PDF herunterladen
Synlett 2007(18): 2829-2832  
DOI: 10.1055/s-2007-991096
LETTER
© Georg Thieme Verlag Stuttgart · New York

Michael Addition of Manganese Enolates to Nitroolefins

Gabriele Michelettia, Salvatore Pollicinoa, Alfredo Ricci*a, Guillaume Berionnia,b, Gérard Cahiezb
a Faculty of Industrial Chemistry, Bologna University, 40136 Bologna, Italy
Fax: +39(051)2093654; e-Mail: ricci@ms.fci.unibo.it;
b Université de Cergy-Pontoise, UMR 8123, 95011 Cergy-Pontoise, France
Weitere Informationen

Publikationsverlauf

Received 26 July 2007
Publikationsdatum:
12. Oktober 2007 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

The Michael addition to nitroolefins of manganese enolates derived from an array of ketones is reported. The desired 1,4-adducts are obtained in high yield and excellent diastereo- and regioselectivity, the sole kinetic adduct being obtained in the case of nonsymmetrical ketones. The effect of a thiourea-type organocatalyst on the addition of several representative nitroolefins to the kinetic manganese enolate derived from isopropyl ethyl ketone is also reported.

Key words

Michael addition - manganese - enolates - nitroolefins - selectivity

16

General Procedure for the Preparation of Enolates via Manganese Enamides: To a suspension of LiBr (417 mg, 4.8 mmol) in freshly distilled THF (6 mL) in a 3-necked 25-mL round-bottomed flask under argon, MnBr2 (516 mg, 2.4 mmol) was introduced and the solution was stirred until complete dissolution (transparent pale yellow solution). After addition of n-butylaniline (380 µL, 2.4 mmol) the temperature was cooled to -20 °C and methyllithium (3 mL, 4.8 mmol) was introduced dropwise. On keeping the temperature under 0 °C, the solution became limpid and red-dark colored after 10 min. The desired ketone (2 mmol) was then slowly added keeping the temperature between -10 °C and 10 °C. All the Mn enolates were formed in 30 min at this temperature.
General Procedure for Michael Addition of Manganese Enolates to Nitroalkenes: The nitroalkenes (1.15 equiv) were added to the enolate solution at the required temperature without previous dissolution. The consumption of the nitroalkenes was monitored by TLC. The reactions were quenched with 1 M HCl (5 mL). The mixture was extracted with Et2O (3 × 10 mL), and the organic phase was washed with brine. The organic layers were combined, dried over Mg2SO4, and concentrated in vacuo. The resulting orange or green oil was purified by flash chromatography.
Michael Additions with Catalytic Amounts of Catalyst A: The experimental protocol was the same as described previously with addition of thiourea A (5 mol%) immediately after the nitroolefin had been introduced. Representative characterizations are given here.
Compound 1d: syn-isomer; R f 0.42 (PE-EtOAc, 9:1); white solid; mp 98 °C; yield: 74%; dr (syn/anti) = 78:22. 1H NMR (300 MHz, CDCl3): δ = 0.75 (d, J = 6.9 Hz, 3 H), 1.04 (d, J = 6.9 Hz, 3 H), 1.27 (d, J = 6.6 Hz, 3 H), 2.45 (sept, J = 6.9 Hz, 1 H), 3.22 (dq, J 1 = 6.6 Hz, J 2 = 2.4 Hz, 1 H), 3.90 (ddd, J 1 = 10.2 Hz, J 2 = 9.6 Hz, J 3 = 2.4 Hz, 1 H), 2.85 (dd, J 1 = 12.6 Hz, J 2 = 10.2 Hz, 1 H), 2.95 (dd, J 1 = 12.6 Hz, J 2 = 9.6 Hz, 1 H), 7.33 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = 15.7, 17.3, 17.5, 41.0, 46.0, 48.2, 77.6, 106.6, 127.9, 128.9, 213.9. IR: 1379, 1467 (Ph, C=C), 1557 (NO2), 1712 (C=O), 2974, 3016 (Ph, CH) cm-1. GC-MS: t R = 8.34 min. MS: m/z = 199, 159, 131, 91, 71, 43. Anal. Calcd for C14H19NO3 (249.1365): C, 67.45; H, 7.68. Found: C, 66.51; H, 7.72.
Compound 2a: syn-isomer; R f 0.21 (PE-EtOAc, 9:1); oil; yield: 74%; dr (syn/anti) = 86:14. 1H NMR (300 MHz, CDCl3): δ = 0.60 (d, J = 6.9 Hz, 3 H), 0.85 (d, J = 6.9 Hz, 3 H), 1.05 (d, J = 6.9 Hz, 3 H), 2.40 (sept, J = 6.9 Hz, 1 H), 3.35 (m, 1 H), 3.85 (s, 3 H), 3.95 (ddd, J 1 = 9.6 Hz, J 2 = 6.9 Hz, J 3 = 5.1 Hz, 1 H), 4.75 (dd, J 1 = 12.6 Hz, J 2 = 5.0 Hz, 1 H), 4.85 (dd, J 1 = 12.6 Hz, J 2 = 9.6 Hz, 1 H), 6.80 (m, 2 H), 7.00-7.10 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ = 14.5, 17.3, 17.9, 40.6, 42.7, 45.0, 55.4, 76.1, 111.1, 120.8, 126.0, 129.0, 130.5, 157.2, 216.1. GC-MS: t R = 9.14 min. MS: m/z = 279, 189, 161, 134, 91, 71, 43. HRMS (EI): m/z [M+] calcd for C15H21NO4: 279.147059; found: 279.14722.
Compound 3b: syn-isomer; R f 0.42 (PE-EtOAc, 9:1); translucent oil; yield: 70%; dr (syn/anti) = 70:30. With catalyst: yield: 78%; dr (syn/anti) >99:1. 1H NMR (300 MHz, CDCl3): δ = 0.95 (d, J = 6.9 Hz, 3 H), 1.10 (d, J = 7.2 Hz, 6 H), 1.20-1.30 (d, J = 6.9 Hz, 6 H), 1.80 (m, 1 H), 2.65 (m, 1 H), 2.90 (sept, J = 6.9 Hz, 1 H), 3.10 (dqd, J 1 = 7.2 Hz, J 2 = 1.8 Hz, 1 H), 4.30 (dd, J 1 = 13.8 Hz, J 2 = 6.3 Hz, 1 H), 4.40 (dd, J 1 = 13.8 Hz, J 2 = 5.1 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 12.6, 18.3, 18.8, 19.1, 20.7, 29.9, 40.0, 43.8, 44.0, 75.91, 216.6. IR: 1220, 1559 (NO2), 1703 (C=O), 2976 cm-1. GC-MS: t R = 6.32 min. MS: m/z = 172, 144, 100, 97, 71, 43. ESI-MS: m/z = 216 [M + 1]+, 238 [M + Na]+, 254 [M + K]+.
Compound 4a: R f 0.7 (PE-EtOAc, 9:1); yellowish oil; yield: 65%; dr (syn/anti) = 82:12. With catalyst: yield: 67%; dr (syn/anti) >99:1. 1H NMR (300 MHz, CDCl3): δ = 0.90 (t, J = 6.9 Hz, 3 H), 0.95 (d, J = 7.2 Hz, 3 H), 1.10 (d, J = 6.9 Hz, 6 H), 1.20-1.40 (m, 8 H), 1.80 (m, 1 H), 2.65 (m, 1 H), 2.8 (sept, J = 6.9 Hz, 1 H), 4.40 (dd, J 1 = 12.6 Hz, J 2 = 4.5 Hz, 1 H), 4.60 (dd, J 1 = 12.6 Hz, J 2 = 7.2 Hz, 1 H). 13C NMR (75 MHz, CDCl3): = 12.9, 14.1, 18.0, 18.5, 22.6, 26.8, 30.3, 31.7, 39.0, 39.9, 44.8, 76.6, 215.3. IR: 1225, 1556 (NO2), 1706 (C=O), 2976 cm-1. GC-MS: t R = 7.38 min. MS: m/z = 201, 172, 125, 97, 83, 71, 43. ESI-MS (+ve mode): m/z = 244 [M + 1]+, 266 [M + Na]+, 282 [M + K]+.
Compound 5a: R f 0.13 (PE-EtOAc, 9:1); crystal; mp 129 °C; yield: 65%; dr (syn/anti) = 75:25. With catalyst: yield: 82%; dr (syn/anti) >99:1. 1H NMR (300 MHz, CDCl3): δ = 1.15 (d, J = 6.9 Hz, 6 H), 1.20 (d, J = 6.6 Hz, 3 H), 2.90 (sept, J = 6.9 Hz, 1 H), 3.30 (m, 1 H), 3.40 (dd, J 1 = 17.9 Hz, J 2 = 5.8 Hz, 1 H), 3.50 (dd, J 1 = 17.9 Hz, J 2 = 0.5 Hz, 1 H), 4.40 (dt, J 1 = 10.5 Hz, J 2 = 0.5 Hz, 1 H), 5.20 (dd, J 1 = 5.8 Hz, J 2 = 0.5 Hz, 1 H), 6.70-7.20 (m, 4 H). 13C NMR (75 MHz, CDCl3): δ = 14.5, 17.3, 17.9, 40.6 (C7), 42.7, 45.1, 55.4, 78.1, 117.0, 117.9, 122.2, 128.0, 129.0, 153.8, 215.4. IR: 1226 (CO), 1460, 1492 (Ph, C=C), 1554 (NO2), 1715 (C=O), 2976, 3023 (Ph, CH) cm-1. GC-MS: t R = 9.65 min. MS: m/z = 277, 227, 184, 159, 131, 71, 43. Anal. Calcd for C15H19NO4 (277.1314): C, 64.97; H, 9.91; N, 5.05. Found: C, 65.02; H, 7.02; N, 5.03.
Compound 6a: R f 0.55 (PE-EtOAc, 9:1); red oil; yield: 79%; dr (syn/anti) = 95:5. 1H NMR (300 MHz, CDCl3): δ = 1.10 (d, J = 6.9 Hz, 3 H), 1.2 (d, J = 6.9 Hz, 3 H), 1.60 (d, J = 7.2 Hz, 3 H), 2.9 (sept, J = 6.9 Hz, 1 H), 4.7 (qd, J = 7.2 Hz, 1 H), 7.60 (s, 1 H). 13C NMR (75 MHz, CDCl3): δ = 18.0, 18.3, 18.7, 40.5 (C2), 45.1, 127.4, 130.6, 135.4, 141.3, 144.1, 148.3, 211.6. GC-MS: t R = 8.87 min. MS: m/z = 249, 234, 210, 114, 71. ESI-MS: 298 [M + H]+, 320 [M + Na]+, 336 [M + K]+. ESI-MS (-ve mode): m/z = 296 [M - H]+.
General Procedure for the Preparation of Pyrrolidines: A mixture of nitroketone (38 mg, 0.15 mmol) and 10% Pd(OH)2 on carbon in anhyd MeOH (7.4 mL) was hydrogenated at 60 psi for 50 h using a Parr apparatus. The crude product was dissolved in CH2Cl2 (2 mL), cooled to 0 °C and treated with Et3N (3 equiv) followed by p-toluene-sulfonyl chloride (1.1 equiv) for 60 h. After aqueous workup, the organic phase was dried on MgSO4 and concentrated in vacuo. The product was purified by flash chromatography (hexane-EtOAc, 90:10).
Compound 7: brown oil; yield: 65%. 1H NMR (300 MHz, CDCl3): δ = 0.69 (t, J = 7.8 Hz, 3 H), 0.92 (t, J = 9.0 Hz, 3 H), 0.95-1.05 (m, 1 H), 1.05-1.22 (m, 2 H), 1.29-1.47 (m, 2 H), 1.70-1.84 (m, 1 H), 1.88-2.00 (m, 1 H), 2.45 (s, 3 H), 3.08 (q, J 1 = 15.2 Hz, J 2 = 6.7 Hz, 1 H), 3.62-3.79 (m, 3 H), 7.13-7.38 (m, 7 H), 7.77 (d, J = 8.9 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 13.4, 14.1, 18.7, 20.6, 21.5, 33.2, 45.8, 48.2, 52.7, 63.9, 126.7, 127.3, 128.1, 128.6, 129.7, 134.6, 139.3, 143.8. ESI-MS: m/z = 394 [M + Na]+.
Compound 8: brown oil; yield: 70%. 1H NMR (300 MHz, CDCl3): δ = 0.70 (d, J = 7.3 Hz, 3 H), 1.10 (d, J = 7.0 Hz, 6 H), 1.29-1.41 (m, 1 H), 2.30-2.50 (m, 5 H), 3.54 (t, J = 6.3 Hz, 1 H), 3.69-3.86 (m, 2 H), 6.96 (d, J = 6.3 Hz, 2 H), 7.13-7.36 (m, 5 H), 7.75 (d, J = 7.5 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 11.3, 14.1, 19.3, 22.6, 29.4, 31.6, 51.0, 69.7, 126.7, 127.7, 127.8, 128.3, 129.7, 138.1, 142.4, 143.4. ESI-MS: m/z = 380 [M + Na]+.