LETTER
Lipase-Catalyzed Kinetic Resolution of 4-(N-Boc-amino)-1-alken-3-ols
2375
NHCbz
NHCbz
NHCbz
OAc
CAL-B
+
PhS
PhS
PhS
OH
OH
syn (±)-3
OAc
(3R,4R)-3-OAc
toluene
(3S,4S)-3
50 °C, 48 h
E value: 922
48% (99%ee)
NHCbz
48% (98%ee)
NHCbz
NHCbz
OAc
+
PhS
PhS
PhS
CAL-B
toluene
OAc
OH
OH
anti (±)-4
(3R,4S)-4-OAc
(3S,4R)-4
50 °C, 48 h
E value> 1000
47% (99%ee)
46% (>99%ee)
Scheme 2
The choice of the amino protecting group is quite impor- pase-catalyzed kinetic resolution to give the correspond-
tant from a synthetic point of view. Thus, we examined ing acetates and alcohols in a highly enantioselective
the kinetic resolution of N-Cbz amino alcohols syn ( )-3 manner. We believe that the present method will largely
and anti ( )-4, in which quite satisfactory results14 were contribute to syntheses of natural products bearing 1,2-
obtained as shown in Scheme 2. Surprisingly, it was amino alcohol units.
found that the reactions with the corresponding N-Bz ami-
no alcohols were too sluggish to be practical.
Acknowledgement
We then executed the enantioselective synthesis of the
We thank The Promotion and Mutual Aid Corporation for Private
taxol side chain starting from syn ( )-5. A solution of
School of Japan for financial support (The Science Research
Promotion Fund). We also thank Toyo Kasei Kogyo Co., Ltd. for a
( )-515 (9.17 mmol) and 2-propenyl acetate (27.5 mmol)
in toluene [27.5 mL, 3 mL per mmol of ( )-5] was stirred
with particles of CAL-B [917 mg, 0.1 g per mmol of
( )-5] at 70 °C for 48 h to give (3R,4R)-5-OAc16 (4.15
mmol, 45%) and (3S,4S)-5 (4.29 mmol, 47%). Benzoyla-
tion (BzCl–Py) of the latter followed by TFA-mediated
cleavage of the Boc group provided a TFA salt of the
amine, which was further treated with Et3N to give benz-
amide 6 in good yield. Finally, the taxol side chain 717 was
afforded by a sequence of protection, oxidation, and
deprotection, the outline being shown in Scheme 3.
generous gift of DPPA.
References
(1) Gargano, J. M.; Lees, W. J. Tetrahedron Lett. 2001, 42,
5845; and references therein.
(2) (a) Umezawa, H.; Aoyagi, T.; Morishima, H.; Matsuzaki,
M.; Hamada, M.; Takeuchi, T. J. Antibiot. 1970, 23, 259.
(b) Yoo, D.; Oh, J. S.; Kim, Y. G. Org. Lett. 2002, 4, 1213;
and references therein.
(3) Jost, S.; Gimbert, Y.; Green, A. E.; Fotiadu, F. J. Org. Chem.
1997, 62, 6672; and references therein.
(4) (a) Sobin, B. A.; Tanner, F. W. Jr. J. Am. Chem. Soc. 1954,
76, 4053. (b) Hulme, A. N.; Rosser, E. M. Org. Lett. 2002,
4, 265; and references therein.
In summary, we have disclosed that the syn- and anti-4-
(N-Boc-amino)-1-alken-3-ols can be resolved by the li-
(5) (a) Kulanthaivel, P.; Hallock, Y. F.; Boros, C.; Hamilton, S.
M.; Janzen, W. P.; Ballas, L. M.; Loomis, C. R.; Jiang, J. B.;
Katz, B.; Steiner, J. R.; Clardy, J. J. Am. Chem. Soc. 1993,
115, 6452. (b) Fürstner, A.; Thiel, O. R. J. Org. Chem. 2000,
65, 1738; and references therein.
(6) (a) Kobayashi, S.; Ueno, M.; Suzuki, R.; Ishitani, H.
Tetrahedron Lett. 1999, 40, 2175. (b) Kikuchi, H.; Tasaka,
H.; Hirai, S.; Takaya, Y.; Iwabuchi, Y.; Ooi, H.;
Hatakeyama, S.; Kim, H.-S.; Wataya, Y.; Oshima, Y. J.
Med. Chem. 2002, 45, 2563; and references therein.
(7) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96,
835.
(8) (a) Review: Johnson, R. A.; Sharpless, K. B. In Catalytic
Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York,
1993, 103. (b) Sharpless, K. B.; Amberg, W.; Bennani, Y.
L.; Crispino, G. A.; Hartung, J.; Jeong, K.-S.; Kwong, H.-L.;
Morikawa, K.; Wang, Z.-M.; Xu, D.; Zhang, X.-L. J. Org.
Chem. 1992, 57, 2768. (c) Bruncko, M.; Schlingloff, G.;
Sharpless, K. B. Angew. Chem., Int. Ed. Engl. 1997, 36,
1483.
NHBoc
OAc
NHBoc
NHBoc
OAc
CAL-B
toluene
70 °C, 48 h
E value> 1000
+
Ph
Ph
Ph
OH
(3S,4S)-5
OH
syn (±)-5
(3R,4R)-5-OAc
45% (>99%ee)
47% (>99%ee)
NHBz
NH2·TFA
c
a, b
(3S,4S)-5
Ph
Ph
OBz
OH
6
NHBz
[α]D25 -35.0 (c 0.95, EtOH)
mp 173–176 °C
[α]D20 –35.5 (c 1.07, EtOH)
d, e, f
CO2H
Ph
OH
lit.17
7
mp 175.5–177 °C
Scheme 3 Reagents and conditions: (a) BzCl–pyridine, 95%; (b)
TFA–CH2Cl2, r. t.; (c) Et3N–THF, 95% in 2 steps; (d) DHP–PPTS–
CH2Cl2, 94%; (e) RuO2–NaIO4–MeCN–CCl4, pH 6.8 phosphate buf-
fer (2:2:3), r.t., 5 h, 72%; (f) p-TsOH–MeOH, r.t., 8 h, 80%.
(9) Mandai, T.; Oshitari, T.; Susowake, M. Synlett 2002, 1665.
(10) Prepared as shown below (Scheme 4).
Synlett 2003, No. 15, 2374–2376 © Thieme Stuttgart · New York