C O M M U N I C A T I O N S
Table 1
direct entry to chiral ynamides via N-alkynylation of amides and
should have a significant impact on the future synthetic utility of
ynamides.
Acknowledgment. The authors thank NSF [CHE-0094005] for
support. J.A.M. thanks UMN for a graduate fellowship. R.P.H.
thanks Professor John Hartwig for insightful discussions. R.P.H.
is a recipient of the 2001 Camille Dreyfus Award. M.O.F. is a
recipient of the 2002 Pfizer Undergraduate Summer Fellowship.
Supporting Information Available: Preliminary screenings of
1
conditions, experimental procedures, H spectra, and characterization
data of new compounds (PDF). This material is available free of charge
References
(1) For a review on chemistry of ynamides, see: Zificsak, C. A.; Mulder, J. A.;
Hsung, R. P.; Rameshkumar, C.; Wei, L.-L. Tetrahedron 2001, 57, 7575.
(2) For reviews on ynamines, see: (a) Himbert, G. In Methoden Der
Organischen Chemie (Houben-Weyl); Kropf, H., Schaumann, E., Eds.;
Georg Thieme Verlag: Stuttgart, 1993; pp 3267-3443. (b) Collard-Motte,
J.; Janousek, Z. Top. Curr. Chem. 1986, 130, 89. (c) Ficini, J. Tetrahedron
1976, 32, 1448.
(3) For the first examples of ynamides, see: Janousek, Z.; Collard, J.; Viehe,
H. G. Angew. Chem., Int. Ed. Engl. 1972, 11, 917.
(4) For other key examples, see: (a) Feldman, K. S.; Bruendl, M. M.;
Schildknegt, K.; Bohnstedt, A. C. J. Org. Chem. 1996, 61, 5440. (b)
Balsamo, A.; Macchia, B.; Macchia, F.; Rossello, A.; Domiano, P.
Tetrahedron Lett. 1985, 26, 4141, and ref 18 therein.
(5) (a) Rainier, J. D.; Imbriglio, J. E. J. Org. Chem. 2000, 65, 7272. (b)
Rainier, J. D.; Imbriglio, J. E. Org. Lett. 1999, 1, 2037.
(6) (a) Witulski, B.; Stengel, T. Angew. Chem., Int. Ed. 1998, 37, 489. (b)
Witulski, B.; Stengel, T. Angew. Chem., Int. Ed. 1998, 38, 2426. (c)
Witulski, B.; Go¨ssmann, M. Chem. Commun. 1999, 1879. (d) Witulski,
B.; Go¨ssmann, M. Synlett 2000, 1793. (e) Witulski, B.; Stengel, T.;
Ferna`ndez-Herna`ndez, J. M. Chem. Commun. 2000, 1965. (f) Witulski,
B.; Buschmann, N.; Bergstra¨sser, U. Tetrahedron 2000, 56, 8473.
(7) Schottelius, M. J.; Chen, P. HelV. Chim. Acta 1998, 81, 2341.
(8) Saito, N.; Sato, Y.; Mori, M. Org. Lett. 2002, 4, 803.
(9) (a) Huang, J.; Xiong, H.; Hsung, R. P.; Rameshkumar, C.; Mulder, J. A.;
Grebe, T. P. Org. Lett. 2002, 4, 2417. (b) Mulder, J. A.; Hsung, R. P.;
Frederick, M. O.; Tracey, M. R.; Zificsak, C. A. Org. Lett. 2002, 4, 1383.
(c) Hsung, R. P.; Zificsak, C.; Wei, L.-L.; Douglas, C. J.; Xiong, H.;
Mulder, J. Org. Lett. 1999, 1, 1237.
a All reactions are carried out using 5 mol % CuCN [OR: CuI; see note
c], 10 mol % N,N′-dimethylethylenediamine, and 2.0 equiv of K3PO4 in
toluene [concentrated 0.1 M based on the amide] at 110 °C for 18-30 h.
b Isolated yields. c 5 mol % CuI was used. d Xylene was the solvent. e An
R-haloenamide derived from addition of HBr to the ynamide was found in
50-60% yield. f Temperature was at 150 °C. g 1 mol % CuI and 3 mol %
ligand were used. h Isolated yields after reactions were terminated at 30-
50% conversion. i 1 mol % CuCN.
(10) For a review, see: Saalfrank, R. W.; Lurz, C. J. In Methoden Der
Organischen Chemie (Houben-Weyl); Kropf, H., Schaumann, E., Eds.;
Georg Thieme Verlag: Stuttgart, 1993; p 3093.
(11) Wei, L.-L.; Mulder, J. A.; Xiong, H.; Zificsak, C. A.; Douglas, C. J.;
Hsung, R. P. Tetrahedron 2001, 57, 459.
Scheme 2
(12) For reviews on palladium-catalyzed N-arylations of amines and amides,
see: (a) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046. (b) Wolfe,
J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998,
31, 805. For an earlier account, see: (c) Kosugi, M.; Kameyama, M.;
Migita, T. Chem. Lett. 1983, 927.
(13) For recent references from Buchwald’s lab, see: (a) Wolfe, J. P.; Tomori,
H.; Sadighi, J. P.; Yin, J.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1158
and references therein. (b) Yin, J.; Buchwald, S. L. Org. Lett. 2000, 2,
1101. (c) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 6043.
(14) For selected references from the Hartwig lab, see: (a) Hamann, B. C.;
Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 3694. (b) Mann, G.; Hartwig,
J. F.; Driver, M. S.; Ferna´ndez-Rivas, C. J. Am. Chem. Soc. 1998, 120,
827. (c) Hartwig, J. F.; Kawatsura, M.; Hauck, S. I.; Shaughnessy, K. H.;
Alcazar-Roman, L. M. J. Org. Chem. 1999, 64, 5575.
(15) Recent examples: (a) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Zappia,
G. Org. Lett. 2001, 3, 2539. (b) Artamkina, G. A.; Sergeev, A. G.;
Beletskaya, I. P. Tetrahedron Lett. 2001, 42, 4381. (c) Edmondson, S.
D.; Mastracchio, A.; Parmee, E. R. Org. Lett. 2000, 2, 1109. (d) Bolm,
C.; Hildebrand, J. J. Org. Chem. 2000, 65, 169.
Given the similar criteria in our reactions, we believe at this
juncture that the course of the catalytic cycle is related to the one
proposed by Buchwald for the N-arylation of amides.18 However,
we are examining other mechanistic details of this Csp-N formation
because urea or sulfonamide-based amides still do not work as well
as urethanes and lactams.
Finally, the chiral oxazolidinones 33 was coupled with 1-bromo-
2-tri-iso-propylsilyl ethyne to give ynamide 34 [70% yield with
1-2 mmol scale] [Scheme 2]. The removal of the silyl group using
TBAF at -10 °C led to the first preparation of parent ynamide 35
in 50% overall yield for the two steps. Subsequently, the concept
of Path B proposed in Figure 2, for the synthesis of new ynamides,
was illustrated using LHMDS to successfully deprotonate 35 and
MeI as the electrophile to give the ynamide 36 in 59% yield.
We have described here a copper-catalyzed new C-N bond
formation involving a sp-hybridized carbon. This route provides a
(16) Results using palladium were carried out three years ago.
(17) For a review on copper mediated C-N and C-O bond formation, see:
(a) Lindley, J. Tetrahedron 1984, 40, 1433. Also see: (b) Goldberg, I.
Ber. Dtsch. Chem. Ges. 1906, 39, 1691.
(18) Recent key papers from Buchwald’s group, see: (a) Klapper, A.; Huang, X.;
Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 7421. (b) Klapars, A.; Antilla,
J. C.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123, 7727.
(c) Kwong, F. Y.; Klapars, A.; Buchwald, S. L. Org. Lett. 2002, 4, 581.
(19) For recent references of copper-catalyzed N-arylations of amides and
enamides: (a) Shen, R.; Porco, J. A., Jr. Org. Lett. 2002, 2, 1333. (b)
Yamada, K.; Kubo, T.; Tokuyama, H.; Fukuyama, T. Synlett 2002, 231.
(c) Lam, P. Y. S.; Deudon, S.; Averill, K. M.; Li, R.; He, M. Y.; DeShong,
P.; Clark, C. G. J. Am. Chem. Soc. 2000, 122, 7600.
(20) All new compounds are characterized by 1H NMR, 13C NMR, FTIR, mass
spectroscopy, and [R]23
.
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