New and efficient approach to the synthesis of pentacoordinate spirobicyclic phosphoranes

Article abstract of DOI:10.1039/a702813j

Pentacoordinate spirobicyclic 2-phenoxy-1,3-phenylenedioxo-1,3,2-imino(alkyl)acetoxyphosphoranes are synthesized through a new and efficient method whereby phosphorus pentachloride is displaced stepwise by catechol, an N,O-bis(trimethylsilyl)amino acid and phenol (pathway A) or catechol, phenol and an N,O-bis-(trimethylsilyl)amino acid (pathway B); this method has advantages of high yields, rapid reaction times and easy operation, which might provide a new route for the synthesis of other pentacoordinate phosphoranes.

Full text of DOI:10.1039/a702813j

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New and efficient approach to the synthesis of pentacoordinate
spirobicyclic phosphoranes
Hua Fu,a Guang-Zhong Tu,b Zhao-Long Li,a Yu-Fen Zhao*,a and
Ri-Qing Zhangb
a
Bioorganic Phosphorus Chemistry Laboratory, Department of Chemistry,
Tsinghua University, Beijing 100084, PR China
b Biomembrane and Biomembrane Engineering National Laboratory, Department of Biological
Science and Biotechnology, Tsinghua University, Beijing 100084, PR China
Pentacoordinate spirobicyclic 2-phenoxy-1,3-phenylene-
dioxo-1,3,2-imino(alkyl)acetoxyphosphoranes are syn-
thesized through a new and efficient method whereby
phosphorus pentachloride is displaced stepwise by cat-
echol, an N,O-bis(trimethylsilyl)amino acid and phenol
(pathway A) or catechol, phenol and an N,O-bis-
(trimethylsilyl)amino acid (pathway B); this method has
advantages of high yields, rapid reaction times and easy
operation, which might provide a new route for the syn-
thesis of other pentacoordinate phosphoranes.
peaks at δP Ϫ29 and Ϫ31 (diastereoisomers 2 and 2Ј) because of
the introduction of the amino acid chiral carbon atom. When 1
completely disappeared, 1 equiv. of phenol was added dropwise
O
Cl
O
P
NH
O
H
R
O
Me3SiNHCHCO2SiMe3
a–e
2a–e
Since the 1960s, much attention has been paid to pentacovalent
phosphorus compounds due to the stereochemistry and chem-
ical reactivity associated with their biologically important
phosphate esters.1,2 For example, it was postulated that five-
membered cyclic acyl phosphates could be intermediates in the
reactions of phosphoenolpyruvate esters.3,4 In our research
group, a series of N-phosphoryl amino acids have been
synthesized.5–9 Previously, it was found that N-phosphoryl
amino acids could catalyze many interesting bioorganic reac-
tions under mild conditions.10,11 For example, phosphoryl
amino acids could autocatalyze to give peptides, esters, phos-
phoryl exchanged esters and phosphoryl group migration
products—their reactivity being dependent on the amino acid
side chains. An intramolecular pentacoordinate phosphoric–
carboxylic mixed anhydride intermediate was considered as an
important transient species.10,11 In 1995, an interesting experi-
ment involving silicon chemistry was applied to trap the penta-
coordinate phosphorus moiety.12 Since Lipmann had also pro-
posed that the biosynthesis of proteins proceeded through a
mixed phosphoric–carboxylic anhydride intermediate,13 we
thought it might be significant to synthesize the stable com-
pounds. To our knowledge, the synthesis and characterization
of the pentacoordinate spirobicyclic imino(alkyl)acetoxyphos-
phoranes have not been reported. In this paper, a series of these
compounds was synthesized using phosphorus pentachloride.
Two synthetic pathways leading to the pentacoordinate
spirobicyclic2-phenoxy-1,3-phenylenedioxo-1,3,2-imino(alkyl)-
acetoxyphosphoranes† are shown in Scheme 1. Pathway A:
under a nitrogen atmosphere at 25 ЊC 1 equiv. of the N,O-
bis(trimethylsilyl)amino acid a–e14 in benzene or dichloro-
methane respectively, was added dropwise to a benzene or
dichloromethane solution of 2,2,2-trichloro-1,3,2-benzo-
dioxaphosphole15 and stirred continuously. A few minutes later,
R
+
O
Cl
Cl
O
P
O
Cl
Cl
1
HN
P
O
R
O
H
OH
O
2′a–e
O
O
HN
P
O
R
H
O
O
3′a–e
+
O
O
O
P
HN
O
R
H
O
3a–e
OH
Me3SiNHCHCO2SiMe3
a–e
R
O
O
Cl
Cl
O
O
P
O
P
Cl
Cl
Cl
4
the
2-chloro-1,3-phenylenedioxo-1,3,2-imino(alkyl)acetoxy-
1
a R = H
phosphorane 2,2Јa–e was obtained. The reaction could be traced
by 31P NMR spectroscopy. For example, the starting material 1
showed a signal at δP Ϫ26.23 which quickly changed into two
b R = CH3
c R = CH(CH3)2
d R = CH(CH3)CH2CH3
e R = CH2Ph
† IUPAC name: 2-phenoxy-2.75-spiro[1,3,2-benzodioxaphosphole-2,2Ј-
1,3,2-oxazaphospholan]-5Ј-one.
Scheme
1
Synthetic pathways to pentacoordinate spirobicyclic
imino(alkyl)acetoxyphosphorane
J. Chem. Soc., Perkin Trans. 1, 1997
2021

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into the reaction mixtures to give 3,3Јa–e quantitatively. Because
1 has a five-membered ring, reaction to form a spirobicycle
system was favored.
Pathway B: under a nitrogen atmosphere at 25 ЊC 1 equiv. of
phenol in benzene or dichloromethane was added dropwise to a
benzene or dichloromethane solution of 2,2,2-trichloro-1,3,2-
benzodioxaphosphole and stirred continuously. A few minutes
2
2′
8
8′
1
1′
6′
3
7
9
9′
7′
3′
6
12
12′
O
O
4
4′
10
10′
17′
H3C
13′
5
5
13
HN
O
O
O
11
O
P
11′ HN
P
O
O
H
CH 16
O
16′
H
H3C
18′
14
14′
15
15′
H
later, 2,2-dichloro-2-phenoxy-1,3,2-benzodioxaphosphole
4
O
CH3 CH3
was quantitatively obtained, showing one peak in the 31P NMR
spectrum at δ Ϫ34.13. Then an N,O-bis(trimethylsilyl)amino
acid a–e was added to the reaction mixture to give 3,3Јa–e.
Compounds 3,3Јa–d were crystallized from dichloromethane–
diethyl ether (1:5) while 3,3Јe was recrystallized from benzene,
to give the products, in some cases, as white solids; yields: 63–
71% (pathway A); 74–83% (pathway B).
17
18
A. Yield of 3,3Јc: 2.56 g, 74%; mp 148–150 ЊC (Found: C, 58.75;
H, 5.18; N, 4.05. C17H18NO5P requires C, 58.79; H, 5.19; N,
4.03%); δH 0.92 (d, 3 H, 17-CH3), 0.99 (d, 3 H, 18-CH3), 1.10
(m, 6 H, 17Ј- and 18Ј-CH3), 2.18 (m, 1 H, 16-CH), 2.26 (m, 1 H,
16Ј-H), 3.76 (d, 1 H, 13-NH, 2JPN H 16.19), 3.81 (d, 1 H, 13Ј-NH,
2JPN H 16.19), 3.87 (m, 1 H, 14-CH), 3.88 (m, 1 H, 14Ј-CH),
6.56–6.68 (dd, 2 H, 1,1Ј-Ph), 6.81–6.94 (m, 8 H, 2,2Ј,3,3Ј-Ph,
7,7Ј,11,11Ј-Ph), 7.07–7.13 (m, 4,4Ј-Ph, 9,9Ј-Ph) and 7.21–7.23
(m, 8,8Ј,10,10Ј-Ph); δC 16.21 (17-CH3), 16.86 (17Ј-CH3), 18.61
(18-CH3), 19.15 (18Ј-CH3), 31.04 (d, 16-CH), 31.12 (d, 16Ј-
CH), 60.45 (14-CH), 60.54 (14Ј-CH), 109.92 (d, 1-Ph), 110.08
(d, 1Ј-Ph), 111.47 (d, 4-Ph), 111.60 (d, 4Ј-Ph), 120.78
(3,3Ј,7,7Ј,11,11Ј-Ph), 123.51 (2,2Ј-Ph), 124.89, 125.10 (9,9Ј-Ph),
129.26, 129.47 (8,8Ј,10,10Ј-Ph); 142.22 (5,5Ј-Ph), 144.96 (6,6Ј-
Since the P᎐O bond of the anhydride P᎐O᎐CO moiety was
longer than expected in the pentacoordinate phosphorane,16 it
implies that this is the apical bond. Indeed, each of the com-
2
pounds 3,3Јa–e had a large JP᎐OCO-value. Because glycine has
no chiral carbon, 2a,2Јa only showed one peak in the 31P NMR
spectrum at δP Ϫ27.89, and their derivatives 3a,3Јa also showed
only one peak at δ Ϫ42.02. The anhydride POC᎐O bond is of
᎐
P
high energy,17 and consequently yields a peptide bond when the
amino group of an amino acid attacks the carboxy group of the
anhydride. Hence, the pentacoordinate imino(alkyl)acetoxy-
phosphoranes might be intermediates in protein biosynthesis
and could have potential in polypeptide synthesis. In summary,
the high yields, rapid reactions and easy availability of the start-
ing materials and reagents render this synthesis an efficient
process.
2
Ph), 152.06 (12,12Ј-Ph), 167.99, 168.17 (dd, 15,15Ј-CO-, JP–C
17.95); δP Ϫ44.64 and Ϫ44.83; m/z (FDMS) 347 (Mϩ).
Acknowledgements
This work was supported by the National Natural Science
Foundation of China, the National Science and Technology
Committee of China, the Chinese National Ministry of Educa-
tion and Tsinghua University.
Experimental
1
1
1H, 13C, H–1H COSY and H–13C COSY NMR spectra were
recorded on a Bruker AM-500 spectrometer at 500 MHz in
CDCl3 solvent with chemical shifts referenced to CDCl3
(δH = 7.24, δC = 77). J Values are given in Hz. 31P NMR spectra
were determined by a Bruker AM-200 spectrometer at 200
MHz using 85% H3PO4 (δP = 0) as an external standard.
Elemental analyses were carried out on a Carlo Erba 1106
CHN analyzer. Field desorption mass spectra were obtained
on a Finnigan MAT 90 double-focusing mass spectrometer.
The preparation of compound 3,3Јc is given as an example.
References
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Synthesis, 1988, 444.
Pathway A
To a stirred solution of 1 (1.23 g, 5 mmol) in anhydrous benzene
(15 ml) at room temperature under a nitrogen atmosphere was
added dropwise N,O-bis(trimethylsilyl)valine (1.31 g, 5 mmol)
in benzene (10 ml). After 10 min, 0.5 ml of the mixture was
withdrawn and its 31P NMR spectrum was taken (δP 1: Ϫ26.23;
2c,2Јc: Ϫ29.39, Ϫ29.92). Phenol (0.47 g, 5 mmol) in benzene (10
ml) was then added dropwise to the mixture. After 10 min the
precipitate was filtered off, the solvent and trimethylchloro-
silane were removed by rotary evaporation, and the remaining
solution (ca. 1 ml), was diluted with dry diethyl ether (5 ml).
A white precipitate appeared which was filtered off, and the
filtrate was washed three times with dry diethyl ether and dried
in vacuo over P2O5 at 39 ЊC for 5 h to afford 3,3Јc (2.32 g,
67%).
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Pathway B
To a stirred solution of 2,2,2-trichloro-1,3,2-benzodioxaphos-
phole (1.23 g, 5 mmol) in anhydrous benzene (15 ml) at room
temperature under a nitrogen atmosphere was added dropwise
phenol (0.47 g, 5 mmol) in benzene (10 ml). After 10 min, 0.5 ml
of the mixture was withdrawn and its 31P NMR spectrum was
taken (δP 1: Ϫ26.23; 4: Ϫ34.13). N,O-Bis(trimethylsilyl)valine
(1.31 g, 5 mmol) in benzene (10 ml) was then added dropwise to
the mixture. After 10 min the reaction was worked-up as for
Pathway A. Isolated yields and purities were similar to pathway
Paper 7/02813J
Received 24th April 1997
Accepted 23rd May 1997
2022
J. Chem. Soc., Perkin Trans. 1, 1997