Methanolysis of the benzylidene acetal under acidic conditions
provided diol 15 in 90% yield. Bis-silylation of 15 and
subsequent acid treatment gave alcohol 16 in 84% yield for
the two steps. Oxidation of 16 to carboxylic acid 17 and
condensation with p-toluenethiol (DCC, DMAP) furnished
thioester 7 in 85% yield (three steps).
23 with MeMgBr20 provided methyl ketone 24 in 96% yield,
which was converted to vinylstannane 6 via Stille coupling
of the corresponding enol triflate with hexamethylditin
under the standard conditions (71%, two steps).21
Scheme 4. Synthesis of Vinylstannane 4
Scheme 3. Synthesis of Vinylstannane 6
The synthesis of vinylstannane 4 started with copper(I)-
catalyzed regioselective allylation of benzyl (S)-glycidyl
ether (25) (Scheme 4). Subsequent silylation and ozonolysis
provided aldehyde 26 in 69% overall yield. Aldehyde 26 was
transformed to alkyne 27 via a dibromoolefin according to
the Corey;Fuchs protocol (95%, two steps).22 Regioselec-
tive hydrostannylation of 27 was performed with (n-Bu3Sn)2-
Cu(CN)Li223 to afford vinylstannane 4 in 84% yield.
Having synthesized the requisite fragments 4, 6, and 7,
we proceeded to assemble these fragments toward com-
pletion of the synthesis (Scheme 5). Coupling of thioester
7 with vinylstannane 6 was best accomplished under the
influence of a Pd2(dba)3/Ph3As catalyst system and
copper(I) diphenylphosphinate (CuDPP) in THF at room
temperature. Under these conditions, enone 28 was isolated
in 96% yield. Chelate-controlled reduction24 of 28 with
Zn(BH4)2 (Et2O, -40 °C) gave a chromatographically
separable 5:1 mixture of allylic alcohol 29 and its C7 epimer
in 63% combined yield. Silylation of 29 and deprotection of
the MPM group led to alcohol 30 almost quantitatively.
Oxidation of 30 to carboxylic acid 31 followed by coupling
with p-toluenethiol delivered thioester 5 in 82% yield for
the three steps. This was coupled with vinylstannane 4
[Pd2(dba)3/Ph3As, CuDPP, THF, room temperature] to
afford enone 3 in 86% yield. Removal of the silyl groups
with tris(dimethylamino)sulfonium difluorotrimethylsilicate
(TASF)25 gave cyclization precursor 32 in 87% yield.
The vinylstannane 6 was prepared as summarized in
Scheme 3. Coupling of the known carboxylic acid 1816
with (R)-4-benzyloxazolidin-2-one (19) (PivCl, Et3N, THF,
-20 °C; then LiCl, 19, rt)17 delivered imide 20 in 89% yield.
Asymmetric methylation of 20 according to the Evans
protocol (NaHMDS, THF, -78 °C; then MeI, -78 to
-40 °C)18 afforded methylated product 21 in 95% yield
1
as a single stereoisomer, as judged by 500 MHz H
NMR. Removal of the chiral auxiliary by exposure to
alkaline peroxide19 yielded carboxylic acid 22 in 98%
yield, which was coupled with N,O-dimethylhydroxya-
mine to give Weinreb amide 23 in 73% yield. Treatment of
(21) Wulff, W. D.; Peterson, G. A.; Bauta, W. E.; Chan, K.-S.;
Faron, K. L.; Gilbertson, S. R.; Kaesler, R. W.; Yang, D. C.; Murray,
C. K. J. Org. Chem. 1986, 51, 277.
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(18) Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem. Soc.
1982, 104, 1737.
(19) Evans, D. A.; Britton, T. C.; Ellman, J. A. Tetrahedron Lett.
(22) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 3769.
(23) Sharma, S.; Oehlschlager, A. C. J. Org. Chem. 1989, 54, 5064.
(24) Oishi, T.; Nakata, T. Acc. Chem. Res. 1984, 17, 338.
(25) (a) Noyori, R.; Nishida, I.; Sataka, J.; Nishizawa, M. J. Am.
Chem. Soc. 1980, 102, 1223. (b) Scheidt, K. A.; Chen, H.; Follows, B. C.;
Chemler, S. R.; Coffey, D. S.; Roush, W. R. J. Org. Chem. 1998, 63,
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1987, 28, 6141.
(20) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815.
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