COMMUNICATIONS
the presence of a larger excess of catalyst. The origin of this
enhanced reactivity and selectivity appears to be an exclusive
endo effect. Opening of the exo alcohol 9e was extremely
sluggish, only proceeding to about 15%. Moreover, the
regioselectivity of the product had decreased to a ratio of
about 6:1. These effects could be a result of the steric
interaction of the axial group with the bridged alkene or an
electronic effect similar to those seen in norbornyl systems.[12]
Although the nature of the effect is unclear, we proposed
that this rate acceleration could be used to improve some of
the previous spirocyclizations. If the reaction proceeds as in
Scheme 3, then the second ring-closing step should be
accelerated by similar structural changes. Therefore, we
examined the spirocyclization with reduced forms of dienes
4a and 4d (Table 4). We examined the five- and seven-
membered ring closures, since these were less efficient than
metathesis reactions. Further studies on these effects and the
synthesis of other types of annulated pyrans are currently
under investigation.
Received: July 8, 2002 [Z19679]
[1] M. C. Elliot, J. Chem. Soc. Perkin Trans. 1 1998, 4175 4200, and
references therein.
[2] D. L. Wright, L. C. Usher, M. Estrella-Jimenez, Org. Lett. 2001, 3,
4275 4277;a) for other approaches to pyrans by RCM, see: M. E.
Maier, M. Bugl, Synlett 1998, 1390 1392; b) B. Schmidt, H. Wild-
emann, J. Org. Chem. 2000, 65, 5817 5822; c) B. Schmidt, H.
Wildemann, J. Chem. Soc. Perkin Trans. 1 2000, 2916 2925.
[3] For excellent reviews, see: a) H. M. R. Hoffmann, Angew. Chem.
1984, 96, 29 48; Angew. Chem. Int. Ed. Engl. 1984, 23, 1 19; b) J. H.
Rigby, F. C. Pigge in Organic Reactions, Vol. 51 (Ed.: L. A. Paquette),
Wiley, New York, 1997, p. 351.
[4] For examples of domino metathesis reactions, see: a) N. Buschmann,
A. R¸ckert, S. Blechert, J. Org. Chem. 2002, 67, 4325 4329; b) O.
Arjona, A. G. Csaky, R. Medel, J. Plumet, J. Org. Chem. 2002, 67,
1380 1383; c) R. Stragies, S. Blechert, J. Am. Chem. Soc. 2000, 122,
9584 9591; d) O. Arjona, A. G. Csaky, M. C. Murcia, J. Plumet,
Tetrahedron Lett. 2000, 41, 9777 9779; e) R. Stragies, S. Blechert,
Tetrahedron, 1999, 55, 8179 8188; f) R. Stragies, S. Blechert, Synlett
1998, 169 170.
[5] a) S. W. Pelletier, N. V. Mody, Z. Djarmati, S. D. Lajsic, J. Org. Chem.
1976, 41, 3042 3044; b) D. J. Aberhart, K. H. Oberton, S. Huneck, J.
Chem. Soc. C. 1970, 11, 1612 1614.
[6] M. A. Walters, F. La, P. Desmukh, D. O. Omencinsky, J. Comb. Chem.
2002, 4, 125 130.
[7] B. Fˆhlisch, E. Gehrlach, B. Geywitz, Chem. Ber. 1987, 120, 1815
1824.
[8] M. Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1, 953
956.
Table 4. Spirocyclizations with reduced derivatives.
Alkene
Product[a]
Yield[b]
83%
12
14
13
15
48%
80%
[9] M. F. Schneider, N. Lucas, J. Velder, S. Blechert, Angew. Chem. 1997,
109, 257 259; Angew. Chem. Int. Ed. Engl. 1997, 36, 257 259; for a
review, see: A. F¸rstner, Angew. Chem. 2000, 112, 3140 3172; Angew.
Chem. Int. Ed. 2000, 39, 3012 3043.
15
17
[10] a) J. Plumet, O. Arjona, A. G. Csaky, Synthesis 2000, 6, 857 861;
b) M. L. Randall, J. A. Tallarico, M. L. Snapper, Tetrahedron, 1997, 48,
16511 16520; c) M. L. Randall, J. A. Tallarico, M. L. Snapper, J. Am.
Chem. Soc. 1995, 117, 9610 9611; d) O. Arjona, A. G. Csaky, M. C.
Murcia, J. Plumet, J. Org. Chem. 1999, 64, 9739 9741; e) J. G.
Hamilton, K. J. Ivin, M. McCann, J. J. Rooney, J. Chem. Soc. Chem.
Commun. 1984, 1379 1381.
[11] Reduction with L-selectride at ꢀ788C gave exclusively the endo
alcohols in 80 90% yield. The exo alcohol was prepared by reduction
with SmI2 (60% yield, one isomer).
cyclizations to form cyclohexyl rings. In the case of cyclo-
pentyl rings it may be somewhat difficult for the shorter tether
to reach the bridged alkene, whereas the seven-membered
ring may be slowed by nonbonded interactions in the tether.
Diene 4a was reduced to the endo alcohol 12, and rearrange-
ment gave 13 in an improved yield of 83%. The more difficult
cyclization to form the seven-membered ring systems was also
better with endo alcohol 14, tripling the yield to 48%. Since
the silyl ethers were more reactive in the intermolecular case,
it seemed possible that an even better rate enhancement could
be produced. Treatment of 16 with the ruthenium catalyst
resulted in a rapid reaction, delivering the spiro product 17 in
80% yield. This study nicely illustrates the potential of tuning
alkene reactivity in these types of reactions.
[12] For some examples, see: a) G. Mehta, G. Gunasekaran, S. R. Gadre,
R. N. Shirsat, B. Ganguly, J. Chandrasekhar, J. Org. Chem. 1994, 59,
1953 1955; b) G. Mehta, F. A. Khan, J. Am. Chem. Soc. 1990, 112,
6140 6142.
Olefin-metathesis reactions have become important bond-
forming reactions in contemporary synthetic chemistry. Dom-
ino ring-opening/ring-closing reactions are a convenient way
to construct polycyclic systems from readily available bridged
bicyclic alkenes. We have been able to develop a method to
prepare spiro-annulated pyrans from furan. An important
aspect of this study is the finding that the reactivity and
selectivity of the metathesis reactions can be tuned by
manipulation of functional groups on the substrate. Although
the origins of these effects are still under investigation, it is
clear that they can play an extremely important part in
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