Allylation of ketones with allylstannanes catalyzed by Lewis acid-Lewis base combined reagents

Article abstract of DOI:10.1016/S0040-4039(00)01755-X

Although the Lewis acid promoted allylation of ketones with allylstannanes gives the corresponding tert-homoallyl alcohols in lower yields in comparison with those of aldehydes, the use of Lewis acid-Lewis base combined catalysts such as Zn(OTf)₂-2,6-lutidine and Zn(OTf)₂-pyridine dramatically enhances the yield of the tert-alcohols. (C) 2000 Published by Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01755-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9883–9887
Allylation of ketones with allylstannanes catalyzed by Lewis
acid–Lewis base combined reagents
Ryo Hamasaki, Yukiyasu Chounan, Hiroshi Horino and Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
Received 2 October 2000; accepted 9 October 2000
Abstract
Although the Lewis acid promoted allylation of ketones with allylstannanes gives the corresponding
tert-homoallyl alcohols in lower yields in comparison with those of aldehydes, the use of Lewis
acid–Lewis base combined catalysts such as Zn(OTf) –2,6-lutidine and Zn(OTf) –pyridine dramatically
2
2
enhances the yield of the tert-alcohols. © 2000 Published by Elsevier Science Ltd.
The Lewis acid promoted allylation of aldehydes with allylstannanes is a useful method for
1
synthesizing homoallyl alcohols. Diastereoselective and enantioselective allylation with allyl-
2
stannanes has been studied mostly for aldehydes. However, allylation of ketones has been
scarcely reported. Perhaps, this is due to the lower reactivity of ketones, compared to aldehydes,
towards allylstannanes. For example, the reaction of benzaldehyde with tetraallylstannane 1 in
the presence of catalytic amounts of aq. HCl gave the corresponding homoallyl alcohol 2 in 88%
3
yield, whereas the reaction of acetophenone with 1 under the same conditions did not give the
3
corresponding allylation product 3 at all (Eq. (1)). The Sc(OTf) catalyzed reaction of 1 with
3
benzaldehyde in THF/H O gave 2 in 94% yield, whereas the Sc(OTf) catalyzed reaction of 1
2
3
Ph
Ph
aq. HCl / THF
aq. HCl / THF
20 ºC, I hr.
Sn
20 ºC, I hr.
4
H C
3
OH
OH
Ph
CH3
Ph
H
(
(
1)
2)
3
~0%
1
1
2
88%
O
O
Ph
Ph
5
mol% Sc(OTf)3
5 mol% Sc(OTf)3
H O/THF(1:9), rt
Sn
CH Cl , rt
4
H C
3
OH
2
2
2
OH
Ph
CH3
Ph
H
3
77%
2
94%
O
O
*
Corresponding author.
0
040-4039/00/$ - see front matter © 2000 Published by Elsevier Science Ltd.
PII: S0040-4039(00)01755-X

9884
4
with acetophenone proceeded only in dry CH Cl affording 3 in 77% yield (Eq. (2)); the Lewis
2
2
acidity of Sc(OTf) in a non-coordinative solvent such as CH Cl seems to be stronger than that
3
2
2
in a coordinative solvent such as THF. As can be seen from the above examples, the reactivity
of simple ketones in the Lewis acid (or protic acid) promoted allylation with allylstannanes is
significantly lower than that of simple aldehydes, primarily due to both steric and electronic
5
effects.
We also observed lower reactivity of acetophenone in the Zn(OTf) catalyzed (10 mol%)
2
allylation with 1: only 16% of 3 was formed after 1 day in CH Cl at room temperature. The
2
2
lower chemical yield (16%) in this case, in comparison with 77% in Eq. (2), is understandable
since the Lewis acidity of Zn(OTf) is weaker than that of Sc(OTf) . However, we have
2
3
6
discovered that a Zn(OTf ) –pyridine combined reagent system enhances dramatically the
2
chemical yield in the allylation of acetophenone with 1; 3 was obtained in 94% yield in the
presence of 10 mol% Zn(OTf) –10 mol% pyridine after 1 day in CH Cl at room temperature
2
2
2
(
Eq. (3)).
1
0 mol% Zn(OTf)2
Ph
CH3
Ph
H C
Sn
10 mol% pyridine
+
4
OH
(3)
3
O
CH Cl , rt, 1 day
2
2
1
3
94%
A detailed investigation on the effect of bases was carried out using acetophenone (1 equiv.),
(1 equiv.), base (10 mol%), and 10 mol% Zn(OTf) The results are summarized in Table 1.
1
2.
The use of Zn(OTf) alone is ineffective (entry 1), as stated above. Pyridine, PhNMe ,
2
2
2
,6-lutidine and 2,6-di-tert-butylpyridine are quite effective (entries 2–5). Et N, Dabco, DBU
3
and 2,2%-dipyridyl are not effective (entries 6–9). Only a trace amount of the allylation product
was obtained in the presence of i-Pr NEt (entry 10). Additives other than the above nitrogen
2
bases were tested; 10 mol% Zn(OTf) –10 mol% PPh and 10 mol% Zn(OTf) –10 mol% HCl in
2
3
2
Et O were examined but the results were unsatisfactory. Next, we examined the effect of the
2
Table 1
Effect of additive on catalytic allylation of acetophenone with tetraallylstannane
Ph
CH3
10 mol% Zn(OTf)2
10 mol% additive
CH Cl , rt, 1 day
Ph
Sn
+
4
H C
3
OH
O
2
2
1
3
a
a
Entry
Additive
Yield (%)
Recovery (%)
1
2
3
4
5
6
7
8
9
–
16
94
84
–
–
–
–
52
89
86
79
83
Pyridine
PhNMe2
2,6-Lutidine
2,6-Di-tert-butylpyridine
Et N
Dabco
DBU
2,2%-Dipyridyl
i-Pr NEt
Quant.
Quant.
Quant.
48
Trace
14
3
21
Trace
1
0
2
a
1
Yields of 3 and recovery of acetophenone were determined by H NMR using an internal standard (1,4-dioxane).

9885
allylstannane (1 equiv.) on the reaction of acetophenone (1 equiv.) in the presence of 10 mol%
Zn(OTf) and 10 mol% pyridine in CH Cl at room temperature for 1 day: 94% of 3 was
2
2
2
obtained with 1, 59% of 3 with (CH ꢀCHCH ) SnBu , and 19% of 3 with (CH ꢀCHCH )SnBu ;
2
2 2
2
2
2
3
acetophenone was recovered in the last two cases. It may be said that the use of 1 is not
necessarily desirable since only one of the four allyl groups can be utilized and the remaining
three allyl groups have to be discarded. Fortunately, the use of 2,6-lutidine, instead of pyridine,
enhanced the yield of 3 even in the reaction of (CH ꢀCHCH )SnBu : 79% of 3 was obtained
2
2
3
along with 20% of the recovered acetophenone. This result should be compared with that of the
Sc(OTf) catalyzed allylation with (CH ꢀCHCH )SnBu : only 54% of 3 was obtained even using
3
2
2
3
the much stronger and expensive Sc(OTf) . Then we searched for the optimized reaction
3
conditions in the Zn(OTf) –2,6-lutidine promoted reaction of acetophenone (1 equiv.) with 1 (1
2
equiv.). The following three conditions (amount of Zn(OTf) , amount of 2,6-lutidine, reaction
2
time) gave 3 in quantitative yield; (10 mol%, 1 mol%, 1 day), (1 mol%, 10 mol%, 1 day), (1
mol%, 1 mol%, 1 day). If we used 10 mol% Zn(OTf) and 10 mol% 2,6-lutidine, 94% of 3 was
2
obtained even after 1 h.
The allylation of several different kinds of ketone with 1 was examined in the presence of 10
mol% Zn(OTf) –10 mol% 2,6-lutidine in CH Cl at room temperature for 1 day, and the results
2
2
2
are summarized in Table 2. Arylmethyl ketones bearing an EWG at the para-position of the
aromatic ring gave the corresponding allylation products in quantitative yield (entries 1–3).
Arylmethyl ketones bearing an EDG such as p-Me or p-MeO gave quantitative or high yields
of the allylation products (entries 4 and 5). However, a p-Me N substituent halted the allylation
2
completely (entry 6), the reason for which is not clear at present. In general, aliphatic ketones
and a,b-unsaturated ketones underwent the allylation without problem (entries 7–11). Not only
arylmethyl ketones but also phenylethyl ketone and benzophenone afforded the corresponding
allylation products in quantitative yield (entries 12 and 13).
It is clear that the Zn(OTf) –2,6-lutidine catalyst is very effective for the allylation of ketones
2
with 1. Two remaining questions at this point were (1) whether other metal triflates can be
6
applied or not, and more importantly (2) whether allyltributylstannane is applicable or not. The
reaction of acetophenone with allyltributylstannane in 10 mol% catalyst in CH Cl at room
2
2
temperature for 1 day was examined. (Catalyst, yield of 3, recovery of acetophenone) is shown
below. (Sc(OTf) , 54, 15), (Sc(OTf) –2,6-lutidine, 93, 7), (Hf(OTf) –2,6-lutidine, 52, 46),
3
3
4
(
Cp Ti(OTf) –2,6-lutidine, 23, 49). Accordingly, the Sc(OTf) –2,6-lutidine catalyst is more
2
2
3
effective than the Zn(OTf) –2,6-lutidine system in the reaction with allyltributylstannane.
2
A representative procedure is shown for the reaction of acetophenone with tetraallylstannane
using a Zn(OTf) –2,6-lutidine catalyst. To a mixture of Zn(OTf) (14.6 mg, 0.04 mmol) and
2
2
2
,6-lutidine (4.7 ml, 0.04 mmol) in dry CH Cl were added acetophenone (48 ml, 0.4 mmol) and
2
2
tetraallylstannane (110 ml, 0.44 mmol) under an Ar atmosphere. The reaction was carried out at
room temperature for 1 day and quenched with sat. aqueous NaHCO solution (4 ml). The
3
product was extracted with Et O and dried with Na SO . The solvent was evaporated, and the
2
2
4
product was purified by silica gel column chromatography, giving 3 (64.8 mg) in a quantitative
yield.
7
In conclusion, we have found that the Lewis acid–Lewis base catalysts, such as Zn(OTf) –2,6-
2
lutidine and Sc(OTf) –2,6-lutidine, are quite effective for converting ketones into the correspond-
3
ing homoallyl alcohols. Further investigation on diastereo- and enantio-selective allylation using
the new catalyst system is currently in progress in our laboratories.

9886
Table 2
Allylation of ketones catalyzed by Zn(OTf) –2,6-lutidine
2
R1
R2
R1
10 mol% Zn(OTf)2
10 mol% 2,6-Lutidine
Sn
+
4
R2 OH
CH Cl , rt, 1 day
O
1
2
2
3
yield (%) a
quant
recovery (%)a
-
entry
R1
R2
p-NO C H
2 6 4
CH3
1
2
3
4
p-ClC6H4
p-FC6H4
CH3
CH3
CH3
quant
quant
quant
-
-
-
p-MeC6H4
5
6
7
8
p-MeOC6H4
p-Me2NC6H4
n-C7H15
CH3
CH3
CH3
CH3
86
-
7
92
-
quant
quant
PhCH=CH
-
9
CH3
80
82
trace
-
10
O
11
O
80
-
1
1
2
3
Ph
Ph
Et
quant
quant
-
-
Ph
a
Isolated yield.
References
1. For review, see: Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207.
2. For examples of diastereoselective and enantioselective allylation of aldehydes with allylstannanes, see: (a)
Yamamoto, Y.; Maruyama, K. Heterocycles 1982, 18, 357. (b) Hoffmann, R. W. Angew. Chem., Int. Ed. Engl.
1982, 21, 555. (c) Yamamoto, Y. Acc. Chem. Res. 1987, 20, 243. (d) Yamamoto, Y. Aldrichim. Acta 1987, 20, 45.
(
e) Yamamoto, Y.; Saito, K. J. Chem. Soc., Chem. Commun. 1989, 1676. (f) Yanagisawa, A.; Nakashima, H.;
Ishiba, A.; Yamamoto, H. J. Am. Chem. Soc. 1996, 118, 4723.
3
. (a) Yanagisawa, A.; Inoue, H.; Morodome, M.; Yamamoto, H. J. Am. Chem. Soc. 1993, 115, 10356. The reaction
of ketones with allylstannanes has been reported in the following papers. Simple ketones such as acetophenone are
not reacted under those reaction conditions, but ketones having rather uncommon structure are handled. (b) Ley,
S. V.; Cox, L. R. J. Chem. Soc., Perkin Trans. 1 1997, 3315. (c) Shibata, I.; Fukuoka, S.; Yoshimura, N.; Matsuda,
H.; Baba, A. J. Org. Chem. 1997, 62, 3790. (d) Takeda, K.; Nakajima, A.; Yoshii, E. Synlett 1996, 753. (e)
Takuwa, A.; Saito, H.; Nishigaichi, Y. Chem. Commun. 1999, 1963. (f) For the reaction of ketones through
transmetallation of allyltin into allylindium, see: Miyai, T.; Inoue, K.; Yasuda, Y.; Baba, A. Synlett 1997, 699.
. Hachiya, I.; Kobayashi, S. J. Org. Chem. 1993, 58, 6958.
4

9887
5
6
7
. (a) Cokley, T. M.; Harvey, P. J.; Marshall, R. L.; McCluskey, A.; Young, D. J. J. Org. Chem. 1997, 62, 1961. (b)
Yasuda, M.; Kitahara, N.; Fujibayashi, T.; Baba, A. Chem. Lett. 1998, 743.
. As stated above, 79% of 3 was obtained with Zn(OTf) –2,6-lutidine, but this was not necessarily satisfactory for
2
us.
. A referee pointed out that the present catalyst system is rather similar to the TiCl /N-methylaniline system for the
4
allylation of allylic alcohols: Saito, T.; Itoh, A.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1979, 37, 3519. We
appreciate this comment.
.