Oxidative opening of cycloalkanols: An efficient entry to ω-iodocarbonyl compounds

Article abstract of DOI:10.1002/1521-3773(20010917)40:18<3389::AID-ANIE3389>3.0.CO;2-V

Simply mix and switch on the light: This is all that is required to obtain ωfunctionalized aldehydes and ketones from readily available cyclic alcohols and IPy₂BF₄. The unusual oxidation process is outlined in Equation (1). R¹

Full text of DOI:10.1002/1521-3773(20010917)40:18<3389::AID-ANIE3389>3.0.CO;2-V

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[
[
1] R. Dagani, Chem. Eng. News 2001, 79(9), 40 ± 43.
2] Reviews: a) J. Burdeniuc, B. Jedlicka, R. H. Crabtree, Chem. Ber.
Oxidative Opening of Cycloalkanols:
An Efficient Entry to w-Iodocarbonyl
1997, 130, 145 ± 154; b) J. L. Kiplinger, T. G. Richmond, C. E. Oster-
berg, Chem. Rev. 1994, 94, 373 ± 431.
Compounds**
[
[
3] T. G. Richmond, Angew. Chem. 2000, 112, 3378 ± 3380; Angew. Chem.
Int. Ed. 2000, 39, 3241 ± 3244.
4] a) M. Aizenberg, D. Milstein, Science 1994, 265, 359 ± 361; b) M.
Aizenberg, D. Milstein, J. Am. Chem. Soc. 1995, 117, 8674 ± 8675;
c) R. J. Young, Jr., V. V. Grushin, Organometallics 1999, 18, 294 ± 296;
d) H. Yang, H. Gao, R. J. Angelici, Organometallics 1999, 18, 2285 ±
Jos e Barluenga,* Francisco Gonz a lez-Bobes,
Sreenivasa R. Ananthoju, Miguel A. García-Martín,
and Jos e M. Gonz a lez
The development of new approaches to elaborate the
carbon backbone of organic compounds is among the central
issues in organic synthesis. In this regard, a general method for
the direct conversion of readily available cyclic alcohols to
bifunctional derivatives, such as w-iodocarbonyl compounds,
is an attractive synthetic goal.[ Herein, we report on a
powerful method for synthesizing iodinated derivatives of
both, aldehydes and ketones.[ Thus, bis(pyridine)iodonium(i)
2
287.
5] G. B. Deacon, C. M. Forsyth, J. Sun, Tetrahedron Lett. 1994, 35, 1095 ±
098.
6] a) J. L. Kiplinger, T. G. Richmond, Chem. Commun. 1996, 1115 ±
[
[
1
1
1
116; b) J. L. Kiplinger, T. G. Richmond, J. Am. Chem. Soc. 1996,
18, 1805 ± 1806.
1]
[
7] a) J. Burdeniuc, R. H. Crabtree, J. Am. Chem. Soc. 1996, 118, 2525 ±
2
1
526; b) J. Burdeniuc, R. H. Crabtree, Organometallics 1998, 17,
582 ± 1586.
2]
[
[
8] B. L. Edelbach, B. M. Kraft, W. D. Jones, J. Am. Chem. Soc. 1999, 121,
0327 ± 10331.
[3]
tetrafluoroborate (IPy BF ) promotes a regioselective open-
2
4
1
ing reaction of 1 upon irradiation leading to compounds 2
9] R. Stürmer, Angew. Chem. 1999, 111, 3509 ± 3510; Angew. Chem. Int.
Ed. 1999, 38, 3307 ± 3308.
4]
(
Scheme 1).[
[
[
10] Y. Kiso, K. Tamao, M. Kumada, J. Organomet. Chem. 1973, 50, C12 ±
C14.
11] a) T. Braun, S. P. Foxon, R. N. Perutz, P. H. Walton, Angew. Chem.
1999, 111, 3543 ± 3545; Angew. Chem. Int. Ed. 1999, 38, 3326 ± 3329;
b) L. Cronin, C. L. Higgitt, R. Karch, R. N. Perutz, Organometallics
1
1
997, 16, 4920 ± 4928; c) D. R. Fahey, J. E. Mahan, J. Am. Chem. Soc.
977, 99, 2501 ± 2508.
[
12] Reviews: a) T. Weskamp, V. P. W. Böhm, W. A. Herrmann, J. Organo-
met. Chem. 2000, 600, 12 ± 22; b) D. Bourissou, O. Guerret, F. P.
Gabbaï, G. Bertrand, Chem. Rev. 2000, 100, 39 ± 91.
-promoted regioselective opening of cycloalkanols. R1,
; n: 2, 3, 4, 10; nine examples (76 ± 94%).
Scheme 1. IPy
2
BF
4
2
R : H, CH
3
[
[
[
13] For catalyst preparations, catalysis procedures, and details on meas-
urements see the Supporting Information.
14] L. Jafarpour, E. D. Stevens, S. P. Nolan, J. Organomet. Chem. 2000,
In preliminary studies, cyclopentanol (1a) was recovered
6
06, 49 ± 54.
15] a) K. Tamao, K. Sumitani, M. Kumada, J. Am. Chem. Soc. 1972, 94,
374 ± 4376; b) R. J. P. Corriu, J. P. Masse, J. Chem. Soc. Chem.
unreacted upon treatment with IPy BF . Moreover, NMR
2
4
experiments revealed that in the absence of visible light no
change had taken place even after several days at room
temperature. Interestingly, when the mixture was photoacti-
vated (irradiation, 100 W lamp) a clean transformation took
place affording 5-iodopentanal (2a)[ in excellent yield after
hydrolysis [Eq. (1)].
4
Commun. 1972, 144.
[
16] Reviews: a) W. A. Herrmann in Applied Homogeneous Catalysis with
Organometallic Compounds (Eds.: B. Cornils, W. A. Herrmann),
Wiley-VCH, Weinheim, 1996, pp. 764 ± 765; b) M. Kumada, Pure
Appl. Chem. 1980, 52, 669 ± 679.
5]
[
17] V. P. W. Böhm, T. Weskamp, C. W. K. Gstöttmayr, W. A. Herrmann,
Angew. Chem. 2000, 112, 1672 ± 1674; Angew. Chem. Int. Ed. 2000, 39,
1602 ± 1604.
[
18] Indications of 12-electron species being responsible for the activity of
zero-valent Group 10 metals bearing bulky ligands were found in the
0
system Pd /P(o-Tol)
3
: J. F. Hartwig, F. Paul, J. Am. Chem. Soc. 1995,
1
17, 5373 ± 5374.
19] F. Terrier, Nucleophilic Aromatic Displacement, VCH, Weinheim,
991.
20] R. W. Hoffmann, Dehydrobenzene and Cycloalkynes, Academic
Press, New York, 1967.
[
[
1
This is an elusive transformation for a secondary alcohol,
only accomplished previously for cyclopentanol derivatives.[
Our method offers a more efficient entry to achieve this
scission reaction even from 1a. This stimulated us to further
investigate its scope and convenience, in search for a clean
[
[
21] G. Smith, J. K. Kochi, J. Organomet. Chem. 1980, 198, 199 ± 214.
22] C. Hansch, A. Leo, Substituent Constants for Correlation Analysis in
Chemistry and Biology, Wiley, New York, 1979.
6]
[
23] Relative rate constants were determined from product ratios in
competition reactions.
[7]
[
*] Prof. Dr. J. Barluenga, F. Gonz a lez-Bobes, Dr. S. R. Ananthoju,
Dr. M. A. García-Martín, Dr. J. M. Gonz a lez
Instituto Universitario de Química Organomet a lica ªEnrique Molesº,
Unidad Asociada al C.S.I.C
Universidad de Oviedo
3
3071 Oviedo (Spain)
Fax : (‡34)98-5103450
E-mail: barluenga@sauron.quimica.uniovi.es
[**] This research was supported by DGES (Grant PB97-1271). F.G.-B.
thanks FICYT for a fellowship.
Angew. Chem. Int. Ed. 2001, 40, No. 18
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and general strategy to produce aldehydes from this rear-
In agreement with this, the reaction of 1c went to
completion by using an excess of cesium carbonate (Table 1,
entry 3, Scheme 2a).
[
8]
rangement. It also provided an opportunity to explore the
behavior of the iodinating reagent IPy BF under this new
2
4
type of activation; thus, expanding the application profile
We were interested in comparing this approach to 2c with
that based on the reaction of PhI(OAc) /I with cyclohexanol,
[3]
already established for IPy BF in electrophilic chemistry.
2
4
2
2
The photolytic reactions were conducted using 2 mmol of
which has not been reported to date. When the reaction was
performed in cyclohexane as solvent,[ the b-scission product
2c was obtained in 20% yield from a mixture that contains
cyclohexanone (3) (21%), iodocyclohexane as the major
reaction product, as well as the expected iodobenzene
(Scheme 2b). The experiment results in a noteworthy C�H
11]
the starting cycloalkanol, typically dissolved in CH Cl2
2
(
20 mL), unless otherwise specified (see Table 1). Under
photoactivation conditions, ring-opening of cyclobutanol (1b)
[9]
by reaction with IPy BF was successful, furnishing 2b in
2
4
9
2% yield, as sole reaction product (Table 1, entry 2).
activation of the alkane used as solvent,[ but it reveals
limitations for the opening of cyclohexanol, subject of
comparison. We also tested the reaction using CH Cl as
12]
Cyclohexanol (1c) was found to undergo a sluggish reaction
in which a significant amount of cyclohexanone (3) was
formed as by-product. The opening of 1c required excess of
the iodonium source, but even in this case, a considerable
amount of unreacted starting material was recovered.
2
2
solvent,[ in this case 2c was isolated in better yield (45%;
Scheme 2c); however, the formation of two new by-products
(4 and 5) was also observed, arising from the evolution of 2c in
the reaction media. A slight improvement of the process was
accomplished by increasing the amount of oxidant system to
achieve full conversion of 1c. Under these conditions, 2c was
obtained in 62% yield but significant overoxidation to 4 and 5
took place (Scheme 2d).
2b]
Alkoxyl radicals are widely accepted as intermediates in b-
[
10]
scission processes. Thus, upon activation of the substrate by
the iodinating reagent, a base might assist the process by
removing hydrogen. This deprotonation might be crucial to
drive the process when the ring-opening of the corresponding
cycloalkanol is not a particularly favored reaction.
Table 1. Synthesis of w-iodocarbonyl compounds 2 from cycloalkanols 1.
Entry
Substrate 1
IPy
2
BF
4
Cs
[equiv]
2
CO
3
Product 2
Reaction
time [h]
Yield[a]
[%]
[
equiv]
OH
O
H
1
2
3
1.25
1.25
2.5
±
12
12
20
91
I
2
a
1a
OH
O
H
I
±
92
1b
2b
OH
O
H
I
85[b]
10
1c
2c
OH
O
H
I
76[b]
4
2.5
10
20
2d
1d
OH
O
O
5
6
1.25
1.25
5
5
8
8
93
88
I
1e
2e
OH
I
1f
2f
OH
O
H
7
8
1.25
1.25
±
5
I
12
14
92
89
+
-1g
2g
OH
O
H
I
+
-1h
2h
O
OH
I
H
9
H
1.25
5
7
94
H
2i
(
–)-1i
[
a] Yield of 2 based on starting cycloalkanol 1. [b] A 0.02m solution of the alcohol was used.
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O
O
O
I
I
I
H
H
HO
2c (45%)
4 (8%)
I
5 (8%)
c
O
I
OH
H
O
2c (20%)
b
a
I
H
O
2c (85%)
1c
3
(21%)
d
O
O
O
Scheme 3. Proposed reaction mechanism for the conversion of cyclo-
I
I
I
H
H
HO
alkanols 1 to the iodocarbonyl compounds 2 by means of IPy BF .
2
4
2c (62%)
4 (29%)
I
5 (7%)
Scheme 2. Approaches for the conversion of cyclohexanol (1c) to
alcohols to useful w-iodocarbonyl derivatives under environ-
mentally friendly and practicable conditions, using simple
commercial reagents and visible light. Further studies on the
reactivity of IPy BF with alcohols are in progress.
6
-iodohexanal (2c). a) 1. IPy
2
‡
BF
4
(2.5 equiv), Cs
O ; b) PhI(OAc) /I (1.1/ 1 equiv), cyclohexane,
/I (1.1/ 1 equiv), CH Cl , RT, hn
(2.2/2 equiv), CH Cl
, RT, hn (2 Â
2 3 2 2
CO (10 equiv), CH Cl ,
RT, hn (100 W), 20 h; 2. H
3
2
2
RT, hn (2 Â 100 W), 3 h; c) PhI(OAc)
2 Â 100 W), 4 h; d) PhI(OAc) /I
00 W), 4 h.
2
2
2
2
(
1
2
2
2
2
2
4
Experimental Section
The efficiency of IPy BF to promote the conversion of
2
4
All reactions were carried out under a positive pressure of nitrogen.
cycloalkanols to iodocarbonyl compounds was also tested on
larger ring-size cycloalkanols, such as 1d. This process opens a
new entry to long-chain w-bifunctional compounds, such as 2d
Dichloromethane was dried by refluxing over CaH and distilled under a
nitrogen atmosphere.
2
Synthesis of 2 f: Cs CO3 (3.72 g, 10 mmol, 5 equiv) was added to a well
2
stirred solution of IPy
20 mL) at room temperature. Then, 1 f (228 mg, 2.0 mmol, 1.0 equiv) was
added, and the mixture was irradiated (100 W) for 8 h. The mixture was
then cooled in an ice ± water bath and then quenched with 1m H SO
2 4 2 2
BF (930 mg, 2.5 mmol, 1.25 equiv) in dry CH Cl
(Table 1, entry 4). Moreover, entries 5 and 6 in Table 1 show
(
that tertiary cycloalkanols 1e and 1 f can be smoothly ring-
[
2]
opened to furnish iodoketones, proving the generality of the
methodology.
2
4
(50 mL). The mixture was extracted by using CH Cl (4 Â 20 mL), and the
2
2
Another interesting feature was observed in reactions of
racemic 1g or 1h which, upon treatment with IPy BF ,
combined organic layers were washed with sodium thiosulfate (5%
solution in water, 2 Â 30 mL) and water (2 Â 30 mL), and dried over
sodium sulfate. The solvent was removed at reduced pressure. The resultant
oil was further purified by column chromatography (hexane/ethyl acetate
2
4
afforded only one regioisomer of pure aldehydes 2g and 2h,
[
13]
respectively, in excellent yield (Table 1, entries 7 and 8).
The preparation of 2h required cesium carbonate to accom-
plish total conversion of the alcohol. The opening of the
1
0/1) yielding 2 f as a pale-yellow oil (422 mg, 88%). Representative data
�
1 1
for 2 f, IR (neat): nÄ : 1714 cm ; H NMR (300 MHz, CDCl ): d ˆ 3.12 (t, J ˆ
3
6
.9 Hz, 2H), 2.39 (t, J ˆ 7.2 Hz, 2H), 2.07 (s, 3H), 1.76 (q, J ˆ 6.9 Hz, 2H),
13
[
14]
1.5 ± 1.1 (m, 4H); C NMR (75 MHz, CDCl
Â2), 22.3, 6.5; elemental analysis (%) calcd for C
found: C 35.17, H 5.31.
3
): d ˆ 208.3, 43.1, 32.9, 29.7
terpene derivative 1i gives a remarkable example of the
(
7
H
13IO: C 35.02, H 5.45;
efficiency and regioselectivity offered by the IPy BF /Cs CO
2
4
2
3
system to generate aldehydes featuring remote iodine func-
tionality (Table 1, entry 9). Again, the structure of the
substrate exerts full control over which C�C bond is cleaved.
Received: February 12, 2001 [Z16597]
This leads to the interesting cyclopropanecarbaldehyde
framework of 2i, as 1:1 mixture of diastereoisomers with
respect to the newly formed stereocenter.
[1] This is in sharp contrast to the existence of many synthetic alternatives
to conduct the reverse process, namely the reductive ring-closing
reaction of w-iodocarbonyl compounds by metal-based Barbier-type
approaches and radical cyclization reactions.
[
15]
In terms of reaction mechanism, this process could involve
the generation of different reactive species in a sequential
[2] The existing methodology is suitable only for the synthesis of ketones
[
16]
manner, as depicted in Scheme 3. Thus, upon mixing the
from tertiary cycloalkanols. For this purpose, the PhI(OAc) /I system,
2
2
reagents, 1c would give the oxonium ion A and Cs CO might
known as Su a rezꢁs reagent, has been used, mainly for compounds
featuring well defined stereoelectronic requirements; for representa-
tive examples, see: a) P. Wipf, D. A. Mareska, Tetrahedron Lett. 2000,
2
3
3
promote its evolution to the l -iodane B. The key alkoxyl
[
10, 17]
radical C, obtained by photolytic homolysis of B,
could
4
1, 4723 ± 4727; b) R. Hern a ndez, E. I. Le o n, P. Moreno, E. Su a rez, J.
[
18]
undergo a well documented b-scission reaction to afford D.
Finally, radical capture by the l -iodanyl radical would lead to
Org. Chem. 1997, 62, 8974 ± 8975; c) A. Boto, C. Betancor, E. Su a rez,
Tetrahedron Lett. 1994, 35, 5509 ± 5512; d) C. W. Elwood, G. Patten-
3
2
c. This mechanism would account for the formation of a
2
den, Tetrahedron Lett. 1991, 32, 1591 ± 1594; for the use of HgO/I see:
e) S. Bond, P. Perlmutter, Chem. Commun. 2000, 567 ± 568; f) H.
Suginome, S. Yamada, Tetrahedron Lett. 1987, 28, 3963 ± 3966.
mixture of diastereomers from 2i as well as for the observed
regioselectivity.
In summary, a mild and efficient process is reported to
smoothly conduct the conversion of representative cyclic
[
19]
[
2 4
3] IPy BF is a commercial reagent available from either Novabiochem
or Aldrich. For a brief overall review of early applications, see: J.
Barluenga, Pure Appl. Chem. 1999, 71, 431 ± 436.
Angew. Chem. Int. Ed. 2001, 40, No. 18
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[
4] All compounds 2 were characterized by IR, 1H, and 13C NMR
spectroscopy, mass spectrometry, and elemental analysis and/or high-
resolution mass spectrometry data.
5] Overall, it represents a formal and selective remote activation of
aldehydes under mild conditions. For alternative syntheses from a
bifuntional system, see: a) C. F. Sturino, A. G. Fallis, J. Am. Chem.
Soc. 1994, 116, 7447 ± 7448; b) G. D. Cuny, S. L. Buchwald, J. Am.
Chem. Soc. 1993, 115, 2066 ± 2068.
Chromium ± Copper Exchange of Fischer
Carbene Complexes: X-Ray Crystal Structure
1
2
of a [Cu{ˆCR (OR )}(MeCN)(Et O)][PF ]
[
2
6
Complex**
Jos e Barluenga,* Luis A. L o pez, Oliver Löber,
Miguel Tom a s, Santiago García-Granda,
Carmen Alvarez-R u a, and Javier Borge
[
2
6] There are scant reports on this transformation. HgO/I leads to related
chemistry in steroids; however, it is not efficient on simple secondary
cycloalkanols, see: a) H. Suginome, S. Yamada, J. Org. Chem. 1984, 49,
3753 ± 3762; b) H. Suginome, H. Senboku, Tetrahedron 1994, 50,
13101 ± 13112; c) M. Akhtar, D. H. R. Barton, J. Am. Chem. Soc.
1964, 86, 1528 ± 1536; N-iodosuccinimide (NIS) gave poor results in
Over the last two decades Fischer-type carbene complexes
have become valuable tools in stoichiometric transition metal
mediated organic synthesis. The carbene nature of these
[1]
this chemistry: d) T. R. Beebe, A. L. Lin, R. D. Miller, J. Org. Chem.
974, 39, 722 ± 724; for sparse reports on the application of the
PhI(OAc) /I system to promote the opening of cyclopentanol
derivatives see: e) U. P. Spitz, P. E. Eaton, Angew. Chem. 1994, 106,
263 ± 2265; Angew. Chem. Int. Ed. Engl. 1994, 33, 2220 ± 2222; f) J. L.
complexes is demonstrated by their ability to transfer the
carbene ligand not only to alkenes (cyclopropanation),[ but
also to oxygen, nitrogen, and carbon through the correspond-
ing ylides (amine oxides and dimethyl sulfoxide; sulfilimines;
1
2]
2
2
2
Courtneidge, Tetrahedron Lett. 1992, 33, 3053 ± 3056.
[3]
P�C, S�C, and N �C ylides). Although transmetalation is
2
[
[
7] The process is efficient not only in terms of the yield of the iodo
derivative with respect to the starting cycloalkanol but also in terms of
the number of iodine atoms required to incorporate just one in the
final product and the ease of the isolation step.
probably the most important single process in organometallic
chemistry, particularly for transition metal catalyzed reac-
tions,[ the simple transfer of a carbene ligand from a metal ±
4]
8] For skeletal reorganizations based on C�C bond-breaking reactions
[5]
carbene complex to another metallic center is rare. Carbene
see: a) P. M. Wovkulich in Comprehensive Organic Synthesis, Vol. 1
complexes of Rh, Pd, Pt, Cu, and Ag have been formed by
transfer of diaminocarbene ligands (imidazolinylidene or
imidazolidinylidene ligands, which are found to be readily
(Eds.: B. M. Trost, I. Fleming, S. L. Schreiber), Pergamon, Oxford,
1991, pp. 843 ± 899; b) P. Weyerstahl, H. Marschall in Comprehensive
Organic Synthesis, Vol. 6 (Eds.: B. M. Trost, I. Fleming, E. Winter-
feldt), Pergamon, Oxford, 1991, pp. 1041 ± 1070.
transferred between metal centers) from Group 6 metal
[
9] 4-Iodobutanal (2b) is a key compound in the synthesis of 2-pyrrolin-
odoxorubicin (an anthracycline antibiotic): A. Nagy, P. Armatis, A. V.
Schally, Proc. Natl. Acad. Sci. USA 1996, 93, 2464 ± 2469.
10] a) D. P. Curran in Comprehensive Organic Synthesis, Vol. 4 (Eds.:
B. M. Trost, I. Fleming, M. F. Semmelhack), Pergamon, Oxford, 1991,
pp. 812 ± 814 and 817; b) P. Gray, A. Williams, Chem. Rev. 1959, 59,
[5±7]
carbene complexes.
However, the transfer of alkoxycar-
bene ligands has been reported only for [Mo{ˆCPh(OMe)}-
[
8]
(CO)(Cp)(NO)] to [Fe(CO) ] and [W{ˆCPh(OMe)}(CO) ]
[
5
5
[9]
to H[AuCl ]. Very recently Sierra et al. have proposed
4
palladium biscarbene complexes as the active intermediates in
the palladium-catalyzed dimerization of alkoxycarbene ±
chromium complexes.[
239 ± 328.
[
[
11] J. I. Concepci o n, C. G. Francisco, R. Hern a ndez, J. A. Salazar, E.
Su a rez, Tetrahedron Lett. 1984, 25, 1953 ± 1956.
10, 11]
12] This C�H activation product is also formed in absence of cyclo-
In the context of our studies on copper-catalyzed coupling
reactions of Fischer carbene complexes we report here on 1)
the cross-coupling of Fischer chromium ± carbene complexes
with ethyl diazoacetate (EDA), and 2) the isolation and full
characterization of the first alkoxycarbene complex of
hexanol. The extension of this observation to related alkanes is being
currently analyzed. For related intramolecular C�H activation using
this reagent, see reference [6e] and H. Togo, T. Muraki, Y. Hoshina, K.
Yamaguchi, M. Yokoyama, J. Chem. Soc. Perkin Trans. 1 1997, 787 ±
7
93; R. L. Dorta, A. Martín, E. Su a rez, T. Prang e , Tetrahedron:
Asymmetry 1996, 7, 1907 ± 1910; A. F. Barrero, J. E. Oltra, A.
Barrag a n, Tetrahedron Lett. 1995, 36, 311 ± 314; K. Furuta, T. Nagata,
H. Yamamoto, Tetrahedron Lett. 1988, 29, 2215 ± 2218.
copper(i). A recent, excellent report by Hofmann and
[12]
Straub
on the characterization of an alkoxycarbonylcar-
bene ± copper complex has prompted us to release our results.
When chromium ± carbene complexes 1 were treated with
EDA (2.5 equiv) and CuBr (15% mol) in THF at room
temperature the alkenes 2 were isolated with high yields
[
[
13] By GC-MS and NMR analysis of crude reaction mixtures.
14] Prepared from (� )-2-carene according to H. C. Brown, J. V. N. Vara-
Prasad, M. Zaislewicz, J. Org. Chem. 1988, 53, 2911 ± 2916.
15] An epimerization reaction of the hydrogen at the a-position to the
carbonyl group was ruled out by a 2D-NOESY experiment. An
intense cross peak for the cyclopropyl hydrogen atoms is observed,
which confirms the cis relationship between them, as in the starting
material 1i.
16] We thank the referees for suggestions and in particular to one of them
for drawing our attention to the mechanism proposed in Scheme 3.
17] For recent evidence on the participation of these intermediates in
related transformations, see: a) J. Madsen, C. Viuf, M. Bols, Chem.
Eur. J. 2000, 6, 1140 ± 1146; b) J. L. Courtneidge, J. Lusztyk, D. Pag e ,
Tetrahedron Lett. 1994, 35, 1003 ± 1006.
[
(
80 ± 95%) along with ethyl maleate and ethyl fumarate
[*] Prof. Dr. J. Barluenga, Dr. L. A. L o pez, Dr. O. Löber,
Prof. Dr. M. Tom a s
[
Instituto Universitario de Química Organomet a lica ªEnrique Molesº
Unidad Asociada al CSIC, Universidad de Oviedo
Juli a n Clavería 8, 33071-Oviedo (Spain)
Fax : (‡34)98-510-34-50
[
E-mail: barluenga@sauron.quimica.uniovi.es
[
18] For b-scission reactions from alkoxy radical intermediates, see: a) S.
Wilsey, P. Dowd, K. N. Houk, J. Org. Chem. 1999, 64, 8801 ± 8811;
b) A. L. Beckwith, B. P. Hay, J. Am. Chem. Soc. 1989, 111, 2674 ± 2681;
c) A. L. Beckwith, B. P. Hay, J. Am. Chem. Soc. 1989, 111, 230 ± 234,
and references therein.
[‡]
[‡]
[‡]
Dr. S. García-Granda, C. Alvarez-R u a, Dr. J. Borge
Departamento de Química Física y Analítica Universidad de Oviedo
Juli a n Clavería 8, 33071-Oviedo (Spain)
‡
[
] X-ray crystal structure analysis.
[
**] This work was supported by DGICYT (PB97-1271) and CICYT
[
19] For an early related observation see: C. Walling, R. T. Clark, J. Am.
Chem. Soc. 1974, 96, 4530 ± 4534.
(
BQU2000-0219). O.L. thanks the Fonds der Chemischen Industrie for
a postdoctoral fellowship.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
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