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7402; (d) White, J. D.; Quaranta, L.; Wang, G. J. Org. Chem. 2007, 72, 1717; (e)
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Part 5.
6a-c. Reasoning that the reaction might be hindered by the bulky
ligands of catalysts 14 and 15, especially given the presence of
the quaternary spirocentre
a to the acetylene, it was decided to
investigate simple gold salts 16 and 17. Elevated temperatures ini-
tially failed to provide any cyclised product 5c in either acetonitrile
or toluene.
3. (a) Bourne, Y.; Radi, Z.; Aráoz, R.; Talley, T.; Benoit, E.; Servent, D.; Taylor, P.;
Molgo, J.; Marchot, P. Proc. Nat. Acad. Sci. 2010, 107, 6076; (b) Aráoz, R.; Servent,
D.; Molgo, J.; Iorga, B. I.; Fruchart-Gaillard, C.; Benoit, E.; Gu, Z.; Stivala, C.;
Finally, we were pleased to discover that heating 6a or 6b in
acetonitrile under sealed-tube conditions, in the presence of gold
phosphine catalyst 17 and triethylamine,14 afforded the respective
five- and six-membered cyclic imines 5a and 5b in 91% and 80%
yields. Based on these results, use of the non-coordinating anti-
mony hexafluoride counterion appears important for any reaction
to occur. The reactions were notably rapid, affording a single prod-
uct cleanly according to TLC in less than 30 min and requiring only
simple filtration to provide nearly pure products.15,16 Contrary to
our initial concerns, the imines 5a and 5b appeared relatively resis-
tant to hydrolysis, proving stable to benchtop storage open to air
for prolonged periods. However, despite all efforts, it remained
impossible to isolate any of the corresponding seven-membered
cyclic imine 5c upon subjecting amino-alkyne 6c to the same con-
ditions used successfully for 6a and 6b. Further studies will be re-
quired to determine whether this is due to a prohibitive energy
barrier or the instability of the product.
4. During preparation of this manuscript
a related cyclic imine study was
published by the Evans group: Marcoux, D.; Bindschädler, P.; Speed, A. W. H.;
Chiu, A.; Pero, J. E.; Borg, G. A.; Evans, D. A. Org. Lett. 2011. doi: 10.1021/
5. Ahn, Y.; Cardenas, G.; Yang, J.; Romo, D. Org. Lett. 2001, 3, 751.
6. (a) Muller, T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. Chem. Rev. 2008,
108, 3795; (b) Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. Rev. 2004, 104, 3079.
7. Doye, S. Synlett 2004, 1653.
8. Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180.
9. (a) Kim, H.; Livinghouse, T.; Lee, P. H. Tetrahedron 2008, 64, 2525; (b) Kim, H.;
Livinghouse, T.; Shim, J. H.; Lee, S. G.; Lee, P. H. Adv. Synth. Catal. 2006, 348, 701;
(c) Li, Y.; Marks, T. J. J. Am. Chem. Soc. 1996, 118, 9295.
10. Kondo, T.; Okada, T.; Suzuki, T.; Mitsudo, T. J. Organomet. Chem. 2001, 622,
149.
11. Tokunaga, M.; Eckert, M.; Wakatsuki, Y. Angew. Chem., Int. Ed. 1999, 38, 3222.
12. Nieto-Oberhuber, C.; Lopez, S.; Munoz, M.; Cardenas, D.; Bunuel, C.;
Echavarren, A. Angew. Chem., Int. Ed. 2005, 44, 6146.
13. Marion, N.; Nolan, S. P. Chem. Soc. Rev. 2008, 37, 1776.
14. Ritter, S.; Horino, Y.; Lex, J.; Schmalz, H. G. Synlett 2006, 3309.
15. Cyclic imines 5a and 5b were stable to TLC and flash chromatography using
10% EtMA (ethyl acetate containing 10% 9:1 MeOH-aq.NH3).
16. General hydroamination procedure: To a stirred solution of amino-alkyne 6a
(20.0 mg, 0.13 mmol) in MeCN (0.5 ml) in a sealed tube were added Au(PPh3)Cl
In summary, we have described the successful synthesis of spi-
rocyclic imines 5a and 5b in high yield via intramolecular alkyne
hydroamination, using the convenient gold phosphine catalyst
Au(PPh3)SbF6. All efforts to obtain the analogous seven-membered
imine 5c have proved fruitless to date. These results demonstrate
(3.30 mg, 6.60 mmol), AgSbF6 (2.30 mg, 6.60 mmol) and Et3N (0.9 ll,
6.60 mmol). The mixture was heated at 95 °C for 0.5 h then filtered and
concentrated in vacuo to afford cyclic imine 5a (18.2 mg, 91%) as a yellow oil:
Rf 0.85 (10% EtMA); IR vmax(film) 2926, 2855, 1641, 1437, 750, 694, 623 cmꢀ1
;
1H NMR (400 MHz, CDCl3) d 1.11–1.50 (6H, m, 6-H0, 7-H, 9-H, 10-H0), 1.68–1.73
(4H, m, 6-H00, 8-H, 10-H00), 1.82 (2H, t, J = 7.2 Hz, 4-H), 1.96 (3H, t, J = 1.6 Hz, 10-
H), 3.68–3.72 (2H, m, 3-H); 13C NMR (100 MHz, CDCl3) d 15.9 (CH3, C-10), 23.1
(CH2, C-6, C-10), 25.7 (CH2, C-8), 32.8 (CH2, C-7, C-9), 33.3 (CH2, C-4), 54.7 (C, C-
5), 56.9 (CH2, C-3), 182.5 (C@N, C-1); m/z (ESI+, %) 152 (M+H+, 100); HRMS M+
found 152.1432, C10H18N+ requires 152.1434.
the feasibility of hydroamination of
a-quaternary alkyne sub-
strates and also suggest that the five- and six-membered cyclic
imine products may be stable enough to be utilised as viable inter-
mediates in synthesis.
Data for 5b: Rf 0.85 (10% EtMA); IR vmax(film) 2927, 2855, 1644, 1449, 695, 657,
623 cmꢀ1 1H NMR (400 MHz, CDCl3) d 1.44–1.72 (14H, m, 4-H, 5-H, 7-H, 8-H,
.
References and notes
9-H, 10-H, 11-H), 2.02 (3H, s, 10-H), 3.51–3.54 (2H, m, 3-H); 13C NMR
(100 MHz, CDCl3) d 18.7 (CH2, C-9), 20.6 (CH2, C-7, C-11), 22.7 (CH3, C-10), 25.7
(CH2, C-5), 27.6 (CH2, C-4), 33.1 (CH2, C-8, C-10), 39.6 (C, C-6), 49.6 (CH2, C-3),
177.0 (C@N, C-1); m/z (ESI+, %) 166 (M+H+, 100); HRMS M+ found 166.1594,
1. Gueret, S. M.; Brimble, M. A. Nat. Prod. Rep. 2010, 27, 1350.
2. Pinnatoxin: (a) Beaumont, S.; Ilardi, E.; Tappin, N. D. C.; Zakarian, A. Eur. J. Org.
Chem. 2010, 5743. and references therein; Gymnodimine: (b) Toumieux, S.;
Beniazza, R.; Desvergnes, V.; Araoz, R.; Molgo, J.; Landais, Y. Org. Biomol. Chem.
C
11H20N+ requires 166.1590.