Chemistry Letters Vol.32, No.11 (2003)
995
the mixture was stirred at ꢂ78 ꢃC for 2 h, and quenched with sat-
urated ammonium chloride. After the reaction mixture was
warmed to room temperature, the organic material was extracted
with ethyl acetate. The organic layers were combined, washed
with brine and dried over anhydrous magnesium sulfate, filtered,
and concentrated. Purification of the crude material by prepara-
tive TLC afforded the ꢁ,ꢀ-unsaturated carbonyl compound in
94% yield.15
Table 3. Butylation and arylation of 1,3-diphenyl diketones
O
O
O
1. P(OEt)3, THF
Ph
2. R2Cu(CN)Li2
O
Ph
P(OEt)2
O
O
+
Ph
Ph
R
Br
.
Ph
Ph
BF3 OEt2, THF
Unreacted
Enol Phosphate
Recovered / %
Organocuprate
Reagent
Entry
Yield / %
1
2
Bu2Cu(CN)Li2
Ph2Cu(CN)Li2
53
58
29
26
It is noted that a new and convenient method for the prepa-
ration of ꢀ-substituted ꢁ,ꢀ-unsaturated carbonyl compounds
was established on treating 2-bromo-1,3-dicarbonyl compounds
with trivalent phosphorus compound such as triethyl phosphite,
followed by the reaction with a higher-order organocuprate in
the presence of a Lewis acid additive. Thus, several correspond-
ing ꢁ,ꢀ-unsaturated carbonyl compounds were obtained in mod-
erate to excellent yields. Further study on this type of reaction is
currently in progress.
phosphate was isolated in 26% yield. Interestingly, both the de-
sired product and unreacted enol phosphate were isolated as their
single isomer. These results demonstrate that only one of two
enol phosphate isomers;namely the trans isomer is reactive
for organocuprate addition while the cis isomer does not react
with the cuprate, and was isolated from the reaction mixture.11
Indeed, these findings are further supported by the result that
higher-order butyl and aryl organocuprate12 did not add in a
1,4-manner with cis-enol phosphate. While, the enol phosphate
intermediate formed from 3-hydroxy-1H-phenalen-1-one exclu-
sively formed the enol phosphate intermediate as a single trans
isomer and subsequent addition with higher-order butyl organo-
cuprate formed the desired unsaturated ketone in 89% yield.13
A proposed reaction mechanism is shown in Scheme 1:
Triethyl phosphite reductively attacks the bromo-dicarbonyl
compound to form the stable enol phosphate intermediate 1
via a Perkow-type reaction. In the presence of a Lewis acid ad-
ditive, the higher-order organocuprate further reacts with the
enol phosphate intermediate to afford the desired ꢀ-substituted
ꢁ,ꢀ-unsaturated carbonyl compound 2.
This work was supported by the Grant of the 21st Century
COE Program from the Ministry of Education, Culture, Sports,
Science and Technology (MEXT), Japan and the JSPS postdoc-
toral fellowship for foreign researchers.
References and Notes
1
2
H. Miyaoka and Y. Yamada, Bull. Chem. Soc. Jpn., 75, 203 (2002).
Y. Kobayashi, M. G. Murugesh, M. Nakano, E. Takahisa, S. B. Usmani, and
T. Ainai, J. Org. Chem., 67, 7110 (2002).
3
S. E. Denmark, M. S. Dappen, and J. A. Sternberg, J. Org. Chem., 49, 4741
(1984);J. P. Gillet, R. Sauvetre, and J. F. Normant, Synthesis, 1982, 297;R.
M. Christie, M. Gill, and R. W. Rickards, J. Chem. Soc., Perkin Trans. 1,
1981, 593.
4
5
I. Fleming and D. A. Perry, Tetrahedron, 37, 4027 (1981).
S. Kobayashi, H. Takei, and T. Mukaiyama, Chem. Lett., 1973, 1097;R. K.
Dieter and L. A. Silks, J. Org. Chem., 51, 4687 (1986);L. A. Paquette, H. Lin,
D. T. Belmont, and J. P. Springer, J. Org. Chem., 51, 4807 (1986).
M. Alderdice, C. Spino, and L. Weiler, Can. J. Chem., 71, 1955 (1993);Y.
Mu, R. A. Gibbs, L. M. Eubanks, and C. D. Poulter, J. Org. Chem., 61,
8010 (1996).
C. P. Casey and D. F. Marten, Synth. Commun., 3, 321 (1963);C. P. Casey, D.
F. Marten, and R. A. Boggs, Tetrahedron Lett., 1973, 2071;C. P. Casey and
D. F. Marten, Tetrahedron Lett., 1974, 925.
The present reaction proceeds by a simple procedure with-
out isolation of the enol phosphate intermediate prior to alkyla-
tion;therefore, it has advantages over a similar addition reaction
reported by Sum and Weiler8 where their procedure involves the
isolation of enol phosphate.
6
7
Typical experimental procedure is as follows: Triethyl phos-
phite (0.22 mmol) was added drop-wise to a stirred solution of 2-
bromo-1,3-diphenyldiketone14 (0.20 mmol) in THF (10 mL) un-
der an argon atmosphere at room temperature and the reaction
mixture was stirred for 1 h and then cooled to ꢂ78 ꢃC. During
this time, a solution of methyl lithium in diethyl ether
(0.58 mmol) was added to a stirred suspension of copper cyanide
(0.30 mmol) in THF (10 mL) at ꢂ78 ꢃC, warmed to 0 ꢃC and stir-
ring was continued for an additional 20 min. (until CuCN dis-
solved). Boron trifluoride diethyl etherate (0.30 mmol) was add-
ed after the solution was cooled back to ꢂ78 ꢃC and the
previously prepared THF solution of enol phosphate intermedi-
ate was added dropwise via canula. After completion of addition,
8
9
F. W. Sum and L. Weiler, Can. J. Chem., 57, 1431 (1979).
H. O. House, L. E. Huber, and M. J. Umen, J. Am. Chem. Soc., 94, 8471
(1972).
´
10 F. Dayer, H. L. Dao, H. Gold, H. Rode-Gowal, H. Dahn, Helv. Chim. Acta,
57, 2201 (1974).
11 Isolation of cis and trans enol phophate isomers was achieved by preparative
thin layer chromatography with repeated elution (1:9;EtOAc:Hexane). No
decomposition or tautomerization was observed for each isomer at room tem-
perature by 1H NMR analysis. However, upon addition of BF3ꢁOEt2, tauto-
merization occurred at room temperature and a 1:1 mixture of cis and trans
isomers was observed within 1 h.
12 A small amount of alkylation product (8% yield) was isolated from the orga-
nocuprate addition of cis enol phosphate in THF at ꢂ78 ꢃC for 2 h, presum-
ably due to tautomerization to the trans isomer. Alkylation of trans enol
phosphate formed the desired product along with reduced 1,3-diketone
(56% and 23% yields, respectively) under similar conditions. No increase
in yield was observed with extended reaction time or higher temperatures
(ꢂ50 and ꢂ30 ꢃC).
O
O
O
P(OEt)
Ph
13 Determined by 1H NMR analysis using an internal standard.
14 For bromination of 1,3-dicarbonyl compounds see;D. W. Gillon, I. J. Forrest,
G. D. Meakins, M. D. Tirel, and J. D. Wallis, J. Chem. Soc., Perkin Trans. 1,
1983, 341;S.-F. Cheng, C.-S. Lin, and L. K. Liu, J. Chin. Chem. Soc., 44, 309
(1997).
2
P(OEt)3
Me2Cu(CN)Li2
1,4-addition
O
O
Ph
Ph
–EtBr
Ph
Br
1
O
15 It was also noted that 1,3-dicarbonyl compound (0.22 mmol) can be bromi-
nated with NBS (0.23 mmol) at room temperature within 30 min in THF
(10 mL) and then addition of triethyl phosphite (0.25 mmol) at 0 ꢃC formed
the enol phosphate intermediate in situ within 1 h. Subsequent addition of
the higher-order organocuprate (0.56 mmol) in the presence of boron trifluor-
ide diethyl etherate (0.56 mmol) via canula at ꢂ78 ꢃC in THF (10 mL) and
stirring for 2 h formed the ꢀ-substituted ꢁ,ꢀ-unsaturated ketone in high yield
in a one-pot procedure.
CuMeLi
Ph
P(OEt)
2
O
CH
3
O
O
–(EtO)2PO2H
CH
Ph
3
Ph
Ph
2
Scheme 1.
Published on the web (Advance View) October 6, 2003;DOI 10.1246/cl.2003.994