were observed experimentally in related substituted systems.
For example, Anthony et al. found an example of predomi-
nant 6-endo cyclization of a more constrained enediyne,6b
whereas Rainier and Kennedy15 reported formation of
mixtures resulted from 5-exo- and 6-endo-dig cyclizations
of vinyl radicals produced by radical addition of Bu3SnH to
arylisonitriles with pendant alkynes. On the other hand,
Schmittel et al. found that triplet diradicals formed photo-
chemically from enyne-carbodiimides and enyne-ketenimines
undergo selective 5-exo-dig cyclization.16 A similar observa-
tion was made by Ko¨nig et al. who provided the only
literature example of a radical 5-exo cyclization of an
enediyne6a reported before our work was started. The
combination of the above computational data and literature
precedents suggests that the 5-exo-dig cyclization is intrinsi-
cally favorable. Moreover, the presence of bulky aryl
substituents in the diaryl enediynes studied in this paper
should further disfavor their 6-endo-dig cyclization and
contribute to the observed selectivity.
Assuming that R- and â-radicals thermally equilibrate with
starting material, the nature of reaction products is likely to
be determined by competition between H-abstraction by the
more thermodynamically stable and, thus, more abundant,
R-radicals and 5-exo-cyclization of â-radicals. The balance
can be rather subtle as illustrated by the results for the TFP
and Ph enediynes 1 and 2, where lesser stabilization of the
â-radical correlates with the decreased yield of the cyclized
product (Scheme 1, Table 1).
Figure 1. Calculated spin density and geometry of fulvene radicals
(Z)-24 (R ) Ph, on the left; R ) TFP, on the right) at the B3LYP/
3-21G* level.
to versatile organometallic reagents, which can be used in
the synthetic routes illustrated in Scheme 3. For example,
the high reactivity of the Bu3Sn moiety in fulvene 26 can
be utilized in reactions with electrophiles such as iodine and
in Stille coupling with aryl iodides under Corey’s condi-
tions.19 X-ray analysis of the Stille coupling and iodination
products further confirmed the 5-exo-cyclization mode and
the regio- and stereoselectivity of the reaction (Scheme 3).
Scheme 3. Reactions of Sn-Substituted Fulvenes with
Electrophiles
The modest E/Z stereoselectivity is consistent with the less
hindered approach by the H-atom donor, which, in turn, is
determined by hybridization and geometry of the fulvene
radical. Conjugation with terminal aryl groups leads to
rehybridization and linearization at the radical center relative
to the unsubstituted vinyl radical. This effect is more
pronounced in the TFP-substituted radical approaching the
perfectly linear geometry of vinyl cations.18 As a result, the
stereoselectivity of H-abstraction by the TFP radical is
slightly lower than by the phenyl- and p-anisyl-substituted
radicals, which are slightly bent in a way that favors
formation of (E)-fulvene (Figure 1, Table 1).
From a practical perspective, tin-promoted 5-exo-dig
radical cyclization of enediynes provides a facile approach
(15) Rainier, J. D.; Kennedy, A. R. J. Org. Chem. 2000, 65, 6213.
(16) Schmittel, M.; Rodriguez, D.; Steffen, J.-P. Angew. Chem., Int. Ed.
2000, 39, 2152.
Furthermore, one can expand the synthetic utility of these
processes by utilizing the intrinsic propensity of the fulvene
moiety toward facile addition of nucleophilic reagents to the
polarized exocyclic double bond (Scheme 4).20 The inter-
mediate cyclopentadienyl anion 29 can be quenched by
aqueous workup or trapped by a different electrophile (e.g.,
TMSCl). The combination of synthetic sequences outlined
in Schemes 3 and 4 should allow for a sequential electrophile/
(17) Only (E)-isomers of aryl-substituted radicals 24 are minima at the
B3LYP/3-21G* potential energy surface. The calculations were performed
using the Gaussian 98 suite of programs: Frisch, M. J.; Trucks, G. W.;
Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski,
V. G.; Montgomery, J. A., Jr.; Stratmann, R. E.; Burant, J. C.; Dapprich,
S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.;
Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.;
Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui,
Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.;
Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.;
Wong, M. W.; Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; Pople, J.
A. Gaussian 98, revision A.9; Gaussian, Inc.: Pittsburgh, PA, 1998.
(18) A similar correlation of hybridization of radical center with acceptor
ability of substituents has been observed earlier. Galli, C.; Guarnieri, A.;
Koch, H.; Mencarelli, P.; Rappoport, Z. J. Org. Chem. 1997, 62, 4072.
Galli, C.; Rappoport, Z. Acc. Chem. Res. 2003, 36, 580.
(19) Han, X.; Stoltz, B. M.; Corey, E. J. J. Am. Chem. Soc. 1999, 121,
7600.
(20) Recent applications of similar reactions in organometallic chemis-
try: Shapiro, P. J.; Kane, K. M.; Vij, A., Stelck, D.; Matare, G. J.; Hubbard,
R. L.; Caron, B. Organometallics 1999, 18, 3468. Rogers, J. S.; Lachicotte,
R. J.; Bazan, G. C. Organometallics 1999, 18, 3976. Wang, S.; Yang, Q.;
Mak, T. C. W.; Xie, Z. Organometallics 2000, 19, 334.
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