Catalytic asymmetric synthesis of both syn- and anti-β-amino alcohols

Full text of DOI:10.1021/ja973527t

J. Am. Chem. Soc. 1998, 120, 431-432
Scheme 1. Chiral â-Amino Alcohol Synthesis
431
Catalytic Asymmetric Synthesis of Both Syn- and
Anti-â-Amino Alcohols
Shuj Kobayashi,* Haruro Ishitani, and Masaharu Ueno
Department of Applied Chemistry, Faculty of Science
Science UniVersity of Tokyo (SUT)
CREST, Japan Science and
Technology Corporation (JST)
Kagurazaka, Shinjuku-ku, Tokyo 162, Japan
ReceiVed October 8, 1997
Table 1. Effects of Enolates and Solvents
â-Amino alcohol units are often observed in biologically
interesting compounds, and several methods for the synthesis of
these units have been developed.1-5 Among them, catalytic
asymmetric processes are the most effective and promising.
Asymmetric ring opening of symmetric epoxides by nitrogen
nucleophiles in the presence of a chiral Lewis acid catalyst2 and
ring opening of chiral epoxides or aziridines, which are prepared
by catalytic asymmetric reactions, are useful methods.3 Recent
progress has been made by Sharpless to introduce direct asym-
metric aminohydroxylation (AA) of alkenes.4 The Sharpless AA
method has realized a high degree of enantioselctivities to afford
syn-â-amino alcohols directly. Herein, we describe an alternative
approach for the synthesis of chiral â-amino alcohols using
catalytic diastereo- and enantioselective Mannich-type reactions
of R-alkoxy enolates with aldimines (Scheme 1). According to
this methodology, both syn- and anti-â-amino alcohols can be
obtained in high selectivities by simply choosing the protective
groups of the R-alkoxy parts and of the R2 (ester) part of the
enolates, accompanied with formation of new carbon-carbon
bonds.5
First, we tested the reaction of aldimine 2a with R-TBSO-
ketene silyl acetal 3a using 10 mol % of zirconium catalyst 1,
which was prepared from Zr(OtBu)4, 2 equiv of (R)-6,6′-dibromo-
1,1′-bi-2-naphthol ((R)-Br-BINOL), and 1-methylimidazole (NMI)
(Table 1).6 The reaction proceeded smoothly to afford the
corresponding R-alkoxy-â-amino ester in a 76% yield with
moderate syn-selectivity,7 and the enantiomeric excess of the syn-
adduct was proven to be less than 10%. We then screened various
reaction conditions. It was found that when 1,2-dimethylimida-
zole (DMI) was used instead of NMI, the selectivity increased
dramatically. Moreover, the diastereo- and enantioselectivities
were improved when the reaction was carried out at -78 °C.
The O-substituents of ketene silyl acetals and solvents also
influenced the yield and selectivity, and finally, the best result
(quantitative, syn/anti ) 96:4, syn ) 95% ee) was obtained when
the reaction was carried out in toluene using ketene silyl acetal
3b(E). It was also interesting from a mechanistic point of view
that geometrically isomeric ketene silyl acetal 3b(Z) also gave
excellent diastereo- and enantioselectivities. We next tried other
substrates, and the results are shown in Table 2. In all cases, the
desired adducts including syn-â-amino alcohol units were obtained
in high diastereo- and enantioselectivities.
On the other hand, it was found that anti-â-amino alcohol
derivatives were obtained by the reaction of aldimine 2a with
R-benzyloxy-ketene silyl acetal 3c under the same reaction
conditions.8 Namely, in the presence of 10 mol % of the above
catalyst, aldimine 2a reacted with 3c smoothly to give the
corresponding adduct quantitatively with anti-preference, and the
enantiomeric excess (ee) of the anti-adduct was 95%. It was
exciting that both syn- and anti-amino alcohol units were prepared
(1) (a) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. ReV. 1996, 96, 835.
(b) Shioiri, T.; Hamada, Y. Heterocycles 1988, 27, 1035. (c) Barlow, C. B.;
Bukhari, S. T.; Guthrie, R. D.; Prior, A. M. Asymmetry in Carbohydrates;
Dekker: New York, 1979; pp 81-99.
(2) (a) Yamashita, H. Bull. Chem. Soc. Jpn. 1988, 61, 1213. (b) Nugent,
W. A. J. Am. Chem. Soc. 1992, 114, 2768. (c) Mart´ınez, L. E.; Leighton, J.
L.; Carsten, D. H.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5897. For
the stoichiometric use of a chiral source, see: (d) Emziane, M.; Sutowardoyo,
K. I.; Sinou, D. J. Organomet. Chem. 1988, 346, C7. (e) Hayashi, M.;
Kohmura, K.; Oguni, N. Synlett 1991, 774.
(3) (a) DuBois, J.; Tomooka, C. S.; Hong, J.; Carreira, E. M. J. Am. Chem.
Soc. 1997, 119, 317. (b) Larrow, J. F.; Schaus, S. E.; Jacobsen, E. N. J. Am.
Chem. Soc. 1996, 118, 7420. (c) Evans, D. A.; Faul, M. M.; Bilodeau, M. T.;
Anderson, B. A.; Barnes, D. M. J. Am. Chem. Soc. 1993, 115, 5328. (d) Noda,
K.; Hosoya, N.; Irie, R.; Ito, Y.; Katsuki, T. Synlett 1993, 469. (e) Trost, B.
M.; Sudhakar, A. R. J. Am. Chem. Soc. 1987, 109, 3792.
(4) (a) Li, G.; Chang, H.-T.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl.
1996, 35, 451. (b) Li, G.; Sharpless, K. B. Acta Chem. Scand. 1996, 50, 649.
(c) Rudolph, J.; Sennhenn, P. C.; Vlaar, C. P.; Sharpless, K. B. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 2810. (d) Li, G.; Angert, H. H.; Sharpless, K. B.
Angew. Chem., Int. Ed. Engl. 1996, 35, 2813. (e) Bruncko, M.; Schlingloff,
G.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl. 1997, 36, 1483.
(5) (a) Shibasaki, M.; Sasai, H. Pure Appl. Chem. 1996, 68, 523. (b) Hattori,
K.; Yamamoto, H. Tetrahedron 1994, 50, 2785. (c) Hwang, G.-I.; Chung,
J.-H.; Lee, W. K. J. Org. Chem. 1996, 61, 6183. (d) Barrett, A. G. M.; Seefeld,
M. A.; White, A. J. P.; Williams, D. J. J. Org. Chem. 1996, 61, 2677. (e) Ito,
H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992, 33, 4469. (f) Lohray,
B. B.; Gao, Y.; Sharpless, K. B. Tetrahedron Lett. 1989, 30, 2623.
(6) Ishitani, H.; Ueno, M.; Kobayashi, S. J. Am. Chem. Soc. 1997, 119,
7153.
(8) We also observed similar dramatic changes in diastereoselectivities in
chiral tin(II)-mediated asymmetric aldol reactions. (a) Kobayashi, S.; Horibe,
M. Synlett 1994, 147. (b) Kobayashi, S.; Horibe, M.; Saito, Y. Tetrahedron
1994, 50, 9629. (c) Kobayashi, S.; Kawasuji, T. Tetrahedron Lett. 1994, 35,
3329. (d) Mukaiyama, T.; Shiina, I.; Uchiro, H.; Kobayashi, S. Bull. Chem.
Soc. Jpn. 1994, 67, 1708. See also ref 5b.
(7) Relative configuration assignment was made after converting to the
corresponding â-lactam (see the Supporting Information).
S0002-7863(97)03527-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/06/1998

432 J. Am. Chem. Soc., Vol. 120, No. 2, 1998
Table 2. Synthesis of Syn-Amino Alcohol Units
Communications to the Editor
Scheme 2. Synthesis of (2R,3S)-3-Phenylisoserine‚
Hydrochloride (6)
a usual workup, the crude product was chromatographed on silica
gel to give the desired adduct. The diastereomer ratio was
1
determined by H NMR analysis, and the optical purity was
determined by HPLC analysis using a chiral column (see the
Supporting Information).
Table 3. Synthesis of Anti-Amino Alcohol Units
Finally, to demonstrate the utility of these reactions, we
undertook the synthesis of (2R,3S)-3-phenylisoserine•hydrochloride
(6), which is a precursor of the C-13 side chain of paclitaxel,
known to be essential for its biological activity.10 The key
catalytic asymmetric Mannich-type reaction of aldimine 2a with
ketene silyl acetal 3b(E) using the chiral zirconium catalyst
prepared using (S)-6,6′-dibromo-1,1′-bi-2-naphthol proceeded
smoothly in toluene at -78 °C to afford the corresponding syn-
adduct quantitatively in excellent diastereo- and enantioselectivi-
ties (syn/anti ) 95:5, syn ) 94% ee). Methylation (MeI, K2CO3)
of the phenolic OH of the adduct 4 and deprotection using cerium
ammonium nitrate (CAN) gave â-amino ester 5. Hydrolysis of
the ester and deprotection of the tert-butyldimethylsilyl (TBS)
group were performed using 10% HCl to afford 6 quantita-
tively.11-12
In conclusion, we have developed an efficient method for the
synthesis of both syn- and anti-amino alcohol units with high
yields and high selectivities via catalytic asymmetric Mannich-
type reactions of aldimines with R-alkoxy silyl enolates. The
protocol includes catalytic diastereo- and enantioselective carbon-
carbon bond-forming processes, and the syn- and anti-selectivities
were controlled by simply choosing the protective groups of the
R-alkoxy parts and of the ester parts of the silyl enolates. Since
both enantiomers of the chiral source, (R)- and (S)-6,6′-dibromo-
1,1′-bi-2-naphthol, are commercially available, all four stereoi-
somers of â-amino alcohol units can be prepared according to
this method. The utility of this protocol has been demonstrated
by the concise synthesis of (2R,3S)-3-phenylisoserine‚hydrochloride
(a precursor of the C-13 side chain of paclitaxel).
by simply choosing the protective groups of the R-alkoxy parts
of the silyl enolates. Several aldimines were then tested and the
results are summarized in Table 3. In most cases, the desired
anti-adducts were obtained in high yields with high diastereo-
and enantioselectivities. While higher diastereoselectivities were
obtained using a ketene silyl acetal derived from a p-methox-
yphenyl (PMP) ester, higher enantiomeric excesses were observed
in the reactions using a ketene silyl acetal derived from isopropyl
or cyclohexyl ester. In the reaction of the aldimine derived from
cyclohexanecarboxaldehyde, use of 2-amino-3-methylphenol in-
stead of 2-aminophenol was effective in affording the corre-
sponding anti-adduct in high selectivities.9
A typical experimental procedure is described for the reaction
of aldimine 2a with ketene silyl acetal 3b(E). To Zr(OtBu)4 (0.04
mmol) in toluene (0.25 mL) were added (R)-6,6′-dibromo-1,1′-
bi-2-naphthol (0.088 mmol) in toluene (0.5 mL) and 1,2-
dimethylimidazole (0.08 mmol) in toluene (0.25 mL) at room
temperature. The mixture was stirred for 1 h at the same
temperature and then cooled to -78 °C. Toluene solutions (0.75
mL) of 2a (0.4 mmol) and 3b(E) (0.5 mmol) were successively
added. The mixture was stirred for 20 h, and saturated aqueous
NaHCO3 was then added to quench the reaction. The aqueous
layer was extracted with dichloromethane, and the crude adduct
was treated with THF/1 N HCl (10:1) at 0 °C for 30 min. After
Acknowledgment. H.I. thanks the JSPS fellowship for Japanese Junior
Scientists. This work was partially supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Science, Sports, and
Culture, Japan, and a SUT Special Grant for Research Promotion.
Supporting Information Available: Experimental procedures and
NMR and HPLC data (10 pages). See any current masthead page for
ordering and Internet access instructions.
JA973527T
(10) (a) Nicolaou, K. C.; Dai, W.-M.; Guy, R. K. Angew. Chem., Int. Ed.
Engl. 1994, 33, 15. (b) Escalante, J.; Juaristi, E. Tetrahedron Lett. 1995, 36,
4397. (c) Wang, Z.-M.; Kolb, H. C.; Sharpless, K. B. J. Org. Chem. 1994,
59, 5104. (d) Deng, L.; Jacobsen, E. N. J. Org. Chem. 1992, 57, 4320. (e)
Georg, G. I.; Mashava, P. M.; Akgu¨n, E.; Milstead, M. W. Tetrahedron Lett.
1991, 32, 3151. (f) Denis, J.-N.; Correa, A. E.; Greene, A. J. Org. Chem.
1990, 55, 1957. See also ref 4b,e.
(11) Mp 223-225 °C (dec.) (lit. 222-224 °C (dec);12 224-226 °C4e). [R]29
D
(9) The NMR spectra of the corresponding aldimine indicated that most
of them existed as stable benzoxazolidine forms. This is only for the
electrophile derived from cyclohexanecarboxaldehyde and 2-amino-3-meth-
ylphenol.
-13.7 (c 0.83, 6 N HCl) (lit. [R]20D -14.6 (c 1.03, 6 N HCl);12 [R]29D -14.9
(c 0.55, 6 N HCl)4e).
(12) Ojima, I.; Habus, I.; Zhao, M.; Zucco, M.; Park, Y. H.; Sun, C. M.;
Brigaud, T. Tetrahedron 1992, 48, 6985.