Scheme 3
Scheme 4a
a (a) 5% Pd-C, H2, Ac2O [as solvent], rt, 4 h; (b) CF3COOH,
Et3SiH, CH2Cl2, rt, 2 h; (c) AIBN [cat.], n-Bu3SnH [as solvent],
130 °C, sealed tube.
64% ee, which is quite comparable to those reported by
Sharpless for asymmetric cis-dihydroxylation of chromenes.23
Likewise, the use of [DHQ]2PHAL [two dihydroquinine
ligands linked with phthalazine] led to ent-19-cis in 50%
yield with 54% ee. In addition, we found that optically pure
dihydropyridine 31 could also undergo cis-dihydroxylation,
although slower, using OsO4 and K3FeCN622 to provide cis-
diol 32 as a single diastereomer in 50% yield. The relative
stereochemistry between C4, C5, and C6 was unambiguously
assigned using NOE experiments. This stereoselective cis-
dihydroxylation protocol provides ocataquinolenone system
31 and offers a potential approach to the AB-ring system of
lepadin A [6].
With these cis-diols in hand, the remaining challenging
issue is the ability to selectively remove the C4 hydroxyl
group which is not very well-known. This stands as a key
transformation for potential total synthesis of relevant natural
products 4-6 using the formal [3 + 3]-cycloaddition
approach.
hydroxylated compound 33 in 74% yield by using a
hydrogenation protocol in which Ac2O is used as solvent.25
The use of alcohol solvents such as MeOH led to isolation
of products with the MeO group substituted at C4. While
TMSH reduction in TFAA was also feasible,26 the most
reliable protocol that provided 33 in 78% yield has been the
two-step sequence consisting of the formation of thiolcar-
bonate 34 followed by a Barton-type deoxygenation of the
more activated allylic hydroxyl group at C4 [Scheme 4].27
We have described here highly stereoselective trans- and
cis-dihydroxylations of these olefinic systems in both 2H-
pyrans and dihydropyridines. This methodology represents
a key transformation in constructing various natural products
using the formal [3 + 3]-cycloaddition approach. Efforts
related to these natural product syntheses are currently
underway.
Acknowledgment. R.P.H. thanks the National Institutes
of Health [NS38049] and the donors of the Petroleum
Research Fund [Type-G].
As shown in Scheme 4, after exploring a variety of
different conditions,24 the C4 hydroxyl group in cis-diol 30
was successfully removed to provide the desired mono-
Supporting Information Available: Experimental pro-
1
cedures as well as H NMR spectral and characterization
(15) For some examples, see: (a) Jacobsen, E. N.; Zhang, W.; Muci, A.
R.; Ecker, J. R.; Deng, L. J. Am. Chem. Soc. 1991, 113, 7063. (b) Yorozu,
K.; Takai, T. Yamada, T.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 1994, 67,
2195. (c) Vander Velde, S. L.; Jacobsen, E. J. J. Org. Chem. 1995, 60,
5380.
data for all new compounds. This material is available free
OL010034R
(16) (a) Costes, N.; Michel, S.; Tillequin, F.; Koch, M.; Pierre´, A.; Atassi,
G. J. Nat. Prod. 1999, 62, 490. (b) David, M.; Boustie, J.; Peilloux, A.;
Poupon, E.; Amoros, M.; Sauleau, A. Pharm. Sci. 1997, 5, 305.
(17) (a) Brown, R. F. C.; Hobbs, J. J.; Hughs, G. K.; Richie, E. Aust. J.
Chem. 1954, 7, 348 and 374. (b) Watters, W. H.; Ramachandran, V. N. J.
Chem. Res., Miniprint 1997, 6, 1201.
(23) The absolute stereochemistry of 19-cis and ent-19-cis were assigned
on the basis of Sharpless’ mnemonics, see: Wang, Z.-M.; Kakiuchi, K.;
Sharpless, K. B. J. Org. Chem. 1994, 59, 6895.
(24) Reductive conditions such as ZnI2 with NaCNBH3, Ph3P with
NaCNBH3, and SOCl2 followed by DIBAL-H did not provide the desired
monohydroxylated products.
(25) (a) Burns, C. J.; Gill, M.; Saubern, S. Aust. J. Chem. 1991, 44,
1427. (b) Rodriguez-Hahn, L.; Esquivel, B.; Sanchez, C.; Estebanes, L.;
Cardenas, J. Phytochemistry 1989, 28, 567.
(18) All new compounds are characterized by 1H NMR, 13C NMR, FTIR,
and mass spectroscopy.
(19) cis/trans-Isomers of diol 14 or 15 were isolated under some of
these conditions.
(20) Appendino, G.; Cravotto, G.; Nano, G. M.; Palmisano, G.; Annun-
zata, R. HelV. Chim. Acta 1993, 76, 1194.
(26) Carey, F. A.; Tremper, H. S. J. Org. Chem. 1971, 36, 758.
(27) (a) Rho, H.-S.; Ko, B.-S. Synth. Commun. 1999, 29, 2875. (b)
Fukukawa, K.; Ueda, T.; Hirano, T. Chem. Pharm. Bull. 1983, 31, 1842.
Many side products such as 25 [from elimination of both hydroxyl groups]
were observed when n-Bu3SnH was not used as solvent or in large excess.
(21) Lau, C. K.; Defresne, C.; Belanger, P. C.; Pietre, S.; Scheigetz, J.
J. Org. Chem. 1986, 51, 3038.
(22) Vedejs, E.; Kruger, A. W. J. Org. Chem. 1999, 64, 4790.
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