Tetrahedron: Asymmetry
Chiral bifunctional organocatalysts bearing a 1,3-propanediamine
unit for the aza-MBH reaction
Shuichi Hirata, Kouichi Tanaka, Katsuya Matsui, Fernando Arteaga Arteaga, Yasushi Yoshida,
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Shinobu Takizawa , Hiroaki Sasai
The Institute of Scientific and Industrial Research (ISIR), Osaka University, Mihogaoka, Ibaraki, Osaka 567-0047, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 July 2013
Accepted 6 August 2013
The introduction of a 1,3-propanediamine unit at the 3-position of (S)-BINOL using a methylene spacer
led to the formation of
a chiral bifunctional organocatalyst for the aza-Morita–Baylis–Hillman
(aza-MBH) reaction. The organocatalyst 1k mediated aza-MBH transformations with high chemical yields
and with up to 82% ee.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
Lewis base units
The design and development of chiral organocatalysts possess-
ing two or more reaction-promoting functionalities have attracted
much attention in the field of asymmetric catalysis.1 In bi- and
multifunctional organocatalysis, acid–base moieties can activate
substrates and control the stereochemistry of reactions to afford
significant chiral induction.2 The balance and appropriate location
of acid and base units in a catalyst are important for the efficient
activation of substrates. Herein we report that (S)-BINOL substi-
tuted at the 3-position with appropriate 1,3-propanediamine
derivatives using a methylene spacer works as an effective chiral
bifunctional organocatalyst. The organocatalyst 1k (Fig. 1) medi-
ates aza-Morita–Baylis–Hillman (aza-MBH) transformations in
high chemical yields and with up to 82% ee.
Bn
N
N
3
OH
OH
Brønsted acid units
1k
Figure 1. Chiral bifunctional organocatalyst 1k bearing a 1,3-propanediamine unit
for the aza-MBH reaction.
introduce a tertiary diamine7 (a strong Lewis base unit) at the
3-position of BINOL (a chiral Brønsted acid) using a spacer. A
tertiary diamine moiety could be used to easily adjust Lewis basi-
city via the introduction of substituents onto the nitrogen atom
and the distance between the acid–base units with an alkyl chain
of appropriate length. As a step toward the development of such
a bifunctional organocatalyst, 1,2-ethanediamine 1a,b, 1,3-pro-
panediamine 1c,d, 1,4-butanediamine 1e, 1,5-pentanediamine 1f,
and 1,6-hexanediamine 1g were introduced at the 3-position of
(S)-BINOL using a methylene or ethylene spacer. Next, the reaction
of methyl vinyl ketone 2a and 4-bromophenyl N-tosyl aldimine 3a
as prototypical substrates was attempted using the above
organocatalysts 1 (Table 1). The aza-MBH adduct 4a was isolated
in 48% yield with 61% ee when using 1,3-propanediamine deriva-
tive 1c with a methylene linker (entry 3). The analogous catalysts
1b and 1d bearing an ethylene spacer were then prepared and
applied to the reaction. These catalysts also promoted the reaction
but at lower rates with lower enantioselectivities (entries 2 and 4)
compared with those obtained using catalyst 1c with the
2. Results and discussion
The aza-MBH reaction is recognized as one of the most useful
and atom-economical carbon–carbon bond forming reactions
between the
a-position of enones and the carbonyl group of
imines, and is catalyzed by nucleophilic amines or phosphines.3
The products of the aza-MBH reaction are highly functionalized
allylic amines that have proven to be valuable building blocks for
biologically important compounds and natural products.4 Obtain-
ing efficient catalysts for the aza-MBH reaction however, has been
a challenge in organic synthesis.5
We envisioned locating both an acidic and a basic unit on one
chiral binaphthyl skeleton, thereby facilitating synergistic cooper-
ation in the aza-MBH reaction.5b,k,6 To that end, it was proposed to
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Corresponding authors. Tel.: +81 6 6879 8466; fax: +81 6 6879 8469.
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
Hirata, Shuichi
