Communications to the Editor
J. Am. Chem. Soc., Vol. 118, No. 46, 1996 11691
Figure 1. Postulated conformations A and B of the Eu(III)-chelated
cis- (5) and trans-5-tert-butyl-1-methyl-2-cyclohexen-1-yl methoxy-
acetates (11), respectively, that lead to their respective favorable
transition states for their Eu(fod)3-catalyzed rearrangements.
Figure 2. Postulated Eu(III)-chelated conformations that lead to the
favorable transitions states for the concerted (C) and dissociative (D)
pathways for the Eu(fod)3-catalyzed rearrangements of cis- (17; R )
Me, R′ ) H) and trans-1-phenyl-2-buten-1-yl methoxyacetates (14; R
) H, R′ ) Me).
severe A1,3 strain between the methyl group and the proton at
C-1 in the transition state.
to 0.10 equiv of Eu(fod)3, at room temperature with the
exception of esters 28 and 32 where the reaction temperature
was raised to 60 °C, resulted in the rearrangement into the more
stable alkene isomers. The results of the rearrangement of the
methoxyacetates 2, 5, 8, and 117 (entries a-d) indicate that these
rearrangements proceed in a stereospecific manner. Surpris-
ingly, the rates of rearrangement of tert-butyl group-containing
allylic methoxyacetates 5 and 11 were found to be quite similar
with ester 5 having the equatorially fixed methoxyacetate group
rearranging slightly faster (t1/2 ) 9 min) than ester 11 with the
axially fixed methoxyacetate group (t1/2 ) 29 min). This
observation on similar rates of rearrangement may be rational-
ized in terms of the two Eu(III)-chelated conformers A and B
(see Figure 1) that may closely resemble the conformations of
their corresponding, most favorable transition states for the
Eu(fod)3-catalyzed rearrangement of methoxyacetates 5 and 11,
respectively. Thus, cis ester 5 might be able to adopt conformer
A where the atoms involved with the allylic rearrangement adopt
a chair conformation if the cyclohexene ring system assumes a
quasi-boat conformation. In contrast, the rearranging atoms in
conformer B is likely to adopt a boat conformation in order to
avoid the unfavorable interaction between the axial H at C-5
and the ester functionality. Therefore, the bicyclic transition
state structure of both cis- and trans-5-tert-butyl-1-methyl-2-
cyclohexen-1-yl methoxyacetate should be close to those having
one chair and one boat conformation for the rearranging allylic
ester system and the tert-butyl group-bearing cyclohexene
skeleton, and thus, the observed rates of rearrangement might
be expected to be similar.
For cis- (17) and trans-1-phenyl-2-buten-1-yl methoxyacetate
(14) (entries f and e, respectively), the rearrangement was found
to proceed 18 times faster for the trans (t1/2 ) 18 min) than the
cis isomer (t1/2 ) 330 min). This large difference in rates may
be regarded as a manifestation of the relative energies of the
two chairlike transition states which should resemble the
conformation C given in Figure 2 (i.e., R ) Me, R′ ) H and R
) H, R′ ) Me for the cis and trans isomers, respectively). Thus,
the difference in the steric energies between the quasi-axial and
quasi-equatorial methyl groups in the chairlike transition states
of the stereospecific concerted process might account for the
observed difference in the rates of the rearrangements. How-
ever, a distinct possibility exists that this doubly activated allylic
and benzylic ester system involves dissociative pathway, and
the rate difference reflects the rate-limiting dissociative process
(see structure D in Figure 2). It is quite conceivable that the
cis isomer (R ) Me, R′ ) H in D) requires a higher activation
energy for the dissociation of the Eu-chelated methoxyacetate
group than the trans isomer (R ) H, R′ ) Me) does due to the
The allylic acetate systems in which Pd(II)-catalyzed rear-
rangements are reported not to proceed effectively include those
containing alkynyl group(s) and those whose proximal alkenyl
carbons are fully substituted.11 In a marked contrast to the
Pd(II)-catalyzed reaction, both of these types of allylic systems
with methoxyacetates undergo facile rearrangements under the
Eu(fod)3-catalysis (see entries g and j12 -l). Interestingly, the
rearrangement of methoxyacetate 35 afforded the byproduct 37
which is likely to have been generated as the result of the two
consecutive rearrangements from 35 via 36. It should be noted
that the Lewis acidity of Eu(fod)3, albeit its weak potency, could
prove potentially problematic, as exemplified by the attempted
rearrangement of the methoxyacetate of the extremely acid-labile
pulegol (38) (entry m). Interestingly, although only the volatile
diene 40 was isolated from the reaction of pulegyl methoxy-
acetate (39), the presence of an intermediate corresponding to
the rearranged product structure in the reaction medium could
be verified when the reaction was monitored by 1H NMR
spectroscopy.
The Eu(fod)3-catalyzed rearrangement of allylic methoxy-
acetates described above is extremely efficient and has a number
of distinct advantages over the existing methods. It does not
seem to be subject to steric hindrance, since the metal associates
with the methoxyacetate “tether” and not with the potentially
congested olefin. This notion was further corroborated by the
observation of the characteristic large downfield shifts and
significant line-broadening of both the methyl and the methylene
peaks of the OC(dO)CH2OCH3 group in the 1H NMR spectra
of all of the methoxyacetates examined. Therefore, it appears
quite reasonable to assume that the Eu(fod)3 reagent exerts its
catalytic activity for the rearrangement through the chelate
formation with the oxygen atoms of the methoxy and ester
carbonyl groups.13 Unlike Pd(II) catalysts, the present method
with Eu(fod)3 is compatible with the presence of alkynyl group-
(s). Additionally, it may be inferred on the basis of the exper-
iments with various type of esters of 2-cyclohexen-1-ol that the
present method seems selective to R-alkoxyacetates, and thus,
other allylic esters should remain unaffected by exposure to the
reagent. All of these advantages should prove the Eu(fod)3-
catalyzed rearrangement to be an excellent complement to the
existing methods for the rearrangement of allylic esters.
Acknowledgment. The authors thank the National Institutes of
Health (DK 30025 awarded to M.K.) for the support of this research.
Supporting Information Available: Full experimental details with
spectral and combustion analytical data of all methoxyacetates and
products from rearrangement as well as 7, 10, and 21 (13 pages). See
any current masthead page for ordering and Internet access instructions.
JA962718D
(7) Synthesis of allylic alcohol precursors 1, 4, 7, and 10: cis-1,5-
Dimethyl-2-cyclohexen-1-ol (1; R ) Me) was prepared by the treatment
of 5-methyl-2-cyclohexen-1-one8 with MeLi at -78 °C in diethyl ether
(87%). The trans isomer 7 (R ) Me) was obtained by Jones oxidation of
the cis isomer to obtain 3,5-dimethyl-2-cyclohexen-1-one (70%), followed
by application of the protocol of Wharton9 involving (i) the H2O2
epoxidation of the enone (65%) and (ii) the hydrazine reduction of the epoxy
ketone (73%) to give a 15:1 mixture of stereoisomers favoring trans-1,5-
dimethyl-2-cyclohexen-1-ol (7: R ) Me). The two tert-butyl containing
cyclohexenols 4 and 10 were prepared in a similar manner starting from
5-tert-butyl-2-cyclohex-1-one.10
(8) Musser, A. K.; Fuchs, P. L. J. Org. Chem. 1982, 47, 3121.
(9) Wharton, P. S.; Bohlen, D. H. J. Org. Chem. 1961, 26, 2615.
(10) (a) Sardina, F. J.; Johnson, A. D.; Mourino, A.; Okamura, W. H. J.
Org. Chem. 1982, 47, 1576. (b) Dominianni, S. J.; Ryan, C. W.; DeArmitt,
C. W. Ibid. 1977, 42, 344.
(11) Oehlschlager, A. C.; Mishra, P.; Dhami, S. Can. J. Chem. 1984,
62, 791.
(12) Stereochemistry in the steroid case was confirmed by de-esterifi-
cation followed by removal of the THP group and comparison of the spectra
to those reported (Benn, W. R. J. Org. Chem. 1963, 28, 3557).
(13) The propensity of the Eu for this methoxyacetoxy system is to the
extent that silica gel chromatography does not rid the substrate of all of the
Eu (the fod ligand is lost). Interestingly, even Kugelrohr distillation of the
methoxyacetates presents the same problem. The Eu reagent is best removed
by washing the ether solution of the product with a 2.5% ethylenebis-
(oxyethylenenitrilo)tetraacetic acid (EGTA) slurry.
Shull, Brian K.
