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Synlett 2006(10): 1554-1558  
DOI: 10.1055/s-2006-944191
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Simple Strategy for Incorporation, Protection, and Deprotection of ­Selenium Functionality

Gianina Logana, Charity Igunbora, Gue-Xiong Chena, Hays Davisa, Arlyne Simona, Jozef Salona, Zhen Huang*a,b
a Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA
b Brooklyn College, Brooklyn, NY 11210, USA
Fax: 01(404)6511416; e-Mail: huang@gsu.edu;
Further Information

Publication History

Received 22 February 2006
Publication Date:
12 June 2006 (online)

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Abstract

Synthesis of di-2-cyanoethyl diselenide is reported for the first time. Using this reagent, incorporation and protection of ­selenium functionality can be achieved in one step with high yield, and the deprotection condition is mild, which allows alkylation ­simultaneously.

Key words

organoselenium compounds - selenium incorporation - selenol protection - deprotection

1

These authors have contributed equally to this publication.

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Di-2-cyanoethyl Diselenide ( 3). Solution of dioxane-EtOH (4:1, 100 mL) was injected into a flask containing selenium metal (7.9 g, 100 mmol; FW = 79) and NaBH4 (2.7 g) under argon. After stirring the dark suspension for 1 h, 3-bromopropionitrile (12.4 mL, 150 mmol, 1.5 equiv; MW = 134, ρ = 1.62 g/mL) was added dropwise in an ice bath. The reaction was stirred for 1 h before it was poured into a beaker containing H2O (400 mL). The suspension (yellow-orange) in the beaker was adjusted to pH 7 and then extracted with EtOAc (3 × 200 mL). The combined organic phases were washed with NaCl (sat., 100 mL) and then dried over MgSO4 (s). After evaporation of the solvent under reduced pressure, the crude product was purified on silica gel column equilibrated with CH2Cl2-hexane (30:70). The gradient was run using CH2Cl2 in hexane (150 mL each, 30%, 40%, 50%, 60%, 70%, and 80%). The eluted product was light orange. The solvents were evaporated under reduced pressure (using rotary evaporator, do not use high vacuum) and co-evaporated with MeOH twice (2 × 30 mL). A light-orange product was obtained (9.65 g, 72% yield). 1H NMR (300 MHz, CDCl3): δ = 2.84 (t, J = 7.2 Hz, 2 H, CH2Se), 3.04 (t, J = 7.2 Hz, 2 H, CH2CN). 13C NMR (75 MHz, CDCl3): δ = 18.65 (CH2Se), 21.53 (CH2CN), 118.27 (CN). HRMS (MALDI-FTMS): m/z [M (with 80Se) + Na]+ calcd for C6H8N2Se2: 290.8916; found: 290.8912. When a large excess of NaBH4 was used in the reaction, colorless di-2-cyanoethyl selenide was also isolated. 1H NMR (300 MHz, CDCl3). δ = 2.91 (t, J = 7.1 Hz, 2 H, CH2Se), 3.53 (t, J = 7.1 Hz, 2 H, CH2CN). 13C NMR (75 MHz, CDCl3): δ = 21.03 (CH2Se), 23.27 (CH2CN), 117.42 (CN). HRMS (MALDI-FTMS): m/z [M with (80Se + Na)]+ calcd for C6H8N2Se: 210.9750; found: 210.9746.

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Benzyl 2-Cyanoethyl Selenide ( 5a).
EtOH (5 mL) was added to NaBH4 (317 mg) placed in an airtight flask under an argon balloon. The supernate of the mixture was added into a round-bottom flask (100 mL, on an ice bath) containing di-2-cyanoethyl diselenide (1.48 mL, 2.67 g, 10 mmol, ρ = 1.8 g/mL) under an argon balloon. After stirring for 5 min, the reaction turned colorless from light orange color. Benzyl chloride (0.75 mL, 821 mg, 6.5 mmol, ρ = 1.1 g/mL) was then injected into the reaction. After completion in 30 min (monitored on TLC, hexane-CH2Cl2 = 9:1; the product R f = 0.61), H2O (50 mL) was added to quench the reaction, and the pH was adjusted to 7 with 10% AcOH. The crude product was extracted three times with EtOAc (50 mL each time), and the organic phases were combined and dried over MgSO4 (s). After removal of the solvent using rotary evaporator under reduced pressure, the crude product was purified by several preparative TLC plates (hexane-CH2Cl2 = 8:2). An oil product (1.412 g) was obtained (97% yield). 1H NMR (CDCl3): δ = 2.48 (t, J = 7.2 Hz, 2 H, CH2Se), 2.55 (t, J = 7.2 Hz, 2 H, CH2CN), 3.83 (s, 2 H, CH2Ph), 7.18-7.32 (m, 5 H, arom. protons). 13C NMR (CDCl3): δ = 17.19 (NCCH2CH2Se), 19.41 (CH2CN), 27.80 (CH2Ph), 118.91 (CN), 127.22 (p-ar.-C), 128.78 (o-ar.-C), 128.94 (m-ar.-C), 138.28 (ar. CCH2Se). MS (ESI): m/z = 91 [benzyl]+, 169, 225 [M + H]+. HRMS (MALDI-FTMS): m/z [M with 80Se]+ calcd for C10H11NSe: 225.0057; found: 225.0054.

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2-Cyanoethyl 2-Phenylethyl Selenide ( 5b).
The synthesis (85% yield) is analogous to the synthesis of 5a. 1H NMR (CDCl3): δ = 2.62-2.81 (m, 4 H, SeCH2CH2CN), 2.94 (t, J = 7.4 Hz, 2 H, SeCH2CH2Ph), 3.04 (t, J = 7.4 Hz, 2 H, SeCH2CH2Ph), 7.18-7.37 (m, 5 H, arom.). 13C NMR (CDCl3): δ = 17.57 (NCCH2CH2Se), 19.64 (CH2CN), 25.95 (CH2CH2Ph), 36.94 (CH2Ph), 118.87 (CN), 126.59 (p-ar.-C), 128.42 (o-ar.-C), 128.58 (m-ar.-C), 140.53 (ar. CCH2Se). HRMS (MALDI-FTMS): m/z [M with 80Se]+ calcd for C11H13NSe: 239.0213; found: 239.0209.

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2-Cyanoethyl (1-Naphthyl)methyl Selenide ( 5c). The synthesis (81% yield) is analogous to the synthesis of 5a. 1H NMR (CDCl3): δ = 2.53 (t, J = 7.0 Hz, 2 H, NCCH2CH2Se), 2.66 (t, J = 7.0 Hz, 2 H, NCCH2CH2Se), 4.36 (s, 2 H, CH2C10H7), 7.20-8.10 (m, 7 H, arom.). 13C NMR (CDCl3): δ = 17.77 (NCCH2CH2Se), 19.48 (CH2CN), 24.47 (CH2C10H9), 118.91 (CN), 123.88, 125.20, 126.14, 126.22, 127.01, 128.39, 128.92, 130.96, 133.57, 134.15 (10 C, arom.). HRMS (ESI-TOF): m/z [M with (80Se + Na)]+ calcd for C14H13NSe: 298.0105; found: 298.0099.

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2-Cyanoethyl 3-(1,3-Dioxoisoindolin-2-yl)propyl Selenide ( 5d). The synthesis (97% yield) is analogous to the synthesis of 5a. In this reaction, mixture of MeOH and toluene (1:9) was used to dissolve N-(3-bromopropyl)phthalimide. 1H NMR (CDCl3): δ = 2.04-2.11 (m, 2 H, NCH2CH2CH2Se), 2.69-2.86 (m, 6 H, NCH2CH2CH2SeCH2CH2CN), 3.81 (t, J = 6.8 Hz, 2 H, NCH2CH2CH2Se), 7.72-7.89 (m, 4 H, arom.). 13C NMR (CDCl3): δ = 17.8 (NCCH2CH2Se), 20.1 (CH2CN), 21.6 (NCH2CH2CH2), 29.4 (NCH2CH2CH2Se), 38.0 (NCH2CH2CH2Se), 123.3 (CN), 132.4, 133.8 and 134.1 (C, arom.), 169.2 (C=O). ESI-MS: m/z [M with 80Se]+ calcd for C14H14N2O2Se: 322.0221; found: 322.0218. When a large excess of NaBH4 was used, reduction of the nitrile to the corresponding imine was also observed. 1H NMR (CDCl3): δ = 1.99-2.08 (m, 2 H, NCH2CH2CH2Se), 2.66-2.78 (m, 6 H, NCH2CH2CH2SeCH2CH2CH=NH), 3.51 (t, J = 6.8 Hz, 2 H, NCH2CH2CH2Se), 4.05 (br, 1 H, NH), 5.76 (s, 1 H, SeCH2CH2CH=NH), 7.43-7.62 (m, 4 H, arom.). ESI-MS: m/z [M with 80Se]+ calcd for C14H16N2O2Se: 324.0377; found: 324.0371.

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Dibenzyl Selenide ( 7a).
A solution of K2CO3 (0.05 M in MeOH, 6 mL, 300 µmol, thoroughly purged with argon) was injected into a round-bottom flask containing benzyl (2-cyanoethyl) selenide (5a, 35.0 mg, 155 µmol) under argon, followed by injection of benzyl chloride (38.9 mg, 307 µmol, 2 equiv). When the reaction was completed over a few hours (monitored on analytical TLC, hexane-CH2Cl2 = 8:2), the solvent was evaporated under reduced pressure and the crude product was purified by preparative TLC (hexanes-CH2Cl2 = 7:3). An oil product was obtained (39.4 mg, 97% yield). 1H NMR (CDCl3): δ = 3.71 (s, 4 H, CH2Ph), 7.19-7.32 (m, 10 H, arom. protons). 13C NMR (CDCl3): δ = 27.2 (CH2Ph), 127.2 (p-ar.-C), 128.7 (o-ar.-C), 128.9 (m-ar.-C), 138.2 (ar. CCH2Se). MS (ESI): m/z = 91 [benzyl]+, 171, 260 and 262 [M+]. HRMS (MALDI-FTMS): m/z [M with 80Se]+ calcd for C14H14Se: 262.0261; found: 262.0264.

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Benzyl 2-Phenylethyl Selenide ( 7b). The synthesis (95% yield) is analogous to the synthesis of 7a. 1H NMR (CDCl3): δ = 2.74 (t, J = 7.3 Hz, 2 H, CH2Se), 2.92 (t, J = 7.3 Hz, 2 H, CH2CH2Ph), 3.78 (s, 2 H, CH2Ph), 7.17-7.36 (m, 10 H, arom.). 13C NMR (CDCl3): δ = 26.1 (CH2CH2Ph), 27.9 (CH2Ph), 38.0 (CH2CH2Ph), 126.3 and 126.7 (p-ar.-C), 128.4 and 128.7 (o-ar.-C), 129.6 and 129.9 (m-ar.-C), 139.4 and 141.2 (ar. CCH2). HRMS (MALDI-FTMS): m/z [M with 80Se]+ calcd for C15H16Se: 276.0417; found: 276.0419.

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Benzyl (1-Naphthyl)methyl Selenide ( 7c). The synthesis (84% yield) is analogous to the synthesis of 7a. 1H NMR (CDCl3): δ = 3.71 (s, 2 H, CH2C10H7), 4.12 (s, 2 H, CH2Ph), 7.19-7.89 (m, 12 H, aromatic). 13C NMR (CDCl3): δ = 25.30 (CH2C10H7), 28.72 (CH2Ph), 124.27, 125.48, 126.11, 126.29, 127.04, 127.10, 128.09, 128.37, 128.66, 128.88, 129.26, 129.34, 131.53, 134.35, 134.91, 139.36 (16 C, arom.). HRMS (MALDI-FTMS): m/z [M with 80Se]+ calcd for C18H16Se: 312.0417; found: 312.0415.

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Dibenzyl Diselenide ( 8a). A MeOH solution of K2CO3 (0.05 M, 6 mL, 300 µmol) was injected into a round-bottom flask containing benzyl (2-cyanoethyl) selenide (5a, 20.0 mg, 89 µmol), which was open to air. When the reaction was complete, (overnight; monitored by TLC, hexane-CH2Cl2 = 7:3, R f = 0.38), the solvent was evaporated under reduced pressure and the crude product was purified by preparative TLC (hexane-CH2Cl2 = 6:4). A solid product was obtained (28.1 mg, 92% yield). 1H NMR (CDCl3): δ = 3.86 (s, 4 H, CH2Ph), 7.23-7.38 (m, 10 H, arom. protons). 13C NMR (CDCl3): δ = 32.58 (CH2Ph), 127.09 (p-ar.-C), 128.43 (o-ar.-C), 129.01 (m-ar.-C), 138.18 (ar. CCH2Se). MS (ESI): m/z = 91 [benzyl]+, 169, 181, 262, and 342 [M + H]+. HRMS (MALDI-FTMS): m/z [M with 80Se]+ calcd for C14H14Se2: 341.9426; found: 341.9428.

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Di(phenylethyl) Diselenide ( 8b). 1H NMR (CDCl3): δ = 3.06 (t, J = 7.6 Hz, 4 H, CH2Se), 3.18 (t, J = 7.6 Hz, 4 H, CH2Ph), 7.22-7.37 (m, 10 H, arom.). 13C NMR (CDCl3): δ = 30.72 (CH2Se), 37.54 (CH2Ph), 126.39 (p-ar.-C), 128.50 (o-ar.-C), 128.54 (m-ar.-C), 140.79 (ar. CCH2Se). HRMS (MALDI-FTMS): m/z [M with 80Se]+ calcd for C16H18Se2: 369.9739; found: 369.9736.