Diastereoselective aldol reaction of tin enolate of cyclohexanone catalyzed by metal triflates

Article abstract of DOI:10.1055/s-1998-5737

The diastereoselective aldol reaction of tributyltin enolale of cyclohexanone with benzaldehyde was studied in the presence of a catalytic amount of various metal triflates. The highest anti selectivity was observed with Pd(OTf)₂, while Zn(OTf)

Full text of DOI:10.1055/s-1998-5737

958
LETTERS
Diastereoselective Aldol Reaction of Tin Enolate of Cyclohexanone Catalyzed by Metal
Triflates
Akira Yanagisawa, Kazutaka Kimura, Yoshinari Nakatsuka, Hisashi Yamamoto*
Graduate School of Engineering, Nagoya University, CREST, Japan Science and Technology Corporation (JST), Chikusa, Nagoya 464-8603, Japan
Received 8 June 1998
Abstract: The diastereoselective aldol reaction of tributyltin enolate of
cyclohexanone with benzaldehyde was studied in the presence of a
catalytic amount of various metal triflates. The highest anti selectivity
was observed with Pd(OTf) , while Zn(OTf) in THF showed moderate
2
2
i
syn selectivity. The use of (S,S)- Pr-pybox 3·Cu(OTf) complex as a
2
catalyst preferentially produced the optically active syn aldol adduct
with 84% ee.
The Mukaiyama aldol reaction is a popular method for preparing β-
hydroxy carbonyl compounds, and has been widely applied to the
1
synthesis of natural products. A variety of achiral and chiral Lewis acid
catalysts have been developed for the stereoselective reaction of silyl
1,2
enol ethers or ketene silyl acetals with carbonyl compounds.
In
contrast, the use of organotin(IV) enolates for aldol reactions has so far
3
received little attention. We report here the diastereoselective aldol
reaction of tributyltin enolate of cyclohexanone with benzaldehyde in
the presence of a catalytic amount of various metal triflates and the
asymmetric version of this process using chiral ligands (eq 1).
The tributyltin enolate of cyclohexanone is easily prepared from the
4
corresponding enol acetate and tributyltin methoxide. The tin enolate
5
itself can react with benzaldehyde in THF even at -78° C, although the
chemical yield of the products is low (entry 1 in Table 1). In the
presence of 5 mol% of metal triflates, however, the yield was
significantly increased, as shown in Table 1. In addition, high
for the reaction and THF was found to give the highest
enantioselectivity (entries 8-10). A complex of CuOTf with 3 also
provided moderate ee with syn selectivity (entry 7), in contrast to the
anti selectivity shown with CuOTf without a ligand (entries 5-7 in Table
1).
diastereoselectivity was observed using these metal triflates. Among
6
them, TMSOTf and Pd(OTf) provided the anti aldol adduct with high
2
selectivity in THF (entries 13 and 17). In contrast, moderate syn
selectivity was seen for Cu(OTf) and Zn(OTf) (entries 8 and 10). The
2
2
1,2-Addition of the cyclohexanone-derived enol tributylstannane to α,β-
unsaturated aldehydes can also be achieved enantio- and
diastereoselectively by this method. For example, the reaction of
anti/syn ratio of the aldol reaction is dependent on the solvent, and
higher anti selectivity was generally obtained in less-polar solvent. The
highest anti/syn selectivity (96/4) was attained using Pd(OTf) in
2
cinnamaldehyde with 5 mol% of ·Cu(OTf) in THF at -78 °C for 3 h
3
2
toluene (entry 18). At present, the origin of the solvent effect is not
clear.
preferentially gave the optically active syn aldol adduct with an anti/syn
13
ratio of 33/67. The syn isomer indicated 88% ee (eq 2).
Next, we investigated the possibility of an enantioselective version of
the present diastereoselective aldol reaction, which is a significant
challenge from the viewpoint of asymmetric synthesis (Table 2). Using
A new catalytic enantio- and diastereoselective aldol reaction using a
tributyltin enolate is described which is significant for the addition of an
enolate of cyclohexanone with aldehydes, since the corresponding
t
7
i
8
(R)-BINAP 1, (S,S)- Bu-box 2, or (S,S)- Pr-pybox 3 as a chiral ligand,
we studied the enantioselectivity of the anti-selective reaction, however,
trimethylsilyl enol ether did not react with benzaldehyde under the
14
influence of 5 mol% of 3·Cu(OTf) even at room temperature (eq 3).
2
only very poor results were obtained with chiral ligand·Pd(OTf)
2
Further work on the catalytic asymmetric aldol addition is now in
progress.
complexes, while the minor syn product showed 53% ee in the case of
6,9
1·Pd(OTf)
(entries 1, 3, and 6). In contrast, for the syn selective
2
10
A representative experimental procedure is given by the reaction of
tributyltin enolate of cyclohexanone with benzaldehyde catalyzed by
reaction, highly asymmetric induction took place when 3·Cu(OTf)
2
was used as a catalyst, and 84% ee of the syn product was formed
11,12
3·Cu(OTf) (entry 8 in Table 2). A mixture of Cu(OTf) (18 mg, 0.050
diastereoselectively (entry 8).
Several different solvents were tested
2
2

September 1998
SYNLETT
959
using a chiral column (Chiralcel OD-H, Daicel Chemical Industries,
Ltd., hexane/i-PrOH = 9/1, flow rate = 0.5 mL/min): t = 14.1
syn-minor
min, t
= 15.4 min, t
= 17.2 min (2S,1’R), t
=
anti-major
syn-major
anti-minor
23.8 min (2R,1’S). The absolute configurations of the syn isomers are
not known.
References and Notes
(1) Review: Gennari, C. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Heathcock, C. H., Eds.; Pergamon Press:
Oxford, U.K., 1991; Vol. 2, p 629.
(2) Examples of catalytic asymmetric aldol reactions using silyl enol
ethers or ketene silyl acetals, reviews: (a) Bach, T. Angew. Chem.
Int. Ed. Engl. 1994, 33, 417. (b) Hollis, T. K.; Bosnich, B. J. Am.
Chem. Soc. 1995, 117, 4570. (c) Braun, M. In Houben-Weyl:
Methods of Organic Chemistry; Helmchen, G., Hoffmann, R. W.,
Mulzer, J., Schaumann, E., Eds.; Georg Thieme Verlag: Stuttgart,
1995; Vol. E 21, p 1730. (d) Nelson, S. G. Tetrahedron:
Asymmetry 1998, 9, 357. Recent communications: (e) Chen, C.-T.;
Chao, S.-D.; Yen, K.-C.; Chen, C.-H.; Chou, I.-C.; Hon, S.-W. J.
Am. Chem. Soc. 1997, 119, 11341. (f) Krüger, J.; Carreira, E. M. J.
Am. Chem. Soc. 1998, 120, 837. (g) Denmark, S. E.; Stavenger, R.
A. J. Org. Chem. 1998, 63, 918.
(3) Reviews: (a) Pereyre, M.; Quintard, J.-P.; Rahm, A. Tin in Organic
Synthesis; Butterworths: London, 1987; p 286. (b) Davies, A. G.
Organotin Chemistry; VCH: Weinheim, 1997; p 185. The first
example of catalytic enantioselective aldol addition of tributyltin
enolates to aldehydes: (c) Yanagisawa, A.; Matsumoto Y.;
Nakashima, H.; Asakawa, K.; Yamamoto, H. J. Am. Chem. Soc.
1997, 119, 9319.
(4) (a) Pereyre, M.; Bellegarde, B.; Mendelsohn, J.; Valade, J. J.
Organomet. Chem. 1968, 11, 97. (b) Lutsenko, I. F.; Baukov, Y. I.;
Belavin, I. Y. J. Organomet. Chem. 1970, 24, 359. (c) Kobayashi,
K.; Kawanisi, M.; Hitomi, T.; Kozima, S. Chem. Lett. 1984, 497.
The tin enolate should be purified by distillation immediately
before use.
(5) (a) Shenvi, S.; Stille, J. K. Tetrahedron Lett. 1982, 23, 627.
(b) Labadie, S. S.; Stille, J. K. Tetrahedron 1984, 40, 2329.
(c) Kobayashi, K. ; Kawanisi, M.; Hitomi, T.; Kozima, S. Chem.
Lett. 1983, 851. See also: (d) Yamamoto, Y.; Yatagai, H.;
Maruyama, K. J. Chem. Soc., Chem. Commun. 1981, 162.
i
mmol) and (S,S)- Pr-pybox 3 (15 mg, 0.050 mmol) was dissolved in dry
THF (6 mL) under an argon atmosphere, and stirred at 20° C for 10 min.
To the resulting solution was added dropwise benzaldehyde (100 µL,
0.98 mmol), and (1-cyclohexenyloxy)tributyltin (342 mg, 1.0 mmol)
was then added over a period of 10 min at -78° C. After being stirred for
3 h at this temperature, the mixture was treated with MeOH (2 mL).
After warming to room temperature, the mixture was treated with solid
KF (ca. 1 g) at ambient temperature for 30 min. The resulting precipitate
(6) For preparation of Pd(OTf) and its complexes with phosphines:
2
Murata, S.; Ido, Y. Bull. Chem. Soc. Jpn. 1994, 67, 1746.
(7) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J. Am.
Chem. Soc. 1991, 113, 726.
(8) Nishiyama, H.; Kondo, M.; Nakamura, T.; Itoh, K.
®
Organometallics 1991, 10, 500.
was filtered off by a glass filter funnel filled with Celite and silica gel.
The filtrate was dried over Na SO and concentrated in vacuo after
(9) Good enantioselectivity has been observed for the BINAP·Pd(II)
complex-catalyzed aldol reaction of silyl enol ethers with
aldehydes: (a) Sodeoka, M.; Ohrai, K.; Shibasaki, M. J. Org.
Chem. 1995, 60, 2648. (b) Sodeoka, M.; Tokunoh, R.; Miyazaki,
F.; Hagiwara, E.; Shibasaki, M. Synlett 1997, 463.
2
4
filtration. The residual crude product was purified by column
chromatography on silica gel to afford a mixture of aldol adducts (148
mg, 74% yield) as a white solid which showed the appropriate spectral
11
1
data. The anti/syn ratio was determined to be 36/64 by H NMR
analysis. The enantioselectivities of the anti and syn isomers were
determined to be 16% ee and 84% ee, respectively, by HPLC analysis
(10) (a) Evans, D. A.; Murry, J. A.; Kozlowski, M. C. J. Am. Chem.
Soc. 1996, 118, 5814. (b) Evans, D. A.; Kozlowski, M. C.;

960
LETTERS
SYNLETT
Tedrow, J. S. Tetrahedron Lett. 1996, 37, 7481. (c) Evans, D. A.;
Kozlowski, M. C.; Burgey, C. S.; MacMillan, D. W. C. J. Am.
Chem. Soc. 1997, 119, 7893.
(13) Spectral data of the syn isomer: TLC R 0.11 (1:5 ethyl acetate/
f
hexane); IR (KBr) 3580-3250, 2934, 2857, 1698, 1599, 1495,
-1
1
1451, 1424, 1314, 1130, 1123, 970, 760, 739, 696 cm
; H NMR
(300 MHz, CDCl ) δ 1.52-1.78 (m, 3 H, CH and one proton of
3
2
(11) Spectral data of the syn isomer: TLC R 0.13 (1:5 ethyl acetate/
f
CH ), 1.86-1.96 (m, 1 H, one proton of CH ), 2.05-2.17 (m, 2 H,
2
2
hexane); IR (KBr) 3600-3125, 2940, 2855, 1701, 1603, 1495,
-1
1
CH ), 2.30-2.49 (m, 2 H, CH ), 2.53-2.62 (m, 1 H, CH), 2.96 (d, 1
2
2
1449, 1406, 1320, 1132, 1063, 986, 696 cm ; H NMR (300
MHz, CDCl ) δ 1.47-1.80 (m, 4 H, 2 CH ), 1.81-1.91 (m, 1 H, one
H, J = 5.0 Hz, OH), 4.77 (ddt, J = 1.8, 5.0, 6.0 Hz, 1 H, CH(OH)),
6.22 (dd, 1 H, J = 6.0, 16.0 Hz, CH), 6.64 (dd, 1 H, J = 1.3, 16.0
3
2
proton of CH ), 2.04-2.15 (m, 1 H, one proton of CH ), 2.32-2.51
2
2
13
Hz, CH), 7.21-7.40 (m, 5 H, aromatic); C NMR (75 MHz,
(m, 2 H, CH ), 2.56-2.65 (m, 1 H, CH), 3.01 (d, 1 H, J = 3.2 Hz,
2
CDCl ) δ 24.8, 27.3, 27.5, 42.5, 55.5, 70.5, 126.3 (2 C), 127.5,
OH), 5.40 (d, 1 H, J = 2.4, 3.2 Hz, CH(OH)), 7.25-7.37 (m, 5 H,
3
31
13
128.5 (2 C), 129.0, 130.8, 136.7, 214.2; [α]
+35.5 (c 1.0,
D
1
aromatic); C NMR (75 MHz, CDCl ) δ 24.7, 25.9, 27.8, 42.5,
3
28.5
CHCl ). Selected spectral data of the anti isomer: H NMR (300
57.1, 70.5, 125.7 (2 C), 126.8, 128.0 (2 C), 141.5, 214.5; [α]
3
D
MHz, CDCl ) δ 3.65 (d, 1 H, J = 3.4 Hz, OH), 4.44 (ddd, 1 H, J =
+132.0 (c 1.1, CHCl ). Selected spectral data of the anti isomer:
3
3
1
3.4, 7.4, 7.9 Hz, CH(OH)) , 6.19 (dd, 1 H, J = 7.4, 15.9 Hz, CH),
H NMR (300 MHz, CDCl ) δ 3.96 (d, 1 H, J = 2.8 Hz, OH), 4.79
3
13
13
6.62 (d, 1 H, J = 15.9 Hz, CH); C NMR (75 MHz, CDCl ) δ
(dd, 1 H, J = 2.8, 8.8 Hz, CH(OH)); C NMR (75 MHz, CDCl ) δ
3
3
24.5, 27.5, 30.4, 42.4, 56.0, 72.8, 126.3 (2 C), 127.5, 128.3 (2 C),
128.8, 131.8, 136.4, 214.7.
24.5, 27.6, 30.6, 42.4, 57.3, 74.5, 126.9 (2 C), 127.7, 128.3 (2 C),
140.9, 215.3.
(12) The corresponding anti isomer can be selectively obtained with
(14) 3·Cu(OTf)2 and related complexes are effective chiral catalysts for
enantioselective aldol additions of silylketene acetals to α-
(benzyloxy)acetaldehyde or pyruvate esters, see ref. 10.
high enantioselectivity by
a BINAP·silver(I)-catalyzed aldol
3c
reaction.