J. Am. Chem. Soc. 1998, 120, 3807-3808
3807
Scheme 1
A Ketyl Radical-Anion “Triggered” [3,3]-Sigmatropic
Shift
Eric J. Enholm,* Kelley M. Moran, Paul E. Whitley, and
Merle A. Battiste
Department of Chemistry, UniVersity of Florida
GainesVille, Florida 32611
ReceiVed December 17, 1997
One of the most important pericyclic reactions in organic
synthesis involves an internal allyl transfer in the [3,3]-sigmatropic
shift.1 A very useful modification of this reaction involves
incorporating anionic charge in the substrate which accelerates
the rearrangement; thus, greatly reduced temperatures are now
used extensively. Metal alkoxides, enolates, and silyl ketene
acetals are often used to accelerate sigmatropic reactions such as
the Cope and Claisen rearrangements.1a,c Reagents which are one-
electron donors, such as samarium(II) iodide and tributyltin
hydride, have the potential to induce a radical-anion into the array
of atoms undergoing rearrangement.2-4 A metal-associated ketyl
radical-anion, readily obtained by partial reduction of a ketone
by a one-electron donor, could initiate or “trigger” a [3,3]-
sigmatropic process; however, these intermediates have not been
studied in this capacity.3
a halogen with a hydrogen atom, and interestingly, it is not
considered to be useful in promoting sigmatropic rearrangements.4
It is noteworthy that 2 f 4 proceeds in a manner somewhat the
opposite of the oxyanion-accelerated Cope rearrangement, where
a metal alkoxide leads to a metal enolate.1a,e In the transformation
in Scheme 1, the tin(IV) enolate in 2 leads to the tin(IV) alkoxide
4. The driving force in the reaction, which shifts the equilibrium
toward the product, is likely the formation of the strong ketone
carbonyl bond.1
This study will show several examples of this sigmatropic
rearrangement which was conducted entirely at 80 °C under
normal free radical conditions with tributyltin hydride. Mecha-
nistic support for the presence of a radical-anion species during
the rearrangement was obtained (vide infra). Moreover, new
carbon-carbon bonds were obtained from intermediate radical-
anion intermediate 3 via a reaction with electron-deficient
allylstannanes. The tin-alkoxide moiety in 4 can be trapped with
an electrophile prior to workup.
In the first example studied, treatment of 6 with tin hydride (1
equiv) and 2,2′-azobisisobutyronitrile (AIBN) (0.2 equiv), fol-
lowed by reflux over 3 h, afforded the rearranged R-hydroxy
ketone 7 in 74% yield.8 Other substrates were studied as well
and are shown in Table 1. Examination of the 1H and 13C NMR
data of products 11 and 13 indicates that only one diastereomer
is present in each case. Enone 8 reacted to form 9 in 51% yield
in entry 2; however, a new method using a catalytic amount of
tin hydride increased the yield to 61% in entry 3.9 Although
nearly all of the enone precursors underwent the [3,3]-sigmatropic
rearrangement, acetylenic ketone 14 did not produce the desired
product. Only the enone was reduced and ketone 15 was isolated,
probably due to difficulty in the alkyne attaining the desired six-
membered transition state normally required for the Claisen.10
Radical-anion intermediate 3, resulting from the sigmatropic
shift, possesses two reactive sites which can further extend the
utility of the rearrangement reaction. In addition to the nucleo-
philic tin-alkoxide, a resonance-stabilized carbon-centered radical
adjacent to the carbonyl should permit free radical reactions. Both
of these centers can be utilized to add further functionalization
in the same reaction vessel. If an ethyl ester substituted allyltin
reagent is reacted with 6 instead of tributyltin hydride, the
diallylcyclohexanone 16 is produced as a single diastereomer in
61% yield as shown in Scheme 2.13 Quenching the intermediate
tin alkoxide with acetyl chloride prepares acetate ester 17 in 46%
overall yield.
Resonance-stabilized allylic O-stannyl ketyls can be readily
prepared from an R,â-unsaturated ketone and tributyltin hydride.5,6
For example, if dienone 1 is reacted with tributyltin hydride, as
shown in Scheme 1, an allylic O-stannyl ketyl intermediate forms
and can be represented by the tin(IV) enolate and allylic radical
species 2. Formed under neutral free radical conditions, these
delocalized bifunctional intermediates possess both radical and
anionic character.6 Intermediate 2 has two ether-tethered olefins
in a 1,5-diene orientation; therefore, the electron-rich tin enolate
in the allylic O-stannyl ketyl is now a potentially reactive partner
in an anion-accelerated [3,3]-sigmatropic shift. This should
“trigger” a [3,3]-Claisen rearrangement to prepare the tin(IV)
alkoxide and radical species 3.7 After hydrogen atom transfer
n
from Bu3SnH to produce 4, followed by water quench, alcohol
5 is expected to be the final product.
This reaction uses an unprecedented allylic O-stannyl ketyl to
promote a [3,3]-sigmatropic shift in which a carbon-oxygen ether
bond is lost and a new ketone carbonyl bond is gained. Tributyltin
hydride is a reagent normally used in organic synthesis to replace
(1) (a) Lutz, R. P. Chem. ReV. 1984, 84, 205. (b) Chubert, P. S.; Srebnik,
M. Aldrichemica Acta 1993, 26, 17. (c) Wipf, P. In ComprehensiVe Organic
Synthesis; Trost, B. M., Ed.; Pergamon Press: New York, 1991; Chapter 7.2,
p 827. (d) Bronson, J. J.; Danheiser, R. L. ComprehensiVe Organic Synthesis;
Trost, B. M., Ed.; Pergamon Press: New York, 1991; Chapter 8.3, p 999. (e)
Wilson, S. R. In Organic Reactions; Paquette, L. A., Ed.; J. Wiley and Sons:
New York, 1993; Vol. 43, Chapter 2.
(2) For reviews of radical-anions, see: (a) Russell, G. A. In Radical Ions;
Kaiser, E. T., Kevan, L., Eds.; Wiley-Interscience: New York, 1968. (b)
Hirota, N. In Radical Ions; Kaiser, E. T., Kevan, L., Eds.; Wiley-Interscience:
New York, 1968. (c) Forrester, A. R.; Hay, J. M.; Thompson, R. H. Organic
Chemistry of Stable Free Radicals; Academic Press: New York, 1968.
(3) Recently SmI2 has been used to promote a [2,3]-sigmatropic rearrange-
ment by an entirely different approach, see: Kunishima, M.; Hioki, K.; Kono,
K.; Kato, A.; Tani, S. J. Org. Chem. 1997, 62, 7542.
(4) For reviews of nBu3SnH in organic synthesis, see: (a) Giese, B. Radicals
in Organic Synthesis: Formation of Carbon-Carbon Bonds; Pergamon
Press: New York, 1986. (b) Ramaiah, M. Tetrahedron 1987, 43, 3541. (c)
Curran, D. P. Synthesis 1988, 417, 489. (d) Hart, D. J. Science 1984, 223,
883. (e) Motherwell, W. B.; Crich, D. Free Radical Chain Reactions in
Organic Synthesis; Academic Press: New York, 1992.
(8) Ikeda, M.; Takahashi, M.; Ohno, K.; Tamura, Y.; Kido, M. Chem.
Pharm. Bull. 1982, 30, 2269.
(9) Hays, D. S.; Fu, G. C. J. Org. Chem. 1996, 61, 4-5.
(10) We could find very few examples of successful Claisen rearragements
with terminal acetylenes: (a) Black, D. K.; Landor, S. R. J. Chem. Soc. 1965,
6784. (b) Fischer, J.; Kilpart, C.; Klein, U.; Steglich, W. Tetrahedron 1986,
42, 2063.
(5) Pereyre, M.; Quitard, J. P.; Rahm A. Tin in Organic Synthesis;
Buttersworths: Boston, 1987.
(6) (a) Enholm, E. J.; Whitley, P. E.; Xie, Y. J. Org. Chem. 1996, 61,
5384. (b) Enholm, E. J.; Kinter, K. S. J. Org. Chem. 1995, 60, 4850. (c)
Enholm, E. J.; Whitley, P. E. Tetrahedron Lett. 1995, 36, 9157.
(7) Koreeda, M.; Luengo, J. I. J. Am. Chem. Soc. 1985, 107, 5572.
(11) At this point, the reaction of 6 f 7 is 69% complete (average of 3
runs).
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