the present context. The low yields and modest stereocontrol
sometimes seen in the few examples heretofore reported6
must obviously be upgraded if applications to targeted
synthesis are to be projected. The present report documents
those steric factors that gain importance in the diastereomeric
transition states. In addition, suitable control of reaction time,
temperature, and solvent are shown to enhance overall
efficiency.
Scheme 2
Advantage was first taken of the ease with which D-glucose
can be transformed into 78 (Scheme 1). Following stepwise
Scheme 1
OPMB substituent at C-3 on the ring contraction stereose-
lectivity (Scheme 2). Two important features emerged. The
first was that only the R-anomer of 14 reacted. Second, the
process was highly stereoselective, giving rise to 15 (98%
de) in 35% yield. Since the independent equilibration of the
â-anomer of 14 with its R-form operates readily, the overall
conversion to 15 after only one additional pass is quite good.
These results bring into focus the fact that transition states
16 and 17 are no longer closely balanced energetically as in
the case of 11 and 12. Presumably the adoption of 17 is
totally disfavored as a consequence of the steric compression
that develops between the OPMB substituent and the allylic
methylene group positioned R to the zirconium as illustrated.
A relevant point made evident in Scheme 2 concerns the
fact that a 3â-oxygenated substituent as in 14 promotes clean
reaction via 16, a transition state prototype otherwise
disfavored at a lower level of functionalization (cf. 11).
introduction of the methyl acetal and SEM groups, the stage
was set for the zirconocene-mediated ring contraction. In this
example, a 1:3 mixture of 9 and 10 was generated in 64%
combined yield. Since both anomers react, it would appear
reasonable to rationalize this product composition in terms
of the faster rate of cyclization within transition state 12
relative to that of 11. The stability of the SEM protecting
group to the reaction conditions holds equally special
significance.
The ready conversion of D-glucose to 138c provided the
opportunity to examine the consequences of a â-oriented
The transformation of D-arabinose into carbinol 18 in four
steps9 made possible the convenient acquisition of 4-vinyl-
furanoside 19 (Scheme 3). When exposed to Cp2Zr and boron
trifluoride etherate, 19 underwent smooth ring contraction
to deliver only 20 in an unoptimized yield of 54%. As hoped
for, a reversal in the configurations at C-2 and C-3 leads to
a switchover in the operational transition state for cyclobu-
tane bond formation. We now see that 21 is so sterically
disadvantaged relative to 22 that it is inoperative at a
detectable level.
(3) (a) Pulici, M.; Sugawara, F.; Koshino, H.; Uzawa, J.; Yoshida,
S.; Lobkovsky, E.; Clardy, J. J. Org.Chem. 1996, 61, 2122. (b) Johnston,
D.; Francon, N.; Edmonds, D. J.; Procter, D. J. Org. Lett. 2001, 3,
2001.
(4) Negishi, E.; Cederbaum, F. E.; Takahashi, T. Tetrahedron Lett. 1986,
27, 2829.
(5) (a) Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992, 33,
1295. (b) Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992, 33,
7873. (c) Ito, H.; Nakamura, T.; Taguchi, T.; Hanzawa, Y. Tetrahedron
Lett. 1992, 33, 3769. (d) Ito, H.; Taguchi, T.; Hanzawa, Y. J. Org. Chem.
1993, 58, 774. (e) Rousset, C. J.; Swanson, D. R.; Lamaty, F.; Negishi, E.
Tetrahedron Lett. 1989, 30, 5105.
(6) (a) Ito, H.; Motoki, Y.; Taguchi, T.; Hanzawa, Y. J. Am. Chem.
Soc. 1993, 115, 8835. (b) Hanzawa, Y.; Ito, H.; Taguchi, T. Synlett 1995,
299.
The generality of this completely stereoselective pathway
was investigated by generating 24 from the known pivalate
(7) Aurrecoechea, J. M.; Lo´pez, B.; Arrate, M. J. Org. Chem. 2000, 65,
6493.
(8) (a) Copland, C.; Stick, R. V. Aust. J. Chem. 1977, 30, 1269. (b)
Weygand, F.; Wolf, H. Chem. Ber. 1952, 85, 256. (c) Jones, J. K. N.;
Thompson, J. L. Can. J. Chem. 1957, 35, 955.
(9) Dahlman, O.; Garegg, P. J.; Mayer, H.; Schramek, S. Acta Chem.
Scand. B 1986, 40, 15.
1928
Org. Lett., Vol. 4, No. 11, 2002