Highly Enantioselective Additions of Diethylzinc to Aldehydes Using 2-Triflamido-methyl-2′-hydroxy-1 ,1′-binaphthyl

Article abstract of DOI:10.1021/ol0358511

(Equation presented) A new N-triflated amino alcohol-titanium catalyst was designed for the asymmetric ethylation of aldehydes. This binaphthyl-based sulfonamido alcohol ligand shows uniformly high yield and enantioselectivity in the diethylzinc additions

Full text of DOI:10.1021/ol0358511

ORGANIC
LETTERS
2003
Vol. 5, No. 23
4517-4519
Highly Enantioselective Additions of
Diethylzinc to Aldehydes Using
2-Triflamido-methyl-2′-hydroxy-1,1′-
binaphthyl
Seung-Wan Kang, Dong-Hyun Ko, Kyoung Hoon Kim, and Deok-Chan Ha*
Department of Chemistry, Korea UniVersity, Seoul 136-701, Korea
dechha@korea.ac.kr
Received September 24, 2003
ABSTRACT
A new N-triflated amino alcohol−titanium catalyst was designed for the asymmetric ethylation of aldehydes. This binaphthyl-based sulfonamido
alcohol ligand shows uniformly high yield and enantioselectivity in the diethylzinc additions of aromatic, aliphatic, and unsaturated aldehydes.
Synthesis of a chiral secondary alcohol by asymmetric
addition of diorganozinc to an aldehyde is one of the
most successful areas in asymmetric C-C bond formation.1
Since the report by Ohno and co-workers on the highly
enantioselective addition of diethylzinc to aldehydes using
Ti(OiPr)4 complexed with chiral bistriflamide 1 (R ) CF3),2
extensive studies have been performed on the structural
derivatives of bissulfonamide and sulfonamido alcohol
1-3,3-5 TADDOLs 4,6 and BINOLs 5.7-9 However, few
studies have been performed with binaphthyl-based sulfona-
mides, and bissulfonamides 6 were recently reported to be
poor asymmetric ligands for the Ti-catalyzed Et2Zn addition
to aldehydes.10 In our previous report, highly enantioselective
(1) (a) Soai, K.; Shibata, T. In ComprensiVe Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999;
pp 911-922. (b) Pu, L.; Yu, H.-B. Chem. ReV. 2001, 101, 757-824.
(2) (a) Yoshioka, M.; Kawakita, T.; Ohno, M. Tetrahedron Lett. 1989,
30, 1657-1660. (b) Takahashi, H.; Kawakita, T.; Yoshioka, M.; Kobayashi,
S.; Ohno, M. Tetrahedron Lett. 1989, 30, 7095-7098. (c) Takahashi, H.;
Kawakita, T.; Ohno, M.; Yoshioka, M.; Kobayashi, S. Tetrahedron 1992,
48, 5691-5700.
(3) (a) Balsells, J.; Walsh, P. J. J. Am. Chem. Soc. 2000, 122, 3250-
3251. (b) Balsells, J.; Walsh, P. J. J. Am. Chem. Soc. 2000, 122, 1802-
1803. (c) Hwang, C.-D.; Uang, B.-J. Tetrahedron: Asymmetry 1998, 9,
3979-3984. (d) Qiu, J.; Guo, C.; Zhang, X. J. Org. Chem. 1997, 62, 2665-
2668. (e) Prieto, O.; Ramon, D. J.; Yus, M. Tetrahedron: Asymmetry 2000,
11, 1629-1644.
Figure 1. Chiral ligands for Ti-catalyzed dialkylzinc addition to
aldehyde.
additions of diethylzinc and diphenylzinc to aldehydes were
accomplished using 2-dialkylaminomethyl-2′-hydroxy-1,1′-
(6) (a) Schmidt, B.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1991, 30,
1321-1323. (b) Weber, B.; Seebach, D. Tetrahedron 1994, 50, 7473-
7484.
(7) (a) Zhang, F.-Y.; Yip, C.-W.; Cao, R.; Chan, A. S. C. Tetrahedron:
Asymmetry 1997, 8, 585-589. (b) Mori, M.; Nakai, T. Tetrahedron Lett.
1997, 38, 6233-6236.
(4) Ito, K.; Kimura, Y.; Okamura, H.; Katsuki, T. Synlett 1992, 573-
574.
(5) Ramon, D. J.; Yus, M. Tetrahedron: Asymmetry 1997, 8, 2479-
2496.
10.1021/ol0358511 CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/21/2003

binaphthyl N,O-ligands,11 which showed much improved
enantioselectivity compared with that of the corresponding
2-dimethylamino-2′-hydroxy-1,1′-binaphthyl.12
prepared from the known O-methyl NOBIN 1115 with
N-triflation followed by demethylation of 12 with BBr3.
The sulfonamido alcohol ligands 10a-c and 13 were
subjected to the ethylation of benzaldehyde with Et2Zn in
the presence of Ti(OiPr)4 in toluene (Table 1). Ligand 10a
In this report, we prepared binaphthyl-based sulfon-
amido alcohols from chiral binaphthol and used them as
ligands for enantioselective Ti(IV)-catalyzed ethylation of
aldehydes.
Table 1. Addition of Diethylzinc to Benzaldehyde Using
Ligands 10a-c and 13
Sulfonamides 10a-c were prepared by conversion of 7
to the amide 8, which was reduced to the amine 9 with LAH
followed by the corresponding sulfonations (Scheme 1).11,13
yielda
(%)
eeb,c
(%)
Scheme 1. Synthesis of
ligand
time
(h)
2-Sulfonamidomethyl-2′-hydroxy-1,1′-binaphthyl Derivativesa
entry
(mol %)
solvent
1
2
3
4
5
6
7
8
10a (5)
10b (5)
10c (5)
13 (5)
10a (3)
10a (1)
10a (1)
10a (1)
toluene
toluene
toluene
toluene
toluene
toluene
hexane
CH2Cl2
2
5
5
5
2
2
2
2
99
60
61
79
99
99
99
99
96
34
23
8
96
95
93
99
a Conversion yield (Chiraldex G-TA column). b Determined by chiral
HPLC (Chiralcel OD column). c Absolute configuration assigned by
comparison to the literature.
showed a very high enantioselection with the use of 5 mol
% in toluene (entry 1). With sulfonamides 10b and 10c, much
decreased conversion yields were observed despite the
extended reaction time under the same condition, and the
enantioselections were very poor (entries 2 and 3). As was
expected from the result of using 6, ligand 13 was a very
poor chiral ligand for the ethylation (entry 4). Decreasing
the amount of ligand 10a used resulted in almost the same
conversion yield and enantioselection (entries 5 and 6). By
changing the solvent from toluene or hexane to dichlo-
romethane, almost quantitative conversion and complete
enantioselection were accomplished with the use of only 1
mol % of 10a (entry 8).
With conditions optimized for benzaldehyde, the use of
ligand 10a was extended to the asymmetric ethylation of
other aromatic, aliphatic, and R,â-unsaturated aldehydes
(Table 2). The yields and enantioselectivities for the substi-
tuted benzaldehydes (entries 2-7) and naphthaldehydes
(entries 8 and 9) were all excellent regardless of the position
of substituents. The additions were completed within 2 h at
-25 °C with the use of 3 mol % of ligand 10a, and the
reduced alcohol products, observed in about 2-5% in our
previous study using 2-dialkylaminomethyl-2′-hydroxy-1,1′-
binaphthyl ligand,10 were not detected at all.
a Reagents and conditions: (a) NaCN (0.1 equiv), NH3, MeOH,
70-80 °C, 48 h, 94%; (b) LiAlH4 (4 equiv), THF, reflux, 24 h,
48%; (c) n-BuLi (2 equiv), THF, -78 °C; Tf2O (2 equiv), -78
°C, 1 h; LiOH-H2O (12 equiv), rt, 12 h, 89% (for 10a); (d) Tf2O
(2 equiv), CH2Cl2, -78 °C, 1 h, 92%; (e) BBr3 (3 equiv), CH2Cl2,
69%.
Ester 7 was highly resistant toward ammonia or amide for
the aminolysis to amide 8, but the conversion proceeded
slowly in methanolic ammonia on heating in the presence
of a catalytic amount of NaCN.14 Selective N-sulfonation of
amino alcohol 9 to 10a-c was not possible, probably because
of the intramolecular hydrogen bonding between the amino
and hydroxy groups. Bis-N,O-sulfonation of 9 followed by
the selective hydrolysis of the resulting sulfonate moiety
provided sulfonamides 10a-c. For comparative purpose,
sulfonamide 13, not having the methylene unit of 10a, was
(8) (a) Zhang, F.-Y.; Chan, A. S. C. Tetrahedron: Asymmetry 1997, 8,
3651-3655. (b) Shen, X.; Guo, H.; Ding, K. Tetrahedron: Asymmetry 2000,
11, 4321-4327.
(9) (a) Kitajima, H.; Ito, K.; Katsuki, T. Chem. Lett. 1996, 343-344.
(b) Kitajima, H.; Aoki, Y.; Katsuki, T. Bull. Chem. Soc. Jpn. 1997, 70,
207-217.
Excellent reactivity and enantioselection were obtained
with both primary and secondary aliphatic aldehydes (entries
10 and 11) and also with trans-cinnamaldehyde (entry 12).
A slight decrease of enantioselection was observed with
phenylpropargyl aldehyde (entry 13).
(10) Yus, M.; Ramon, D. J.; Prieto, O. Tetrahedron: Asymmetry 2003,
14, 1103-1114.
(11) Ko, D.-H.; Kim, K. H.; Ha, D.-C. Org. Lett. 2002, 4, 3759-3762.
(12) (a) Vyskocil, S.; Jaracz, S.; Smrcina, M.; Sticha, M.; Hanus, V.;
Polasek, M.; Kocovsky, P. J. Org. Chem. 1998, 63, 7727-7737. (b)
Bringmann, G.; Breuning, M. Tetrahedron: Asymmetry 1998, 9, 667-679.
(13) Ohta, T.; Ito, M.; Inagaki, K.; Takaya, H. Tetrahedron Lett. 1993,
34, 1615-1616.
(15) (a) Hattori, T.; Hotta, H.; Suzuki, T.; Miyano, S. Bull. Chem. Soc.
Jpn. 1993, 66, 613-622. (b) Hattoro, T.; Shijo, M.; Sakamoto, J.; Kumagai,
S.; Nakajima, A.; Miyano, S. J. Chem. Res., Miniprint 1995, 124-134.
(14) Hogberg, T.; Strom, P.; Ebner, M.; Ramsby, S. J. Org. Chem. 1987,
52, 2033-2036.
4518
Org. Lett., Vol. 5, No. 23, 2003

Table 2. Addition of Diethylzinc to Aldehydes Using Ligand
10a
entry
R
yield (%)a
ee (%)b
1
2
3
4
5
6
7
8
Ph
p-MeO-Ph
o-Cl-Ph
m-Cl-Ph
p-Cl-Ph
99
96
97
95
95
96
94
95
95
90
91
97
95
99c
91c
96d
99c
98c
96e
99e
98c
98c
98f
99f
96c
89c
o-Me-Ph
p-Me-Ph
1-naphthyl
2-naphthyl
hexyl
cyclohexyl
trans-Ph-CHdCH
Ph-CtC
Figure 2. Correlation between the ee of ligand 10a and the ee of
ethylation product of benzaldehyde (1 mol % 10a, 1.8 equiv of
Et2Zn, 1.2 equiv of Ti(OiPr)4, -25 °C, 2 h in CH2Cl2).
9
10
11
12
13g
selective addition of diethylzinc to aldehyde. This N,O-lig-
and-Ti(OiPr)4 catalyst provides excellent yields and enan-
tioselectivities in the reactions of diethylzinc with a broad
range of aromatic, aliphatic, and unsaturated aldehydes.
a Isolated yields. b Absolute configuration assigned by comparison to the
literature. c Determined by chiral HPLC (Chiralcel OD column). d Deter-
mined by chiral HPLC (Chiralcel OB-H column). e Determined by chiral
HPLC (Chiralpak AD-H column). f Determined by chiral GC (Chiraldex
G-TA column) of the corresponding acetate derivatives. g Using 5 mol %
of 10a.
Acknowledgment. This work was financially supported
by the Center for Molecular Design and Synthesis (CMDS)
at KAIST.
Unlike with the BINOL-Ti(OiPr)4 system, which shows
no nonlinear effect under catalytic conditions,7b small but
distinctive negative nonlinear effect can be seen in the
catalytic system using ligand 10a, as shown in Figure 2. It
was clearly demonstrated by Walsh16 that a complex between
(BINOLate)Ti(OiPr)2 and Ti(OiPr)4 is preferentially involved
in the catalytic condition. Although the transition structure
for the ethylation using 10a-titanium cannot be drawn at
this stage, interactions between the 10a-ligated titanium
intermediates may be present in this catalytic system to
induce such a nonlinear effect.17
Supporting Information Available: Experimental details
and characterization data for all new compounds and
conditions for determining the enantiopurity of the alcohol
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL0358511
(16) (a) Balsells, J.; Davis, T. J.; Caroll, P.; Walsh, P. J. J. Am. Chem.
Soc. 2002, 124, 10336-10348. (b) Gao, G.; Moore, D.; Xie, R.-G.; Pu, L.
Org. Lett. 2002, 4, 4143-4146.
(17) Girard, C.; Kagan, H. B. Angew. Chem., Int. Ed. 1998, 37, 2922-
2959.
In summary, we prepared a new binaphthyl-based N-
triflated amino alcohol ligand and applied it to the enantio-
Org. Lett., Vol. 5, No. 23, 2003
4519