a) or inside double bond (Scheme 1, path b) were obtained
by intramolecular nucleophilic attack of the nitrogen atom
to a π-allylic palladium complex generated by carbopalla-
dation of the allene starting from organic halides4or hyper-
valent iodinonium salts.5
propargylamine 2, followed by t-BuOK promoted isomer-
ization of the resulting propargylamides 3 (Scheme 2). The
Following our continuing interest in the development of
new protocols toward nitrogen-containing heterocycles via
intramolecular Pd-catalyzed reactions,6 we turned our atten-
tion to the heterocyclization of substrates bearing an allene
moiety and a nitrogen nucleophile. In particular, our studies
were aimed at obtaining 2-vinylimidazolidin-4-ones from
R-amino acid derived R-amino allenamides via a palladium-
catalyzed domino carbopalladation/5-exo-allylic amination
process. It should be noted that this type of procedure has
never been reported on substrates wherein an amide group
tethers the reacting function.
Scheme 2. Preparation of Allenamides 4
Because imidazolidine derivatives show interesting bio-
logical activities7 and are used successfully as organocata-
lysts,8 the discovery of new pathways for their enantiopure
synthesis represents a valuable goal. Moreover, the presence
of the vinylic substituent makes them important building
blocks suitable for further functionalization, increasing their
interest as organocatalysts.
exposure time of 3 to the base is crucial and must not exceed
1 min, so as to prevent the base-promoted cyclization path.9
The reaction conditions tested in the preliminary cycliza-
tion experiments gave straightforwardly satisfactory yields
of the desired imidazole products. In fact, use of Pd(PPh3)4
(0.02 equiv), PhI (1.2 equiv), and K2CO3 (4 equiv) in DMF
as solvent gave the products 5a-e and 6a-e in 2.5:1-5.5:1
diastereoisomeric ratio through an exo-cyclization of the
π-allyl intermediate A (Scheme 3).
Amino allenamides 4 were obtained in near quantitative
yields by reaction of L-R-amino acids 1 and the N-methyl-
(2) Pd(0)-promoted heterocyclization reactions: (a) Hamaguchi, A.;
Kosaka, S.; Ohno, H.; Fujii, N.; Tanaka, T. Chem. Eur. J. 2007, 13, 1692.
(b) Ma, S.; Zhao, S. J. Am. Chem. Soc. 1999, 121, 7943. (c) Karstens,
W. F. J.; Klomp, D.; Rutjes, F. P. J. T.; Hiemstra, H. Tetrahedron 2001,
57, 5123.
(3) Pd(II)-promoted heterocyclization reactions: (a) Beccalli, E. M.;
Broggini, G.; Martinelli, M.; Sottocornola, S. Chem. ReV. 2007, 107, 5318.
(b) Yu, F.; Lian, X.; Ma, S. Org. Lett. 2007, 9, 1703.
Scheme 3. Heterocyclization Reaction of Allenamides 4 by
Intermolecular Carbopalladation-Intramolecular Amination
(4) (a) Cheng, X.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 4581. (b)
Ma, S.; Yu, F.; Li, J.; Gao, W. Chem. Eur. J. 2007, 13, 247. (c) Yang, Q.;
Jiang, X.; Ma, S. Chem. Eur. J. 2007, 13, 9310. (d) Rutjes, F. P. J. T.;
Tjen, K. C. M. F.; Wolf, L. B.; Karstens, W. F. J.; Schoemaker, H. E.;
Hiemstra, H. Org. Lett. 1999, 1, 717. (e) Karstens, W. F. J.; Rutjes,
F. P. J. T.; Hiemstra, H. Tetrahedron Lett. 1997, 38, 6275. (f) Davies, I. W.;
Scopes, D. I. C.; Gallagher, T. Synlett 1993, 85. (g) Anzai, M.; Toda, A.;
Ohno, H.; Takemoto, Y.; Fujii, N.; Ibuka, T. Tetrahedron Lett. 1999, 40,
7393. (h) Ohno, H.; Anzai, M.; Toda, A.; Ohishi, S.; Fujii, N.; Tanaka, T.;
Takemoto, Y.; Ibuka, T. J. Org. Chem. 2001, 66, 4904. (i) Grigg, R.;
Sansano, J. M.; Santhakumar, V.; Sridharan, V.; Thangavelanthum, R.;
Thornton-Pett, M.; Wilson, D. Tetrahedron 1997, 53, 11803.
(5) (a) Kang, S.-K.; Baik, T.-G.; Kulak, A. N. Synlett 1999, 324. (b)
Kang, S.-K.; Baik, T.-G.; Hur, Y. Tetrahedron 1999, 55, 6863.
(6) (a) Abbiati, G.; Beccalli, E. M.; Broggini, G.; Zoni, C. J. Org. Chem.
2003, 68, 7625. (b) Beccalli, E. M.; Broggini, G.; Paladino, G.; Penoni,
A.; Zoni, C. J. Org. Chem. 2004, 69, 5627. (c) Beccalli, E. M.; Broggini,
G.; Paladino, G.; Zoni, C. Tetrahedron 2005, 61, 61. (d) Beccalli, E. M.;
Broggini, G.; Martinelli, M.; Paladino, G. Tetrahedron 2005, 61, 1077. (e)
Beccalli, E. M.; Broggini, G.; Martinelli, M.; Paladino, G.; Rossi, E.
Synthesis 2006, 2404. (f) Beccalli, E. M.; Broggini, G.; Martinelli, M.;
Masciocchi, N.; Sottocornola, S. Org. Lett. 2006, 8, 4521. (g) Abbiati, G.;
Beccalli, E. M.; Broggini, G.; Martinelli, M.; Paladino, G. Synlett 2006,
73. (h) Beccalli, E. M.; Borsini, E.; Broggini, G.; Rigamonti, M.;
Sottocornola, S. Synlett 2008, 1053. (i) Beccalli, E. M.; Borsini, E.; Broggini,
G.; Palmisano, G.; Sottocornola, S. J. Org. Chem. 2008, 73, 4746. (j) Basolo,
L.; Beccalli, E. M.; Borsini, E.; Broggini, G.; Pellegrino, S. Tetrahedron
2008, 64, 8182.
(7) (a) Vale, N.; Collins, M. S.; Gut, J.; Ferraz, R.; Rosenthal, P. J.;
Cushion, M. T.; Moreira, R.; Gomes, P. Bioorg. Med. Chem. Lett. 2008,
18, 485. (b) Araujo, M. J.; Bom, J.; Capela, R.; Casimiro, C.; Chambel, P.;
Gomes, P.; Iley, J.; Lopes, F.; Morais, J.; Moreira, R.; De Oliveira, E.; Do
Rosario, V.; Vale, N. J. Med. Chem. 2005, 48, 888. (c) Elrod, D. B.; Worley,
S. D. Ind. Eng. Chem. Res. 1999, 38, 4144.
Change of the catalyst (palladium acetate), the base (Et3N,
Cs2CO3, t-BuOK), or the solvent (acetonitrile, DMSO)
(8) (a) Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2000, 122, 4243. (b) Jen, W. S.; Wiener, J. J. M.; MacMillan, D. W. C.
J. Am. Chem. Soc. 2000, 122, 9874. (c) Quellet, S. J.; Tuttle, J. B.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127, 32.
(9) Broggini, G.; Galli, S.; Rigamonti, M.; Sottocornola, S.; Zecchi, G.
Tetrahedron Lett. 2009, 50, 1447.
1564
Org. Lett., Vol. 11, No. 7, 2009