Scheme 2
the keto ester 4 (85%) with 93:7 Z/E selectivity.5 Reduction
cleavage of the cyclic urethane subunit of 10 was effected
by a mild and novel procedure consisting of treatment at
-78 °C with 1 equiv of diisobutyl-n-butylaluminum hydride
(from an equimolar mixture of n-BuLi and DIBAL-H)7
followed by quenching with aqueous acid. The resulting
amino alcohol (53% yield, not optimal) was methylated to
11 and methoxycarbonylated by reaction with 1 atm of CO
in MeOH-dimethylformamide-Et3N in the presence of 0.2
equiv of Pd(OAc)2 and 0.22 equiv of 1,3-bis(diphenylphos-
phino)propane (dppp) at 75 °C for 6 h to give the methyl
of 4 with diisobutylaluminum hydride and subsequent
selective silylation of the primary hydroxyl function with
triisopropylsilyl chloride (TIPSCl) afforded the secondary
alcohol 5 (55% overall), which was transformed by Swern
oxidation (initially at -60 °C with warming after addition
of Et3N to room temperature over 4 h) into the corresponding
methyl ketone 6 (94%). Wittig isopropylidination and
desilylation of 6 gave 3 in 92% overall yield.
The completion of the synthesis of (()-virantmycin is
outlined in Scheme 2. The carbamate 7 was prepared from
the isocyanate 2 and the allylic alcohol 3 by reaction in CH2-
Cl2 in the presence of 0.2 equiv of DMAP at 23 °C for 1.5
h (84%) and converted to the chloro carbamate 8 by
sequential desilylation at 23 °C for 15 min (92%) and
chlorination with 1.1 equiv of SOCl2 and 1.2 equiv of Et3N
in CH2Cl2 at 23 °C for 3 h (75%). Stirring of 8 in CH2Cl2
solution at 23 °C for 48 h with 5 equiv of Cs2CO3 resulted
in completely stereoselective formation of the hydroquinoline
derivative 10 (90%) by way of an internal [4 + 2]
cycloaddition of the intermediate o-azaxylylene 9.6 Reductive
1
ester of (()-virantmycin (12; 85%). The H and 13C NMR,
infrared, and mass spectral data for synthetic 12 were
identical with those previously reported.2a,b Hydrolysis of 12
using 3 equiv of LiOH in 3:1 CH3CN/H2O produced (()-
virantmycin (1), which was identical spectroscopically and
chromatographically with an authentic sample.8
The synthesis of (()-virantmycin reported herein is simple
and expeditious and should, with appropriate modification,
be applicable to the synthesis of the natural enantiomer of
virantmycin (1).
Acknowledgment. We are indebted to the National
Institutes of Health and the Deutscher Akademischer Aus-
tauchdienst (DAAD) for financial assistance of this research.
(4) Nowick, J. S.; Holmes, D. L.; Noronha, G.; Smith, E. M.; Nguyen,
T. M.; Huang, S.-L. J. Org. Chem. 1996, 61, 3929.
(5) (a) Wang, Z.; Lu, X. J. Org. Chem. 1996, 61, 2254. (b) Wang, Z.;
Lu, X. Tetrahedron Lett. 1997, 29, 5213. (c) Wang, Z.; Lu, X. J. Chem.
Soc., Chem. Commun. 1996, 535.
(6) Any E-isomeric chloroolefin which may be present in the starting
material 8 is lost in this step because it does not undergo cyclization under
the conditions of the conversion 8 f 10.
OL9908575
(7) Kim, S.; Ahn, K. H. J. Org. Chem. 1984, 49, 1717.
(8) Graciously provided by Prof. Satoshi Ohmura, to whom we are very
grateful.
824
Org. Lett., Vol. 1, No. 5, 1999