The selective 1,2-addition of ketene silyl acetals to α,β-unsaturated ketones promoted by a copper(I)-phosphine complex

Article abstract of DOI:10.1246/cl.2002.1142

The thermal reaction of an α,β-unsaturated ketones with a ketene silyl acetal in the presence of the copper(I)halide-phosphine complex brought about the selective formation of the products based on 1,2-addition, while use of the copper(I)halide alone affo

Full text of DOI:10.1246/cl.2002.1142

1142
Chemistry Letters 2002
The Selective 1,2-Addition of Ketene Silyl Acetals to ꢀ,ꢁ-unsaturated Ketones Promoted by
a Copper(I)-Phosphine Complex
Michiharu Mitaniꢀ, Kouji Ishimoto, and Ryuhei Koyama
Department of Chemistry and Material Engineering, Faculty of Engineering, Shinshu University, Wakasato, Nagano 380-8553
(Received August 21, 2002; CL-020711)
The thermal reaction of an ꢀ,ꢁ-unsaturated ketones with a
ketene silyl acetal in the presence of the copper(I)halide-
phosphine complex brought about the selective formation of the
products based on 1,2-addition, while use of the copper(I)halide
alone afforded the 1,4-adduct type of product.
ꢀ,ꢁ-unsaturated carbonyl compounds have two alternative
modes of addition with nucleophiles, i.e., 1,2- or 1,4-addition.
While 1,2-direct addition to a carbonyl group is favored with alkyl
lithium reagents1 which are hard nucleophiles, 1,4-conjugated
addition is realized with alkyl copper reagents.2 Stabilized
carbanions also perform direct or conjugated addition depending
upon the types of reagent; for example, enolates3 from ꢁ-
Scheme 1.
dicarbonyl compounds or ketones, ꢀ-nitro anions,4 and thioacetal
monosulfoxide anions5 selectively undergo 1,4-addition, ꢀ-
that in the procedure using 2 isolated. Again, omitting the copper
species from this reaction system did not bring about formation of
nitrile anions6 and dithiane anions7 effect 1,2- and 1,4-addition.
Enolates derived from esters have been reported to prefer 1,4-
an addition product. Thus, the investigations were hereafter
addition under thermodynamically controlled conditions, while
1,2-addition under kinetically controlled conditions; i.e.,
performed using a method to prepare in situ the ketene silyl
acetals. Use of CuBr instead of CuCl gave 3a in an almost same
although 1,2-adducts are preferentially formed at low tempera-
yield (51%) as that in CuCl.
ture (ꢁ78 ꢂC), warming a reaction mixture to room temperature
Then, the reactions were performed in some solvents other
than THF, in which tributylphosphine was used as a ligand
results in selective formation of 1,4-adducts.8 Silyl enol ethers
and ketene silyl acetals, which have more covalent character than
because the triphenylphosphine complex of cuprous bromide was
alkali metal enolates, are able to give ꢁ-substituted ketones based
on 1,4-addition under promotion by a conventional Lewis acid
little solved in those solvents except for THF. The results are
shown in Table 1. Although the well-defined relationship
between yields of 3a and the polarities of solvents was not
such as titanium tetrachloride.9 We have previously reported that
cuprous chloride catalyzes 1,4-addition accompanying the silyl
observed, it is worth noting that diethyl ether was the best of the
group transfer of silyl enol ethers and ketene silyl acetals to
conjugated enones under photo-irradiation.10 To contrary to our
previous findings, we have recently found that the copper(I)-
phosphine complex promotes the 1,2-addition reaction of ketene
silyl acetals to conjugated enones under thermal conditions.
examined solvents (Table 1, run 2), while other ether solvents
(THF and 1,2-dimethoxyethane) afforded the lower yields of 3a
(Table 1, run 1 and 3) along with remaining of the starting
material 1 than the hydrocarbon solvents (i.e., hexane and
cyclohexane, Table 1, run 5 and 6). In turn, the reaction using
At first, a solution composed of 2-cyclohexen-1-one 1a
(2 mmol), the methyl propionate-derived ketene silyl acetal 2
Table 1. Recation of 2-cyclohexen-1-one 1a with the ketene
silyl acetal generated in situ from methyl propionate
(3 mmol), CuCl(PPh3)2 (2 mmol) andTHF (5 ml) was refluxed for
4 h under a nitrogen atmosphere. VPC analysis of the resulting
mixture revealed appearance of one volatile product, which was
assigned to be the 1,2-adduct 3a from spectral data11 after
isolation (52% yield) (Scheme 1). Use of CuCl alone instead of
CuCl(PPh3)2 resulted in selective formation of the 1,4-addition
product 4 albeit in a low yield (24%) (Scheme 1). Furthermore, a
reaction without CuCl did not form any addition product. Next, a
method consisting of in situ preparation of 2 was examined in
order to avoid rather troublesome isolation procedure of the
ketene silyl acetal. When methyl propionate (3.3 mmol), Me3SiCl
(8 mmol), LDA (3.3 mmol), 1a (2 mmol), and CuCl(PPh3)2
(2 mmol) were successively added to a THF solvent (5 ml) in a
flask under a nitrogen atmosphere and then refluxed for 4 h, 3a
was obtained in 49% yield, which was almost comparable with
Run
Solvent
Temp./ꢂC
PR3
3a Yielda/%
1
2
3
4
5
6
THF
66
35
85
70
69
81
PBu3
PBu3
PBu3
PBu3
PBu3
PBu3
39
63
16
55
57
60
diethyl ether
1,2-DME
DMF
hexane
cyclohexane
7diethyl ether
aDetermined by VPC analysis.
bIsolated yield after column chromatography.
35
PPh
75 (72)b
3
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
1143
triphenylphosphine as a ligand in diethyl ether, although the
soluble complex of cuprous bromide was not formed at the initial
stage of mixing, was examined, resulting in the better yield than
that in the reaction using tributylphosphine (Table 1, run 2 and 7).
Methyl alkanoates other than methyl propionate also gave
1,2-adducts with 1a in the reaction in a diethyl ether solution
containing cuprous bromide and triphenylphosphine.12 N,N-
dimethylacetamide similarly effected the 1,2-adduct, although in
a lower yield (54%) compared with methyl acetate being the
corresponding ester analogue. The reactions of methyl propionate
with ꢀ,ꢁ-unsaturated ketones other than 1a were in turn
performed to afford the 1,2-adducts. These results are shown in
Table 2, in which the reactions afforded the 1,2-adducts 3 (e.g.,
run, 5, 7, and 9) in moderate yields with some starting materials
remained 1.
acids. Thus, peculiar promotion with the copper(I)-phosphine
complex probably operates in our reaction to effect selective
formation of the 1,2-adducts, and it might be likely as a working
hypothesis that simultaneous coordination of the conjugated
enone and the ketene silyl acetal to the copper(I)-phosphine
complex triggers the 1,2-addition reaction, although the precise
mechanism is unclear at this stage.
Our method necessitates the use of a stoichiometric amount
of the copper(I)halide-phosphine complex, which might be owing
to its relatively low Lewis acidity as revealed by requisition of
rather severe reaction conditions (reflux, 4 h). Thus, possibility
that the 1,2-addition reaction of this type may be catalytically
performed by using the phosphine complexes of metal species
bearing the enhanced Lewis acidities compared with CuBr
remains to be investigated. Furthermore, for development of the
asymmetric version, the reaction using the chiral phosphine
complexes will be a target to be challenged.
Table 2. Reaction of ꢀ,ꢁ-unsaturated ketones with ketene silyl
acetals generated in situ
References and Notes
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A. G. Schultz and Y. K. Yee, J. Org. Chem., 41, 4045 (1976).
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11 Spectral data of 3a: 1H NMR(CDCl3/CCl4, 60 MHz) ꢂ 0.04 (s,
9H), 1.08 (d, J ¼ 6:8 Hz, 3H), 1.52–2.31 (m, 6H), 2.55 (q,
J ¼ 6:8 Hz, 1H), 3.65 (s, 3H), 5.98 (br.s, 2H); 13C NMR
(CDCl3/CCl4, 15 MHz) ꢂ 1.90, 12.77, 25.06, 31.64, 32.83,
49.14, 50.76, 134.32, 134.86; MS (EI) m/z (%) 256 (0.5, Mþ),
241 (50), 170 (100), 145 (94), 107 (75), 89 (98), 73 (96); HRMS
m/z Calcd for C13H24O3Si 256.1493, Found 256.1521.
12 A typical experiment is as follows. To a solution consisting of an
ester (3.3 mmol), TMSCl (8 mmol) and Et2O (5 ml), LDA
(3.3 mmol, 2.0 mol dmꢁ3 in heptane/THF/ethylbenzene) was
added under nitrogen atmosphere at 0 ꢂC and stirred for 30 min.
Then, a conjugated enone (2 mmol), CuBr (2 mmol) and PPh3
(4 mmol) were successively added and the reaction mixture was
refluxed for 4 h. After the solid parts were filtered off, the filtrate
was submitted to preparative VPC.
Concerning the reaction mechanism, the activating effect of
the Lewis acid such as titanium tetrachloride on the reaction of
conjugated enones with silyl enol ethers has been assumed to be
brought about by coordination to the oxygen atom of the
conjugated enone to enhance its electrophilicity and facilitate
attack by silyl enol ethers to form the 1,4-adducts.13 Actually, use
of cuprous chloride alone in our reaction also brought about the
1,4-adduct similarly to promotion by the conventional Lewis
13 C. H. Heathcock, M. H. Norman, and D. E. Uehling, J. Am.
Chem. Soc., 107, 2797 (1985).