the stage for the oxidation of the dihyrohaphthalene unit to
the acyloin unit of 3.
Scheme 7. Synthesis of Acyloin 3
Osmium45 and ruthenium46 based keto-hydroxylation
reactions were first examined as a means to convert 23 to 3.
These reactions yielded the 1,2-diol as the major product.
In contrast, a protocol employing KMnO4 and CuSO4·5H2O
under phase transfer conditions47 gave only acyloin 3.
However, this reaction required a large excess of oxidant
and long reaction times, even with sonication.48 It was
ultimately found that treatment of ketone 23 in acidic acetone
with KMnO449 furnished a 9:1:1 mixture of 3, the hemiketal
isomer of 3 and the C(2) diastereomer of 3 (which appears
to exist exclusively as a hemiketal). This mixture was
separated by column chromatography to afford the major
diastereomer, acyloin 3, in 55% yield as an 8:1 mixture of
the hydroxy ketone and hemiketal tautomers, respectively,
in CDCl3.50,51 Coupling constant analysis of the hydroxy
ketone tautomer of 3 (3JH2,H3 ) 12.0 Hz) indicated that the
newly formed C(2) carbinol proton is anti to the C(3) methine
proton.
In summary, we have completed the synthesis of an
advanced model system for the aglycone of durhamycin A.
The highlights of this synthesis include the diastereoselective
allylboration of aldehyde 5 and (Z)-δ-(alkoxyallyl)dialky-
lborane 6 to give 4, the selective Bu3SnH reduction of
xanthate 21, the RCM cyclization of the diene derived from
4, and the keto-hydroxylation of the highly functionalized
dihydronapththalene 23. Further progress towards the total
synthesis of durhamycin A and aureolic acid analogues will
be reported in due course.
catalyst42 in the presence of Ti(i-OPr)4 to give the dihy-
dronaphthalene, and the TCE protecting group was removed
by using activated zinc.43 This three-step sequence furnished
alcohol 22 in 34% yield. Oxidation of 22 by using the
Dess-Martin reagent44 provided ketone 23, thereby setting
(36) (a) Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512.
(b) Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J. Am. Chem. Soc.
1991, 113, 4092.
Acknowledgment. This work was supported by the
National Institutes of Health (GM038436)
(37) Lautens, M.; Hiebert, S. J. Am. Chem. Soc. 2004, 126, 1437.
(38) Similar assignments by half-chair coupling constants: (a) Hobbs-
Mallyon, D.; Li, W.; Whiting, D. A. J. Chem. Soc., Perkin Trans. 1 1997,
1511. (b) Thorey, C.; Bouquillon, S.; Helimi, A.; He´nin, F.; Muzart, J. Eur.
J. Org. Chem. 2002, 2151.
Supporting Information Available: Experimental pro-
cedures and tabulated spectroscopic data for all new com-
pounds. This material is available free of charge via the
(39) (a) For formation of (E)-allyl(diisopinocampheyl)boranes by room
temperature allene hydroboration: Naria, G.; Brown, H. C. Tetrahedron
Lett. 1997, 38, 219. (b) For low-temperature formation of (Z)- and (E)-
crotyl(diisopinocampheyl)boranes: Brown, H. C.; Bhat, K. S. J. Am. Chem.
Soc. 1986, 108, 5919. (c) For formation of a kinetic (Z)-silylallyl(diiso-
pinocampheyl)borane by allene hydroboration and isomerization studies:
Heo, J.-N.; Micalizio, G. C.; Roush, W. R. Org. Lett. 2003, 5, 1693. (d)
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G. W.; Brown, H. C. J. Organomet. Chem. 1977, 132, 9.
OL8018727
(45) Fleming, J. J.; McReynolds, M. D.; Dubois, J. J. Am. Chem. Soc.
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(46) Plietker, B. Synthesis 2005, 15, 2453.
(47) Baskaran, S.; Das, J.; Chandrasekaran, S. J. Org. Chem. 1989, 54,
5182.
(40) Efforts to convert the benzylic alcohol to a halide, tosylate, or
mesylate leaving group resulted in either elimination or cyclization of the
TCE-protected alcohol to form a tetrahydrofuran.
(48) Ryoo, E. S.; Shin, D. H.; Han, B. H. J. Korean Chem. Soc. 1987,
31, 359.
(41) (a) For BEt3-intiated Bu3SnH xanthate reductions, see: Nozaki, K.;
Oshima, K.; Utimoto, K. Tetrahedron Lett. 1988, 29, 6125. (b) For a review
on Bu3SnH reductions, see: Neumann, W. P. Synthesis 1987, 665.
(42) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999,
1, 953.
(49) Srinivasan, N. S.; Lee, D. G. Synthesis 1979, 7, 520.
(50) Keto-hydroxylation of substrates (not shown) lacking the C(2′)
ketone (and therefore incapable of forming hemiketals) gave 8-10:1
mixtures of C(2) acyloin epimers.
(51) Hemiketal formation, analogous to that indicated here for 2, is well
documented in the olivin series (e.g., ref 22 and Roush, W. R.; Briner, K.;
(43) Jacobson, R. M.; Clader, J. W. Synth. Commun. 1979, 9, 57.
(44) Dess, P. B.; Martin, J. C. J. Am. Chem. Soc. 1978, 100, 300.
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.
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