toluene. We report here the enantioselective Mannich-type
reaction of N-alkylaldimines with ketene silyl acetals cata-
lyzed by chiral Brønsted acid through hydrogen bonding with
the nitrogen of imine. Our catalytic cycle was attained by
capturing a trialkylsilyl cation from a siloxocarbenium ion
intermediate6 with stoichiometric amounts of achiral proton
sources under anhydrous conditions.7
catalyst (Type III). The OH‚‚‚N hydrogen bond may be
rotationally fixed with regard to the R*-O axis and its proton
may be suitably activated by intramolecular OH‚‚‚OH
hydrogen bonding.
On the basis of the concept of BBA (Type III), we
designed chiral 2-bis(triflyl)methyl-2′-hydroxy-1,1′-binaph-
thyl (1)9 as a new asymmetric Mannich catalyst (Figure 1).
Scheme 1 shows the activation of N-alkylaldimine with
Scheme 1. Activation of Aldimine with Chiral Brønsted Acid
Figure 1. Possible intramolecular hydrogen bondings in (R)-1.
1 is a chiral dibasic Brønsted acid10-13 bearing a hydroxy
proton and a bis(triflyl)methyl proton. Recently, we devel-
oped a practical method for not only aromatic but also
aliphatic alkylbis(triflyl)methanes.14 In general, the acidity
of arylbis(triflyl)methane is the same as that or stronger than
that of the corresponding sulfonic acid. For example, the pK
value of PhCHTf2 in MeCN is 7.83,15 while that of TsOH is
8.6. We expected that 1 might be effective as a chiral BBA
catalyst for the enantioselective Mannich-type reaction.
(R)-1 was prepared from (S)-2′-(methoxymethoxy)-2-
methyl-1,1′-binaphthyl (3), which was easily derived from
chiral Brønsted acid. If N-alkylaldimine is activated by OH‚
‚‚N hydrogen bonding with chiral Brønsted acid (R*OH),
moderate enantioselectivity may be induced because this
hydrogen bond can rotate around the R*-O axis (Type I).
In contrast, if N-alkylaldimine is activated as an iminium
cation intermediate with a relatively strong chiral Brønsted
acid, the enantioselectivity may be induced through a tight
ion pair between the protonated iminium cation and the chiral
Brønsted base, but it is relatively difficult to induce higher
enantioselectivity than that of Type I (Type II).5 Therefore,
the suitable Brønsted acidity and conformational control of
the OH‚‚‚N hydrogen bond are important for the design of
Brønsted acid catalysts. To overcome these problems, we
introduced the concept of Brønsted acid-assisted chiral
Brønsted (BBA)8 for the design of a new Brønsted acid
Ishihara, K.; Yamamoto, H. J. Am. Chem. Soc. 2000, 122, 8120. (h)
Nakamura, S.; Ishihara, K.; Yamamoto, H. J. Am. Chem. Soc. 2000, 122,
8131. (i) Ishihara, K.; Ishibashi, H.; Yamamoto, H. J. Am. Chem. Soc. 2001,
123, 1505. (j) Ishihara, K.; Ishibashi, H.; Yamamoto, H. J. Am. Chem. Soc.
2002, 124, 3647. (k) Ishihara, K.; Nakashima, D.; Hiraiwa, Y.; Yamamoto,
H. J. Am. Chem. Soc. 2003, 125, 24. (l) Kumazawa, K.; Ishihara, K.;
Yamamoto, H. Org. Lett. 2004, 6, 2551. (m) Ishibashi, H.; Ishihara, K.;
Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 11122. (n) Muhammet, U.;
Ishibashi, H.; Ishihara, K.; Yamamoto, H. Org. Lett. 2005, 7, 1601. (o)
Muhammet, U.; Ishihara, K.; Yamamoto, H. Bioorg. Med. Chem. 2005,
13, 5055.
(9) triflyl ) trifluoromethanesulfonyl; triflate ) trifluoromethane-
sulfonate.
Chem. Soc. 2004, 126, 11804. (c) Akiyama, T.; Morita, H.; Itoh, J.; Fuchibe,
K. Org. Lett. 2005, 7, 2583. (d) Hofmann, S.; Seayad, A. M.; List, B. Angew.
Chem., Int. Ed. 2005, 44, 7424. (e) Terada, M.; Sorimachi, K.; Uraguchi,
D. Synlett 2006, 133. (f) Storer, R. I.; Carrera, D. E.; Ni, Y.; MacMilaalan,
D. W. C. J. Am. Chem. Soc. 2006, 128, 84. (g) Terada, M.; Machioka, K.;
Sorimachi, K. Angew. Chem., Int. Ed. 2006, 45, 2254. (h) Rueping, M.;
Sugiono, E.; Azap, C. Angew. Chem., Int. Ed. 2006, 45, 2617.
(6) (a) Ishihara, K.; Hiraiwa, Y.; Yamamoto, H. Chem. Commun. 2002,
1564. (b) Hiraiwa, Y.; Ishihara, K.; Yamamoto, H. Eur. J. Org. Chem. 2006,
1837.
(7) If we consider our experimental results, the HBF4-promoted Mannich
reaction in aqueous media reported by Akiyama et al.3 might also
catalytically proceed by capturing a trialkylsilyl cation with excess amounts
of aqueous solvents. Furthermore, in the case of Akiyama’s enantioselective
version catalyzed by chiral monophosphoric acid in toluene,4 N-2-
hydroxyphenylaldimine might play a role as a stoichiometric achiral proton
source as well as our present catalytic system.
(8) The concept of a chiral BBA originates in that of a Lewis acid-assisted
chiral Brønsted acid (chiral LBA). For LBA, see: (a) Ishihara, K.; Kaneeda,
M.; Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 11179. (b) Ishihara, K.;
Nakamura, S.; Yamamoto, H. Croat. Chem. Acta 1996, 69, 513. (c) Ishihara,
K.; Nakamura, S.; Kaneeda, M.; Yamamoto, H. J. Am. Chem. Soc. 1996,
118, 12854. (d) Ishihara, K.; Ishida, Y.; Nakamura, S.; Yamamoto, H. Synlett
1997, 758. (e) Ishihara, K.; Nakamura, H.; Nakamura, S.; Yamamoto, H.
J. Org. Chem. 1998, 63, 6444. (f) Ishihara, K.; Nakamura, S.; Yamamoto,
H. J. Am. Chem. Soc. 1999, 121, 4906. (g) Nakamura, S.; Kaneeda, M.;
(10) For a review of asymmetric catalysis by chiral hydrogen bond
donors, see: Taylor, M. S.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2006,
45, 1520.
(11) For chiral R-hydroxycarboxylic acid catalysts, see: Momiyama, N.;
Yamamoto, H. J. Am. Chem. Soc. 2005, 127, 1080.
(12) For chiral diol catalysts, see: (a) Huang, Y.; Unni, A. K.; Thadani,
A. N.; Rawal, V. H. Nature 2003, 424, 146. (b) McDougal, N. T.; Schaus,
S. E. J. Am. Chem. Soc. 2003, 125, 12094. (c) McDougal, N. T.; Trevellini,
W. L.; Rodgen, S. A.; Kliman, L. T.; Schaus, S. E. AdV. Synth. Catal. 2004,
346, 1231. (d) Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2005,
127, 1080. (e) Unni, A. K.; Takenaka, N.; Yamamoto, H.; Rawal, V. J.
Am. Chem. Soc. 2005, 127, 1336. (f) Gondi, V. B.; Gravel, M.; Rawal, V.
H. Org. Lett. 2005, 7, 5657.
(13) For chiral disulfonamide catalysts, see: (a) Tonoi, T.; Mikami, K.
Tetrahedron Lett. 2005, 46, 6355. (b) Zhuang, W.; Poulsen, T. B.; Jørgensen,
K. A. Org. Biomol. Chem. 2005, 3, 3284.
(14) (a) Ishihara, K.; Hasegawa, A.; Yamamoto, H. Angew. Chem., Int.
Ed. 2001, 40, 4077. (b) Ishihara, K.; Hasegawa, A.; Yamamoto, H. Synlett
2002, 1296. (c) Ishihara, K.; Hasegawa, A.; Yamamoto, H. Synlett 2002,
1299. (d) Hasegawa, A.; Ishihara, K.; Yamamoto, H. Angew. Chem., Int.
Ed. 2003, 42, 5731. (e) Kokubo, Y.; Hasegawa, A.; Kuwata, S.; Ishihara,
K.; Yamamoto, H.; Ikariya, T. AdV. Synth. Catal. 2005, 347, 220. (f)
Hasegawa, A.; Ishikawa, T.; Ishihara, K.; Yamamoto, H. Bull. Chem. Soc.
Jpn. 2005, 78, 1401.
(15) Leito, I.; Kaljurand, I.; Koppel, I. A.; Yagupolskii, L. M.; Vlasov,
V. M. J. Org. Chem. 1998, 63, 7868.
3176
Org. Lett., Vol. 8, No. 15, 2006