Checked by David A. Favor and Amos B. Smith, III.
1. Procedure
D.
(Z)-β-Iodoacrolein, 4. A 100-mL, dry (Note
4),
four-necked, round-bottomed flask equipped with a mechanical stirrer, an internal thermometer, a rubber septum, and a nitrogen gas inlet, is charged with
2.26 g (10 mmol) of ethyl (Z)-β-iodoacrylate, 2, and
20 mL of anhydrous dichloromethane (Note
5). The stirred solution is cooled to −78°C in a liquid nitrogen bath and
10 mL (10 mmol) of a 1 M solution of diisobutylaluminum hydride in hexane (Note
6) is added dropwise with a syringe at such a rate that the temperature does not exceed −75°C. After the solution is stirred at −78°C (Note
7),
5 mL of cold methanol (Note
12) is added dropwise through the septum with a syringe at −80°C. Immediately after this addition,
25 mL of aqueous 20% potassium sodium tartrate is added to the cold reaction mixture in one portion, which causes the temperature to reach 0°C within a few seconds. The cooling bath is removed and
20 mL of ether is added to the hydrolyzed reaction mixture, which is further stirred for 20 min at room temperature (Note
13). It is then filtered through a pad of Celite and extracted with
30 mL of ether. The organic layer is washed with
brine and dried over
potassium carbonate. After careful rotary evaporation of the solvents,
1.6 g of
(Z)-β-iodoacrolein is obtained as a yellow liquid (
88%) (Note
14), which can be handled easily as
ether or
dichloromethane solutions, and can be stored in the refrigerator for a few weeks without decomposition or isomerization.
2. Notes
1. Part A of the procedure should be carried out in an
efficient fume hood to avoid exposure to noxious vapor (
acetic acid) and to lachrymatory
ethyl propiolate.
2.
Sodium iodide, 99%, was purchased from Janssen Chimica and used as received.
Glacial acetic acid, 99%, was purchased from Prolabo.
Ethyl propiolate was obtained from Janssen Chimica and used as received.
3. The product exhibits the following physical and spectral properties: IR (film) cm
−1: 3080, 2940, 1735, 1640, 1425, 1365, 1230, 1170, 1020, 925, 730;
1H NMR (400 MHz, CDCl
3) δ: 1.32 (t, 3 H, J = 7.15, C
H3CH
2), 4.25 (q, 2 H, J = 7.14, OC
H2), 6.89 (d, 1 H, J = 9.34, =C
H-CO
2Et), 7.44 (d, 1 H, J = 9.34, =C
HI);
13C NMR (100 MHz, CDCl
3) δ: 14.2, 60.8, 94.6, 129.9, 164.6.
4. All glassware is oven dried at 140°C overnight and assembled while hot under a
nitrogen atmosphere.
9.
Silica gel was purchased from Merck: Geduran SI 60.
10. The product exhibits the following spectral properties:
1H NMR (400 MHz, CDCl
3) δ: 0.90 (t, 3 H, J = 7.15, C
H3), 1.31–1.36 (m, 4 H), 1.51–1.63 (m, 2 H), 1.7 (s, 1 H, O
H), 4.4 (m, 1 H, C
HOH), 6.20 (t, 1 H, J = 7.69, =C
H), 6.33 (d, 1 H, J = 7.69, =C
HI);
13C NMR (100 MHz, CDCl
3) δ: 14.0, 22.6, 27.1, 35.6, 74.4 (CHOH), 82.2 (=CI), 143.4 (=CH).
11. The product exhibits the following spectral properties: IR (film) cm
−1: 3350, 3060, 2950, 2920, 2850, 1605, 1450, 1265, 1165, 1015, 930;
1H NMR (400 MHz, CDCl
3) δ: 0.90 (t, 3 H, J = 7.15, C
H3), 1.31–1.36 (m, 4 H), 1.51–1.63 (m, 2 H), 1.71 (s, 1 H), 4.1 (m, 1 H, C
HOH), 6.34 (dd, 1 H, J = 14.3, 1.1, =C
HI), 6.58 (dd, 1 H, J = 14.3, 6.6, =C
H);
13C NMR (100 MHz, CDCl
3) δ: 13.9, 22.5, 27.2, 36.2, 74.6 (CHOH), 77.2 (=CI), 148.6 (=CH).
12.
Methanol was obtained from Merck & Company, Inc., and used as received.
13. The workup should be carried out under an efficient fume hood since the title compound is a lachrymator.
14. The
(Z)-β-iodoacrolein exhibits the following spectral properties: IR (CCl
4) cm
−1: 3050, 2820, 2730, 1675, 1610, 690;
1H NMR (400 MHz, CDCl
3) δ: 6.77 (dd, 1 H, J = 8.25, 6.6, =C
H-CHO), 7.79 (d, 1 H, J = 8.25, =C
HI), 9.67 (d, 1 H, J = 6.6, C
HO);
13C NMR (100 MHz, CDCl
3) δ: 103.0 (=CHI), 136.4 (=CH), 195.4 (C=O).
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
The present procedure illustrates the simplest convenient method for the preparation of (Z)- or (E)-γ-iodo allylic alcohols and
(Z)-β-iodoacrolein. It uses
ethyl propiolate as a unique starting material:
ethyl propiolate and
ethyl tetrolate can be hydroiodinated regio- and stereospecifically (Z > 99%) by reaction with inexpensive
sodium iodide in
acetic acid3 4 5 6 7 8 (Scheme 1). The same methodology has been applied recently to the synthesis of enantiomerically pure (Z)-2-haloalkenyl sulfoxides.
9 By reaction of
2 with
diisobutylaluminum hydride at low temperature, and subsequent reaction with a Grignard reagent, one can obtain, very easily, the secondary (Z)-γ-iodo allylic alcohols with good chemical yield and exclusive Z stereochemistry of the double bonds (Table I). This one-pot "reduction-C-alkylation" sequence of the ester group allows the preparation of very sensitive derivatives (entry 5 or 6), which are difficult to prepare by usual methods.
10 11 12 13
However, reaction of
ethyl (Z)-β-iodoacrylate with DIBAL-H at low temperature (−78°C, 15 min) followed by warming to 0°C and addition of a Grignard reagent (−20°C to 0°C) now leads to the E isomers of the secondary
γ-iodo allylic alcohols with an E/Z ratio of 96/4 (Table II). This isomerization can be rationalized as occurring by the influence of the weak Lewis acid, Al(iBu)
2OEt, generated by α-elimination of the thermally labile aluminooxyacetal.
14 The
(Z)-β-iodoacrolein 4 and
crotonaldehyde 6 (Scheme 2) are also easily obtained by dropwise addition of an excess of
methanol to the aluminooxyacetal at low temperature, immediately followed by alkaline hydrolysis. (3Z)-Iodopropenals are valuable intermediates in organic synthesis because of the presence of three functional groups on three
carbon atoms.
14,15
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved