Reaction of TPP-azodicarboxylate zwitterions and aryl aldehydes: unprecedented synthesis of acyl carbamates

Article abstract of DOI:10.1016/j.tetlet.2007.10.092

An efficient synthesis of acyl carbamates from aryl aldehydes by the reaction of triphenylphosphine and dialkyl azoesters is described.

Full text of DOI:10.1016/j.tetlet.2007.10.092

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Tetrahedron Letters 48 (2007) 9018–9020
Reaction of TPP-azodicarboxylate zwitterions and aryl
aldehydes: unprecedented synthesis of acyl carbamates
a
a
c
Vijay Nair,a,b, Smitha C. Mathew, A. T. Biju and E. Suresh
*
aOrganic Chemistry Section, National Institute for Interdisciplinary Science and
Technology—(Formerly Regional Research Laboratory), Trivandrum, Kerala 695 019, India
bJawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560 064, India
cAnalytical Science Discipline, Central Salt and Marine Chemicals Research Institute, Bhavnagar 364 002, India
Received 24 August 2007; revised 11 October 2007; accepted 17 October 2007
Available online 22 October 2007
Abstract—An efficient synthesis of acyl carbamates from aryl aldehydes by the reaction of triphenylphosphine and dialkyl azoesters
is described.
Ó 2007 Elsevier Ltd. All rights reserved.
The formation of a zwitterion by the reaction of triphen-
ylphosphine (TPP) and azoesters has been known for a
long time1 and the critical role of this species in the Mits-
unobu reaction is well established.2 Other synthetically
useful reactions of this zwitterion commonly called the
Huisgen zwitterion, include preparation of vinyl hydra-
zine dicarboxylates from ketones,3 oxadiazolines from
a-ketoesters,4 and protected hydrazones from salicyl-
aldehydes.5 Recent studies on the chemistry of this
zwitterion have uncovered a number of interesting
reactions, which include the formation of a monohydra-
zone from benzil via an unprecedented rearrange-
ment,6 formation of novel pyrazolopyridazines from
dienones,7 spirooxadiazolines from isatins,8 and pyra-
zoles from allenes.9 In this context, and in view of the
general interest in the chemistry of zwitterions,10 we
undertook an investigation of the reactivity of this zwit-
terion toward aldehydes. Our results describing the
unprecedented, direct transformation of aryl aldehydes4
to acyl carbamates form the subject matter of this
Letter. It is noteworthy that acyl carbamates are impor-
tant due to their pesticidal activity.11,12
of acyl carbamates,14,15 all of them involve multistep
processes; to the best of our knowledge no direct conver-
sion of an aldehyde to an acyl carbamate has been
reported.
Our studies commenced with an experiment in which a
solution of 4-trifluoromethylbenzaldehyde 3a and diiso-
propyl azodicarboxylate (DIAD) 2a in anhydrous THF
was allowed to react with a stoichiometric quantity of
triphenylphosphine at room temperature under an
argon atmosphere. Work-up followed by column chro-
matography afforded a white crystalline solid in 90%
yield which was characterized as the acyl carbamate 4a
(Scheme 1).16
The structure of the product was assigned on the basis of
spectroscopic analysis and further confirmation was
achieved unambiguously using single crystal X-ray anal-
ysis (Fig. 1).17
i
O
NHCO2 Pr
CHO
Acyl carbamate groups also find application as protect-
ing groups in organic synthesis.13 Although a number of
methods are available in the literature for the synthesis
iPr O2C
+
N
N
THF, rt, 3 h, Ar
90%
PPh3
+
i
CO2 Pr
CF3
CF3
4a
1
2a
3a
*
Corresponding author. Tel.: +91 471 2515231; fax: +91 471 2491712/
0406; e-mail: vijaynair_2001@yahoo.com
Scheme 1.
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.10.092

V. Nair et al. / Tetrahedron Letters 48 (2007) 9018–9020
9019
R
RO2C
CO2R
Ph3P
R
N
N
N
Ph3P
N
H
O
OR
RO2C
O
O
5
6
R
RO2C
Figure 1. ORTEP diagram for compound 4a.
N
N
CO2R
-PPh3=O
R
N
OR
O
N
H
PPh3
O
O
Table 1. Reactions of aldehydes with TPP-azoester zwitterion
8
7
RO
O
NHCO2R
R3
O
CHO
R3 RO2C
+
CO2R
- ROCN
N
H
N
N
THF, rt, 6 h, Ar
R2
9
PPh3
+
R2
CO2R
R
R1
R1
10
3
2
4
1
Scheme 2.
Entry
R
R1
Isopropyl Cl
Isopropyl
R2
R3 Product Yield (%)
1
2
3
4
5
6
7
8
9
Cl
NO2
H
H
Cl
H
F
H
H
H
Cl
H
H
H
H
H
H
H
H
H
H
H
F
4b
4c
4d
4e
4f
85
76
Acknowledgments
H
Isopropyl Br
Isopropyl Cl
50 (67)a
78
Financial assistance from the Council of Scientific and
Industrial Research (CSIR), New Delhi is acknowl-
edged. The authors thank Priya M. Nair, Soumini
Mathew and Sreemathi Viji for recording IR spectra,
NMR spectra, and mass spectra, respectively.
Isopropyl
Isopropyl
Isopropyl
Isopropyl
Isopropyl
Ethyl
Ethyl
Ethyl
Ethyl
Ethyl
H
F
F
H
75
75
86
4g
4h
4i
37 (83)a
64
H
H
H
H
H
H
H
H
H
4j
10
11
12
13
14
15
16
CF3
Cl
NO2
Br
Cl
F
4k
4l
86
74
73
64
71
75
89
References and notes
4m
4n
4o
4p
4q
1. (a) Cookson, R. C.; Locke, J. M. J. Chem. Soc. 1963,
6062; (b) Brunn, E.; Huisgen, R. Angew. Chem., Int. Ed.
Engl. 1969, 8, 513; (c) Huisgen, R. In The Adventure
Playground of Mechanisms and Novel Reactions: Profiles;
Seeman, J. I., Ed.; Pathways and Dreams; American
Chemical Society: Washington DC, 1994; p 62.
2. (a) Mitsunobu, O.; Eguchi, M. Bull. Chem. Soc. Jpn. 1971,
44, 3427; (b) Mitsunobu, O. Synthesis 1981, 1.
3. Liu, Y.; Xu, C.; Liu, L. Synthesis 2003, 1335.
4. Otte, R. D.; Sakata, T.; Guzei, I. A.; Lee, D. Org. Lett.
2005, 7, 495. These authors have observed that aliphatic
aldehydes on reaction with a phosphine-azoester zwitter-
ion delivered bis-adducts; no work on aryl aldehydes was
reported.
5. Girard, M.; Murphy, P.; Tsou, N. Tetrahedron Lett. 2005,
46, 2449.
6. (a) Nair, V.; Biju, A. T.; Abhilash, K. G.; Menon, R. S.;
Suresh, E. Org. Lett. 2005, 7, 2121; (b) Nair, V.; Biju, A.
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7. Nair, V.; Mathew, S. C.; Biju, A. T.; Suresh, E. Angew.
Chem., Int. Ed. 2007, 46, 2070.
8. Nair, V.; Biju, A. T.; Vinod, A. U.; Suresh, E. Org. Lett.
2005, 7, 5139.
Ethyl
tert-Butyl Cl
Cl
a Recovered yield.
The reaction was found to be general with a variety of
aromatic aldehydes. The results are summarized in
Table 1.
The following mechanistic postulate may be invoked to
rationalize the formation of the acyl carbamate from
aldehyde. Initially zwitterion 5 generated from the azo-
dicarboxylate and triphenylphosphine adds to the alde-
hyde carbonyl to form intermediate 7 which then
eliminates triphenylphosphine oxide by a well prece-
dented step to form the oxadiazoline derivative 8. It is
conceivable that the oxadiazoline can undergo ring frag-
mentation and concomitant hydride transfer to deliver
the acyl carbamate 10 with the loss of alkyl cyanate.
Although we have no direct evidence for this mechanis-
tic pathway, the detection of a peak corresponding to
the alkyl cyanate (m/z = 85.46, R = iPr) 9 in the low
resolution mass spectrum of the reaction mixture may
validate the proposed mechanism (Scheme 2).
9. Nair, V.; Biju, A. T.; Mohanan, K.; Suresh, E. Org. Lett.
2006, 8, 2213.
10. (a) Nair, V.; Menon, R. S.; Sreekanth, A. R.; Abhilash,
N.; Biju, A. T. Acc. Chem. Res. 2006, 39, 520; (b) Nair, V.;
Rajesh, C.; Vinod, A. U.; Bindu, S.; Sreekanth, A. R.;
Mathen, J. S.; Balagopal, L. Acc. Chem. Res. 2003, 36,
899.
11. Seiller, B.; Heins, D.; Bruneau, C.; Dixneuf, P. H.
Tetrahedron 1995, 51, 10901.
12. (a) Wellinga, K.; Mulder, R.; van Daalen, J. J. J. Agric.
Food. Chem. 1973, 21, 348; Wellinga, K.; Mulder, R.; van
In conclusion, we have developed a novel, direct trans-
formation of aromatic aldehydes to acyl carbamates. It
is reasonable to assume that this reaction will be useful
in organic synthesis.

9020
V. Nair et al. / Tetrahedron Letters 48 (2007) 9018–9020
Daalen, J. J. Chem. Abstr. 1973, 79, 88264d; (b) Nakag-
(0.66 mmol) in dry THF (3 mL) under an atmosphere of
Ar was added triphenylphosphine (216 mg, 0.83 mmol)
and the reaction mixture was stirred at room temperature
for 3 h. The solvent was removed under reduced pressure
on a rotary evaporator. The residue was subjected to
column chromatography on silica gel (100–200 mesh)
using 85:15 petroleum ether-ethyl acetate as eluent to
afford the corresponding acyl carbamate derivative 4a as
white crystals. Mp: 145–147 °C, IR (KBr) mmax: 3352,
3055, 2985, 1742, 1642, 1477, 1421, 1381, 1323, 1269, 1259,
awa, Y.; Kithahara, K.; Nishioka, T.; Iwamura, H.;
Fujita, T. Pestic. Biochem. Physiol. 1984, 21, 309; Nakag-
awa, Y.; Kithahara, K.; Nishioka, T.; Iwamura, H.;
Fujita, T. Chem. Abstr. 1984, 101, 19044t.
13. (a) Evans, D. A.; Rajapakse, H. A.; Chiu, A.; Stenkamp,
D. Angew. Chem., Int. Ed. 2002, 41, 4573; (b) Evans, D.
A.; Katz, J. L.; Peterson, G. S.; Hintermann, T. J. Am.
Chem. Soc. 2001, 123, 12411; (c) Evans, D. A.; Carter, P.
H.; Carreirra, A. B.; Prunet, J. A.; Lautens, M. J. Am.
Chem. Soc. 1999, 121, 7540, and references cited therein.
14. (a) Vidal, J.; Damestoy, S.; Guy, L.; Hannachi, J.-C.;
Aubry, A.; Collet, A. Chem. Eur. J. 1997, 3, 1691; (b)
Wasserman, H. H.; Desimone, R. W.; Ho, W.-B.;
McCarthy, K. E.; Prowse, K. S.; Spada, A. P. Tetrahedron
Lett. 1992, 33, 7207.
1172, 1109, 1072, 896, 759, 734, 700 cmÀ1 1H NMR
.
(300 MHz, CDCl3, rt): d 8.52 (bs, 1H), 7.49 (d, J = 7.8 Hz,
2H), 7.73 (d, J = 8.2 Hz, 2H), 5.09–5.02 (m, 1H), 1.30 (d,
J = 6.2 Hz, 6H). 13C NMR (CDCl3): d 164.3, 150.6, 136.5,
134.6, 128.3, 125.7, 125.3, 121.6, 70.6, 21.8. HRMS (EI)
for C12H12F3NO3, Calcd (M+): 275.0769, found:
275.0780.
15. Li, Z.; Wu, Z.; Luo, F. J. Agric. Food Chem. 2005, 53,
3872.
16. Typical experimental procedure: To a solution of 4-tri-
fluoromethylbenzaldehyde 3a (0.55 mmol) and DIAD
17. The crystal structure of compound 4a has been deposited
at the Cambridge Crystallographic Data Centre and
allocated the reference no. CCDC 642242.