Organic Letters
Letter
Application 20050267096, December 1, 2005. (b) Fleck, M.; Nosse, B.;
Roth, G. J. PCT International Application Nouveaux derives azetidine,
́ ́
Scheme 2. Sequential Cyclization/Arylation of 7
compositions pharmaceutiques correspondantes et leurs utilisations. WO
2013098375, July 4, 2013. (c) Cramp, S. M.; Dyke, H. J.; Pallin, T. D.;
Zahler, R. Partially Saturated Tricyclic Compounds and Methods of Making
and Using Same. PCT International Application WO 2012154676,
November 15, 2012. (d) Kim, R. M.; Parmee, E. R.; Sinz, C. J.; Ziouzina,
O. A. Soluble Guanylate Cyclase Activators. U.S. Patent Application
20100216764, August 26, 2010. (e) Billotte, S. Synlett 1998, 379.
(7) Duncton, M. J. A.; Estiarte, M. A.; Tan, D.; Kaub, C.; O’Mahony, D.
J. R.; Johnson, R. J.; Cox, M.; Edwards, W. T.; Wan, M.; Kincaid, J.; Kelly,
M. G. Org. Lett. 2008, 10, 3259. See also (a) Svenstrup, N.; Simonsen, K.
B.; Rasmussen, L. K.; Juhl, K.; Langaard, M.; Wen, K.; Wang, Y. PCT
International Application WO 2012EP69936, April 18, 2013. (b) Oslob,
J. D.; McDowell, R. S.; Johnson, R.; Yang, H.; Evanchik, M.; Zaharia, C.
A.; Cai, H.; Hu, L. W. Heterocyclic Modulators of Lipid Synthesis. PCT
International Application WO 2014008197, January 09, 2014.
(8) For other cross-coupling involving (pseudo)halogeno-azetidines,
see (a) Cheung, C. W.; Ren, P.; Hu, X. Org. Lett. 2014, 16, 2566.
(b) Molander, G. A.; Traister, K. M.; O’Neill, B. T. J. Org. Chem. 2014,
79, 5771. (c) Allwood, D. M.; Blakemore, D. C.; Brown, A. D.; Ley, S. V.
J. Org. Chem. 2014, 79, 328. (d) Ni, C.; Park, M.; Shao, B.; Tafesse, L.;
Yao, J.; Youngman, M. Pyrimidines as Sodium Channel Blockers. PCT
International Application WO 2013030665, March 7, 2013.
was observed. This selectivity as well as the cyclization of the 4-
allyloxy-3-iodo-pyrrolidine 7 suggests the formation of a radical
intermediate. This coupling is efficient, easy-to-run, scalable,
cheap and, thus, may appear as a powerful tool for the
functionalization of saturated N-heterocycles.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and spectral data for all new
compounds. This material is available free of charge via the
AUTHOR INFORMATION
Corresponding Author
■
(9) (a) Guer
2007, 46, 6521. (b) Reymond, S.; Ferrie,
P.; Cossy, J. Pure Appl. Chem. 2008, 80, 1683. (c) Nicolas, L.; Angibaud,
P.; Stansfield, I.; Bonnet, P.; Meerpoel, L.; Reymond, S.; Cossy, J. Angew.
Chem., Int. Ed. 2012, 51, 11101.
́
inot, A.; Reymond, S.; Cossy, J. Angew. Chem., Int. Ed.
L.; Guerinot, A.; Capdevielle,
Notes
́
́
The authors declare no competing financial interest.
(10) For selected Co- and Fe-catalyzed cross-coupling, see (a) Jana, R.;
Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011, 111, 1417. (b) Nakamura,
REFERENCES
■
(1) (a) Roberts, M. F.; Wink, M. In Alkaloids: Biochemistry, Ecology and
Medicinal Applications; Plenum: New York, 1998. (b) Buckingham, J.;
Baggaley, K. H.; Roberts, A. D.; Szabo, L. F. In Dictionary of Alkaloids,
́
E.; Yoshikai, N. J. Org. Chem. 2010, 75, 6061. (c) Sherry, B. D.; Furstner,
̈
A. Acc. Chem. Res. 2008, 41, 1500. (d) Enthaler, S.; Junge, K.; Beller, M.
Angew. Chem., Int. Ed. 2008, 47, 3317. (e) Bolm, C.; Legros, J.; Le Paih, J.;
Zani, L. Chem. Rev. 2004, 104, 6217. (f) Cahiez, G.; Moyeux, A. Chem.
Rev. 2010, 110, 1435. (g) Gosmini, C.; Begouin, J.-M.; Moncomble, A.
Chem. Commun. 2008, 28, 3221. (h) Steib, A. K.; Thaler, T.; Komeyama,
K.; Mayer, P.; Knochel, P. Angew. Chem., Int. Ed. 2011, 50, 3303.
(11) This catalytic system has already been described: (a) Ohmiya, H.;
Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2006, 128, 1886. (b) Araki,
K.; Inoue, M. Tetrahedron 2013, 69, 3913.
2nd ed.; CRC Press: Boca Raton, FL, 2009. (c) De Risi, C.; Fanton, G.;
Pollini, G. P.; Trapella, C.; Valente, F.; Zanirato, V. Tetrahedron:
Asymmetry 2008, 19, 131. (d) Brandi, A.; Cicchi, S.; Cordero, F. M.
Chem. Rev. 2008, 108, 3988. (e) Singh, G. S.; D’hooghe, M.; De Kimpe,
N. Azetidines, Azetines and Azetes: Monocyclic. In Comprehensive
Heterocyclic Chemistry III; Stevens, C. V., Ed.; Elsevier: Oxford, U.K.,
2008; Vol. 2, Chapter 2.01, p 1. (f) Couty, F.; Evano, G. Synlett 2009, 19,
3053 and references therein. (g) Allerton, C. M. N. 3-Phenylazetidine
Derivatives As Dopamine Agonists. PCT International Application WO
2006134487, December 21, 2006. (h) Schultz, T.; Braje, W.; Turner, S.
C.; Haupt, A.; Lange, U.; Drescher, K.; Wicke, K.; Unger, L.; Mezler, M.;
Mayner, M. Azetidine compounds suitable for treating disorders that respond
to modulation of the serotonin 5-ht6 receptor. PCT International
Application WO 2008116833, October 2, 2008.
(12) With 5 mol % of FeCl2 and 5 mol % of L1, an incomplete
conversion of 83% was observed. The use of Fe(acac)3 (10 mol %) with
L1 (10 mol %) led to an incomplete conversion of 1a (92%) while the
combination of FeCl2 (10 mol %) and TMEDA (10 mol %) allowed the
formation of 2a in 75% yield (instead of 81% when 10 mol % of FeCl2
and diamine L1 were used).
(13) The coupling product could not be separated from the starting
material by flash chromatography on silica gel.
(14) Piller, F. M.; Appukkuttan, P.; Gavryushin, A.; Helm, M.; Knochel,
P. Angew. Chem., Int. Ed. 2008, 47, 6802.
(15) Ishida, N.; Shimamoto, Y.; Yano, T.; Murakami, M. J. Am. Chem.
Soc. 2013, 135, 19103.
(16) The N-tosyl substrate was found to be easier to prepare than the
N-Boc.
(17) The isolated yield was not determined.
(2) For a review on cross-coupling reactions involving secondary alkyl
halides, see Rudolph, A.; Lautens, M. Angew. Chem., Int. Ed. 2009, 48,
2656.
(3) For selected examples of Pd- and Ni-catalyzed arylation of
halogeno-piperidines, see (a) Wang, S.; Qian, Q.; Gong, H. Org. Lett.
2012, 14, 3352. (b) Vechorkin, O.; Proust, V.; Hu, X. J. Am. Chem. Soc.
2009, 131, 9756. (c) Strotman, N. A.; Sommer, S.; Fu, G. C. Angew.
Chem., Int. Ed. 2007, 46, 3556. (d) Powell, D. A.; Fu, G. C. J. Am. Chem.
Soc. 2004, 126, 7788. (e) Gonzal
2006, 128, 5360.
̀
ez-Bobes, F.; Fu, G. C. J. Am. Chem. Soc.
(18) For selected examples, see (a) Martin, R.; Furstner, A. Angew.
̈
Chem., Int. Ed. 2004, 43, 3955. (b) Holzer, B.; Hoffmann, R. W. Chem.
̈
(4) Some examples of Fe- and Co-catalyzed arylation of halogeno-
piperidines have been reported: (a) Nakamura, M.; Ito, S.; Matsuo, K.;
Nakamura, E. Synlett 2005, 11, 1794. (b) Bica, K.; Gaertner, P. Org. Lett.
2006, 8, 733. (c) Despiau, C. F.; Dominey, A. P.; Harrowven, D. C.;
Linclau, B. Eur. J. Org. Chem. 2014, 4335.
(5) For Cu-catalyzed arylation of tosylated pyrrolidines, see Yang, C.-
T.; Zhang, Z.-Q.; Liang, J.; Liu, J.-H.; Lu, X.-Y.; Chen, H.-H. J. Am. Chem.
Soc. 2012, 134, 11124.
Commun. 2003, 732. (c) Noda, D.; Sonada, Y.; Nakamura, M.;
Nagashima, H. J. Am. Chem. Soc. 2009, 131, 6078. (d) Jahn, U. Top.
Curr. Chem. 2012, 320, 191. (e) Ohmiya, H.; Wakabayashi, K.;
Yorimitsu, H.; Oshima, K. Tetrahedron 2006, 62, 2207. (f) Someya,
H.; Ohmiya, H.; Yorimitsu, H.; Oshima, K. Tetrahedron 2007, 63, 8609.
(19) Kuriyama, M.; Takeichi, T.; Ito, M.; Yamasaki, N.; Yamamura, R.;
Demizu, Y.; Onomura, O. Chem.Eur. J. 2012, 18, 2477.
(6) Some Negishi reactions between the organozinc reagent prepared
from iodo-azetidine and aryl halides have been described, see, for
example, (a) Allerton, C. M. N.; Hepworth, D.; Miller, D. C. New
indazole and indolone derivatives and their use pharmaceuticals. U.S. Patent
D
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