Highly stereoselective hydroformylation of olefins possessing chiral sugar templates

Article abstract of DOI:10.1055/s-1998-1680

Hydroformylation of 1,1-disubstituted olefins possessing chiral sugar templates gave β-substituted aldehydes in good to excellent yields with up to 99% diastereoselectivity.

Full text of DOI:10.1055/s-1998-1680

April 1998
SYNLETT
381
Highly Stereoselective Hydroformylation of Olefins Possessing Chiral Sugar Templates
Takashi Takahashi,* Satoshi Ebata and Haruo Yamada
Department of Chemical Engineering, Tokyo Institute of Technology, Ookayama, Meguro, Tokyo 152-8552, JAPAN
Received 21 January 1998
Abstract: Hydroformylation of 1,1-disubstituted olefins possessing
chiral sugar templates gave β-substituted aldehydes in good to excellent
yields with up to 99% diastereoselectivity.
The stereoselective introduction of a formyl group to olefins is an
important goal in synthetic organic chemistry, as the formyl group can
be used for further functionalization of the molecule. Many methods
have been developed for the stereoselective synthesis of β-substituted
aldehydes 2 as chiral building blocks for several important classes of
1
natural products. Many of these syntheses involve 1,4-addition of
2
nucleophiles to α,β-unsaturated aldehydes 3 or their equivalents. In
devising a new catalytic process for the stereoselective and facile
3
synthesis of β-substituted aldehydes 2, hydroformylation of 1,1-
4
disubstituted olefins 1 should provide an effective alternative approach.
It has been reported that the diastereoselective hydroformylation of 1,1-
disubstituted allylic alcohols gave threo- and erythro-hydroxyalkanals
Scheme 2
The resulting substrates 11a - e were subjected to hydroformylation
5
in a ratio of up to 82 : 18. However, it is generally difficult to achieve
using 10 mol% of Rh(CO) (acac) as the catalyst. A toluene solutions of
2
high stereoselectivity in the hydroformylation without introducing a
the Rh catalyst and substrates 11a - e were heated in an autoclave under
6
catalyst directing group into the substrates. It was conceived that 1,1-
80 atm of syn gas (H / CO = 1) at 80 °C for 48 h. The hydroformylation
2
disubstituted olefins 4 possessing a sugar moiety might be very useful
substrates for the stereoselective hydroformylation, as the
stereochemical outcome of the hydroformylation would be controlled
by the bulky sugar substituent adjacent to the olefin and sugar
derivatives have been extensively used as chiral synthons in the
proceeded smoothly to give the corresponding aldehydes 12 in excellent
10
yields and with high (S)-selectivities of up to 99%. The results are
shown in Table 1. It was found that the protecting group at the C-2
hydroxyl group exerted an influence on the diastereoselectivities of the
hydroformylation. When 11a without protective group was employed,
α-12a and β-12a were formed in an 83 : 17 ratio. Protection of the
alcohol with pivalate 11b, benzoate 11c, and acetate 11d improved the
diastereomeric ratios to 90 : 10, 97 : 3 and 98 : 2, respectively, favoring
the (S) configuration. The hydroformylation of the TBS ether 11e, in
7
synthesis of natural products. Herein, we report that the
hydroformylation of 1,1-disubstituted olefins 4 possessing a chiral sugar
template is an effective method for the highly diastereoselective,
catalytic synthesis of β-substituted aldehydes 5.
11
which only α-12e was obtained, is extremely noteworthy.
Scheme 1
At first, we examined the hydroformylation of 1,1-disubstituted olefins
possessing a methyl group and a glucose moiety with various protective
groups at the C-2 position in glucose. The substrates for the
hydroformylation were prepared as shown in Scheme 2. Epoxidation of
D-(+)-glucal tribenzylether 6, which was obtained from commercially
available D-(+)-glucal triacetate in two steps, with dimethyldioxirane in
The relative stereochemistries were assigned for the products 12 by
transformation to the lactone 13 and subsequent NOE experiments
8
11
acetone at 0 °C, followed by acetolysis of the resulting epoxide gave
the acetate 7 in 71% yield. Protection of the C-2 alcohol with ethyl vinyl
(Figure 1). The observed independence of the diastereoselectivity on the
ether and deacetylation of the resulting product with K CO in MeOH
nature of protective group at C-2 seemed to indicate that a
2
3
afforded the lactol 8. Swern oxidation of 8, followed by removal of the
ethoxy ethyl group with p-TsOH gave the lactone 9 in 46% overall yield
conformational preference inherent to the 1,1-disubstituted olefin might
be the origin of the observed stereoselectivity. A plausible explanation
for the hydroformylation of 11 is shown in Figure 1. The compounds 11
from 7. Addition of isopropenylmagnesium bromide to
subsequent reduction of the ketol with triethylsilane in the presence of
9
and
9
have two preferred conformations 11A and 11B where there is overlap
*
BF ·Et O gave the C-glycosylated olefin 10 in 99% yield. Protection of
of σ
orbital with the alkene π-orbitals. The compounds 11 prefer
CO
3
2
the C-2 alcohol afforded the substrates 11b - e in 30%, 48%, 52% and
conformation 11A over than 11B in order to relieve the steric repulsions
50%, respectively.
between the vinyl methyl group and the anomeric hydrogen. If we

382
LETTERS
SYNLETT
2.
3.
Kozlowski, J. A. In Comprehensive Organic Synthesis, Trost. B. M.;
Fleming, I.; Semmelhack, M. F. Eds.; Pergamon Press, Oxford, 1991,
Vol. 4, 183.
assume coordination of the rhodium catalyst from a less hindered Re-
face of the olefin, hydroformylation would provide the α-12, which was
found experimentally.
For reviews of hydroformylation, see: (a) Cornils, B. In New Syntheses
with Carbon Monoxide; Fable, J. Ed.; Springer-Verlag: New York,
1980. (b) Tolman, C. A.; Faller, J. In Homogeneous Catalysis with
Metal Phosphine Complexes; Pignolet, L. H. Ed.; Plenum Press: New
York, 1983; Chapt. 2. (c) Dickson, R. S. In Homogeneous Catalysis
with Compounds of Rhodium and Iridium; Ugo, R.; James B. R. Eds.;
D. Reidel Publish Company: Dordrecht, 1985. (d) Beller, M.; Cornils,
B.; Frohning, C.D.; Kohlpaintner, C. W. J. Mol. Cat. A, 1995, 104, 17.
For reviews of stereoselectivity in the rhodium-catalyzed
hydroformylation, see: (a) Lazzaroni, R.; Pucci, S.; Bertozzi, S.; Pini,
D. J. Organomet. Chem. 1983, 247, C56. (b) Lazzaroni, F.; Biscarini,
P.; Bordoni, S.; Longoni, G.; Venturini, E. J. Organomet. Chem. 1996,
508, 59. For a review of asymmetric hydroformylation, see: Agbossou,
F.; Carpentier, J.-F.; Mortreux, A. Chem. Rev. 1995, 95, 2485. For
examples of asymmetric hydroformylation, see: (a) Nozaki, K.; Sakai,
N.; Nanno, T.; Higashijima, T.; Mano, S.; Horiuchi, T.; Takaya, H.
J. Am. Chem. Soc. 1997, 119, 4413 and references cited herein.
(b) Sakai, N.; Mano, S.; Nozaki, K.; Takaya, H. J. Am. Chem. Soc.
1993, 115, 7033. For an example of diastereoselective
hydroformylation, see: Leighton, J. L.; O'Neil, D, N.; J. Am. Chem.
Soc. 1997, 119, 11118. For examples of 1,1-disubstituted alkenes, see:
(a) Botteghi, C.; Consiglio, G.; Ceccarelli, G.; Stefani, A. J. Org. Chem.
1972, 37, 1835. (b) Hoffmann, W.; Siegel, H. Tetrahedron Lett. 1975,
533. (c) Kollár, L.; Consiglio, G.; Pino, P. Chimia 1986, 40, 428.
(d) Gladiali, S.; Pinna, L. Tetrahedron: Asymmetry, 1991, 2, 623. For
examples of application to fine chemical synthesis, see: (a) Wuts, P. G.
M.; Obrzut, M. L.; Thompson, P. A. Tetrahedron Lett. 1984, 25, 4051.
(b) Nozaki, K.; Li. W.; Horiuchi, T.; Takaya, H.; Saito, T.; Yoshida, A.;
Matsumura, K.; Kato, Y.; Imai, T.; Miura, T.; Kumobayashi, H. J. Org.
Chem. 1996, 61, 7658.
Figure 1
To test the versatility of the olefins bearing a sugar moiety as substrates
for hydroformylation, we examined the hydroformylation of 1,1-
disubstituted olefins possessing hydroxy methyl 14, acetoxy methyl 16
and acetal 17 moieties. Hydroformylation of 14 under 80 atm of syn gas
at 80 °C for 60 h gave the aldehyde 15, in which the (R) isomer was
obtained exclusively in 66% yield. While the acetoxy methyl derivative
16 was less reactive than 14, only the (R) isomer 17 was obtained in
54% yield. When the acetal 18 was subjected to hydroformylation,
starting material was recovered quantitatively. It seems that the reaction
did not proceed due to steric hindrance of the acetal group.
4.
Takahashi, T.; Machida, K.; Kido, Y.; Nagashima, K.; Ebata, S.; Doi,
T. Chem. Lett. 1997, 1291.
5.
6.
Doi, T.; Komatsu, H.; Yamamoto, K. Tetrahedron Lett. 1996, 37, 6877.
(a) Burke, S. D.; Cobb, J. E. Tetrahedron Lett. 1986, 27, 4237.
(b) Burke, S. D.; Cobb, J. E.; Takeuchi, K. J. Org. Chem. 1990, 55,
2138. (c) Jackson, W. R.; Perlmutter, P.; Suh, G.-H. J. Chem. Soc.,
Chem. Commun. 1987, 724. (d) Jackson, W. R.; Perlmutter, P.;
Tasdelen, E. E. Tetrahedron Lett. 1990, 31, 2461. (e) Jackson, W. R.;
Moffat, M. R.; Perlmutter, P.; Tasdelen, E. E. Aust. J. Chem. 1992, 45,
823. (f) Breit, B. Angew. Chem., Int. Ed. Engl. 1996, 35, 2835. (g)
Breit, B. Chem. Commun. 1997, 591.
Scheme 3
7.
8.
Hanessian, S. In The Total Synthesis of Natural Products, The Chiron
Approach, Pergamon Press, Oxford, 1983.
(a) Friesen, R. W.; Danishefsky, S. J. J. Am. Chem. Soc. 1989, 111,
6656. (b) Halcomb, R. L.; Danishefsky, S. J. J. Am. Chem. Soc. 1989,
111, 6661.
In conclusion, we have demonstrated that 1,1-disubstituted olefins
bearing a sugar moiety undergo hydroformylation in good to excellent
yields and with high stereoselectivities to provide the corresponding
aldehydes.
9.
Lewis, M. D.; Cha, J. K.; Kishi, Y. J. Am. Chem. Soc. 1982, 104, 4976.
10. The ratio was determined by HPLC analysis after conversion of the
aldehydes 12 to the corresponding diols.
References and Notes
11. Spectral data for α-12e 1H NMR (270 MHz, CDCl3) δ -0.01 (s, 3H),
0.04 (s, 3H), 0.88 (s, 9H), 1.15 (d, J = 6.60 Hz, 3H), 2.18-2.53 (m, 2H),
3.13 (d, J = 7.72 Hz, 1H), 3.42-3.57 (m, 7H), 4.54-4.69 (m, 4H), 4.79
(d, J = 11.55 Hz, 1H), 5.05 (d, J = 11.88Hz, 1H), 7.06-7.34 (m, 15H),
9.81 (brs); IR (neat) 2922, 1726, 1494, 1452, 1360, 1254, 1066, 861,
836, 778, 734, 698 cm-1; for 13 1H NMR (270 MHz, CDCl3) δ 1.12 (d,
J = 6.60 Hz, 3H), 2.41-2.52 (2H, m), 2.72-2.82 (m, 1H), 3.51-3.81 (m,
1.
Examples of synthesis of β-substituted aldehydes, see: (a) Yamada, K.;
Ojika, M.; Ishigaki, T.; Yoshida, Y.; Ekimoto, H.; Arakawa, M. J. Am.
Chem. Soc. 1993, 115, 11020. (b) Cha, J. K.; Christ, W. J.; Finan, J. M.;
Fujioka, H.; Kishi, Y.; Klein, L. L.; Ko, S. S.; Leder, J.; McWhorter Jr.,
W. W.; Pfaff, K.-P.; Yonaga, M.; Uemura, D.; Hirata, Y. J. Am. Chem.
Soc. 1982, 104, 7369. (c) Sasaki, M.; Matsumori, N.; Maruyama, T.;
Nonomura, T.; Murata, M.; Tachibana, K.; Yasumoto, T. Angew.
Chem., Int. Ed. Engl. 1996, 35, 1672. (d) Bottini, A. T.; Gilchrist, D. G.
Tetrahedron Lett. 1981, 22, 2719. (e) Bezuidenhout, S. C.; Gelderblom,
W. C. A.; Gorst-Allman, C. P.; Horak, R. M.; Marasas, W. F. O.;
Spiteller, G.; Vleggaar, R. J. Chem. Soc., Chem. Commun. 1988, 743.
6H), 4.24 (dd,
J = 9.24, 9.90 Hz, 1H), 4.48-5.05 (m, 6H), 7.14-7.44 (m,
15H); 13C NMR (67.8 MHz, CDCl3) δ 14.5, 28.1, 36.8, 69.0, 73.5,
74.2, 75.4, 77.3, 77.4, 79.6, 84.3, 127.7-128.4 (aromatic), 138.0, 138.2,
170.0; IR (neat) 2920, 1741, 1452, 1204, 1095, 789, 753, 699 cm-1
.