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DOI: 10.1055/s-0029-1219572
Intramolecular Cobalt-Catalyzed [2+2+2] Cycloaddition of O-Protected Diyne-Cyanohydrins
Publication History
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
- For [2+2+2] cycloadditions in general, see:
-
1a
Vollhardt KPC.Bergman RG. J. Am. Chem. Soc. 1974, 96: 4996 -
1b
Hillard RL.Vollhardt KPC. J. Am. Chem. Soc. 1977, 99: 4058 -
1c
Wakatsuki Y.Yamazaki H.
J. Organomet. Chem. 1977, 139: 169 -
1d
Vollhardt KPC. Angew. Chem., Int. Ed. Engl. 1984, 23: 539 -
1e
Lecker SH.Nguyen NH.Vollhardt KPC. J. Am. Chem. Soc. 1986, 108: 856 -
1f
Saá C.Crotts DD.Hsu G.Vollhardt KPC. Synlett 1994, 487 -
1g
Malacria M. Chem. Rev. 1996, 96: 289 -
1h
Groth U.Richter N.Kalogerakis A. Eur. J. Org. Chem. 2003, 4634 -
1i
Kalogerakis A.Groth U. Synlett 2003, 1886 -
1j
Varela JA.Saá C. Chem. Rev. 2003, 103: 3787 -
1k
Chouraqui G.Petit M.Aubert C.Malacria M. Org. Lett. 2004, 6: 1519 -
1l
Kesenheimer C.Groth U. Org. Lett. 2006, 8: 2507 -
1m
Gandon V.Aubert C.Malacria M. Chem. Commun. 2006, 21: 2209 -
1n
Chopade P.Louie J. Adv. Synth. Catal. 2006, 348: 2307 -
1o
Heller B.Hapke M. Chem. Soc. Rev. 2007, 36: 1085 -
1p
Koegl M.Brecker L.Warrass R.Mulzer J. Angew. Chem. Int. Ed. 2007, 46: 9320 -
1q
Heller B.Gutnov A.Fischer C.Drexler H.-J.Spannenberg A.Redkin D.Sundermann C.Sundermann B. Chem. Eur. J. 2007, 13: 1117 -
1r
Varela JA.Saá C. Synlett 2008, 2571 -
1s
Omae I. Appl. Organomet. Chem. 2008, 22: 149 -
1t
Shibata T.Tsuchikama K. Org. Biomol. Chem. 2008, 6: 1317 -
1u
Nicolaus N.Strauss S.Neudörfl J.-M.Prokop A.Schmalz H.-G. Org. Lett. 2009, 11: 341 -
1v
Shibata T.Uchiyama T.Endo K. Org. Lett. 2009, 11: 3906 -
2a
Bönnemann H.Brinkmann R.Schlenkluhn H. Synthesis 1974, 575 -
2b
Bönnemann H. Angew. Chem. 1978, 90: 517 -
2c
Bönnemann H. Angew. Chem. 1985, 97: 264 -
3a
Groth U.Huhn T.Kesenheimer C.Kalogerakis A. Synlett 2005, 1758 -
3b
Groth U.Richter N.Kalogerakis A. Synlett 2006, 905 -
3c
Garcia P.Moulin S.Miclo Y.Leboeuf D.Gandon V.Aubert C.Malacria M. Chem. Eur. J. 2009, 15: 2129 - 4
Chelucci G.Cabras MA.Saba A. Tetrahedron: Asymmetry 1994, 5: 1973 -
5a
Heller B.Sundermann B.Fischer C.You J.Chen W.Drexler H.-J.Knochel P.Bonrath W.Gutnov A.
J. Org. Chem. 2003, 68: 9221 -
5b
Heller B.Redkin D.Gutnov A.Fischer C.Bonrath W.Karge R.Hapke M. Synthesis 2008, 69 - 6
Hrdina R.Dračínský M.Valterová I.Hodačová J.Císařová I.Kotora M. Adv. Synth. Catal. 2008, 350: 1449 - 7
Slowinski F.Aubert C.Malacria M. Eur. J. Org. Chem. 2001, 3491 - 8
Dickschat JS.Bode HB.Kroppenstedt RM.Müller R.Schulz S. Org. Biomol. Chem. 2005, 3: 2824 - 9
Bengtsson M.Liljefors T. Synthesis 1988, 250 - 10
Rawal VH.Rao JA.Cava MP. Tetrahedron Lett. 1985, 26: 4275 - For acidic protodesilylation, see:
-
14a
Geiger RE.Lalonde M.Stoller H.Schleich K. Helv. Chim. Acta 1984, 67: 1274 -
14b
Parnell CA.Vollhardt KPC. Tetrahedron 1985, 41: 5791 - For the Tamao oxidation in general, see:
-
15a
Tamao K.Yoshida J.-L.Takahashi M.Yamamoto H.Kakui T.Matsumoto H.Kurita A.Kumada M. J. Am. Chem. Soc. 1978, 100: 290 -
15b
Tamao K.Kakui T.Kumada M.
J. Am. Chem. Soc. 1978, 100: 2268 -
15c
Tamao K.Ishida N.Tanaka T.Kumada M. Organometallics 1983, 2: 1694 -
15d
Tamao K.Maeda K.Yamaguchi T.Ito Y.
J. Am. Chem. Soc. 1989, 111: 4984 -
15e
Tamao K.Hayashi T.Ito Y. In Frontiers of Organosilicon ChemistryBassindale AR.Gaspar PP. RSC; Cambridge: 1991. p.197 - For reviews of the Hiyama reaction, see, for example:
-
16a
Hiyama T.Shirakawa E. Top. Curr. Chem. 2002, 219: 61 -
16b
Denmark SE.Sweis RF. In Metal-Catalyzed Cross-Coupling ReactionsDe Meijere A.Diederich F. Wiley-VCH; Weinheim: 2004. Chap. 4.
References and Notes
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.
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.