A R T I C L E S
Nowlan et al.
ments that all of the styrene be present at the beginning of the
reaction and that the styrene be taken to high conversion. This
was accomplished by adding 1 slowly, by syringe pump, to a
solution of styrene and 0.1 mol % Rh2(octanoate)4 in dry
pentane. Reactions on an ≈100 mmol scale at 25 °C were taken
to 84 and 83% conversion (based on the remaining styrene
determined by NMR, ≈(1%), and the unreacted styrene was
recovered by chromatography followed by distillation. The
recovered material was analyzed by 13C NMR along with a
standard sample of the styrene not subjected to the reaction
conditions. The changes in isotopic composition were deter-
mined relative to the para carbon, assuming that its isotopic
composition does not change. From the changes in isotopic
composition, the 13C isotope effects were calculated as previ-
ously described.12
The comparison reaction of styrene with ethyl diazoacetate
was studied similarly, with the presumably minor differences
that the reaction employed 0.04 mol % Rh2(OAc)4 as catalyst
and was carried out in dichloromethane. The ethyl diazoacetate
reaction is much less diastereoselective than that of 1, affording
a 1.5:1 mixture of trans and cis cyclopropanation products as
previously reported.13 Three reactions on a 130 mmol scale at
25 °C were taken to 80, 81, and 88% conversion, and the
unreacted styrene was recovered and analyzed as above to
determine the 13C isotope effects.
A final isotope effect determination was performed to
compare the reaction with 1 catalyzed by Rh2(octanoate)4 with
an asymmetric cyclopropanation catalyzed by Rh2(S-DOSP)4.
The Rh2(S-DOSP)4-catalyzed reaction proceeds in 91% ee and
94% de.14 The 13C KIEs in this case were determined from
analysis of styrene recovered from a reaction taken to 84%
conversion at 0 °C.
13
12
13
Figure 2. C KIEs (k C/k C) for the reaction of styrene with 1 or ethyl
diazoacetate. Standard deviations (n ) 6) in the last digit are shown in
parentheses.
are highly exothermic, so that both should have a relatively early
transition state, the 13C KIEs would be qualitatively interpreted
as implying a significantly earlier transition state with ethyl
diazoacetate than with 1.
Theoretical Calculations. The pathway for reaction of
models methyl diazoacetate (2) and methyl vinyldiazoacetate
(3) with styrene catalyzed by model Rh2(O2CH)4 16 was studied
in B3LYP calculations employing a LANL2DZ basis set and
effective core potential on rhodium and a 6-31G* basis set on
the remaining atoms.17 Previous work has supported the ability
of these calculations to adequately predict ground-state structures
and reasonable mechanistic pathways for reactions of dirhodium
tetracarboxylate complexes.,18,19,20 The accuracy of these cal-
culations for transition structures in rhodium-mediated cyclo-
The resulting isotope effects are summarized in Figure 2. The
Rh2(octanoate)4-catalyzed cyclopropanation with 1 exhibits a
substantial 13C KIE at the terminal olefinic carbon, a smaller
but consistently significant KIE at the internal olefinic carbon
and small or negligible KIEs at the aromatic ring carbons. The
large isotope effect at the terminal olefinic carbon qualitatively
suggests substantial bond formation to this carbon in the rate-
limiting step. In combination with the much smaller isotope
effect at the internal olefinic carbon, the results suggest a highly
asynchronous cyclopropanation transition state. In fact, the KIEs
by themselves would not qualitatively exclude a stepwise
process,15 but this seems unlikely given the general stereospeci-
ficity of rhodium-catalyzed cyclopropanations. A quantitative
interpretation of the KIEs will be given below. The isotope
effects observed for the Rh2(S-DOSP)4-catalyzed reaction are
within experimental error of the Rh2(octanoate)4-catalyzed
results. This suggests that the use of the bulky chiral catalyst
does not greatly affect the geometry of the cyclopropanation
transition state.
(16) The minimal Rh2(O2CH)4 was judged to be a sufficient model for Rh2-
(octanoate)4 based on similar geometries for transition structure 13 versus
the corresponding transition structure with Rh2(OAc)4 (see Supporting
Information; differences of 0.018, 0.006, 0.042, and 0.028 Å were predicted
for the Rh-Rh, Rh-C, and the two incipient C-C bonding distances,
respectively). Although the experimental reactions could have been carried
out using Rh2(O2CH)4, the low solubility of Rh2(O2CH)4 would have
increased concerns over the identity of the actual catalyst.
(17) 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.11.2; Gaussian,
Inc.: Pittsburgh, PA, 2001.
The most notable difference in the cyclopropanation with
ethyl diazoacetate is that the terminal olefinic KIE is much
smaller. Since the reactions of both 1 and ethyl diazoacetate
(13) Anciaux, A. J.; Hubert, A. J.; Noels, A. F.; Petiniot, N.; Teyssie´, P. J.
Org. Chem. 1980, 45, 695-702.
(14) Davies, H. M. L.; Rusiniak, L. Tetrahedron Lett. 1998, 39, 8811-8812.
(15) The 13C KIEs observed here are consistent with those observed in
asynchronous but concerted Diels-Alder reactions. See: (a) Singleton, D.
A.; Merrigan, S. R.; Beno, B. R.; Houk, K. N. Tetrahedron Lett. 1999, 40,
5817-21. (b) Singleton, D. A.; Schulmeier, B. E.; Hang, C.; Thomas, A.
A.; Leung, S.-W.; Merrigan, S. R. Tetrahedron 2001, 57, 5149-5160.
(18) (a) Sheehan, S. M.; Padwa, A.; Snyder, J. P. Tetrahedron Lett. 1998, 39,
949-952. (b) Padwa, A.; Snyder, J. P.; Curtis, E. A.; Sheehan, S. M.;
Worsencroft, K. J.; Kappe, C. O. J. Am. Chem. Soc. 2000, 122, 8155-
8167.
(19) Nakamura, E.; Yoshikai, N.; Yamanaka, M. J. Am. Chem. Soc. 2002, 124,
7181-7192.
9
15904 J. AM. CHEM. SOC. VOL. 125, NO. 51, 2003