Checked by T. R. Vedananda and James D. White.
1. Procedure
A.
(1-Ethenyl)heptanyl 3-ketobutanoate. 3-Hydroxy-1-nonene ((Note 1), 7.5 g, 0.053 mol) is stirred in
250 mL of anhydrous ether (Note
2) in a
500-mL, three-necked, round-bottomed flask, fitted with a thermometer, a nitrogen/mineral oil bubbler, a Teflon-covered magnetic stirring bar, and a
rubber septum. A constant flow of
nitrogen is maintained throughout the reaction. To this clear homogeneous solution,
diketene ((Note 3), 5.04 g, 0.060 mol) is added in one portion by
syringe, followed by
4-dimethylaminopyridine (DMAP) (0.591 g, 0.0049 mol, (Note
4)). A slightly exothermic reaction (to 32°C) is observed. After 15 min, the reaction is complete (Note
5). The reaction mixture is quenched with
100 mL of 0.1% sodium hydroxide solution and
100 mL of anhydrous ether. The layers are separated and the organic phase is washed once with
50 mL of 0.1% sodium hydroxide solution and once with
brine. Drying over
magnesium sulfate and concentration under reduced pressure affords
11.3 g (0.05 mol,
94%) of a pale-yellow oil. The β-keto ester is of high purity, as shown by TLC, GLC, and spectral analyses (Note
6); however, distillation (bp
113–114°C/1.4 mm) leads to a colorless oil.
B.
2-Carboxy-5-dodecen-2-one. A solution of
lithium diisopropylamide (LDA, (Note
7)) in
150 mL of tetrahydrofuran (Note
8) is prepared from
0.199 mol (20.12 g) of diisopropylamine (Note
9) and
0.181 mol of butyllithium (Note
10) and (Note
11). The solution is cooled to −78°C (acetone–dry ice) and a solution of
10.0 g (0.044 mol) of (1-ethenyl)heptanyl 3-ketobutanoate in
50 mL of tetrahydrofuran (Note
8) is added via a
12-mL, pressure-equalizing dropping funnel at −78°C over a 15-min period. After the addition is complete, the reaction mixture is stirred at −78°C for 45 min and is then allowed to warm gradually to room temperature. When the reaction mixture finally reaches 25°C (about 2 hr), it has a deep-red color. After the mixture is stirred for 18 hr at room temperature, the reaction is complete (Note
12). To this mixture, 100 mL of water and
100 mL of pentane are added in portions with stirring, maintaining the temperature below 25°C with an
ice bath. As the deep-red reaction mixture is quenched, an orange heterogeneous mixture results. The layers are separated and the
pentane layer is extracted 2 times with
50 mL of 0.1% sodium hydroxide solution (Note
13). All aqueous layers are combined in a
800-mL beaker equipped with a Teflon-covered magnetic stirring bar. A
100-mL aliquot of pentane is added to this aqueous mixture, which is stirred vigorously, and then
100 mL of 10% hydrochloric acid solution is added in 10-mL portions until pH 2 is reached (Note
14). The heterogeneous solution is poured into a
1-L separatory funnel and the layers are quickly separated. The aqueous layer is extracted 3 times more, each time with
50 mL of pentane. The combined organic layers (ca. 250–300 mL) are dried
(MgSO4), and evaporated at reduced pressure without heating, to give
9.6 g (0.04 mol,
97%) of a red-orange oil. This carboxylic acid is of high purity as shown by TLC and spectral analyses (Note
15).
C.
5-Dodecen-2-one. The
3-carboxy-5-dodecen-2-one (9.0 g, 0.040 mol) is stirred in
150 mL of carbon tetrachloride (Note
16) in a 500-mL, three-necked, round-bottomed flask that is fitted with a
reflux condenser, a thermometer, a Teflon-covered magnetic stirrer, and a
ground-glass stopper. After the orange-yellow solution is heated at reflux for 1 hr, TLC analysis shows the reaction to be complete (Note
17). The reaction mixture is concentrated under reduced pressure with warming to afford
7.1 g (0.039 mol,
98%) of a red-orange oil. The product is sufficiently pure for most purposes. It may be purified by vacuum distillation at
105–107°C/2.7 mm (
5.2 g, 0.03 mol,
71%), which yields a pale-yellow oil (Note
18).
2. Notes
1.
3-Hydroxy-1-nonene was prepared by the following procedure. First,
0.219 mol (25.0 g) of heptaldehyde (Eastman Kodak Co.), distilled prior to use, was stirred in
450 mL of anhydrous ether (Note
2) under a
nitrogen atmosphere. The solution was cooled to 0°C with an ice bath and
0.260 mol (260.4 mL) of vinylmagnesium bromide (1.0 M solution in tetrahydrofuran, Aldrich Chemical Company, Inc., 1.2 equiv) was then added dropwise over a 0.5-hr period. The reaction mixture was allowed to warm gradually to room temperature and was stirred for 0.5 hr. The reaction mixture was added, in portions with stirring, to
400 mL of a saturated ammonium chloride solution, maintaining the temperature below 25°C with an ice bath. This quenched reaction mixture was stirred for 15 min. The layers were separated and the aqueous layer was extracted 2 times, each time with
200 mL of ether. The combined organic layers were extracted with
200 mL of brine, dried (
MgSO4), and concentrated under reduced pressure with warming to afford a yellow oil in quantitative yield. The allylic alcohol was distilled (bp
185°C/760 mm,
25 g,
0.158 mol,
73%) before use. Silica gel TLC showed one spot:
Rf = 0.34 (
20% ethyl acetate/ligroin). GLC: retention time, 4.56 min. Program: 40°C/1 min; 20°C/1 min to 320°C; 2% OV-101, 0.2% Carbowax on Chromosorb. This program and column were used throughout the entire sequence of reactions. IR (neat) cm
−1: 3610 (OH); 3000 (C-H, alkenes); 1650 (C=C); 1000 (C-O). Mass spectrum:
m/e 57 [100% M
+-CH
2(CH
2)
4CH
3], 85 (7.7% M
+-CHOHCH=CH
2), 113 (2.5% M
+-CH
2CH
3).
1H NMR (CDCl
3) δ: 0.91 (t, 1 H,
J = 6.9), 1.54–1.31 (m, 11 H), 4.12 (q, 1 H,
J = 6.3), 5.27–5.11 (m, 1 H), 5.95–5.84 (m, 1 H);
13C NMR (CDCl
3) δ: 14.0, 22.6, 25.4, 29.3, 31.9, 37.1, 72.9, 114.0, 141.5.
2.
Anhydrous ether (Fisher Scientific Company) was used without further drying.
3.
Diketene (Aldrich Chemical Company, Inc.) was distilled immediately prior to use.
5. Reaction progress can be monitored by GLC analysis of the disappearance of
diketene.
6. Silica gel TLC shows one spot at
Rf = 0.45 (
20% ethyl acetate/ligroin); GLC shows >95% purity of the β-keto ester. The β-keto ester undergoes partial cleavage to the corresponding allylic alcohol under the following GLC conditions. Retention time, 7.8 [
(1-ethenyl)heptanyl 3-ketobutanoate]; retention time, 4.88 (
3-hydroxy-1-nonene). Mass spectrum for the β-keto ester:
m/e 43 (100% M
+-COCH
3), 85 [46.5% (CH
2)
5CH
3], 141 (13.3% M
+-COCH
2COCH
3). Mass spectrum for allylic alcohol:
m/e 57 [100% M
+-CH
2(CH
2)
4CH
3], 85 (8.7% M
+-CHOHCH=CH
2), 113 (2.8% M
+-CH
2CH
3). IR (neat) cm
−1: 3000 (C-H, alkenes); 1725 (C=O); 1650 (C=C);
1H NMR (CDCl
3) δ: 0.89 (t, 3 H), 1.30–1.64 (m, 10 H), 2.3 (s, 3 H), 3.47 (s, 2 H), 5.19–5.31 (m, 3 H), 5.72–5.84 (m, 1 H). Anal. calcd. for C
13H
22O
3: C, 68.99; H, 9.8. Found: C, 69.25; H, 10.06.
9.
Diisopropylamine, purchased from Aldrich Chemical Company, Inc., was distilled immediately prior to use.
12. Reaction progress can be followed most accurately by silica gel TLC and GLC analysis. In TLC analysis, one sees the disappearance of
(1-ethenyl)heptanyl 3-ketobutanoate,
Rf = 0.45 (
20% ethyl acetate/ligroin) and the appearance of baseline material that is indicative of the corresponding carboxylic acid salt. In GLC analysis, an aliquot (3 drops of reaction mixture, 3 drops of
ether, 3 drops of
10% hydrochloric acid) will show complete disappearance of peaks at
Rt = 7.44 and 4.56 [which correspond to
(1-ethenyl)heptanyl 3-ketobutanoate and cleavage of this β-keto ester under GLC conditions to the
3-hydroxy-1-nonene, respectively] and appearance of a peak at
Rt = 7.04 that corresponds to
5-dodecen-2-one. The
3-carboxy-5-dodecen-2-one decarboxylates upon injection yielding the GLC spectrum of the ultimate product.
13.
Sodium hydroxide (0.1%) is used to extract all of the carboxylate from the ether layer in the form of the sodium salt.
14. A slight exotherm was noted from 25 to 32°C. Acidification is necessary to extract all of the desired carboxylate from the aqueous layer into the organic layer.
15. Silica gel TLC shows one major spot at the baseline (
20% ethyl acetate/ligroin) with a very slight impurity (<5%) at
Rf = 0.47. Mass spectrum of 5-dodecen-2-one:
m/e 43 (100% COCH
3), 97 [6.1% M
+-CH
2(CH
2)
4CH
3], 125 (1.7% M
+-CH
2COCH
3). IR (neat) cm
1: 3000 (COOH); 1725 (COOH, RCOR);
1H NMR (CDCl
3) δ: 0.90 (t, 3 H,
J = 6.3); 1.28 (m, 8 H); 2.00 (m, 2 H); 2.31 (s, 3 H); 2.60 (t, 2 H,
J = 6.9); 3.48–3.59 (m, 1 H); 5.27–5.44 (m, 1 H,
trans J = 15.3); 5.49–5.61 (m, 1 H,
trans J = 15.3).
17. Reaction progress was followed most accurately by TLC analysis. The disappearance of the baseline material (i.e.,
3-carboxy-5-dodecen-2-one) and appearance of the desired ketone at
Rf = 0.33 (
10% ethyl acetate/ligroin) indicates the completeness of the reaction.
18. Silica gel TLC shows one spot at
Rf = 0.33 (
10% ethyl acetate/ligroin). GLC shows >95% purity; one peak at
Rt = 7.04. Mass spectrum:
m/e 43 (100% COCH
3), 97 [6.3% M
+-CH
2(CH
2)
4CH
3], 125 (2.0% M
+-CH
2COCH
3). IR (neat) cm
−1: 1700 (R'COR);
1H NMR (CDCl
3) δ: 0.90 (t, 3 H,
J = 6.5), 1.28 (m, 8 H), 1.98 (q, 2 H,
J = 6.3), 2.16 (s, 3 H), 2.28 (q, 2 H,
J = 6.6), 2.51 (t, 2 H,
J = 7.4), 5.34–5.51 (m, 2 H);
13C NMR (CDCl
3) δ: 14.0, 22.6, 26.9, 28.8, 29.5, 29.8, 31.7, 32.5, 43.6, 128.2, 131.5, 207.9. Anal. calcd. for C
12H
22O: C, 79.06; H, 12.17. Found: C, 78.79; H, 12.10.
3. Discussion
The Carroll rearrangement,
3,4 an old and well-established thermal rearrangement, involves the rearrangement of allylic esters to β-keto acids followed by decarboxylation to provide γ,δ-unsaturated methyl ketones. Even though the Carroll rearrangement is a versatile complement to the Claisen rearrangement,
5 it is not of widespread use. This may be due to (a) the lack of a convenient, high-yield method for the formation of β-keto esters and (b) the harsh conditions required to effect rearrangement.
6 Often, procedures involve direct conversion of allylic alcohols to the rearranged and decarboxylated products in one step and low yield.
Table I contains representative examples of the method of preparation described here.
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