J. Am. Chem. Soc. 1999, 121, 10865-10874
10865
Reinvestigation of the Isotope Effects for the Claisen and Aromatic
Claisen Rearrangements: The Nature of the Claisen Transition States
Matthew P. Meyer, Albert J. DelMonte, and Daniel A. Singleton*
Contribution from the Department of Chemistry, Texas A & M UniVersity, College Station, Texas 77843
ReceiVed July 8, 1999
Abstract: The aliphatic Claisen rearrangement of allyl vinyl ether and the aromatic Claisen rearrangement of
allyl phenyl ether are investigated in a combined experimental and calculational study. Theoretically predicted
kinetic isotope effects (KIEs) at all levels disagree with about half of the literature experimental heavy-atom
isotope effects. New experimental 13C and 2H isotope effects were determined by multisite NMR methodology
at natural abundance, and 17O isotope effects were determined by novel NMR methodology. These new
experimental isotope effects are inconsistent with the literature values and agree well the high-level predicted
KIEs, suggesting that the prior theory/experiment disagreement results from inaccuracy in the experimental
KIEs. A one-dimensional tunneling correction is found to improve kinetic isotope effect predictions in a number
of reactions and is found to be sufficient to provide differences between predicted and experimental heavy-
atom isotope effects on the order of the experimental uncertainty in the reactions studied. The best agreement
between experimental and predicted isotope effects is seen for the highest-level calculations. On the basis of
the experimentally supported transition state geometries, the nature of the Claisen and aromatic Claisen transition
states is discussed.
Introduction
concerted, and all correctly predict a chairlike transition state.
However, there is considerable disagreement over the transition
state geometry (Figure 1). CASSCF calculations predict a
dissociative bis-allyl-like transition structure while the AM1 and
MP2 structures are more toward the 1,4-diyl extreme, with the
RHF and Becke3LYP structures between (along with a partially
optimized MP4 structure).10-13 The differing geometries en-
gender significantly different predictions and understanding of
substituent, solvent, and catalysis effects in these reactions.15
Several experimental studies have used kinetic isotope effects
(KIEs) as a probe of the Claisen and aromatic Claisen transition
state geometry.6,16,17 Secondary deuterium KIEs have been
interpreted qualitatively in terms of a fairly dissociative, early
transition state for the aliphatic Claisen and a similarly dis-
sociative but much later transition state for the aromatic
Claisen.17 However, the assumption in these interpretations of
a linear relationship between bond order and isotope effect has
been questioned.18 Heavy-atom KIEs have been interpreted in
terms of early transition states for both the aliphatic and aromatic
The Claisen rearrangement of allyl vinyl and allyl aryl ethers
is a synthetically and biosynthetically important reaction. The
intramolecular and cyclic character of the rearrangement has
long been established,1 but considerable effort has gone into
understanding the detailed nature and geometry of the transition
state. Interest in the Claisen transition state has been spurred
by its relation to the synthetically important substituent and
stereochemical effects observed in these reactions,2 as well as
the observation of intriguing solvent effects3-7 and the catalysis
of a Claisen rearrangement by chorismate mutase and catalytic
antibodies.8 Theoretical predictions of transition structures for
the Claisen rearrangement have been made at many levels.9-12,14
The calculations uniformly agree that the rearrangement is
(1) Hurd, C. D.; Pollack, M. A. J. Am. Chem. Soc. 1939, 3, 550. Ralls,
J. W.; Lundin, R. E.; Bailey, G. F. J. Org. Chem. 1963, 28, 3521. Schuler,
F. W.; Murphys, G. W. J. Am. Chem. Soc. 1950, 72, 3155. Brower, K. R.
J. Am. Chem. Soc. 1961, 83, 4370. Walling, C.; Naiman, M. J. Am. Chem.
Soc. 1962, 84, 2628.
(2) For a review, see: Ziegler, F. E. Chem. ReV. 1988, 88, 1423.
(3) White, W. N.; Wolfarth, E. F. J. Org. Chem. 1970, 35, 2196, 3585.
Coates, R. M.; Rogers, B. D.; Hobbs, S. J.; Peck, D. R.; Curran, D. P. J.
Am. Chem. Soc. 1987, 109, 1160. Grieco, P. A.; Brandes, E. B.; McCann,
S.; Clark, J. D. J. Org. Chem. 1989, 54, 5849. Brandes, E. B.; Grieco, P.
A.; Gajewski, J. J. J. Org. Chem. 1989, 54, 515.
(9) Dewar, M. J. S.; Healy, E. F. J. Am. Chem. Soc. 1984, 106, 7127.
Vance, R. L.; Rondan, N. G.; Houk, K. N.; Jensen, F.; Borden, W. T.;
Komornicki, A.; Wimmer, E. J. Am. Chem. Soc. 1988, 110, 2314-5.
(10) Wiest, O.; Black, K. A.; Houk, K. N. J. Am. Chem. Soc. 1994, 116,
10336-7.
(11) Dewar, M. J. S.; Jie, C. J. Am. Chem. Soc. 1989, 111, 511.
(12) Davidson, M. M.; Hillier, I. H.; Vincent, M. A. Chem. Phys. Lett.
1995, 246, 536. The partially optimized MP4/6-31G* structure (with all
parameters but the O-C4 and C1-C6 distances optimized at the MP2 level)
had O-C4 and C1-C6 distances of 1.87 and 2.26 Å, respectively.
(13) Yoo, H. Y.; Houk, K. N. J. Am. Chem. Soc. 1994, 116, 12047-8.
(14) Yamabe, S.; Okumoto, S.; Hayashi, T. J. Org. Chem. 1996, 61,
6218-6226.
(15) See, for example, the discussions in refs 5c and 5d on the relationship
of solvent effects to transition state geometry.
(16) (a) Kupczyk-Subotkowska, L.; Subotkowski, W.; Saunders, W. H.,
Jr.; Shine, H. J. J. Am. Chem. Soc. 1992, 114, 3441. (b) Kupczyk-
Subotkowska, L.; Saunders, W. H., Jr.; Shine, H. J. J. Am. Chem. Soc.
1988, 110, 7153-9. (c) Kupczyk-Subotkowska, L.; Saunders, W. H., Jr.;
Shine, H. J.; Subotkowski, W. J. Am. Chem. Soc. 1993, 115, 5957.
(4) Gajewski, J. J. Acc. Chem. Res. 1997, 30, 219.
(5) (a) Cramer, C. J.; Truhlar, D. G. J. Am. Chem. Soc. 1992, 114, 8794-
9. (b) Severance, D. L.; Jorgensen, W. L. J. Am. Chem. Soc. 1992, 114,
10966-8. (c) Storer, J. W.; Giesen, D. J.; Hawkins, G. D.; Lynch, G. C.;
Cramer, C. J.; Truhlar, D. G.; Liotard, D. A. In Structure and ReactiVity in
Aqueous Solution; ACS Symposium Series 568; Cramer, C. J., Truhlar, D.
G., Eds.; American Chemical Society: Washington, DC, 1994; p 24. (d)
Sehgal, A.; Shao, L.; Gao, J. J. Am. Chem. Soc. 1995, 117, 11337.
(6) Gajewski, J. J.; Brichford, N. L. J. Am. Chem. Soc. 1994, 116, 3165.
(7) Gajewski, J. J. Acc. Chem. Res. 1997, 30, 219.
(8) Hilvert, D.; Nared, K. D. J. Am. Chem. Soc. 1988, 110, 5593. Hilvert,
D.; Carpenter, S. H.; Nared, K. D.; Auditor, M.-T. Proc. Natl. Acad. Sci.
U.S.A. 1988, 85, 4953. Jackson, D. Y.; Jacobs, J. W.; Sugasawara, R.; Reich,
S. H.; Bartlett, P. A.; Schultz, P. G. J. Am. Chem. Soc. 1988, 110, 4841.
10.1021/ja992372h CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/05/1999