Facile ring opening of siloxy cyclopropanes by photoinduced electron transfer. A new way to β-keto radicals

Article abstract of DOI:10.1016/j.tet.2006.03.060

Siloxy cyclopropanes undergo ring opening and fragmentation of formal silyl cations under formation of β-keto radicals. These reactive intermediates can be used in inter- and intramolecular addition reactions leading to complex ring systems if more than one unsaturated side chain is present in the starting material. Beside some synthetic examples mainly the mechanism will be discussed focusing on the structure of the primarily formed radical cations, the regioselectivity of cyclopropane cleavage (endo vs exo ring opening), leaving of the silyl group, and termination by H-transfer.

Full text of DOI:10.1016/j.tet.2006.03.060

Tetrahedron 62 (2006) 6589–6593
Facile ring opening of siloxy cyclopropanes by photoinduced
electron transfer. A new way to b-keto radicals
*
Heiko Rinderhagen, Prashant A. Waske and Jochen Mattay
Organische Chemie I, Fakultat fu€r Chemie, Universitat Bielefeld, Postfach 100131, 33501 Bielefeld, Germany
¨
¨
Received 6 December 2005; accepted 12 February 2006
Available online 17 April 2006
Abstract—Siloxy cyclopropanes undergo ring opening and fragmentation of formal silyl cations under formation of b-keto radicals. These
reactive intermediates can be used in inter- and intramolecular addition reactions leading to complex ring systems if more than one unsaturated
side chain is present in the starting material. Beside some synthetic examples mainly the mechanism will be discussed focusing on the struc-
ture of the primarily formed radical cations, the regioselectivity of cyclopropane cleavage (endo vs exo ring opening), leaving of the silyl
group, and termination by H-transfer.
Ó 2006 Elsevier Ltd. All rights reserved.
R2
R2
R2
Me3SiO
R1
Me3SiO
R1
O
1. Introduction
PET
-
R3
-SiMe3(+)
R
-e
R3
R3
Single Electron Transfer (SET)1 and especially Photo-
induced Electron Transfer (PET)2 has become a powerful
tool in organic synthesis3 after fundamental research, which
started already in 1960s, e.g., by Marcus,4 Weller,5 and
others.6 Early highlights of synthetic applications are related
to the work of Arnold,7 Mariano,8 Schuster,9a Steckhan,9b
and many other groups10 including ourselves.11
A
B
C
hv
+A
Sens *
PET: Sens
Sens + A
Sens: electron transfer sensitizer (cyano arenes)
Scheme 1. Cleavage and fragmentation of siloxy cyclopropanes A to radical
cations B and b-keto radicals C.
The very simple but even most powerful concept behind this
methodology is based on the weakening of bonds by oxida-
tion/reduction under formation of radical cations/radical
anions leading to an increased reactivity of the molecules.12
Examples of synthetic applications cover addition,13 cyclo-
addition,14 fragmentation,15 substitutions,16 and other reac-
tions.17 Often the details of the mechanisms involved in
these reactions are not yet completely known although the
primary and initiating step is always PET. Especially in frag-
mentation and addition reactions radical species may also be
involved.18
Both the radical cation B and the b-keto radical C are very
useful intermediates especially in intramolecular addition
reactions to p-systems leading to new cyclized products.
We have made use of this method for synthesizing poly-
cyclic compounds.19 Beside some exemplary reactions
we will discuss in more detail the mechanism involved
especially regarding bicyclic siloxy cyclopropanes
(Scheme 2).
O
Me3SiO
In this report we will focus on a new method of generating
b-keto radicals from siloxy cyclopropanes by oxidative
PET (Scheme 1). The primary step is oxidation of the start-
ing material under cleavage of the cyclopropane A leading to
a distonic radical cation B, which finally forms the b-keto
radical C.
(+)
-SiMe3
( )n
E
( )n
F
Me3SiO
( )n
D
O
Me3SiO
(+)
( )n -SiMe3
Keywords: Siloxy cyclopropanes; Photoinduced electron transfer; Radical
cations; Radicals; Radical cascade reactions; Reaction mechanism.
* Corresponding author. Tel.: +49 521 1062072; fax: +49 521 1066417;
e-mail: mattay@uni-bielefeld.de
( )n
H
G
Scheme 2. exo- and endo-cleavage of bicyclic siloxy cyclopropanes.
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.03.060

6590
H. Rinderhagen et al. / Tetrahedron 62 (2006) 6589–6593
1.490 Å
Important questions concern the structure of siloxy cyclo-
propane radical cations in comparison with unsubstituted
or alkyl-substituted cyclopropane radical cations, the regio-
selectivity of endo- versus exo-cleavage of bicyclic cyclo-
propanes D yielding E and G, and the factors controlling
the fragmentation of D to the b-keto radicals F and H.
1.498 Å
MeO
1.297 Å
2.166 Å
6
B3LYP 6-31G*
geometry optimization
2. Structure of siloxy cyclopropane radical cations
Upon ionization, cyclopropane derivatives can form two
types of radical cations depending on the substitution pattern
(Scheme 3, top).20,21 The 2N1L type (2 normal, 1 long)
shows a long one electron-two center bond in the range of
MeO
MeO
a
geometry optimization
5
˚
1.85–1.95 A. The calculated bond lengths of the radical
cations 2–4 indeed confirm this classification (Scheme 3,
bottom). On the contrary, aryl- and vinyl-substituted cyclo-
propanes prefer the 2L1S type (2 long, 1 short) as shown
for 1-phenylcyclopropane 1 (Scheme 3).
B3LYP 6-31G*
(i) geometry optimization at
constant bond length 'a'
(ii) repeated geometry optimization
2N1L
2L1S
2.175 Å
R
R
R
MeO
1.292 Å
1.4996 Å
R
R
R = H, Alkyl
R=Ph, Vinyl
1.499 Å
7
1.463 Å
1.523 Å
1.450 Å
1.591 Å
Ph
1.591 Å
CH3
Scheme 4. Structural details of radical cations of 1-methoxy-1,2-dimethyl-
cyclopropane.
Ph
1.723 Å
2
1
1.483 Å
CH3
1.511 Å
1.469 Å
CH3
SiMe3
1.450 Å
Ph
AM1
O
OSiMe3
OSiMe3
a
HF 631G*
B3LYP 631G*
geometry optimization
CH3
Ph
1.789 Å
3
1.943 Å
4
9
geometry
optimised
8
SiMe3
AM1
O
Scheme 3. Types of cyclopropane radical cations according to Hudson and
structural details of selected examples (for Refs. 20 and 21 see text).
HF 631G*
B3LYP 631G*
(i) geometry optimization at
constant bond length 'a'
(ii) repeated geometry
optimization
Following this classification for siloxy cyclopropanes of the
type D should give radical cations of the type 2N1L after
oxidation. Scheme 4 shows the results of an ab initio calcula-
tion of the model compound 1-methoxy-1,2-dimethylcyclo-
propane 5. Note, that the elongated C–C bonds of 6 and 7
10
Scheme 5. Quantum chemical calculations on the structure of radical
cations 9 and 10.
˚
are even longer (ca. 2.17 A) compared to 2–4 (ca. 1.72–
˚
1.94 A). However, the results considering only the energetics
show that it is not possible to differentiate between the two
ways of cleavage leading to 6 and 7, respectively.
3. Experimental studies on endo- versus
exo-cleavage of bicyclic siloxy
cyclopropanes of structure D
Even similar calculations on the radical cations 9 and 10
generated from the bicyclic siloxy cyclopropane 8 upon
oxidation (cf. Scheme 2, D, n¼2) do not allow a differentia-
tion between endo- versus exo-cleavage (Scheme 5). Both
Irradiation of bicyclic siloxy cyclopropanes D leads to the
ring opening of the three-membered ring under ring enlarge-
ment (endo-cleavage) or under preservation of the ring (exo-
cleavage) depending on the ring size (Scheme 6). However,
in presence of methyl acrylate as scavenger only the ring
enlarged addition products are formed (e.g., 8/13 and
14/17). This observation strongly indicates that the pri-
mary step after oxidation is ring opening of the endocyclic
bond of 8 and 14.
semiempirical and ab initio methods lead to extremely
22
˚
elongated endo- and exo-bonds (ca. 2.4–2.5 A). Only a
calculation of the transition states and the complete potential
hypersurface clearly verify the preferred cleavage of the en-
docyclic bond under formation of 9. Details of this theoret-
ical analysis including matrix isolation studies on the
reactive intermediates will be published separately.23

H. Rinderhagen et al. / Tetrahedron 62 (2006) 6589–6593
6591
OSiMe3
O
O
O
O
Me3SiO
PET
PET
PET
COOMe
+
+
+ Oligo(poly)mers
COOMe
COOMe
COOMe
COOMe
12
11
8
13
18
19
11:12 = 1:1
O
O
O
Me3SiO
PET
PET
80
+
COOMe
70
60
50
40
30
20
10
0
16
15
15:16 = 1:3
14
17
Scheme 6. PET reactions of bicyclic siloxy cyclopropanes in the absence
and presence of methyl acrylate as scavenger.
The ring opening may already occur at the level of the radi-
cal cation of the D (leading to G) or at the level of the oxy
radical I generated after fragmentation of the trimethylsilyl
cation (leading to H). These results also show that the possi-
ble equilibrium between ring-preserved and ring-opened in-
termediates (E4G and F4H) is slow compared to the fast
scavenging reactions in the presence of the methyl acrylate
(Scheme 7).
0
10
Concentration of methylacrylate [mmol/l]
20
30
Scheme 8. Yield of the trapping product 19 in dependence on the methyl
acrylate concentration.
4. Fragmentation of the trimethylsilyl group
One important question concerns the timing of loss of the
silyl group. Recent studies on the PET reactions of silyl
enol ethers have shown that this cleavage is strongly influ-
enced by nucleophiles such as alcohols or even the solvents
(most often acetonitrile whose nucleophilicity can be in-
creased by high pressure).18,24 Silyl enol ethers give nondis-
tonic radical cations on PET-oxidation, whereas siloxy
cyclopropane radical cations undergo C–C bond cleavage
activationless according to quantum chemical calcula-
tions.22,25 Therefore, we assume that the loss of the silyl
group takes place only at the stage of the distonic radical cat-
ions E and G. Using silyl enol ethers the course of the reac-
tion, i.e., radical cation versus radical reaction pathway, can
be controlled by timing the cleavage of the silyl group. For
example, in solvent mixtures of high nucleophilicity loss
of the silyl group leads to the corresponding a-keto radical
23, which preferentially undergoes 5-exo cyclization to 24
if a suitable unsaturated side chain is present.18,24 However,
in the absence of nucleophiles 6-endo is the preferred cycli-
zation mode leading to 22 (Scheme 9).
O
(CH2)n
+H
SiMe3
SiMe3
O
O
+Nu
-NuSiMe3
+
(CH2)n
F
(CH2)n
E
SiMe3
O
O
O
+Nu
-NuSiMe3
PET
+
(CH2)n
(CH2)n
D
(CH2)n
I
SiMe3
O
O
+Nu
-NuSiMe3
+
(CH2)n
(CH2)n
O
OSiMe3
G
H
+H
O
20
24
(CH2)n
PET
O
OSiMe3
O
Scheme 7. Equilibrium between ring-opened and ring-preserved intermedi-
ates (radical cations E and G structures are presented with already broken
C–C bond, cf. Scheme 2).
+Nu
-NuSiMe3+
22
21
23
Further studies on the kinetics of 18 as model compound in
the presence of methyl acrylate confirm these findings and
furthermore, show that the termination step (H-abstraction)
is relatively slow (Scheme 8). A detailed analysis is reported
elsewhere.22,24
Scheme 9. Radical cations versus radical cyclization pathways in PET
reactions of the silyl enol ethers.
In the case of siloxy cyclopropanes this dependency on the
reaction medium is not as pronounced as for silyl enol

6592
H. Rinderhagen et al. / Tetrahedron 62 (2006) 6589–6593
ethers.19a,22 This might be taken as an indication for the
higher reactivity of the distonic radical cations compared
to nondistonic ones.
O
OSiMe3
DCN
H
H
H
350 nm
25
26 (57%)
O
5. Termination by H-transfer
Me3SiO
DCN
An often discussed question is related to the mechanism of
the final step of PET-induced cyclizations of unsaturated
silyl enol ethers and siloxy cyclopropanes. In all examples
studied by us this termination is based on H-transfer to the
final radical intermediate of the cascade fragmentation addi-
tion process (cf. Schemes 6–9). Two mechanisms can be dis-
cussed, i.e., a formal H-atom transfer (e.g., from the solvent)
and a two-step process via electron and proton transfer
(Scheme 10). The reduction of the radical Rꢀ may occur by
electron transfer from the radical anion of the sensitizer
(cf. Scheme 1).
H
350 nm
27
28 (49%)
O
H
OSiMe3
DCN
H
O
350 nm
29
30 (66%)
O
OSiMe3
DCN
350 nm
+
+H
32 (37%)
31
33 (11%)
O
O
OSiMe3
O
H
H
R
R
H
-
+e
+ H(+)
R(-)
DCA
H
H
+
+
420 nm
( )
( )
n
n
Scheme 10. Possible H-saturation pathways.
36 (30%)
37 (6%)
34
35 (15%)
OSiMe3
O
We have shown by a comprehensive study using deuterated
solvents that both acetonitrile and water are sources for this
saturation. In addition, kinetic isotope effects of H-transfer
from acetonitrile influence the ratio of direct and two-step
H-transfer as well. These effects are even stronger for sec-
ondary radicals.
H
H
DCA
( )
( )
n
420 nm
n
38 n = 1
39 n = 2
40 n = 1 (20%)
41 n = 2 (11%)
Scheme 11. Examples of radical cationic/radical cascade cyclization reac-
tions (DCA¼9,10-dicyanoanthracene; DCN¼1,4-dicyanonaphthalene).
In summary, both H-atom transfer from the solvent and re-
turn electron transfer followed by protonation from water
are responsible for the final saturation process.
and 37 demonstrate that even more complicated condensed
ring systems are accessible by this method.19b
6. Synthetic examples of radical cationic/radical
cascade cyclizations
Acknowledgements
As shown above siloxy cyclopropanes are useful starting
materials for generation of b-keto radicals. These radicals
can be used in further cyclization reactions leading to new
rearranged products or even in radical cascade reactions
involving two cyclization steps. Examples are shown in
Scheme 11 and were taken from recent reports.19 The pri-
mary step after PET-oxidation is cleavage of the endocyclic
C–C-bond of the cyclopropane followed by transannular
cyclization (e.g., 25/26, 27/28, and 29/30).
Our studies on PET reactions have been supported by
Deutsche Forschunggemeinschaft DFG (Bonn) and the
Volkswagenstiftung (Hannover). We are very grateful to
these funding agencies. In particular we are very grateful
to Thomas Bally (Fribourg) for fruitful discussions and crit-
ical reading of the manuscript.
References and notes
The PET reaction of 31 is somewhat more complicated.
Compound 32 is probably formed via a cyclopropyloxy radi-
cal rearrangement, whereas the formation of 33 requires
first transannular addition of the b-keto radical to the benz-
ene ring followed by second C–C bond cleavage.19a This
latter example already indicates some limitations of the
method regarding aryl substituents. However, examples
38/40 and 39/41 show that this protocol is still applica-
ble to arene systems in moderate yields.19b Example 34/36
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