Checked by Antonino Focella, Mittira Amornmarn, and David L. Coffen.
1. Procedure
2. Notes
2.
Selenium dioxide was obtained from Alfa Products, Morton/Thiokol Inc. and used without purification.
3. The solid material containing
selenium waste was placed in a container for heavy metal wastes and disposed of by a commercial service according to approved procedures.
4. Spectral characteristics are as follows: IR (CHCl
3) cm
−1: 3000, 1630, 1580, 1515, 1470, 1210;
1H NMR (300 MHz, CDCl
3) δ: 6.88–7.11 (series of m, 6 H).
7. The R
f for this adduct is 0.6 in CH
2Cl
2. Its presence is clearly visible when
anisaldehyde is employed as the staining agent.
8. The adduct exhibits the following spectral properties: IR (CHCl
3) cm
−1: 2930, 1665, 1603, 1380, 1165;
1H NMR (300 MHz, CDCl
3) δ: 2.72 (d, 1 H, J = 15.5), 2.87 (dd, 1 H, J = 6.8, 15.5), 3.21–3.45 (m, 5 H), 3.66 (t, 1 H, J = 7.7), 5.77 (dd, 1 H, J = 2.0, 11.1), 6.13 (t, 1 H, J = 7.9), 6.60 (dt, 1 H, J = 0.8, 7.6), 6.92 (dd, 1 H, J = 8.5, 11.1);
13C NMR (75 MHz, CDCl
3) δ: 40.2, 40.6, 42.9, 51.9, 52.1, 70.8, 126.5, 129.4, 139.4, 150.6, 196.3. A sample recrystallized from
hexane afforded off-white crystals with mp
62–63°C. As an alternative to chromatography, the Diels-Alder adduct can be purified by pouring the cooled, crude product into
100 mL of ether and rinsing the dark viscous gum with additional
ether (2 × 25 mL). The material obtained from evaporation of the combined ethereal extracts is then subjected to bulb-to-bulb distillation. After removal of the volatile impurities, the product distils during the ramping of the temperature from 110–165°C at 0.5 mm. This modification affords a comparable yield of adduct on a 6-fold scale.
9.
Copper iodide was purified prior to use by the method of Kauffman.
2
10.
Tetrahydrofuran was distilled from
sodium-benzophenone ketyl before use.
12. Attempts were made to substitute other polar solvents for HMPA in this reduction. Under similar reaction conditions but with substitution of
1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) no reaction took place, and the starting material was recovered unchanged. The slightly more polar
1,3-dimethyl-2-imidazolidinone (DMI) allowed reduction to take place, but with only 80% conversion to a mixture of 1,2- and 1,4-reduction products after 10 hr. With L-selectride in
tetrahydrofuran (THF) at −78°C, 1,4-reduction was achieved in 30–60% yield alongside competitive 1,2-reduction.
14. Before use, this material should be thoroughly dried by heating to 50°C under high vacuum to constant weight (1–2 hr).
15. The R
f of this product is 0.6 in CH
2Cl
2.
Anisaldehyde was employed as the staining agent.
16. Spectral characteristics are as follows: IR (CHCl
3) cm
−1: 2930, 2860, 1700, 1425;
1H NMR (300 MHz, CDCl
3) δ: 1.82–1.94 (m, 1 H), 2.28–2.38 (m, 1 H), 2.52–2.70 (m, 3 H), 2.83–2.94 (m, 2 H), 3.10 (t, 1 H, J = 7.3), 3.22–3.48 (m, 4 H), 6.14 (t, 1 H, J = 7.9), 6.51 (t, 1 H, J = 8.2);
13C NMR (75 MHz, CDCl
3) δ: 27.1, 38.1, 39.4, 39.8, 42.9, 46.8, 49.1, 69.9, 127.3, 137.3, 206.9. An analytical sample recrystallized from ether melts at
74–75°C. Anal. Calcd for C
11H
14OS
2: C, 58.37; H, 6.23; S, 28.33. Found: C, 58.32, H, 6.22; S, 28.63.
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
Although examples of inverse electron-demand Diels-Alder reactions involving ketene thioacetals and α,β-unsaturated aldehydes, ketones, and esters abound,
3 the formation of six-membered carbocyclic products is rarely encountered. Isoquinolinium salts and 4a-azoniaanthracenes are recognized as good 2π acceptors,
4 but the use of positively charged reaction partners is not necessary as the condensation with
tropone illustrates. An important advantage of such cycloadditions is their ability to distinguish two carbonyl groups from the outset. Furthermore, the example provided illustrates the regiospecificity with which carbon-carbon bond formation occurs.
The second stage of the procedure describes a method for the fully regiocontrolled saturation of conjugated double bonds in the presence of isolated pi bonds. The agent perhaps responsible for this discrimination is a coordinated form of
copper hydride. Although "CuH" has been generated in several different ways, the
diisobutylaluminum hydride-methyl copper-HMPA complex developed by Tsuda and Saegusa
7 is especially attractive because of its quantitative capacity for 1,4-reduction and its ease of generation.
8 This chemistry results in regiospecific enolate anion formation and permits ready trapping of these intermediates as illustrated below:
9
Consequently, this mild, conjugate reduction may become a powerful tool in synthetic organic chemistry.
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