Synthesis and decarboxylation of N-acyl-α-triphenylphosphonio-α-amino acids: a new synthesis of α-(N-acylamino)alkyltriphenylphosphonium salts

Article abstract of DOI:10.1016/j.tetlet.2008.01.051

4-Phosphoranylidene-5(4H)-oxazolones 1 undergo hydrolysis in THF in the presence of HBF₄ at room temperature to give N-acyl-α-triphenylphosphonioglycines 3 (R² = H) in very good yields. 4-Alkyl-4-triphenylphosphonio-5(4H)-oxazolones

Full text of DOI:10.1016/j.tetlet.2008.01.051

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 1801–1803
Synthesis and decarboxylation of
N-acyl-a-triphenylphosphonio-a-amino acids: a new synthesis
of a-(N-acylamino)alkyltriphenylphosphonium salts
Roman Mazurkiewicz *, Agnieszka Paz´dzierniok-Holewa, Mirosława Grymel
Department of Organic and Bioorganic Chemistry and Biotechnology, Silesian University of Technology, Krzywoustego 4, PL 44-100 Gliwice, Poland
Received 20 November 2007; revised 22 December 2007; accepted 10 January 2008
Available online 15 January 2008
Abstract
4-Phosphoranylidene-5(4H)-oxazolones 1 undergo hydrolysis in THF in the presence of HBF4 at room temperature to give N-acyl-a-
triphenylphosphonioglycines 3 (R2 = H) in very good yields. 4-Alkyl-4-triphenylphosphonio-5(4H)-oxazolones 2 react with water in
CH2Cl2/THF solution without any acidic catalyst at 0–5 °C in a few days yielding N-acyl-a-triphenylphosphonio-a-amino acids 3
(R2 = Me) or a-(N-acylamino)alkyltriphenylphosphonium salt 4 (R2 = CH2OMe). a-Triphenylphosphonio-a-amino acids 3, on heating
up to 105–115 °C under reduced pressure (5 mmHg) or on treatment with diisopropylethylamine in CH2Cl2 at 20 °C undergo decarboxy-
lation to give the corresponding a-(N-acylamino)alkyltriphenylphosphonium salts 4, usually in very good yields.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: 4-Triphenylphosphoranylidene-5(4H)-oxazolone hydrolysis; 4-Alkyl-4-triphenylphosphonio-5(4H)-oxazolone hydrolysis; N-Acyl-a-triphenyl-
phosphonio-a-amino acids; Decarboxylation; a-(N-Acylamino)alkyltriphenylphosphonium salts
a-Amino acid derivatives with a Ca–P bond have
attracted significant attention from organic chemists due
R2
N
O
O
to their many important applications in organic synthesis.1
In 1996, we described a simple synthesis of 4-triphenyl-
phosphoranylidene-5(4H)-oxazolones (TPO) 1 from N-acyl-
glycines2 and effective methods for their 4-C alkylation to
4-alkyl-4-triphenylphosphonio-5(4H)-oxazolones (ATPO)
23 (Scheme 1).
Ph3P
Ph3P
R2Y
Y
O
O
Y = I
N
R1
R1
2
1
B
A
B
HBF4
H2O
In the present Letter, we report methods for the hydro-
lysis of TPO 1 and ATPO 2 to hitherto unknown N-acyl-a-
triphenylphosphonio-a-amino acids (PAA) 3, which were
subsequently decarboxylated to a-(N-acylamino)alkyltri-
phenylphosphonium salts (APS) 4 (Scheme 1).
a-(N-Acylamino)alkyltriphenylphosphonium salts 4 are
valuable bifunctional organic reagents used for syntheses
of heterocyclic systems, including oxazole,4–6 thiazole,5–7
imidazole,7,8 tetrazole9,10 and quinazoline derivatives.10
O R2 PPh3
H2O
R1
O
N
X
H
OH
C
3
D
(
20 o
i
-Pr)2EtN
C
5 mmHg
105 -115 o
C
O
PPh3
1
R
N
R2
X
+
CO2
H
4
X = BF4 or I
*
Corresponding author. Tel.: +48 32 2371724; fax: +48 32 2371549.
Scheme 1.
E-mail address: Roman.Mazurkiewicz@polsl.pl (R. Mazurkiewicz).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.01.051

1802
R. Mazurkiewicz et al. / Tetrahedron Letters 49 (2008) 1801–1803
Table 1
The synthesis of N-acyl-a-triphenylphosphonio-a-amino acids 3
TPO 1 or ATPO 2
Reaction conditions
Solvent Temperature (°C)
PAA 3
Yield (%)
R1
R2
Y
Procedure
Time
Mp (°C)
1a
1b
1c
2a
2b
t-Bu
Ph
Me
t-Bu
Ph
—
—
—
Me
Me
—
—
—
I
A
A
A
B
B
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2/THF
CH2Cl2/THF
20
20
20
0–5
0–5
10 min
10 min
10 min
7 d
3a
3b
3c
3d
3e
99
93
97
71
65
114.0–115.0
144.0–145.0
95.0–97.0
117.5–118.0
122.0–123.0
I
6 d
Table 2
The synthesis of a-(N-acylamino)alkyltriphenylphosphonium salts 4
ATPO 2 or PAA 3
Reaction conditions
APS 4
R1
R2
X
Procedure
Temperature (°C)
Time
Yield (%)
Mp (°C)
3a
3a
3b
3b
3c
3c
3d
3d
3e
2c
t-Bu
t-Bu
Ph
Ph
Me
H
H
H
H
H
H
Me
Me
BF4
BF4
BF4
BF4
BF4
BF4
I
I
I
I
C
D
C
D
C
D
C
D
D
B
105
20
105
20
105
20
115
20
4.5 h
24 h
2.5 h
24 h
1 h
12 d
1 h
19 h
18 h
8 d
4a
4a
4b
4b
4c
4c
4d
4d
4e
4f
99
99
94
98
99
89
36
72
90
69
183.0–183.5
192.0–192.5
168.5–169.0
Me
t-Bu
t-Bu
Ph
178.5–179.5
166.5–167.0
146.5–148.0
Me
MeOCH2
20
0–5
t-Bu
They have also been applied as a-amidoalkylating
Another milder procedure for the decarboxylation of
a-triphenylphosphonio-a-amino acids 3 involves their
decarboxylation in CH2Cl2 at 20 °C, in the presence of a
catalytic amount of diisopropylethylamine (Table 2,
Procedure D).20
agents.11,12 The most frequently used method for the
synthesis of APS consists in the alkylation of triphenyl-
phosphine with N-(a-chloroalkyl)amides,4,9–11,13,14 N-(a-
hydroxyalkyl)amides7,14,15 or N-(a-alkoxyalkyl)amides.15
Unfortunately, these methods are applicable mainly for
the synthesis of N-acylaminomethyltriphenylphosphonium
salts (4, R2 = H).
The structures of N-acyl-a-triphenylphosphonio-a-
amino acids 3a–e and a-(N-acylaminomethyl)triphenyl-
phosphonium salts 4a–f were confirmed by spectroscopy
1
Phosphoranylidene-5(4H)-oxazolones 1, dissolved in
CH2Cl2, react smoothly with an equimolar amount of
water in the presence of tetrafluoroboric acid at room
temperature to give N-acyl-a-triphenylphosphonioglycine
tetrafluoroborates 3 in excellent yields in 10 min (Table 1,
Procedure A).17 The obtained a-triphenylphosphoniogly-
cine derivatives 3a–c are stable crystalline compounds.
Phosphonium salts 2 undergo hydrolysis in CH2Cl2/
THF solution without any acidic catalyst at 0–5 °C in a
few days; however, only in the case of phosphonium salts
2a and 2b were we able to isolate relatively stable a-tri-
phenylphosphonio-a-amino acids 3d and 3e (Table 1, Pro-
cedure B).18 In the case of phosphonium salt 2c, we
obtained directly the corresponding a-(N-acylamino)alkyl-
triphenylphosphonium salt 4f as the product of hydrolysis
and consecutive decarboxylation. (Table 2).
(IR, H and 13C NMR); in the case of new compounds
satisfactory elemental analyses were obtained.16
In conclusion, the hydrolysis of 4-triphenylphospho-
ranylidene-5(4H)-oxazolones 1 and 4-alkyl-4-triphenylphos-
phonio-5(4H)-oxazolones 2 provides hitherto unknown
N-acyl-a-triphenylphosphonio-a-amino acids 3. Their
decarboxylation offers an effective and convenient method
for the synthesis of a-(N-acylamino)alkyltriphenylphos-
phonium salts 4, including a-substituted derivatives
(R2 ¼ H), which are difficult to obtain by other synthetic
methods.
References and notes
1. Mazurkiewicz, R.; Kuz´nik, A.; Grymel, M.; Paz´dzierniok-Holewa, A.
Arkivoc 2007, VI, 193–216.
The a-triphenylphosphonio-a-amino acids 3a–d, when
heated up to 105–115 °C under reduced pressure
(5 mmHg), underwent decarboxylation to the correspond-
ing a-(N-acylamino)alkyltriphenylphosphonium salts 4a–d,
usually in very good yields. Only in the case of com-
pound 4d the yield of decarboxylation was poor (Table 2,
Procedure C).19
2. Mazurkiewicz, R.; Pierwocha, A. Monatsh. Chem. 1996, 127, 219–
225.
3. Mazurkiewicz, R.; Pierwocha, A. Monatsh. Chem. 1997, 128, 893–
900.
4. Drach, B. S.; Dolgushina, I. Yu.; Sinitsa, A. D. Zh. Obshch. Khim.
1975, 45, 1251–1255.
5. Brovarets, V. S.; Lobanov, O. P.; Drach, B. S. Zh. Obshch. Khim.
1983, 53, 660–664.

R. Mazurkiewicz et al. / Tetrahedron Letters 49 (2008) 1801–1803
1803
6. Brovarets, V. S.; Lobanov, O. P.; Kisilenko, A. A.; Kalinin, V. N.;
Drach, B. S. Zh. Obshch. Khim. 1986, 56, 1492–1504.
7. Brovarets, V. S.; Lobanov, O. P.; Vinogradova, T. K.; Drach, B. S.
Zh. Obshch. Khim. 1984, 54, 288–301.
8. Smolii, O. B.; Brovarets, V. S.; Pirozhenko, V. V.; Drach, B. S. Zh.
Obshch. Khim. 1988, 58, 2635–2643.
9. Smolii, O. B.; Brovarets, V. S.; Drach, B. S. Zh. Obshch. Khim. 1986,
56, 2802–2803.
10. Smolii, O. B.; Brovarets, V. S.; Pirozhenko, V. V.; Drach, B. S. Zh.
Obshch. Khim. 1988, 58, 2465–2471.
1H NMR (300 MHz, CDCl3): d 8.30 (br dd, J = 5.8 Hz, J = 5.8 Hz,
1H), 7.56 (m, 20H), 5.30 (dd, J = 6.1 Hz, J = 3.1 Hz, 2H); 13C NMR
(75 MHz, CDCl3):
d 168.3, 135.2 (d, J = 3.0 Hz), 134.1 (d,
J = 10.0 Hz), 132.2, 131.6, 130.1 (d, J = 12.6 Hz), 128.5, 127.2,
117.1 (d, J = 84.1 Hz), 37.8 (d, J = 56.9 Hz); Anal. Calcd for
C26H23BF4NOP: C, 64.62; H, 4.80; P, 6.41. Found: C, 64.25; H,
4.72; P, 6.52. Compound 4c: IR (CH2Cl2, cmꢀ1): 3364br, 1688vs,
1524vs;1H NMR (300 MHz, CDCl3): d 7.77 (m, 16H), 5.06 (dd,
J = 6.4 Hz, J = 3.4 Hz, 2H), 1.81 (d, J = 1.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3):
d 171.9, 135.3 (d, J = 3.0 Hz), 134.0 (d,
11. Drach, B. S.; Sviridov, E. P.; Kirsanov, A. V. Zh. Obshch. Khim. 1972,
42, 953–954.
12. Kozhushko, B. N.; Gumenyuk, A. V.; Palichuk, Yu. A.; Shokol, V.
A. Zh. Obshch. Khim. 1977, 47, 333–339.
13. Shokol, V. A.; Kozushko, B. N.; Gumenyuk, A. V. Zh. Obshch. Khim.
1977, 47, 1110–1118.
14. Kasukhin, L. F.; Brovarets, V. S.; Smolii, O. B.; Kurg, V. V.; Budnik,
L. V.; Drach, B. S. Zh. Obshch. Khim. 1991, 61, 2679–2684.
15. Petersen, H.; Reuther, W. Justus Liebigs Ann. Chem. 1972, 766, 58–
72.
J = 10.1 Hz), 130.3 (d, J = 12.5 Hz), 117.0 (d, J = 84.1 Hz), 37.1 (d,
J = 57.9 Hz), 21.9; Anal. Calcd for C21H21BF4NOP: C, 59.89; H,
5.03; P, 7.35. Found: C, 59.86; H, 4.76; P, 7.46. Compound 4d: IR
(CH2Cl2, cmꢀ1): 3230br, 1652vs, 1512vs; 1H NMR (300 MHz,
CDCl3): d 8.72 (dd, J = 6.7 Hz, J = 6.7 Hz, 1H), 7.76 (m, 15H),
6.18 (m, 1H); 1.76 (dd, J = 17.4 Hz, J = 7.3 Hz, 3H), 0.94 (s, 9H); 13C
NMR (75 MHz, CDCl3): d 179.3 (d, J = 2.2 Hz), 134.7 (d, J =
9.4 Hz), 134.4 (d, J = 3.0 Hz), 129.8 (d, J = 12.2 Hz), 118.8 (d,
J = 82.4 Hz), 44.6 (d, J = 51.9 Hz), 38.5, 27.3, 17.4 (d, J = 4.8 Hz);
Anal. Calcd for C25H29INOP: C, 58.04; H, 5.65; N, 2.71; P, 5.99.
Found: C, 58.04; H, 5.64; N, 2.73; P, 5.86. Compund 4e: IR (CH2Cl2,
cmꢀ1): 3210br, 1656vs, 1528vs;1H NMR (300 MHz, CDCl3): d 9.53
(dd, J = 7.6 Hz, J = 4.3 Hz, 1H), 7.63 (m, 20H), 6.33 (m, 1H); 1.93
(dd, J = 17.5 Hz, J = 7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3): d
167.8 (d, J = 2.2 Hz), 134.6 (d, J = 9.5 Hz), 134.6 (d, J = 3.5 Hz),
132.2, 131.5, 129.9 (d, J = 12.4 Hz), 128.3, 127.8, 118.4 (d, J =
82.1 Hz), 45.8 (d, J = 51.3 Hz), 17.6 (d, J = 4.9 Hz); Anal. Calcd for
16. Spectral and analytical data for compound: 3a: IR (CH3CN, cmꢀ1):
3350br, 1764vs, 1732vs, 1672vs, 1516s; 1H NMR (300 MHz, CD3CN):
d 7.77 (m, 15H), 7.45 (dd, J = 7.5 Hz, J = 2.7 Hz, 1H), 6.35 (dd,
J = 14.7 Hz, J = 8.1 Hz, 1H), 0.88 (s, 9H); 13C NMR (75 MHz,
CD3CN): d 179.6 (d, J = 2.0 Hz), 166.4 (d, J = 7.0 Hz), 136.1 (d,
J = 3.0 Hz), 135.8 (d, J = 10.0 Hz), 130.9 (d, J = 13.0 Hz), 119.2 (d,
J = 85.5 Hz), 54.0 (d, J = 62.4 Hz), 39.1, 26.9; Anal. Calcd for
C25H27BF4NO3P: C, 59.19; H, 5.36; P, 6.11. Found: C, 59.07; H, 5.78;
P, 5.80. Compound 3b: IR (CH3CN, cmꢀ1): 3320br, 1768vs, 1740vs,
C
27H25INOP: C, 60.35; H, 4.69; N, 2.61; P, 5.76. Found: C, 60.25; H,
4.59; N, 2.59; P, 5.92. Compound 4f: IR (CH2Cl2, cmꢀ1): 3220br,
1656vs, 1512vs; 1H NMR (300 MHz, CDCl3): d 8.75 (dd, J = 7.5 Hz,
J = 4.8 Hz, 1H), 7.77 (m, 15H), 6.27 (m, 1H), 4.12 (ddd, J = 9.6 Hz,
J = 9.6 Hz, J = 9.6 Hz, 1H), 3.77 (ddd, J = 31.8 Hz, J =
9.0 Hz,J = 5.1 Hz, 1H), 2.67 (s, 3H), 0.91 (s, 9H); 13C NMR
(75 MHz, CDCl3): d 179.9 (d, J = 1.8 Hz), 135.2 (d, J = 9.7 Hz),
134.0 (d, J = 3.0 Hz), 129.4 (d, J = 12.7 Hz), 119.1 (d, J = 83.0 Hz),
67.8 (d, J = 2.5 Hz), 57.8, 49.3 (d, J = 51.2 Hz), 38.6, 27.3; Anal.
Calcd for C26H31INO2P: C, 57.05; H, 5.71; N, 2.56; P, 5.66. Found: C,
57.09; H, 5.56; N, 2.51; P, 5.46.
1676vs, 1526s; 1H NMR (300 MHz, CD3CN):
d 8.11 (br d,
J = 7.8 Hz, 1H), 7.64 (m, 20H), 6.74 (dd, J = 14.7 Hz, J = 8.7 Hz,
1H); 13C NMR (75 MHz, CD3CN): d 168.5 (d, J = 2.6 Hz), 166.2 (d,
J = 7.0 Hz), 136.3 (d, J = 3.0 Hz), 135.7 (d, J = 10.0 Hz), 133.8,
132.7, 131.0 (d, J = 12.6 Hz), 129.6, 128.4, 118.5 (d, J = 85.1 Hz), 54.0
(d, J = 61.0 Hz); Anal. Calcd for C27H23BF4NO3P: C, 61.51; H, 4.40;
P, 5.87. Found: C, 61.58; H, 4.29; P, 5.57. Compound 3c: IR
(CH3CN, cmꢀ1): 3324br, 1760vs, 1744vs, 1700vs, 1520s; 1H NMR
(300 MHz, CD3CN): d 7.80 (m, 15H), 7.63 (br d, J = 8.7 Hz, 1H),
6.63 (dd, J = 14.7 Hz, J = 9.0 Hz, 1H), 1.76 (s, 3H); 13C NMR
(75 MHz, CD3CN): d 171.4 (d, J = 2.6 Hz), 166.3 (d, J = 7.1 Hz),
136.4 (d, J = 3.0 Hz), 135.6 (d, J = 9.6 Hz), 131.0 (d, J = 12.5 Hz),
118.0 (d, J = 85.6 Hz), 52.9 (d, J = 60.4 Hz), 26.2; Anal. Calcd for
C22H21BF4NO3PꢁTHF: C, 58.12; H, 5.44; P, 5.76. Found: C, 58.52;
H, 5.53; P, 5.65. Compound 3d: IR (Nujol, cmꢀ1): 3340br, 1740vs, br,
1672vs, 1516s; 1H NMR (300 MHz, CD3CN): d 7.72 (m, 15H), 7.52
(br d, J = 7.5 Hz, 1H), 1.91 (d, J = 18.9 Hz, 3H), 0.80 (s, 9H); 13C
NMR (75 MHz, CD3CN): d 179.4, 169.8 (d, J = 11.1 Hz), 135.7 (d,
J = 9.1 Hz), 134.6 (d, J = 3.0 Hz), 129.6 (d, J = 12.6 Hz), 120.5 (d,
J = 83.1 Hz), 64.5 (d, J = 61.0 Hz), 38.0, 26.5, 26.0; Anal. Calcd for
17. Procedure A: To a stirred solution of 4-triphenylphosphoranylidene-
5(4H)-oxazolone 1 (5 mmol) in CH2Cl2 (7.5 cm3), water (0.09 cm3,
5 mmol) and an ethereal solution of tetrafluoroboric acid (54%,
0.70 cm3, 5.1 mmol) were added. After 10 min, the solvent was
evaporated under reduced pressure and the residue was crystallized
from THF (3a and 3c) or chloroform (3b).
18. Procedure B: To a suspension of 4-alkyl-4-triphenylphosphonio-
5(4H)-oxazolone 2 (5 mmol) in CH2Cl2 (6.75 cm3 for 2a and 2c or
13.5 cm3 for 2b), a solution of water (0.22 cm3, 12.5 mmol) in THF
(6.75 cm3) was added and the mixture was stirred at 0–5 °C for the
time given in Table 1 or 2. The reaction mixture was diluted with
CH2Cl2, (ꢂ25 cm3) dried over MgSO4 and the solvent was evaporated
under reduced pressure. Crude 3d, 3e or 4f were dissolved in CH2Cl2
and the pure product was precipitated by the addition of diethyl ether.
19. Procedure C: N-Acyl-a-triphenylphosphonio-a-amino acid 3 was
heated at 105–115 °C under reduced pressure (5 mmHg) for the time
given in Table 2. The residue was crystallized from ethyl acetate (4c)
or purified by dissolving in CH2Cl2 and precipitating by means of
addition of diethyl ether (4a–b).
20. Procedure D: To a stirred suspension of N-acyl-a-triphenylphos-
phonio-a-amino acid 3 (4 mmol) in CH2Cl2 (32 cm3), diisopropyleth-
ylamine (0.14 cm3, 0.8 mmol) was added. The reaction mixture was
left for the time given in Table 2 at room temperature and then the
solvent was evaporated under reduced pressure. The residue was
purified by crystallization from a mixture of toluene and methanol
(6:1, v/v; 4a–c) or ethyl acetate (4d) or by dissolving in CH2Cl2 and
precipitating by means of addition of diethyl ether (4e).
C
26H29INO3P: C, 55.63; H, 5.21; N, 2.50; P, 5.52. Found: C, 55.52; H,
5.30; N, 2.52; P, 5.17. Compound 3e: IR (Nujol, cmꢀ1): 3336br,
1728vs, br, 1660vs, 1520s; 1H NMR (300 MHz, CD3CN): d 8.23 (br d,
J = 5.4 Hz, 1H), 7.60 (m, 20H), 2.00 (d, J = 18.3 Hz, 3H); 13C NMR
(75 MHz, CD3CN):
d 170.3 (d, J = 10.6 Hz), 168.8, 136.5 (d,
J = 9.1 Hz), 135.5 (d, J = 3.1 Hz), 133.8, 132.7, 130.4 (d,
J = 12.8 Hz), 129.4, 128.5, 120.7 (d, J = 82.1 Hz), 65.8 (d,
J = 59.8 Hz), 26.4; Anal. Calcd for C28H25INO3P: C, 57.84; H,
4.33; N, 2.41; P, 5.33. Found: C, 57.67; H, 4.39; N, 2.45; P, 5.43.
Compound 4a: IR (CH2Cl2, cmꢀ1): 3384br, 1668vs, 1520vs; 1H NMR
(300 MHz, CDCl3): d 7.73 (m, 16H), 5.08 (dd, J = 6.0 Hz, J = 3.3 Hz,
2H), 0.92 (s, 9H); 13C NMR (75 MHz, CDCl3): d 180.3, 135.0 (d,
J = 3.0 Hz), 134.2 (d, J = 9.6 Hz), 130.1 (d, J = 12.6 Hz), 117.7 (d,
J = 84.1 Hz), 38.5, 37.6 (d, J = 56.9 Hz), 26.8; Anal. Calcd for
C
24H27BF4NOP: C, 62.22; H, 5.87; P, 6.69. Found: C, 61.83; H, 5.77;
P, 6.42. Compound 4b: IR (CH2Cl2, cmꢀ1): 3368br, 1664vs, 1528vs;