Source: http://www.orgsyn.org/demo.aspx?prep=V78P0152
Timestamp: 2019-04-21 23:19:53+00:00

Document:
Submitted by Sergey A. Kozmin, Shuwen He, and Viresh H. Rawal1 .
Checked by Ruth Figueroa and David J. Hart.
A. (E)-4-Dimethylamino-3-buten-2-one , 1.2 A 250-mL, round-bottomed flask equipped with a magnetic stirring bar is charged with acetylacetaldehyde dimethyl acetal (Note 1) (19.8 g, 0.15 mol), freshly distilled prior to use (67°C, 12 mm). A 2.0 M solution of dimethylamine in methanol (Note 1) (85 mL, 0.17 mol) is then added in one portion. The resulting yellow solution is stirred at room temperature for 4 hr, and concentrated on a rotary evaporator. The resulting oil is purified by bulb-to-bulb distillation (0.25 mm, oven temp 100-120°C) (Note 2) to afford 15.3 g (90%) of the desired vinylogous amide as a pale-orange oil (Note 3).
B. (E)-1-Dimethylamino-3-tert-butyldimethylsiloxy-1,3-butadiene , 2. A dry, 500-mL, three-necked, round-bottomed flask is equipped with a pressure equalizing addition funnel, a large egg-shaped magnetic stirring bar, and a nitrogen/vacuum adapter. The apparatus is evacuated and flushed with nitrogen. The flask is charged with a 1.0 M solution of sodium bis(trimethylsilyl)amide (NaHMDS) in tetrahydrofuran (THF) (Note 1) (100 mL, 0.100 mol) and the flask is cooled in a dry ice-acetone bath (−70°C bath temp), causing a viscous, yellowish-white suspension to form. To this suspension is added, over a period of 30 min via an addition funnel, a solution of (E)-4-dimethylamino-3-buten-2-one (11.3 g, 0.100 mol) in THF (50 mL). The funnel is rinsed with a small amount of THF, and the resulting clear-yellow solution is stirred for 1.0 hr at −78°C. A solution of tert-butylchlorodimethylsilane (Note 4) (15.8 g, 0.105 mol) in THF (50 mL) is added over a 5-min period, via an addition funnel. The funnel is again rinsed with a small amount of THF. The cooling bath is removed and the reaction mixture is allowed to reach room temperature, which requires about 1.5 hr. The reaction mixture is poured into a 1-L Erlenmeyer flask containing 600 mL of anhydrous ether (Note 5). The resulting suspension is allowed to stand for 30 min and then suction filtered through a pad of dry Celite (60 g) (Note 6) packed in a 600-mL sintered glass filter funnel (Note 7). The filter cake is washed with three 50-mL portions of ether (Note 8), and the filtrate is concentrated on a rotary evaporator (heating bath temp <45°C). The resulting dark orange oil, containing the diene and hexamethyldisilazane, is subjected to bulb-to-bulb distillation (110-120°C, 0.3 mm) (Note 9) to yield 20.4 g (90%) of the desired 1-amino-3-siloxy-1,3-butadiene (Note 10) as a light-yellow oil (Note 10).
1. This reagent was purchased from the Aldrich Chemical Company, Inc.
2. The receiver bulb was cooled with ice as soon as the product started to distill.
3. On occasion the vinylogous amide was obtained as a dark oil, but exhibited good spectroscopic properties. A cleaner-looking sample of the product was obtained by resubjecting the dark oil to bulb-to-bulb distillation. The checkers used a coffee-maker bulb-to-bulb distillation apparatus and recorded a bp of 60-80°C at 0.1 mm. Characterization data follow: IR (neat) cm−1: 1660, 1575, 1436, 1356, 1258, 1112, 962 ; 1H NMR (300 MHz, CDCl3 ) δ: 2.10 (s, 3 H), 2.88 (br s, 3 H), 2.99 (br s, 3 H), 5.05 (d, 1 H, J = 12.8), 7.47 (d, 1 H, J = 12.8) ; 13C NMR (75 MHz, CDCl3 ) δ: 28.0, 36.9, 44.5, 96.6, 152.6, 195.2 ; mass spectrum (EI) 113 (C6H11NO), 98 (base) .
4. This reagent was purchased from Lithco, a division of the FMC Corporation.
5. Anhydrous ether was purchased from Fisher Scientific Company and used without further purification.
6. Celite 545 was purchased from Fisher Scientific Company and was flame-dried under vacuum just prior to filtration. The Celite was packed tightly into the funnel using the bottom of a beaker.
7. A sintered-glass Büchner funnel having a C-porous frit was employed.
8. When the filtration became very slow, the filter cake was stirred with a spatula to break up the pasty layer on top. The filtration must be done carefully to minimize transfer of sodium chloride (NaCl) to the filtrate. Lower yields of less pure product are obtained if considerable amounts of NaCl are present during the subsequent distillation. If a gel is obtained after removal of solvent on the rotary evaporator, too much NaCl is present.
9. A 250-mL flask is used as the pot, connected to a 100-mL collection bulb, connected to a cold trap (dry ice-acetone) to protect the vacuum pump. Hexamethyldisilazane is collected first in the cold finger (−78°C). Then, as soon as the diene starts to distill, the collection bulb is cooled with ice. The checkers recorded a bp of 60-80°C at 0.07 mm.
10. The diene displays the following spectral data: IR (neat) cm−1: 1648 ; 1H NMR (500 MHz, CDCl3) δ: 0.19 (s, 6 H), 0.98 (s, 9 H), 2.70 (s, 6 H), 3.84 (s, 1 H), 3.92 (s, 1 H), 4.78 (d, 1 H, J = 13.2 ), 6.57 (d, 1 H, J = 13.2) ; 13C NMR (75 MHz, CDCl3) δ: −4.6, 18.3, 25.9, 40.5, 85.8, 95.9, 140.9, 156.4 ; mass spectrum (EI) 227 (C12H25NOSi), 156 (base) . This material contains trace impurities by 1H and 13C NMR.
11. The submitters report that an alternate purification method involves distillation through a micro short-path distillation apparatus fittted with a Vigreux column (10 cm). Under this protocol, diene 2 (bp 60°C at 0.5 mm) is obtained as a clear, colorless liquid in 82% yield. (This modification was not checked).
Aminosiloxy dienes are highly reactive in Diels-Alder reactions, considerably more so than the analogous dialkoxy dienes.5a, 9 They undergo [4+2] cycloadditions with a broad range of electron-deficient dienophiles.5,7 The reactions generally occur under very mild conditions and afford the corresponding cycloadducts in good yields and with complete regioselectivity. A full study on the preparation and cycloadditions of amino siloxy dienes has been carried out.7 In the procedure that follows, a preparative scale procedure is described for the Diels-Alder reaction of an aminosiloxy diene, reduction of the electron-withdrawing group in the adduct, and hydrolysis of the β-aminoenolsilyl ether moiety to the 4-substituted cyclohexenone.
Department of Chemistry, The University of Chicago, 5735 S. Ellis Avenue, Chicago, IL 60637.
Maggiulli, C. A.; Tang, P.-W. Org. Prep. Proc. Int. 1984, 16, 31.
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(a) Petrzilka, M.; Grayson, J. I. Synthesis 1981, 753; (b) Fringuelli, F.; Taticchi, A. "Dienes in the Diels-Alder Reaction"; Wiley: New York, 1990.
(a) Kozmin, S. A.; Rawal, V. H. J. Org. Chem. 1997, 62, 5252; (b) Kozmin, S. A.; Rawal, V. H. J. Am. Chem. Soc. 1997, 119, 7165; (c) Kozmin, S. A.; Rawal, V. H. J. Am. Chem. Soc. 1998, 120, 13523; (d) Kozmin, S. A.; Rawal, V. H. J. Am. Chem. Soc. 1999, 121, 9562.
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Kozmin, S. A.; Janey, J. M.; Rawal, V. H., J. Org. Chem. 1999, 64, 3039.
Danishefsky, S.; Kitahara, T.; Schuda, P. F. Org. Synth., Coll. Vol. VII 1990, 312.
Kozmin, S. A.; Green, M. T.; Rawal, V. H. J. Org. Chem. 1999, 64, 8045.

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