11-Phenyl-6,7-dihydropyrimido[2,1-a]-5-isoquinolinium trifluo-
d (ppm) = 28.72 (C-8), 40.23 (C-19), 56.18 (C-7), 113.41 (C-17),
125.45 (C-14), 125.61 (C-3), 127.22 (C-12), 127.75 (C-15), 129.75
(C-5), 131.05 (C-16), 131.87 (C-10), 133.60 (C-11), 140.23 (C-9),
144.12 (C-13), 144.19 (C-4), 145.88 (C-2), 150.97 (C-6), 151.62
-1
˜
(C-18). IR (CHCl3): n (cm ) = 476 vw, 518 m, 544 vw, 561 vw, 574
m, 638 vs, 823 m, 948 w, 1005 vw, 1030 vs, 1064 w, 1135 m, 1163 s,
1170 s, 1264 vs, 1276 vs, 1363 m, 1428 w, 1445 m, 1473 m, 1508 s,
1526 s, 1552 w, 1567 m, 1580 m, 1593 m, 1610 s, 1626 m, 2811 w,
3091 w. MS (ESI) m/z (%): 301 [(M-OTf)+] (100). HRMS (ESI)
m/z: [(M-OTf)+] (C21H21N2) calc.: 301.1699, found: 301.1699.
romethanesulfonate (26).
[Rh(PPh3)3Cl] (15 mg,
0.02 mmol, 9.7 mol %) and compound 25 (61 mg, 0.16 mmol, 1
equiv.) were added to a Schlenk tube. The tube was sealed with
a septum, and the system was purged with Ar (3x). Degassed
DMF (7 mL) was added via needle and syringe. A balloon
with acetylene was connected to the Schlenk tube, and argon
atmosphere was changed to atmosphere of acetylene. The reaction
◦
Acknowledgements
mixture was stirred for 20 h at 80 C. The reaction mixture was
concentrated in vacuo and the resultant residue was purified by
flash chromatography on silica gel (column diameter 1.5 cm,
plug height 9 cm, CH2Cl2–MeOH 10 : 1). The compound 26 was
obtained as a brownish liquid in 82% yield (54 mg, 0.13 mmol). 1H
NMR (600 MHz, (CD3)2CO): d (ppm) = 3.60–3.63 (m, 2H, H-8);
5.19–5.22 (m, 2H, H-7); 7.37–7.43 (m, 5H, H-16, H-17, H-18);
7.58 (ddt, J = 0.6, 1.3, 7.7 Hz, 1H, H-10); 7.66 (ddt, J = 0.8, 1.3,
7.6 Hz, 1H, H-12); 7.85 (t, J = 7.6 Hz, 1H, H-11); 8.06 (dd, J = 4.7,
6.3 Hz, 1H, H-3); 9.00 (dd, J = 2.0, 4.7 Hz, 1H, H-4); 9.49 (ddt,
J = 0.8, 2.0 6.3 Hz, 1H, H-2). 13C NMR (151 MHz, (CD3)2CO):
d (ppm) = 27.71 (C-8), 55.96 (C-7), 121.72 (C-3), 125.73 (C-14),
128.14 (C-12), 128.23 (C-18), 129.04 (C-16), 129.58 (C-17), 132.56
Financial Support by Czech Science Foundation (203/09/1614,
203/09/0705), IOCB (Z4 055 0506), and COST (D36 OC140) is
gratefully acknowledged. I.C. thanks MSM0021620857. We thank
Dr S. V. Volkov, Dr P. Fiedler for their experimental help and Dr
L. Adriaenssens for fruitful discussions.
Notes and references
1 For reviews, see: (a) W. Sliwa, Curr. Org. Chem., 2003, 7, 995; (b) H.
Ihmels and D. Otto, Top. Curr. Chem., 2005, 258, 161; For a recent
review on quaternary protoberberine alkaloids, see: (c) L. Grycova´,
J. Dosta´l and R. Marek, Phytochemistry, 2007, 68, 150. Review on
the anti-tumor benzo[c]phenanthridine alkaloids fagaronine, nitidine,
coralyne: (d) S. D. Phillips and R. N. Castle, J. Heterocycl. Chem., 1981,
18, 223. For further references on cationic alkaloids with wide-ranging
bioactivities, see: (e) A. Fu¨rstner and A. Ernst, Tetrahedron, 1995, 51,
773. For examples, see: (f) G. R. Rosania, J. W. Lee, L. Ding, H. S.
Yoon and Y. T. Chang, J. Am. Chem. Soc., 2003, 125, 1130; (g) A.
D. C. Parenty, L. V. Smith, K. M. Guthrie, D. L. Long, J. Plumb, R.
Brown and L. Cronin, J. Med. Chem., 2005, 48, 4504; (h) U. Al-Atar,
R. Fernandes, B. Johnsen, D. Baillie and N. R. Branda, J. Am. Chem.
Soc., 2009, 131, 15966.
(C-10), 135.05 (C-11), 141.93 (C-15), 142.20 (C-13), 145.89 (C-9),
-1
˜
153.74 (C-2), 158.01 (C-6), 164.33 (C-4). IR (CHCl3): n (cm ) =
482 vw, 518 w, 542 vw, 575 w, 623 w, 639 s, 702 m, 810 w, 1001 vw,
1030 vs, 1076 vw, 1094 vw, 1166 s, 1260 vs, 1273 vs, 1319 w, 1423
w, 1436 w, 1455 w, 1471 w, 1484 s, 1498 w, 1556 s, 1576 w, 1593 m,
1619 m, 3066 w, 3083 w. MS (ESI) m/z (%): 259 [(M-OTf)+] (100).
HRMS (ESI) m/z: [(M-OTf)+] (C18H15N2) calc.: 259.1230, found:
259.1229.
2 For an elegant entry to cationic N-heteroaromatic species based on
pyridine ring construction via [2+2+2] cycloaddition followed by
spontaneous intramolecular N-quaternization, see: (a) A. McIver, D.
D. Young and A. Deiters, Chem. Commun., 2008, 39, 4750; (b) A.
McIver and A. Deiters, Org. Lett., 2010, 12, 1288.
11-(4-(Dimethylamino)phenyl)-6,7-dihydropyrido[2,1-a]isoqui-
3 Economy of steps is one of the most important criterion for efficiency in
chemical synthesis, see: T. Newhouse, P. S. Baran and R. W. Hoffmann,
Chem. Soc. Rev., 2009, 38, 3010.
4 (a) A. Nu´n˜ez, A. M. Cuadro, J. Alvarez-Builla and J. J. Vaquero, Chem.
Commun., 2006, 25, 2690; For related RCM approach, see: (b) A.
Nu´n˜ez, A. M. Cuadro, J. Alvarez-Builla and J. J. Vaquero, Org. Lett.,
2004, 6, 4125; (c) A. Nu´n˜ez, B. Abarca, A. M. Cuadro, J. Alvarez-Builla
and J. J. Vaquero, J. Org. Chem., 2009, 74, 4166.
nolinium
trifluoromethanesulfonate
(29).
[Rh(PPh3)3Cl] (11 mg, 0.01 mmol, 10.2 mol %) and compound 28
(47 mg, 0.11 mmol, 1 equiv.) were added to a Schlenk tube. The
tube was sealed with a septum, and the system was purged with
Ar (3x). Degassed DMF (3 mL) was added via needle and syringe.
A balloon with acetylene was connected to the Schlenk tube,
and argon atmosphere was changed to atmosphere of acetylene.
ˇ
5 (a) L. Adriaenssens, L. Severa, T. Sa´lova´, I. C´ısarˇova´, R. Pohl, D.
ˇ
Saman, S. V. Rocha, N. S. Finney, L. Posp´ısˇil, P. Slav´ıcˇek and F. Teply´,
Chem.–Eur. J., 2009, 15, 1072; (b) L. Adriaenssens, L. Severa, J. Va´vra,
ˇ
ˇ
ˇ
T. Sa´lova´, J. Hy´vl, M. C´ızˇkova´, R. Pohl, D. Saman and F. Teply´, Collect.
Czech. Chem. Commun., 2009, 74, 1023; (c) L. Severa, L. Adriaenssens,
◦
The reaction mixture was stirred for 24 h at 80 C. The reaction
ˇ
J. Va´vra, D. Saman, I. C´ısarˇova´, P. Fiedler and F. Teply´, Tetrahedron,
2010, 66, 3537; (d) L. Severa, D. Koval, P. Novotna´, M. Oncˇa´k, P.
Sa´zelova´, D. Saman, P. Slav´ıcˇek, M. Urbanova´, V. Kasˇicˇka and F.
mixture was concentrated in vacuo and the resultant residue
was purified by flash chromatography on silica gel (column
diameter 1.5 cm, plug height 10 cm, CH2Cl2–MeOH 10 : 1). The
compound 29 was obtained as an orange liquid in 89% yield
(44 mg, 0.10 mmol). 1H NMR (600 MHz, (CD3)2CO): d (ppm) =
2.90 (s, 6H, H-19); 3.48 (bt, J = 6.8 Hz, 2H, H-8); 5.10 (bt, J =
6.8 Hz, 2H, H-7); 6.80–6.82 (m, 2H, H-17); 7.29–7.32 (m, 2H,
H-16); 7.54 (ddt, J = 1.0, 1.3, 7.6 Hz, 1H, H-12); 7.55 (ddt, J =
0.7, 1.3, 7.6 Hz, 1H, H-10); 7.61 (bdd, J = 1.4, 8.4 Hz, 1H, H-5);
7.71 (t, J = 7.6 Hz, 1H, H-11); 7.94 (ddd, J = 1.4, 6.2, 7.6 Hz,
1H, H-3); 8.26 (ddd, J = 1.6, 7.6, 8.4 Hz, 1H, H-4); 9.12 (ddq,
J = 0.7, 1.6, 6.2 Hz, 1H, H-2). 13C NMR (151 MHz, (CD3)2CO):
ˇ
Teply´, New J. Chem., 2010, 34, 1063.
6 For recent reviews on metal-catalyzed [2+2+2] cycloadditions, see:
(a) N. Agenet, O. Buisine, F. Slowinski, V. Gandon, C. Aubert and
M. Malacria, in Organic Reactions, ed. L. E. Overman, Wiley, New
York, 2007; Vol. 68, p 1; (b) K. Tanaka, Synlett, 2007, 13, 1977; (c) P.
R. Chopade and J. Louie, Adv. Synth. Catal., 2006, 348, 2307; (d) S.
Kotha, E. Brahmachary and K. Lahiri, Eur. J. Org. Chem., 2005, 22,
4741.
7 For examples of metal-catalyzed [2+2+2] cycloaddition of diynes: (a) Y.
Yamamoto, T. Arakawa, R. Ogawa and K. Itoh, J. Am. Chem. Soc.,
2006, 128, 8336; (b) Y. Yamamoto, K. Hattori and H. Nishiyama, J. Am.
Chem. Soc., 2003, 125, 12143; (c) R. Grigg, R. Scott and P. Stevenson,
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