Unprecedented c-acylation of imines with tervalent phosphorus isocyanates

Article abstract of DOI:10.1080/10426500902719727

Reaction of trifluoropyruvate N-phosphorylimine with tervalent phosphorus isocyanates leads to unexpected acylation of the imine carbon atom to afford phosphorylaminocarbonylated trifluoroalanine derivatives.

Full text of DOI:10.1080/10426500902719727

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Phosphorus, Sulfur, and Silicon
and the Related Elements
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Unprecedented C-Acylation
of Imines with Tervalent
Phosphorus Isocyanates
Yu. V. Rassukana a , P. P. Onys'ko a , A. I. Arkhypchuk
a & A. D. Sinitsa a
a Institute of Organic Chemistry, National Academy
of Sciences of Ukraine, Kyiv, Ukraine
Published online: 26 Mar 2009.
To cite this article: Yu. V. Rassukana , P. P. Onys'ko , A. I. Arkhypchuk & A. D. Sinitsa
(2009) Unprecedented C-Acylation of Imines with Tervalent Phosphorus Isocyanates,
Phosphorus, Sulfur, and Silicon and the Related Elements, 184:4, 992-997, DOI:
10.1080/10426500902719727
To link to this article: http://dx.doi.org/10.1080/10426500902719727
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Phosphorus, Sulfur, and Silicon, 184:992–997, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902719727
Unprecedented C-Acylation of Imines with Tervalent
Phosphorus Isocyanates
Yu. V. Rassukana, P. P. Onys’ko, A. I. Arkhypchuk,
and A. D. Sinitsa
Institute of Organic Chemistry, National Academy of Sciences
of Ukraine, Kyiv, Ukraine
Reaction of trifluoropyruvate N-phosphorylimine with tervalent phosphorus iso-
cyanates leads to unexpected acylation of the imine carbon atom to afford phospho-
rylaminocarbonylated trifluoroalanine derivatives.
Keywords Acylation; N-phosphorylimines; phosphorus isocyanates; trifluoroalanine;
umpolung
INTRODUCTION
Polyfluoroalkaneimines are promising building blocks for the syn-
thesis of various acyclic and heterocyclic functionalized nitrogen-
containing organofluorine compounds.1–4 N-Phosphorylimines are
considered as new reactive intermediates for stereoselective or-
ganic synthesis.5 Recently we have developed a synthesis for α-
trifluoromethyl-N-phosphoryliminocarboxylate 1, the first representa-
tive of the highly electrophilic trifluropyruvate N-phosphorylimines.6 It
was shown that 1 reacts readily with C-, N-, O-, and S-centered nucle-
ophiles and undergoes a Diels–Alder reaction with 1,3-dienes to afford
functionalized derivatives of biorelevant trifluoromethyl substituted
aminoacids.6,7
The highly polarized C N bond makes possible the use of imine
1 as dipolarophile in reactions with 1,3-dipolar substrates, and this
offers new perspectives for the synthesis of heterocyclic compounds
bearing the trifluoroalanine fragment. In this article, we report on the
Received 28 December 2007; accepted 18 February 2008.
Dedicated to Professor Marian Mikolꢀajczyk from the CBMiM PAN in Lꢀ o´dz´, Poland,
on the occasion of his 70th birthday.
Address correspondence to P. P. Onys’ko, Institute of Organic Chemistry, NAS of
Ukraine, 5 Murmans’ka St., 02094 Kyiv, Ukraine. E-mail: onysko@rambler.ru
992

C-Acylation of Imines with Tervalent Phosphorus
993
reaction of N-phosphoryliminocarboxylate 1 with tervalent phosphorus
isocyanates, a reaction route that is novel for imines.
RESULTS AND DISCUSSIONS
We have found that imine 1 under mild conditions (ether, 0◦C) eas-
ily reacts with tervalent phosphorus isocyanates 2a,b. The final prod-
uct of the reaction is rather unexpected: dipole R2PNCO acylates the
electrophilic imine carbon atom with its electrophilic center to afford
C-acylated derivatives 3, 4 (Scheme 1).
+
R
R
PN=C=O
R2PN=C=O
O
F3C
2a,b
F3C
1,2-P
N
P(OEt)2
N
P(OEt)2
MeOOC
MeOOC
1
O
A
O
O C
N
F3C
+
R
R
F3C
C
P
N
N
MeOOC
(EtO)2P
N
PR2
MeOOC
P(OEt)2
O
B
O
3a,b
O
O
F3C
PR2
(H2O)
N
H
MeOOC
90-95%
N
P(OEt)2
H
O
4a,b
2a-4a R = EtO
2b-4b R = Ph
SCHEME 1
It is apparent that the transformation 1 → 3 is a complex process.
The reaction most probably starts with the nucleophilic attack of the
phosphite on the most electrophilic center of 1, the imine carbon atom.
The subsequent C N migration of the phosphorus group in the dipo-
lar intermediates A results in the formation of betaines B undergoing
intramolecular cyclization to give heterocyclic iminophosphoranes 3.
Note that we have already reported examples of C N transfer (similar

994
Y. V. Rassukana et al.
to A→B) of other phosphorus groups upon nucleophilic phosphorylation
of activated haloalkaneimines.4,8–10
Compounds 3 were identified only spectroscopically, as they are un-
stable and transform into the acylated trifluoroalanine derivatives 4
when kept at room temperature or during the work-up of the reaction
mixture. Monitoring the progress of the reaction with 31P, 19F NMR
spectroscopy reveals that conversion of 3a into 4a involves an inter-
mediate [δP 49.7 (1P) and –4.5 (1P), δF –69]. At room temperature, the
reaction is completed within 36 h.
Diagnostic for the structural identification of the 4H-diazaphoshol-
4-ones 3 is the typical position of 31P NMR signals of the endocyclic
phosphazo group (δP 48.4–56.2) and of the exocyclic amidophosphate
group (δ from –3.7 to –2.4 ppm) of equal intensities and rather strong
spin–spin interaction (2JPP = 40–58 Hz). A rather low value of the
coupling constant of the endocyclic C-atom with the phosphorus nucleus
in the 13C NMR spectrum (δC 74.7, 2JPC = 7 Hz,2JCF = 28 Hz) indicates
the absence of a P C bond in compounds 3. The observed doublet for
N C=O (δC 161.9, 2JPC = 5 Hz) and singlet for C(O)O group (δC 163.8)
suggests that heterocycle 3 is formed with the participation of the NCO
moiety rather than the COOMe group. The spectroscopic and analytical
data of the acylated compounds 4 are in complete agreement with their
structure.
The new direction found for the reaction of imine 1 with PIII
-
isocyanates (Scheme 1) has no analogies in the literature. In particu-
lar, chloral aldimines, when treated with phosphorus isocyanates, give
[3 + 2]-cycloaddition products in which a P-C bond with the imine car-
bon atom is formed.11–13 The reaction of N-benzoyltrifluoroacetimidoyl
chloride, CF3C(Cl)=NCOPh, with 2a proceeds as the cheletropic
1,4-cycloaddition of the P-atom of the phosphite to the hetero-
diene C=NC=O fragment, whereas the isocyanate group remains
unaltered.14 These differences result most probably from the simul-
taneous influence of electronic and steric effects of the substiutents in
imine 1 on the reaction route. The three strongly electron-withdrawing
groups at the N- and C-atoms favor stabilization of the anionic cen-
ter in dipolar ion A. Moreover, C-N migration of the phosphorus group
(A → B) is promoted by the release of steric strains at the quaternary
carbon atom in intermediate A and is accompanied by umpolung of C-
and N-reaction centers.
It is worthwhile to note that despite the complexity and multistep
character of the process in Scheme 1, the final compounds are formed in
high yields, and this fact is indicative of high chemoselectivity. Taking
into account the ease of the transformation, the new reaction can find

C-Acylation of Imines with Tervalent Phosphorus
995
application in the synthesis of biorelevant C-acylated trifluoroalanine
derivatives.
EXPERIMENTAL
1
IR spectra were obtained with an UR-20 spectrophotometer. H, 19F,
31P, and 13C NMR spectra were recorded with a Varian VXR-300
spectrometer at 299.95, 282.20, 121.42, and 75.43 MHz, respectively.
Chemical shifts are reported relative to TMS (1H, 13C), and CFCl3
(19F) as internal standards or relative to external 85% H3PO4 (31P).
Solvents were dried before use according to standard methods. All
reactions were carried out under atmosphere of argon in oven-dried
glassware.
Reaction of Imine 1 with Isocyanate 2a
A solution of imine 1 (0.41 g, 1.4 mmol) in benzene (5 mL) was cooled to
5◦C, and isocyanate 2a (0.23 g, 1.4 mmol) was added. After 15 min at
room temperature, the 19F and 31P NMR spectra show the formation of
1-diethoxyphosphoryl-2,2-diethoxy-5-methoxycarbonyl-4-oxo-5-trifluo-
romethyl-1,3,2-diaza-2-phospholine (3a). 19F NMR (C6H6): δ = –65.
31P NMR (C6H6): δ = –3.7 (d, JPP = 58 Hz, 1P), 56.2 (d, JPP = 58
Hz, 1P). After 48 h, the solvent was evaporated in vacuo, and the
residue was washed with petroleum ether to give methyl 2-[(dietho-
xyphosphoryl)amino]-2-[[(diethoxyphosphoryl)amino]carbonyl]-3,3,3-
trifluoropropanoat (4a) as colorless oil; 0.54 g (90%). IR (film, ν, cm1):
1050 (POC), 1280 (P=O), 1720 (C=O), 1775 (C=O), 3150 (NH). 1H NMR
(CDCl3): δ = 1.30–1.38 (m, 12H, CH3CH2), 3.91 (s, 3H, CH3O), 4.09–
2
2
3
3
4.28 (m, 8H, CH2O), 4.89 (d, JPH = 7.2 Hz, 1H, NH), 9.08 (d, JPH
=
7.5 Hz, 1H, NH). 19F NMR (CDCl3): δ = –72.8. 31P NMR (CDCl3):
δ –4.0 (1P), 2.7 (1P). Anal. Calcd. for C13H25F3N2O9P2(472.30):
C, 33.06; H, 5.34; P, 13.12. Found: C, 32.94; H, 5.39; P,
13.28%.
Reaction of Imine 1 with Isocyanate 2b
A solution of imine 1 (0.07 g, 0.23 mmol) in benzene-d6 (1 mL) was
cooled to 5◦C, and isocyanate 2b (0.05 g, 0.23 mmol) was added. After 1
h at room temperature, the 1H, 13C,19F, and31P NMR spectra show the
formation of 1-diethoxyphosphoryl-2,2-diphenyl-5-methoxycarbonyl-4-
oxo-5-trifluoromethyl-1,3,2-diaza-2-phospholine (3b).1H NMR (C6D6):
δ = 1.32–1.34 (m, 6H, CH3C), 3.21 (s, 3H, CH3O), 4.41–4.60 (m, 4H,

996
Y. V. Rassukana et al.
CH2O), 7.19–7.35 (m, 6H, Ph), 8.00–8.15 (m, 4H, Ph).13C NMR (C6D6):
3
δ = 16.1 (d, JPC = 6 Hz, MeC), 52.6 (s, MeO), 64.1 (d,2JPC = 5 Hz,
2
OCH2), 64.8 (d,2JPC = 5 Hz, OCH2), 74.7 (dq,2JCF = 28 Hz, JPC = 7
1
Hz, CF3C), 125.2 (q, JCF = 283 Hz, CF3), 123.0–134.0 (Ph), 161.9 (d,
2JPC = 5 Hz, NCO), 163.8 (s, COOMe). 19F NMR (C6D6): δ = –62.8. 31
P
NMR (CDCl3): δ = –2.4 (d, 3JPP = 40.5 Hz, 1P), 48.4 (d, 3JPP = 40.5 Hz,
1P).
After 48 h, the solvent was evaporated in vacuo, and the
residue was washed with diethyl ether to give methyl 2-[(diethoxy-
phosphoryl)amino]-2-[[(diphenylphosphinoyl)amino]-carbonyl]-3,3,3-
trifluoropropanoat (4b) as white powder, 0.11 g (95%), mp 139–140◦C.
IR (KBr, ν, cm1): 1050 (POC), 1230 (P=O), 1280 (P=O), 1730 (C=O),
1770 (C=O), 3150 (NH). 1H NMR (CDCl3): δ = 1.30–1.38 (m, 6H,
2
CH3C), 3.69 (s, 3H, CH3O), 4.27–4.31 (m, 4H, CH2O), 4.76 (d, JPH
=
9.6 Hz, 1H, NH), 7.48–7.55 (m, 6H, Ph), 7.81–7.89 (m, 4H, Ph), 9.37
(d, JPH = 9 Hz, 1H, NH). 13C NMR (CDCl3): δ = 15.8 (d, JPC = 6 Hz,
2
3
MeC), 53.0 (s, MeO), 58.2 (q,2JCF = 34 Hz, CF3C), 65.3 (d,2JPC = 5 Hz,
1
2
OCH2), 122.1 (q, JCF = 283 Hz, CF3), 152.2 (d, JPC = 8 Hz, CONH),
163.3 (s, COOMe). 19F NMR (CDCl3): δ = 66.4. 31P NMR (CDCl3):
δ = 2.4 (1P), 17.0 (1P). Anal. Calcd. for C21H25F3N2O7P2(536.39): C,
47.02; H, 4.70; N, 5.22; P, 11.55. Found: C, 47.05; H, 4.71; N, 5.25; P,
11.73%.
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