Novel N-phosphonio imine-catalyzed epoxidation reactions

Article abstract of DOI:10.1021/ol800690c

(Chemical Equation Presented) A new type of acyclic N-phosphonio imine catalyst for selective epoxidations has been synthesized. The activity of these imine catalysts can easily be modulated by varying its substituents. The substituent attached to the imine nitrogen atom is particularly important for an efficient oxygen transfer.

Full text of DOI:10.1021/ol800690c

ORGANIC
LETTERS
2008
Vol. 10, No. 11
2291-2294
Novel N-Phosphonio Imine-Catalyzed
Epoxidation Reactions
David Prieur, Aime´e El Kazzi, Tsuyoshi Kato,* Heinz Gornitzka, and
Antoine Baceiredo*
Laboratoire He´te´rochimie Fondamentale et Applique´e du CNRS, UMR 5069,
UniVersite´ Paul Sabatier, 118 route de Narbonne, F-31062 Toulouse cedex 9, France
baceired@chimie.ups-tlse.fr
Received March 28, 2008
ABSTRACT
A new type of acyclic N-phosphonio imine catalyst for selective epoxidations has been synthesized. The activity of these imine catalysts can
easily be modulated by varying its substituents. The substituent attached to the imine nitrogen atom is particularly important for an efficient
oxygen transfer.
Organocatalysis has become a field of central importance in
organic synthesis as an alternative to the well-established
transition-metal-catalyzed transformations.1 The organocata-
lytic oxidation of functionalized and unfunctionalized olefins
has emerged as a very versatile and important synthetic tool
since the resulting epoxides are highly useful building blocks
for the synthesis of complex molecules.2 The most productive
organocatalytic processes so far have involved ketones (I)
and iminium salts (II) as catalysts which can be converted
using oxone, into, respectively, highly reactive dioxiranes
(I-O) and oxaziridinium (II-O) species.3 In contrast, ox-
aziridines (III-O) constitute a class of strained heterocycles
exhibiting a remarkable stability. Therefore, they are much
less reactive in oxidation reactions compared to dioxiranes
(I-O) and oxaziridinium salts (II-O)2–5 and, depending on
the substituents, show a different reactivity such as electro-
philic amination.6 However, the relatively inert oxaziridines
III-O have been activated by Lewis acids to achieve the
selective oxidation of sulfides.4i In fact, the oxidizing power7
and reactivity of oxaziridines8 is strongly related to steric
(4) For selective oxidation of sulfides: (a) Davis, F. A.; Billmers, J. M.
J. Org. Chem. 1983, 48, 2672. (b) Davis, F. A.; McCauley, J. P., Jr.; Harakal,
M. E. J. Org. Chem. 1984, 49, 1467. (c) Davis, F. A.; Billmers, J. M.;
Gosciniak, D. J.; Towson, J. C. J. Org. Chem. 1986, 51, 4240. (d) Davis,
F. A.; McCauley, J. P.; Chattopadhyay, S.; Harkal, M. E.; Towson, J. C.;
Watson, W. H.; Tavanaiepour, I. J. Am. Chem. Soc. 1987, 109, 3370. (e)
Davis, F. A.; Lal, S. G. J. Org. Chem. 1988, 53, 5004. (f) Davis, F. A.;
ThimmaReddy, R.; Weismiller, M. C. J. Am. Chem. Soc. 1989, 111, 5964.
(g) Davis, F. A.; Reddy, T.; Han, W.; Carroll, P. J. J. Am. Chem. Soc.
1992, 114, 1428. (h) Davis, F. A.; Weismiller, K. M.; Reddy, R. T.; Chen,
B.-C. J. Org. Chem. 1992, 57, 7274. (i) Schoumacker, S.; Hamelin, O.;
Te´ti, S.; Pe´caut, J.; Fontecave, M. J. Org. Chem. 2005, 70, 301.
(5) For oxidation of enolate anions: (a) Davis, F. A.; Chen, B.-C. Chem.
ReV. 1992, 92, 919. (b) Davis, F. A.; Kumar, A.; Reddy, R.; Chen, B.-C.;
Wade, P. A.; Shah, S. W. J. Org. Chem. 1993, 58, 7591. (c) Davis, F. A.;
Reddy, R. E.; Kasu, P. V. N.; Portonovo, S. P.; Carroll, P. J. J. Org. Chem.
1997, 62, 3625.
(6) (a) Page, P. C. B.; Heer, J. P.; Bethell, D.; Collington, E. W.;
Andrews, D. M. Tetrahedron: Asymmetry 1995, 6, 2911. (b) Wolfe, M. S.;
Dutta, D.; Aube´, J. J. Org. Chem. 1997, 62, 654. (c) Vidal, J.; Hannachi,
J.-C.; Hourdin, G.; Mulatier, J.-C.; Collet, A. Tetrahedron Lett. 1998, 39,
8845. (d) Choong, I. C.; Ellman, J. A. J. Org. Chem. 1999, 64, 6528. (e)
Bonnet, D.; Rommes, C.; Gras-Masse, H.; Melnyk, O. Tetrahedron 1999,
40, 7315. (f) Page, P. C. B.; Heer, J. P.; Bethell, D.; Lund, A.; Collington,
E. W.; Andrews, D. M. J. Org. Chem. 1997, 62, 6093. (g) Messina, F.;
Botta, M.; Corelli, F.; Paladino, A. Tetrahedron: Asymmetry 2000, 11, 4895.
(h) Messina, F.; Botta, M.; Corelli, F.; Paladino, A. Tetrahedron: Asymmetry
2000, 11, 4895. (i) Armstrong, A.; Edmods, I. D.; Swarbric, M. E.
Tetrahedron Lett. 2003, 44, 5335. (j) Washington, I.; Houk, K. N. J. Org.
Chem. 2003, 68, 6597. (k) Hannachi, J.-C.; Vidal, J.; Mulatier, J.-C.; Collet,
A. J. Org. Chem. 2004, 69, 2367. (l) Armstrong, A.; Jones, L. H.; Knight,
J. D.; Kelsey, R. D. Org. Lett. 2005, 7, 713.
(1) (a) Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2004, 43, 5185.
(b) Special issue for organocatalysis: Chem. ReV. 2007, 107, 12.
(2) For review see: Adam, W.; Shara-Mo¨ller, C. R.; Ganeshpure, P. A.
Chem. ReV. 2001, 101, 3499.
(3) For epoxidation: (a) Davis, F. A.; Jenkins, R. H.; Awad, S. B.;
Stringer, O. D.; Watson, H. W.; Galloy, J. J. Am. Chem. Soc. 1982, 104,
5412. (b) Davis, F. A.; Abdul-Malik, N. F.; Jenkins, L. A. J. Org. Chem.
1983, 48, 5128.
10.1021/ol800690c CCC: $40.75
Published on Web 05/07/2008
2008 American Chemical Society

and electronic factors. Indeed, it has been recently reported
that the benzoxathiazine 1 (cyclic imine III) shows an
extraordinary catalytic activity in epoxidation reactions and
in the hydroxylation of aliphatic C-H bonds.9 This suggests
that the reactivity of imines III should be more easily tuned
compared to that of ketones I and iminium salts II, which
are only strong oxidizing catalysts.
In order to develop a new family of electron-deficient
imine catalysts, we present here the synthesis of N-phos-
phonio imines, which are remarkably stable in aqueous
media, and the preliminary results obtained in selective
catalytic epoxidation of olefins.
The previously reported N-phosphinoyl oxaziridines pre-
pared from the corresponding imines 2 show a poor reactivity
in oxidation reactions.10 Therefore, the epoxidation proceeds
very slowly and sometimes requires thermal activation. In
fact, we have confirmed that 2 does not show any catalytic
activity for the epoxidation of olefins in the presence of a
stoichiometric amount of oxidant (buffered oxone solution
with K2CO3 in CH3CN/H2O). Taking into account that
reactivity of oxaziridines III-O is strongly related to the
electron-withdrawing character of the substituents,8 N-
phosphonio imines 3, instead of N-phosphinoyl imines, were
considered.
The catalyst candidates (3a-d) were synthesized as shown
in Figure 1: (i) in the first step, the N-phosphino imines
(4a-d) were obtained from the corresponding N-trimethyl-
silyl imines11 which readily react with the bis(diisopropy-
lamino)chlorophosphine;12,13 (ii) in the second step, the
phosphine center was alkylated using 1 equiv of methyl
triflate, affording N-phosphonio imines (3a-c) in good yields
Figure 1. Synthesis of N-phosphonio imines (3a-d) and X-ray
diffraction structure of 3d. The counteranion (trifluoromethane-
sulfonate) was omitted for clarity.
(67-74%).14 In the case of 3d, bearing an electronegative
alkoxy substituent, the N-phosphinoyl imine 5d was first
prepared by oxidation of 4d with hydrogen peroxide. The
structure of 3d was unambiguously established by an X-ray
diffraction analysis (Figure 1).
The corresponding N-phosphonio oxaziridines (6a-d)
were obtained by oxidation in CH2Cl2 at 0 °C with meta-
chloroperbenzoic acid (m-CPBA, 1 equiv) in the presence
of sodium hydrogen carbonate (1 equiv) (Figure 2).15
Oxaziridines (6a-c) are perfectly stable in organic solvents
(CH2Cl2, THF) under air and moisture conditions, whereas
the higly reactive 6d slowly gives back imine 3d.
(7) Although the highly electrophilic perfluorooxaziridines show the
exceptionally strong oxidizing power, any catalytic oxidation reaction using
corresponding imines have been reported: Petrov, V. A.; Resnati, G. Chem.
ReV. 1996, 96, 1.
(8) Vidal, J.; Damestoy, S.; Guy, L.; Hanachi, J.; Aubry, A.; Collet, A.
Chem.—Eur. J. 1997, 3, 1691.
The reactivity of the oxaziridines 6a-d with trans-ꢀ-
methylstyrene was found to be strongly dependent on the
nature of the P and Ar substituents. Particularly, the presence
(9) Brodsky, B. H.; Du Bois, J. J. Am. Chem. Soc. 2005, 127, 15391.
(10) (a) Jennings, W. B.; Schweppe, A. W. B.; Testa, L. M.; Zaballos-
Garcia, J.; Sepulveda-Arques, E. Synlett 2003, 121. (b) Jennings, W. B.;
O’Shea, J. H.; Schweppe, A. Tetrahedron Lett. 2001, 42, 101.
(11) Hart, D. J.; Kanai, K.; Thomas, D. G.; Kuei. Yang, T. J. Org. Chem.
1983, 48, 289.
(14) Typical procedure for the synthesis of 3: To a CH2Cl2 solution of
4a (840 mg, 2.5 mmol) was slowly added, at 0 °C, methyl trifluoromethane-
sulfonate (310 µl, 2.5 mmol). After 30 min at rt, all volatiles were removed
under vacuum. Compound 3a was obtained by crystallization in CH2Cl2/
Et2O at -30 °C (74%).
(12) A similar reactivity of N-trimethylsilylimine with sulfonylchlorides
is already known: Georg, G. I.; Harriman, G. C. B.; Peterson, S. A. J. Org.
Chem. 1992, 57, 1224
.
(13) Typical procedure for the synthesis of 4: To a CH2Cl2 solution of
bis(diisopropylamino)chlorophosphine (1.0 g, 3.75 mmol) was slowly added,
at 0 °C, the N-trimethylsilyl benzaldimine (0.66 g, 3.75 mmol). After 2 h
at rt, all volatiles were removed under vacuum. After precipitation by adding
(15) Typical procedure for the synthesis of 6: To a mixture of 3a (150
mg, 0.3 mmol) and sodium hydrogen carbonate (79.5 mg, 0.75 mmol) in
CH2Cl2 (1 mL) was added, at rt, a solution of m-chloroperbenzoic acid
(129.5 mg, 0.75 mmol). After 3 h, the solution was filtrated, and the
evaporation of the solvent gave the corresponding oxaziridine 6a (41%).
CH3CN, compound 4a was obtained as a yellow powder (50%)
.
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Org. Lett., Vol. 10, No. 11, 2008

methylstyrene, the reaction catalyzed by 3c proceeded
slower (79%, 16 h) compared to the reaction with 3d
(75%, 5 h).
These results clearly show that the rates of the two steps
of the catalytic cycle (oxaziridine formation/oxygen atom
transfer) are strongly dependent on the imine substituents.
With the less reactive trans-ꢀ-methylstyrene as substrate, the
rate of the reaction is limited by the kinetic of the second
step (oxygen atom transfer) which depends of the reactivity
of the oxaziridine. Therefore, the high catalytic activity of
imine 3d for this substrate suggests that the oxygen atom
transfer step is strongly affected by the nature of the
phosphonio fragment, which is in agreement with the
reactivity of the corresponding oxaziridine (6d).
Figure 2. Synthesis of N-phosphonio oxaziridines (6a-d) and their
reaction with trans-ꢀ-methylstyrene.
On the other hand, with a more reactive substrate (1-
methylcyclohexene) the rate-determining step is the oxaziri-
dine formation which goes faster with 3c than with 3d.
Indeed, electron-withdrawing groups at the imine carbon
mainly accelerate the formation of the active oxaziridine
species, which starts with the nucleophilic attack of peroxide
salt. In fact, after the reaction, partial decompositions of
catalysts 3b and 3c were observed (hydrolysis of the imine
fragment), while 3a and 3d remained intact in the same
conditions. This result is in agreement with a stronger
electrophilic character of the imine function in 3b and 3c.
of the alkoxy substituent at the phosphorus center has the most
pronounced influence on reactivity. Indeed, the oxaziridine 6d
oxidizes the alkene much faster (76% of conversion in 5 min)
than 6a (26% in 1 h) or 6c (56% in 30 min).16
In contrast to the previously reported air-sensitive N-
phosphinoyl imines 2,11 the N-phosphonio imines 3a-d are
stable in aqueous media, allowing the development of a
catalytic process. Therefore, we tested, at 0 °C,17 the
epoxidation reaction of 1-phenylcyclohexene in the presence
of 3d as catalyst (10 mol %) and oxone (200 mol %) as
oxidant, in CH3CN/H2O (1/1) solution. The reaction gave
quantitatively the corresponding epoxide in 3 h, whereas any
trace of epoxide was observed without catalyst 3d, clearly
indicating the catalytic activity of 3d.
The scope of the epoxidation reaction catalyzed by 3d was
then evaluated using various olefins (Table 2). The results
To evaluate the substituent effect on the catalytic activity
of N-phosphonio imines (3a-d), the epoxidation reactions
of two different olefins, 1-methylcyclohexene and the less
reactive trans-ꢀ-methylstyrene, were considered.
Table 2. Catalytic Epoxidation Reactions of Various Alkenes
Using 3da
As shown in Table 1, good to high catalytic activities of
3a-d were observed with the reactive 1-methylcyclohexene.
As expected, the catalyst bearing the electron-donating
methyl group on the phosphorus atom and an unactivated
phenyl substituent (3a) is the less active. The highest catalytic
activity was observed with imine 3c, which presents the 2,4-
dichloroaryl substituent. However, with the less reactive
Table 1. Epoxidation of Olefins (1-Methylcyclohexene,
trans-ꢀ-Methylstyrene) Using Different Imine Catalysts (3a-d)a
a Olefin (0.39 mmol, 1.0 equiv), Oxone (0.79 mmol, 2.0 equiv), 3d
(0.039 mmol, 0.1 equiv), and Na2CO3 (1.5 mmol, 4.0 equiv) in CH3CN/
H2O (2 mL, 1:1) at 0 °C. b Determined by GC.
show that catalyst 3d is particularly efficient for di- or
trisubstituted alkenes. Moreover, this system is highly
selective for internal olefins. Indeed, in the case of dienes
presenting both internal and terminal double bonds, only the
latter one was oxidized (entries 3-5).
a Olefin (0.39 mmol, 1.0 equiv), Oxone (0.79 mmol, 2.0 equiv), catalyst
(0.039 mmol, 0.1 equiv), and Na2CO3 (1.5 mmol, 4.0 equiv) in CH3CN/
H2O (2 mL, 1:1) at 0 °C. b Determined by GC.
Org. Lett., Vol. 10, No. 11, 2008
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In conclusion, we successfully synthesized a new type of
imine catalyst for epoxidation reactions: the N-phosphonio
imines. Of particular interest, the rates of the two catalytic
steps (oxaziridine formation and oxygen atom transfer) are
strongly related to the nature of the imine substituents.
Electron-withdrawing substituents on the imine carbon
mainly increase the electrophilic character and therefore
accelerate the oxaziridine formation. Whereas, the oxygen
transfer step from the active oxaziridine species is dramati-
cally affected by the electron-withdrawing character of the
phosphonio fragment. The development of a chiral version
of N-phosphonio imine catalysts is under active research.
Acknowledgment. We are grateful to the CNRS for
financial support of this work.
Supporting Information Available: Experimental pro-
cedures and full spectroscopic data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(16) To a CDCl3 solution of oxaziridine 6 (0.036 mmol) was added, at
rt, trans-ꢀ-methylstyrene (0.036 mmol). The reaction was monitored by
1H NMR to determine the conversion of the olefin into the corresponding
epoxide.
(17) Probably due to the slow decompositon of oxone at rt, the
epoxidation reaction is more efficient at 0 °C.
OL800690C
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