The next chain extension made use of the Paterson/Evans
1,5-asymmetric induction:5,6 The newly generated hydroxyl
functions were first protected as PMB ethers. Conversion
of the diketone to the bis-enolborinate was followed by
reaction with the appropriate aldehyde to furnish in one step
the doubly extended aldol 22 with 5:1 diastereoselectivity.
The configuration of the major (symmetrical) diastereomer
could be shown to be 1,5-anti by the arguments given in the
next paragraph. The further elaboration relied on the 1,3-
anti-selective reduction7 to give tetraol 23. Because of the
poor solubility of 21 in acetonitrile, a slower reduction in
acetone was adopted. The p-methoxybenzyl- and -benzyl-
idene groups were removed simultaneously by hydrogenoly-
sis. The resulting decaol could readily be converted to the
desired penta-acetonide 5.
taken together prove that the aldol addition of 21 to give 22
had generated a 1,5-anti arrangement of the oxygen func-
tionalities.
The syntheses described here show that stereodefined
skipped polyols can be obtained using solely substrate-based
asymmetric induction. The 1,3-asymmetric induction in the
Mukaiyama aldol reaction, the 1,5-asymmetric induction in
the Paterson/Evans enol borinate aldol addition, and the 1,3-
induction in the triacetoxyborohydride reduction of aldols
turned out to be reliable tools. Conformational analysis by
advanced NMR techniques of the compounds obtained is
now in progress and the results will be reported in due course.
Acknowledgment. We thank the Deutsche Forschungs-
gemeinschaft (Graduierten-Kolleg “Metallorganische Che-
mie”), the Volkswagenstiftung, and the Fonds der Chemi-
schen Industrie for support of this study. We thank Dr. B.
C. Kahrs for initial experiments toward the synthesis of
compounds 2 and 3.
The 13C NMR spectra of 5 showed the presence of only
syn-acetonides.11 The reduction of aldol 22 to tetraol 23
should have given an anti-1,3-diol.7 These two statements
(11) (a) Rychnovsky, S. D.; Skalitzky, D. J. Tetrahedron Lett. 1990, 31,
945-948. (b) Evans, D. A.; Rieger, D. L.; Gage, J. R. Tetrahedron Lett.
1990, 31, 7099-7100 The Rychnovsky/Evans rules hold also for 5,5-
disubstituted 1,3-dioxanes, see: Pihlaja, K.; Kivima¨ki, M.; Ari-Matti, M.;
Nurmi, T. J. Org. Chem. 1982, 47, 4688-4692.
OL0056325
(10% tert-butyl methyl ether in pentane). 1H NMR (500 MHz, C6D6): δ )
0.54 (s, 6H), 0.67 (s, 6H), 0.98 (s, 6H), 1.09 (s, 6H), 1.41 (s, 6H), 1.50 (m,
4H), 1.52 (s, 6H), 1.54 (m, 2H), 1.55 (s, 6H), 1.56 (s, 6H), 3.25 (d, J )
11.3 Hz, 2H), 3.51 (d, J ) 11.3 Hz, 2H), 3.87 (dd, J ) 9.3, 2.8 Hz, 2H),
3.91 (m, 4H). 13C NMR (100 MHz, C6D6): δ ) 18.2 (2C), 18.4 (2C), 19.2
(2C), 20.5 (2C), 21.5 (2C), 21.7 (2C), 29.4 (2C), 29.5 (2C), 30.1, 30.7 (2C),
32.7 (2C), 35.3 (2C), 72.3 (2C), 73.9 (2C), 74.0 (2C), 74.4 (2C), 74.5 (2C),
98.5 (2C), 98.7 (2C). HRMS (FAB): C35H64O8 requires for ([M + Na]+)
635.4601, found 635.4474. (4S*,6R*)-2,2,5,5-Tetramethyl-4-{(4S*,6R*)-
2,2,5,5-tetramethyl-6-[(4R*)-2,2,5,5-tetramethyl-1,3-dioxan-4-ylmethyl]-1,3-
dioxan-4-ylmethyl-6-(4R*,6S*)-2,2,5,5-tetramethyl-6-[(4S*)-2,2,5,5-tetramethyl-
1,3-dioxan-4-ylmethyl]}-1,3-dioxan-4-ylmethyl-1,3-dioxane (5): Rf ) 0.54
(10% tert-butyl methyl ether in pentane). 1H NMR (500 MHz, CDCl3): δ
) 0.65 (s, 6H), 0.75 (s, 6H), 0.77 (s, 6H), 0.78 (s, 3H), 0.81 (s, 6H), 1.15
(s, 3H), 1.15 (s, 3H), 1.16 (s, 6H), 1.17 (s, 6H), 1.21 (s, 6H), 1.22 (s, 6H),
1.49 (m, 4H), 1.51 (m, 4H), 2.96 (d, J ) 8.5 Hz, 2H), 3.10 (d, J ) 8.5 Hz,
2H), 3.51 (m, 8H). 13C NMR (125 MHz, CDCl3): δ ) 18.4 (2C), 18.5
(2C), 18.8, 20.1 (2C), 20.3 (2C), 21.1, 24.5 (2C), 24.6 (2C), 24.7, 24.8
(2C), 26.0 (2C), 28.1 (2C), 28.3 (2C), 28.4, 37.6 (2C), 40.0 (2C), 40.8,
66.6 (2C), 69.8 (2C), 70.1 (2C), 70.2 (2C), 70.4 (2C), 99.5 (2C), 99.8 (2C),
99.9. HRMS (FAB): C44H80O10 requires 768.5752, found 768.5414.
(12) Bis[(4R*)-2,2,5,5-tetramethyl-1,3-dioxan-4-yl]methane (2): Rf )
0.35 (20% tert-butyl methyl ether in pentane). 1H NMR (500 MHz,
CDCl3): δ ) 0.67 (s, 6H), 0.93 (s, 6H), 1.27 (m, 2H), 1.34 (s, 6H), 1.35
(s, 6H), 3.24 (d, J ) 11.3 Hz, 2H), 3.50 (d, J ) 11.3 Hz, 2H), 3.58 (m,
2H). 13C NMR (125 MHz, CDCl3): δ ) 18.0 (2C), 18.8 (2C), 21.6 (2C),
28.7 (2C), 30.0 (2C), 32.4, 72.0 (2C), 72.1 (2C), 98.4 (2C). Anal. Calcd
for C17H32O4: C, 67.96; H, 10.74. Found: C, 67.91; H, 10.96. (4R*,6S*)-
2,2,5,5-Tetramethyl-4-[(4R*)-2,2,5,5-tetramethyl-1,3-dioxan-4-ylmethyl]-6-
[(4S*)-2,2,5,5-tetramethyl-1,3-dioxan-4-ylmethyl]-1,3-dioxane (3): Rf )
0.17 (10% tert-butyl methyl ether in pentane). 1H NMR (500 MHz,
CDCl3): δ ) 0.70 (s, 9H), 0.81 (s, 3H), 0.99 (s, 6H), 1.34 (ddd, J ) 13.6,
9.6, 2.4 Hz, 2H), 1.35 (m, 9H), 1.38 (s, 9H), 1.39 (m, 2H), 3.27 (d, J )
11.3 Hz, 2H), 3.59 (d, J ) 11.3 Hz, 2H), 3.62 (dd, J ) 9.6, 2.4 Hz, 2H),
3.68 (dd, J ) 9.6, 2.4 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ ) 13.0,
18.2 (2C), 19.0 (2C), 19.5, 20.5, 21.7 (2C), 28.7 (2C), 29.7 (2C), 30.3,
32.6 (2C), 35.1, 72.4 (2C), 72.6 (2C), 73.3 (2C), 98.2, 98.5 (2C). HRMS
(FAB): C26H48O6 requires for ([M + H]+) 457.3529, found 456.3531.
(4R*,6S*)-2,2,5,5-Tetramethyl-4-[(4R*)-2,2,5,5-tetramethyl-1,3-dioxan-4-
ylmethyl]-6-{(4S*,6R*)-2,2,5,5-tetramethyl-6-[(4R*)-2,2,5,5-tetramethyl-1,3-
dioxan-4-ylmethyl]}-1,3-dioxan-4-ylmethyl-1,3-dioxane (4): Rf ) 0.21
1212
Org. Lett., Vol. 2, No. 9, 2000