Reaction of γ,γ-dialkoxyallylic zirconium species with aldehyde as protected acryloyl anion

Full text of DOI:10.1021/jo991107b

918
J . Org. Chem. 2000, 65, 918-921
Sch em e 1
Rea ction of γ,γ-Dia lk oxya llylic Zir con iu m
Sp ecies w ith Ald eh yd e a s P r otected
Acr yloyl An ion
Azusa Sato, Hisanaka Ito, and Takeo Taguchi*
Tokyo University of Pharmacy and Life Science,
1432-1 Horinouchi, Hachioji, Tokyo 192-0392, J apan
Received J uly 12, 1999
Introduction of the R,â-unsaturated carbonyl unit into
an organic molecule should be an important process due
to the synthetic usefulness of this functional group. One
efficient method for the introduction of such functional
group involves the carbon-carbon bond forming reaction
of heteroatom-containing allylic or allenic organometal-
lics as an R,â-unsaturated acyl anion equivalent.1-4 In
particular, as an acryloyl anion equivalent, 1-alkoxyal-
lenyllithium has been widely employed due to its high
reactivity with a variety of electrophiles and the further
utilization of the allenyl unit in the products including
the acidic hydrolysis to the vinyl ketone structure.5,6
Recently, we reported that the reaction of γ,γ-dialkoxy-
allylic zirconium species 2, generated in situ by the
reaction of orthoacrylic acid triethyl ester 17 with zir-
conocene-butene complex (“Cp2Zr”),8 with aromatic or
R,â-unsaturated aldehyde provides 1-substituted-2,2-
dialkoxy-3-buten-1-ol derivative 3, which is easily con-
verted to the vinyl ketone form 4 by treating with 50%
trifluoroacetic acid in CHCl3.9 Thus, in this reaction, γ,γ-
dialkoxyallylic zirconium species 2 acts as an acryloyl
anion equivalent (Scheme 1). Under the similar condi-
tions, however, the reaction of 2 with aliphatic aldehyde
in toluene gave only a complex mixture. Therefore,
further examination has been focused on the improve-
ment of reaction conditions for the reaction with aliphatic
aldehyde to reveal that the desired γ-adduct 3 can be
obtained in a good yield when the reaction is carried out
in the presence of 0.2-0.3 equiv of boron trifluoride
diethyl ether complex (BF3‚Et2O) and THF as a cosolvent.
We report herein the detail of these reactions.
The zirconium species 2 could be easily obtained in situ
by the reaction of orthoacrylic acid triethyl ester 17 with
zirconocene-butene complex (“Cp2Zr”)8 in toluene at
room temperature, possibly through the formation of
zirconacyclopropanes and the following â-elimination of
alkoxyl group (Scheme 1).10 The zirconium species 2 was
found to be thermally stable (at ca. 40 °C) under inert
atmosphere, and its γ,γ-dialkoxyallylic structure was
confirmed by the NMR experiments (1H, 13C, and NOE
experiment, in benzene-d6). As shown in Figure 1, an
olefinic and methylene protons were observed at 4.50
ppm (t, J ) 8.7 Hz) and 1.97 ppm (d, J ) 8.7 Hz),
respectively, and three nonequivalent methylene peaks
of ethoxy groups were at 4.04, 3.91, and 3.80 ppm. In
the 13C NMR spectrum, R, â, and γ carbons of allylic part
appeared at 34.3, 93.9, and 152.6 ppm, respectively.11
Results of the reaction of γ,γ-dialkoxyallylic zirconium
species 2 with aldehydes are summarized in Table 1. The
zirconium species 2, generated in situ by the reaction of
“Cp2Zr” with orthoacrylic acid triethyl ester 1 in toluene,
smoothly reacted with aromatic and R,â-unsaturated
aldehydes in the same solvent at room temperature to
give hydroxy acetal derivatives 3 in good yields (entries
1-6).9 With aliphatic aldehyde under the similar condi-
tions, however, the desired γ-adduct 3 was not obtained
and the detectable side-reaction was self-aldolization of
the aldehyde in the case of 3-phenylpropanal. We as-
sumed that the diethoxy substituents at the γ-position
would cause the decrease in the reactivity of the allylic
zirconium species 2. We reported that in the reaction of
γ-alkoxyallylic zirconium species with aldehyde improve-
* Corresponding author: Takeo Taguchi, Tokyo University of
Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-
0392, J apan. Tel: +81-426-76-3257. Fax: +81-426-76-3257. e-mail:
taguchi@ps.toyaku.ac.jp.
(1) (a) Murphy, W. S.; Wattanasin, S. Tetrahedron Lett. 1979, 1827.
(b) Fang, J .-M.; Chen. M.-Y.; Yang, W.-J . Tetrahedron Lett. 1988, 29,
5937. (c) J acobson, R. M.; Lahm, G. P.; Clader, J . W. J . Org. Chem.
1980, 45, 395. (d) J acobson, R. M.; Clader, J . W. Tetrahedron Lett. 1980,
21, 1205. (e) Andersen, N. H.; Denniston, A. D. J . Org. Chem. 1982,
47, 1145. (f) Bridges, A. J .; Thomas, R. D. J . Chem. Soc., Chem.
Commun. 1984, 694.
(2) γ, γ-Dialkoxyallylic lithium species; Seyferth, D.; Mammarella,
R. E.; Klein, H. A. J . Organomet. Chem. 1980, 194, 1.
(3) Reviews of R,â-unsaturated acyl anion equivalent based on the
heteroatom stabilized allylic and allenic anions: (a) Yamamoto, Y. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, 1991; Vol. 2, Chapter 1.2. (b) Yamamoto, H.
In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, 1991; Vol. 2, Chapter 1.3.
(4) Addition of R,â-unsaturated acylmetals as unmasked acyl anions
with aldehyde and ketone: (a) Harada, S.; Taguchi, T.; Tabuchi, N.;
Narita, K.; Hanzawa, Y. Angew. Chem., Int. Ed. 1998, 37, 1696 and
references cited. See also; (b) Hanzawa, Y.; Tabuchi, N.; Taguchi, T.
Tetrahedron Lett. 1998, 39, 8141.
(5) (a) Hoff, S.; Brandsma, L.; Arens, J . F. Recl. Trav. Chim. Pays-
Bas 1968, 87, 1179. (b) Hormuth, S.; Reissig, H. U. J . Org. Chem. 1994,
59, 67. (c) For a review of the chemistry of alkoxyallenes; Zimmer, R.
Synthesis 1993, 165. (d) For NMR and theoretical studies on 1-lithio-
1-methoxyallene: Lambert, C.; Schleyer, P. v. R.; Wu¨rthwein, E. U.
J . Org. Chem. 1993, 58, 6377.
(6) Electrophilic substitution of 3-(triethylsilyloxy)pentadienyl-
lithium proceeds in regioselective manner to give the γ-substituted
silyloxy diene, which is considered as a protected form of the vinyl
ketone. Oppolzer, W.; Snowden, R. L. Tetrahedron Lett. 1976, 4187.
(7) Stetter, H.; Uerdingen, W. Synthesis 1973, 207.
(10) (a) Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992,
33, 1295. (b) Ito, H.; Nakamura, T.; Taguchi, T.; Hanzawa, Y.
Tetrahedron 1995, 51, 4507.
(11) NMR spectra of various allylic zirconium species were reported.
See ref 10b and references cited.
(8) Negishi, E.; Cederbaum, F. E.; Takahashi, T. Tetrahedron Lett.
1986, 27, 2829.
(9) Ito, H.; Taguchi, T. Tetrahedron Lett. 1997, 38, 5829.
10.1021/jo991107b CCC: $19.00 © 2000 American Chemical Society
Published on Web 01/20/2000

Notes
J . Org. Chem., Vol. 65, No. 3, 2000 919
Sch em e 2
F igu r e 1.
Ta ble 1. Rea ction of Zir con iu m Sp ecies 2 w ith Ald eh yd e
entry
R
methoda
3
yield (%)b
Sch em e 3
1
2
3
4
5
6
7
8
9
Ph
A
A
A
A
A
A
B
B
B
B
B
3a
3b
3c
3d
3e
3f
3f
3g
3h
3i
91
96
90
90
58
66
76
70
74
48
78
2-naphthyl
2-furyl
(E)-PhCHdCH
CH2dC(CH3)
(E)-n-C3H7CHdCH
(E)-n-C3H7CHdCH
PhCH2CH2
n-C7H15
c-C6H11
PhCH2OCH2
10
11
3j
a
Method A: in toluene. Method B: in toluene-THF (2:1), 0.3
b
equiv of BF3‚Et2O. Isolated yield.
ment of the yield of the product was achieved by the
addition of Lewis acid such as BF3‚OEt2 presumably
through the activation of carbonyl group by coordina-
tion.10 After the survey of Lewis acid and solvent in the
reaction of 2 with aliphatic aldehyde, we found that
addition of 0.2-0.3 equiv of BF3‚OEt2 and THF as a
cosolvent works nicely giving rise to the desired product
3 (entries 7-11), although in the presence of more than
1 equiv of Lewis acid (BF3‚OEt2, TMSOTf or TiCl4) the
reaction of 2 with aldehyde in toluene resulted in the
different reaction pathway to give gem-dialkoxycyclopro-
pane derivatives.12 It should be noted that without the
addition of THF in the case of 0.2-0.3 equiv of BF3‚OEt2
or the use of TMSOTf (0.2-0.4 equiv) either in toluene
or in toluene-THF both reactions occurred competitively
to give a mixture of the γ-adducts 3 and the gem-
dialkoxycyclopropane derivative. As shown in Table 1,
aliphatic aldehyde without R-alkyl branching and R-oxy-
genated aldehyde gave the γ-adduct 3 in a reasonable
yield (entries 8-11, see also the result with glyceralde-
hyde acetonide). With R,â-unsaturated aldehyde, a slight
improvement in the yield was observed (entry 6 vs entry
7). The γ-adducts 3 were stable enough to be purified by
neutral silica gel column chromatography.
Deprotection of diethyl acetal group in 3 derived from
both aromatic and aliphatic aldehydes could be achieved
by simply treating with 50% trifluoroacetic acid (TFA)
in chloroform at 0 °C within 10 min to give the vinyl
ketone 4 in a good yield (Scheme 2).
Since we could find out improved reaction conditions
for the coupling reaction of 2 with aliphatic aldehyde, we
examined the diastereoselectivity in the reaction of 2 with
glyceraldehyde acetonide. Reaction of 2 with (R)-glycer-
aldehyde acetonide13 in the presence of 0.2 equiv of BF3‚
OEt2 in THF-toluene at 0 °C gave the adduct 3k (78%
yield) as a mixture of diastereomers anti-3k and syn-3k
in a ratio of 12:1, which are separable by column
chromatography. To determine the stereochemistry, the
adducts 3k were converted to the tetraol derivatives as
shown in Scheme 3, since Roush reported the spectra
data of these compounds obtained by his allylic borane
chemistry.14 Thus, treatment of anti-3k with aqueous
TFA gave the relatively unstable vinyl ketone anti-4k ,
which was reduced with NaBH4-CeCl3‚7H2O15 to give a
mixture of tetraol derivatives 5 and 6 in 80% yield (two
steps) in a ratio of 10.5:1. Likewise, syn-3k provided a
mixture of tetraol derivatives 7 and 8 in a ratio of 8.3:1.
1H and 13C NMR spectra of each tetraol derivative thus
obtained were clearly different from each other, and by
comparing the spectra data and specific rotation values
of 5 and 7 with those reported by Roush,14 stereochemical
assignment can be deduced as shown in Scheme 3. That
is, addition of the zirconium species 2 to glyceraldehyde
acetonide under the above conditions proceeds in anti-
selective manner and the NaBH4-CeCl3 reduction of the
hydroxy ketone 4 gave the anti-diol 5 or 7 as a major
product. On the basis of these results, the observed highly
anti-selective addition of the zirconium species 2 to
glyceraldehyde acetonide is possibly explained by con-
sidering the chairlike six-membered transition state as
(12) Reaction of the zirconium species 2 with a variety of carbonyl
compounds in the presence of more than 1 equiv Lewis acid: (a) Ito,
H.; Kuroi, H.; Ding, H.; Taguchi, T. J . Am. Chem. Soc. 1998, 120, 6623.
(b) Ito, H.; Sato, A.; Taguchi, T. Tetrahedron Lett. 1999, 40, 3217. (c)
Ito, H.; Sato, A.; Kusanagi, T.; Taguchi, T. Tetrahedron Lett. 1999,
40, 3397.
(14) Roush, W. R.; Grover, P. T. Tetrahedron 1992, 48, 1981.
(15) Brooks, D. W.; Bevinakatti, M. S.; Kennedy, E.; Hathaway, J .
J . Org. Chem. 1985, 50, 628.
(13) Daumas, M.; Vo-Quang, Y.; Vo-Quang, L.; Goffic, E. L. Synthesis
1989, 64.

920 J . Org. Chem., Vol. 65, No. 3, 2000
Notes
Gen er a l P r oced u r e of th e Rea ction of 2 w ith Alip h a tic
Ald eh yd e. A solution of triethyl orthoacrylate (174 mg, 1 mmol)
in toluene (2 mL) was added to a solution of “Cp2Zr” (1.2 mmol),
prepared from Cp2ZrCl2 with n-BuLi8,10 at -78 °C. After being
stirred for 3 h at room temperature, the reaction mixture was
cooled with dry ice/acetone bath. To the mixture were succes-
sively added THF (1 mL), BF3‚Et2O (0.3 mmol), and aliphatic
aldehyde (1.2 mmol), and the whole was stirred at 0 °C for 1-2
h (in the case of glyceraldehyde acetonide 0.2 mmol of BF3‚Et2O
was used). The reaction mixture was extracted with diethyl ether
after addition of NH4Cl aq, and the extract was washed with
brine and dried over MgSO4. Purification of the residue, obtained
by evaporation of the solvent, by neutral silica gel column
chromatography (hexane-AcOEt) gave the product 3f-k .
4,4-Dieth oxy-1-p h en yl-5-h exen -3-ol (3g): colorless oil; IR
(neat) ν cm-1; 3476, 1411, 1049. 1H NMR (500 MHz, CDCl3) δ
7.31-7.15 (5H, m), 5.74 (1H, dd, J ) 10.9, 17.5 Hz), 5.52 (1H,
dd, J ) 2.1, 17.5 Hz), 5.36 (1H, dd, J ) 2.1, 10.9 Hz), 3.74 (1H,
ddd, J ) 2.1, 2.1, 10.4 Hz), 3.50 (2H, q, J ) 7.1 Hz), 3.47 (1H,
qd, J ) 7.0, 9.4 Hz), 3.28 (1H, qd, J ) 7.0, 9.4 Hz), 2.90 (1H,
ddd, J ) 4.8, 10.0, 14.0 Hz), 2.64 (1H, ddd, J ) 7.5, 9.4, 14.0
Hz), 2.28 (1H, s), 1.82 (1H, m), 1.62 (1H, ddd, J ) 4.8, 9.4, 19.8
Hz), 1.18 (3H, t, J ) 7.1 Hz), 1.12 (3H, t, J ) 7.0 Hz). 13C NMR
(125.7 MHz, CDCl3) δ 142.3, 134.5, 128.6, 128.2, 125.7, 119.4,
101.6, 72.5, 56.9, 56.5, 32.6, 32.5, 15.4, 15.3. EI-MS m/z: 264
(M+), 219 (M+ - OEt). Anal. Calcd for C16H24O3: C, 72.69; H,
9.15. Found: C, 72.52; H, 9.09.
in the cases of other allylic metals such as allylic
boranes.10b,16 It should be noted that such a high diaste-
reoselection in the addition reaction of 2 with glyceral-
dehyde acetonide, and the functionality of the product 3
would provide an efficient procedure for the carbohydrate
chemistry from acyclic precursors.
In conclusion, γ,γ-dialkoxyallylic zirconium species 2
reacts with a variety of aldehydes at γ-position of the
zirconium metal as normal allylic organometallics to give
1-substituted-2,2-dialkoxy-3-buten-1-ol derivatives 3, which
is easily converted to the vinyl ketone form 4 by simply
treating with trifluoroacetic acid. Thus, in this reaction,
the zirconium species 2 acts as a synthetically useful
acryloyl anion equivalent.
Exp er im en ta l Section
Gen er a l. THF was distilled from sodium benzophenone ketyl
before use. Zirconocene dichloride was purchased from Tokyo
Kasei Kogyo. All reactions were conducted under an argon
1
atmosphere. H and 13C NMR spectra were recorded in CDCl3,
and the chemical shifts are given in ppm using CHCl3 (7.26 ppm)
in CDCl3 for 1H NMR and CDCl3 (77.01 ppm) for 13C NMR as
an internal standard, respectively. Mass spectra and HRMS
were recorded by electron impact ionization at 70 eV. Column
chromatography was performed on neutral silica gel (75-150
µm). Medium-pressure liquid chromatography (MPLC) was
performed on a 30 × 2.2 cm i.d. prepacked column (silica gel, 50
µm) with a UV or RI detector.
γ,γ-Dieth oxya llylic Zir con iu m Sp ecies (2). A solution of
triethyl orthoacrylate (174 mg, 1 mmol) in toluene (2 mL) was
added to a solution of “Cp2Zr” (1.2 mmol), prepared from Cp2-
ZrCl2 with n-BuLi8,10 at -78 °C. After being stirred for 3 h at
room temperature, the mixture was concentrated under reduced
pressure. To the residue was added benzene-d6, and the NMR
was measured. 1H NMR (300 MHz, benzene-d6) δ 6.00-5.92
(10H, m), 4.50 (1H, t, J ) 8.7 Hz), 4.04 (2H, q, J ) 7.2 Hz), 3.91
(2H, q, J ) 7.0 Hz), 3.80 (2H, q, J ) 6.9 Hz), 1.97 (2H, d, J )
8.7 Hz), 1.33 (3H, t, J ) 7.2 Hz), 1.25 (3H, t, J ) 6.9 Hz), 1.08
(3H, t, J ) 7.0 Hz). 13C NMR (100.6 MHz, CDCl3) δ 152.6, 110.7,
93.9, 68.8, 64.2, 64.0, 34.3, 20.1, 15.6, 15.1.
Gen er a l P r oced u r e of Gen er a tion of 2 a n d Its Rea ction
w ith Ar om a tic or r,â-Un sa tu r a ted Ald eh yd e. A solution of
triethyl orthoacrylate (174 mg, 1 mmol) in toluene (2 mL) was
added to a solution of "Cp2Zr" (1.2 mmol), prepared from Cp2-
ZrCl2 with n-BuLi8,10 at -78 °C. After being stirred for 3 h at
room temperature, a solution of aromatic or R,â-unsaturated
aldehyde (1.2 mmol) shown in Table 1 in toluene (2 mL) was
added at -78 °C and then stirred at room temperature for 3 h.
The reaction mixture was extracted with diethyl ether after
addition of NH4Cl aq, and the extract was washed with brine
and dried over MgSO4. Purification of the residue, obtained by
evaporation of the solvent, by neutral silica gel column chro-
matography (hexane-AcOEt) gave the product 3 shown in Table
1.
2,2-Dieth oxy-1-p h en yl-3-bu ten -1-ol (3a ): colorless oil; IR
(neat) ν cm-1; 3478, 1410, 1057. 1H NMR (400 MHz, CDCl3) δ
7.54-7.40 (2H, m), 7.33-7.23 (3H, m), 5.43 (1H, s), 5.42 (1H, d,
J ) 3.1 Hz), 5.28 (1H, dd, J ) 5.0, 8.1 Hz), 4.88 (1H, d, J ) 2.0
Hz), 3.67 (2H, q, J ) 7.0 Hz), 3.53 (1H, qd, J ) 7.0, 9.8 Hz), 3.48
(1H, qd, J ) 7.0, 9.8 Hz), 2.66 (1H, d, J ) 2.0 Hz), 1.27 (3H, t,
J ) 7.0 Hz), 1.16 (3H, J ) 7.0 Hz). 13C NMR (100.6 MHz, CDCl3)-
δ 139.2, 134.1, 127.6, 127.4, 127.2, 119.7, 101.8, 74.4, 57.6, 56.6,
15.3, 15.2. EI-MS m/z 219 (M+ - OH), 191 (M+ - OEt). HRMS
calcd for C14H19O2: 219.1385 (M+ - OH). Found: 219.1389.
Anal. Calcd for C14H20O3: C, 71.16; H, 8.53. Found: C, 71.04;
H, 8.52.
(1R)-1-[(4R)-2,2-Dim eth yl-1,3-dioxolan -4-yl]-2,2-dieth oxy-
3-bu ten -1-ol (a n ti-3k ): colorless oil; [R]22D +8.8 (c 1.18, CHCl3).
1
IR (neat) ν cm-1; 3481, 1057. H NMR (400 MHz, CDCl3) δ 5.70
(1H, dd, J ) 10.7, 17.5 Hz), 5.54 (1H, dd, J ) 2.1, 17.5 Hz), 5.37
(1H, dd, J ) 2.1, 10.7 Hz), 4.21 (1H, dt, J ) 3.2, 6.8 Hz), 4.08
(1H, dd, J ) 2.0, 3.2 Hz), 3.98 (1H, dd, J ) 6.8, 8.2 Hz), 3.87
(1H, dd, J ) 6.8, 8.2 Hz), 3.62-3.48 (2H, m), 3.49 (2H, q, J )
7.0 Hz), 2.31 (1H, d, J ) 2.0 Hz), 1.42 (3H, s), 1.34 (3H, s), 1.19
(3H, t, J ) 7.0 Hz), 1.18 (3H, t, J ) 7.0 Hz). 13C NMR (100.6
MHz, CDCl3) δ 134.4, 119.7, 108.0, 100.2, 75.3, 73.7, 64.6, 57.1,
56.9, 26.3, 25.3, 15.4, 15.3. EI-MS m/z: 245 (M+ - Me), 215 (M+
- OEt). Anal. Calcd for C13H24O5: C, 59.98; H, 9.29. Found: C,
59.85; H, 9.23.
(1S)-1-[(4R)-2,2-Dim eth yl-1,3-dioxola n -4-yl]-2,2-dieth oxy-
3-bu ten -1-ol (syn -3k ): colorless oil; [R]26D -8.0 (c 1.78, CHCl3).
1
IR (neat) ν cm-1; 3445, 1065. H NMR (400 MHz, CDCl3) δ 5.74
(1H, dd, J ) 10.7, 17.3 Hz), 5.56 (1H, dd, J ) 1.9, 17.3 Hz), 5.41
(1H, dd, J ) 1.9, 10.7 Hz), 4.14 (1H, dt, J ) 6.2, 8.0 Hz), 4.02
(1H, dd, J ) 6.2, 8.4 Hz), 3.79 (1H, dd, J ) 8.0, 8.4 Hz), 3.73
(1H, dd, J ) 5.0, 6.2 Hz), 3.60-3.37 (4H, m), 2.42 (1H, d, J )
5.0 Hz), 1.41 (3H, s), 1.38 (3H, s), 1.23 (3H, t, J ) 7.0 Hz), 1.15
(3H, t, J ) 7.0 Hz). 13C NMR (100.6 MHz, CDCl3) δ 134.5, 119.9,
108.9, 100.6, 75.9, 72.4, 67.0, 57.2, 56.3, 26.6, 25.9, 15.3, 15.2.
EI-MS m/z: 245 (M+ - Me), 215 (M+ - OEt). Anal. Calcd for
C13H24O5: C, 59.98; H, 9.29. Found: C, 60.01; H, 9.11.
4-Hyd r oxy-6-p h en yl-1-h exen -3-on e (4g). To a solution of
3g (42 mg, 0.17 mmol) in chloroform (1 mL) cooled with an ice-
bath was added 50% trifluoroacetic acid (0.2 mL), and the
mixture was stirred for 10 min. The reaction mixture was
neutralized by addition of NaHCO3 aq and extracted with
chloroform. The organic layer was washed with brine, dried over
MgSO4, and then concentrated under reduced pressure. The
residue was purified by neutral silica gel column chromatogra-
phy (hexane-AcOEt ) 3:1) to give 4g (30 mg, 95%) as a colorless
1
oil. IR (neat) ν cm-1; 3465, 1695. H NMR (400 MHz, CDCl3) δ
7.32-7.17 (5H, m), 6.47 (1H, dd, J ) 10.4, 17.4 Hz), 6.33 (1H,
dd, J ) 1.2, 17.4 Hz), 5.87 (1H, dd, J ) 1.2, 10.4 Hz), 4.41 (1H,
ddd, J ) 3.5, 5.2, 8.4 Hz), 3.55 (1H, d, J ) 5.2 Hz), 2.85-2.69
(2H, m), 2.19-2.08 (1H, m), 1.81 (1H, dddd, J ) 5.0, 8.4, 8.4,
13.9 Hz). 13C NMR (100.6 MHz, CDCl3) δ 201.0, 141.1, 131.2,
130.5, 128.6, 128.5, 126.1, 74.3, 36.1, 31.1. EI-MS m/z 190 (M+).
HRMS Calcd for C12H14O2: 190.0994 (M+). Found: 190.0994.
(1S,2S)- a n d (1S,2R)-1-[(4R)-2,2-Dim eth yl-1,3-d ioxola n -
4-yl]-3-bu ten e-1,2-d iol (5 a n d 6). After a solution of anti-3k
(31 mg, 0.12 mmol) in 50% trifluoroacetic acid (0.3 mL) and
chloroform (1.5 mL) was stirred for 10 min at 0 °C, the reaction
mixture was neutralized by addition of NaHCO3 aq and ex-
tracted with chloroform. The organic layer was washed with
brine, dried over MgSO4, and then concentrated under reduced
pressure to give the crude hydroxy ketone anti-4k (20.6 mg) after
(16) (a) Roush, W. R.; Adam, M. A.; Walts, A. E.; Harris, D. J . J .
Am. Chem. Soc. 1986, 108, 3422. (b) Hoffmann, W. R.; Endesfelder,
A.; Zeiss, H. J . Carbohyd. Res. 1983, 123, 320. (c) Wuts, P. G. M.;
Bigelow, S. S. J . Org. Chem. 1983, 48, 3489. (d) Roush, W. R.;
Michaelides, M. R.; Tai, D. F.; Lesur, B. M.; Chong, W. K. M.; Harris,
D. J . J . Am. Chem. Soc. 1989, 111, 2984.

Notes
J . Org. Chem., Vol. 65, No. 3, 2000 921
briefly purified by passing neutral silica gel column chromatog-
raphy (hexane-AcOEt ) 5:1). To a solution of anti-4k (20.6 mg)
in THF (1.5 mL) cooled with ice-bath were added CeCl3‚7H2O
(41.2 mg) in H2O (0.5 mL) and NaBH4 (38 mg) in H2O (0.5 mL),
and the mixture was stirred for 15 min. Extractive workup
(AcOEt for extraction) and purification by silica gel column
chromatography (hexane-AcOEt ) 1:2) gave a mixture of the
dihydroxy compounds 5 and 6 (17.9 mg, 80%) in a ratio of 10.5:1
as determined by 1H NMR. Further purification by MPLC
(CHCl3-i-PrOH ) 7:1) gave pure 5 and 6, respectively. 5:
colorless oil; [R]28 +4.44 (c 1.71, CHCl3), [lit.14 [R]23 +7.0 (c
NMR (100.6 MHz, CDCl3) δ 137.1, 117.1, 109.2, 75.9, 73.7, 72.1,
66.0, 26.7, 25.2.
(1R,2R)-1-[(4R)-2,2-Dim eth yl-1,3-d ioxola n -4-yl]-3-bu ten e-
1,2-d iol (7). In a similar manner as above, syn-3 (10.4 mg) gave
syn-4 (6.8 mg), which was reduced to a mixture of the alcohol 7
and 8 (5.4 mg, 72%) in a ratio of 8.3:1. MPLC purification
(CHCl3-AcOEt ) 1:2) gave pure 7 and a mixture of 7 and 8. 7:
colorless oil; [R]26 +13.4 (c 1.00, CHCl3), [lit.14 [R]23 +13.9 (c
D
D
0.72, CHCl3)]. 1H NMR (400 MHz, CDCl3)14 δ 5.95 (1H, ddd, J
) 5.6, 10.6, 17.2 Hz), 5.38 (1H, ddd, J ) 1.5, 1.5, 17.2 Hz), 5.28
(1H, ddd, J ) 1.5, 1.5, 10.6 Hz), 4.30-4.22 (2H, m), 4.03 (2H,
dd, J ) 6.5, 8.2 Hz), 3.88 (1H, dd, J ) 7.2, 8.2 Hz), 3.53 (1H,
ddd, J ) 4.5, 4.5, 7.1 Hz), 2.62 (1H, m), 2.15 (1H, m), 1.44 (3H,
s), 1.37 (3H, s). 13C NMR (100.6 MHz, CDCl3) δ 136.7, 116.8,
109.4, 75.4, 74.4, 72.9, 66.3, 26.3, 25.3.
D
D
0.95, CHCl3)]. 1H NMR (400 MHz, CDCl3)14 δ 5.92 (1H, ddd, J
) 6.3, 10.6, 17.3 Hz), 5.39 (1H, ddd, J ) 1.4, 2.9, 17.3 Hz), 5.29
(1H, ddd, J ) 1.4, 2.9, 10.6 Hz), 4.30 (1H, dd, J ) 5.0, 6.3 Hz),
4.09-4.02 (2H, m), 3.99-3.93 (1H, m), 3.72 (1H, dd, J ) 5.0,
5.0 Hz), 2.75 (1H, brs), 2.50 (1H, brs), 1.42 (3H, s), 1.34 (3H, s).
13C NMR (100.6 MHz, CDCl3) δ 135.8, 118.0, 109.0, 76.3, 74.1,
73.5, 66.2, 26.6, 25.3. 6: colorless oil; [R]27D +35.3 (c 0.16, CHCl3).
1H NMR (400 MHz, CDCl3) δ 5.95 (1H, ddd, J ) 5.8, 10.5, 17.3
Hz), 5.39 (1H, ddd, J ) 1.4, 1.4, 17.3 Hz), 5.28 (1H, ddd, J )
1.4, 1.4, 10.5 Hz), 4.28-4.23 (1H, m), 4.16 (1H, ddd, J ) 6.2,
6.2, 6.2 Hz), 4.08 (1H, dd, J ) 6.2, 8.4 Hz), 3.97 (1H, dd, J )
6.2, 8.4 Hz), 3.62 (1H, ddd, J ) 3.4, 5.7, 6.2 Hz), 2.32 (1H, d, J
) 5.1 Hz), 2.25 (1H, J ) 5.7 Hz), 1.43 (3H, s), 1.37 (3H, s). 13C
Su p p or tin g In for m a tion Ava ila ble: Characterization
data (1H and 13C NMR, IR, MS, and elemental analyses data)
of 3b-f,h -j and 4d ,h ; 1H and 13C NMR spectra of 3e and
1
4d ,g,h ; 1H, H-1H COSY, and 13C NMR spectra of 5-7. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O991107B