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Synlett 2007(8): 1274-1278  
DOI: 10.1055/s-2007-977448
LETTER
© Georg Thieme Verlag Stuttgart · New York

Lithium Naphthalenide Induced Reductive Selenenylation of α-Cyano Ketones: A Regiocontrolled Process for α-Phenylseleno Ketones and One-Pot Conversion into Enone System

Jia-Liang Zhu*a, Yen-Chun Koa, Chun-Wei Kuob, Kak-Shan Shia*b
a Department of Chemistry, National Dong-Hwa University, Hualien 974, Taiwan, R.O.C.
Fax: +886(38)633570; e-Mail: jlzhu@mail.ndhu.edu.tw;
b Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 350, Taiwan, R.O.C.
Fax: +886(37)586456; e-Mail: ksshia@nhri.org.tw;
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Publication History

Received 29 January 2007
Publication Date:
08 May 2007 (online)

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Abstract

An efficient procedure for the regiocontrolled synthesis of α-phenylseleno ketones has been developed, making use of the lithium naphthalenide induced reductive selenenylation of the α-cyano ketone system as a key operation. Moreover, seleno ketones thus generated in situ, upon subsequent treatment with hydrogen peroxide and acetic acid, could be further converted into the corresponding enones with a high degree of regioselectivity, presumably due to the lithium salt mediated selenoxide syn-elimination process.

Key words

lithium naphthalenide - α-phenylseleno ketones - regio­selectivity - α-cyano ketones - reductive selenenylation

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Satisfactory spectral and LC-MS or HRMS analytical data were obtained for all new compounds. A typical experiment is outlined as follows: To a solution of α-cyano ketone 1 (110 mg, 0.55 mmol) in THF (10 mL) at -40 °C was added LN (7.5 mL, 0.365 M, 2.75 mmol) dropwise. The resulting dark green solution was stirred at the same temperature for 20 min followed by addition of phenylselenyl bromide (156 mg, 0.66 mmol) in one portion. The resulting mixture was continued to stir for additional 30 min at -40 °C and then quenched with sat. aq NH4Cl and extracted with EtOAc (2 × 10 mL). The combined extracts were washed with brine, dried with Na2SO4, and concentrated to give the crude residue, which was subjected to flash chromatography on silica gel (EtOAc-n-hexane, 1:50) to afford the corresponding α-phenylseleno ketone 2 as a colorless oil (165 mg, 90%). IR (neat): 1729, 1604, 1577 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.72-2.13 (m, 5 H), 2.59 (ddd, J = 18.1, 8.1, 2.0 Hz, 1 H), 3.08 (d, J = 13.7 Hz, 1 H), 3.27 (d, J = 13.7 Hz, 1 H), 7.08-7.11 (m, 2 H), 7.19-7.25 (m, 3 H), 7.30-7.35 (m, 2 H), 7.39-7.45 (m, 1 H), 7.52-7.61 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ = 18.4, 33.0, 36.1, 41.0, 59.5, 126.5, 126.6, 128.3, 129.0, 129.6, 130.5, 137.6, 138.0, 211.6. MS (EI): m/z = 331.2 [M + 1]. Instead of quenching with sat. aq NH4Cl, after ketone 2 was generated in situ following the aforementioned protocol, AcOH (0.13 mL, 2.21 mmol) and H2O2 (0.43 mL of 35% H2O2, 4.41 mmol) were sequentially added to the above reaction mixture at -40 °C. The resulting solution was then warmed to 0 °C in 40 min and quenched with sat. aq NaHCO3 followed by extraction with EtOAc (2 × 10 mL). The combined organic layers were washed with H2O, brine, dried with Na2SO4, and concentrated to give the crude product, which was purified by flash chromatography on silica gel (EtOAc-n-hexane, 1:25) to give exo-(E)-13 9a,b (81 mg) in 85% yield over two steps.
(E)-2-Benzylidenecyclopentanone (13): IR (neat): 1706, 1622, 1487 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.04 (m, 2 Η), 2.42 (t, J = 7.9 Hz, 2 H), 2.98 (dt, J = 7.2, 2.7 Hz, 2 H), 7.36-7.44 (m, 4 H), 7.54 (dd J = 7.4, 1.1 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 20.2, 29.4, 37.8, 128.7, 129.3, 130.5, 132.3, 135.6, 136.1, 208.0. HRMS (EI): m/z calcd for C12H12O: 172.0889; found: 172.0877.
2-Allyl-2-phenylselenocycloheptanone (6a): IR (KBr): 3072, 2926, 2855, 1686, 740, 691 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.14-1.27 (m, 1 H), 1.33-1.46 (m, 2 H), 1.61 (dd, J = 14.7, 10.7 Hz, 1 H), 1.73-1.94 (m, 3 H), 2.21-2.30 (m, 2 H), 2.40-2.48, (m, 2 H), 3.17 (td, J = 11.2, 2.4 Hz, 1 H), 5.06 (br d, J = 17.1 Hz, 1 H), 5.14 (br d, J = 10.5 Hz, 1 H), 5.92-6.05 (ddm, J = 17.1, 10.5 Hz, 1 H), 7.26-7.31 (tm, J = 7.2 Hz, 2 H), 7.34-7.41 (m, 1 H), 7.41-7.46 (dm, J = 7.2 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 24.9, 26.3, 30.4, 32.1, 36.9, 39.6, 60.7, 118.2, 127.2, 129.0, 129.4, 135.1, 137.5, 207.3. LC-MS (ES): m/z = 331 [M + 23]+.
(E)-2-Allylidenecycloheptanone (18): IR (neat): 1699, 1613, 1579 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.62-1.80 (m, 6 H), 2.47-2.57 (m, 2 H), 2.62-2.68 (m, 2 H), 5.49 (dd, J = 9.9, 1.7 Hz, 1 H), 5.63 (dd, J = 16.7, 1.7 Hz, 1 H), 6.63 (ddd, J = 16.7, 11.5, 9.9 Hz, 1 H), 7.00 (d, J = 11.5 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 25.3, 27.5, 29.8, 31.3, 43.4, 125.4, 131.6, 135.2, 140.3, 204.8. LC-MS (ES): m/z = 151 [M + 1]+.

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1-Benzoyl-4,6,6-trimethylcyclohex-3-enecarbonitrile (10): IR (KBr): 2232, 1692, 1596, 1578 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.12 (s, 3 H), 1.21 (s, 3 H), 1.72 (br s, 3 H), 1.96 (d, J = 17.9 Hz, 1 H), 2.31 (d, J = 17.9 Hz, 1 H), 2.58 (br d, J = 17.8 Hz, 1 H), 2.90 (br d, J = 17.8 Hz, 1 H), 5.32 (br s, 1 H), 7.42-7.48 (tm, J = 7.3 Hz, 2 H) 7.52-7.58 (tm, J = 7.3 Hz, 1 H), 8.04-8.08 (dm, J = 7.3 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 22.7, 23.8, 27.7, 33.1, 36.7, 44.0, 53.2, 115.2, 121.7,128.4, 129.1, 132.9, 133.9, 137.5, 195.3. LC-MS (ES): m/z = 253 [M]+.
1-Benzoyl-3,4,6,6-tetramethylcyclohex-3-enecarbonitrile (11): IR (KBr): 2232, 1692, 1595, 1578 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.08 (s, 3 H), 1.20 (s, 3 H), 1.66 (br s, 6 H), 1.90 (d, J = 17.8 Hz, 1 H), 2.38 (br d, J = 18.0 Hz, 1 H), 2.44 (d, J = 17.8 Hz, 1 H), 2.88 (br d, J = 18.0 Hz, 1 H), 7.43-7.48 (tm, J = 7.8 Hz, 2 H), 7.53-7.59 (tm, J = 7.8 Hz, 1 H), 8.04-8.08 (dm, J = 7.8 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 18.4, 19.0, 22.5, 27.7, 36.6, 38.6, 45.7, 51.4, 120.3, 121.8, 125.2, 128.4, 129.1, 132.8, 137.8, 195.4. LC-MS (ES): m/z = 267 [M]+.

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It was reported by Reich et al.,9a that treatment of compound 2 with H2O2 (8.8 equiv) in CH2Cl2 containing a small portion of pyridine at 25 °C gave rise to a mixture of the exo- and endocyclic enones in a ratio of 1:1.3.