C O M M U N I C A T I O N S
Scheme 3 a
a Reagents: (a) 10, Cy2BCl, EtNMe2 0 f -78 °C then 9-(S). (b) Me4NBH(OAc)3, MeCN, AcOH, 0 °C. (c) HN(CH2CH2OH)2, EtOAc, rt. (d)
HNMe(OMe)‚HCl, AlMe3, CH2Cl2, 0 °C f rt. (e) Me2C(OMe)2, PPTS, acetone, rt. (f) LiAlH4, Et2O, rt. (g) BF3‚OEt2, toluene, -90 °C. (h) TBSOTf,
2,6-lutidine, CH2Cl2, -78 °C. (i) PPTS, MeOH, rt. (j) MeOTf, 2,6-di-tert-butylpyridine, CH2Cl2, rt. (k) TBAF, THF, rt. (l) MsCl, Et3N, DMAP, CH2Cl2, 0
°C. (m) LiOH, H2O, MeOH, THF, rt. (n) 1.5 mM, Cs2CO3, 18-crown-6, toluene, 110 °C. (o) TBAF, THF, rt. (p) 3, NIS, TfOH, 2,6-di-tert-butyl-4-methylpyridine,
CH2Cl2, -15 °C f rt. (q) DDQ, MeOH, CH2Cl2, H2O, rt. (r) SO2‚pyr, Et2N, DMSO, CH2Cl2, 0 °C.
Scheme 4 a
Acknowledgment. Support has been provided by the NIH (GM
33328-18), NSF, and Merck Research Laboratories.
Supporting Information Available: Full characterization data of
all new compounds (PDF). This material is available free of charge
References
(1) Zampella, A.; D’Auria, M. V.; Minale, L.; Debitus, C.; Roussakis, C. J.
Am. Chem. Soc. 1996, 118, 11085-11088.
(2) (a) Paterson, I.; Davies, R. D. M.; Marquez, R. Angew. Chem., Int. Ed.
2001, 40, 603-607. (b) Trost, B. M.; Dirat, O.; Gunzner, J. L. Angew.
Chem., Int. Ed. 2002, 41, 841-843.
(3) (a) Evans, D. A.; Hu, E.; Tedrow, J. S. Org. Lett. 2001, 3, 3133-3136.
(b) Evans, D. A.; Burch, J. D. Org. Lett. 2001, 3, 503-505.
(4) Celmer, W. D. Ann. N.Y. Acad. Sci. 1986, 471, 299-303.
(5) Evans, D. A.; Kozlowski, M. C.; Murray, J. A.; Burgey, C. S.; Connell,
B. J. Am. Chem. Soc. 1999, 121, 669-685.
(6) Concurrent with this work, the Paterson group published a route to the
a Reagents: (a) LiHMDS, 4a, THF, -78 °C f rt. (b) LiHMDS, 4b,
THF, -78 °C f rt. (c) I2, CH2Cl2, rt. (d) TBAF, AcOH, THF, rt.
callipeltoside aglycon that utilizes a racemic vinylogous aldol reaction to
set the C10-C11 olefin geometry, ref 2a.
(7) For a review of the vinylogous aldol reaction see: Casiraghi, G.; Zanardi,
F.; Appendino, G.; Rassu, G. Chem. ReV. 2000, 100, 1929-1972.
(8) Hoffmann, R. V.; Kim, H.-O. J. Org. Chem. 1991, 56, 1014-1019.
refluxing toluene effected the desired macrocyclization to produce
macrolactone 17 in 66% yield after Bu4N+F- (TBAF) deprotection.
NIS-mediated glycosidation16 of thioglycoside 3 with alcohol
acceptor 17 formed the glycoside bond in 95% yield as a single
anomer.
(9) The absolute stereochemistry of 8, established by Mosher ester analysis,
is consistent with prior precedent for these reactions, ref 5.
(10) Evans, D. A.; Ng, H. P.; Clark, J. S.; Rieger, D. L. Tetrahedron 1992,
48, 2127-2142.
(11) (a) Due to the chromatographic instability of ketones 11a and 11b,
diastereoselectivity was deteremined by HPLC analysis (Zorbax SiO2
column) of lactones 12. Relative stereochemistry of all lactones was
verified by NOESY analysis, indicating that in all cases the reduction
step proceeded with complete diastereocontrol. (b) As a reference, the
sterically and electronically similar senecialdehyde exhibited a 5:1
diastereoselectivity in this reaction.
(12) For a successful Mitsunobu cyclization on a similar system see: Evans,
D. A.; Ratz, A. M.; Huff, B. E.; Sheppard, G. S. J. Am. Chem. Soc. 1995,
117, 3448-3467.
Consecutive deprotection of the C14 p-methoxybenzyl (PMB)
ether and hydrolysis of the C3 ketal to lactol with DDQ afforded
18 in 83% yield, which was oxidized to 19 under Parikh-Doering
conditions.17 Although olefination of phosphonate 4 was only
moderately selective (E:Z ) 3:1), this mixture could be cleanly
isomerized to the trans olefin (E:Z >11:1) by using a catalytic
amount of iodine (Scheme 4). Finally, desilylation with TBAF/
AcOH furnished 20 in 56% overall yield from alcohol 18. The other
trans-chlorocyclopropane side chain isomer 21 was prepared in a
similar manner. Indeed, while the spectral data of the diastereomers
20 and 21 were both completely consistent with natural callipelto-
side, the optical rotations of the two diastereomers differed in both
sign and magnitude: diastereomer 20 exhibited a rotation of -17°
(c 0.19, MeOH) while diastereomer 21 registered a rotation of
+140° (c 0.05, MeOH). Since natural callipeltoside A has a reported
optical rotation of -17.6° (c 0.04, MeOH),1 we conclude that 20
is the structure of callipeltoside A, in full agreement with the
conclusions drawn by Trost.
(13) Evans, D. A.; Chapman, K. T.; Carreira, E. M. J. Am. Chem. Soc. 1988,
110, 3560-3578.
(14) (a) Chan, T.-H.; Brownbridge, P. J. Am. Chem. Soc. 1980, 102, 3534-
3538. (b) For a review of the chemistry of Chan’s diene see: Langer, P.
Synthesis 2002, 4, 441-459.
(15) Felkin selectivity in this substrate is expected to be high due to the
reinforcing stereochemical relationships of the R-methyl and â-OR
relationships: Evans, D. A.; Yang, M. G.; Dart, M. J.; Duffy, J. L. J.
Am. Chem. Soc. 1996, 37, 1957-1960.
(16) (a) Konradsson, P.; Udodong, U. E.; Fraser-Reid, B. Tetrahedron Lett.
1990, 31, 4313-4316. (b) Konradsson, P.; Mootoo, D. R.; McDevitt, R.
E.; Fraser-Reid, B. J. Chem. Soc., Chem. Commun. 1990, 270-272. (c)
Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J. H. Tetrahedron
Lett. 1990, 31, 1331-1334.
(17) Parikh, J. R.; Doering, W. v. E. J. Am. Chem. Soc. 1967, 89, 5505-5507.
JA026235N
9
J. AM. CHEM. SOC. VOL. 124, NO. 20, 2002 5655