ing ketone, followed by nucleophilic addition, would furnish
homoallylic tertiary alcohols. Chelation-controlled dia-
stereoselective nucleophilic additions on R-alkoxyketones6
are well-known. On this basis, we undertook a project
involving diastereoselective nucleophilic additions on R-
alkoxyketones derived from syn-alkoxy homoallylic alcohols.
We started with syn-monoalkoxy homoallylic alcohols 4a
and 4b derived from reaction of B-γ-methoxyethoxymethoxy-
allyldiisopinocampheylborane7 3 with acetaldehyde and
benzaldehyde, respectively. The alcohols 4a and 4b were
oxidized to the corresponding ketones 5a and 5b using
Dess-Martin periodinane (DMP).8 We chose various nu-
cleophiles as representative examples for the present study.
Reduction of ketones 5a and 5b with Zn(BH4)2 at -78 °C
afforded anti-homoallylic 2°-alcohols 6a and 6e in 50 and
95% de, respectively. Addition of organometallic reagents
took place very smoothly, and the product anti-homoallylic
tertiary alcohols were obtained in very high de (Scheme 1
respectively, in good yields by cleaving the MEM group
under acidic conditions (Scheme 2).
Scheme 2
Application of this methodology was further demonstrated
by the synthesis of the C8 epimer of the C1-C11 subunit of
fostriecin (Figure 1). Fostriecin is a natural product isolated
Scheme 1a
Figure 1.
from Streptomyces pulVeraceus exhibiting potent anti-cancer
properties against a wide range of cell lines.9 Accordingly,
there have been several reports of the synthesis of this
molecule in the recent past.10 We have employed a strategy
similar to our ongoing program on “allyl”boration-ring-
closing metathesis for the synthesis of biologically active
natural products.11
a Conditions: (a) sec-BuLi, THF, -78 °C, 0.5 h. (b) (+)-
Ipc2BOMe, -78 °C, 1 h. (c) BF3.Et2O, -78 °C, 5 min. (d) RCHO,
-78 °C, 10 h. (e) NaOH/H2O2, rt, 6 h. (f) DMP, CH2Cl2, (g) Nu-.
and Table 1). In all of these cases, metal coordination with
carbonyl oxygen and alkoxy oxygen atom leads to a five-
membered transition state followed by nucleophilic addition
from the opposite face providing the anti products.
To demonstrate the utility of this procedure, we converted
the anti-alcohols 6e and 6f into anti-diols 7e and 7f,
(6) (a) Reetz, M. T. Angew Chem., Int. Ed. 1984, 23, 556. (b) Still, W.
C.; McDonald, J. H., III. Tetrahedron Lett. 1980, 21, 1031. (c) Nicolaou,
K. C.; Claremon, D. A.; Barnette, W. E. J. Am. Chem. Soc. 1980, 102,
6611. (d) McGarvey, G. J.; Kimura, M. J. Org. Chem. 1982, 47, 5422. (e)
Kobayashi, Y.; Kumar, G. B.; Kurachi, T.; Acharya, H. P.; Yamazaki, T.;
Kitazume, T. J. Org. Chem. 2001, 66, 2011. (f) Carven, A.; Tapolczay, D.
J.; Thomas, E. J.; Whiteland, J. W. F. Chem. Commun. 1985, 145.
(7) (a) Nicolaou, K. C.; Smith, A. L.; Mizuno, Y. J. Am. Chem. Soc.
1993, 115, 7612. (b) Ramachandran, P. V. Prabhudas, B.; Pratihar, D.;
Chandra, J. S.; Reddy, M. V. R. Tetrahedron Lett. 2003, 44, 3745.
(8) (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155. (b)
Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 13, 7277.
Table 1.
(9) (a) Tunac, J. B.; Graham, B. D.; Dobson, W. E. J. Antibiot. 1983,
36, 1595. (b) Stampwala, S. S.; Bunge, R. H.; Hurley, T. R.; Willmer, N.
E.; Brankiewicz, A. J.; Steinman, C. E.; Smittka, T. A.; French, J. C. J.
Antibiot. 1983, 36, 1601. (c) Leopold, W. R.; Shillis, J. L.; Nelson, J. M.;
Roberts, B. J. Cancer Res. 1984, 44, 1928.
(10) (a) Boger, D. L.; Hikota, M.; Lewis, B. M. J. Org. Chem. 1997,
62, 1748. (b) Boger, D. L.; Ichikawa, S.; Zhong, W. J. Am. Chem. Soc.
2001, 123, 4161. (c) Chavez, D. E.; Jacobsen, E. N. Angew Chem. Int. Ed.
2001, 40, 3667. (d) Reddy, Y. K.; Falck, J. R. Org. Lett. 2002, 4, 969. (e)
Miyashita, K.; Ikejiri, M.; Kawasaki, H.; Maemura, S.; Imanishi, T. Chem.
Commun. 2002, 742. (f) Wang, Y.-G.; Kobayashi, Y. Org. Lett. 2002, 4,
4615. (g) Esumi, T.; Okamoto, N.; Hatakayema, S. Chem. Commun. 2002,
3042. (h) Fujii, K.; Maki, K.; Kanai, M.; Shibasaki, M. Org. Lett. 2003, 5,
733. (i) Miyashita, K.; Ikejiri, M.; Kawasaki, H.; Maemura, S.; Imanishi,
T. J. Am. Chem. Soc. 2003, 125, 8238.
compd
R
Nu
yield
de
6a
6b
6c
6d
6e
6f
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Zn(BH4)2
EtMgBr
(CH2dCH)MgBr
CH3-CtCMgBr
Zn(BH4)2
EtMgBr
(CH2dCH)MgBr
CH3-CtCMgBr
90
85
78
75
92
88
81
77
50
>95
>95
85
>95
>95
>95
>95
6g
6h
3756
Org. Lett., Vol. 5, No. 20, 2003