Organic Letters
Letter
(7) (a) Evans, D. A.; Bartroli, J.; Shih, T. L. J. Am. Chem. Soc. 1981,
103, 2127. (b) Nicolaou, K. C.; Brenzovich, W.; Bulger, P.; Francis, T.
Org. Biomol. Chem. 2006, 4, 2119.
(8) The first-generation synthesis used dimethoxy acetaldehyde in
the aldol addition reaction and required 2 days to convert the alcohol
to the benzyl ether under more forcing conditions (3 equiv of Ag2O
and 2 equiv of BnBr).
(9) (a) Hua, Z.; Yu, W.; Jin, Z. Org. Lett. 2004, 6, 3217. (b) Because
the α-position of aldehyde 6 epimerizes during silica gel chromatog-
raphy, the crude material was used for the subsequent coupling
reaction without purification.
(10) The use of the alkene avoids the problematic dimethyl acetal of
the first-generation synthesis, which slowly hydrolyzed and decom-
posed upon storage.
(21) To our knowledge, this functionality has not been explored
outside our laboratory.
(22) The structure of new compounds were assigned unambiguously
(23) (a) Joyasawal, S.; Lotesta, S. D.; Akhmedov, N. G.; Williams, L.
J. Org. Lett. 2010, 12, 988. (b) Ghosh, P.; Cusick, J. R.; Inghrim, J.;
Williams, L. J. Org. Lett. 2009, 11, 4672. (c) Zhang, Y.; Cusick, J. R.;
Ghosh, P.; Shangguan, N.; Katukojvala, S.; Inghrim, J.; Emge, T. J.;
Williams, L. J. J. Org. Chem. 2009, 74, 7707. (d) Wang, Z.; Shangguan,
N.; Cusick, J. R.; Williams, L. J. Synlett 2008, 2008, 213. (e) Lotesta, S.
D.; Kiren, S.; Sauers, R. R.; Williams, L. J. Angew. Chem., Int. Ed. 2007,
46, 7108. (f) Ghosh, P.; Lotesta, S. D.; Williams, L. J. J. Am. Chem. Soc.
2007, 129, 2438. (g) Lotesta, S. D.; Hou, Y.; Williams, L. J. Org. Lett.
2007, 9, 869. (h) Katukojvala, S.; Barlett, K. N.; Lotesta, S. D.;
Williams, L. J. J. Am. Chem. Soc. 2004, 126, 15348.
(11) Mead, K. T. Tetrahedron Lett. 1987, 28, 1019.
(24) Other than ref 5b, allene oxidation with osmium tetroxide has
been only tentatively examined: (a) Fleming, S. A.; Liu, R.; Redd, J. T.
Tetrahedron Lett. 2005, 46, 8095. (b) Fleming, S. A.; Carroll, S. M.;
Hirschi, J.; Liu, R.; Pace, J. L.; Redd, J. T. Tetrahedron Lett. 2004, 45,
3341. (c) Mereyala, H. B.; Gurrala, S. R.; Mohan, S. K. Tetrahedron
1999, 55, 11331. (d) Manabe, S. Chem. Commun. 1997, 737.
(12) This procedure was more expeditious than the earlier synthesis
(ref 5b), which generated the aldehyde through acetic acid/TFA/water
(4:1:1) cleavage of the corresponding acetal over the course of 14 h at
rt. Acetic acid and water were insufficient.
(13) Glycosylation, which is essential for erythronolide bioactivity,
will be discussed elsewhere.
(14) Woodward, R. B.; Logusch, E.; Nambiar, K. P.; Sakan, K.; Ward,
D. E.; Au-Yeung, B.-W.; Balaram, P.; Browne, L. J.; Card, P. J.; Chen,
C. H.; Chenevert, R. B.; Fliri, A.; Frobel, K.; Gais, H.-J.; Garratt, D. G.;
Hayakawa, K.; Heggie, W.; Hesson, D. P.; Hoppe, D.; Hoppe, I.;
Hyatt, J. A.; Ikeda, D.; Jacobi, P. A.; Kim, K. S.; Kobuke, Y.; Kojima,
K.; Krowicki, K.; Lee, V. J.; Leutert, T.; Malchenko, S.; Martens, J.;
Matthews, R. S.; Ong, B. S.; Press, J. B.; Rajan Babu, T. V.; Rousseau,
G.; Sauter, H. M.; Suzuki, M.; Tatsuta, K.; Tolbert, L. M.; Truesdale,
E. A.; Uchida, I.; Ueda, Y.; Uyehara, T.; Vasella, A. T.; Vladuchick, W.
C.; Wade, P. A.; Williams, R. M.; Wong, H. N.-C. J. Am. Chem. Soc.
1981, 103, 3210 , 3213, 3215.
́
(e) David, K.; Ariente, C.; Greiner, A.; Gore, J.; Cazes, B. Tetrahedron
Lett. 1996, 37, 3335. (f) Wolff, S.; Agosta, W. C. Can. J. Chem. 1984,
62, 2429. (g) Biollaz, M.; Haefliger, W.; Velarde, E.; Crabbe, P.; Fried,
J. H. J. Chem. Soc. D 1971, 0, 1322.
(15) For cyclization with cyclic protecting groups spanning C3−C5
and C9−C11 as well as the S configuration at C9: (a) Stork, G.;
Rychnovsky, S. D. J. Am. Chem. Soc. 1987, 109, 1565. (b) Nakata, M.;
Arai, M.; Tomooka, K.; Ohsawa, N.; Kinoshita, M. Bull. Chem. Soc. Jpn.
1989, 62, 2618. (c) Hikota, M.; Tone, H.; Horita, K.; Yonemitsu, O. J.
Org. Chem. 1990, 55, 7. (d) Myles, D. C.; Danishefsky, S. J.; Schulte,
G. J. Org. Chem. 1990, 55, 1636. (e) Sviridov, A. F.; Borodkin, V. S.;
Ermolenko, M. S.; Yashunsky, D. V.; Kochetkov, N. K. Tetrahedron
1991, 47, 2317. (f) Sturmer, R.; Ritter, K.; Hoffmann, R. W. Angew.
̈
Chem., Int. Ed. Engl. 1993, 32, 101. (g) Evans, D. A.; Kim, A. S.;
Metternich, R.; Novack, V. J. J. Am. Chem. Soc. 1998, 120, 5921.
(h) Peng, Z. H.; Woerpel, K. J. Am. Chem. Soc. 2003, 125, 6018.
(i) Stang, E. M.; White, M. C. Nat. Chem. 2009, 1, 547. (j) Chandra,
B.; Fu, D.; Nelson, S. G. Angew. Chem., Int. Ed. 2010, 49, 2591. For
cyclization with a cyclic protecting group spanning C3−C5 and the S
configuration at C9: (k) Corey, E. J.; Hopkins, P. B.; Kim, S.; Yoo, S.
E.; Nambiar, K. P.; Falck, J. R. J. Am. Chem. Soc. 1979, 101, 7131. For
cyclization without cyclic protecting group and with the S
configuration at C9: (l) Paterson, I.; Rawson, D. J. Tetrahedron Lett.
1989, 30, 7463.
(16) This interesting selectivity may reflect the increased accessibility
of the C-9 benzyl compared to the C-3 benzyl.
(17) Mitsunobu, O.; Yamada, Y. Bull. Chem. Soc. Jpn. 1967, 40, 2380.
(18) The macrolactone 19 resisted various hydrolysis conditions
(e.g., LiOOH, 5 M KOH in H2O/MeOH). Nevertheless concentrated
sodium methoxide was found to open the macrolactone. The seco acid
20 was obtained as a mixture of inseparable C2 epimers (dr = 2:1).
This finding is reminiscent of the findings of Martin et al., where the
hydrolysis of a 14-membered lactone derived from erythromycin B
proved stubbornly resistant to cleavage under a wide variety of
reaction conditions. Martin, S. F.; Yamashita, M. J. Am. Chem. Soc.
1991, 113, 5478.
(19) Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi, M.
Bull. Chem. Soc. Jpn. 1979, 52, 1989.
HOAc and buffer.
D
Org. Lett. XXXX, XXX, XXX−XXX