Electron transfer promoted regioselective ring-opening reaction of cyclopropyl silyl ethers

Article abstract of DOI:10.1021/ol0709937

Oxidative ring-opening reactions of cyclopropyl silyl ethers incorporated into bicyclo[m.1.0]alkane framework were investigated. The results show that the regioselectivities for ring-opening of intermediate radical cations, formed by single electron transfer, are governed by the nature of the nucleophile as well as oxidizing species.

Full text of DOI:10.1021/ol0709937

ORGANIC
LETTERS
2
007
Vol. 9, No. 15
811-2814
Electron Transfer Promoted
2
Regioselective Ring-Opening Reaction
†
of Cyclopropyl Silyl Ethers
Eietsu Hasegawa,* Naoto Yamaguchi, Hiroyasu Muraoka, and Hiroyuki Tsuchida
Department of Chemistry, Faculty of Science, Niigata UniVersity, Ikarashi-2 8050,
Niigata 950-2181, Japan
ehase@chem.sc.niigata-u.ac.jp
Received April 27, 2007
ABSTRACT
Oxidative ring-opening reactions of cyclopropyl silyl ethers incorporated into bicyclo[m.1.0]alkane framework were investigated. The results
show that the regioselectivities for ring-opening of intermediate radical cations, formed by single electron transfer, are governed by the nature
of the nucleophile as well as oxidizing species.
Radical ions that are generated by single electron transfer
SET) reduction and oxidation (redox) of neutral organic
derivatives with various metal-based oxidizing agents have
been reported. Surprisingly, only a few examples of PET-
5
(
molecules have been extensively investigated due to the
frequent role they play as intermediates in chemical and
biological redox processes.1,2 Photoinduced electron transfer
induced cyclopropane ring-opening reactions of cyclopro-
panol derivatives have been described in spite of the fact
6
(
PET) is a repeatedly employed method used to generate
(3) (a) Photoinduced Electron Transfer; Fox, M. A., Chanon, M., Eds.;
Elsevier: Amsterdam, The Netherlands, 1988; Parts A-D. (b) Kavarnos,
G. J. Fundamental of Photoinduced Electron Transfer; VCH Press: New
York, 1993. (c) CRC Handbook of Organic Photochemistry and Photo-
biology, 1st ed.; Horspool, W. M., Song, P. S., Eds.; CRC Press: Boca
Raton, FL, 1994; and CRC Handbook of Organic Photochemistry and
Photobiology, 2nd ed; Horspool, W. M., Lenci, F., Eds.; CRC Press: Boca
Raton, FL, 2004. (d) Hasegawa, E. J. Photosci. 2003, 10, 61-69. (e) Cossy,
J.; Belloti, D. Tetrahedron 2006, 62, 6459-6470. (f) Floreancig, P. E. Synlett
2007, 191-203. (g) Waske, P. A.; Tzvetkov, N. T.; Mattay, J. Synlett 2007,
669-685.
1
,3
radical ions. Owing to the characteristic reactivity of their
radical cations, cyclopropanol derivatives are both mecha-
nistically and synthetically attractive substrates. Many
4
examples of electron transfer reactions of cyclopropanol
†
Dedicated to Professor Patrick S. Mariano (University of New Mexico),
who is a pioneer of mechanistic as well as synthetic photoinduced electron
transfer chemistry, on the occasion of his 65th birthday.
(1) (a) Eberson, L. Electron Transfer Reactions in Organic Chemistry;
(4) Kulinkovich, O. G. Chem. ReV. 2003, 103, 2597-2632.
Springer-Verlag: Berlin, Germany, 1987. (b) AdVances in Electron
Transfer Chemistry; Mariano, P. S., Ed.; JAI Press: Greenwich, CT, 1991-
(5) (a) DePuy, C. H.; Van Laren, R. J. J. Org. Chem. 1974, 39, 3360-
3365. (b) Ito, Y.; Fujii, S.; Saegusa, T. J. Org. Chem. 1976, 41, 2073-
2074. (c) Paolobelli, A. B.; Gioacchinia, F.; Ruzziconi, R. Tetrahedron Lett.
1993, 34, 6333-6336. (d) Booker-Milburn, K. I.; Thompson, D. F. J. Chem.
Soc., Perkin Trans. 1 1995, 2315-2321. (e) Iwasawa, N.; Funahashi, M.;
Hayakawa, S.; Ikeno, T.; Narasaka, K. Bull. Chem. Soc. Jpn. 1999, 72,
85-97. (f) Iwaya, K.; Tamura, M.; Nakamura, M.; Hasegawa, E. Tetra-
hedron Lett. 2003, 44, 9317-9320. (g) Hasegawa, E.; Tsuchida, H.; Tamura,
M. Chem. Lett. 2005, 34, 1688-1689. (h) Kirihara, M.; Kakuda, H.;
Ichinose, M.; Ochiai, Y.; Takizawa, S.; Mokuya, A.; Okubo, K.; Hatano,
A.; Shiro, M. Tetrahedron 2005, 61, 4831-4839. (i) Chiba, S.; Cao, Z.;
Bialy, S. A. A.; Narasaka, K. Chem. Lett. 2006, 35, 18-19.
1
999; Vols. 1-6. (c) Electron Transfer in Chemistry; Balzani, V., Ed.;
Wiley-VCH: Weinheim, Germany, 2001; Vols. 1-5.
2) (a) Schmittel, M.; Burghart, A. Angew. Chem., Int. Ed. Engl. 1997,
6, 2550-2589. (b) Berger, D. J.; Tanko, J. M. In The Chemistry of Double-
Bonded Functional Groups; Patai, S., Ed.; Wiley: New York, 1997; pp
281-1354. (c) Schmittel, M.; Ghorai, M. K. In Electron Transfer in
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(
3
1
2
, pp 5-54. (d) Roth, H. D. In ReactiVe Intermediate Chemistry; Moss, R.
A., Platz, M. S., Jones, M., Jr., Eds.; John Wiley & Sons: New York, 2004;
Chapter 6, pp 205-272.
1
0.1021/ol0709937 CCC: $37.00
© 2007 American Chemical Society
Published on Web 06/27/2007

that cyclopropanes are among the most thoroughly investi-
gated target molecules in PET chemistry.3,7,8
Scheme 2
The regioselectivity of bicyclo[m.1.0]alkane containing
cyclopropanol radical cation ring-opening, viz., internal-bond
cleavage vs external-bond cleavage (Scheme 1), is an
Scheme 1
that radical cations, formed as intermediates in these SET
oxidation reactions, undergo regioselective cleavage of the
internal-bond of the cyclopropane ring.
Next, the redox sensitization method was chosen to explore
the PET reactivity of these substrates. This method employs
9
interesting mechanistic and synthetic issue. In this Letter,
we report the preliminary results of a study probing the
factors that govern the reaction pathways followed in PET
reactions of cyclopropyl silyl ethers embedded in bicyclo-
9
,10-dicyanoanthracene (DCA) and biphenyl (BP) to generate
11,12
the biphenyl radical cation, which acts as the hole catalyst.
By using DCA (0.1 equiv) and BP (1.2 equiv) in MeCN
with irradiation (λ > 340 nm) for 8 h, 1a was quantitatively
recoverd. In contrast, these conditions promoted PET reaction
of 1b to form the unexpected product 4 (58%) and a small
amount of 2b (4%) at 73% conversion (Scheme 3). Surpris-
[m.1.0]alkane frameworks.
Initially, we probed reactions of cyclopropyl silyl ethers
with tris-p-bromophenylaminium hexachloroantimonate
TBPA), a well-known hole catalyst,10 to determine if and
1
(
how these compounds react with a nonmetal-based oxidizing
agent. Treatment of 1a with TBPA (2 equiv) in MeCN at
room temperature for 2 h resulted in the generation of ring-
expanded product 3a5g (Scheme 2). Subjecting the crude
reaction mixture to refluxing methanolic NaOAc (5 equiv)
for 2 h produced enone 2a (60%). In a similar manner,
enones 2b and 2c were obtained in 76% and 52% yields,
starting with 1b and 1c, respectively. The results clearly show
Scheme 3
(
6) (a) Sheller, M. E.; Mathies, P.; Petter, B.; Frei, B. HelV. Chim. Acta
1
5
8
1
6
984, 67, 1748-1754. (b) Gassman, P. G.; Burns, S. J. J. Org. Chem. 1988,
3, 5576-5578. (c) Rinderhagen, H.; Mattay, J. Chem. Eur. J. 2004, 10,
51-874. (d) Waske, P. A.; Mattay, J. Tetrahedron, 2005, 61, 10321-
0330. (e) Rinderhagen, H.; Waske, P. A.; Mattay, J. Tetrahedron 2006,
2, 6589-6593.
(7) Representative reviews for PET reaction of cyclopropanes. (a)
Miyashi, T.; Ikeda, H.; Takahashi, Y.; Akiyama, K. In AdVances in Electron
Transfer Chemistry; Mariano, P. S., Ed.; JAI Press: Greenwich, CT, 1999;
Vol. 6, pp 1-39. (b) Mizuno, K.; Ichinose, N.; Yoshimi, Y. J. Photochem.
Photobiol. C 2000, 1, 167-193.
(8) On the contrary, PET reactions of cyclopropanone silyl acetals have
been well investigated. (a) Abe, M.; Oku, A. J. Chem. Soc., Chem. Commun.
1
994, 1673-1674. (b) Oku, A.; Abe, M.; Iwamoto, M. J. Org. Chem. 1994,
5
9, 7445-7452. (c) Mizuno, K.; Konishi, G.; Nishiyama, T.; Inoue, H.
Chem. Lett. 1995, 1077-1078. (d) Abe, M.; Oku, A. J. Org. Chem. 1995,
6
0, 3065-3073. (e) Mizuno, K.; Nishiyama, T.; Takahashi, N.; Inoue, H.
Tetrahedron Lett. 1996, 37, 2975-2978. (f) Abe, M.; Nojima, M.; Oku,
A. Tetrahedron Lett. 1996, 37, 1833-1836. (g) Oku, A.; Miki, T.; Abe,
M.; Ohira, M.; Kamada, T. Bull. Chem. Soc. Jpn. 1999, 72, 511-517. (h)
Oku, A.; Takahashi, H.; Asmus, S. J. Am. Chem. Soc. 2000, 122, 7388-
7
389.
9) Lewis acids are known to prefer regioselective external bond cleavage
ingly, PET reaction of 1c again generated the spirocyclic
ketone 5 (59% based on 83% conversion), a product that is
different from that formed by using TBPA as the oxidant.
In the cases of 1b and 1c, no reaction took place in the
(
of cyclopropanols incorporated into bicyclic systems. (a) Murai, S.; Aya,
T.; Renge, T.; Ryu, I.; Sonoda, N. J. Org. Chem. 1974, 39, 858-859. (b)
Ryu, I.; Ando, M.; Ogawa, A.; Murai, S.; Sonoda, N. J. Am. Chem. Soc.
1
1
983, 105, 7192-7194. (c) Ryu, I.; Murai, S.; Sonoda, N. J. Org. Chem.
986, 51, 2389-2361. (d) Nakahira, H.; Ryu, I.; Han, L.; Kambe, N.;
Sonoda, N. Tetrahedron Lett. 1991, 32, 229-232. (e) Nakahira, H.; Ryu,
I.; Ikebe, M.; Oku, Y.; Ogawa, A.; Kambe, N.; Sonoda, N.; Murai, S. J.
Org. Chem. 1992, 57, 17-28.
(11) (a) Schaap, A. P.; Lopez, L.; Gagnon, S. D. J. Am. Chem. Soc.
1983, 105, 663-664. (b) Schaap, A. P.; Siddiqui, S.; Gagnon, S. D.; Lopez,
L. J. Am. Chem. Soc. 1983, 105, 5149-5150.
(10) (a) Bellville, D. J.; Wirth, D. D.; Bauld, N. L. J. Am. Chem. Soc.
(12) On the basis of the redox potentials of the compounds, both the
1
•+
1
981, 103, 718-720. (b) Bauld, N. L.; Bellville, D. J.; Harirchian, B.;
singlet excited state of DCA ( DCA*) and the radical cation of BP (BP )
Lorentz, K. T.; Pabon, R. A.; Reynolds, D. W.; Wirth, D. D.; Chiou, H. S.;
Marsh, B. K. Acc. Chem. Res. 1987, 20, 371-378. (c) Bauld, N. L. In
AdVances in Electron Transfer Chemistry; Mariano, P. S., Ed.; JAI Press:
Greenwich, CT, 1992; Vol. 2, pp 1-66.
could accept a single electron from 1. However, the former electron transfer
generates a radical ion pair that often undergoes energy wasting back
6
electron transfer. Detailed redox data and discussion are described in the
Supporting Information.
2812
Org. Lett., Vol. 9, No. 15, 2007

absence of BP. Noteworthy is the observation that 1d, a side
chain homolog of 1c, was inert under the redox senstitization
conditions. However, when the solvent mixture contained
MeOH (MeCN-MeOH ) 3:1), reaction of 1d took place
to form the spirocyclic product 6 although its yield was not
high, ca. 30% yield at 83% conversion. Also, the presence
of MeOH enabled the conversion of 1c to 5 to occur (57%
yield at 37% conversion) in the absence of BP. The silophilic
nature of MeOH, which promotes desilylation of the silyl
ether radical cations, is the apparent source of these differ-
ences.13
Scheme 5
The observations summarized above show that reactions
of 1 promoted by the tris-p-bromophenylamine radical cation
and the PET generated biphenyl radical cation follow
different cyclopropane ring-opening pathways. In addition,
the presence of nucleophiles, such as chloride ion and MeOH,
alter the SET reactions by enhancing desilylation of the
radical cation derived from 1. A plausible explanation for
these findings is found in the reaction mechanism presented
in Scheme 4. Single electron transfer of 1 and subsequent
The proposal made above leads to the suggestion that
addition of external oxidants to the PET system should alter
the course of the reactions, favoring pathways via cationic
intermediates. Indeed, PET reaction of 1a in the presence
Scheme 4
16,17
of Cu(OAc)
2
(1.2 equiv) (Scheme 6)
led to production
Scheme 6
nucleophile assisted desilylation of 1•+ gives the cyclopro-
poxy radical 7, which undergoes either external- or internal-
bond cleavage to generate the respective primary alkyl radical
14
8
or tertiary alkyl radical 9. In the reaction promoted by
TBPA, 9 is oxidized by another equivalent of TBPA to form
the tertiary carbocation 10, from which 3 and finally 2 is
formed. On the contrary, when formed under PET conditions,
of 2a (54%), the same product that is generated in the TBPA-
promoted reaction, along with 15 (26%). A control experi-
ment, involving direct irradiation of 1a in the presence and
8
c, 9b, and 9d undergo radical rearrangements to give the
15
products 5, 4, and 6, respectively (Scheme 5). In these
1
•+
cases, the oxidizing species such as DCA* and BP have
short lifetimes and, as a result, their steady-state concentra-
tions are too low to oxidize 9.
(15) (a) While 5-exo hexenyl radical cyclization corresponding to the
1
5b
rearrangements 8c f 13 and 9d f 14 is a well-known process, same
type of rearrangement as the transformation of 9b f 11 f 12 was
previously reported.6c (b) Griller, D.; Ingold, K. U. Acc. Chem. Soc. 1980,
13, 317-323.
(13) (a) Hasegawa, E.; Xu, W.; Mariano, P. S.; Yoon, U. C.; Kim, J. U.
J. Am. Chem. Soc. 1988, 110, 8099-8111. (b) Zhang, X.; Yeh, S. R.; Hong,
S.; Freccero, M.; Albini, A.; Falvey, D. E.; Mariano, P. S. J. Am. Chem.
Soc. 1994, 116, 4211-4220. (c) Su, Z.; Mariano, P. S.; Falvey, D. E.; Yoon,
U. C.; Oh, S. W. J. Am. Chem. Soc. 1998, 120, 10676-10686.
(16) Cu(II) ion is known to act as an effective oxidant toward alkyl
radicals. Snider, B. B. Chem. ReV. 1996, 96, 339-363.
(17) Use of Cu(II) salts for PET reactions. (a) Mizuno, K.; Yoshioka,
K.; Otsuji, Y. Chem. Lett. 1983, 941-944. (b) Takahashi, Y.; Nishioka,
N.; Endoh, F.; Ikeda, H.; Miyashi, T. Tetrahedron Lett. 1996, 37, 1841-
1844. (c) Lee, J.; Jong, S. U.; Blackstock, S. C.; Cha, J. K. J. Am. Chem.
Soc. 1997, 119, 10241-10242. (d) Lee, H. B.; Sung, M. J.; Blackstock, S.
C.; Cha, J. K. J. Am. Chem. Soc. 2001, 123, 11322-11324.
(14) (a) Ryu, I.; Fukushima, H.; Okuda, T.; Matsu, K.; Kambe, N.;
Sonoda, N.; Komatsu, M. Synlett 1997, 1265-1268. (b) Chatgilialoglu, C.;
Ferreri, C.; Lucarini, M.; Venturini, A.; Zavitsas, A. Chem. Eur. J. 1997,
3
, 376-387.
Org. Lett., Vol. 9, No. 15, 2007
2813

absence of Cu(OAc)
a. Unexpectedly, PET reactions of 1c and 1d with Cu(OAc)
present produced the respective spirocyclic products 16
2
, resulted in the complete recovery of
cyclopropane radical cations,21 and that it reacts intra-
molecularly with the pendant alkene group prior to cyclo-
propane ring-opening.
1
2
(
69%) and 17 (76%) along with small amounts of 2c (4%)
To further evaluate the redox sensitization method, we
explored the reactivity of the aliphatic substrate 18 (Scheme
7). DCA photosensitized PET reaction of 18 was already
18
and 2d (3%).
As discussed above, nucleophiles such as chloride ion,
MeOH, and acetate anion would promote the desilylation
of 1 to produce 7 (see Scheme 4). However, information
•
+
Scheme 7
about the reactivity of such radical cations in the absence of
6
e
nucleophiles is limited. According to the literature, cyclo-
propyl silyl ether radical cations that possess long-bond
character rearrange to ring-opened distonic radical cations,
which behave as alkyl radicals. If this description is
•
+
applicable to 1 (Figure 1), it would be difficult to
reported6d to produce an extremely low yield (10%) of 19,
likely formed through an internal-bond cleavage and 5-exo
cyclization sequence. In contrast, we observed that PET
reaction of 18, using the DCA-BP system, afforded 19 in a
much higher yield (76%). We also observed that 18 did not
react to form 19 when BP was absent and a complicated
product mixture was formed when 18 was treated with
TBPA.
Figure 1. Structures of cyclopropyl silyl ether radical cations.
Our studies of electron transfer promoted oxidative ring-
opening reactions of aryl-substituted cyclopropyl silyl ethers
have shown that the regioselectivity for cyclopropane ring-
opening can be controlled by the choice of electron transfer
conditions. The above results and discussion allow us to
conclude that reaction pathways of the radical cations of these
compounds are strongly influenced by the control of the
following steps. In other words, the initial cyclopropane bond
cleavage, which would be reversible, is not a product-
determing step if a rapid follow-up step is not available.
Another notable finding is the cooperative effect seen in PET
processes promoted by DCA, BP, and Cu(II). Observations
have been made which suggest that cyclopropyl silyl ether
radical cations have long-bond structures and are reactive
with intramolecularly existing carbon-carbon double bonds.
Finally, although not optimized, a redox sensitization reaction
of an aliphatic cyclopropyl silyl ether has been observed.
understand why 1c undergoes PET reaction and 1d does not
in the absence of MeOH. In both cases, in-distonic and ex-
distonic radical cations can be formed even though some
differences should exist in the rate constants for their ensuing
5
-exo-radical cyclizations.19 Also, PET reaction of 1a does
not take place in MeCN in the presence of 1,4-cyclohexa-
diene (CHD), a hydrogen atom donor expected20 to trap the
ex-distonic radical efficiently and form 15. In contrast, PET
reaction of 1a with CHD in 3:1 MeCN-MeOH produces
1
5 in 43% yield (30% conversion). These results suggest
•
+
that 1 has long-bond character in a manner similar to
(
18) Compounds 16 and 17 could be formed through the sequence
•-
described as follows. Electron transfer between Cu(II) and DCA produces
Cu(I) ion. Then, the Cu(I) ion reacts with the alkyl radicals 13 and 14 to
give the organo copper compounds, which undergo â-hydride elimination
to produce 16 and 17, respectively.
1
7a
9e
(
19) (a) The rate constants for 5-exo hexenyl radical cyclizations for
Acknowledgment. We thank Professors Ilhyong Ryu and
Hiroshi Ikeda of Osaka Prefecture University for their
valuable comments. We also thank Mr. Junichi Sakai of
Niigata University for his assistance in measuring HRMS.
5
primary and tertiary alkyl radicals are reported to be 2.3 × 10 to 3. 6 ×
6
-1
5
-1
19b
1
0 s and 3.5 × 10 s , respectively. (b) Beckwith, A. L. J.; Schiesser,
C. H. Tetrahedron 1985, 41, 3925-3941.
20) (a) It is reported that the rate constant of hydrogen atom abstraction
(
5
-1
-1 20b
from CHD by a primary alkyl radical is 5 × 10 s
M
.
Under this
at 2.1 M of CHD. (b)
Newcomb, M. Tetrahedron 1993, 49, 1151-1176.
21) (a) Dinnocenzo, J. P.; Todd, W. P.; Simpson, T. R.; Gould, I. R. J.
6
-1
condition, the estimated rate is 1.1 × 10
s
Supporting Information Available: General and reaction
procedures, spectral data of cyclopropyl silyl ethers and
products, and additional discussion. This material is available
free of charge via the Internet at http://pubs.acs.org.
(
Am. Chem. Soc. 1990, 112, 2462-2464. (b) Krogh-Jespersen, K.; Roth, H.
D. J. Am. Chem. Soc. 1992, 114, 8388-8394. (c) Dinnocenzo, J. P.; Zuilhof,
H.; Lieberman, D. R.; Simpson, T. R.; McKechney, M. W. J. Am. Chem.
Soc. 1997, 119, 994-1004. (d) Herbertz, T.; Roth, H. D. J. Am. Chem.
Soc. 1998, 120, 11904-11911.
OL0709937
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Org. Lett., Vol. 9, No. 15, 2007