BINAP/AgOTf/KF/18-crown-6 as new bifunctional catalysts for asymmetric Sakurai-Hosomi allylation and Mukaiyama aldol reaction

Article abstract of DOI:10.1021/jo020691c

A catalytic amount of KF·18-crown-6 complex is effective as a soluble fluoride source to activate an asymmetric Sakurai-Hosomi allylation with BINAP and silver(I) triflate catalyst. The allylation of a variety of aromatic, α,β-unsaturated and aliphatic al

Full text of DOI:10.1021/jo020691c

BINAP /AgOTf/KF /18-Cr ow n -6 a s New Bifu n ction a l Ca ta lysts for
Asym m etr ic Sa k u r a i-Hosom i Allyla tion a n d Mu k a iya m a Ald ol
Rea ction
Manabu Wadamoto,†,§ Nobuko Ozasa,† Akira Yanagisawa,‡ and Hisashi Yamamoto*,†,§
Graduate School of Engineering, Nagoya University, SORST, J apan Science and Technology Corporation
(J ST), Chikusa, Nagoya 464-8603, J apan, and Department of Chemistry, Faculty of Science,
Chiba University, Inage, Chiba 263-8522, J apan
yamamoto@uchicago.edu
Received November 11, 2002
A catalytic amount of KF‚18-crown-6 complex is effective as a soluble fluoride source to activate
an asymmetric Sakurai-Hosomi allylation with BINAP and silver(I) triflate catalyst. The allylation
of a variety of aromatic, R,â-unsaturated and aliphatic aldehydes with allylic trimethoxysilane
resulted in high yields and remarkable enantioselectivities. In addition, the asymmetric Mukaiyama-
type aldol reaction is achieved by using trimethoxysilyl enol ethers in the presence of the same
catalysts. High anti selectivity is obtained from E-silyl enol ether, while Z-silyl enol ether gives
syn selectivity.
In tr od u ction
1). These reactions, however, have the disadvantage of
requiring the use of toxic trialkyltin compounds, and we
therefore reported an alternative BINAP‚Ag(I)-catalyzed
Enantioselective allylation of carbonyl compounds1,2
and aldol synthesis1c,j,3,4 are powerful and important
processes based on nucleophilic addition to carbonyl
derivatives giving optically active homoallylic alcohols
and â-hydroxy carbonyl compounds, respectively. These
functional groups are often seen in natural products or
biologically active molecules and therefore efficient and
enantioselective methods to construct such functional
groups are strongly desired. In recent years, numerous
chiral Lewis acid catalysts have been developed and
applied for these processes.
We have previously shown that the BINAP‚AgOTf
complex is an excellent chiral catalyst for asymmetric
allylation of aldehydes with allyltributyltin5a,b,e,f as well
as the asymmetric aldol reaction of tributyltin enolates,5c
and can provide the corresponding optically active prod-
ucts with high diastereo- and enantioselectivities (Figure
(2) Notable examples of chiral Lewis acid-catalyzed asymmetric
allylations with allylic trimethylsilanes: (a) Furuta, K.; Mouri, M.;
Yamamoto, H. Synlett 1991, 561. (b) Ishihara, K.; Mouri, M.; Gao, Q.;
Maruyama, T.; Furuta, K.; Yamamoto, H. J . Am. Chem. Soc. 1993,
115, 11490. (c) Aoki, S.; Mikami, K.; Terada, M.; Nakai, T. Tetrahedron
1993, 49, 1783. (d) Gauthier, D. R., J r.; Carreira E. M. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 2363. See also: (e) Duthaler, R. O.; Hafner,
A. Angew. Chem., Int. Ed. Engl. 1997, 36, 43. Notable examples of
chiral Lewis base-catalyzed asymmetric allylations with allylic trichlo-
rosilanes: (f) Denmark, S. E.; Coe, D. M.; Pratt, N. E.; Griedel, B. D.
J . Org. Chem. 1994, 59, 6161. (g) Iseki, K.; Kuroki, Y.; Takahashi, M.;
Kobayashi, Y. Tetrahedron Lett. 1996, 37, 5149. (h) Iseki, K.; Kuroki,
Y.; Takahashi, M.; Kishimoto, S.; Kobayashi, Y. Tetrahedron 1997, 53,
3513. (i) Iseki, K.; Mizuno, S.; Kuroki, Y.; Kobayashi, Y. Tetrahedron
Lett. 1998, 39, 2767. (j) Nakajima, M.; Saito, M.; Shiro, M.; Hashimoto,
S. J . Am. Chem. Soc. 1998, 120, 6419. (k) Iseki, K.; Mizuno, S.; Kuroki,
Y.; Kobayashi, Y. Tetrahedron 1999, 55, 977. (l) Denmark, S. E.; Fu,
J . J . Am. Chem. Soc. 2000, 122, 12021. (m) Denmark, S. E.; Fu, J . J .
Am. Chem. Soc. 2001, 123, 9488. (n) Denmark, S. E.; Fu, J . J . Am.
Chem. Soc. 2001, 123, 6199. Catalytic asymmetric Nozaki-Hiyama
reactions with chromium catalysts: (o) Bandini, M.; Cozzi, P. G.;
Melchiorre, P.; Umani-Ronchi, A. Angew. Chem., Int. Ed. 1999, 38,
3357. (p) Bandini, M.; Cozzi, P. G.; Umani-Ronchi, A. Angew. Chem.,
Int. Ed. 2000, 38, 2327. Asymmetric allyl-transfer reactions; (q)
Nokami, J .; Ohga, M.; Nakamoto, H.; Matsubara, T.; Hussain, I.;
Kataoka, K. J . Am. Chem. Soc. 2001, 123, 9168. (r) Loh, T.-P.; Hu,
Q.-Y.; Chok, Y.-K.; Tan, K.-T. Tetrahedron Lett. 2001, 42, 9277.
(3) Review for catalytic asymmetric aldol reactions: (a) Gennari,
C. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Heathcock, C. H., Eds.; Pergamon Press: Oxford, UK, 1991; Vol. 2, p
629. Reviews for catalytic asymmetric aldol reactions with silyl enol
ethers or ketene silyl acetals: (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, Germany, 1995;
Vol. E21, p 1730. (d) Nelson, S. G. Tetrahedron: Asymmetry 1998, 9,
357. (e) Gro¨ger, H.; Vogl, E. M.; Shibasaki, M. Chem. Eur. J . 1998, 4,
1137. (f) Mahrwald, R. Chem. Rev. 1999, 99, 1095. (g) Carreira, E. M.
In Comprehensive Asymmetric Catalysis; J acobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer; Heidelberg, Germany, 1999; Vol. 3, p
997. (h) Arya, P.; Qin, H. Tetrahedron 2000, 56, 917. (i) Machajewski,
T. D.; Wong, C.-H. Angew. Chem., Int. Ed. 2000, 39, 1353. (j) Carreira,
E. M. In Modern Carbonyl Chemistry; Otera, J ., Ed.; Wiley-VCH:
Weinheim, Germany, 2000; Chapter 8, p 227.
† Graduate School of Engineering, Nagoya University, SORST.
‡ Department of Chemistry, Faculty of Science, Chiba University.
§ Current address: Department of Chemistry, University of Chicago,
5735 South Ellis Avenue, Chicago, IL 60637.
(1) Reviews for catalytic asymmetric allylations: (a) Roush, W. R.
In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Heathcock, C. H., Eds.; Pergamon Press: Oxford, UK, 1991; Vol. 2, p
1. (b) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207. (c) Bach, T.
Angew. Chem., Int. Ed. Engl. 1994, 33, 417. (d) Hoppe, D. In Houben-
Weyl: Methods of Organic Chemistry; Helmchen, G., Hoffmann, R. W.,
Mulzer, J ., Schaumann, E., Eds.; Georg Thieme Verlag: Stuttgart,
Germany, 1995; Vol. E21, p 1357. (e) Hoveyda, A. H.; Morken, J . P.
Angew. Chem., Int. Ed. Engl. 1996, 35, 1262. (f) Cozzi, P. G.; Tagliavini,
E.; Umani-Ronchi, A. Gazz. Chim. Ital. 1997, 127, 247. (g) Yanagisawa,
A. In Comprehensive Asymmetric Catalysis; J acobsen, E. N., Pfaltz,
A., Yamamoto, H., Eds.; Springer: Heidelberg, Germany, 1999; Vol.
2, p 965. (h) Denmark, S. E.; Almostead, N. G. In Modern Carbonyl
Chemistry; Otera, J ., Ed.; Wiley-VCH: Weinhein, Germany, 2000;
Chapter 10, p 299. (i) Chemler, S. R.; Roush, W. R. In Modern Carbonyl
Chemistry; Otera, J ., Ed.; Wiley-VCH: Weinhein, Germany, 2000;
Chapter 11, p 403. (j) Lewis Acids in Organic Synthesis; Yamamoto,
H., Ed.; Wiley-VCH: Weinheim, Germany, 2000; Vols. 1 and 2.
10.1021/jo020691c CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/19/2003
J . Org. Chem. 2003, 68, 5593-5601
5593

Wadamoto et al.
F IGURE 1. Enantioselective allylation and aldol reaction
with tin compounds catalyzed by BINAP‚AgOTf.
asymmetric aldol reaction of cyclohexanone-derived enol
trichloroacetate using a catalytic amount of tributyltin
methoxide.5d
Unfortunately, we attempted to use less toxic allylic
trialkylsilanes or trialkylsilyl enol ethers in the BINAP‚
Ag(I)-catalyzed reactions but no products were obtained,
probably due to less reactivity of the silane compounds
than that shown by the corresponding stannanes. Yam-
agishi and co-workers independently examined the
BINAP‚Ag(I)-catalyzed asymmetric Mukaiyama aldol
reaction using trimethylsilyl enol ether and found that
the reaction was accelerated by BINAP‚AgPF6 in DMF
containing a small amount of water to obtain the aldol
product with high enantioselectivity.6 In contrast, Car-
reira has shown the utility of metal fluoride-chiral
ligand complexes as chiral catalysts in the reactions of
silyl compounds including asymmetric Sakurai-Hosomi
F IGURE 2. Enantioselective allylation and aldol reaction
with chiral ligand-metal fluoride complexes as catalysts.
allylation, and the Mukaiyama-type aldol reaction (eqs
1 and 2 in Figure 2).2d,7 We also reported that the BINAP‚
AgF complex is a reactive chiral catalyst of choice for
asymmetric allylation and aldol reaction using trimeth-
oxysilanes in methanol (eqs 3 and 4 in Figure 2).8
Most metal fluorides are difficult to use as catalysts
because of their insolubility in common organic solvents.9
To solve this problem, Carreira documented the use of
(Bu4N)Ph3SiF2 (TBAT) as a source of fluoride ion for the
in situ generation of copper fluoride, whereas we used
methanol as a solvent to dissolve AgF. Although metha-
nol is an excellent solvent for various reactions, it
sometimes causes undesired protonation of the active
species if the reactivity of substrates is high enough.
Therefore, a more general method is required that is
usable in an aprotic solvent system. In this paper we
introduce a new system for the combined use of KF‚18-
crown-6 ether with the BINAP‚AgOTf complex in polar
aprotic solvent.
(4) Reviews for chiral Lewis base-catalyzed asymmetric aldol reac-
tions with trichlorosilyl enol ethers: (a) Denmark, S. E.; Stavenger,
R. A.; Su, X.; Wong, K.-T.; Nishigaichi, Y. Pure Appl. Chem. 1998, 70,
1469. (b) Denmark, S. E.; Stavenger, R. A. Acc. Chem. Res. 2000, 33,
432. Chiral rhodium catalysts: (c) Reetz, M. T.; Vougioukas, A. E.
Tetrahedron Lett. 1987 28, 793. Chiral palladium catalysts: (d)
Sodeoka, M.; Ohrai, K.; Shibasaki, M. J . Org. Chem. 1995, 60, 2648.
(e) Sodeoka, M.; Tokunoh, R.; Miyazaki, F.; Hagiwara, E.; Shibasaki,
M. Synlett 1997, 463. (f) Sodeoka, M.; Shibasaki, M. Pure Appl. Chem.
1998, 70, 414. (g) Fujii A.; Sodeoka, M. Tetrahedron Lett. 1999, 40,
8011. See also: (h) Hagiwara, E.; Fujii, A.; Sodeoka, M. J . Am. Chem.
Soc. 1998, 120, 2474. (i) Fujii, A.; Hagiwara, E.; Sodeoka, M. J . Am.
Chem. Soc. 1999, 121, 5450. Chiral platinum catalysts: (j) Fujimura,
O. J . Am. Chem. Soc. 1998, 120, 10032. Reviews on direct catalytic
asymmetric aldol reactions of aldehydes with unmodified ketones: (k)
Groger, H.; Wilken, J . Angew. Chem., Int. Ed. 2001, 40, 529. (l) List,
B. Synlett 2001, 1675. Recent examples of direct catalytic asymmetric
aldol reactions of aldehydes: (m) Yamada, Y. M. A.; Yoshikawa, N.;
Sasai, H.; Shibasaki, M. Angew. Chem., Int. Ed. Engl. 1997, 36, 1871.
(n) Yamada, Y. M. A.; Shibasaki, M. Tetrahedron Lett. 1998, 39, 5561.
(o) Yoshikawa, N.; Yamada, Y. M. A.; Das, J .; Sasai, H.; Shibasaki, M.
J . Am. Chem. Soc. 1999, 121, 4168. (p) List, B.; Lerner, R. A.; Barbas,
C. F., III J . Am. Chem. Soc. 2000, 122, 2395. (q) Notz, W.; List, B. J .
Am. Chem. Soc. 2000, 122, 7386. (r) List, B.; Pojarliev, P.; Castello, C.
Org. Lett. 2001, 3, 573. (s) Saito, S.; Nakadai, M.; Yamamoto, H. Synlett
2001, 1245. (t) Trost, B. M.; Ito, H. J . Am. Chem. Soc. 2000, 122, 12003.
(u) Trost, B. M.; Ito, H.; Silcoff, E. R. J . Am. Chem. Soc. 2001, 123,
3367. (v) Trost, B. M.; Silcoff, E. R.; Ito, H. Org. Lett. 2001, 3, 2497.
(w) Yoshikawa, N.; Kumagai, N.; Matsunaga, S.; Moll, G.; Ohshima,
T.; Suzuki, T.; Shibasaki, M. J . Am. Chem. Soc. 2001, 123, 2466. (x)
Kumagai, N.; Matsunaga, S.; Yoshikawa, N.; Ohshima, T.; Shibasaki,
M. Org. Lett. 2001, 3, 1539. (y) Suzuki, T.; Yamagiwa, N.; Matsuo, Y.;
Sakamoto, S.; Yamaguchi, K.; Shibasaki, M.; Noyori, R. Tetrahedron
Lett. 2001, 42, 4669. (z) Yoshikawa, N.; Shibasaki, M. Tetrahedron
2001, 57, 2569.
Resu lts a n d Discu ssion
First, we examined the (R)-BINAP‚Ag(I)-catalyzed
reaction of allyltrimethoxysilane with benzaldehyde to
search for silver salts possessing sufficient catalytic
activity. No silver salts other than AgF (AgX; X ) OTf,
I, BF4, SbF6, ClO4, NTf2, NO3, IO4), however, gave any
allylated product in THF or MeOH (entry 1 in Table 1).
Next, fluoride compounds were investigated as additives
in combination with (R)-BINAP‚AgOTf catalyst. Adding
1 equiv of KF in methanol gave the desired product in
5% yield and 59% ee (entry 2). Although KF cannot act
as an activator of allylsilanes in THF because of its
insolubility in this solvent, a catalytic amount of tetrabu-
tylammonium fluoride (TBAF) showed good catalytic
activity in this reaction in THF with almost no enantio-
selectivity (entry 3). 18-Crown-6 is known to improve the
(5) (a) Yanagisawa, A.; Nakashima, H.; Ishiba, A.; Yamamoto, H.
J . Am. Chem. Soc. 1996, 118, 4723. (b) Yanagisawa, A.; Nakashima,
H.; Nakatsuka, Y.; Ishiba, A.; Yamamoto, H. Bull. Chem. Soc. J pn.
2001, 1129. (c) Yanagisawa, A.; Matsumoto, Y.; Nakashima, H.;
Asakawa, K.; Yamamoto, H. J . Am. Chem. Soc. 1997, 119, 9319. (d)
Yanagisawa, A.; Matsumoto, Y.; Asakawa, K.; Yamamoto, H. J . Am.
Chem. Soc. 1999, 121, 892. Since these communications appeared,
other papers on chiral silver-catalyzed asymmetric allylation have been
reported: (e) Shi, M.; Sui, W.-S. Tetrahedron: Asymmetry 2000, 11,
773. (f) Loh, T.-P.; Zhou, J .-R. Tetrahedron Lett. 2000, 41, 5261.
(6) (a) Ohkouchi, M.; Yamaguchi, M.; Yamagishi, T. Enantiomer
2000, 5, 71. (b) Ohkouchi, M.; Masui, D.; Yamaguchi, M.; Yamagishi,
T. J . Mol. Catal. A: Chemical 2001, 170, 1.
(7) (a) Kru¨ger, J .; Carreira, E. M. J . Am. Chem. Soc. 1998, 120, 837.
(b) Pagenkopf, B. L.; Kru¨ger, J .; Stojanovic, A.; Carreira, E. M. Angew.
Chem., Int. Ed. 1998, 37, 3124.
(8) (a) Yanagisawa, A.; Kageyama, H.; Nakatsuka, Y.; Asakawa, K.;
Matsumoto, Y.; Yamamoto, H. Angew. Chem., Int. Ed. 1999, 38, 3701.
(b) Yanagisawa, A.; Nakatsuka, Y.; Asakawa, K.; Kageyama, H.;
Yamamoto, H. Synlett 2001, 69. (c) Yanagisawa, A.; Nakatsuka, Y.;
Asakawa, K.; Wadamoto, M.; Kageyama, H.; Yamamoto, H. Bull.
Chem. Soc. J pn. 2001, 1477.
(9) Pagenkopf, B. L.; Carreira, E. M. Chem. Eur. J . 1999, 5, 3437.
5594 J . Org. Chem., Vol. 68, No. 14, 2003

BINAP/ AgOTf/ KF/ 18-Crown-6
TABLE 1. Effects of Ad d itives on Ch em ica l Yield a n d
En a n tioselectivitya
allylsilane
[equiv]
additive
(mol %)
yieldb eec
[%] [%]
entry solvent Ag(I)
1
2
3
4
5
6
7
THF
MeOH AgOTf
AgXd
1.8
1.0
2.0
1.0
1.8
1.8
1.0
<1
KF (100)
TBAF (5)
KF,18-crown-6 (5)
KF (5)
18-crown-6 (5)
KF (50),
5
92
59
1
90
THF
THF
THF
THF
THF
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
61
<1
<1
56
3
F IGURE 3. Plot of ee dependence of allylation as a function
of ee of BINAP.
18-crown-6 (5)
KF (5),
8
THF
AgOTf
1.0
82
58
18-crown-6 (50)
raised the ee of the product and a combination of 2 or 3
mol % of BINAP and 5 mol % of silver triflate gave the
best results with 3 equiv of allyltrimethoxysilane (entries
3 and 4).
a
Unless otherwise noted, the reaction was carried out with
allyltrimethoxysilane (1.8 equiv) and benzaldehyde (1 equiv) with
(R)-BINAP (5 mol %) and silver salt (5 mol %) at -20 °C for 4 h.
b Yield of isolated product. c Determined by HPLC analysis (Chiral
d
To substantiate the effect of these ratios, the enantio-
selectivity of homoallyl alcohol obtained from the reaction
of allyltrimethoxysilane and benzaldehyde was plotted
against the ee of BINAP using the two different ratios of
BINAP and AgOTf (Figure 3).11 When the reaction was
performed in the presence of a catalyst prepared from a
1:1 mixture of (R)-BINAP and AgOTf, a negative non-
linear effect was observed (0). In contrast, the linear
behavior was observed with a 1:0.4 mixture of (R)-BINAP
and AgOTf (4). These phenomena support the hypothesis
that at least two BINAP‚silver complexes have certain
catalytic activity and contribute to the allylation when a
1:1 mixture of BINAP and AgOTf is used as a catalyst,
and a single BINAP silver complex is formed with use of
the 1:0.4 mixture. Moreover, these experiments support
the inference that a 1:1 complex is a key species to
promote the reaction highly enantioselectively.
OD-H, Daicel Chemical Industries, Ltd.). AgOTf, AgI, AgBF4,
AgSbF6, AgClO4, AgNTf2, AgNO3, and AgIO4 were used.
TABLE 2. Th e Op tim u m Rea ction Con d ition s of
Asym m etr ic Allyla tion of Ben za ld eh yd e: Con cer n in g th e
Am ou n t of BINAP a
(R)-BINAP
[mol %]
allylsilane
[equiv]
yieldb
[%]
eec
[%]
entry
1
2
3
4
5
6
5
5
3
2
10
0
1.0
3.0
3.0
3.0
3.0
3.0
61
90
92
91
21
<1
90
69
93
95
2
a
Unless otherwise specified, the reaction was carried out with
AgOTf (5 mol %), KF (5 mol %), and 18-crown-6 (5 mol %) at -20
°C for 4 h in THF. Yield of isolated product. c Determined by
b
HPLC analysis (Chiral OD-H, Daicel Chemical Industries, Ltd.).
To obtain higher enantioselectivity, we screened vari-
ous BINAP derivatives and other related chiral bisphos-
phines as chiral ligands (Table 3). When the (R)-Tol-
BINAP was used for this allylation, the enantioselectivity
was slightly higher than that obtained with the (R)-
BINAP catalyst (entries 1 and 2). (S)-DM-BINAP also
gave high enantioselectivity though in low yield (entry
4). Among the chiral bisphosphines resulting, H8-BINAP
showed the highest reactivity; however, (R)-H8-DM-
BINAP did not give good results in either yield or
enantioselectivity (entries 5 and 6). Use of (R)-MeO-
BIPHEP and (R)-SEGPHOS12 resulted in moderate yields
and enantioselectivity (entries 7 and 8).
Some reaction temperatures were examined, and al-
lylation at -20 °C gave a satisfactory result with respect
to both chemical yield and ee of the product (Table 4,
entries 1-3). Among the solvents tested, aprotic and
polar solvents proved to be effective for the reaction, and
THF provided the best result (entries 1 and 4-6).
Allylation at high concentration improved the chemical
yield and the reaction could be achieved with a reduced
amount of allyltrimethoxysilane without decreasing the
yield. In fact, the reaction of benzaldehyde with an
solubility of KF in THF or other aprotic polar organic
solvents and also to generate a reactive fluoride species.
In fact, when a catalytic amount of KF and 18-crown-6
was added, the reaction proceeded smoothly in THF with
90% ee (entry 4). In the absence of KF, however, the
product was not obtained at all (entry 6). Use of an
increased amount of 18-crown-6 improved the chemical
yield but the enantioselectivity was lower (entry 8).
The optimum reaction conditions of (R)-BINAP, AgOTf,
KF, and 18-crown-6 catalyzed asymmetric allylation with
benzaldehyde are shown in Table 2. Three equivalents
of allyltrimethoxysilane raised the yield but resulted in
a decrease of the enantioselectivity (entry 2). We recently
showed that the ratio of BINAP to a silver salt is a very
important factor in obtaining better yield and better
enantioselectivity, because a significant amount of a 2:1
complex of (R)-BINAP and silver(I) salt was formed in
addition to a 1:1 complex when (R)-BINAP was mixed
with an equimolar amount of silver(I) salt at room
temperature.8,10 In fact, a mixture of 10 mol % of (R)-
BINAP and 5 mol % of AgOTf gave only a 21% yield of
the product with 2% ee (entry 5). When this reaction was
carried out by changing the ratio of (R)-BINAP to AgOTf,
it was found that an excess amount of silver triflate
(11) Kagan, H. B.; Luukas, T. O. In Comprehensive Asymmetric
Catalysis; J acobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer:
Heidelberg, Germany, 1999; Vol. 1, p 102.
(12) Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura,
T.; Kumobayashi, H. Adv. Synth. Catal. 2001, 3, 264.
(10) Yamagishi et al. also detected the 2:1 complex by 31P NMR;
see ref 6b.
J . Org. Chem, Vol. 68, No. 14, 2003 5595

Wadamoto et al.
TABLE 3. Effects of Liga n d on Ch em ica l Yield a n d
En a n tioselectivitya
TABLE 5. Asym m etr ic Allyla tion of Ald eh yd es
Ca ta lyzed by BINAP , AgOTf, KF , a n d 18-Cr ow n -6a
yieldb
eec
entry
aldehyde
PhCHO
(E)-PhCHdCHCHO
2-furyl-CHO
1-naphthyl-CHO
4-MeOC6H4CHO
4-BrC6H4CHO
2-MeC6H4CHO
c-C6H11CHO
condition
[%]
[%]
1
A
A
A
A
A
A
A
B
B
91
81
57
95
61
95
82
62
76
95 (R)
87 (R)
95 (R)
92 (R)
95 (R)
96 (R)
97 (R)
93f (R)
86 (S)
2
3d
4
5
6d
7e
8
9
PhCH2CH2CHO
a
Unless otherwise specified, the reaction was carried out wth
condition A or B. Condition A: The reaction was carried out with
allyltrimethoxysilane (3 equiv) and aldehyde (1 equiv) in the
presence of chiral silver(I) catalyst prepared from (R)-BINAP (2
mol %), AgOTf (5 mol %), KF (5 mol %), and 18-crown-6 (5 mol %)
in THF at -20 °C for 4 h. Condition B: The reaction was carried
out with allyltrimethoxysilane (3 equiv) and aldehyde (1 equiv)
in the presence of chiral silver(I) catalyst prepared from (R)-BINAP
(6 mol %), AgOTf (15 mol %), KF (15 mol %), and 18-crown-6 (15
b
mol %) in THF at -20 °C for 24 h. Isolated yield. c Determined
by HPLC analysis (Chiralcel OD-H or OJ , Daicel Chemical
d
Industries, Ltd.). 2 mol % of (R)-BINAP and 2 equiv of allyltri-
methoxysilane were used. e 3 mol % of (R)-p-Tol-BINAP was used.
f Determined by HPLC analysis of the 3,5-dinitrobenzoate from
the esterification (3,5-dinitrobenzoyl chloride, triethylamine/1,2-
dichloromethane).
yieldb
[%]
eec
[%]
TABLE 6. Dia ster eo- a n d En a n tioselective Ad d ition of
Cr otyltr im eth oxysila n e to Ben za ld eh yd e Ca ta lyzed by
BINAP , AgOTf, KF , a n d 18-Cr ow n -6
entry
ligand
(R)-BINAP
(R)-p-Tol-BINAP
(R)-p-tBuC6H4-BINAP
(S)-DM-BINAP
1
2
3
4
5
6
7
8
97
49
80
6
>99
29
95
96
58
92
65
59
81
81
E/ Z
ratio
yield
[%]
anti (% ee):syn (% ee)
<1/99
87/13
91
44
85 (95):15 (75)
85 (95):15 (75)
(R)-H8-BINAP
(R)-H8-DM-BINAP
(R)-MeO-BIPHEP
(R)-SEGPHOS
80
52
the addition of allyltrimethoxysilane to various aldehydes
(Table 5). All reactions of aromatic and R,â-unsaturated
aldehydes gave satisfactory yields and good ee values.
When an R,â-unsaturated aldehyde was used, 1,2-addi-
tion took place exclusively (entry 2). In contrast, aliphatic
aldehydes gave relatively low chemical yield with 2 mol
% of (R)-BINAP and 5 mol % of other catalysts (condition
A), while treatment of cyclohexanecarboxaldehyde with
allyltrimethoxysilane and 6 mol % of (R)-BINAP and 15
mol % of the other catalysts (condition B) gave the
allylated product in 62% yield with 93% ee (entry 8).
Aliphatic aldehydes do not give any product in the
presence of (R)-BINAP‚AgF complex in MeOH.8a
Condensation of γ-substituted allylmetal reagents with
carbonyl compounds is a challenging problem with regard
to regioselectivity (R/γ) and stereoselectivity (E/ Z or anti/
syn).1 The reaction of (Z)-crotyltrimethoxysilane (E/ Z <
1/99) in the presence of (R)-BINAP, AgOTf, KF, and 18-
crown-6 ether in THF at 0 °C for 24 h gave the γ-adduct
almost exclusively with an anti/syn ratio of 85:15 (Table
6). The anti isomer had 95% ee and the 1R,2R config-
uration. (E)-enriched crotyltrimethoxysilane (E/ Z )
87/13) gave the same selectivities and configuration.
These results were quite similar to those given by the
BINAP‚AgOTf-catalyzed reaction with crotyltributyltin.
We have reported that trimethoxysilyl enol ethers gave
aldol adducts in the condensation with aldehydes cata-
lyzed by BINAP‚AgF in MeOH.8b,c This reaction, however,
caused undesired hydrolysis of the silyl enol ether by
a
Unless otherwise specified, the reaction was carried out with
allyltrimethoxysilane (2 equiv) and benzaldehyde (1 equiv) in the
presence of a specified ligand (2 mol %), AgOTf (5 mol %), KF (5
b
mol %), and 18-crown-6 (5 mol %) at -20 °C for 4 h in THF. Yield
of isolated product. c Determined by HPLC analysis (Chiral OD-
H, Daicel Chemical Industries, Ltd.).
TABLE 4. Th e Op tim u m Rea ction Con d ition s of
Asym m etr ic Allyla tion of Ben za ld eh yd e: Con cer n in g
Tem p er a tu r e, Solven t, a n d Con cen tr a tion a
solvent
(mL)
T
[°C]
allylsilane
[equiv]
yieldb
[%]
eec
[%]
entry
1
2
3
4
5
6
7
8
THF (6)
THF (6)
THF (6)
toluene (6)
DMF (6)
CH2Cl2 (6)
THF (3)
THF (3)
-20
0
3
3
3
3
3
3
2
1
91
54
4
<1
67
29
97
78
95
92
95
-40
-20
-20
-20
-20
-20
71
71
95
96
a
Unless otherwise specified, the reaction was carried out with
benzaldehyde (1.0 mmol), (R)-BINAP (2 mol %), AgOTf (5 mol %),
KF (5 mol %), and 18-crown-6 (5 mol %) in a specified solvent for
4 h. Yield of isolated product. c Determined by HPLC analysis
b
(Chiral OD-H, Daicel Chemical Industries, Ltd.).
equimolar amount of the allylsilane gave 78% yield with
96% ee in the presence of 2 mol % of (R)-BINAP in THF
(entries 7 and 8).
Optimized conditions were established for THF as
solvent at -20 °C, and we employed these conditions in
5596 J . Org. Chem., Vol. 68, No. 14, 2003

BINAP/ AgOTf/ KF/ 18-Crown-6
TABLE 7. Dia ster eo- a n d En a n tioselective Ald ol
Rea ction of Tr im eth oxysilyl En ol Eth er s Ca ta lyzed by
(R)-BINAP , AgOTf, KF , a n d 18-Cr ow n -6a
TABLE 8. Dia ster eo- a n d En a n tioselective Ald ol
Rea ction of Tr im eth oxysilyl En ol Eth er s w ith Ald eh yd es
Ca ta lyzed by (R)-BINAP , AgOTf, KF , a n d 18-Cr ow n -6a
yieldb
[%]
eed
[%]
entry
aldehyde
PhCHO
(E)-PhCHdCHCHO
1-naphthyl-CHO
4-MeOC6H4CHO
4-BrC6H4CHO
syn/antic
1
2
3
4
78
68
70
55
86
41
9/91
27/73
5/95
9/91
8/92
93
89
90
93
95
83
5
6e
PhCH2CH2CHO
21/79
a
Unless otherwise specified, the reaction was carried out with
trimethoxysilyl enol ether (1 equiv) and benzaldehyde (1 equiv)
in the presence of (R)-BINAP (6 mol %), AgOTf (10 mol %), KF
(10 mol %), and 18-crown-6 (10 mol %) in THF at -20 °C for 4 h.
a
Unless otherwise specified, the reaction was carried out with
d
b Yield of isolated product. c Determined by 1H NMR analysis. Ee
condition A or B. Condition A: The reaction was carried out with
trimethoxysilyl enol ether (1 equiv) and benzaldehyde (1 equiv)
in the presence of (R)-p-Tol-BINAP‚AgF (10 mol %) in MeOH-
acetone at -78 °C for 5 h. Condition B: The reaction was carried
out with trimethoxysilyl enol ether (1.0 equiv) and benzaldehyde
(1.0 equiv) in the presence of (R)-BINAP (6 mol %), AgOTf (10
mol %), KF (10 mol %), and 18-crown-6 (10 mol %) in THF at -20
of the major diastereomer. Determined by HPLC analysis (Chiral
OD-H, Daicel Chemical Industries, Ltd.). e (R)-BINAP (12 mol %)
and AgOTf (20 mol %) were used.
silyl enol ether under the influence of the catalyst. All
the reactions resulted in remarkable anti- and enantio-
selectivities. In the reaction with cinnamaldehyde, only
a 1,2-adduct was observed (entry 2). In the case of
hydrocinnamaldehyde, a 2-fold amount of (R)-BINAP‚
AgOTf was necessary to obtain the desired product in a
satisfactory yield (entry 6), which was not available in
the BINAP‚AgF-catalyzed aldol reaction.8b,c
°C for 24 h. Yield of isolated product. c Determined by 1H NMR
b
d
analysis. Ee of the major diastereomer. Determined by HPLC
analysis (Chiral OD-H, Daicel Chemical Industries, Ltd.).
MeOH and the yield and enantioselectivity were im-
proved by using mixed solvents of MeOH with an aprotic
solvent. Thus, the present BINAP/AgOTf/KF/18-crown-6
catalyst system was expected to be successfully applied
to the Mukaiyama-type aldol reaction because the new
mixed catalysts are also used in aprotic THF solvent.
Furthermore, employment of substituted enol silanes for
the present catalytic aldol reaction is quite attractive
from the viewpoint of diastereoselectivity (anti/syn se-
lectivity). In general, silyl enol ethers are known to react
with aldehydes with syn selectivity irrespective of the
double-bond geometry (E or Z) of the ether in the
presence of a catalytic amount of chiral Lewis acids. In
contrast, reagent-controlled diastereoselective aldol reac-
tion of trichlorosilyl enol ethers catalyzed by chiral Lewis
bases is known to be a useful method for obtaining both
diastereomers of the aldol product selectively.4a,b,13 BINAP‚
AgF catalyst showed similar diastereoselectivity to that
of typical chiral Lewis acid catalysts and gave syn
adducts from both (E) and (Z) enolates.8b,c Interestingly,
the reaction of the trimethoxysilyl enol ether of cyclo-
hexanone and benzaldehyde in the presence of a catalytic
amount of (R)-BINAP, AgOTf, KF, and 18-crown-6 in
THF preferentially gave an anti adduct (syn/anti ) 9/91)
with 93% ee (entry 2 in Table 7). In contrast, tert-butyl
ethyl ketone-derived (Z)-silyl enol ether gave a syn
product exclusively with 90% ee (entry 4 in Table 7).
These results were quite similar to those given by the
BINAP‚AgOTf-catalyzed reaction with tin enolate.
Table 8 summarizes the results obtained for the
reaction of aromatic, R,â-unsaturated, and primary ali-
phatic aldehydes with cyclohexanone-derived trimethoxy-
From these results, BINAP‚AgOTf and 18-crown-6‚KF
complexes are believed to act separately as catalysts and
not to generate AgF because it is insoluble in THF. To
confirm this working hypothesis, we performed 19F NMR
experiments: (R)-BINAP‚AgOTf complex was treated
with a 1:1 mixture of 18-crown-6‚KF in THF-d8 at room
temperature; however, no peaks assignable to AgF or
related fluoride species appeared, and only peaks of TfO-
species were observed. Two probable reaction mecha-
nisms for the catalytic asymmetric allylation are shown
in Figure 4. J udging from the fact that crotyltrimeth-
oxysilane reacted with benzaldehyde anti-selectively
regardless of the E/ Z stereochemistry in the presence of
BINAP‚AgOTf/KF/18-crown-6 as catalysts, the Lewis acid
mechanism via an acyclic antiperiplanar transition state
structure seems more preferable (path a).14 However, the
transmetalation pathway b cannot be denied completely
because the anti product can be obtained from both E-
and Z-crotylsilanes when rapid E/ Z isomerization of a
crotyl silver compound occurs. At present, we have no
further experimental evidence for the mechanism.
In marked contrast to the case of allylation, the
diastereoselectivity of the aldol reaction depends on the
geometry of trimethoxysilyl enol ether. In the reaction,
BINAP‚AgOTf plays an important role in accomplishing
the diastereoselectivity. For example, when the aldol
reaction of cyclohexane-derived trimethoxysilyl enol ether
with benzaldehyde was performed with KF (1 eq) and
18-crown-6 (1 eq) without BINAP‚AgOTf, the opposite
syn-selectivity was obtained (eq 5).
(13) (a) Denmark, S. E.; Winter, S. B. D.; Su, X.; Wong, K.-T. J .
Am. Chem. Soc. 1996, 118, 7404. (b) Denmark, S. E.; Wong, K.-T.;
Stavenger, R. A. J . Am. Chem. Soc. 1997, 119, 2333. (c) Denmark, S.
E.; Stavenger, R. A.; Wong, K.-T.; Su, X. J . Am. Chem. Soc. 1999, 121,
4982.
(14) (a) Yamamoto, Y.; Yatagai, H.; Naruta, Y.; Maruyama, K. J .
Am. Chem. Soc. 1980, 102, 7107. (b) Yamamoto, Y.; Yatagai, H.;
Ishihara, Y.; Maeda, N.; Maruyama, K. Tetrahedron 1984, 40, 2239.
J . Org. Chem, Vol. 68, No. 14, 2003 5597

Wadamoto et al.
F IGURE 4. Probable reaction mechanisms of the catalytic asymmetric allylation.
for these asymmetric reactions in which both an aldehyde
and a trimethoxysilyl compound are activated separately;
(2) a negative nonlinear effect is observed when a 1:1
mixture of BINAP and AgOTf is used; (3) not only
aromatic and R,â-unsaturated aldehydes but aliphatic
aldehydes also give the coupling products in satisfactory
yields in both allylation and aldol reaction; (4) remark-
able γ and anti-selectivities are observed for the reaction
with crotyltrimethoxysilanes, irrespective of the config-
uration at the double bond; (5) (E)-trimethoxysilyl enol
ether gives anti-products, while (Z)-trimethoxysilyl enol
ether gives the syn-adduct with high selectivity; and (6)
these processes are environmentally friendlier because
less toxic trimethoxysilyl compounds are used instead of
tin compounds. Further work is now in progress on the
catalytic allylation and aldol reaction and the detailed
reaction mechanism.
F IGURE 5. Probable cyclic transition-state structure in the
aldol reaction.
Exp er im en ta l Section
These results unambiguously indicate that cyclic tran-
sition state structures (A and B, Figure 5) are probable
models. In these assemblies, the BINAP‚Ag(I) complex
coordinates as a chiral Lewis acid to both an aldehyde
and a silyl enol ether to form a six-membered cyclic
structure, in which fluoride ion activates the silyl enol
ether to form a pentacoordinated silicate. Thus, from the
E-enolate, the anti aldol product can be obtained via a
cyclic transition state model A, and another model B
connects the Z-enolate to the syn product. Similar cyclic
models containing a BINAP-coordinated silver atom
instead of a fluorinated trimethoxysilyl group are also
possible alternatives when the transmetalation to silver
enolate occurs rapidly.
Gen er a l. Analytical TLC was done on precoated (0.25 mm)
silica gel plates. Column chromatography was conducted with
230-400 mesh silica gel. Infrared (IR) spectra were recorded
1
on a FTIR spectrometer. H NMR spectra were measured on
a 300-MHz spectrometer. Chemical shifts of 1H NMR spectra
were reported relative to tetramethylsilane (δ 0) or chloroform
(δ 7.26). Splitting patterns are indicated as s, singlet; d,
doublet; t, triplet; q, quartet; m, multiplet; and br, broad. 13C
NMR spectra were measured on a 75-MHz spectrometer.
Chemical shifts of 13C NMR spectra were reported relative to
CDCl3 (δ 77.0). Analytical high-performance liquid chroma-
tography (HPLC) was done with a chiral column (4.6 mm ×
25 cm, CHIRALCEL OB-H, OD-H, OJ , or CHIRALPAK AD).
Optical rotation was measured on a polarimeter. Microanaly-
ses were accomplished at the Faculty of Agriculture, Nagoya
University.
Con clu sion
We have described here novel methods for highly
enantioselective allylation and aldol reaction of aldehydes
with trimethoxysilyl compounds using a catalytic amount
of BINAP, AgOTf, KF, and 18-crown-6 ether in THF. The
main features of these processes are as follows: (1) the
mixed catalysts behave as bifunctional chiral catalysts
All experiments were carried out under an atmosphere of
standard grade argon gas (oxygen <10 ppm) and exclusion of
direct light. Tetahydrofuran (THF) was distilled from sodium-
bezophenone ketyl prior to use. Allyltrimethoxysilane and
aldehydes were purified by distillation before use. (R)-p-
tBuC6H4-BINAP was prepared according to the reported
5598 J . Org. Chem., Vol. 68, No. 14, 2003

BINAP/ AgOTf/ KF/ 18-Crown-6
procedure.15 (E)-enriched crotyltrimethoxysilane (E/ Z ) 83/
17) was prepared by treatment of crotylmagnesium chloride
with tetramethoxysilane in dry ether and purified by distil-
lation before use. (Z)-Crotyltrimethoxysilane (E/ Z < 1/99) was
prepared by reaction of (Z)-crotyltrichlorosilane with MeOH
in the presence of triethylamine and purified by distillation
before use. The (Z)-crotylsilane was synthesized from trichlo-
rosilane, 1,3-butadiene, and Pd(PPh3)4 according to Iseki’s
procedure.2h Trimethoxysilyl enol ethers of cyclohexanone were
prepared by 1,4-hydrosilylation of 2-cyclohexen-1-one with
(MeO)3SiH catalyzed by (Ph3P)3RhCl or (Ph3P)4RhH.16 Tri-
methoxysilyl enol ethers of tert-butyl ethyl ketone were
prepared by treating the ketone with LDA in ether followed
by silylation with (MeO)3SiCl.17 Other chemicals were used
as purchased.
(c 1.0, Et2O). The enantioselectivity was determined to be 87%
ee by HPLC analysis, using a chiral column (Chiralcel OD-H,
hexane/i-PrOH ) 20/1, flow rate ) 1.0 mL/min): tmajor ) 14.0
min (R), tminor ) 25.5 min (S). Elemental Anal. Calcd for
C
12H14O: C 82.72, H 8.10. Found: C 82.73, H 8.10.
(R)-1-(2-F u r yl)-3-bu ten -1-ol (En tr y 3 in Ta ble 5).20 TLC
Rf 0.30 (1:3 ethyl acetate/hexane); IR (neat) 3750-3040, 3079,
2980, 1644, 1505, 1436, 1341, 1229, 1150, 1057, 1011, 922, 885,
1
864, 812, 739 cm-1; H NMR (300 MHz, CDCl3) δ 2.00 (br, 1
H), 2.61-2.66 (m, 2 H), 4.76 (m, 1 H), 5.14-5.23 (m, 2 H), 5.82
(m, 1 H), 6.26 (d, 1 H, J ) 3.2 Hz), 6.34 (dd, 1 H, J ) 3.1, 1.6
Hz), 7.39 (d, 1 H, J ) 1.8 Hz); 13C NMR (75 MHz, CDCl3) δ
40.0, 66.8, 106.0, 110.0, 118.4, 133.6, 141.9, 155.9; [R]26D +29.9°
(c 1.0, Et2O). The enantioselectivity was determined to be 95%
ee by HPLC analysis, using a chiral column (Chiralcel OJ , Ltd.,
hexane/i-PrOH ) 40/1, flow rate ) 1.0 mL/min): tminor ) 15.4
min (S), tmajor ) 16.6 min (R). Elemental Anal. Calcd for
C8H10O2: C 69.54, H 7.30. Found: C 69.60, H 7.25.
Typ ica l Exp er im en ta l P r oced u r e for Asym m etr ic Al-
lyla tion of Ald eh yd es w ith Allylic Tr im eth oxysila n e
Rea gen ts Ca ta lyzed by BINAP ‚AgOTf a n d KF ‚18-Cr ow n -
6: Syn th esis of (R)-1-P h en yl-3-bu ten -1-ol (En tr y 4 in
(R)-1-(1-Na p h th yl)-3-bu ten -1-ol (En tr y 4 in Ta ble 5).19,21
TLC Rf 0.36 (1:3 ethyl acetate/hexane); IR (neat) 3650-3120,
3071, 2979, 2940, 2908, 1640, 1597, 1510, 1433, 1395, 1167,
Ta ble 2, En tr y 1 in Ta ble 4, a n d En tr y 1 in Ta ble 5).18
A
mixture of AgOTf (12.8 mg, 0.0498 mmol), (R)-BINAP (12.5
mg, 0.0201 mmol), KF (2.9 mg, 0.0499 mmol), and 18-crown-6
(200 µL, 0.25 M in THF) was dissolved in dry THF (6 mL)
under argon atmosphere and with direct light excluded, and
stirred at 20 °C for 20 min. To the resulting solution was added
dropwise benzaldehyde (102 mg, 1.00 mmol) and allyltri-
methoxysilane (505 µL, 3.00 mmol) successively at -20 °C.
The mixture was stirred for 4 h at this temperature and
treated with 1 M ()1 mol dm-3) HCl (5 mL) at ambient
temperature for 30 min. The resulting suspension was filtered
off by a glass filter funnel filled with Celite and silica gel and
concentrated in vacuo. The residual crude product was purified
by column chromatography on silica gel (1:10 ethyl acetate/
hexane as the eluant) to afford the homoallylic alcohol (135
mg, 91% yield) as a colorless oil. The enantioselectivity was
determined to be 95% ee by HPLC analysis, using a chiral
column (Chiralcel OD-H, hexane/i-PrOH ) 40/1, flow rate )
1.0 mL/min): tmajor ) 12.7 min (R), tminor ) 14.3 min (S). The
absolute configuration was determined to be R by comparison
of the [R]D value with reported data: (R)-enriched alcohol (90%
ee), [R]D +43.7° (c 6.7, benzene).19 The observed [R]D value of
1
1055, 916, 801, 777 cm-1; H NMR (300 MHz, CDCl3) δ 2.16
(d, 1 H, J ) 2.8 Hz), 2.57-2.72 (m, 1 H), 2.72-2.85 (m, 1 H),
5.17-5.27 (m, 2 H), 5.54 (m, 1 H), 5.94 (m, 1 H), 7.46-7.55
(m, 3 H), 7.67 (d, 1 H, J ) 7.1 Hz), 7.79 (d, 1 H, J ) 8.2 Hz),
7.87-7.90 (m, 1 H), 8.08 (d, 1 H, J ) 7.8 Hz); 13C NMR (75
MHz, CDCl3) δ 42.7, 69.8, 118.0, 122.7, 122.9, 125.3 (2 C),
125.9, 127.8, 128.8, 130.1, 133.6, 134.7, 139.4; [R]23D +97.3° (c
1.0, benzene). The enantioselectivity was determined to be 92%
ee by HPLC analysis, using a chiral column (Chiralcel OD-H,
hexane/i-PrOH ) 9/1, flow rate ) 1.0 mL/min): tminor ) 8.6
min (S), tmajor ) 14.8 min (R). Elemental Anal. Calcd for
C
12H14O: C 84.81, H 7.12. Found: C 84.83, H 7.10.
(R)-1-(p-Meth oxyph en yl)-3-bu ten -1-ol (En tr y 5 in Table
5).18b,21,22 TLC Rf 0.27 (1:3 ethyl acetate/hexane); IR (neat)
3700-3120, 3075, 3002, 2936, 2900, 2838, 1642, 1613, 1586,
1514, 1464, 1443, 1302, 1248, 1175, 1036, 1003, 918, 872, 833,
812, 770 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.94 (d, 1 H, J )
0.9 Hz), 2.50 (d, 2 H, J ) 6.6 Hz), 3.81 (s, 3 H), 4.69 (t, 1 H,
J ) 6.3 Hz), 5.11-5.18 (m, 2 H), 5.80 (m, 1 H), 6.89 (d, 2 H,
J ) 8.8 Hz), 7.29 (d, 2 H, J ) 8.8 Hz); 13C NMR (75 MHz,
CDCl3) δ 43.7, 55.2, 72.9, 113.7 (2 C), 118.1, 127.0 (2 C), 134.6,
the product with 95% ee: [R]22 +56.5° (c 1.0, benzene).
D
136.0, 158.9; [R]23 +30.5° (c 1.0, benzene). The enantioselec-
Elemental Anal. Calcd for C10H12O: C 81.04, H 8.16. Found:
C 81.06, H 8.16. Spectral data of the product: TLC Rf 0.34
(1:3 ethyl acetate/hexane); IR (neat) 3700-3120, 3077, 3031,
2907, 1642, 1603, 1493, 1455, 1316, 1198, 1115, 1076, 1048,
916, 870, 758, 700 cm-1; 1H NMR (300 MHz, CDCl3) δ 2.01 (d,
1 H, J ) 2.5 Hz), 2.52 (m, 2 H), 4.75 (dt, 1 H, J ) 6.9, 2.5 Hz),
5.14-5.20 (m, 2 H), 5.82 (m, 1 H), 7.25-7.37 (m, 5 H); 13C NMR
(75 MHz, CDCl3) δ 43.5, 73.2, 117.8, 125.7 (2 C), 127.2, 128.1
(2 C), 134.3, 143.8.
D
tivity was determined to be 95% ee by HPLC analysis, using
a chiral column (Chiralcel OD-H, hexane/i-PrOH ) 20/1, flow
rate ) 0.5 mL/min): tmajor ) 10.4 min (R), tminor ) 12.3 min
(S). Elemental Anal. Calcd for C11H14O: C 74.13, H 7.92.
Found: C 74.14, H 7.92.
(R)-1-(p-Br om op h en yl)-3-bu ten -1-ol (En tr y 6 in Ta ble
5).18b,22-24 TLC Rf 0.39 (1:3 ethyl acetate/hexane); IR (neat)
3680-3120, 3079, 2979, 2934, 2905, 1642, 1593, 1489, 1431,
1406, 1297, 1194, 1071, 1011, 918, 870, 826, 777, 739, 718
(R),(E)-1-P h en yl-1,5-h exa d ien -3-ol (E n t r y 2 in Ta b le
5).18 TLC Rf 0.28 (1:3 ethyl acetate/hexane); IR (neat) 3670-
3120, 3079, 3026, 2979, 1642, 1599, 1579, 1493, 1449, 1130,
1
cm-1; H NMR (300 MHz, CDCl3) δ 2.03 (d, 1 H, J ) 3.0 Hz),
2.48 (m, 2 H), 4.71 (m, 1 H), 5.14-5.20 (m, 2 H), 5.80 (m, 1
H), 7.24 (d, 2 H, J ) 8.3 Hz), 7.48 (d, 2 H, J ) 8.3 Hz); 13C
NMR (75 MHz, CDCl3) δ 43.6, 72.5, 118.6, 121.1, 127.5 (2 C),
1071, 1030, 967, 916, 749, 693 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 1.78 (br, 1 H), 2.39 (m, 2 H), 4.37 (dd, 1 H, J ) 12.3,
6.1 Hz), 5.16-5.22 (m, 2 H), 5.87 (m, 1 H), 6.25 (dd, 1 H, J )
15.9, 6.3 Hz), 6.62 (d, 1 H, J ) 15.7 Hz), 7.22-7.40 (m, 5 H);
13C NMR (75 MHz, CDCl3) δ 41.9, 71.7, 118.4, 126.4 (2 C),
131.3 (2 C), 133.9, 142.7; [R]24 +23.2° (c 1.0, benzene). The
D
enantioselectivity was determined to be 96% ee by HPLC
analysis, using a chiral column (Chiralcel OJ , hexane/i-PrOH
127.6, 128.5 (2 C), 130.3, 131.5, 134.0, 136.6; [R]26 -12.3°
D
(20) (a) Kusakabe, M.; Kitano, Y.; Kobayashi, Y.; Sato, F. J . Org.
Chem. 1989, 54, 2085. (b) Racherla, U. S.; Liao, Y.; Brown, H. C. J .
Org. Chem. 1992, 57, 6614.
(21) Sugimoto, K.; Aoyagi, S.; Chibayashi, C. J . Org. Chem. 1997,
62, 2322.
(22) Motoyama, Y.; Okano, M.; Narusawa, H.; Makihara, N.; Aoki,
K.; Nishiyama, H. Organometallics 2001, 20, 1580.
(23) For another method of preparation of the racemic compound,
see: (a) Chen, C.; Shen, Y.; Huang, Y.-Z. Tetrahedron Lett. 1988, 29,
1395. For a method of analytical resolution of the racemic compound,
see: (b) Halterman, R. L.; Roush, W. R.; Hoong, L. K. J . Org. Chem.
1987, 52, 1152.
(15) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi,
H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J . Org. Chem. 1986, 51,
629.
(16) (a) Ojima I.; Kogure, T. Organometallics 1982, 1, 1390. (b)
Zheng G. Z.; Chan, T. H. Organometallics 1995, 14, 70.
(17) (a) Peppard, D. F.; Brown, W. G.; J ohnson, W. C. J . Am. Chem.
Soc. 1946, 68, 70. (b) Moedritzer, K.; Van Wazer, J . R. Inorg. Chem.
1964, 3, 268.
(18) (a) Hoffmann, R. W.; Herold, T. Chem. Ber. 1981, 114, 375. (b)
Denmark, S. E.; Coe, D. M.; Pratt, N. E.; Griedel, B. D. J . Org. Chem.
1994, 59, 6161.
(19) Riediker, M.; Duthaler, R. O. Angew. Chem., Int. Ed. Engl.
1989, 28, 494.
(24) Yamada, K.; Tozawa, T.; Nishida, M.; Mukaiyama, T. Bull.
Chem. Soc. J pn. 1997, 70, 2301.
J . Org. Chem, Vol. 68, No. 14, 2003 5599

Wadamoto et al.
) 9/1, flow rate ) 0.5 mL/min): tminor ) 15.1 min (S), tmajor
)
Typ ica l Exp er im en ta l P r oced u r e for Asym m etr ic Al-
d ol Rea ction of Tr im eth oxysilyl En ol Eth er s w ith Ald e-
h ydes Catalyzed by (R)-BINAP ‚AgOTf an d KF‚18-Cr own -6
Com p lexes: Syn th esis of 2-(Hyd r oxyp h en ylm eth yl)cy-
cloh exa n on e (En tr y 2 in Ta ble 7, En tr y 1 in Ta ble 8).13,27
A mixture of AgOTf (51.4 mg, 0.200 mmol), (R)-BINAP (74.7
mg, 0.120 mmol), KF (5.8 mg, 0.1 mmol), and 18-crown-6 (400
µL, 0.25 M in THF) was dissolved in anhydrous THF (12 mL)
under argon atmosphere and with direct light excluded and
stirred at 20 °C for 30 min. To the resulting solution was added
dropwise benzaldehyde (203.3 µL, 2.00 mmol) and (1-cyclo-
hexenyloxy)trimethoxysilane (414.7 µL, 2.00 mmol) succes-
sively at -20 °C. The mixture was stirred for 6 h at this
temperature and then treated with brine (6 mL) and solid KF
(ca. 1 g) at ambient temperature for 30 min. The resulting
precipitate was filtered off by a glass filter funnel filled with
Celite and silica gel. The filtrate was dried over Na2SO4 and
concentrated in vacuo after filtration. The residual crude
product was purified by column chromatography on silica gel
(1:10 ethyl acetate/hexane as the eluant) to afford a mixture
of the aldol adducts (317.2 mg, 78% yield) as white solids. The
anti (R*,S*)/ syn (R*,R*) ratio was determined to be 91/9 by
1H NMR analysis. The enantioselectivities of the anti and syn
isomers were determined to be 93% ee and 22% ee, respec-
tively, by HPLC analysis, using a chiral column (Chiralcel
OD-H, hexane/i-PrOH ) 20/1, flow rate ) 0.5 mL/min):
tsyn-minor ) 18.3 min (2S,1′S), tsyn-major ) 20.4 min (2R,1′R),
tanti-major ) 24.4 min (2S,1′R), tanti-minor ) 39.4 min (2R,1′S).
The absolute configurations of all stereoisomers were unam-
biguously established by Denmark and co-workers.13c Specific
16.2 min (R). Elemental Anal. Calcd for C10H11BrO: C 52.89,
H 4.88. Found: C 52.88, H 4.88.
(R)-1-(o-Tolyl)-3-bu ten -1-ol (En tr y 7 in Ta ble 5).2h,18b,22
TLC Rf 0.40 (1:3 ethyl acetate/hexane); IR (neat) 3650-3125,
3075, 3025, 2979, 1640, 1489, 1462, 1051, 916, 870, 756, 725
1
cm-1; H NMR (300 MHz, CDCl3) δ 1.94 (d, 1 H, J ) 2.5 Hz),
2.36 (s, 3 H), 2.47 (m, 2 H), 4.99 (m, 1 H), 5.16-5.23 (m, 2 H),
5.88 (m, 1 H), 7.13-7.27 (m, 3 H), 7.50 (d, 1 H, J ) 7.4 Hz);
[R]24 +75.5° (c 1.0, benzene). The enantioselectivity was
D
determined to be 97% ee by HPLC analysis, using a chiral
column (Chiralcel AD, hexane/i-PrOH ) 20/1, flow rate ) 0.5
mL/min): tmajor ) 15.7 min (R), tminor ) 18.2 min (S). Elemental
Anal. Calcd for C11H14O: C 81.44, H 8.70. Found: C 81.44, H
8.69.
(R)-1-Cycloh exyl-3-b u t en -1-ol (E n t r y 8 in Ta b le 5).2k
TLC Rf 0.25 (1:5 ethyl acetate/hexane); IR (neat) 3700-3120,
1641, 1451, 1036, 986, 911, cm-1; 1H NMR (300 MHz, CDCl3)
δ 0.8-1.4 (m, 5 H), 1.54 (d, 1 H, J ) 6.9 Hz), 1.60-1.92 (m, 6
H), 2.07-2.18 (m, 1 H), 2.29-2.38 (m, 1 H), 3.40 (m, 1 H), 5.15
(m, 2 H), 5.87 (m, 1 H); [R]25 +13.7° (c 1.0, ethanol). The
D
enantioselectivity was determined to be 93% ee by HPLC
analysis of the 3,5-dinitrobenzoate of the product prepared by
esterification (3,5-dinitrobenzoyl chloride, triethylamine/1,2-
dichloroethane), using a chiral column (Chiralcel OD-H, hex-
ane/EtOH ) 50/1, flow rate ) 1.0 mL/min): tmajor ) 12.1 min
(R), tminor ) 13.1 min (S). Elemental Anal. Calcd for C10H17O:
C 77.87, H 11.76. Found: C 77.87, H 11.76.
(S)-1-P h en yl-5-h exen -3-ol (En tr y 9 in Ta ble 5).2k,21,22,24,25
TLC Rf 0.33 (1:3 ethyl acetate/hexane); IR (neat) 3700-3120,
3027, 2930, 2863, 1642, 1603, 1497, 1455, 1075, 1049, 1040,
995, 916, 747, 700 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.60 (d,
1 H, J ) 1.9 Hz), 1.80 (m, 2 H), 2.16-2.23 (m, 1 H), 2.29-2.36
(m, 1 H), 2.64-2.84 (m, 2 H), 3.68 (m, 1 H), 5.15 (d, 2 H, J )
11.8 Hz), 5.75-5.86 (s, 1 H), 7.16-7.31 (m, 5 H); [R]24D -26.4°
(c 1.0, benzene). The enantioselectivity was determined to
be 86% ee by HPLC analysis, using a chiral column (Chiral-
cel OD-H, hexane/i-PrOH ) 20/1, flow rate ) 0.5 mL/min):
tmajor ) 19.6 min (S), tminor ) 30.2 min (R). Elemental Anal.
Calcd for C12H16O: C 81.77, H 9.15. Found: C 81.77, H 9.16.
rotation of the anti isomer (93% ee): [R]29 +20.1° (c 1.0,
D
CHCl3). Elemental Anal. Calcd for C13H16O2: C 76.44, H 7.90.
Found: C 76.35, H 7.96. Specific rotation of the syn isomer
(22% ee): [R]28 +37.1° (c 1.0, CHCl3). Elemental Anal. Calcd
D
for C13H16O2: C 76.44, H 7.90. Found: C 76.10, H 8.23. Other
spectral data (TLC, IR, 1H NMR, and 13C NMR) of the anti
and syn isomers indicated good agreement with reported
data.8c,13,27
1-Hyd r oxy-2,4,4-tr im eth yl-1-p h en yl-3-p en ta n on e (En -
tr y 4 in Ta ble 7).5c,8c,28 The anti/syn ratio was determined to
be <1/99 by 1H NMR analysis. The enantioselectivity of the
syn isomer was determined to be 90% ee by HPLC analysis,
using a chiral column (Chiralcel OD-H, hexane/i-PrOH ) 40/
(1R,2R)-2-Meth y-1-p h en yl-3-bu ten -1-ol (Ta ble 6).26 The
R/γ and anti/syn ratios were determined to be <1/99 and 85/
15, respectively, by 1H NMR analysis. The enantioselectivities
of the anti and syn isomers were determined to be 95% ee and
75% ee, respectively, by HPLC analysis, using a chiral column
(Chiralcel OD-H, hexane/i-PrOH ) 40/1, flow rate ) 0.5 mL/
min): tanti-minor ) 15.0 min (1S,2S), tsyn-minor ) 15.5 min
(1S,2R), tanti-major+syn-major ) 17.8 min (1R,2R + 1R,2S). The
absolute configuration of the major anti isomer was deter-
mined to be 1R,2R by comparison of the [R]D value with
reported data. (1S,2S)-enriched alcohol (66% ee): [R]25D -73.4
(c 2.0, CHCl3).26 (1S,2R)-Isomer (55% ee): [R]25D -15.0 (c 0.93,
CHCl3).26 Observed [R]D value of the product: [R]25D +112.4 (c
1.0, CHCl3; data obtained on a 85:15 mixture of anti and syn
isomers). The absolute configuration of the major syn isomer
was determined to be 1R,2S by HPLC analysis.22 Elemental
Anal. Calcd for C11H14O: C 81.44, H 8.70. Found: C 81.44, H
8.70. Spectral data obtained on a 85:15 mixture of anti and
syn isomers: TLC Rf 0.38 (1:5 ethyl acetate/hexane); IR (neat)
3630-3130, 3081, 3065, 3031, 2977, 2932, 2872, 1640, 1603,
1, flow rate ) 0.5 mL/min): tsyn-minor ) 17.8 min, tsyn-major
)
D
19.0 min. Specific rotation of the syn isomer (90% ee): [R]29
-75.3° (c 1.0, CHCl3). Other spectral data (IR and 1H NMR)
of the syn isomer indicated good agreement with reported
data.5c,8c,28
2-[(E )-1-H y d r o x y -3-p h e n y l-2-p r o p e n y l]c y c lo h e x a -
n on e (En tr y 2 in Ta ble 8).5d,8c,13,27 The anti (R*,S*)/syn
(R*,R*) ratio was determined to be 73/27 by 1H NMR analysis.
The enantioselectivities of the anti and syn isomers were
determined to be 89% ee and 33% ee, respectively, by HPLC
analysis, using a chiral column (Chiralpak AD, hexane/
i-PrOH ) 40/1, flow rate ) 0.5 mL/min): tsyn-minor ) 77.2 min,
tsyn-major
) 98.2 min, tanti-major ) 106.3 min (2S,1′R),
tanti-minor ) 121.9 min (2R,1′S). The absolute configurations of
the anti isomers were assigned by Denmark and co-workers.13
Specific rotation of the anti isomer (89% ee): [R]29 -18.3° (c
D
1.0, CHCl3). Elemental Anal. Calcd for C15H18O2: C 78.23, H
7.88. Found: C 78.22, H 8.14. Specific rotation of the syn
1495, 1455, 1374, 1196, 1117, 1076, 1021, 914, 762, 702 cm-1
;
isomer (33% ee): [R]30 -6.6° (c 1.0, CHCl3). Elemental Anal.
D
1H NMR (300 MHz, CDCl3, anti isomer) δ 0.87 (d, 3 H, J )
6.9 Hz), 2.16 (d, 1 H, J ) 2.7 Hz), 2.48 (m, 1 H), 4.36 (dd, 1 H,
J ) 8.1, 2.4 Hz), 5.17-5.24 (m, 2 H), 5.75-5.87 (m, 1 H), 7.26-
7.36 (m, 5 H); 13C NMR (75 MHz, CDCl3, anti isomer) δ 16.5,
46.3, 77.8, 116.9, 126.8 (2 C), 127.6, 128.2 (2 C), 140.6, 142.4.
Calcd for C15H18O2: C 78.23, H 7.88. Found: C 78.12, H 8.12.
Other spectral data (TLC, IR, H NMR, and 13C NMR) of the
1
anti and syn isomers indicated good agreement with reported
data.5d,8c,13a-c
2-[(1-Na p h th yl)h yd r oxym eth yl]cycloh exa n on e (En tr y
3 in Ta ble 8).13b,c The anti (R*,S*)/syn (R*,R*) ratio was
1
(25) (a) Seebach, D.; Imwinkelried, R.; Stucky, G. Helv. Chim. Acta
1987, 70, 448. (b) Minowa, N.; Mukaiyama, T. Bull. Chem. Soc. J pn.
1987, 60, 3697.
determined to be 95/5 by H NMR analysis. The enantioselec-
(26) Roush, W. R.; Ando, K.; Powers, D. B.; Palkowitz, A. D.;
Halterman, R. L. J . Am. Chem. Soc. 1990, 112, 6339.
(27) J uaristi, E.; Beck, A. K.; Hansen, J .; Matt, T.; Mukhopadhyay,
T.; Simson, M.; Seebach, D. Synthesis 1993, 1271.
5600 J . Org. Chem., Vol. 68, No. 14, 2003

BINAP/ AgOTf/ KF/ 18-Crown-6
tivities of the anti and syn isomers were determined to be
90% ee and 48% ee, respectively, by HPLC analysis, using a
chiral column (Chiralcel OD-H, hexane/i-PrOH ) 40/1, flow
rate ) 0.5 mL/min): tsyn-major ) 34.3 min, tsyn-minor ) 47.8 min,
tanti-minor ) 92.4 min (2R,1′S), tanti-major ) 98.6 min (2S,1′R).
The absolute configurations of the anti isomers were assigned
by Denmark and co-workers.13b,c Specific rotation of the anti
rotation of the anti isomer (white solids, 95% ee): [R]29D +17.4°
(c 1.0, CHCl3). Elemental Anal. Calcd for C13H15O2Br: C 55.14,
H 5.34. Found: C 55.07, H 5.41. The enantioselectivity was
determined to be 95% ee by HPLC analysis, using a chiral
column (Chiralcel OB-H, hexane/i-PrOH ) 40/1, flow rate )
0.5 mL/min): tmajor ) 43.3 min, tminor ) 52.9 min. Specific
rotation of the syn isomer (white solids, 37% ee): [R]29D +49.5
(c 1.0, CHCl3). Elemental Anal. Calcd for C13H15O2Br: C 55.14,
H 5.34. Found: C 55.04, H 5.39. The enantioselectivity was
determined to be 37% ee by HPLC analysis, using a chiral
column (Chiralcel OD-H, Daicel Chemical Industries, Ltd.,
hexane/i-PrOH ) 40/1, flow rate ) 0.5 mL/min): tmajor ) 45.8
isomer (90% ee): [R]28 +7.1° (c 1.0, CHCl3). Elemental Anal.
D
Calcd for C17H18O2: C 80.28, H 7.13. Found: C 80.29, H 7.31.
Specific rotation of the syn isomer (48% ee): [R]29 +40.1°
D
(c 1.0, CHCl3). Elemental Anal. Calcd for C17H18O2: C 80.28,
H 7.13. Found: C 80.27, H 7.27. Other spectral data (TLC,
IR, 1H NMR, and 13C NMR) of the anti and syn isomers
indicated good agreement with reported data.13b,c
1
min, tminor ) 58.9 min. Spectral data (TLC, IR, H NMR, and
13C NMR) of the anti and syn isomers indicated good agree-
ment with reported data.8c,29c,30
2-[H y d r o x y (4-m e t h o x y p h e n y l)m e t h y l]c y c lo h e x a -
n on e (En tr y 4 in Ta ble 8).29 The anti (R*,S*)/syn (R*,R*)
ratio was determined to be 91/9 by 1H NMR analysis. The
enantioselectivities of the anti and syn isomers were deter-
mined to be 93% ee and 19% ee, respectively, by HPLC
analysis, using a chiral column (Chiralcel OD-H, hexane/i-
PrOH ) 20/1, flow rate ) 0.25 mL/min): tsyn-major ) 53.0 min,
tsyn-minor ) 55.8 min, tanti-major ) 70.2 min, tanti-minor ) 99.8 min.
2-(1-Hyd r oxy-3-p h en ylp r op yl)cycloh exa n on e (En tr y 6
in Ta ble 8).13b,c The anti (R*,R*)/syn (R*,S*) ratio was
1
determined to be 79/21 by H NMR analysis. The enantiose-
lectivities of the anti and syn isomers were determined to be
83% ee and 57% ee, respectively, by HPLC analysis, using a
chiral column (Chiralcel OD-H and AD, hexane/i-PrOH ) 20/
1, flow rate ) 0.5 mL/min): tanti-major ) 45.0 min, tsyn-minor
)
Specific rotation of the anti isomer (93% ee): [R]29 +19.2°
47.1 min, tanti-minor ) 51.2 min, tsyn-major ) 56.8 min. Observed
D
[R]D value of the product: [R]26 -11.8 (c 1.0, CHCl3; data
(c 1.0, CHCl3). Elemental Anal. Calcd for C14H18O3: C 71.77,
D
obtained on a 79:21 mixture of anti and syn isomers). Elemen-
tal Anal. Calcd for C14H18O3: C 77.55, H 8.68. Found: C 77.35,
H 8,84. Other spectral data (TLC, IR, 1H NMR, and 13C NMR)
of the anti and syn isomers indicated good agreement with
reported data.13b,c
H 7.74. Found: C 71.70, H 7.86. Specific rotation of the syn
isomer (19% ee): [R]27 +9.8° (c 1.0, CHCl3). Elemental Anal.
D
Calcd for C14H18O3: C 71.77, H 7.74. Found: C 71.61, H 7.78.
1
Other spectral data (TLC, IR, H NMR, and 13C NMR) of the
anti and syn isomers indicated good agreement with reported
data.29
Note Ad d ed a fter ASAP P ostin g. There was an
error in the E/Z ratio of the first entry in Table 6, an
erroneous graphic in Table 6, an error in the spelling of
trimethoxysilyl enol ether in Condition B of Table 7, and
other minor typographical errors in the version posted
J une 19, 2003; the corrected version was posted J une 20,
2003.
2-[(4-Br om oph en yl)h ydr oxym eth yl]cycloh exan on e (En -
tr y 5 in Ta ble 8).8c,29c,30 The anti (R*,S*)/syn (R*,R*) ratio
was determined to be 92/8 by 1H NMR analysis. Specific
(28) (a) Ando, A.; Shioiri, T. Tetrahedron 1989, 45, 4969. (b) Ando,
A.; Tatematsu, T.; Shioiri, T. Chem. Pharm. Bull. 1991, 39, 1967. (c)
Heathcock, C. H.; Buse, C. T.; Kleschick, W. A.; Prirung, M. C.; Sohn,
J . E.; Lampe, J . J . Org. Chem. 1980, 45, 1066.
(29) (a) Nakamura, E.; Shimizu, M.; Kuwajima, I.; Sakata, J .;
Yokoyama, K.; Noyori, R. J . Org. Chem. 1983, 48, 932. (b) Kobayashi,
S.; Hachiya, I. J . Org. Chem. 1994, 59, 3590. (c) Yanagisawa, A.;
Asakawa, K.; Yamamoto, H. Chirality 2000, 12, 421.
(30) Huang, Y.-Z.; Chen, C.; Shen, Y. J . Chem. Soc., Perkin Trans.
1 1988, 2855.
Ack n ow led gm en t. We thank Takasago Interna-
tional Corporation for its generous gift of (R)-SEGPHOS,
(S)-DM-BINAP, (R)-H8-BINAP, and (R)-H8-DM-BINAP.
J O020691C
J . Org. Chem, Vol. 68, No. 14, 2003 5601