ORGANIC
LETTERS
2009
Vol. 11, No. 9
2023-2025
Rate Enhancement of Phase Transfer
Catalyzed Conjugate Additions by CsCl
Taichi Kano, Takeshi Kumano, and Keiji Maruoka*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity,
Sakyo, Kyoto 606-8502, Japan
Received March 7, 2009
ABSTRACT
A rate enhancement of phase transfer catalyzed conjugate additions was accomplished using a catalytic amount of CsCl. The utility of this
method was demonstrated in the asymmetric synthesis of glutamic acid derivatives by using a chiral phase transfer catalyst.
Asymmetric phase transfer catalysis using optically pure
quaternary ammonium salts has become a field of growing
importance.1 In this area, asymmetric reactions promoted by
inorganic bases were most well-known, and the inorganic
base having appropriate basicity was chosen depending on
the reaction system. In some cases, however, the use of a
strong base to promote the reaction would lead to the loss
of enantioselectivity due to a partial contribution of a racemic
pathway without involving the chiral phase transfer catalyst.2
Most phase transfer catalyzed asymmetric conjugate addi-
tions, for instance, addition of N-(diphenylmethylene)glycine
ester to acrylates using strong bases such as CsOH·H2O and
Cs2CO3, were performed at low temperature to achieve high
levels of enantioselectivity.3-8 In this context, we have been
interested in the development of a novel method for
acceleration of the phase transfer catalyzed reaction under
mild conditions without using a strong base. Herein we wish
to report a rate enhancement of phase transfer catalyzed
conjugate additions by adding catalytic CsCl. Using catalytic
CsCl, the first highly enantioselective conjugate addition of
an alanine derivative to methyl acrylate was also achieved
at the synthetically useful level.4b
With the expectation of accelerating the reaction, metal
salts were chosen as additives.9 Thus, we first investigated
the conjugate addition of N-(diphenylmethylene)glycine ester
(1) For reviews, see: (a) Shioiri, T. In Handbook of Phase Transfer
Catalysis; Sasson, Y., Neumann, R., Eds.; Blackie Academic&Professional:
London, 1997; Chapter 14. (b) Ebrahim, S.; Wills, M. Tetrahedron:
Asymmetry 1997, 8, 3163. (c) Esikova, I. A.; Nahreini, T. S.; O’Donnell,
M. J. In Phase-Transfer Catalysis; Halpern, M. E., Ed.; ACS Symposium
Series 659; American Chemical Society: Washington, DC, 1997; Chapter
7. (d) Shioiri, T.; Ando, A.; Masui, M.; Miura, T.; Tatematsu, T.; Bohsako,
A.; Higashiyama, M.; Asakura, C. In Phase-Transfer Catalysis; Halpern,
M. E., Ed.; ACS Symposium Series 659; American Chemical Society:
Washington, DC, 1997; Chapter 11. (e) O’Donnell, M. J. In Catalytic
Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH: New York, 2000;
Chapter 10. (f) O’Donnell, M. J. Aldrichimica Acta 2001, 34, 3. (g) Maruoka,
K.; Ooi, T. Chem. ReV. 2003, 103, 3013. (h) Ooi, T.; Maruoka, K. Angew.
Chem., Int. Ed. 2007, 46, 4222.
(3) Corey, E. J.; Noe, M. C.; Xu, F. Tetrahedron Lett. 1998, 39, 5347
.
(4) (a) Arai, S.; Tsuji, R.; Nishida, A. Tetrahedron Lett. 2002, 43, 9535.
(b) Arai, S.; Takahashi, F.; Tsuji, R.; Nishida, A. Heterocycles 2006, 67,
495
.
(5) (a) Shibuguchi, T.; Fukuta, Y.; Akachi, Y.; Sekine, A.; Ohshima,
T.; Shibasaki, M. Tetrahedron Lett. 2002, 43, 9539. (b) Ohshima, T.;
Gnanadesikan, V.; Shibuguchi, T.; Fukuta, Y.; Nemoto, T.; Shibasaki, M.
J. Am. Chem. Soc. 2003, 125, 11206. (c) Ohshima, T.; Shibuguchi, T.;
Fukuta, Y.; Shibasaki, M. Tetrahedron 2004, 60, 7743
.
(6) Arai, S.; Tokumaru, K.; Aoyama, T. Chem. Pharm. Bull. 2004, 52,
(2) For instance, the conjugate addition of N-(diphenylmethylene)glycine
ester 1a to methyl acrylate with Cs2CO3 in CPME proceeded at 0 °C to
give the corresponding 1,4-addition product 2 in quantitative yield, while
the reaction using a weaker base K2CO3 resulted in no product formation.
See Supporting Informationfor details.
646
.
(7) Lygo, B.; Allbutt, B.; Kirton, E. H. M. Tetrahedron Lett. 2005, 46,
4461
.
(8) Akiyama, T.; Hara, M.; Fuchibe, K.; Sakamoto, S.; Yamaguchi, K.
Chem. Commun. 2003, 1734
.
10.1021/ol900476e CCC: $40.75
Published on Web 04/06/2009
2009 American Chemical Society