LETTER
Synthesis of Oxazolidinone and Tosyl Enamines
701
O
O
EWG
EWG
N
R
Et3N
C
N
R
Et3N
O
Et3N
C
Et3N
O
C
+
O
O
EWG
EWG
EWG
+ H+
EWG
N
N
R
N
R
N
R
R
Scheme 2 Proposed mechanism of enamine formation; EWG = electron-withdrawing group
(4) Vignola, N.; List, B. J. Am. Chem. Soc. 2004, 126, 450.
bel (70% for DABCO and 58% for Et3N), while the a-
position contained lower levels (26% for DABCO and
39% for Et3N). The data suggest that it is more likely that
deprotonation occurs through residual water than by di-
rect deprotonation of the acetylenic hydrogen. Quenching
the reaction mixture with TMSCl or 20% aqueous DCl in
D2O resulted in no incorporation of the trapping species in
the final enamine product. Thus, the vinyl anion may not
be neutralized during the aqueous workup, and the proton
must be incorporated during the reaction.
(5) (a) List, B.; Lerner, R. A.; Barbas, C. F. III. J. Am. Chem.
Soc. 2000, 122, 2395. (b) List, B.; Pojarliev, P.; Castello, C.
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Chem. Soc. 2005, 127, 15036. (b) Garcia-Garcia, P.;
Ladepeche, A.; Halder, R.; List, B. Angew. Chem. Int. Ed.
2008, 47, 4719.
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Chem. Int. Ed. 2004, 43, 6660. (b) Ouellet, S. G.; Tuttle,
J. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127, 32.
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13368. (d) Tuttle, J. B.; Ouellet, S. G.; MacMillan, D. W. C.
J. Am. Chem. Soc. 2006, 128, 12662.
We have found that N-propynoyl oxazolidinones and to-
syl imides will form enamine products when exposed to
catalytic amounts of Et3N and DABCO.15 The reaction in-
volves conjugate addition of the tertiary amine onto the
alkynoyl imide b carbon to furnish a putative allenoate in-
termediate. The allenoate then undergoes elimination of
an amide (or carbamate) anion, generating the final nu-
cleophile for product formation. This reaction could be
used to furnish alternative enamines to yield asymmetric
aldol products.
(8) Chouthaiwale, P. V.; Kotkar, S. P.; Sudalai, A. ARKIVOC
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(12) Compound 2 appeared as a single band from chromatog-
raphic techniques; additionally, compound 2 underwent
palladium hydrogenation, and its spectra were in accordance
with the reduced enamine (see Supporting Information).
(13) (a) Winterfeldt, E. Chem. Ber. 1964, 97, 1952. (b) Crisp,
G. T.; Millan, M. J. Tetrahedron 1998, 54, 637.
Supporting Information for this article is available online at
Acknowledgment
We thank Profs. Philip P. Garner, Duncan J. Wardrop, John T.
Wood and an anonymous reviewer for helpful comments. This
work was supported by the National Institutes of Health
(GM077622).
References and Notes
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Chem. Eur. J. 2005, 11, 5408. (e) Fan, M.-J.; Li, G.-Q.;
Liang, Y.-M. Tetrahedron 2006, 62, 6782.
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Chem. Soc. Jpn. 1991, 64, 2122. (b) List, B. Tetrahedron
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(d) Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B.
Chem. Rev. 2007, 107, 5471. (e) Hodgson, D. M.; Kaka,
N. S. Angew. Chem. 2008, 120, 10106.
(14) The freed allenone yielded a black tar, possibly the result of
decomposition or polymerization.
(15) For experimental procedures and compound characteri-
zation data, see Supporting Information.
(3) Brown, S. P.; Brochu, M. P.; Sinz, C. J.; MacMillan,
D. W. C. J. Am. Chem. Soc. 2003, 125, 10808.
Synlett 2011, No. 5, 699–701 © Thieme Stuttgart · New York