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Synlett 2010(7): 1051-1054  
DOI: 10.1055/s-0029-1219572
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Intramolecular Cobalt-Catalyzed [2+2+2] Cycloaddition of O-Protected Diyne-Cyanohydrins

Anja Meißner, Ulrich Groth*
Department of Chemistry and Konstanz Research School Chemical Biology, University of Konstanz, Universitätsstr. 10, 78457 Konstanz, Germany
Fax: +49(7531)884155; e-Mail: Ulrich.Groth@uni-konstanz.de;
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Publication History

Received 19 January 2010
Publication Date:
05 March 2010 (online)

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Abstract

O-Protected cyanohydrins were found to serve as a source of the nitrile within the intramolecular cobalt-mediated [2+2+2] cycloaddition to pyridines. Several 6-substituted 1,2,3,4,7,8,9,10-octahydrophenanthridines were synthesized using this cycloaddition of diyne-cyanohydrins. By introduction a TMS group a divergent way to such phenanthridine derivatives was elaborated.

Key words

cyanohydrin - cycloaddition - pyridines - alkynes - heterocycles

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11

A Typical Procedure for the Cycloaddition Reaction To the diyne-cyanohydrin (0.5 mmol) a solution of CpCo(CO)2 (0.05 mmol) in toluene (15 mL) was added. The reaction mixture was refluxed with contemporaneous irradiation by a 250 W tungsten lamp until no starting material could be detected by TLC. After addition of silica gel and evaporation of the solvent the product was subjected to column chromatography yielding the desired product.

12

4-( tert -Butyldimethylsilyloxy)-1,2,3,4,7,8,9,10-octahydrophenanthridine (2)
Yellowish solid; mp 60-62 ˚C. R f = 0.43 (petroleum benzene-EtOAc = 5:1). ¹H NMR (400 MHz, CDCl3): δ = 0.06 [s, 3 H, Si(CH3)2 t-Bu], 0.21 [s, 3 H, Si(CH3)2 t-Bu], 0.89 [s, 9 H, SiMe2C(CH3)3], 1.76 (m, 6 H, 3 × CH2), 1.94-2.13 (m, 2 H, CH2), 2.37-2.64 (m, 4 H, 2 × CH2), 2.71 (m, 2 H, CH2), 4.78 (m, 1 H, H4), 8.15 (s, 1 H, H6) ppm. ¹³C NMR (100.5 MHz, CDCl3): δ = -4.9, -4.0 [Si(CH3)2 t-Bu], 16.9 (C2), 18.3, 22.2, 22.7, 25.0, 25.5 (C7, C8, C9, C10, and SiMe2CMe3), 25.9 [SiMe2C(C)H3)3], 26.8 (C1), 31.9 (C3), 70.2 (C4), 130.0, 131.3 (C6a and C10a), 144.2 (C10b), 147.4 (C5), 153.8 (C4a) ppm. GC-MS: m/z (%) = 317 (1) [M]+, 260 (100) [ M - t-Bu]+, 186 (16) [M - OTBS]+, 75 (10).
IR (neat): 2927.1 (m), 2854.4 (m), 1580.7 (w), 1567.2 (w), 1461.9 (w), 1243.0 (m), 1077.7 (s), 1030.5 (s), 831.2 (s), 777.1 (s) cm-¹. Anal. Calcd for C19H31NOSi: C, 71.87; H, 9.84; N, 4.41. Found: C, 71.89; H, 9.79; N, 3.50.

13

4-( tert -Butyldimethylsilyloxy)-6-methyl-1,2,3,4,7,8,9,10-octahydrophenanthridine (9a)
Yellow wax; R f = 0.67 (petroleum benzene-EtOAc = 5:1). ¹H NMR (400 MHz, CDCl3): δ = 0.06 [s, 3H, Si(CH3)2 t-Bu], 0.23 [s, 3 H, Si(CH3)2 t-Bu], 0.90 [s, 9 H, SiMe2C(CH3)3], 1.77 (m, 6 H, 3 × CH2), 1.95, 2.06 (2 × m, 2 × 1 H, CH2), 2.34 (s, 3 H, CH3), 2.40, 2.52 (2 × m, 2 × 1 H, CH2), 2.59 (m, 6 H, 3 × CH2), 4.75 (t, 1 H, ³ J = 3.6 Hz, H4) ppm. ¹³C NMR (100.5 MHz, CDCl3): δ = -4.8, -4.0 [Si(CH3)2 t-Bu], 17.5, 18.4 (2 × CH2), 22.0 (CH3), 22.3 (CH2), 22.4 (SiCMe3), 25.0 (CH2), 26.0 [SiC(CH3)3], 26.1, 26.4 (2 × CH2), 32.1 (C3), 70.3 (C4), 127.6, 129.1 (C6a and 10b), 143.9 (C10b), 152.5, 153.5 (C4a and C6) ppm. GC-MS: m/z (%) = 331 (1) [M]+, 274 (100), 200(14), 75 (12). IR (neat): 2928.6 (m), 2854.4 (m), 1575.9 (w), 1427.0 (m), 1247.3 (m), 1080.9 (s), 1028.8 (s), 1003.8 (m), 956.8 (m), 877.0 (m), 832.1 (s), 774.2 (s) cm-¹. Anal. Calcd for C20H33NOSi: C, 72.45; H, 10.03; N, 4.22. Found: C, 71.12; H, 9.76; N, 4.21.
4-( tert -Butyldimethylsilyloxy)-6-phenyl-1,2,3,4,7,8,9,10-octahydrophenanthridine (9b)
Colorless solid; mp 116 ˚C. R f = 0.70 (petroleum benzene-EtOAc = 5:1). ¹H NMR (400 MHz, CDCl3): δ = 0.05 [s, 3 H, Si(CH3)2 t-Bu], 0.19 [s, 3 H, Si(CH3)2 t-Bu], 0.90 [s, 9 H, SiMe2C(CH3)3], 1.55 (m, 2 H, H9), 1.77, 1.93 (2 × m, 2 × 1 H, H10), 1.82, 2.16 (2 × m, 2 × 1H, H2), 1.84, 2.02 (2 × m, 2 × 1 H, H3), 2.49, 2.70 (2 × m, 2 × 1 H, H1), 2.60, 2.77 (2 × m, 2 × 1 H, H7), 2.62 (m, 2 H, H8) ppm. ¹³C NMR (100.5 MHz, CDCl3): δ = -4.9, -4.0 [Si(CH3)2 t-Bu], 17.1 (C2), 18.4 (SiMe2CMe3), 22.4 (C10), 22.5 (C9), 25.2 (C1), 25.9 [SiMe2C(CH3)3], 26.4 (C8), 28.4 (C7), 31.9 (C3), 70.2 (C4), 127.3 (C4′), 127.7 (C2′), 129.0 (C10a), 129.1 (C1′), 129.3 (C3′), 141.1 (C6a), 144.9 (C10b), 153.1 (C4a), 155.6 (C6) ppm. GC-MS: m/z (%) = 393 (1) [M]+, 336 (100), 262 (11), 75 (15). IR (neat): 3050.3 (w), 2925.8 (s), 2853.4 (m), 1571.9 (m), 1558.2 (m), 1471.4 (m), 1460.5 (m), 1451.9 (m), 1416.5 (m), 1358.8 (m), 1252.4 (m), 1068.0 (s), 1021.2 (s), 957.7 (s), 878.2 (s), 830.3 (s), 769.8 (s), 742.1 (s), 695.5 (s) cm-¹. Anal. Calcd for C25H35NOSi: C, 76.28; H, 8.96; N, 3.56. Found: C, 75.45; H, 8.89; N, 3.31.
4-( tert -Butyldimethylsilyloxy)-6-(trimethylsilyl)-1,2,3,4,7,8,9,10-octahydrophenanthridine (11)
Yellowish solid; mp 58 ˚C. R f = 0.60 (PE-Et2O = 5:1). ¹H NMR (400 MHz, CDCl3): δ = 0.06 [s, 3 H, OSi(CH3)2], 0.24 [s, 3 H, OSi(CH3)2], 0.34 [s, 9 H, Si(CH3)3], 0.90 [s, 9 H, OSiMe2C(CH3)3], 1.68-1.88 (m, 6 H, 3 × CH2), 1.97-2.14 (m, 2 H, CH2), 2.38-2.68 (m, 4 H, 2 × CH2), 2.82 (m, 2 H, H3), 4.82 (s, 1 H, H4) ppm. ¹³C NMR (100.5MHz, CDCl3): δ = -4.9, -4.0 [OSi(CH3)2], 0.03 [Si(CH3)3], 16.9, 18.3, 22.5, 22.6, 25.3 (5 × CH2), 25.9 (OSiMe2CCH3)3), 26.0 [OSiMe2CCH3)3], 28.4 (CH2), 32.0 (C3), 70.3 (C4), 129.7, 137.4, 141.9 (C7, C10a, C10b), 153.5, 162.6 (C4a, C6) ppm. GC-MS: m/z (%) = 389 (1) [M]+, 374 (4) [M - Me]+, 332 (100) [M - t-Bu]+, 316 (5) [M - TMS]+, 258 (9) [M - OTBS]+, 242 (12), 73 (26), 57 (13). IR (neat): 2943.7 (m), 2928.1 (m), 2854.9 (m), 1558.5 (w), 1542.6 (w), 1470.9 (m), 1243.9 (s), 1076.3 (s), 1033.2 (s), 826.8 (s), 775.8 (s) cm-¹. Anal. Calcd for C22H39NOSi2: C, 67.80; H, 10.09; N, 3.59. Found: C, 67.33; H, 10.15; N, 3.25.