Chiral 2-(1-dimethylaminoethyl)ferrocenecarbaldehyde as an effective catalyst for asymmetric alkylation of aldehydes with dialkylzinc

Article abstract of DOI:10.1055/s-1998-1776

The chiral ferrocenecarbaldehyde bearing an amino group was used as a ligand of diethylzinc in the asymmetric alkylation of aldehydes. It effectively catalyzed the reaction with either aromatic, straight chain or branched aliphatic aldehydes to afford chi

Full text of DOI:10.1055/s-1998-1776

July 1998
SYNLETT
727
Chiral 2-(1-Dimethylaminoethyl)ferrocenecarbaldehyde as an Effective Catalyst for
Asymmetric Alkylation of Aldehydes with Dialkylzinc
Shin-ichi Fukuzawa* and Hirohisa Kato
Department of Applied Chemistry, Chuo University, Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan
Received 26 March 1998
Abstract: The chiral ferrocenecarbaldehyde bearing an amino group
was used as a ligand of diethylzinc in the asymmetric alkylation of
aldehydes. It effectively catalyzed the reaction with either aromatic,
straight chain or branched aliphatic aldehydes to afford chiral alcohols
in good yields with high enantiomeric excess (up to 93 % ee).
Planar chiral ferrocenes are of current interest as ligands and chiral
1
building blocks in asymmetric synthesis. The unique structure of
ferrocenes allows one to design a variety of chiral substituted
ferrocenes. Well-designed chiral ferrocenes may produce high
stereoselectivities
during
organic
reactions.
Chiral
ferrocenecarbaldehydes have recently been reported by Kagan et al. as
precursors for ligands of transition metal catalysts in asymmetric
2
organic synthesis. We would like to now report the catalytic ability of
the chiral ferrocenecarbaldehyde bearing an amino group (2) as a
chelating ligand of dialkylzinc during the alkylation of aldehydes.
product (run 2). These results suggest that both the formyl and amino
groups are required for high catalytic and high asymmetric induction
abilities. The trick of the reaction may be shown by the following
experimental results. The ferrocene-carbaldehyde (2) was alkylated with
diethylzinc without catalyst to give the ferrocenyl alcohol (3) after
Scheme 1
5
hydrolysis with high diastereoselectivity (>99 de) (Scheme 3). The
The chiral 2-(1-dimethylaminoethyl)ferrocenecarbaldehyde (2) was
readily prepared by the ortho-lithiation of the (2-(S)-
dimethylaminoethyl)ferrocene (1) using s-BuLi and the subsequent
ferrocenyl alcohol (3) also worked as an effective catalyst for the highly
enantioselective ethylation with diethylzinc (run 3). The actual catalyst,
therefore, should be the zinc ferrocenyl alkoxide. High
diastereoselective alkylation of 2 with dialkylzinc was the key point of
3
reaction with dimethylformamide (Scheme 1). We used 2 as a catalyst
for the ethylation of aldehydes with diethylzinc. As shown in Table 1,
the reaction smoothly proceeded in toluene at 0 °C to give the
corresponding alcohol in good to excellent yields with high
enantiomeric excess (ee) values (up to 93 % ee) (Scheme 2). The
reaction of benzaldehyde with (S,R)- and (R,S)-(2) gave the (R)- and (S)-
isomers of 1-phenyl-1-propanol, respectively (runs 1-2). A slight
difference in the ee values between 4-methoxy- and 4-
nitrobenzaldehyde suggests that the reaction is not be affected by an
electronic factor (runs 3-4). With either the aromatic, the straight chain
or branched aliphatic aldehyde, the stereoselective alkylation
successfully produced the corresponding alcohol in high optical purity.
6
the reaction. The advantage of this method is that the reaction can
conveniently be carried out using 2 itself as a catalyst without isolation
7
of a diastereomerically pure ferrocenyl amino alcohol. The use of
8
2
chiral ferrocene-carbaldehyde bearing the oxazoline (4) or acetal (5)
group as a catalyst resulted in a low yield with a low ee value (runs 4-5).
Scheme 2
It is well established that asymmetric alkylation of aldehydes with
dialkylzinc needs a certain catalyst such as a Lewis acid, a sulfonamide,
4
and an amino alcohol including a ferrocenyl amino alcohol. It is
The general procedure for the ethylation of aldehyde with diethylzinc
catalyzed by 2 is as follows. In a two-neck 50 mL round-bottom flask
containing a magnetic stirrer bar was placed 2 (14.3 mg, 0.05 mmol, 5
mol %) under nitrogen. Dry toluene (5.0 mL) was then added to the
interesting that the aldehyde works as a catalyst in the reaction: the
catalyst employed here was an amino aldehyde not an amino alcohol.
We then examined the origin of the catalytic activity of 2. The results of
the reaction with benzaldehyde using ferrocene compounds as catalysts
are summarized in Table 2. Simple ferrocenecarbaldehyde did not
catalyze the reaction (run 1). The parent aminoferrocene (1) showed
poor catalytic activity giving a low yield (29%) and ee (7 %) value of the
flask followed by the addition of 1.0 mol/l hexane solution of Et Zn (1.5
2
mL, 1.5 mmol) at 0 °C. After 30 min, benzaldehyde (100 mg, 1.0 mmol)
was added to the resulting solution at 0 °C and stirred for 15 h. The
reaction was quenched by the addition of diluted HCl. The aqueous

728
LETTERS
SYNLETT
(400 MHz, CDCl ) δ 1.48 (d, 3H, J = 6.8 Hz), 2.08 (s, 6H), 4.23
3
13
(s, 5H), 4.5-4.8 (m, 3H), 10.50 (s, 1H); C NMR (CDCl ) δ 14.6,
3
40.3, 55.5, 68.5, 69.3, 70.3, 71.2, 72.3, 91.5, 193.2; IR (KBr)
-1
ν
= 1671cm . Anal. Calcd for C
H FeNO: C, 63.17; H,
15 19
C=O
6.72; N, 4.91. Found: C, 63.15; H, 6.74; N, 6.69.
(4) For reviews, a) Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833.
b) Butsugan, Y.; Araki, S.; Watanabe, M. In Ferrocenes; Hayashi,
T.; Togni, A. Eds.; VCH: Weinheim, 1995; pp143-168. c) Erdik,
E. Organozinc Reagents in Organic Synthesis; CRC: Boca Raton,
1996. d) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
Wiley; New York, 1994; Chap 5.
25
(5) Analytical data for 3: red oil; [α]
= -35.3 (c = 0.33, CHCl ). IR
3
D
-1
1
(KBr) ν = 3172 cm ; H NMR (400 MHz, CDCl ) δ 1.12 (t,
OH
3
3H, J = 7.4 Hz), 1.21 (d, 3H, J = 6.6 Hz), 1.6-1.7 (m, 1H), 1.8-2.0
(m, 1H), 2.07 (s, 6H), 3.94 (s, 5H), 3.9-4.2 (m, 3H), 4.60 (dd, 1H,
13
J = 3.2, 9.6 Hz); C NMR (CDCl ) δ 7.0, 11.3, 26.8, 38.5, 57.1,
3
Scheme 3
65.2, 66.3, 67.0, 69.0, 69.5, 89.0, 91.3. Anal. Calcd for
C
H FeNO: C, 64.77; H, 7.99; N, 4.44. Found: C, 64.81; H,
17 25
7.96; N, 4.41.
layer was extracted with two portions of diethyl ether (20 mL), washed
(6) Taudien, S.; Riant, O.; Kagan, H. B. Tetrahedron Lett. 1995, 36,
3513. Highly diastereoselective addition of organometallic
reagents to chiral ferrocenecarbaldehydes will be reported in due
course.
with brine and dried (MgSO ); the ferrocenyl amino alcohol (3) was
4
extracted into an acidic aqueous solution. The GC/MS analysis of the
ethereal solution revealed the presence of 1-phenyl-1-propanol. After
evaporation of the solvent, the product was isolated by preparative TLC
(hexane/ethyl acetate = 5/1) (127.9 mg, 0.94 mmol, 94% yield).
Enantiomeric excess was determined by HPLC analysis using a Daicel
Chiralcel OD column and/or by GC with a chiral capillary column
(Astec Chiraldex B-PH, 30 m). The absolute configuration was
(7) Trapping of α-lithio ferrocene of 1 with an aldehyde gives a
diastereomeric mixture of a ferrocenyl amino alcohol with a low
diastereomeric excess. Battelle, L. F.; Bau, R.; Oyakawa, R. T.;
Ugi, I. K. J. Am. Chem. Soc. 1973, 95, 482; Watanabe, M.; Araki,
S.; Butugan, Y.; Uemura, J. Org. Chem. 1991, 56, 2218.
4,7,9
determined by chiroptical comparison with literature values.
(8) Samakia, T.; Latham, H. A.; Schaad, D. R. J. Org. Chem. 1995,
60, 10; Richard, C. J.; Damalidis, T.; Hibbs, D. E.; Hursthouse, M.
B. Synlett 1995, 74; Nishibayashi, Y.; Uemura, S. Synlett 1995,
79. Analytical data for 4: orange solid; mp = 78-80 °C dec.;
References and notes
(1) For reviews, a) Ferrocenes; Togni, A.; Hayashi, T., Eds.; VCH:
Weinheim, 1995. b) Kagan, H. B.; Riant, O. In Advances in
Asymmetric Synthesis Vol 2; Hassner, A., Ed.; JAI: London, 1997;
pp189-235. c) Togni, A. Angew. Chem. Int. Ed. Engl. 1996, 35,
1475. d) Kagan, H. B.; Diter, P.; Gref. A.; Guillaneux, D.;
Masson-Szymczak, A.; Rebiere, F.; Riant, O.; Samuel, O.;
Tauden, S. Pure&Appl. Chem. 1996, 68, 29.
25
-1
[α]
= -1105 (c = 0.75, MeOH). IR (KBr) ν
= 1673 cm ;
C=O
D
1
H NMR (400 MHz, CDCl ) δ 0.92 (d, 3H, J = 6.8 Hz), 0.97 (d,
3
3H, J = 6.6 Hz), 1.77 (sextet, 1H, J = 6.6 Hz), 3.9-4.0 (m, 1H),
4.05 (t, 1H, J = 5.2 Hz), 4.22 (s, 5H), 4.66 (m, 1H), 4.90 (m, 2H),
13
10.6 (m, 1H); C NMR (CDCl ) δ18.3, 18.6, 32.6, 69.7, 70.2,
3
72.6, 73.1, 74.8, 78.8, 163.8, 195.3. Anal. Calcd for
(2) Riant, O.; Samuel, O.; Flessner, T.; Taudien, S.; Kagan, H. B. J.
Org. Chem. 1997, 62, 6733.
C
H FeNO : C, 62.79; H, 5.89; N, 4.31. Found: C, 62.75; H,
17 19 2
5.94; N, 4.35.
(3) Marquarding, D.; Klusacek, H.; Gokel, G.; Hoffmann, P.; Ugi, I. J.
Am. Chem. Soc. 1970, 92 5389. Analytical data for 2: red solid;
(9) Kitajima, H.; Ito, K.; Aoki, Y. and Katsuki, T. Bull. Chem. Soc.
Jpn. 1997, 70, 207.
28
1
mp = 64-66 °C dec. [α]
= 168.4 (c = 0.77, MeOH); H NMR
D