1.51; rac-
8b: δ ϭ 1.58].
Scheme 3
This reaction has already been observed by Okawa and co-
workers[17] in the ring opening of benzyl (2S)-1-benzyloxy-
carbonylaziridine-2-carboxylate and methyl (2S,3S)-1-
benzyloxycarbonyl-3-methylaziridine-2-carboxylate,
ob-
tained from serine and threonine, respectively. In the pres-
ence of a catalytic amount of BF3 Et2O and several alco-
hols, β-alkoxy α-amino acids were obtained in generally
good yields and with complete control of regioselectivity.
In our hands, by treating N-benzoylaziridines rac-3a–g with
BF3 Et2O in ethanol-containing chloroform, the exclusive
formation of the β-alkoxy α-benzamido methyl esters rac-
5a–d was observed. The regiochemistry was confirmed by
1H-NMR analysis: the signal for the hydrogen of the amide
group was a singlet, thus the amido group was in the α
position. When the ring opening of rac-3a–g with
BF3 Et2O was performed in dichloromethane (thus in the
absence of ethanol), a regioisomeric mixture of oxazolines
was obtained. It is well known that N-activated aziridines
can undergo ring expansion[18] with the formation of oxazo-
lines, which, upon mild hydrolysis, can furnish α-hydroxy β-
amino acids or β-hydroxy α-amino acids. In our case, mix-
tures of 5-(methoxycarbonyl)oxazolines and 4-(methoxy-
carbonyl)oxazolines were obtained so that other solvents
Scheme 5
The formation of these heterocycles was previously ob-
were tested, in order to achieve stereochemical control. We served by Hiyama[22] and more recently by Zwanenburg[15]
utilised the commercially available BF3 2 H2O as Lewis in the reaction of methyl 3-alkylaziridine-2-carboxylates, for
acid, so that water could act as an external nucleophile.[19] the synthesis of α,β-diamino acids. In both cases, the reac-
The reaction was performed in THF, dichloromethane, tion afforded a single product: Zwanenburg assumed that
Eur. J. Org. Chem. 2000, 1569Ϫ1576
1571

C. Papa, C. Tomasini
FULL PAPER
exchange resin, afforded the syn-2-amino-3-hydroxy-2-
methyl-3-phenylpropanoic acid rac-11e and the anti-2-am-
ino-3-hydroxy-2-methyl-3-phenylpropanoic acid rac-12e, re-
spectively. The structures were confirmed by comparison
with data reported in the literature[5c,6,23] (Scheme 7).
Figure 2. Determination of the stereochemistry of 4,5-dihydro-1H-
imidazoles 8a and 8b by means of NOEDIFF experiments
this reaction proceeded by means of an initial attack of ace-
tonitrile at C3 of the aziridine with inversion of configura-
tion, followed by ring closure involving a reaction of the
nitrogen atom, which was originally in the three membered
ring, with the nitrilium group.
iii. Ring Opening of Methyl 2-Alkyl-1-benzoyl-3-
phenylaziridine-2-carboxylates 3e–g
Scheme 7
The behaviour of methyl 2-alkyl-1-benzoyl-3-phenylaziri-
dine-2-carboxylates rac-3e–g and rac-4e was quite different
from what we have just shown. Indeed they easily under- Conclusions
went ring expansion, regardless of the solvent and the li-
In this paper we have shown a new method for the syn-
gand of the BF3 utilised. Hence, by utilising ethanol-con-
taining chloroform or acetonitrile as solvent or BF3 H2O
as Lewis acid, no evidence of the addition products was
obtained; on the contrary the exclusive formation of methyl
trans-4-alkyl-2,5-diphenyloxazoline-4-carboxylates rac-9e–g
from trans-N-benzoylaziridines rac-3e–g and of methyl cis-
thesis of 2,2,3-trisubstituted N-benzoylaziridines. As these
molecules contain a methoxycarbonyl group, they can be
easily transformed into polysubstituted α- or β-amino acids.
The N-benzoylaziridine ring can undergo both ring opening
at C2 or C3 and ring expansion: methyl 2-alkyl-1-benzoyl-
3-methylaziridine-2-carboxylates preferentially undergo re-
gioselective ring opening at C2 or C3, depending on the
reaction conditions, while methyl 2-alkyl-1-benzoyl-3-
phenylaziridine-2-carboxylates preferentially undergo ring
expansion, with total regio- and stereocontrol and the ex-
clusive formation of methyl 4-alkyl-2,5-diphenyloxazoline-
4-carboxylates.
4-methyl-2,5-diphenyloxazoline-4-carboxylates
rac-10e
from cis-N-benzoylaziridine rac-4e was observed
(Scheme 6).
Following these methods, both α-substituted α-hydroxy
β-amino acids and α-substituted β-hydroxy α-amino acids
have been obtained. Furthermore, the synthesis of 4,5-dihy-
dro-1H-imidazoles has been obtained by ring opening of
methyl 2-alkyl-1-benzoyl-3-methylaziridine-2-carboxylates
in acetonitrile, which behaves both as solvent and as nucle-
ophile. These compounds are precursors of α-substituted
α,β-diamino acids.
Scheme 6
The aziridine exclusively underwent ring expansion,
which was totally stereo- and regioselective. Starting from
trans-N-benzoylaziridines, only trans-oxazolines are ob-
tained. The regiochemistry was confirmed by comparison
of the 1H-NMR spectra with similar compounds[22]
and with methyl 4-alkyl-2,5-diphenyloxazoline-4-carb-
oxylates[10b], and the stereochemistry was confirmed by
Experimental Section
General: NMR spectra were recorded with a Gemini Varian spec-
trometer at 300 or 200 MHz (1H NMR) and at 75 or 50 MHz (13C
NMR). – Chemical shifts are reported in δ values relative to the
solvent peak of CHCl3, set at δ ϭ 7.27. – Infrared spectra were
recorded with an FT-IR NICOLET 205 spectrometer. – Melting
NOEDIFF experiments performed on rac-9f. Indeed, the points were determined in open capillaries and are uncorrected. –
Flash chromatography was performed with Merck silica gel 60
(230–400 mesh). – THF was distilled from sodium benzophenone
ketyl.
irradiation of signals of rac-9f showed no NOEDIFF ef-
fects, owing to the trans relationship between the C3 hydro-
gen and the C2 allyl group, as we previously observed for
rac-3f.
General Method for the Alkylation of Methyl 3-Benzamidobutanoate
(rac-1a) and Methyl 3-(Benzamido)-3-phenylpropanoate (rac-1b):
The hydrolysis of oxazolines rac-9e and rac-10e with 6 
HCl in refluxing methanol followed by purification on ion- LiHMDS (4.2 mmol, 1  sol. in THF, 4.2 mL) was added to a
1572 Eur. J. Org. Chem. 2000, 1569Ϫ1576

Synthesis of Polysubstituted Amino Acids
stirred solution of ester 1 (2 mmol) in dry THF (10 mL) under C20H21NO3 (323.4): calcd. C 74.28, H 6.55, N 4.33; found C 74.20,
FULL PAPER
nitrogen at 0 °C. The mixture was stirred for 1 h, then cooled to –
60 °C for 1a and to –30 °C for 1b. The alkylating agent (see Table 1)
(3 mmol) in dry THF (10 mL) was added and the mixture was
stirred overnight, while the temperature was increased to room tem-
perature. An aqueous saturated solution of ammonium chloride
(20 mL) was added, THF was removed under reduced pressure and
replaced with dichloromethane. The organic layer was separated,
washed twice with water, dried with sodium sulfate, and concen-
trated. The compounds were obtained pure as oils or solids (if
solid, m.p. is reported) after silica gel chromatography (cyclohex-
ane/ethyl acetate 9:1 as eluent).
H 6.52, N 4.36.
rac-2g: IR (film): ν˜ ϭ 3317, 1736, 1642 cm–1. – 1H NMR (CDCl3):
δ ϭ 2.96–3.16 (m, 2 H, CH2Ph), 3.16–3.28 (m, 2 H, CHCH2Ph),
3.46 (s, 3 H, OCH3), 5.44 (dd, 1 H, J ϭ 3.6, 8.7 Hz, CHN), 7.06–
7.30 (m, 13 H, Ph), 7.92–7.98 (m, 2 H, Ph), 8.08 (d, 1 H, J ϭ
8.7 Hz, NH). – 13C NMR (CDCl3): δ ϭ 37.1, 51.8, 53.0, 126.0,
126.8, 127.0, 127.5, 128.6, 128.8, 131.6, 137.9, 140.4, 166.5, 175.4. –
C24H23NO3 (373.5): calcd. C 77.19, H 6.21, N 3.75; found C 77.23,
H 6.24, N 3.81.
General Method for the Synthesis of Methyl 2-Alkyl-3-(alkyl/aryl)-
1-benzoylaziridine-2-carboxylates
trans-rac-3
and
cis-rac-4:
rac-2a: M. p. 71–73 °C. – IR (film): ν˜ ϭ 3353, 1733, 1638 cm–1. –
1H NMR (CDCl3): δ ϭ 1.25 (d, 6 H, J ϭ 7.0 Hz, CH3CHN ϩ
CH3CHCO), 2.74 (dq, 1 H, J ϭ 3.8, 7.0 Hz, CH3CHCO), 3.72 (s,
3 H, OCH3), 4.33–4.45 (m, 1 H, CHN), 7.21 (d, 1 H, J ϭ 8.3 Hz,
NH), 7.35–7.52 (m, 3 H, Ph), 7.79–7.83 (m, 2 H, Ph). – 13C NMR
(CDCl3): δ ϭ 14.6, 19.0, 43.5, 47.2, 51.5, 126.6, 128.1, 131.0, 134.3,
166.5, 175.9. – C13H17NO3 (235.3): calcd. C 66.36, H 7.28, N 5.95;
found C 66.31, H 7.22, N 5.99.
LiHMDS (5.5 mmol, 1  sol. in THF, 5.5 mL) was added to a
stirred solution of α-alkyl β-benzamido methyl esters rac-2a–g
(2.5 mmol) in dry THF (10 mL) under nitrogen at room temper-
ature. The mixture was stirred for 5 h at room temperature, then
cooled to the temperature reported in Table 2, and iodine was ad-
ded (6 mmol, 1.52 g) in dry THF (10 mL). The mixture was stirred
overnight while the temperature reached room temperature, then
an aqueous saturated solution of ammonium chloride was added,
THF was removed under reduced pressure and replaced with ethyl
acetate. The organic layer was separated, washed twice with an
aqueous saturated solution of sodium thiosulfate, twice with water,
dried with sodium sulfate, and the solvent was removed under re-
duced pressure. The residue was purified by silica gel chromato-
graphy (cyclohexane/ethyl acetate 9:1 as eluent).
rac-2b: IR (film): ν˜ ϭ 3319, 1736, 1643 cm–1. – 1H NMR (CDCl3):
δ ϭ 0.85 (t, 3 H, J ϭ 6.9 Hz, CH2CH3), 1.14 (d, 3 H, J ϭ 7.0 Hz,
CH3CHN), 1.43–1.62 (m, 2 H, CH2CH3), 2.42 (ddd, 1 H, J ϭ 4.0,
6.5, 8.8 Hz, CHCH2CH3), 3.62 (s, 3 H, OCH3), 4.31–4.42 (m, 1 H,
CHN), 7.18–7.41 (m, 3 H, Ph), 7.58–7.77 (m, 2 H, Ph). – 13C NMR
(CDCl3): δ ϭ 11.7, 19.6, 23.3, 45.3, 51.2, 51.3, 126.6, 128.2, 131.0,
134.2, 166.3, 176.0. – C14H19NO3 (249.3): calcd. C 67.45, H 7.68,
N 5.62; found C 67.47, H 7.70, N 5.59.
rac-3a: IR (film): ν˜ ϭ 1738, 1685 cm–1. – H NMR (CDCl3): δ ϭ
1
1.34 (d, 3 H, J ϭ 5.7 Hz, CH3CHN), 1.56 (s, 3 H, CH3CCO2CH3),
3.09 (q, 1 H, J ϭ 5.7 Hz, CHN), 3.37 (s, 3 H, OCH3), 7.31–7.43
(m, 3 H, Ph), 7.69–7.78 (m, 2 H, Ph). – 13C NMR (CDCl3): δ ϭ
13.4, 14.0, 42.2, 45.7, 52.1, 127.9, 128.1, 128.5, 132.1, 133.6, 169.7,
176.4. – C13H15NO3 (233.3): calcd. C 66.94, H 6.48, N 6.00; found
C 66.98, H 6.44, N 5.95.
rac-2c: IR (film): ν˜ ϭ 3264, 1733, 1636 cm–1. – 1H NMR (CDCl3):
δ ϭ 1.16 (d, 3 H, J ϭ 6.9 Hz, CHNCH3), 2.13–2.41 (m, 2 H,
CH2CHϭCH2), 2.53–2.66 (m, 1 H, CHCHN), 3.62 (s, 3 H, OCH3),
4.28–4.48 (m, 1 H, CHN), 4.85–5.05 (m, 2 H, CH2CHϭCH2),
5.53–5.78 (m, 1 H, CH2CHϭCH2), 7.05–7.37 (m, 4 H, NH ϩ Ph),
7.58–7.70 (m, 2 H, Ph). – 13C NMR (CDCl3): δ ϭ 19.5, 34.2, 45.4,
49.4, 51.4, 117.2, 126.6, 128.2, 131.1, 134.2, 166.2, 175.2. –
C15H19NO3 (261.3): calcd. C 68.94, H 7.33, N 5.62; found C 68.89,
H 7.37, N 5.68.
rac-4a: IR (film): ν˜ ϭ 1747, 1678 cm–1. – H NMR (CDCl3): δ ϭ
1
1.29 (s, 3 H, CH3CCO2CH3), 1.36 (d, 3 H, J ϭ 5.8 Hz, CH3CHN),
2.78 (q, 1 H, J ϭ 5.8 Hz, CHN), 3.83 (s, 3 H, OCH3), 7.32–7.58
(m, 3 H, Ph), 8.01–8.10 (m, 2 H, Ph). – 13C NMR (CDCl3): δ ϭ
13.6, 17.8, 42.5, 48.4, 52.6, 128.4, 132.8, 133.7, 169.4, 176.9. –
C13H15NO3 (233.3): calcd. C 66.94, H 6.48, N 6.00; found C 66.91,
H 6.50, N 5.99.
rac-2d: M.p. 111–113 °C. – IR (film): ν˜ ϭ 3351, 1733, 1635 cm–1. –
1H NMR (CDCl3): δ ϭ 1.23 (d, 3 H, J ϭ 6.9 Hz, CHNCH3), 2.84–
3.06 (m, 3 H, CHCH2Ph), 3.61 (s, 3 H, OCH3), 4.43–4.55 (m, 1 H,
CHN), 7.13–7.58 (m, 9 H, NH ϩ Ph), 7.81–7.88 (m, 2 H, Ph). –
13C NMR (CDCl3): δ ϭ 19.7, 36.1, 45.5, 51.1, 51.8, 126.4, 126.7,
128.1, 128.6, 131.2, 134.3, 138.1, 166.4, 175.3. – C19H21NO3
(311.4): calcd. C 73.29, H 6.80, N 4.50; found C 73.34, H 6.89,
N 4.52.
rac-3b: IR (film): ν˜ ϭ 1734, 1684 cm–1. – H NMR (CDCl3): δ ϭ
1
1.10 (t, 3 H, J ϭ 7.4 Hz, CH2CH3), 1.45 (d, 3 H, J ϭ 5.8 Hz,
CH3CHN), 1.75 (dq, 1 H, J ϭ 7.4, 14.3 Hz, CHHCH3), 2.25 (dq,
1 H, J ϭ 7.0, 14.3 Hz, CHHCH3), 3.21 (q, 1 H, J ϭ 5.8 Hz, CHN),
3.48 (s, 3 H, OCH3), 7.31–7.58 (m, 3 H, Ph), 7.75–7.86 (m, 2 H,
Ph). – 13C NMR (CDCl3): δ 10.1, 13.7, 22.2, 43.0, 49.8, 52.0, 128.2,
132.2, 133.7, 169.4, 176.5. – C14H17NO3 (247.3): calcd. C 68.00, H
6.93, N 5.66; found C 68.06, H 6.95, N 5.71.
rac-2e: IR (film): ν˜ ϭ 3419, 1735, 1638 cm–1. – 1H NMR (CDCl3):
δ ϭ 1.37 (d, 3 H, J ϭ 7.1 Hz, CHCH3), 3.11 (dq, 1 H, J ϭ 4.7,
7.1 Hz, CHCH3), 3.61 (s, 1 H, OCH3), 5.39 (dd, 1 H, J ϭ 4.8,
9.0 Hz, CHN), 7.18–7.56 (m, 9 H, NH ϩ Ph), 7.82–7.92 (m, 2 H,
Ph). – 13C NMR (CDCl3): δ ϭ 29.6, 44.6, 51.9, 55.4, 126.1, 127.0,
127.5, 128.6, 131.6, 134.2, 140.5, 166.8, 176.3. – C18H19NO3
(297.4): calcd. C 72.71, H 6.44, N 4.71; found C 72.66, H 6.49,
N 4.74.
rac-4b: IR (film): ν˜ ϭ 1734, 1684 cm–1. – H NMR (CDCl3): δ ϭ
1
0.78 (t, 3 H, J ϭ 7.4 Hz, CH2CH3), 1.35 (d, 3 H, J ϭ 5.7 Hz,
CH3CHN), 1.62 (q, 2 H, J ϭ 7.4 Hz, CH2CH3), 2.80 (q, 1 H, J ϭ
5.7 Hz, CHN), 3.82 (s, 3 H, OCH3), 7.31–7.58 (m, 3 H, Ph), 8.02–
8.15 (m, 2 H, Ph). – 13C NMR (CDCl3): δ 10.4, 13.9, 25.7, 40.1,
52.0, 52.2, 128.3, 132.7, 133.9, 169.4, 176.4. – C14H17NO3 (247.3):
calcd. C 68.00, H 6.93, N 5.66; found C 67.95, H 6.99, N 5.68.
1
rac-2f: IR (film): ν˜ ϭ 3320, 1733, 1635 cm–1. – H NMR (CDCl3):
δ ϭ 2.28–2.56 (m, 2 H, CH2CHϭCH2), 3.02–3.12 (m, 1 H,
CHCHN), 3.53 (s, 3 H, OCH3), 5.02–5.14 (m, 2 H, CH2CHϭCH2), rac-3c: IR (film): ν˜ ϭ 1735, 1683 cm–1. – H NMR (CDCl3): δ ϭ
1
5.48 (dd, 2 H, J ϭ 4.9, 8.8 Hz, CHN), 5.69–5.86 (m, 1 H, CH2CHϭ
1.48 (d, 3 H, J ϭ 5.8 Hz, CHNCH3), 2.50 (dd, 1 H, J ϭ 6.6,
CH2). – 13C NMR (CDCl3): δ ϭ 35.1, 50.6, 51.8, 53.5, 118.1, 126.0, 15.2 Hz, CHHCHϭCH2), 3.06 (dd, 1 H, J ϭ 6.4, 15.2 Hz,
127.0, 127.5, 128.1, 131.7, 133.9, 134.0, 140.5, 166.6, 175.4. – CHHCHϭCH2), 3.28 (q, 1 H, J ϭ 5.8 Hz, CHN), 3.50 (s, 3 H,
Eur. J. Org. Chem. 2000, 1569Ϫ1576
1573

C. Papa, C. Tomasini
FULL PAPER
OCH3), 5.11–5.29 (m, 2 H, CH2CHϭCH2), 5.62–6.06 (m, 1 H, rac-5a: 88% yield. – IR (film): ν˜ ϭ 3417, 1739, 1652 cm–1. – 1H
CH2CHϭCH2), 7.31–7.55 (m, 3 H, Ph), 7.85–7.98 (m, 2 H, Ph). – NMR (CDCl3 ): δ ϭ 1.18 (t, 3 H, J ϭ 6.5 Hz, CH3CH2O ), 1.26
13C NMR (CDCl3): δ ϭ 14.5, 33.9, 43.4, 48.6, 52.8, 118.5, 128.8, (d, 3 H, J ϭ 5.8 Hz, CH3CHO), 1.74 (s, 3 H, CH3CN), 3.48 (dq,
129.5, 132.9, 133.5, 169.8, 176.7. – C15H17NO3 (259.3): calcd. C
69.48, H 6.61, N 5.40; found C 69.52, H 6.66, N 5.37.
1 H, J ϭ 6.5, 12 Hz, CH3CHHO), 3.67 (dq, 1 H, J ϭ 6.5, 12.0 Hz,
CH3CHHO), 3.78 (s, 3 H, OCH3), 3.92 (q, 1 H, J ϭ 5.8 Hz, CHN),
7.08 (s, 1 H, NH), 7.30–7.60 (m, 3 H, Ph), 7.70–7.85 (m, 2 H, Ph). –
13C NMR (CDCl3): δ ϭ 15.1, 15.5, 20.2, 52.5, 63.8, 65.5, 78.1,
126.9, 128.5, 131.4, 134.8, 166.9, 172.4. – C15H21NO4 (279.3):
calcd. C 64.50, H 7.58, N 5.01; found C 64.55, H 7.63, N 5.08.
1
rac-4c: IR (film): ν˜ ϭ 1735, 1683 cm–1. – H NMR (CDCl3): δ ϭ
1.38 (d, 3 H, J ϭ 5.7 Hz, CHNCH3), 2.39–2.44 (m, 2 H, CH2CHϭ
CH2), 2.86 (q, 1 H, J ϭ 5.7 Hz, CHN), 3.82 (s, 3 H, OCH3), 4.78–
4.92 (m, 2 H, CH2CHϭCH2), 5.29–5.55 (m, 1 H, CH2CHϭCH2),
7.31–7.55 (m, 3 H, Ph), 8.00–8.08 (m, 2 H, Ph). – 13C NMR
(CDCl3): δ ϭ 14.3, 36.8, 40.7, 48.6, 52.8, 119.7, 128.9, 129.5, 133.3,
133.5, 169.8, 176.7. – C15H17NO3 (259.3): calcd. C 69.48, H 6.61,
N 5.40; found C 69.54, H 6.57, N 5.37.
rac-5b: 92% yield. – IR (film): ν˜ ϭ 3413, 1734, 1669 cm–1. – 1H
NMR (CDCl3 ): δ ϭ 0.80 (t, 3 H, J ϭ 7.5 Hz, CCH2CH3), 1.06 (t,
3 H, J ϭ 6.6 Hz, OCH2CH3), 1.31 (d, 3 H, J ϭ 6.8 Hz, CH3CHO),
1.90–2.15 (m, 1 H, CCHHCH3), 2.42–2.63 (m, 1 H, C–CHH–CH3),
3.31–3.45 (m, 1 H, OCHHCH3), 3.52–3.64 (m, 1 H, OCHHCH3),
3.82 (s, 3 H, OCH3), 4.32 (q, 1 H, J ϭ 6.8 Hz, CH3CHO), 7.21 (s,
1 H, NH), 7.40- 7.63 (m, 3 H, Ph), 7.80–7.98 (m, 2 H, Ph). – 13C
NMR (CDCl3): δ ϭ 8.5, 15.5, 24.4, 29.7, 52.7, 64.0, 65.7, 78.4,
126.9, 128.6, 131.4, 135.0, 167.2, 172.2. – C16H23NO4 (293.4):
calcd. C 65.51, H 7.90, N 4.77; found C 65.58, H 7.84, N 4.79.
1
rac-3d: IR (film): ν˜ ϭ 1734, 1676 cm–1. – H NMR (CDCl3): δ ϭ
1.53 (d, 3 H, J ϭ 5.9 Hz, CH3CHN), 3.20 (d, 1 H, J ϭ 15.6 Hz,
CHHPh), 3.39 (q, 1 H, J ϭ 5.9 Hz, CHN), 3.46 (s, 3 H, OCH3),
3.58 (d, 1 H, J ϭ 15.6 Hz, CHHPh), 7.15–7.58 (m, 8 H, Ph), 7.65–
7.80 (m, 2 H, Ph). – 13C NMR (CDCl3): δ ϭ 14.6, 34.1, 43.4, 49.2,
52.3, 126.4, 126.8, 128.2, 128.8, 129.3, 132.3, 132.7, 136.8, 169.3,
176.6. – C19H19NO3 (309.4): calcd. C 73.77, H 6.19, N 4.53; found
C 73.82, H 6.12, N 4.55.
rac-5c: 90% yield. – IR (film): ν˜ ϭ 3417, 1734, 1669 cm–1. – 1H
NMR (CDCl3 ): δ ϭ 1.09 (t, 3 H, J ϭ 6.6 Hz, OCH2CH3), 1.31 (d,
3 H, J ϭ 6.6 Hz, CH3CHO), 2.82 (dd, 1 H, J ϭ 6.9, 13.8 Hz,
CHHCHϭCH2), 3.28 (dd, 1 H, J ϭ 8.1, 13.8 Hz, CHHCHϭCH2),
3.35–3.48 (m, 1 H, OCHHCH3), 3.55–3.65 (m, 1 H, OCHHCH3),
3.81 (s, 3 H, OCH3), 4.28 (q, 1 H, J ϭ 6.6 Hz, CH3CHO), 4.95–
5.13 (m, 2 H, CHHCHϭCH2), 5.60–5.68 (m, 1 H, CHHCHϭCH2),
7.35 (s, 1 H, NH), 7.40–7.58 (m, 3 H, Ph), 7.68–7.85 (m, 2 H, Ph). –
13C NMR (CDCl3): δ ϭ 15.4, 35.8, 52.6, 65.6, 68.3, 76.4, 118.8,
126.8, 128.5, 131.4, 132.4, 135.2, 166.6, 172.2. – C17H23NO4
(305.4): calcd. C 66.86, H 7.59, N 4.59; found C 66.90, H 7.60,
N 4.63.
1
rac-3e: IR (film): ν˜ ϭ 1736, 1684 cm–1. – H NMR (CDCl3): δ ϭ
1.42 (s, 3 H, CH3CN), 3.57 (s, 3 H, OCH3), 4.32 (s, 1 H, CHN),
7.25–7.56 (m, 8 H, Ph), 7.82–7.95 (m, 2 H, Ph). – 13C NMR
(CDCl3): δ ϭ 14.2, 21.0, 29.7, 49.3, 52.6, 60.4, 127.8, 128.3, 128.5,
132.6, 133.2, 133.6, 143.7, 169.2, 176.4. – C18H17NO3 (295.3):
calcd. C 73.20, H 5.80, N 4.74; found C 73.27, H 5.79, N 4.77.
1
rac-4e: IR (film): ν˜ ϭ 1736, 1684 cm–1. – H NMR (CDCl3): δ ϭ
1.49 (s, 3 H, CH3CN), 3.51 (s, 3 H, OCH3), 3.78 (s, 1 H, CHN),
7.25–7.56 (m, 8 H, Ph), 7.82–7.95 (m, 2 H, Ph). – 13C NMR
(CDCl3): δ ϭ 14.0, 21.0, 48.5, 52.6, 60.4, 127.8, 128.3, 128.5, 132.6,
133.2, 133.6, 143.7, 169.2, 176.4. – C18H17NO3 (295.3): calcd. C
73.20, H 5.80, N 4.74; found C 73.27, H 5.79, N 4.77.
rac-5d: 90% yield. – IR (film): ν˜ ϭ 3412, 1727, 1651 cm–1. – 1H
NMR (CDCl3): δ ϭ 1.06 (t, 3 H, J ϭ 6.9 Hz, OCH2CH3), 1.46 (d,
3 H, J ϭ 6.6 Hz, CH3CHO), 3.27–3.48 (m, 2 H, OCHHCH3
ϩ
CHHPh), 3.52–3.64 (m, 1 H, OCHHCH3), 3.74–3.85 (m, 1 H,
CHHPh), 3.87 (s, 3 H, OCH3), 4.55 (q, 1 H, J ϭ 6.6 Hz,
CH3CHO), 6.98–7.24 (m, 6 H, NH ϩ Ph), 7.30–7.55 (m, 3 H, Ph),
7.60–7.78 (m, 2 H, Ph). – 13C NMR (CDCl3): δ ϭ 15.5, 15.8, 36.7,
52.5, 65.7, 69.9, 76.0, 126.7, 128.1, 128.3, 128.5, 128.7, 129.7, 131.3,
136.1, 167.2, 171.7. – C21H25NO4 (355.4): calcd. C 70.96, H 7.09,
N 3.94; found C 70.99, H 7.04, N 3.89.
1
rac-3f: IR (film): ν˜ ϭ 1737, 1680 cm–1. – H NMR (CDCl3): δ ϭ
2.38 (dd, 1 H, J ϭ 7.12 Hz, CHHCHϭCH2), 2.65 (dd, 1 H, J ϭ
9.1 Hz, CHHCHϭCH2), 3.65 (s, 3 H, OCH3), 4.41 (s, 1 H, CHN),
4.72–5.02 (m, 2 H, CH2CHϭCH2), 5.55–5.79 (m, 1 H, CH2CHϭ
CH2), 7.22–7.63 (m, 10 H, Ph), 7.85–7.98 (m, 2 H, Ph). – 13C NMR
(CDCl3): δ ϭ 32.1, 49.9, 50.7, 52.5, 118.1, 127.9, 128.4, 128.5,
128.6, 132.3, 132.6, 132.9, 133.3, 168.7, 176.0. – C20H19NO3
(321.4): calcd. C 74.75, H 5.96, N 4.36; found C 74.81, H 6.00,
N 4.40.
Ring Opening of Methyl trans-1-Benzoyl-2,3-dimethylaziridine-2-
carboxylate rac-3a with BF3 2H2O in CH2Cl2. – Synthesis of Methyl
anti-2-Benzamido-3-hydroxy-2-methyl-3-phenylpropanoate rac-6a: A
solution of aziridine 3a (0.22 mmol, 50 mg) and BF3 2 H2O
(0.66 mmol, 0.016 mL) in dichloromethane (5 mL) was stirred at
room temperature for 16 h. The reaction mixture was then diluted
with dichloromethane, washed twice with a 1  aqueous solution
of Na2CO3, dried with sodium sulfate, and concentrated. The prod-
uct 6a was obtained pure as an oil after silica gel chromatography
(cyclohexane/ethyl acetate 9:1 as eluent) in 90% yield. – IR (film)
1
rac-3g: IR (film): ν˜ ϭ 1744, 1671 cm–1. – H NMR (CDCl3): δ ϭ
3.10 (AB, 2 H, J ϭ 15.0 Hz, CH2Ph), 3.61 (s, 3 H, OCH3), 4.46 (s,
1 H, CHN), 7.01–7.52 (m, 8 H, Ph), 7.62–7.77 (m, 2 H, Ph). – 13C
NMR (CDCl3): δ ϭ 32.9, 50.5, 51.8, 52.5, 126.4, 128.1, 128.3,
128.5, 128.7, 129.4, 132.5, 133.5, 136.6, 168.8, 176.1. – C15H17NO3
(371.4): calcd. C 77.61, H 5.70, N 3.77; found C 77.65, H 5.73,
N 3.79.
1
ν˜ ϭ 3395, 1734, 1653, 1522 cm–1. – H NMR (CDCl3): δ ϭ 1.12
(d, 3 H, J ϭ 6.4 Hz, CH3CHO), 1.74 (s, 3 H, CH3CN), 3.86 (s, 3
H, OCH3), 4.21 (dq, 1 H, J ϭ 6.4, 10.1 Hz, CHO), 5.28 (d, 1 H,
J ϭ 10.1 Hz, OH), 7.35–7.65 (m, 4 H, NHϩPh), 7.75–7.85 (m, 2
H, Ph). – 13C NMR (CDCl3): δ ϭ 18.9, 20.2, 53.3, 59.6, 65.7, 71.2,
127.1, 128.7, 132.1, 167.8, 178.9. – C13H17NO4 (251.3): calcd. C
62.14, H 6.82, N 5.57; found C 62.11, H 6.84, N 5.53.
Ring Opening of Methyl trans-2-Alkyl-1-benzoyl-3-methylaziridine-
2-carboxylates rac-3a–d with BF3/Et2O in CHCl3. – Synthesis of
Methyl 2-Alkyl 2-benzamido-3-ethoxybutanoates rac-5a–d: A solu-
tion of aziridine rac-3a–d (0.2 mmol) and BF3 Et2O (0.6 mmol,
0.076 mL) in chloroform (5 mL) was stirred at room temperature
for 1.5 h. Then the reaction mixture was diluted with dichlorome-
thane, washed twice with water, dried with sodium sulfate, and con- Ring Opening of Methyl trans-1-Benzoyl-2,3-dimethylaziridine-2-
centrated. The product rac-5 was obtained pure as an oil after silica
gel chromatography (cyclohexane/ethyl acetate 9:1 as eluent).
carboxylate rac-3a with BF3 2 H2O in DMF. – Synthesis of Methyl
anti-3-Benzamido-2-hydroxy-2-methyl-3-phenylpropanoate rac-7a:
1574
Eur. J. Org. Chem. 2000, 1569Ϫ1576

Synthesis of Polysubstituted Amino Acids
A solution of aziridine rac-3a (0.22 mmol, 50 mg) and BF3 2H2O 1 H, CHO), 7.20–7.60 (m, 8 H, Ph), 8.05–8.15 (m, 2 H, Ph). – 13C
FULL PAPER
(1.1 mmol, 0.027 mL) in N,N-dimethylformamide (5 mL) was
stirred at room temperature for 16 h. Then the reaction mixture
was diluted with dichloromethane, washed twice with water, dried
with sodium sulfate and concentrated. The product rac-7a was ob-
tained pure as an oil after silica gel chromatography (cyclohexane/
ethyl acetate 9:1 as eluent) in 75% yield. – IR (film) ν˜ ϭ 3360, 1743,
1638 cm–1. – 1H NMR (C6D6 ): δ ϭ 1.01 (d, J ϭ 7.0 Hz, 3 H,
CH3CHN), 1.38 (s, 3 H, CH3CN), 3.18 (s, 3 H, OCH3), 4.83 (dq,
1 H, J ϭ 7.0, 10.0 Hz, CHN), 6.33 (d, J ϭ 10.0 Hz, NH), 6.91–
7.50 (m, 3 H, Ph), 7.65–7.88 (m, 2 H, Ph). – 13C NMR (CDCl3):
δ ϭ 16.1, 23.7, 30.3, 50.3, 53.2, 77.2, 126.8, 127.0, 128.0, 128.6,
131.5, 131.6, 134.5, 167.1, 176.2. – C13H17NO4 (251.3): calcd. C
62.14, H 6.82, N 5.57; found C 62.18, H 6.79, N 5.58.
NMR (CDCl3 ): δ ϭ 26.0, 51.8, 79.9, 90.1, 125.8, 128.1, 128.4,
128.7, 131.9, 136.1, 164.8, 174.4. – C13H15NO3 (233.3): calcd. C
66.94, H 6.48, N 6.00; found C 66.99, H 6.53, N 5.95.
rac-9f: 98% yield. – IR (film) ν˜ ϭ 1732, 1652 cm–1. – 1H NMR
(CDCl3 ): δ ϭ 2.17 (ABX, 2 H, J ϭ 6.9, 7.5, 13.9 Hz, CH2CHϭ
CH2), 3.85 (s, 3 H, OCH3), 4.81–4.96 (m, 2 H, CH2CHϭCH2),
5.51–5.66 (m, 1 H, CH2CHϭCH2), 6.01 (s, 1 H, CHO), 7.31–7.60
(m, 8 H, Ph), 8.08–8.15 (m, 2 H, Ph). – 13C NMR (CDCl3 ): δ ϭ
40.8, 52.7, 81.1, 85.7, 118.5, 126.6, 128.1, 128.4, 128.7, 131.9, 132.4,
135.6, 164.0, 173.8. – C15H17NO3 (259.3): calcd. C 69.48, H 6.61,
N 5.40; found C 69.54, H 6.66, N 5.38.
rac-9g: 98% yield. – IR (film) ν˜ ϭ 1727, 1654 cm–1. – 1H NMR
(CDCl3 ): δ ϭ 2.52 (d, 1 H, J ϭ 13.6 Hz, CHHPh), 2.68 (d, 1 H,
J ϭ 13.6 Hz, CHHPh), 3.69 (s, 3 H, OCH3), 5.97 (s, 1 H, CHO),
7.30–7.60 (m, 13 H, Ph), 8.07–8.12 (m, 2 H, Ph). – 13C NMR
(CDCl3): δ ϭ 42.9, 52.5, 81.9, 86.6, 126.6, 126.7, 127.2, 127.9,
128.2, 128.4, 128.7, 128.8, 130.2, 131.9, 135.5, 136.1, 163.8, 174.0. –
C19H19NO3 (309.4): calcd. C 73.77, H 6.19, N 4.53; found C 73.74,
H 6.20, N 4.50.
Ring Opening of Methyl trans-1-Benzoyl-2,3-dimethylaziridine-2-
carboxylate rac-3a with BF3 E t2O in CH3CN. – Synthesis of
Methyl cis-2,4,5-Trimethyl-4,5-dihydro-1H-imidazole-4-carboxylate
rac-8a and of Methyl cis-2,4,5-Trimethyl-4,5-dihydro-1H-imidazole-
5-carboxylate rac-8b: A solution of aziridine 3a (0.22 mmol, 50 mg)
and BF3 Et2O (0.66 mmol, 0.016 mL) in acetonitrile (5 mL) was
stirred at room temperature for 16 h. Then the solvent was removed
and replaced with dichloromethane, the mixture was washed twice
with a 1  aqueous solution of Na2CO3, dried with sodium sulfate,
and concentrated. The products rac-8a and rac-8b were obtained
pure as an oil after silica gel chromatography (cyclohexane/ethyl
acetate 9:1 as eluent) in 80% and 10% yield.
Hydrolysis of Methyl trans-4-Methyl-2,5-diphenyloxazoline-4-carb-
oxylate rac-9e. – Synthesis of syn-2-Amino-3-hydroxy-2-methyl-3-
phenylpropanoic Acid rac-11e: A solution of oxazoline rac-9e
(0.21 mmol, 50 mg) in methanol (1 mL) and 6  HCl (5 mL) was
heated at reflux for 15 h, then cooled and concentrated under re-
duced pressure, before water (5 mL) was added. The mixture was
adsorbed on cation exchange resin. The resin was then washed with
water until the washing came out neutral, then with 2  aqueous
NH4OH to recover the amino acid rac-11e in 85% yield. – M.p.
rac-8a: IR (film) ν˜ ϭ 1734, 1684, 1624 cm–1. – 1H NMR (CDCl3 ):
δ ϭ 1.29 (d, 3 H, J ϭ 6.6 Hz, CH3CHN), 1.51 (s, 3 H, CH3CN),
1.80 (s, 3 H, CH3CϭN), 3.78 (s, 3 H, OCH3), 4.50 (q, 3 H, J ϭ
6.6.Hz, CH3CHN), 7.32–7.58 (m, 5 H, Ph). – 13C NMR (CDCl3):
δ ϭ 15.8, 24.4, 25.0, 52.3, 64.5, 75.3, 128.4, 128.5, 131.0, 131.5,
158.2, 168.1, 172.2 – C15H18N2O2 (274.3): calcd. C 65.68, H 6.61,
N 10.21; found C 65.73, H 6.64, N 10.25.
1
195–198 °C (dec.). – H NMR (D2O): δ ϭ 1.29 (s, 3 H, CH3CN),
5.10 (s, 1 H, CHO), 7.30–7.45 (m, 5 H, Ph). – 13C NMR (D2O):
δ ϭ 18.4, 65.3, 74.7, 127.4, 129.2, 129.7, 137.9, 161.2.
Hydrolysis of Methyl cis-4-Methyl-2,5-diphenyloxazoline-4-carb-
oxylate rac-10e. – Synthesis of anti-2-Amino-3-hydroxy-2-methyl-3-
phenylpropanoic Acid rac-12e: For the procedure see hydrolysis of
rac-9e: 80% yield. M.p. 202–205 °C (dec.); ref.[6] m.p. 204–206 °C
rac-8b: IR (film) ν˜ ϭ 1734, 1669, 1634 cm–1. – 1H NMR (CDCl3 ):
δ ϭ 1.18 (d, 3 H, J ϭ 6.6 Hz, CH3CHN), 1.58 (s, 3 H, CH3CN),
1.99 (s, 3 H, CH3CϭN), 3.79 (s, 3 H, OCH3), 4.28 (q, 3 H, J ϭ
6.6.Hz, CH3CHN), 7.32–7.58 (m, 5 H, Ph). – 13C NMR (CDCl3):
δ ϭ 15.3, 19.2, 24.7, 29.7, 52.3, 64.7, 74.7, 127.0, 127.6, 128.6,
131.5, 136.0, 157.9, 168.5, 172.0 – C15H18N2O2 (274.3): calcd. C
65.68, H 6.61, N 10.21; found C 65.73, H 6.64, N 10.25.
1
(dec.). – H NMR (D2O): δ ϭ 1.55 (s, 3 H, CH3CN), 5.00 (s, 1 H,
CHO), 7.28–7.45 (m, 5 H, Ph). – 13C NMR (D2O): δ ϭ 20.4, 65.8,
75.6, 127.7, 129.4, 129.9, 139.7, 160.4.
Ring Opening of Methyl trans-2-Alkyl-1-benzoyl-3-phenylaziridine-
2-carboxylates rac-3e–g and Methyl cis-1-Benzoyl-2-methyl-3-
phenylaziridine-2-carboxylate rac-4e with BF3 Et2O in CHCl3. –
Synthesis of Methyl trans-4-Alkyl-2,5-diphenyloxazoline-2-carb-
oxylates rac-9e–g and Methyl cis-4-Methyl-2,5-diphenyloxazoline-2-
carboxylate rac-10e: A solution of aziridine (0.2 mmol) and
BF3 Et2O (0.6 mmol, 0.076 mL) in chloroform (5 mL) was stirred
at room temperature for 1.5 h. The reaction mixture was then di-
luted with dichloromethane, washed twice with water, dried with
sodium sulfate, and concentrated. The product was obtained pure
as an oil after silica gel chromatography (cyclohexane/ethyl acetate
9:1 as eluent).
Acknowledgments
This work was supported in part by M.U.R.S.T. Cofin Ј98 (Roma)
and by University of Bologna (funds for Selected Research Topics).
[1]
For general reviews see:[1a] R. M. Williams, Synthesis of Optic-
[1b]
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[1c]
R. O. Duthaler, Tetrahedron 1994, 50, 1539–1650. –
M.
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See for example:
[2]
[2a]
J. S. Panek, C. E. Masse, Angew. Chem.
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–1
rac-9e: 95% yield. – IR (film) ν ϭ 1734, 1652 cm . – 1H NMR
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Int. Ed. 1999, 38, 1093–1095. –
Reichard, J. Am. Chem. Soc. 1998, 120, 2330–2336. –
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(CDCl3 ): δ ϭ 1.10 (s, 3 H, CH3CN), 3.87 (s, 3 H, OCH3), 6.12 (s,
1 H, CHO), 7.20–7.60 (m, 8 H, Ph), 8.05–8.15 (m, 2 H, Ph). – 13C
NMR (CDCl3 ): δ ϭ 22.2, 52.9, 77.7, 85.7, 126.1, 127.1, 128.2,
128.3, 128.6, 131.8, 136.1, 163.8, 174.4. – C13H15NO3 (233.3):
calcd. C 66.94, H 6.48, N 6.00; found C 66.99, H 6.53, N 5.95.
E. J.
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1
rac-10e: 94% yield. – IR (film) ν˜ ϭ 1736, 1653 cm–1. – H NMR
[3]
(CDCl3 ): δ ϭ 1.81 (s, 3 H, CH3CN), 3.17 (s, 3 H, OCH3), 5.42 (s,
Eur. J. Org. Chem. 2000, 1569Ϫ1576
1575

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[O99465]
1576
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