2862 J . Org. Chem., Vol. 64, No. 8, 1999
Reddy et al.
to an equilibrium or kinetic isotope effect in the electron
transfer step or a kinetic or equilibrium isotope effect in
the chemical step. In previous studies of electron transfer
induced reactions, the isotope effects on the electron
transfer were considered to be small and IEobs is assumed
to represent the kinetic isotope effect of the reaction.16
Our model systems 1 and 2 are suitable to test these
assumptions. The highly exothermic cycloreversion is
irreversible and consequently has no equilibrium isotope
effect in the chemical step. For the same reason, the
reaction should have an extremely early transition state.
Therefore, a kinetic isotope effect on the chemical step
of unity or a very small normal isotope effect due to the
sp3 to sp2 rehybridization would be expected. With an
excited state oxidation potential of 1.98 V vs NHE for
11+,17 the difference in redox potentials between 11+ and
2 is more than 400 mV. The electron transfer step should
be diffusion controlled, and therefore should not have a
kinetic isotope effect. Consequently, the observed isotope
effect for these systems should correspond to the isotope
effect of forward and back electron transfer, i.e., the
isotope effect on the pseudoequilibrium between 2 and
F igu r e 5. Calculated structures (B3LYP/6-31G*) of 1 (left)
and 2 (right). Plain text: results for 1/2; parentheses: results
for 1•+/2•+
.
2•+
.
We prepared the isotopically labeled naphthalene-
benzene dimer 2-d8 starting from predeuterated naph-
thalene 4-d8 as outlined in Figure 2 and subjected it to
intermolecular competition experiments at low (∼10%)
conversion using PET conditions with 0.02 equiv of 11+
F igu r e 6. Synthesis of 1-d12: (a) E. coli J M109(pDTG601)
fermentation; (b) hν, thioxanthone, methanol; (c) N,N-dimeth-
ylformamid dimethyl acetal, 55 °C; (d) triflic anhydride,
methylene chloride, N,N-diisopropylamine, 0 °C.
as sensitizer. Interestingly, an inverse isotope effect, kH8
/
kD8, of 0.91 ( 0.02 was observed. This indicates that the
IEobs is indeed due to the electron transfer and not the
chemical step. To confirm these findings, we also calcu-
lated the isotope effect of the equilibria of 1 and 1•+, as
well as of 2 and 2•+, using the B3LYP/6-31G* method.18
Selected results of these calculations are shown in Figure
5.
Upon electron transfer, the C2h symmetry of 1 is
lowered to C2 in 1•+ by substantial elongation by 0.12 Å
of one of the bonds in the four membered ring. These
changes are in agreement with a stepwise pathway
corresponding to the biradicaloid mechanism of neutral
benzene dimers where the bonds are broken sequentially.
The cycloreversion of 1 and 2 can therefore be seen as a
higher analogue of the electron transfer catalyzed cyclo-
reversions of tricyclo[2.2.0.0]octa-2,6-diene13 and 5,8-
methano-4,5,8,9-tetrahydroindene,19 where the singly
linked intermediates have been detected spectroscopi-
cally. Other changes in the bond lengths in the four-
membered ring of 1 and 2 are only 0.03-0.05 Å where
the bonds connecting the aromatic systems are length-
ened and the bonds within the six-membered rings are
shortened. There is a large change in the puckering angle
of the cyclobutane upon electron transfer. It was pointed
out by Aida et al. that although the puckering potentials
in the cyclobutane radical cation are relatively soft, the
changes in orbital alignment are important for the
cycloreversion reaction.20 The calculated isotope effect of
0.89 for the electron transfer in 2 is in excellent agree-
ment with the experimental value, demonstrating that
the observed isotope effect is indeed due to the equilib-
rium isotope effect of electron transfer.
The isotope effect in the electron transfer catalyzed
[2 + 2] cycloreversion of 1 was also studied experi-
mentally. Perdeuterated 1 was synthesized as outlined
in Figure 6 by oxidation of perdeuteriobenzene in a
whole cell fermentation with a recombinant strain of
Escherichia coli which was engineered to overproduce
Pseudomonas putida toluene dioxygenase as described
by Gibson and co-workers.21 Alternatively, the known cis-
diol derived from bromobenzene-d5 and obtained in
higher yield22 could be reduced by tributyltin deuteride
to give 3-d6. Photocycloaddition and reductive deoxy-
(16) (a) McMordie, R. A.; Begley. T. P. J . Am. Chem. Soc. 1992, 114,
1886-1887. (b) Witmer, M. R.; Altmann, E.; Young, H.; Begley, T. J .
Am. Chem. Soc. 1989, 111, 9264-9265. (c) J acobsen, J . R.; Cochran,
A. G.; Stephans, J . C.; King, D. S.; Schultz, P. G. J . Am. Chem. Soc.
1995, 117, 5453-5461.
(17) Martiny, M.; Steckhan, E.; Esch, T. Chem. Ber. 1993, 126,
1671-1682.
genation as described earlier7 then gave 1-d12
.
Because 1-d12 does not contain any hydrogens, the
intermolecular competition experiment relies on the
2
separate recording of 1H and H NMR spectra, which are
(18) B3LYP calculations were performed using the G94 series of
programs: (a) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M.
W; J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.; Keith, T.; Petersson,
G. A.; Montgomery, J . A.; Raghavachari, K.; l-Laham, M. A.; Zakrze-
wski, V. G.; Ortiz, J . V.; Foresman, J . B.; Peng, C. Y.; Ayala, P. Y.;
Chen, W.; Wong, M. W.; Andres, J . L.; Replogle, E. S.; Gomperts, R.;
Martin, R. L.; Fox, D. J .; Binkley, J . S.; Defrees, D. J .; Baker, J .;
Stewart, J . P.; Head-Gordon, M.; Gonzalez, C.; Pople, J . A. Gaussian
94; Gaussian, Inc.: Pittsburgh, PA, 1995. Isotope effects were calcu-
lated from the harmonic frequency analysis using QUIVER with a
scaling factor of 0.961. (b) Saunders, M.; Laidig, K. E.; Wolfsberg, M.
J . Am. Chem. Soc. 1989, 111, 8989-8994.
then related to each other by an internal standard, 4-d3-
methylpyridine, which gives signals in both spectra.
Although the integration of the 2H spectrum was not
accurate enough to yield reliable quantitative informa-
(20) Aida, M.; Inoue, F.; Kaneko, M.; Dupuis, M. J . Am. Chem. Soc.
1997, 119, 12274-12779.
(21) Zylstra, G. J .; Gibson, D. T. J . Biol. Chem. 1989, 264, 14940-
14946.
(22) Hudlicky, T.; Pitzer, K. K.; Stabile, M.; Thorpe, A. J . J . Org.
Chem. 1996, 61, 4151-4153.
(19) Roth, H.; Schilling, M. L. M. J . Am. Chem. Soc. 1985, 107, 716-
721.