Organic Letters
Letter
(2) For a review on enantioselective organocatalytic reactions with N-
carbamoyl imines, see: Vesely, J.; Rios, R. Chem. Soc. Rev. 2014, 43,
611.
(15) With a cyclic β-keto ester, the Mannich reaction gave the
product 4u in excellent dr but only moderate enantioselectivity. As
such, the present catalyst system appears to be optimal for β-keto
esters without an α substituent. See the Supporting Information for
details.
(16) Presumably, 2b is less likely to generate an enecarbamate 5b due
to the presence of an exocyclic double bond to a 6-membered ring in
5b. For a discussion, see: Brown, H. C.; Brewster, J. H.; Shechter, H. J.
Am. Chem. Soc. 1954, 76, 467.
(3) For a review, see: (a) Benohoud, M.; Hayashi, Y. In Science of
Synthesis: Asymmetric Organocatalysis 1; List, B., Ed.; Georg Thieme
Verlag: Stuttgart, 2012; pp 73−134. Selected examples of enamine
́
catalysis in Mannich reactions leading to ketones: (b) Cordova, A.;
Notz, W.; Zhong, G.; Betancort, J. M.; Barbas, C. F. J. Am. Chem. Soc.
2002, 124, 1842. (c) Yang, J. W.; Stadler, M.; List, B. Angew. Chem.,
Int. Ed. 2007, 46, 609.
(17) The catalyst−β-keto ester ion pair is expected to be more acidic
than the corresponding ion pair with malonate esters, thus rendering
this problem more acute with β-keto ester substrates.
(4) Selected enantioselective Mannich reactions with enol silanes/
ketene silyl acetals: (a) Hagiwara, E.; Fujii, A.; Sodeoka, M. J. Am.
Chem. Soc. 1998, 120, 2474. (b) Ferraris, D.; Young, B.; Dudding, T.;
Lectka, T. J. Am. Chem. Soc. 1998, 120, 4548. (c) Wenzel, A. G.;
Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 12964. (d) Nakamura, Y.;
Matsubara, R.; Kiyohara, H.; Kobayashi, S. Org. Lett. 2003, 5, 2481.
(e) Kobayashi, S.; Arai, K.; Shimizu, H.; Ihori, Y.; Ishitani, H.;
Yamashita, Y. Angew. Chem., Int. Ed. 2005, 44, 761. (f) Wang, Q.;
Leutzsch, M.; van Gemmeren, M.; List, B. J. Am. Chem. Soc. 2013, 135,
15334.
(18) Terada, M.; Sorimachi, K. J. Am. Chem. Soc. 2007, 129, 292.
(19) Lewis acid promoted tautomerization and dimerization of
aliphatic imines and enecarbamates: Kobayashi, S.; Gustafsson, T.;
Shimizu, Y.; Kiyohara, H.; Matsubara, R. Org. Lett. 2006, 8, 4923.
(20) The methyl ketone moiety was cleaved via the Lieben iodoform
reaction. See the Supporting Information for experimental details.
Moutevelis-Minakakis, P.; Sinanoglou, C.; Loukas, V.; Kokotos, G.
Synthesis 2005, 933.
(5) Selected enantioselective Mannich reactions with malonate
esters: (a) Song, J.; Wang, Y.; Deng, L. J. Am. Chem. Soc. 2006, 128,
6048. (b) Song, J.; Shih, H.-W.; Deng, L. Org. Lett. 2007, 9, 603.
(c) Hatano, M.; Horibe, T.; Ishihara, K. Org. Lett. 2010, 12, 3502. See
also ref 6b. For a review, see: (d) Verkade, J. M. M.; van Hemert, L. J.
C.; Quaedflieg, P. J. L. M.; Rutjes, F. P. J. T. Chem. Soc. Rev. 2008, 37,
29.
(6) Enantioselective Mannich reactions of β-keto esters with aromatic
imines: (a) Lou, S.; Taoka, B. M.; Ting, A.; Schaus, S. E. J. Am. Chem.
Soc. 2005, 127, 11256. (b) Tillman, A. L.; Ye, J.; Dixon, D. J. Chem.
Commun. 2006, 1191. (c) Ting, A.; Lou, S.; Schaus, S. E. Org. Lett.
2006, 8, 2003. (d) Kang, Y. K.; Kim, D. Y. J. Org. Chem. 2009, 74,
5734. (e) Hatano, M.; Horibe, T.; Ishihara, K. J. Am. Chem. Soc. 2010,
132, 56.
(7) Enantioselective Mannich reaction of β-keto esters with
glyoxalate derived imine: Hamashima, Y.; Sasamoto, N.; Hotta, D.;
Somei, H.; Umebayashi, N.; Sodeoka, M. Angew. Chem., Int. Ed. 2005,
44, 1525.
(8) For reviews, see: (a) Zhang, S.; Wang, W. In Catalytic Asymmetric
Conjugate Reactions; Cordova, A., Ed.; Wiley: Weinheim, 2010; pp
́
295−299. (b) Xu, L.-W.; Xia, C.-G. Eur. J. Org. Chem. 2005, 633. For
selected examples of this approach, see: (c) Taylor, M. S.; Zalatan, D.
N.; Lerchner, A. M.; Jacobsen, E. N. J. Am. Chem. Soc. 2005, 127, 1313.
(d) Lu, X.; Deng, L. Angew. Chem., Int. Ed. 2008, 47, 7710. (e) Ma, S.;
Wu, L.; Liu, M.; Xu, X.; Huang, Y.; Wang, Y. RSC Adv. 2013, 3, 11498.
́
́ ́
(9) Probst, N.; Madarasz, A.; Valkonen, A.; Papai, I.; Rissanen, K.;
Neuvonen, A.; Pihko, P. M. Angew. Chem., Int. Ed. 2012, 51, 8495. In
this study, we also established that the urea moiety provides
cooperative assistance to the thiourea through intramolecular
hydrogen bonds.
(10) For the seminal paper on cooperatively assisted urea−thiourea
catalysts, see: Jones, C. R.; Pantos,̧ G. D.; Morrison, A. J.; Smith, M. D.
Angew. Chem., Int. Ed. 2009, 48, 7391. In contrast to the original
design, our catalyst uses a more rigid trans-1,2-aminoindanol linker,
resulting in a more active catalyst (see ref 9 for details).
(11) Okino, T.; Hoashi, Y.; Takemoto, Y. J. Am. Chem. Soc. 2003,
125, 12672.
(12) (a) Ye, J.; Dixon, D. J.; Hynes, P. S. Chem. Commun. 2005, 4481.
́ ́
(b) Vakulya, B.; Varga, S.; Csampai, A.; Soos, T. Org. Lett. 2005, 7,
1967. (c) Li, B.-J.; Jiang, L.; Liu, M.; Chen, Y.-C.; Ding, L.- S.; Wu, Y.
Synlett 2005, 603.
(13) For example, cinchona alkaloid derived bifunctional catalysts
typically afford lower yields and enantioselectivities with β-keto esters
compared to malonate esters. See ref 6b. The differential reactivity and
selectivity of malonate esters and β-keto esters has also been noted
with metal enolates; see ref 5c.
(14) Aliphatic imines such as 2a are prone to decomposition, and
they cannot typically be purified by chromatography. See the
Supporting Information for a discussion on the effect of additives.
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dx.doi.org/10.1021/ol5025025 | Org. Lett. 2014, 16, 5152−5155