Organic Syntheses, Vol. 75, 189
Checked by Aimee Reed and Louis S. Hegedus.
1. Procedure
A
1-L, three-necked, round-bottomed flask equipped with a
2-cm magnetic stirring bar,
rubber septum,
50-mL graduated addition funnel, and an
argon inlet tube is charged with
10.0 g (0.1019 mol) of 1,3-cyclopentanedione (Note
1),
55.0 g (0.6106 mol) of 1,3,5-trioxane (Note
2),
5 g of activated, powered, 4 Å molecular sieves, and
500 mL of freshly distilled dichloromethane (Note
3). The resultant suspension is stirred at room temperature and
37.6 mL (0.3057 mol) of boron trifluoride etherate (Note
4) is added dropwise over 2 hr via the addition funnel (Note
5). After 48 hr, the reaction mixture is filtered through a
pad of Celite and the yellow solid is washed twice with
100 mL of dichloromethane. The filtrate is poured into a
3-L separatory funnel containing 500 g of ice and
1 L of saturated sodium bicarbonate (Note
6). The aqueous phase is extracted with two
100-mL portions of dichloromethane, and the combined organic solutions are washed with
500 mL of brine, dried over
magnesium sulfate, filtered, and concentrated under reduced pressure. Flash chromatography on
500 g of silica gel (Note
7) with
hexane-acetone (3 : 1) as eluant (Note
8) gives
10.3 g (
72% yield) of
2 as a white crystalline solid (Note
9) and (Note
10).
2. Notes
1.
1,3-Cyclopentanedione (ca. 97%) is purchased from Aldrich Chemical Company, Inc., and used without purification.
2.
1,3,5-Trioxane (99+%) is purchased from Aldrich Chemical Company, Inc., and used without purification.
6.
CAUTION: A large amount of
carbon dioxide is generated in this extraction and appropriate care should be taken.
7. The crude residue is applied to the column head using a minimum of
dichloromethane. The submitters use
flash-grade (230-400 mesh) silica gel purchased from E. Merck and a column 10 cm in diameter. TLC values for
2 are R
f = 0.18 (
hexane :
acetone = 3 : 1) and for
3 (see (Note
10)) are R
f = 0.08 (
hexane :
acetone = 3 : 1), employing Whatman K6F silica gel TLC plates 60 Å. In a typical purification, collecting 200-mL fractions,
2 would elute in fractions 9-18 and
3 in fractions 20-30. The checkers found that immediate purification of the crude residue was necessary. Yields decreased dramatically with time between isolation and purification. Furthermore, the activity (related to the degree of dehydration) of the silica gel greatly affected yields. Only half the amount of silica mentioned above was used by the checkers to get the reported yields. When the full amount was used, the yield decreased to 40-50%.
8.
Reagent-grade hexanes (Fisher Scientific Company) and
HPLC-grade acetone (Baxter Diagnostics Inc.) were used without further purification.
9. The product can be recrystallized from
hexane-
ethyl acetate (5:1): mp
73-75°C; IR (CHCl
3) cm
−1: 3000 (m), 1690 (m), 1640 (s), 1430 (m), 1310 (m), 1180 (m), 1090 (br m), 910 (s), 890 (s);
1H NMR (CDCl
3, 500 MHz) δ: 2.36-2.38 (m, 2 H), 2.59-2.62 (m, 2 H), 4.44 (t, 2 H, J = 2.2), 5.20 (s, 2 H);
13C NMR (CDCl
3, 125 MHz) δ: 26.4, 32.6, 63.1, 92.7, 114.7, 181.9, 201.0; high resolution mass spectrum (CI, NH
3) m/z 140.0482 (M
+; calcd for C
7H
8O
3: 140.0473). Anal. Calcd for C
7H
8O
3: C, 60.00; H, 5.75. Found: C, 60.19; H, 5.82.
10. Further elution furnishes a small amount (
0.57 g,
2% yield) of crystalline
propellane 3: mp
178-180°C; IR (CHCl
3) cm
−1: 3000 (m), 1760 (s), 1700 (m), 1650 (s), 1450 (s), 1400 (s), 1195 (m), 1165 (m), 970 (m);
1H NMR (500 MHz, CDCl
3) δ: 1.95-2.06 (m, 3 H), 2.33-2.38 (m, 1 H), 2.42-2.74 (m, 6 H), 3.28 (d, 1 H, J = 11.7), 4.21 (d, 1 H, J = 11.7), 4.80 (d, 1 H, J = 6.4), 4.82 (d, 1 H, J = 6.6);
13C NMR (125 MHz, CDCl
3) δ: 20.4, 25.9, 30.7, 33.3, 44.7, 64.7, 87.7, 106.8, 111.0, 180.7, 202.1, 210.2; high resolution mass spectrum (CI, NH
3) m/z 250.0841 (M
+; calcd for C
13H
14O
5: 250.0836). Structure
3 is confirmed by single-crystal X-ray analysis.
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
1,3-Dioxin vinylogous esters derived from cyclic 1,3-diketones (e.g.,
4) are valuable building blocks for the construction of natural and unnatural carbocyclic products.
2 In connection with a synthesis of plant-growth regulators, Crow and co-workers reported the preparation of substituted 1,3-dioxins
5-7 in 1982.
3 To account for their formation, Crow proposed a Prins mechanism whereby the enol of the 1,3-diketone adds to the BF
3-aldehyde complex (Scheme 1).
4 Incorporation of a second equivalent of aldehyde and cyclization then yields the
dioxin. Use of a slight excess of aldehyde (ca. 2.5-3.0 equiv) was recommended.
3
The synthetic usefulness of dioxin vinylogous esters as
β-keto vinyl cation equivalents was demonstrated by a variety of reductive and alkylative 1,3-carbonyl transpositions.
5,7 Regioselective alkylation and hydroxylation at the α'-position (and, in some cases, at the γ-position)
8,9 further extend the usefulness of 1,3-dioxin vinylogous ester templates in organic synthesis.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
6,7-Dihydrocyclopenta-1,3-dioxin-5(4H)-one: Cyclopenta-1,3-dioxin-5(4H)-one, 6,7-dihydro- (11);
(102306-78-5)
1,3-Cyclopentanedione (8,9);
(3859-41-4)
1,3,5-Trioxane (8,9);
(110-88-3)
4 Å Molecular sieves: Zeolites, 4 Å (10);
(70955-01-0)
Boron trifluoride etherate: Ethyl ether, compd. with boron fluoride (BF3) (1:1) (8); Ethane, 1,1'-oxybis-, compd. with trifluoroborane (1:1) (9);
(109-63-7)
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