T. J. Blackburn et al. / Tetrahedron Letters 50 (2009) 3550–3554
3553
Regioselective monosilylation of the dihydroxyepoxide 31 gave
the silyl ether 40, see Scheme 7, and alkylation of the free hydroxyl
group gave the benzyl ether 41 which was desilylated to give the
required hydroxyepoxide 42. Oxidation with TPAP proceeded as
expected to give keto-aldehyde 43 but reduction using di-iso-
butylaluminium hydride gave mainly diol 44 which was shown
to have the wrong configuration at C(14) by determination of the
X-ray crystal structure of its diacetate 45, see Figure 3.
The reductions of keto-aldehydes 33 and 43 using di-isobutylal-
uminium hydride proceed with opposite stereoselectivities with
respect to the ketone functionality at C(14). This unexpected result
may be due to the phenylsulfonyl group in keto-aldehyde 33
shielding the lower face of the 14-carbonyl group so directing hy-
dride attack leading to the required configuration at C(14) in alco-
hol 34. Keto-aldehyde 43 lacks the 10-phenylsulfonyl substituent
and steric hindrance by the cis-disposed 12- and 13-methyl sub-
stituents would appear to dominate leading to the undesired con-
figuration at C(14).
Moreover, the introduction of the C(3)–C(4) epoxide, which relies
on the presence of a hydroxyl group at C(2), needs to take place
before the introduction of C(1)–C(15) double bond. Therefore it
would appear necessary to have a protecting group on the
2-hydroxyl substituent which can be removed without concomi-
tant reductive cleavage of the phenylsulfone. Introduction of the
C(3)–C(4)-epoxide, TPAP oxidation and DIBAL-H reduction, fol-
lowed by reductive removal of the phenylsulfone, may then lead
to phomactin A.
Conclusions
This work has led to advanced intermediates and provided use-
ful chemical insight which may be useful in syntheses of phomac-
tins. Of interest is the complementary stereoselectivity observed
for [2,3]-Wittig rearrangements of the lithiated methyl ethers gen-
erated from the sulfide 17 and sulfone 18, the oxidations using
TPAP of the homoallylic alcohols 29, 31 and 42, and the stereo-
chemical dichotomy observed during the reduction of the keto-
aldehydes 33 and 43 using di-isobutylaluminium hydride. Present
work is concerned with the further development of these studies
and the completion of a synthesis of phomactin A 1.
In our system, the phenylsulfonyl group at C(10) may be influ-
encing the stereoselectivity of reduction of a ketone at C(14).
OBn
OP
2
H
H
H
O
H
O
Me
Me
Me
Me
Acknowledgement
14
i, ii
iii
Me
OH
Me
OTBS
We thank the EPSRC for studentships (to M.J.K. and T.J.B.).
References and notes
31
Me
iv
Me
40 P = H
42
1. (a) Sugano, M.; Sato, A.; Iijima, Y.; Oshima, T.; Furuya, K.; Kuwano, H.; Hata, T.;
Hanzawa, H. J. Am. Chem. Soc. 1991, 113, 5463; (b) Chu, M.; Patel, M. G.; Gullo,
V. P.; Truumees, I.; Puar, M. S. J. Org. Chem. 1992, 57, 5817; (c) Chu, M.;
Truumees, I.; Gunnarsson, I.; Bishop, W. R.; Kreutner, W.; Horan, A. C.; Patel, M.
G.; Gullo, V. P.; Puar, M. S. J. Antibiot. 1993, 46, 554; (d) Sugano, M.; Sato, A.;
Iijima, Y.; Furuya, K.; Haruyama, H.; Yoda, K.; Hata, T. J. Org. Chem. 1994, 59,
564; (e) Sugano, M.; Sato, A.; Iijima, Y.; Furuya, K.; Kuwano, H.; Hata, T. J.
Antibiot. 1995, 48, 1188; (f) Koyama, K.; Ishino, M.; Takatori, K.; Sugita, T.;
Kinoshita, K.; Takahashi, K. Tetrahedron Lett. 2004, 45, 6947.
41 P = Bn
PO
Me
OBn
CHO
OBn
H
O
Me
Me
H
O
14
v, vi
Me
Me
Me
O
Me
OP
Me
2. (a) Goldring, W. P. D.; Pattenden, G. Chem. Commun. 2002, 1736; (b) Diaper, C.
M.; Goldring, W. P. D.; Pattenden, G. Org. Biomol. Chem. 2003, 1, 3949; (c) Mohr,
P. J.; Halcomb, R. L. J. Am. Chem. Soc. 2003, 125, 1712.
43
44 P = H
3. Miyaoka, H.; Saka, Y.; Miura, S.; Yamada, Y. Tetrahedron Lett. 1996, 37, 7107.
4. Goldring, W. P. D.; Pattenden, G. Org. Biomol. Chem. 2004, 2, 466.
5. Huang, J.; Wu, C.; Wulff, W. D. J. Am. Chem. Soc. 2007, 129, 13366.
6. (a) Foote, K. M.; Hayes, C. J.; Pattenden, G. Tetrahedron Lett. 1996, 37, 275; (b)
Chen, D.; Wang, J.; Totah, N. I. J. Org. Chem. 1999, 64, 1776; (c) Seth, P. P.; Totah,
N. I. J. Org. Chem. 1999, 64, 8750; (d) Seth, P. P.; Chen, D.; Wang, J.; Gao, X.;
Totah, N. I. Tetrahedron 2000, 56, 10185; (e) Seth, P. P.; Totah, N. I. Org Lett.
2000, 2, 2507; (f) Chemler, S. R.; Danishefsky, S. J. Org. Lett. 2000, 2, 2695; (g)
Chemler, S. R.; Iserloh, U.; Danishefsky, S. J. Org. Lett. 2001, 3, 2949; (h) Foote, K.
M.; John, M.; Pattenden, G. Synlett 2001, 365; (i) Mi, B.; Maleczka, R. E., Jr. Org.
Lett. 2001, 3, 1491; (j) Houghton, T. J.; Choi, S.; Rawal, V. H. Org. Lett. 2001, 3,
3615; (k) Mohr, P. J.; Halcomb, R. L. Org. Lett. 2002, 4, 2413; (l) Cheing, J. W. C.;
Goldring, W. P. D.; Pattenden, G. Chem. Commun. 2003, 2788; (m) Foote, K. M.;
Hayes, C. J.; John, M. P.; Pattenden, G. Org. Biomol. Chem. 2003, 1, 3917; (n) Cole,
K. P.; Hsung, R. P. Org. Lett. 2003, 5, 4843; (o) Cole, K. P.; Hsung, R. P. Chem.
Commun. 2005, 5784; (p) Ryu, K.; Cho, Y.-S.; Jung, S.-I.; Cho, C.-G. Org. Lett.
2006, 8, 3343; (q) Teng, D.; Wang, B.; Augatis, A. J.; Totah, N. I. Tetrahedron Lett.
2007, 48, 4605; (r) Huang, J.; Wang, H.; Wu, C.; Wulff, W. D. Org. Lett. 2007, 9,
2799; (s) Kallan, N. C.; Halcomb, R. L. Org. Lett. 2000, 2, 2687; (t) Goldring, W. P.
D.; Alexander, S. P. H.; Kendall, D. A.; Pattenden, G. Bioorg. Med. Chem. Lett.
2005, 15, 3263.
45 P = Ac
Scheme 7. Reagents and conditions: (i) TBSCl, imid., rt, 16 h (99%); (ii) KHMDS,
BnBr, THF, À78 °C to rt, 16 h (99%); (iii) TBAF, THF, rt 16 h (99%); (iv) TPAP, NMO,
4 Å MS, DCM, rt, 1 h (62%); (v) DIBAL-H, DCM, À78 °C, 1 h [69% plus 11% of its
epimer at C(14)]; (vi) Ac2O, Et3N, DMAP, rt, 16 h (99%).
7. Goldring, W. P. D.; Pattenden, G. Acc. Chem. Res. 2006, 39, 354.
8. (a) Balnaves, A. S.; McGowan, G.; Shapland, P. D. P.; Thomas, E. J. Tetrahedron
Lett. 2003, 44, 2713; (b) McGowan, G.; Thomas, E. J. Org. Biomol. Chem., accepted
for publication.
9. Still, W. C.; Mitra, A. J. Am. Chem. Soc. 1978, 100, 1927.
10. Yang, D.; Wong, M.-K.; Yip, Y.-C. J. Org. Chem. 1995, 60, 3887.
11. Luche, J. L. J. Am. Chem. Soc. 1978, 100, 2226.
12. Analogous
[2,3]-Wittig
rearrangements
were
investigated
for
(trimethylsilylethoxy)methyl (SEM) ethers corresponding to the tert-
butyldiphenyl ethers 17 and 18 and for the epimeric SEM-ethers with the
opposite configurations at C(3). In all cases the sulfones and sulfides
rearranged with complementary stereoselectivity as observed for sulfide and
sulfone 17 and 18.
Figure 3. An ORTEP projection of the structure of the diacetate 45 as determined by
13. Vinyl iodide 24 was prepared from the corresponding alkyne using a Negishi
reaction (see Ref. 14).
X-ray crystallography.17