LETTER
Reactions of Vinylcyclopropane Epoxides
2689
Complete stereocontrol has been found in the deoxygen- expected to better stabilize the radical intermediate 6¢
ation of ethyl oxido-chrysanthemate 1a or of its dides- (R2 = Me). The reverse is in fact observed (Table 1, entry
methyl analogues 1b and 1c leading to the corresponding a compare to entry c).
vinylcyclopropanes 2. Some stereoisomerization has
been, however, found from the analogous compound 1d
bearing an aryl instead of the ethoxycarbonyl group on the
cyclopropane ring (Scheme 1, Table 1, entry 4; de 74%).
These results cannot be either properly rationalized by as-
suming that the ring-opening of those epoxides derived
from vinylcyclopropane carboxylates 1a–c occurs by ini-
tial reduction of the C–O double bond of their carboxy
It was also expected that each stereoisomer of 1 reacts at groups followed by cyclopropane ring-opening (Table 1,
a different rate. To test this hypothesis, we have moni- entries a–c; Scheme 4, Route E).
tored the reaction of a mixture of stereoisomeric ethyl
oxido-chrysanthemates4b 1a by 1H NMR, using 1,3,5-tri-
O
R2
O
O
R2
O
methoxybenzene as a standard. We observed that the re-
activity of the compounds disclosed in Figure 1 decreases
from the left to the right. In each series the cis-stereo-
isomer is the most reactive one.
R2
OR
R2
OR
SmI2, t-BuOH
Route E
R1 R1
R1 R1
1
CO2Et
CO2Et
or
or
O
O
OH
O
O
O
CO2Et
R2
R2
R2
R2
CO2Et
OR
OR
O
O
SmI2
t-BuOH
R1
R1
R1
R1
Figure 1 Order of reactivity of vinylcyclopropane epoxides with
samarium diiodide related to their stereochemistry
7'
3
Scheme 4 Postulated mechanism rationalizing the reaction of epo-
xides derived from vinylcyclopropane carboxylates with samarium
diiodide (Route E)
Since samarium diiodide reacts via a stepwise single elec-
tron transfer, the epoxide ring-opening of 1 can occur
from both sides leading to each of the two possible b-
alkoxyalkyl radicals 6, the structures of which are dis-
closed in Scheme 3.
Furthermore, although the intermediate formation of the
cyclopropylcarbinyl radical 6¢¢ (Scheme 3) can adequate-
ly rationalize the formation of:
– the benzylic radical 7d precursor of the allyl alcohol 3d
from the phenylcyclopropane 1d (Scheme 1, Table 1,
entry d; Scheme 3, route C),
– the tertiary alkyl radical 8e from the methoxymethyl-
enecyclopropane derivative 1e (Scheme 2, Scheme 3,
route D),
R2
O
O
O
R2
R2
A
R2
R2
R2
A
SmI2, t-BuOH
A
+
R1 R1
R1 R1
R1 R1
1
6'
6''
it does not properly explain why the deoxygenation
(Scheme 3, Route B) competes so well in the former case
(Scheme 1, entry d) and it is not at all observed in the
latter (Scheme 2).5 We are presently designing new ex-
periments to try to rationalize these results.
Route A
Route B
R2
R2
Route C
Route D
A
O
R2
R2
R2
R2
O
A
A
R1 R1
R1
R1
R1
R1
Anyhow, we took advantage of the reaction described
above to propose, in the case of methyl chrysanthemate
2a¢, a novel method, which allows recycling of the non-
biologically active stereoisomers (Scheme 5). This meth-
od uses the sequential racemization–resolution trick.
2
7
8
Scheme 3 Proposed mechanisms rationalizing the reaction of vinyl-
cyclopropane epoxides with samarium diiodide
It involves (i) the SmI2-mediated cyclopropane ring-open-
ing of 2a¢, which at the same time destroys the two chiral
centers present on the cyclopropane ring1,6 and leads to
achiral 3a¢, and (ii) the base-promoted ring-closure of the
resulting benzoate 9a¢ which produces a racemic mixture
of methyl trans- and cis-chrysanthemate.7
The former 6¢ can only produce the vinylcyclopropane 2
via a b-elimination reaction (Scheme 3, Route A) whereas
the latter 6¢¢ can generate either the same vinylcyclopro-
pane 2 (Scheme 3, Route B) or can undergo ring-opening,
as cyclopropylcarbinyl radicals usually do, to generate 7
and/or 8 bearing an allylic alkoxide and a radical
(Scheme 3, Routes C and/or D).
During the course of this work, we have confirmed that
diphosphorus tetraiodide and phosphorus triiodide which,
as samarium diiodide, are known to exhibit a high propen-
sity to reduce epoxides to olefins,1,8 allows the clean
deoxygenation of all the epoxide vinylcyclopropane de-
rivatives whose structures are disclosed in Table 2.
Anyhow, the Scheme reported above does not explain all
the results disclosed in this paper. For instance, if the vi-
nylcyclopropane 2 is exclusively produced via Route A
(Scheme 3), its amount should increase by increasing the
substitution at the carbon bearing the R2 group which is
Synlett 2005, No. 17, 2688–2690 © Thieme Stuttgart · New York