2
336
L. El Kaim et al.
LETTER
allyloxy group, gave the rearranged phosphate 4e in a low Other promising applications such as the use of silylated
6% yield along with its hydroxyphosphonate precursor hydroxyphosphonates to induce pinacol-type couplings
21% isolated yield). Furfural 2j does not rearrange under are underway and will be reported in due course.
2
(
these conditions whereas electron-poor pyridine-2-alde-
hyde (2f) gives phosphate 4g in good yield after a short
reaction time.
Phosphate 4a; Typical Procedure
To a solution of 2a in DMF (0.3 M, solvent distilled and stored on
molecular sieves) was added dimethylphosphite (1 equiv) in DBU
a,b-Unsaturated aldehydes give various products in mod-
erate to poor yields. Although one report of phosphate
formation from cinnamaldehyde upon treatment with
(10%) under argon. The reaction was left at r.t. for 1 h and was then
heated for 2 h at 80 °C. The solvent was distilled under reduced
pressure and the crude was purified by flash chromatography on
silica gel (CH Cl –EtOAc, 70:30).
7
dialkylphosphite was found in the literature, under our
conditions, inseparable mixtures are obtained with
cinnamaldehyde 2l. However, when citral 2m is used, the
phosphate adduct 4j is isolated in 51% isolated yield.
These facts can be best explained by the lower efficiency
of competing Michael additions when the substitution pat-
tern on the olefin is increased. Simple aliphatic aldehyde
2
2
IR: 1500, 1460, 1270, 1040 cm–1.
1
H NMR (CDCl , 400 MHz): d = 7.91–7.37 (m, 7 H), 5.30 (d, J =
3
1
2.0 Hz, 2 H), 3.76 (d, J = 12.0 Hz, 6 H).
1
3
C NMR (CDCl , 100.6 MHz): d = 135.2, 133.5, 131.6, 127.9,
3
1
27.5, 127.4, 127.2, 126.7, 125.7, 124.8, 71.7, 49.5.
2
k forms the related hydroxyphosphonate as the only
isolable compound (90% isolated yield). In contrast to the
results observed with dimethylphosphite; hydroxyphos- Anal. Calcd for C13
+
MS (ID, IC, NH ): m/z = 268 (MH ).
3
H O P: C, 58.65; H, 5.68. Found: C, 58.82; H,
15 4
5
.86.
phonates obtained from diethylphosphite are reluctant to
rearrange under these conditions, forming phosphates in
low yields with long reaction times (4b).
References
Ketones are less reactive and do not form phosphates (e.g.
(
1) (a) Pudovik, A. N.; Konovalova, I. V. Synthesis 1979, 81.
b) Texier-Boullet, F.; Foucaud, A. Synthesis 1982, 916.
2
i) unless substituted by electron withdrawing groups: 2-
pyridyl methyl ketone (2g) and trifluoroacetophenone
2h) gave phosphates 4h and 4i in 57% and 58% isolated
(
(c) Patel, D. V.; Rielly-Gauvin, K.; Ryono, D. E.; Free, C.
A.; Rogers, W. L.; Smith, S. A.; DeForrest, J. M.; Oehl, R.
S.; Petrillo, E. W. J. Med. Chem. 1995, 38, 4557.
(
yields, respectively.
(
2) Rowe, B. J.; Spilling, C. D. Tetrahedron: Asymmetry 2001,
These new conditions afford a straightforward reductive
procedure for the formation of allylic and benzylic mixed
phosphate esters. Besides their biological interest, these
esters can be used as intermediates in further synthetic
transformations. In this sense, the presence of a nitro
1
2, 1701.
(3) (a) Pudovik, A. N.; Gur’yanova, I. V.; Zimin, M. G.;
Durnova, A. V. Zh. Obshch. Khim. 1969, 39, 1018.
(b) Pudovik, A. N.; Konovalova, I. V.; Dedova, L. V. Zh.
Obshch. Khim. 1964, 34, 2902. (c) Konovalova, I. V.;
Burnaeva, L. A.; Loginova, I. V.; Pudovik, A. N. Zh.
Obshch. Khim. 1991, 61, 1018. (d) Polezhaeva, N. A.;
Ovodova, O. V.; Litivinov, I. A.; El’shina, E. V.; Naumov,
V. A.; Arbuzov, B. A. Izv. Akad. Nauk. SSSR, Ser. Khim.
1986, 8, 1860.
group on the aromatic aldehyde could trigger both phos-
8
phite addition and photostimulated S 1 reaction of the
RN
resulting phosphate with various nucleophiles. Indeed, the
addition of dimethylphosphite to nitrobenzaldehyde (2c)
followed by further addition of nitroethylcyclohexene,
potassium tert-butoxide and irradiation of the mixture
afforded the new nitro derivatives 5 in 56% isolated yield
(4) (a) Fokin, A. V.; Studnev, Y. N.; Rapkin, A. I.; Pasevina, K.
I.; Verenikin, O. V.; Kolomiets, A. F. Izv. Akad. Nauk. SSSR,
Ser. Khim. 1981, 7, 1655. (b) Krutikov, V. I.; Aleinikov, S.
F.; Rogozina, I. N.; Lavrent’ev, A. N. Zh. Obshch. Khim.
(
Scheme 2).
1
986, 56, 2027.
5) Timmler, H.; Kurz, J. Chem. Ber. 1971, 104, 3740.
(6) (a) Gallagher, M. J.; Jenkins, I. D. J. Chem. Soc. C 1969,
605. (b) Floyd, A. J.; Symes, K. C.; Fray, G. I.; Gymer, G.
(
O
O
O2N
2
1) HP(OMe)2, DBU cat
E.; Oppenheimer, A. W. Tetrahedron Lett. 1970, 20, 1735.
(7) There is one report of phosphate formation (without yield
given) from a-hydroxycinnamylphosphate by treatment with
sodium methoxide in methanol: Arbuzov, B. A.; Tudrii, G.
A.; Fuzhenkova, A. V. Izv. Akad. Nauk. SSSR, Ser. Khim.
Me
NO2
Me
NO2
56%
2)
(2 equiv)
2c
5
NO2
t-BuOK (2 equiv), hν
1
977, 9, 2156.
8) Rossi, R. A.; Pierini, A. B.; Penenory, A. B. Chem. Rev.
003, 103, 71.
Scheme 2
(
2
Synlett 2005, No. 15, 2335–2336 © Thieme Stuttgart · New York