Catalytic Asymmetric Vinylogous Mukaiyama-Aldol (CAVM) reactions: The enolate activation

Article abstract of DOI:10.1021/jo015567s

The Catalytic Asymmetric Vinylogous Mukaiyama (CAVM) reactions of various aldehydes with dienolate 1 using different enolate activations (CuF·(S)-TolBinap, t-BuOCu·(S)-Tol-Binap, and various chiral nonracemic ammonium fluorides derived from cinchona alkal

Full text of DOI:10.1021/jo015567s

J . Org. Chem. 2001, 66, 4293-4298
4293
Ca ta lytic Asym m etr ic Vin ylogou s Mu k a iya m a -Ald ol (CAVM)
Rea ction s: Th e En ola te Activa tion
Guillaume Bluet and J ean-Marc Campagne*
Institut de Chimie des Substances Naturelles, CNRS, F-91198 Gif-sur-Yvette, France
J ean-Marc.Campagne@icsn.cnrs-gif.fr
Received February 13, 2001
The Catalytic Asymmetric Vinylogous Mukaiyama (CAVM) reactions of various aldehydes with
dienolate 1 using different enolate activations (CuF‚(S)-TolBinap, t-BuOCu‚(S)-Tol-Binap, and
various chiral nonracemic ammonium fluorides derived from cinchona alkaloids) are described.
These reactions proved to be highly regioselective leading exclusively to the R-aldol products in
good yields and poor to good enantioselectivities.
In tr od u ction
Sch em e 1
The vinylogous aldol reaction,1 the reaction of an
aldehyde with a γ-dienolate, allows the direct formation
of 1,5 difunctional compounds (Scheme 1). However, the
development of this reaction was longer hampered by the
formation of a mixture of both R (kinetic) and γ (ther-
modynamic) products (Scheme 2).2
These problems of regioselectivity in direct vinylogous
aldol reactions were, only very recently, overcome by
3
using the bulky Lewis acid ATPH. Another solution has
previously appeared, in the early seventies, using silyl
dienolates as nucleophiles. In the presence of a suitable
Lewis acid, these nondirect vinylogous Mukaiyama-aldol
reactions allowed for the exclusive formation of the
γ-aldol products (Scheme 2).4
Although the vinylogous Mukaiyama-aldol reactions
have found wide interest in the total synthesis of natural
products,5 to the best of our knowledge, no asymmetric
version of this reaction was described when this work
was initiated. However, related, but mechanistically quite
different, asymmetric and catalytic asymmetric vinylo-
-10
Sch em e 2
1
,11
gous aldol reactions using aceto-acetate derivatives,
1
,12
or cyclic dienolates,
and asymmetric vinylogous Man-
nich reactions1 have been previously reported.
,13
(
1) For a comprehensive review, see: Casiraghi, G.; Zanardi, F.;
Appendino, G.; Rassu, G. Chem. Rev. 2000, 100, 1929.
2) (a) Dugger, R. W.; Heathcock, C. H. J . Org. Chem. 1980, 45, 1181.
b) Lei, B.; Fallis, A. Can. J . Chem. 1991, 69, 1450.
3) ATPH ) aluminium tris(2,6-diphenyl)phenoxide. Saito, S.; Yama-
moto, H. Chem. Eur. J . 1999, 5, 1959.
4) (a) Mukaiyama, T.; Ishida, A. Chem. Lett. 1975, 319. (b) Fleming,
I.; Goldhill, J .; Paterson, I. Tetrahedron Lett. 1979, 34, 3205.
(
(
(
(
(
5) Evans, D. A.; Cameron, W. C. J . Am. Chem. Soc. 1993, 115, 4497.
(6) Patron, A. P.; Richter, P. K.; Tomaszewski, M. J .; Miller, R. A.;
Nicolaou, K. C. J . Chem. Soc., Chem. Commun. 1994, 1147.
(
(
7) Paterson, I.; Smith, J . D. J . Org. Chem. 1992, 57, 3261.
8) Barloy-Da Silva, C.; Benkouider, A.; Pale, P. Tetrahedron Lett.
2
000, 41, 3077.
9) Moun e´ , S.; Niel, G.; Busquet, M.; Eggleston, I.; J ouin, P. J . Org.
Chem. 1997, 62, 3332.
10) Christmann, M.; Bhatt, U.; Quitschalle, E. C.; Kalesse, M.
Angew. Chem., Int. Ed. 2000, 39, 4364.
11) (a) Evans, D. A.; Kozlowski, M. C.; Murry, J . A.; Burgey, C. S.;
Campos, K. R.; Connell, B. T.; Staples, R. J . J . Am. Chem. Soc. 1999,
(
(
In the aim of constructing the side-chain of Octalactin
A,14 we embarked on the catalytic asymmetric vinylogous
(
1
5
Mukaiyama-aldol (CAVM) using silyl-dienolate 1. In a
previous communication,16 we have reported our prelimi-
nary results on catalytic asymmetric vinylogous reactions
using either an aldehyde or enolate activation (Scheme
3).
1
1
1
21, 669. (b) Singer, A. R.; Carreira, E. M. J . Am. Chem. Soc. 1995,
17, 12360. (c) Kr u¨ ger, J .; Carreira, E. M. J . Am. Chem. Soc. 1998,
20, 837. (d) Pagenkopf, B. L.; Kr u¨ ger, J .; Stojanovic, A.; Carreira, E.
M. Angew. Chem., Int. Ed. 1998, 37, 3124. (e) Kim, Y.; Singer, A. R.;
Carreira, E. M. Angew. Chem., Int. Ed. 1998, 37, 1261. (f) Kr u¨ ger, J .;
Carreira, E. M. Tetrahedron Lett. 1998, 39, 7013.
1
0.1021/jo015567s CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/12/2001

4
294 J . Org. Chem., Vol. 66, No. 12, 2001
Bluet and Campagne
Sch em e 3
F igu r e 1. Influence of the temperature on yield (O) and
enantioselectivity (9) in the model reaction of 1 with benzal-
dehyde in the presence of 10% of CuF‚(S)-TolBinap.
Sch em e 4
Ta ble 1. CAVM Rea ction s of Ald eh yd es w ith 1 Usin g
1
0% of Cu F ‚(S)-Tol-Bin a p a t Room Tem p er a tu r e
aldehyde
benzaldehyde
-naphthaldehyde
cinnamaldehyde
isobutyraldehyde
product
yield (%)
ee (%)
γ/R ratio
2a
2b
2c
2d
80
70
35
68
70
48
56
77
100:0
100:0
100:0
100:0
2
In this paper, we would like to report our efforts and
results in developing asymmetric catalytic systems for
the enolate activation.
Resu lts a n d Discu ssion
When this project was initiated, our major concerns
were (1) the possibility of R-alkylation when generating
a metal-dienolate (vide supra) and (2) the asymmetric
induction from the dienolate to the prochiral aldehyde.
To our delight, using Carreira’s catalyst CuF‚(S)-Tol-
Binap gave 75% ee but in 42% yield, and among different
bis-oxazolines, the best results were obtained with bis-
(isopropyloxazolinyl)pyridine but with bad efficiency:
3
5% yield and 15% ee) or conditions (solvents, concentra-
Binap,1 the γ-aldol products were obtained exclusively
1c
17
tion, ligand amount, etc.) proved to be unsuccessful.
As shown in Figure 1, temperature has a small effect
on the enantioselectivities, but yields decreased rapidly
at temperature below -30 °C. The optimum temperature
between enantioselectivities and chemical efficiency was
found to be approximately 0 °C.
at room temperature in good yields and enantioselectivi-
ties with both aromatic and aliphatic aldehydes (Table
1
).
With cinnamaldehyde, the yield proved to be rather
low (35%) due to the presence in the crude material of a
1
1
:1 ratio ( H NMR) of 2c and the unstable aldehyde 3
To determine the absolute configuration of adducts 2,
compound 2a (RdPh) was converted in two steps into the
previously described compound 4.18 A rotation of -44.3
which results from the 1,4 addition of the silyl-dienolate
on cinnamaldehyde.
(for 70% ee) compares favorably with the rotation of
+
63.8 for the enantiomerically pure (R) compound.
Consequently, adducts 2a -c obtained with CuF‚(S)-Tol-
Binap were tentatively assigned to the (S) configuration
(
Scheme 4).
Examining the relationship19 between ee (ligand) and
ee (product), a small negative nonlinear effect (-)-NLE
was observed for low ee (ligand) and a very slight positive
Attempts to optimize the reaction either by changing
the ligand (in the model reaction with benzaldehyde,
(
15) Fleming, I.; Leslie, C. P. J . Chem. Soc., Perkin Trans. 1 1996,
(12) (a) Pichon, M.; J ullian, J .-C.; Figad e` re, B.; Cav e´ , A. Tetrahedron
1198.
Lett. 1998, 39, 1755. (b) Dudot, B.; Micouin, L.; Baussane, I.; Royer, J .
Synthesis 1999, 688. (c) Szlosek, M.; Figad e` re, B. Angew. Chem., Int.
Ed. 2000, 39, 1799-1801. (d) Casiraghi, G.; Rassu, G.; Zanardi, F.;
Battistini, L. Adv. Asymmetric Synth. 1998, 3, 113-189.
(16) Bluet, G.; Campagne, J .-M. Tetrahedron Lett. 1999, 40, 221-
222.
(17) The absence of R-alkylation products was checked by NMR on
2
5a
the crude material by synthesising
products.
the corresponding R-aldol
(
13) (a) Bur, S. C.; Martin, S. F. Org. Lett. 2000, 22, 3445. (b) Dudot,
B.; Royer, J .; Sevrin, M.; George, P. Tetrahedron Lett. 2000, 22, 4367.
14) (a) Tapiolas, D. M.; Roman, M.; Fenical, W.; Stout, T. J .; Clardy,
(18) (a) St u¨ hmer, W.; Frey, H.-H. Arch. Pharm. Ber. dtsch. Pharm.
Ges. 1953, 286, 26. (b) Santaniello, E.; Ferraboschi, P.; Grisenti, P.;
Manzocchi, A.; Trave, S. Gazz. Chim. Ita. 1989, 119, 581. (c) Reed, P.
E.; Katzenellenbogen, J . A. J . Med. Chem. 1991, 34, 1162.
(19) (a) Girard, C.; Kagan, H. B. Angew. Chem., Int. Ed. Engl. 1998,
37, 2923. (b) Heller, D.; Drexler, H.-J .; Fischer, C.; Buschmann, H.;
Baumann, W.; Heller, B. Angew. Chem., Int. Ed. 2000, 39, 495. (c)
Girard, C.; Kagan, H. B. Can. J . Chem. 2000, 78, 816. (d) Mikami, K.;
Terada, M.; Korenaga, T.; Matsumoto, Y.; Ueki, M.; Angelaud, R.
Angew. Chem., Int. Ed. 2000, 39, 3532 and references cited therein.
(
J . J . Am. Chem. Soc. 1991, 113, 4682. (b) Buszek, K. R.; Sato, N.; J eong,
Y. J . Am. Chem. Soc. 1994, 116, 5511. (c) McWilliams, J . C.; Clardy,
J . J . Am. Chem. Soc. 1994, 116, 8378. (d) Hulme, A. N.; Howells, G.
E. Tetrahedron Lett. 1997, 38, 8245. (e) Komada, M.; Matsushita, M.;
Terada, Y.; Takeuchi, A.; Yoshio, S.; Fukuyama, Y. Chem. Lett 1997,
1
(
1
17. (f) Andrus, M. B.; Argade, A. B. Tetrahedron Lett. 1996, 37, 5049.
g) Bach, J .; Berenguer, R.; Garcia, J .; Villarrasa, J . Tetrahedron Lett.
995, 36, 3425.

CAVM Reactions
J . Org. Chem., Vol. 66, No. 12, 2001 4295
Sch em e 5
F igu r e 2. Relationship between ee (Tol-Binap) and ee (2a )
in the CAVM reaction between benzaldehyde and 1 in the
presence of 10% of CuF‚(S)-Tol-Binap.
nonlinear effect (+)-NLE was observed for the higher
(>40%) ee (ligand) (Figure 2).
Such an intriguing shape has been previously ob-
served,20 and is supported by a mathematical calculation
1
9a
described by Kagan and co-workers, which suggests a
nonlinear curve for ML complexes. Such behavior im-
plies a rather complicated mechanism whereby some
aggregation is believed to take place.
4
catalyst but surprisingly the enantioselectivity was much
lower (50% ee) than that observed using CuF‚(S)-Tol-
Binap) (70% ee). This result highlights the fact that CuF‚
(S)-Tol-Binap (or salts generated during its formation)
does not only play the role of precatalyst but seems to
interfere in the catalytic cycle.
We attempted to modify the structure of the dienolate
by increasing the size of the silyl group hoping to change
the course of the reaction. The synthesis of higher
derivatives of 1 proved to be difficult, and only the
triethylsilyl derivative 1b could be isolated in reasonable
yield. Catalytic asymmetric vinylogous Mukaiyama-aldol
reactions using this dienolate were somewhat slower
(with benzaldehyde, the vinylogous aldol product was
isolated, after 24 h, in 40% yield) and a small enantio-
selectivity decrease (60% ee) could be observed.
Nevertheless, according to the mechanism described
by Carreira for the asymmetric aldol reactions of aceto-
acetate derivatives,1 a catalytic cycle can be postulated
for the CAVM reactions.
1d
In the catalytic cycle, CuF‚(S)-Tol-Binap (generated in
2
1
2
situ from TBAT, Cu(OTf) , and (S)-Tol-Binap) acts as
a precatalyst and generates the copper dienolate I which
is the real catalytic species. This species, or further
species generated thereof, can then react with the alde-
hyde to create the vinylogous copper alcoholate II as a
mixture of two diastereomers IIa and IIb. This alcoholate
further reacts with the silyl dienolate to regenerate the
catalytic species I and the vinylogous aldol product is
formed protected as the TMS ether (Scheme 5).
However, compared to Carreira’s reactions,1 two
major changes should be pointed out. First, the reactions
are run at room temperature, under thermodynamic
conditions: consequently the influence of the retro-aldol
1d
2
2
in the enantiodiscrimination can be questioned. Second,
contrary to Carreira’s dienolate,1
1c-f
there is no oxygen
atom present in our dienolate that could participate in
transmitting the chiral information from the copper
dienolate to the prochiral aldehyde.
The influence of the retro-aldol reaction in the enan-
tiodiscrimination was then questioned. According to the
isoinversion principle, when two transient diastereo-
meric species are in a dynamic equilibrium, the stereo-
selectivity can be controlled at two levels (Scheme 6). At
the “first selection level” the two diastereomeric inter-
mediates [Dia1] and [Dia2] (in our case, IIa and IIb) are
formed from the reaction between the prochiral starting
material B and the chiral substrate A* (in our case, the
prochiral aldehyde and the copper dienolate I). At the
22
To gain an insight into the reaction mechanism and
understand the factors that govern the enantiodiscrimi-
nation, we tried to play around the catalytic cycle.
2
1
First, since the synthesis of TBAT was reported to
be quite unreliable,2 we tried to develop a more conve-
nient precatalyst for these reactions. It was found that
tBuO‚Cu (S)-tol-Binap23 (generated in situ from NaOtBu,
CuCl and (S)-tol-Binap) proved to be an efficient pre-
1b
“second selection level” competition between conversion
of the intermediates to the products Ent1 and Ent2 and
then reversion to the starting materials (A* and B) can
modify the initial selection.
Usually the iso-inversion principle can be observed by
plotting an Eyring diagram (ln(Ent1/Ent2) vs 1/T).
However in our case, the temperature domain (-30 °C
(
20) (a) Puchot, C.; Samuel, O.; Du n˜ ach, E.; Zhao, S.; Agami, C.;
Kagan, H. B. J . Am. Chem. Soc. 1986, 108, 2353. (b) Tanaka, K.;
Matsui, J .; Suzuki, H. J . Chem. Soc., Perkin Trans. 1 1993, 153.
(
21) TBAT) tetrabutylammonium triphenyldifluorosilicate. (a) Pilcher
S. A.; Ammon, H. L.; Deshong P. J . Am. Chem. Soc. 1995, 117, 5166.
b) Handy, C. J .; Lam, Y.-F.; Deshond, P. J . Org. Chem. 2000, 65, 3542.
22) (a) Buschman, H.; Scharf, H.-D.; Hoffmann, N.; Esser, P. Angew.
(
(
Chem., Int. Ed. Engl. 1991, 30, 477. (b) Hale, K. J .; Ridd, J . H. J . Chem.
Soc., Perkin Trans. 2 1995, 357. (c) Hale, K. J .; Ridd, J . H. J . Chem.
Soc., Perkin Trans. 2 1995, 1601. (d) Gypser, A.; Norrby, P. J . Chem.
Soc., Perkin Trans. 2 1997, 939.
(23) Appella, D. H.; Moritani, Y.; Shintani, R.; Ferreira, E. M.;
Buchwald, S. L. J . Am. Chem. Soc. 1999, 121, 9473.

4
296 J . Org. Chem., Vol. 66, No. 12, 2001
Bluet and Campagne
Sch em e 6
Sch em e 7
Ta ble 2. CAVM Rea ction s of Isobu tyr a ld eh yd e w ith 1
Usin g 10% of Va r iou s Ch ir a l Non r a cem ic Am m on iu m
F lu or id es a t Room Tem p er a tu r e
to 40 °C) is too small to get any clear conclusion.24
Nevertheless, the possibility that the enantiodiscrimi-
nation could be controlled during the “second selection
level” led us to investigate the case where chiral non-
racemic “naked” dienolates are involved. To test this
hypothesis, we turned our attention to chiral nonracemic
ammonium fluorides derived from cinchona alkaloids.26
Ammonium fluoride 5 derived from cinchonidine was first
synthesized. The CAVM reaction of isobutyraldehyde
with dienolate 1 in the presence of 10% of catalyst 5 led
to the formation of the vinylogous aldol product 2d in
configuration of
ammonium
fluoride
the major
enantiomer
yield (%) γ/R ratio
ee (%)
5
6
7
8
9
0
1
2
3
70
25
15
<10%
54
61
42
35
30
100: 0
100: 0
100: 0
100: 0
100: 0
100: 0
100: 0
100: 0
100: 0
20 (30)a
26
18
n. d.
17
14
11
18
11
(S)
(S)
(S)
(S)
(S)
(S)
(S)
(R)
(R)
2
5
1
1
1
1
7
0% yield and 20% ee thus confirming our initial hy-
a
Reaction carried out at 0 °C.
pothesis (Scheme 7).
This somewhat encouraging result led us to tune the
electronic and steric properties of the catalyst. Conse-
quently catalysts 6-10 derived from cinchonidine, 11
derived from quinine, 12 derived from cinchonine and 13
derived from brucine were synthesized.
selectivity could not be raised to useful levels (Table 2).
The best result, with isobutyraldehyde, was obtained
with catalyst 5 in 30% ee, performing the reaction at 0
2
7
°C. The ammonium fluoride 12 derived from cinchonine,
pseudo-enantiomer of 5, indeed gave the opposite enan-
tiomer.
Quite surprisingly, the corresponding ammonium hy-
droxide 14 was also found to be an excellent catalyst
(quantitative yields in the reaction of 1 with isobutyral-
dehyde) for these reactions but again with low levels of
enantioselectivity (<30% ee).
Con clu sion
In conclusion, among the different catalytic asymmetric
enolate activations (CuF‚(S)-TolBinap, t-BuOCu‚(S)-Tol-
Binap, and various chiral nonracemic ammonium fluo-
rides derived from cinchona alkaloids) tested, the Car-
reira’s catalyst CuF‚(S)-Tol-Binap proved to be the more
efficient in terms of enantioselectivity and led us to
propose an efficient synthesis of the Octalactin side-chain
constructed in five steps starting from isobutyraldehyde
However, by using these catalysts with different
structural, steric, and electronic properties, enantio-
(
1
Scheme 8).28 The key step was a CAVM reaction, using
0% Carreira’s catalyst at 0 °C, to introduce the C13
(24) To suppress the second step (copper alcoholate quenching with
the silyldienolate) and see the influence on the enantioselectivity, the
chirality in 80% ee and 90% yield.
reaction was run with a stoichiometric amount of precatalyst tBuOCu‚
(S)-Tol-Binap, and, indeed, a small influence on the enantioselectivity
could be observed (60% ee to be compared to the 50% ee obtained with
0% of the precatalyst) showing the negative influence of this second
step on the global enantioselectivity.
25) (a) Hertler, W. R.; Reddy, G. S.; Sogah, D. Y. J . Org. Chem.
988, 53, 3532. (b) Noyori, R.; Nishida, I.; Sakata, J . J . Am. Chem.
Soc. 1981, 103, 2106. (c) Noyori, R.; Nishida, I.; Sakata, J . J . Am. Chem.
Soc. 1983, 105, 1598.
(26) Ando, A.; Miura, T.; Tatematsu, T.; Shioiri, T. Tetrahedron Lett.
1993, 34, 1507 and references cited herein.
(27) During the course of this work, a highly enantioselective
Mukaiyama-aldol reaction using chiral ammonium fluoride 8 was
described: Horikawa, M.; Busch-Petersen J .; Corey, E. J . Tetrahedron
Lett. 1999, 40, 3843.
1
(
1
(28) Bluet, G.; Campagne, J .-M. Synlett 2000, 221.

CAVM Reactions
J . Org. Chem., Vol. 66, No. 12, 2001 4297
Sch em e 8
lyst. A mixture of copper (II) trifluoromethanesulfonate (0.05
mmol, 18.4 mg, 10%) and (S)-Tol-Binap (0.055 mmol, 38 mg,
1
1%) in 10 mL of THF was strirred for 15 min (a clear yellow
2
1a
solution was obtained). A solution of TBAT (0.1 mmol, 55.6
mg, 20%) in 0.5 mL of THF was added dropwise and after 15
min a bright yellow solution was obtained. Then, 1-ethoxy-1-
(trimethylsilyloxy)-2-methyl-1,3 butadiene 1 (0.75 mmol, 150
mg, 1.5 equiv) was added dropwise (the resulting solution
turned to red-brown) followed by the aldehyde (0.5 mmol, 1
equiv) slowly added and the reaction mixture was stirred for
2
2
4 h at room temperature. After quenching (MeOH/HCl 9:1
0 min), the reaction mixture was diluted with a satured
aqueous solution of NH
organic layers were washed with brine, dried over MgSO
4
Cl and extracted with ether. The
, and
4
concentrated in vacuo. The crude residue was then purified
by flash chromatography on silicagel (pentane/EtOAc, 80/20).
(
S)-E t h yl-2-m et h yl-5-h yd r oxy-5-p h en yl-2-p en t en oa t e
2
5
(
2a ). 80% yield, clear yellow oil; [R]
CHCl ); 70% ee (HPLC: chiralcel OJ , hexane/2-propanol 95:
3
D
) -26.2 (c ) 0.56,
0
5, flow rate 1 mL/min, major enantiomer 19.7 min, minor
1
13
enantiomer 23.9 min). The H, C NMR data were in ac-
cordance with the literature.2
5a
(
S)-Eth yl-2-m eth yl-5-h yd r oxy-5-n a p h th a len -2-yl-2-p en -
The study of CAVM reactions involving other substi-
tuted and nonsubstituted silyldienolates is currently
under investigation.
25
ten oa te (2b). 70% yield, yellow oil; [R]
CHCl ); 48% e.e. (HPLC: chiralcel OD, hexane: 2-propanol
90:10, flow rate 1 mL/min, major enantiomer 18.8 min, minor
enantiomer 21.6 min); IR (KCl) 3445, 2980, 1703, 1698, 1651,
279, 1080, 748 cm ; H NMR δ (200 MHz) 1.28 (t, J ) 7.0
D
) -16.0 (c ) 1,
3
-
1
1
1
Exp er im en ta l Section
Hz, 3H), 1.82 (s, 3H), 2.17 (bs, OH), 2.73 (m, 2H), 4.18 (q, J )
7.0 Hz, 2H), 4.98 (m, 1H), 6.86 (m, 1H), 7.49 (m, 3H), 7.82 (m,
4H); 13C NMR δ (75 MHz) 12.5, 14.0, 38.2, 60.3, 73.4, 123.5,
Gen er a l. Unless otherwise specified, the reactions were
carried out in oven-dried glassware under an argon atmo-
1
13
sphere. H and C NMR spectra were recorded at 300 and 75
MHz, respectively, or at 250 MHz, in CDCl as solvent:
124.3, 125.8, 126.1, 127.5, 127.8, 128.2, 131.0, 134.1 (2C),
+
3
137.1, 140.9, 167. 7; MS (CI) m/e 302 (M + NH
(38%), 267 (100%). Anal. Calcd for C18
Found: C, 75.88; H, 7.25;
(S )-E t h yl-2-m e t h yl-5-h yd r oxy-5-cin n a m yl-2-p e n t e -
n oa te (2c). 35% yield, yellow oil; [R]
CHCl ); 56% ee (HPLC: chiralcel OD hexane/2-propanol 80:
4
, 92%), 268
chemical shifts are given in ppm. Column chromatography was
performed on silica gel 230-400 mesh. THF was distilled from
sodium/benzophenone. Diisopropylamine and Chlorotrimeth-
20 3
H O : C, 76.03; H, 7.09.
2
5
ylsilane were freshly distilled over CaH
II) trifluoromethanesulfonate, purchased from ACROS was
dried over P under vacuum prior to use. (S)-Tol-Binap was
purchased from STREM. TBAT was synthesized according to
2
prior to use. Copper-
D
) -37.0 (c ) 1.62,
(
3
2
O
5
20, flow rate 1 mL/min, major enantiomer 12.0 min, minor
enantiomer 8.1 min); IR (KCl) 3446, 2982, 1706, 1649, 1369,
2
1
-1
1
the procedure described by Deshong (also commercialy avail-
able from Aldrich). Elemental analyses were carried out by
1277, 1097 cm ; H NMR δ (250 MHz) 1.22 (t, J ) 7.1 Hz,
3H), 1.66 (bs, OH), 1.82 (s, 3H), 2.48 (m, 2H), 4.13 (q, J ) 7.1
Hz, 2H), 4.40 (q, J ) 6.4 Hz, 1H), 6.19 (dd, J ) 6.52 and 15.9
Hz, 1H), 6.57 (d, J ) 15.8 Hz, 1H), 6.78 (m, 1H), 7.15-7.35
(m, 5H); 13C NMR δ (75 MHz) 12.8, 14.3, 36.8, 60.6, 72.0, 126.6,
127.9, 128.6 (2C), 130.4 (2C), 130.9, 131.3, 136.4, 137.0, 168.0;
MS (CI) m/e 261 (M + H , 25%), 243 (100%), 157 (23%). Anal.
Calcd for C16
7.96.
“laboratoire de micro-analyse ICSN - Gif/Yvette”. IR Spectra
were recorded with an FTIR spectrometer. Mass spectra were
recorded by chemical ionization (CI) on a AEI MS-9 mass
spectrometer with isobutane and otherwise as indicated.
Optical rotations were determined operating at the sodium D
line. HPLC analyses were conducted using CHIRALCEL OD
or OJ column with solvent mixtures of hexane/2-propanol and
flow rates as indicated.
+
20 3
H O : C, 73.82; H, 7.74. Found: C, 73.65; H,
(S)-Eth yl-2-m eth yl-5 h ydr oxy-5-isopr opyl-2-pen ten oate
2
5
1
-Eth oxy-1-(tr im eth ylsilyloxy)-2-m eth yl-1,3 Bu ta d ien e
(2d ). 68% yield, yellow oil; [R]
77% ee (HPLC: chiralcel OD, hexane/2-propanol 98:2, flow rate
1 mL/min, major enantiomer 10.7 min, minor enantiomer 12.6
min); IR (KCl): 3451, 1709, 1648, 1279 cm ; H NMR δ (200
MHz) 0.92 (∼d, J ) 6.8 Hz, 6H), 1.26 (t, J ) 7 Hz, 3H), 1.68
(m, 1H), 1.82 (s, 3H), 1.98 (s, OH), 2.31 (m, 2H), 3.53 (m, 1H),
4.16 (q, J ) 7 Hz, 2H), 6.82 (m, 1H). 13C NMR δ (75 MHz)
12.5, 14.1, 17.1, 18.6, 33.2, 33.5, 60.4, 71.1, 129.2, 138.4, 168.1;
D
3
) -16.1 (c ) 0.97, CHCl );
(
1). To a solution of diisopropylamine (22 mmol, 3 mL) in THF
n
(
50 mL) at -20 °C was added BuLi (22 mmol, 14 mL, 1.6 M
-
1 1
in hexane). After 30 min at -20 °C, the solution was cooled to
-
78 °C and HMPA (22 mmol, 3.8 mL) was added slowly. After
0 min, ethyl trans-but-2-enoate (20 mmol, 2.5 mL) was added
3
dropwise. The mixture was stirred for a further 15 min and
quenched with methyl iodide (22 mmol, 1.4 mL). The solution
was allowed to warm to 0 °C over 1h and then recooled to -78
+
MS (CI) m/e 201 (M + H , 100%), 183 (41%), 155 (24%), 146
(12%), 73 (45%), 59 (85%), 43 (40%). Anal. Calcd for C11H O :
20 3
°
C. A solution of LDA prepared as above at 0 °C was added
dropwise over 20 min at -78 °C via a syringe pump. After 15
min, the mixture was quenched with chlorotrimethylsilane (30
mmol, 4 mL) in THF (4 mL) added over 15 min via a syringe
pump. The solution was allowed to warm to room temperature
and stirred for 1.5 h and the solvent was evaporated in vacuo
in a cold bath. Then pentane (100 mL) was added to the
residue, and the resulting mixture was filtered on Celite to
remove the precipitated HMPA-lithium chloride complex and
evaporated in vacuo. The residue was distilled under reduced
pressure using a Kugelrhor apparatus (40-45 °C/1.5 mmHg)
to give 1 as an inseparable mixture of isomers Z and E
C, 65.97; H, 10.07; O, 23.97. Found: C, 65.71; H, 10.10; O,
23.74.
P r ep a r a tion of (S)-3-(Acetyloxy)-3-p h en ylp r op a n oic
Acid (4). To a solution of compound 2a (0.34 mmol, 80 mg,
70% ee) in acetic anhydride (0.5 mL) was added pyridine (0.5
mL) dropwise. The reaction was monitored by TLC on silica
gel (pentane/ethyl acetate, 80/20). After 1.5 h, the mixture was
diluted in toluene and evaporated in vacuo (three times). The
corresponding product, (S)-ethyl-2-methyl-5-(acetyloxy)-5-
phenyl-2-pentenoate, was obtained in quantitative yield and
used without further purification. This product (0.115 mmol,
(
70:30) (2.5 g, 63%, clear yellow oil). The spectroscopic data of
31.7 mg) was diluted in CCl
then distilled water (0.6 mL) was added. To this mixture was
added RuCl ‚3H O (6% molar in water, 70 µL) and NaIO (4.2
equiv). The mixture was then heated at 60 °C for 24 h. After
4 3
(0.4 mL) and CH CN (0.4 mL),
1
5
the compound 1 were in accordance with the litterature.
Typ ica l Rea ction P r oced u r e for th e P r ep a r a tion of
3
2
4
Vin ylogou s Ald ol P r od u cts 2a -d Usin g Ca r r eir a ’s Ca ta -

4
298 J . Org. Chem., Vol. 66, No. 12, 2001
Bluet and Campagne
cooling, distilled water was added and the solution was
extracted with CH Cl (three times). The aqueous layer was
acidified with 1 M HCl and extracted with CH Cl . The
combined organic phases were dried over MgSO and evapo-
then with methanol. A solution of the cinchona ammonium
bromide or chloride (0.4 mmol) in methanol (10 mL) was slowly
passed through the column and the column then washed with
methanol. The eluent was neutralized until pH ) 7 with HF
and the solvents were removed in vacuo. The residue was
coevaporated with toluene three times and dried over P O
2 5
under vaccum overnight and the chiral nonracemic ammonium
fluorides were used without further purification.
2
2
2
2
4
rated in vacuo. Compound 4 was obtained as a cream-colored
solid in 45% yield (10.7 mg). The 1H NMR, IR, and mass
spectroscopy data were identical with those reported in the
1
8c
25
18a,b
1
25
literature. [R]
D
) -44.3 (c ) 0.97, MeOH), lit.
[R]
D
)
3
+
63.8 (c ) 5, MeOH) for the (R)-(+) pure enantiomer. C NMR
δ (75 MHz) 21.3, 41.2, 72.0, 126.7 (2C), 128.7 (2C), 128.9, 139.2,
Ack n ow led gm en t. We thank Prof. Pierre Potier for
his kind interest in this project. We are grateful to Prof.
H. B. Kagan for helpful discussion about the reaction
mechanism and nonlinear effects and to Dr. R. Weaving
for the revision of the manuscript.
1
70.1, 175.2.
Gen er a l P r oced u r e for th e P r ep a r a tion of th e Ch ir a l
Non r a cem ic Am on iu m F lu or id es (5-13). According to
2
6
-
Shiori, Amberlyst A-26 (Cl form, 1 g, 10 mol equiv) was
-
transformed into the OH form by passing 1 N NaOH until
complete exchange of the chloride anion was achieved. The
column was washed carefully with water until neutral and
J O015567S