Three new in situ syntheses of N-acyl-α-triphenylphosphonioglycinates

Article abstract of DOI:10.1007/s00706-003-0166-2

N-Acyl-α-hydroxyglycinates were transformed into N-acyl-α- triphenylphosphonioglycinates by (i) phosphorylation with Ph₃PBr ₂ in the presence of Et₃N or (ii) in reaction with DCC and Ph₃P·HBF₄ in the

Full text of DOI:10.1007/s00706-003-0166-2

Monatshefte f€ur Chemie 135, 799–806 (2004)
DOI 10.1007/s00706-003-0166-2
Three New in situ Syntheses of N-Acyl-
a-triphenylphosphonioglycinates
ꢀ
´
Roman Mazurkiewicz , Mirosława Grymel, and Anna Kuznik
Department of Organic and Bioorganic Chemistry and Biotechnology, The Silesian
University of Technology, PL 44-100 Gliwice, Poland
Received November 24, 2003; accepted (revised) December 5, 2003
Published online April 26, 2004 # Springer-Verlag 2004
Summary. N-Acyl-ꢀ-hydroxyglycinates were transformed into N-acyl-ꢀ-triphenylphosphoniogly-
cinates by (i) phosphorylation with Ph3PBr2 in the presence of Et3N or (ii) in reaction with DCC and
Ph3P ꢁ HBF4 in the presence of catalytic amounts of Ph3P as well as (iii) by a new kind of Mitsunobu
reaction with Ph3P ꢁ HBF4 as a nucleophile conjugated acid. The N-acyl-ꢀ-triphenylphosphoniogly-
cinates can be effectively used without isolation for a nucleophilic displacement of the triphenylphos-
phonium group to obtain corresponding ꢀ-substituted ꢀ-amino acid derivatives.
Keywords. N-Acyl-ꢀ-triphenylphosphonioglycinates; Cationic glycine equivalent; Glycine ꢀ-func-
tionalization; Nucleophilic substitution; ꢀ-Heterosubstituted glycine derivatives.
Introduction
Since the pioneering works of Ben-Ishai et al. [1] on the first synthetic equivalents of
glycine ꢀ-cation, the important problem of synthesizing ꢀ-amino acids by reactions
of glycine ꢀ-cation equivalents with nucleophiles has drawn the attention of many
authors [1–4]. Many electrophilic glycine equivalents have been introduced for the
synthesis of ꢀ-amino acids in the course of the last 25 years [1–20]. With the advent
of peptide-derived chemotherapeutics, the synthesis of both, natural non-protein-
ogenic and unnatural ꢀ-amino acids by the functionalization of the glycine ꢀ-posi-
tion with nucleophiles has attracted significant attention of organic chemists [2].
In our previous paper [21] we described a convenient and effective synthesis of
crystalline stable N-acyl-ꢀ-triphenylphosphonioglycinates 2 from 4-triphenylphos-
phoranylidene-5(4H)-oxazolones 1 and a simple method of displacing their triphe-
nylphosphonium group by a variety of oxygen, sulfur, nitrogen, and carbon
nucleophiles, demonstrating in this way that N-acyl-ꢀ-triphenylphosphoniogly-
cinates may be considered as new interesting cationic glycine equivalents [21, 22]
(Scheme 1).
ꢀ
Corresponding author. E-mail: romanm@zeus.polsl.gliwice.pl

800
R. Mazurkiewicz et al.
Scheme 1
Phosphoranylidene-5(4H)-oxazolones 1 were obtained by the phosphorylation
of 5(4H)-oxazolones with dibromotriphenylphosphorane (Ph3PBr2) in the presence
of triethylamine; 5(4H)-oxazolones being obtained in situ from the corresponding
N-acylglycine and DCC [23]. The described transformations enable an easy and
effective functionalization of the glycine ꢀ-position with heteroatom or carbon
nucleophiles. Our attempts to synthesize in this way the especially interesting N-
alkoxycarbonyl-ꢀ-triphenylphosphonioglycinates have failed, because of the
instability of the corresponding 2-alkoxy-5(4H)-oxazolones [24].
N-Acyl-ꢀ-triphenylphosphonioglycinates were obtained for the first time by
Kober and Steglich in 1983 by the photochemical bromination of N-benzoylgly-
cinates with bromine or NBS to ꢀ-bromoglycinates, followed by the displacement
of the bromide anion by triphenylphosphine [7]. The authors did not examine the
reaction of the obtained compounds with nucleophiles.
In the present paper we report three new convenient in situ syntheses of N-acyl-ꢀ-
triphenylphosphonioglycinates from easily accessible N-acyl-ꢀ-hydroxyglycinates,
which allow to synthesize also N-alkoxycarbonyl-ꢀ-triphenylphosphonioglycinates.
Results and Discussion
Syntheses of N-acyl-ꢀ-hydroxyglycinates 5 were carried out from the glyoxalic
acid methyl ester hemiacetale 4 according to the procedure described by Bernstein
[25] and Abood and Losse [26]. The latter compound was also obtained according
to Bernstein’s procedure from glyoxalic acid hydrate [25] (Scheme 2).
The following three methods for the transformation of N-acyl-ꢀ-hydroxygly-
cinates into N-acyl-ꢀ-triphenylphosphonioglycinates were developed.
The first one consists in the bromination of N-acyl-ꢀ-hydroxyglycinates with
dibromotriphenylphosphorane followed by the displacement of the bromide anion
by triphenylphosphine (Scheme 3). The second step of this method is analogous to
the method mentioned above described by Kober and Steglich [7].
Referring to the second method, we believe that the hydroxy group of N-acyl-
ꢀ-hydroxyglycinate is first activated by DCC and then replaced by triphenyl-
Scheme 2

Syntheses of N-Acyl-ꢀ-triphenylphosphonioglycinates
801
Scheme 3
Scheme 4
Scheme 5
phosphine to give the corresponding N-acyl-ꢀ-triphenylphosphonioglycinate
(Scheme 4). A small amount of free triphenylphosphine is necessary in this reac-
tion as an active nucleophile to facilitate the displacement of the activated hydroxyl
group.
The third reaction can be considered as a kind of the Mitsunobu reaction with
triphenylphosphine tetrafluoroborate as a nucleophile conjugated acid. According
to our best knowledge, the Mitsunobu reaction has not been used up to now for the
condensation of alcohols with phosphorus nucleophiles [27] (Scheme 5).
Previously, we have described a method for the isolation and purification of
crude N-acyl-ꢀ-triphenylphosphonioglycinates which consists in dissolving the
crude product in dichloromethane and precipitation of the pure phosphonium salt
with diethyl ether [21]. Our attempts to apply this method to isolate N-acyl-ꢀ-
triphenylphosphonioglycinates in all the described syntheses failed. Nevertheless,
the presence of the expected products in reaction mixtures was confirmed by IR, 1H
and 13C NMR spectroscopies. The spectral data of the synthesized compounds are
closely similar to those described earlier [21]. In all the three cases the yields of the
expected products 2 in the reaction mixtures were estimated based on the ratio of
the 1H NMR signals of the methine groups (in some cases also the methoxy group)
to the signals of all aromatic protons. The estimated yields were, in most cases,
fairly good.
We have also demonstrated further, that N-acyl-ꢀ-triphenylphosphoniogly-
cinates synthesized in situ by any one of the three methods described above can be

802
R. Mazurkiewicz et al.
Scheme 6
used without purification for the nucleophilic displacement of the triphenylphos-
phonium group by a variety of nucleophiles in order to get the corresponding ꢀ-
substituted-ꢀ-aminoacid derivatives 6 in good yields. The structure of the obtained
1
nucleophilic substitution products was confirmed by spectral data (IR, H and 13C
NMR) and satisfactory elemental analyses or, in some cases, by the results of high-
resolution mass spectrometry.
Experimental
Mps were determined in capillary tubes. IR spectra were recorded on a Zeiss Specord M 80 spectro-
photometer; the measurements were carried out in CHCl3 (0.2M) using cells of 0.075mm. 1H and 13
C
NMR spectra were recorded in CDCl3 on a Varian UNITY INOVA-300 spectrometer at operating
frequencies of 300 and 75.5MHz using TMS as an internal standard. High-resolution mass spectra
were recorded on an AMD 604 Spectrometer with ESI ionisation (MeOH, CH2Cl2, NaOAc). The yields
of isolated products 6 given were based on the N-acyl-ꢀ-hydroxyglycinates and were not optimized.
Starting Materials
Commercial grade acetonitrile, methylene chloride, THF, and triethylamine were distilled and dried over
˚
molecular sieves 4 A. Kieselgel 60 Merck (0.063–0.200mm) was used for column chromatography. The
glyoxalic acid methyl ester hemiacetale was obtained according to Bernstein’s procedure from glyoxalic
acid hydrate [25]. Synthesis of N-acyl-ꢀ-hydroxyglycinate was carried out according to the procedure
described by Bernstein [25] and Abood and Losse [26]. The other reagents were of commercial quality.
Synthesis of N-Acyl-ꢀ-triphenylphosphonioglycinates 2
Procedure A
A solution of 0.18g of Br2 (1.1mmol) in 0.5 cm3 of CH2Cl2 was added at 0–2ꢂC under Ar to a stirred
solution of 0.29g of triphenylphosphine (1.1mmol) in 5 cm3 of CH2Cl2. The pale-yellow crystals of
Ph3PBr2 precipitated almost immediately. The suspension was stirred at room temperature for 30min,
the mixture was cooled to 0–5ꢂC and then 0.15cm3 of triethylamine (0.11 g, 1.1mmol), 0.26 g of
triphenylphosphine (1.0mmol) and 1 mmol of N-acyl-ꢀ-hydroxyglycinate 5 were added with stirring.
The mixture was stirred for the time given below. The yield of 2 in the reaction mixture was estimated
1
by H NMR spectroscopy. The reaction mixture was evaporated to dryness in vacuo and the residue
was used for farther syntheses without purification.
Procedure B
To a stirred suspension of 1 mmol of N-acyl-ꢀ-hydroxyglycinate 5 in 3 cm3 of CH2Cl2, 0.21g of DCC
(1mmol), a catalytic amount of triphenylphosphine (0.026g, 0.1 mmol) and 0.70 g of triphenyl-

Syntheses of N-Acyl-ꢀ-triphenylphosphonioglycinates
803
phosphine tetrafluoroborate (2mmol) were added at room temperature. The mixture was stirred for the
1
time given below. The yield of the product in the reaction mixture was estimated by H NMR
spectroscopy. The reaction mixture was evaporated to dryness in vacuo and the residue was used
for farther syntheses without purification.
Procedure C
To a stirred suspension of 1 mmol of N-acyl-ꢀ-hydroxyglycinate 5 in 5 cm3 of THF, 0.20 cm3 of DEAD
(0.22 g, 1.25mmol), 0.29 g of triphenylphosphine (1.1mmol), and 0.38g of triphenylphosphine tetra-
fluoroborate (1.1mmol) were added at room temperature. The mixture was stirred for the time given
below. The yield of the product in the reaction mixture was estimated by 1H NMR spectroscopy. The
reaction mixture was evaporated to dryness in vacuo and the residue was used for farther syntheses
without purification.
Methyl N-benzoyl-ꢀ-triphenylphosphonioglycinate bromide (2a, C28H25BrNO3P)
1
Procedure A, 48 hrs; yield 62%; H NMR (CDCl3, 300 MHz): ꢁ ¼ 10.50 (s, br, NH), 8.00–7.20 (m,
Ph3Pꢃ, Ph), 6.74 (dd, JP–H ¼ 16.5Hz, JH–H ¼ 7.4 Hz, CH), 3.59 (s, MeO) ppm; 13C NMR (CDCl3,
75.5MHz): ꢁ ¼ 166.7 (d, J ¼ 0.5 Hz, CONH), 54.6 (d, J ¼ 58.9Hz, CHPþ), 164.8 (d, J ¼ 8.7 Hz,
COOMe), 53.2 (OMe), 118.3 (d, J ¼ 85.1Hz, Ph3P, C1), 134.4 (d, J ¼ 10.1Hz, Ph3P, C2), 129.3 (d,
J ¼ 12.8Hz, Ph3P, C3), 134.2 (d, J ¼ 0.5 Hz, Ph3P, C4), 132.6, 130.8, 127.9, 127.2 (Ph) ppm; IR
(CH2Cl2): ꢂꢀ¼ 3040, 1770, 1730, 1662 cmꢄ1
.
Methyl N-benzoyl-ꢀ-triphenylphosphonioglycinate tetrafluoroborate
(2b, C28H25BF4NO3P) [21]
Procedure B, 96 hrs; yield 71%; 1H NMR (CDCl3, 300MHz): ꢁ ¼ 9.00 (dd, JP–H ¼ 4.3 Hz,
JH–H ¼ 7.6 Hz, NH), 8.00–7.20 (m, Ph3Pꢃ, Ph), 6.59 (dd, JP–H ¼ 15.6Hz, JH–H ¼ 7.6 Hz, CH), 3.60
(s, MeO) ppm; 13C NMR (CDCl3, 75.5MHz): ꢁ ¼ 167.6 (d, J ¼ 0.5 Hz, CONH), 54.8 (d, J ¼ 59.8Hz,
CHPþ), 164.9 (d, J ¼ 7.6 Hz, COOMe), 53.7 (OMe), 118.0 (d, J ¼ 85.1Hz, Ph3P, C1), 134.5 (d,
J ¼ 10.1Hz, Ph3P, C2), 129.8 (d, J ¼ 13.1 Hz, Ph3P, C3), 134.9 (d, J ¼ 0.5 Hz, Ph3P, C4), 132.2,
130.8, 128.4, 127.2 (Ph) ppm; IR (CH2Cl2): ꢂꢀ¼ 3310, 1770, 1730, 1670 cmꢄ1
.
Methyl N-benzyloxycarbonyl-ꢀ-triphenylphosphonioglycinate tetrafluoroborate
(2c, C29H27BF4NO4P)
Procedure B, 120 hrs; yield 62%; 1H NMR (CDCl3, 300MHz): ꢁ ¼ 8.18 (dd, JP–H ¼ 13.8Hz,
JH–H ¼ 6.7 Hz, NH), 7.90–7.28 (m, Ph3Pꢃ, Ph), 6.37 (dd, JP–H ¼ 16.3Hz, JH–H ¼ 8.2 Hz, CH), 4.88
(d, J ¼ 12.2Hz, 1H, PhCH2), 4.81 (d, J ¼ 12.4Hz, 1H, PhCH2), 3.59 (s, MeO) ppm; 13C NMR (CDCl3,
75.5MHz): ꢁ ¼ 155.8 (d, J ¼ 0.5 Hz, CONH), 55.2 (d, J ¼ 59.4Hz, CHPþ), 165.1 (d, J ¼ 9.6 Hz,
COOMe), 53.9 (OMe), 117.3 (d, J ¼ 84.6Hz, Ph3P, C1), 134.4 (d, J ¼ 10.1Hz, Ph3P, C2), 129.9 (d,
J ¼ 13.1Hz, Ph3P, C3), 135.1 (d, J ¼ 0.5 Hz, Ph3P, C4), 132.5, 130.5, 128.3, 127.8 (PhCH2), 67.5
(PhCH2) ppm; IR (CH2Cl2): ꢂꢀ¼ 3310, 1772, 1725–1680 cmꢄ1
.
Procedure C, 170 hrs; yield 78%; 1H NMR (CDCl3, 300MHz): ꢁ ¼ 7.90–7.28 (m, Ph3Pꢃ, Ph), 7.10
(m, NH), 6.40 (dd, JP–H ¼ 16.5Hz, JH–H ¼ 7.8 Hz, CH), 4.85 (d, J ¼ 12.3Hz, 1H, PhCH2), 4.81 (d,
J ¼ 12.6Hz, 1H, PhCH2), 3.60 (s, MeO) ppm; 13C NMR (CDCl3, 75.5 MHz): ꢁ ¼ 155.6 (d, J ¼ 0.5 Hz,
CONH), 55.0 (d, J ¼ 58.4Hz, CHPþ), 164.7 (d, J ¼ 9.6 Hz, COOMe), 53.5 (OMe), 116.8 (d,
J ¼ 84.6Hz, Ph3P, C1), 134.1 (d, J ¼ 10.1Hz, Ph3P, C2), 129.7 (d, J ¼ 12.6Hz, Ph3P, C3), 134.0 (d,
J ¼ 0.5 Hz, Ph3P, C4), 132.2, 129.4, 128.0, 127.5 (PhCH2), 67.4 (PhCH2) ppm; IR (CH2Cl2): ꢂꢀ¼ 3320,
1780, 1750, 1738 cmꢄ1
.

804
R. Mazurkiewicz et al.
Methyl N-t-butoxycarbonyl-ꢀ-triphenylphosphonioglycinate tetrafluoroborate
(2d, C26H29BF4NO4P)
Procedure B, 24hrs; yield 79%; 1H NMR (CDCl3, 300 MHz): ꢁ ¼ 8.14 (dd, JP–H ¼ 14.2 Hz,
JH–H ¼ 7.6 Hz, NH), 7.99–7.35 (m, Ph3Pꢃ), 6.31 (dd, JP–H ¼ 16.2Hz, JH–H ¼ 8.1 Hz, CH), 3.56 (s,
MeO), 1.17 (s, t-Bu) ppm; 13C NMR (CDCl3, 75.5MHz): ꢁ ¼ 154.6 (d, J ¼ 0.5 Hz, CONH), 55.3 (d,
J ¼ 59.5Hz, CHPþ), 165.2 (d, J ¼ 9.5 Hz, COOMe), 53.4 (OMe), 117.8 (d, J ¼ 84.5Hz, Ph3P, C1),
134.5 (d, J ¼ 9.8 Hz, Ph3P, C2), 129.9 (d, J ¼ 12.8 Hz, Ph3P, C3), 135.0 (d, J ¼ 0.5 Hz, Ph3P, C4), 81.6
(Me3CO), 27.6 (Me3CO) ppm; IR (CH2Cl2): ꢂꢀ¼ 3320, 1774, 1730–1686 cmꢄ1
.
Methyl N-methoxycarbonyl-ꢀ-triphenylphosphonioglycinate tetrafluoroborate
(2e, C23H23BF4NO4P)
Procedure B, 96hrs; yield 87%; 1H NMR (CDCl3, 300 MHz): ꢁ ¼ 8.10 (dd, JP–H ¼ 13.2 Hz,
JH–H ¼ 7.1 Hz, NH), 7.88–7.38 (m, Ph3Pꢃ), 6.33 (dd, JP–H ¼ 16.5Hz, JH–H ¼ 8.4 Hz, CH), 3.60 (s,
MeO), 3.41 (s, MeO) ppm; 13C NMR (CDCl3, 75.5MHz): ꢁ ¼ 154.4 (d, J ¼ 0.5 Hz, CONH), 55.6 (d,
J ¼ 58.9Hz, CHPþ), 165.1 (d, J ¼ 9.9 Hz, COOMe), 53.9 (OMe), 117.4 (d, J ¼ 85.1Hz, Ph3P, C1),
134.6 (d, J ¼ 10.0Hz, Ph3P, C2), 130.0 (d, J ¼ 13.1Hz, Ph3P, C3), 135.2 (d, J ¼ 0.5 Hz, Ph3P, C4), 53.1
(MeO) ppm; IR (CH2Cl2): ꢂꢀ¼ 3060, 1770, 1729, 1700 cmꢄ1
.
Procedure C, 120 hrs; yield 94%; 1H NMR (CDCl3, 300 MHz): ꢁ ¼ 7.85–7.41 (m, Ph3Pꢃ and NH),
6.37 (dd, JP–H ¼ 16.6 Hz, JH–H ¼ 8.6Hz, CH), 3.61 (s, MeO), 3.40 (s, MeO) ppm; 13C NMR (CDCl3,
75.5MHz): ꢁ ¼ 156.7 (d, J ¼ 0.5 Hz, CONH), 55.4 (d, J ¼ 58.9Hz, CHPþ), 165.0 (d, J ¼ 9.6 Hz,
COOMe), 53.7 (OMe), 117.3 (d, J ¼ 84.6Hz, Ph3P, C1), 134.4 (d, J ¼ 10.1Hz, Ph3P, C2), 129.9 (d,
J ¼ 13.1Hz, Ph3P, C3), 135.0 (d, J ¼ 0.5 Hz, Ph3P, C4), 52.9 (MeO) ppm; IR (CH2Cl2): ꢂꢀ¼ 3060, 1750,
1730, 1686 cmꢄ1
.
General Procedure for Reactions of N-Acyl-ꢀ-triphenylphosphonioglycinates
2 with Heteroatom Nucleophiles
A nucleophile (2mmol) and 0.37 cm3 of DBU (0.38 g, 2.5 mmol) or 0.35cm3 of triethylamine (0.25 g,
2.5 mmol) were added to a stirred solution of the crude N-acyl-ꢀ-triphenylphosphonioglycinates 2 in
4 cm3 of acetonitrile. The mixture was stirred at room temperature for the time given below. The
solvent was removed under reduced pressure. The pure product 6 was isolated by column chromatog-
raphy on silica gel (Kieselgel 60 Merck, 0.063–0.200 mm, 45cm3) eluting with a mixture of ethyl
acetate and benzene in a volume ratio of 1:10. The product was recrystallized from benzene or from a
mixture of benzene and n-hexane.
Methyl N-benzoyl-ꢀ-t-butylthioglycinate (6a, C14H19NO3S)
Starting from 2a (procedure A) and carrying out the reaction in the presence of Et3N for 120 h 64%
yield of 6a was obtained; mp 71.0–71.5ꢂC; 1H NMR (CDCl3, 300MHz): ꢁ ¼ 7.82–7.39 (m, 5H-Ph),
6.88 (d, J ¼ 8.4 Hz, NH), 5.80 (d, J ¼ 8.7 Hz, CH), 3.80 (s, MeO), 1.45 (s, Me3CS) ppm; 13C NMR
(CDCl3, 75.5MHz): ꢁ ¼ 170.4 (CONH), 53.0, 52.6 (CHNu and MeO), 166.0 (COOMe), 133.4, 132.0,
128.6, 127.1 (Ph), 46.0 (Me3CS), 31.1 (Me3CS) ppm; IR (CH2Cl2): ꢂꢀ¼ 3440, 1740, 1660cmꢄ1
Methyl N-benzyloxycarbonyl-ꢀ-(benzotriazol-1-yl)glycinate (6b, C17H16N4O4)
.
Starting from 2c (procedure B) and carrying out the reaction in the presence of DBU for 24h 60% yield
of 6b was obtained; mp 116.5–117.5ꢂC; 1H NMR (CDCl3, 300 MHz): ꢁ ¼ 8.14–7.28 (m, 9H, C6H4N3
and Ph), 7.01 (d, J ¼ 8.4Hz, CH), 6.66 (d, J ¼ 7.8 Hz, NH), 5.17 (d, J ¼ 12.1Hz, PhCH2O), 5.04 (d,
J ¼ 12.1Hz, PhCH2O), 3.82 (s, MeO) ppm; 13C NMR (CDCl3, 75.5MHz): ꢁ ¼ 155.1 (CONH), 63.8

Syntheses of N-Acyl-ꢀ-triphenylphosphonioglycinates
805
(CHNu), 165.5 (COOMe), 53.9 (MeO), 131.9, 128.4, 128.3, 128.2 (PhCH2), 67.8 (PhCH2), 145.7,
132.1, 128.5, 124.4, 120.0, 109.9 (C6H4N3: C3a, C7a, C6, C5, C4, C7) ppm; IR (CH2Cl2): ꢂꢀ¼ 3310,
1698, 1652 cmꢄ1
.
Methyl N-benzyloxycarbonyl-ꢀ-benzylthioglycinate (6c, C18H19NO4S)
Starting from 2c (procedure B) and carrying out the reaction in the presence of Et3N for 24 h 76% yield
1
of 6c was obtained; mp 54.0–54.5ꢂC; H NMR (CDCl3, 300 MHz): ꢁ ¼ 7.40–7.19 (m, 10H, PhCH2S
and PhCH2O), 5.79 (d, br, J ¼ 8.4 Hz, NH), 5.35 (d, J ¼ 8.8 Hz, CH), 5.09 (s, 2H, PhCH2O), 3.90 (d,
1H, J ¼ 13.4Hz, PhCH2S), 3.84 (d, 1H, J ¼ 13.3Hz, PhCH2S), 3.65 (s, MeO) ppm; 13C NMR (CDCl3,
75.5MHz): ꢁ ¼ 154.5 (CONH), 55.5 (CHNu), 169.0 (COOMe), 52.8 (MeO), 135.8, 128.4, 128.1,
128.0 (PhCH2O), 67.2 (PhCH2), 136.8, 128.8, 128.4, 127.2 (PhCH2S), 35.0 (PhCH2S) ppm; IR
(CH2Cl2): ꢂꢀ¼ 3430, 1742, 1728 cmꢄ1
.
Starting from 2c (procedure C) and carrying out the reaction in the presence of Et3N for 96h 42%
yield of 6c was obtained.
Methyl N-t-butoxycarbonyl-ꢀ-(benzotriazol-1-yl)glycinate (6d, C14H18N4O4)
Starting from 2d (procedure B) and carrying out the reaction in the presence of DBU for 190 h 46% yield
of 6d was obtained; mp 117.5–118.0ꢂC; 1H NMR (CDCl3, 300 MHz): ꢁ ¼ 8.10–7.36 (m, 4H, C6H4N3),
6.98 (d, J ¼ 8.6 Hz, CH), 6.37 (d, J ¼ 7.0 Hz, NH), 3.82 (s, MeO), 1.41 (s, Me3CO) ppm; 13C NMR
(CDCl3, 75.5 MHz): ꢁ ¼ 154.1 (CONH), 63.6 (CHNu), 165.9 (COOMe), 53.9 (MeO), 81.7 (Me3CO),
28.1 (Me3CO), 145.7, 132.0, 128.2, 124.4, 120.0, 110.0 (C6H4N3: C3a, C7a, C6, C5, C4, C7) ppm; IR
(CH2Cl2): ꢂꢀ¼ 3430, 1762, 1722 cmꢄ1; MS (ESI): calcd. for C14H18N4O4Na 329.1220, found 329.1236.
Methyl N-t-butoxycarbonyl-ꢀ-benzylthioglycinate (6e, C15H21NO4S)
Starting from 2d (procedure B) and carrying out the reaction in the presence of Et3N for 190 h 45%
yield of 6e was obtained (resin); 1H NMR (CDCl3, 300 MHz): ꢁ ¼ 7.40–7.20 (m, 5H-Ph), 5.34 (d, br,
J ¼ 0.5 Hz, NH), 5.25 (d, J ¼ 8.7 Hz, CH), 3.85 (d, J ¼ 13.2 Hz, 1H, PhCH2S), 3.78 (d, J ¼ 13.5Hz, 1H,
PhCH2S), 3.62 (s, MeO), 1.36 (s, Me3CO) ppm; 13C NMR (CDCl3, 75.5MHz): ꢁ ¼ 153.9 (CONH),
55.4 (CHNu), 169.3 (COOMe), 52.8 (MeO), 80.6 (Me3CO), 28.2 (Me3CO), 137.1, 128.9, 128.5, 127.2
(PhCH2S), 35.0 (PhCH2S) ppm; IR (CH2Cl2): ꢂꢀ¼ 3435, 1718, 1745 cmꢄ1; MS (ESI): calcd. for
C15H21NO4NaS 334.1084, found 334.1102.
Methyl N-methoxycarbonyl-ꢀ-phenylthioglycinate (6f, C11H13NO4S)
Starting from 2e (procedure B) and carrying out the reaction in MeCN in the presence of Et3N for 24h
1
84% yield of 6f was obtained (resin); H NMR (CDCl3, 300MHz): ꢁ ¼ 7.55–7.28 (m, Ph), 6.64 (d,
J ¼ 8.5 Hz, NH), 5.54 (d, J ¼ 9.2 Hz, CH), 3.74 (s, MeO), 3.71 (s, MeO) ppm; 13C NMR (CDCl3,
75.5MHz): ꢁ ¼ 154.9 (CONH), 58.8 (CHNu), 168.6 (COOMe), 52.8, 52.6 (COOMe and
MeO(CO)NH), 135.5, 129.8, 129.5, 129.1 (PhS) ppm; IR (CH2Cl2): ꢂꢀ¼ 3422, 1685brcmꢄ1; MS
(ESI): calcd. for C11H13NO4NaS 278.0458, found 278.0473.
Starting from 2e (procedure C) and carrying out the reaction in MeCN in the presence of Et3N for
96h 45% yield of 6f was obtained.
Acknowledgements
The financial help of the Polish State Committee for Scientific Research (Grant No 4 T09A 026 24) is
gratefully acknowledged.

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R. Mazurkiewicz et al.: Syntheses of N-Acyl-ꢀ-triphenylphosphonioglycinates
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