Organic Syntheses, CV 8, 13
Submitted by Donald R. Deardorff and David C. Myles
1.
Checked by Helmut Grebe and Ekkehard Winterfeldt.
1. Procedure
An
oven-dried,
300-mL, two-necked, round-bottomed flask is equipped with a
Teflon-coated magnetic stirring bar, a
pressure-equalizing dropping funnel, and a
rubber septum with an
18-gauge needle connected to a
dry-nitrogen source. The nitrogen-flushed apparatus is charged with
125 mL of dry tetrahydrofuran (Note
1) and
0.28 g (0.24 mmol, 0.2 mol%) of tetrakis(triphenylphosphine)palladium(0) (Note
2). The mixture is stirred at room temperature until all of the
palladium catalyst dissolves (Note
3). The solution is cooled in an
ice–water bath and
7.0 mL (7.3 g, 122 mmol) of acetic acid (Note
4) is added via syringe. At this point a slight darkening of the solution is observed. A room temperature solution containing
10.9 g of 92% cyclopentadiene monoepoxide (10.0 g, 122 mmol, (Note
5)) in
40 mL of tetrahydrofuran is added over 10 min with the aid of the addition funnel. The original pale-yellow color gives way to a deeper transparent orange. After 5 min (Note
6), the solution is concentrated at ambient temperature under reduced pressure and the resulting reddish-brown oil is passed through a plug of
silica gel (50 g, (Note 7) with 450 mL of ethyl ether (Note
8). The slightly cloudy filtrate is washed through a plug of anhydrous
magnesium sulfate (60 g, 5 × 7-cm coarse glass frit) with an additional
150 mL of ether (Note
9) The solvent is removed under reduced pressure to yield a pale-yellow oil. The material is distilled through a short-path apparatus at 73–75°C (0.15 mm) to afford
12.5–13.2 g (
72–76%) of colorless oil that crystallizes upon refrigeration (mp
36–39°C) . The material is homogeneous by TLC and
1H NMR (Note
10), but can be further purified by recrystallization from an
ether–
hexane mixture to give colorless crystals, mp
38.5–41°C (Note
11).
2. Notes
3. Dissolution takes approximately 2–3 min.
4.
Glacial acetic acid was purchased from J. T. Baker Chemical Company (Baker Analyzed Reagent) and distilled prior to use.
6. TLC analysis using Baker Si250F precoated glass plates with a
hexane–
ethyl acetate (1 : 1) solvent system indicates that all of the starting material is consumed.
7. Baker Analyzed Reagent silica gel 60–200 mesh was used in a
4.5 × 9.0-cm column. This step removes most palladium-containing compounds from the reaction mixture. In order to ensure that the
palladium is efficiently separated, itis important that all
tetrahydrofuran be removed from the crude oil prior to filtration.
8.
Anhydrous ether (purified) was purchased from J. T. Baker Chemical Company and used without additional purification.
10.
cis-3-Acetoxy-5-hydroxycyclopent-1-ene has the following spectral characteristics:
1H NMR (200 MHz, CDCl
3) δ: 1.59 (dt, 1 H,
J = 4.0 and 14.5, CH
2), 2.00 (s, 3 H, CH
3), 2.38 (br s, 1 H, OH), 2.76 (quintet, overlapping dt, 1 H,
J = 7.4 and 14.5, CH
2), 4.67 (m, 1 H, CHOH), 5.45 (m, 1 H, CHOAc), 5.92 (m, 1 H, CH=CH), 6.05 (m, 1 H, CH=CH); IR (neat) cm
−1: 3410 (s), 1720 (s), 1250 (s).
3. Discussion
Functionalized cyclopentenoids have been used extensively as key building blocks for the synthesis of many biologically active molecules.
4 This procedure details the facile preparation of one such versatile intermediate:
cis-3-acetoxy-5-hydroxycyclopent-1-ene. Although important in its own right, this material also serves as a one-step precursor to the highly useful synthetic substrate
4-acetoxy-2-cyclopenten-1-one.
4 Only the
acetic acid adduct with
cyclopentadiene monoepoxide is described here. However, this palladium-catalyzed reaction appears to be general for other acidic substrates as well.
5,6 For example, the corresponding benzoate and phenyl ether adducts have been successfully prepared
5 from both
benzoic acid and
phenol in yields of 87 and 82%, respectively. Moreover, the reaction is not limited to just the monoprotected versions of
cis-cyclopentene-3,5-diol. The corresponding diesters can be similarly prepared by replacement of the carboxylic acid component with an anhydride. This minor modification permits direct synthetic access to either the dibenzoate or diacetate in equally good yields (74 and 79%, respectively). Recently, silyl carboxylates and silyl phenoxides were also found to react analogously with
cyclopentadiene monoepoxide in the presence of Pd(0) catalyst.
7 It should be stressed that in each case only the
cis-1,4-adducts are observed, despite the fact that three other stereoisomers are possible. This remarkable stereo- and regiospecificity is undoubtedly a manifestation of an intermediate palladium π-allyl complex.
8
Racemic cis-monoesters of cyclopentene-3,5-diol were previously prepared by the selective acylation
9 10 11 of the
meso-diol and the copper-mediated
12 addition of carboxylic acid salts to
cyclopentadiene monoepoxide. Optically active monoacetates can be accessed by enzymatic hydrolysis
13 14 15 16 17 of the corresponding diester. The present method offers four principal advantages over the earlier reports: (1) it is operationally simple; (2) it requires a much shorter reaction time; (3) it gives better yields; and (4) it has widespread applicability, since reactants other than carboxylic acids may be employed with equally good results.
A major disadvantage with the acylation method
9,10,11 is that the starting material,
cis-cyclopentene-3,5-diol, is not readily available and must be prepared via photoxygenation procedures.
18 Furthermore, acylation occurs with the concomitant formation of diacylated product, which results in reduced yields and associated purification problems. The copper-mediated
12 and palladium-catalyzed procedures share some similarities in that both use
cyclopentadiene monoepoxide as their starting material and deliver the desired product in good yield. But, unlike the palladium-catalyzed method, copper-mediated reactions require two full equivalents of carboxylate salt, much lower reaction temperatures (−78°C), and substantially longer reaction times. Finally, the enantioselective hydrolysis
13,14,15,16,17 of
cis-3,5-diacetoxycyclopent-1-ene by hydrolase enzymes is an effective two-step method for generating optically enriched product.
This preparation is referenced from:
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