Organic Syntheses, CV 7, 443
Submitted by Hideki Sakurai, Akira Hosomi, and Josabro Hayashi
1.
Checked by Todd A. Blumenkopf and Clayton H. Heathcock.
1. Procedure
A
2-L, three-necked, round-bottomed flask is fitted with a
dropping funnel (Note
1),
mechanical stirrer, and
reflux condenser attached to a
nitrogen inlet. In the flask are placed
29.2 g (0.20 mol) of benzalacetone (Note
2) and
300 mL of dichloromethane (Note
3). The flask is immersed in a
dry ice–methanol bath (−40°C) and
22 mL (0.20 mol) of titanium tetrachloride (Note
4) is slowly added by syringe to the stirred mixture. After 5 min, a solution of
30.2 g (0.26 mol) of allyltrimethylsilane (Note
5) and (Note
6) in
300 mL of dichloromethane is added dropwise with stirring over a 30-min period. The resulting red–violet reaction mixture is stirred for 30 min at −40°C (Note
7), hydrolyzed by addition of 400 mL of
H2O, and, after the addition of
500 mL of ethyl ether with stirring, allowed to warm to room temperature. The nearly colorless organic layer is separated and the aqueous layer is extracted with three
500-mL portions of ethyl ether. The organic layer and
ether extracts are combined and washed successively with
500 mL of saturated sodium bicarbonate and
500 mL of saturated sodium chloride, dried over anhydrous
sodium sulfate, and evaporated at reduced pressure. The residue is distilled under reduced pressure through a
6-in. Vigreux column to give
29.2–30.0 g (
78–80%) of
4-phenyl-6-hepten-2-one, bp
69–71°C (0.2 mm),
nD20 1.5156, as a colorless liquid (Note
8).
2. Notes
1. A
500-mL dropping funnel, with pressure-equalizing arm, is used.
2.
Benzalacetone is purchased from Wako Pure Chemical Ind., Ltd. or Aldrich Chemical Company, Inc.
5. The starting
allyltrimethylsilane can be prepared in satisfactory yield by the procedure of Sommer.
2 It can also be purchased from PCR, Inc.; Aldrich Chemical Company, Inc.; Fluka A. G., Petrarch Systems, Inc.; and Tokyo Kasei Kogyo Co., Ltd. The checkers employed material from Petrarch.
6. The use of more than 1.2 equiv of
allyltrimethylsilane is essential for shortening the reaction time as well as to avoid contamination of the product by unreacted
benzalacetone.
7. Disappearance of
benzalacetone and appearance of product can be readily monitored by thin-layer or gas chromatographic analysis on a
1-m column packed with 20% Silicone SE-30 at 180°C. The reaction should be stopped as soon as disappearance of
benzalacetone is confirmed.
8. Gas chromatographic analysis of the product on a 1-m column packed with 20% Silicone SE-30 at 180°C should give a single peak. The product has the following spectral properties: IR (film) cm
−1: 1710, 1630 (C=C);
1H NMR (CDCl
3) δ: 1.97 (s, 3 H, CH
3CO), 2.35 (t, 2 H,
J = 7.5, CH
2C=C), 2.72 (d, 2 H,
J = 7.5, CH
2CO), 3.27 (quintet, 1 H,
J = 7.5, PhCH), 4.8–5.1 (m, 2 H, CH
2=C), 5.4–5.9 (m, 1 H, CH=C), 7.0–7.4 (m, 5 H, aromatic).
3. Discussion
This procedure is general for the conjugate allylation of α,β-unsaturated ketones with allysilanes.
3 Some representative examples are listed in Table I. The main advantages of the method are its wide generality and the ready availability of the necessary starting materials. The procedure is often useful for the preparation of δ,ε-unsaturated ketones that cannot be obtained in satisfactory yield by the use of
allylcuprate (e.g., entry 13) reagents.
4 Another useful aspect of the reaction is the regiospecific coupling of the allyl group. Examples of this feature can be seen in entries 2 and 5. Although cyclic as well as acyclic α,β-unsaturated ketones give satisfactory results, the reaction is slower in sterically hindered systems (entries 13 and 14). However, even in these cases, good yields are obtained by using excess allylsilane and by conducting the reaction at higher temperature. Since the allyl group can be modified by the regioselective addition of various reagents to the double bond,
5,6 the method is applicable to the synthesis of a wider variety of compounds than are shown in the Table. By oxidation of the double-bond 1,5-diketones may be obtained.
7 Conjugate allylation with allylsilanes can be used in conjunction with a suitable electrophile to achieve "one-pot" double alkylation at the adjacent vinyl position of an α,β-unsaturated ketone.
8 The method has also been utilized in the synthesis of
perhydroazulenones.
9 Allylsilanes also undergo regioselective, Lewis acid-catalyzed reaction with carbonyl compounds,
10 acetals,
11 α,β-unsaturated acetals,
12 acyl halides,
13 tertiary alkyl halides,
14 and oxiranes.
14 Such allylations can also be achieved by using allystannanes.
15
TABLE I
CONJUGATE ALLYLATION OF α,β-ENONES WITH ALLYLSILANES PROMOTED BY TITANIUM TETRACHLORIDEa
|
Entry |
Allylsilane |
α,β-Enone |
Conditions Temp., °C, time |
δ,ε-Enone |
Yield (%)b |
|
1 |
Ic |
CH2=CHCOCH3 |
−78, 1 min |
CH2=CH(CH2)3COCH3 |
59 |
2 |
IId |
CH2=CHCOCH3 |
−78, 3 hr |
CH2=C(CH3)2CH2CH2COCH3 |
79 |
3 |
I |
(CH3)2C=CHCOCH3 |
25, 5 min |
CH2=CHCH2C(CH3)2CH2COCH3 |
87 |
4 |
IIIe |
PhCH=CHCOCH3f |
−78, 0.5 min |
CH2=C(CH3)CH2CH(Ph)CH2COCH3 |
69 |
5 |
IVg |
PhCH=CHCOCH3 |
−78, 5 hr |
CH2=CHCH(CH3)CH(Ph)CH2COCH3 |
76 |
6 |
I |
PhCH=CHCOPh |
−78, 1 min |
CH2=CHCH2CH(Ph)CH2COCH3 |
96 |
7 |
I |
|
−78, 2 hr |
|
70 |
8 |
III |
|
−78, 10 min |
|
70 |
9 |
I |
|
−78, 2 hr |
|
54 |
10 |
III |
|
−78, 30 min |
|
82h |
11 |
I |
|
−78, 1 hr |
|
80i |
12 |
III |
|
−78, 10 min |
|
99j |
13 |
I |
|
−78, 18 hr then −30, 5 hr |
|
85k |
14 |
I |
|
−78, 2 hr then 0, 15 min |
|
88 |
|
|
b Yields after isolation by distillation or thin-layer chromatography.
|
|
d II = Me3SiCH2CH=C(CH3)2.
|
e III = Me3SiCH2C(CH3)=CH2.
|
f Three equivalents of the allylsilane were used.
|
g IV = trans-Me3SiCH2CH=CHCH3.
|
|
i BP 56–60°C (3 mm), nD20 1.4719.
|
j Two equivalents of the allylsilane were used.
|
k Bp 83–85°C (0.6 mm), nD20 1.5111. A diallylated product, assigned the structure 2,8a-diallyl-3,4,4a,5,6,7,8,8a-octahydronaphthalene, was obtained as a forerun in less than 5% yield.
|
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
H2O
perhydroazulenones
Me3SiCH2CH=CH2
Me3SiCH2CH=C(CH3)2
Me3SiCH2C(CH3)=CH2
trans-Me3SiCH2CH=CHCH3
CH2=CHCOCH3
CH2=C(CH3)2CH2CH2COCH3
(CH3)2C=CHCOCH3
CH2=CHCH2C(CH3)2CH2COCH3
PhCH=CHCOCH3
CH2=C(CH3)CH2CH(Ph)CH2COCH3
CH2=CHCH(CH3)CH(Ph)CH2COCH3
PhCH=CHCOPh
CH2=CHCH2CH(Ph)CH2COCH3
calcium chloride (10043-52-4)
ether,
ethyl ether (60-29-7)
sodium bicarbonate (144-55-8)
sodium chloride (7647-14-5)
sodium sulfate (7757-82-6)
copper powder (7440-50-8)
Benzalacetone (122-57-6)
dichloromethane (75-09-2)
titanium tetrachloride (7550-45-0)
calcium hydride (7789-78-8)
4-Phenyl-6-hepten-2-one,
6-Hepten-2-one, 4-phenyl- (69492-29-1)
allyltrimethylsilane (762-72-1)
allylcuprate
allylsilane (18191-59-8)
2,8a-diallyl-3,4,4a,5,6,7,8,8a-octahydronaphthalene
1-methyl-1-trimethylsilylmethyl-3-n-propylspiro[3,4]octan-5-one
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