Allyl sulfoxides as precursors for radical two-carbon ring expansion of cyclobutanones

Article abstract of DOI:10.1002/1521-3773(20021115)41:22<4323::AID-ANIE4323>3.0.CO;2-9

The two-carbon ring expansion of cycloalkanones is now possible in a two-step procedure. This procedure is based on an unusual cascade reaction that consists of a [2,3]-sigmatropic rearrangement (Mislow-Braverman-Evans rearrangement) of an allylic sulfoxide followed by a radical fragmentation-cyclization process (see scheme; AIBN = azobisisobutyronitrile).

Full text of DOI:10.1002/1521-3773(20021115)41:22<4323::AID-ANIE4323>3.0.CO;2-9

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65, 1933; O. Arjona, R. Fernandez de la Pradilla, J. Plumet, A. Viso, J.
Org. Chem. 1992, 57, 772.
[17] Both NIS and NBS furnished iodide 7b; we assume that NBS reacts
rapidly with Bu3SnI to give Bu3SnBr and NIS.
[18] For a first attempt, see the following communication: R. Chuard, A.
Giraud, P. Renaud, Angew. Chem. 2002, 114, 4499; Angew. Chem. Int.
Ed. 2002, 41, 4323
extension of this chemistry to more complex substrates is
currently under investigation, along with the development of
alternative methods to generate the starting tertiary alkoxyl
radicals.[18]
Experimental Section
6b: 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU; 1.08 mL, 7.24 mmol) was
added to a solution of allylic alcohol 1b (1.00 g, 7.24 mmol) in dry CH2Cl2
(123 mL) at room temperature. NIS (5.32 g, 21.7 mmol) was added in
portions over 3 h at ꢀ408C. The reaction was stirred overnight at room
temperature and then water was added. After extraction with CH2Cl2, the
organic phases were washed with aqueous Na2S2O3 and brine, dried over
MgSO4, and concentrated. Flash column chromatography (Et2O/hexane
1:12) of the crude product afforded 6b (1.4 g, 73%) as a white solid. M.p.:
74 768C; IR (KBr): n˜ ¼ 3009, 2930, 2361, 1633, 1408, 1147, 1049, 964,
927 cmꢀ1; 1H NMR (360 MHz, CDCl3): d ¼ 5.87 (dd, J ¼ 17.7, 10.9 Hz, 1H;
CH ¼ CH2), 5.31 (dd, J ¼ 17.2, 0.9 Hz, 1H; CH ¼ CHH), 5.23 (m, CH ¼
CHH, 2H; 1-H), 5.06 (d, J ¼ 5.0 Hz, 1H; 6-H), 4.90 (dd, J ¼ 3.2, 1.4 Hz, 1H;
3-H), 4.29 (s, 1H; I-CH), 2.26 (d, J ¼ 12.7 Hz, 1H; endo 8-H), 1.93 ppm (dd,
J ¼ 12.9, 4.5 Hz, 1H; exo 8-H); 13C NMR (90.5 MHz, CDCl3): d ¼ 135.1 (d),
116.4 (t), 92.7 (s), 85.9 (d), 83.8 (d), 82.1 (d), 43.4 (d), 28.2 ppm (t). MS (CI):
m/z (%): 265 (26) [Mþ þ 1], 137 (72) [M-I]þ, 109 (100), 95 (95), 83 (50), 55
(51); elemental analysis: calcd for C8H9IO2 (264.06): C 36.39, H 3.44;
found: C 36.44, H 3.39.
Allyl Sulfoxides as Precursors for Radical Two-
Carbon Ring Expansion of Cyclobutanones**
Rachel Chuard, Anne Giraud, and Philippe Renaud*
Ring-expansion reactions are extremely useful processes
that take advantage of existing ring structures for the
construction of larger cyclic systems. Various ion-based
methods have been developed for selective ring-expansion
reactions.[1] More recently, following the tremendous devel-
opment of preparative radical chemistry, ring expansion of
ketones by using alkoxyl radicals (Dowd Beckwith reaction)
7: A solution of Bu3SnH (0.3 mL, 1.14 mmol) and AIBN (6 mg, 0.04 mmol)
in benzene (3 mL) was added over 15 h (syringe pump) to the iodide 6b
(200 mg, 0.76 mmol) in refluxing tBuOH (74 mL). Heating was stopped at
the end of the addition process and CH2Cl2 (30 mL) was added. The
mixture was cooled at ꢀ208C and NBS[17] (137 mg, 0.77 mmol) was added
in portions over 15 min. After 2 h at ꢀ208C, the organic layer was washed
with water, dried over Na2SO4, and concentrated. Flash column chroma-
tography of the residue (EtOAc/hexane 1:9) gave the stable iodoacetal 7
(143 mg, 60%) as a colorless oil. IR (film): n˜ ¼ 2974, 2936, 1722, 1368,
5]
has been reported.[2 This approach proved to be quite
efficient for one-, three-, and four-carbon ring expansions.
However, enlargement by two carbon atoms is not possible.[3]
For this purpose, Galatsis et al. developed a three-step
method based on the rearrangement of 1-vinylcycloalkoxyl
8]
radicals.[6 The low yields and lack of regioselectivity make
1003 cmꢀ1
;
1H NMR (360 MHz, CDCl3): d ¼ 5.51 (d, J ¼ 3.2 Hz, 1H;
this procedure unsatisfactory for preparative purposes.[6]
Therefore, an efficient two-step procedure for the ring
expansion of cycloalkanones would be useful.[9,10] The strategy
that we developed is based on an unusual cascade reaction,
OCHO), 4.57 (td, J ¼ 6.4, 6.4 Hz, 1H; 7a-H), 3.88 (dd, J ¼ 3.9, 4.1 Hz,
1H; ICH), 2.6 2.82 (m, 3H, 2 î 7-H, 3a-H), 2.43 2.54 (m, 1H; 5-H), 1.95
2.26 (m, 3H; 2 î 4-H, 5-H), 1.23 ppm (s, 9H; tBu); 13C NMR (125.8 MHz,
CDCl3): d ¼ 209.6 (s), 106.5 (d), 75.7 (d), 75.6 (s), 47.2 (d), 44.3 (t), 36.8 (t),
31.0 (d), 28.6 (q), 24.5 ppm (t); MS (CI): m/z (%):339 (1) [Mþ], 265 (100)
[MþꢀOtBu], 137 (29); HRMS (CI, isobutane) for C12H19O3I ([Mþ-OtBu]):
calcd 264.97199; found 264.97194.
which consists of a [2,3]-sigmatropic rearrangement (Mis-
13]
low Braverman Evans rearrangement)[11
of an allylic
sulfoxide followed by a radical fragmentation cyclization
process (Scheme 1). The experimental reaction sequence
involves the one-pot preparation of an allylic sulfoxide from
the ketone according to the procedure of Evans et al.,[14]
followed by treatment of the sulfoxide with tributyltin hydride
in refluxing benzene. The challenge of this approach is to
develop a chain process with a radical precursor that is
available from an equilibrium reaction. The efficacy of the
reaction will depend on the ability of the intermediate
sulfenate, present only in small amounts, to sustain a chain
reaction.
Received: July 17, 2002 [Z19749]
[1] R. K. Hill in Comprehensive Organic Synthesis, Vol. 5 (Eds.: B. M.
Trost, I. Fleming, L. A. Paquette), Pergamon Press, Oxford, 1991, p.
785.
[2] L. A. Paquette, Tetrahedron 1997, 53, 13971.
[3] L. A. Paquette, Angew. Chem. 1990, 102, 642; Angew. Chem. Int. Ed.
Engl. 1990, 29, 609.
[4] I. Fleming, N. K. Terrett, Tetrahedron Lett. 1984, 25, 5103.
[5] W. L. Brown, A. G. Fallis, Tetrahedron Lett. 1985, 26, 607.
[6] T. J. Sprules, J. D. Galpin, D. Macdonald, Tetrahedron Lett. 1993, 34,
247.
[7] D. A. Evans, D. J. Baillargeon, J. V. Nelson, J. Am. Chem. Soc. 1978,
100, 2242.
[8] F. Haeffner, K. N. Houk, Y. R. Reddy, L. A. Paquette, J. Am. Chem.
Soc. 1999, 121, 11880.
[*] Prof. P. Renaud, R. Chuard
Department of Chemistry and Biochemistry, University of Bern
Freiestrasse 3, 3000 Berne 9 (Switzerland)
Fax : (þ 41)31-631-4359
[9] E. S. Huyser, L. R. Munson, J. Org. Chem. 1965, 30, 1436.
[10] E. L. Stogryn, E. L. Gianni, Tetrahedron Lett. 1970, 3025.
[11] A. Suzuki, N. Miyaura, M. Itoh, H. C. Brown, G. W. Holland, E.
Negishi, J. Am. Chem. Soc. 1971, 93, 2792.
[12] A. Johns, J. Murphy, Tetrahedron Lett. 1988, 29, 837.
[13] R. C. Gash, F. MacCorquodale, J. Walton, Tetrahedron 1989, 45, 5531.
[14] S. Kim, S. Lee, Tetrahedron Lett. 1991, 32, 6575.
[15] V. Rawal, S. Iwasa, Tetrahedron Lett. 1992, 33, 4687.
[16] For a related reaction with PhSCl, see W. L. Brown, A. G. Fallis,
Tetrahedron Lett. 1985, 26, 607; W. L. Brown, A. G. Fallis, Can. J.
Chem. 1987, 65, 1828; S. M. Tuladhar, A. G. Fallis, Can. J. Chem. 1987,
E-mail: philippe.renaud@ioc.unibe.ch
A. Giraud
Department of Chemistry, University of Fribourg
Pÿrolles, 1700 Fribourg (Switzerland)
[**] This work was supported by the Swiss National Science Foundation
and by the Federal Office for Science and Education (OFES/BBW).
We are also very grateful to the Stiftung zur Fˆrderung der
Wissenschaftlichen Forschung and the Universit‰t Bern for financial
support.
Angew. Chem. Int. Ed. 2002, 41, No. 22
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limitation of the regioselectivity control of the ring-opening
process is demonstrated by the reaction of sulfoxide 1 f
(Table 1, entry 6). In this case, a 1:1 mixture of two secondary
alkyl radicals is generated and their cyclization furnishes 2 f
(36%) and 2 f’ (36%).
The ring expansion of a cyclopentanone derivative was
examined next (Scheme 2). Galatsis et al.[6] and Walton and
co-workers[7] have shown that the ring expansion of cyclo-
pentanones provides mainly 2-methylcyclohexanone through
a 6-exo cyclization. Our result confirms this observation, as
O
S
Ph
[2,3]-sigm.
O
S
O
Bu3Sn
O
Ph
O
O
O
endo-trig
cyclization
Bu3SnH
fragmentation
–Bu3Sn
O
S
Bu3SnH, AIBN
benzene
O
Ph
ref. [14]
H
H
1) CH2=CHLi
2) PhSCl
Scheme 1. General strategy for the two-carbon ring expansion.
O
O
O
O
Ph
O
O
S
H
Allylic sulfoxides are easily prepared from cyclobutanones
by treatment with vinyllithium followed by phenylsulfenyl
chloride.[14] Yields for this transformation lie between 40 and
75%, depending on the freshness of phenylsulfenyl chloride
(see Experimental Section for a typical example). The radical
rearrangement [Eq. (1)] was examined and optimized with
H
5 (41%)
4
H
H
O
O
O
Bu3SnH, AIBN
benzene
+
O
H
O
H
O
6 (50%)
7 (22%)
O
R
O
Scheme 2. Ring expansion of cyclopentanone.
S
Bu3SnH, AIBN
R
(1)
Ph
sulfoxide 5 obtained from the ketone 4 gives the bicyclo[4.3.0]
ketone 6 as the major product (50% yield) together with the
bicyclo[5.3.0] ketone 7 (22% yield). Interestingly, the yield of
this transformation (72%) is much higher than that obtained
by the procedure of Galatsis et al. (29% yield).[16]
1a–f
2a–f
the sulfoxide 1a, which was prepared from 3-phenylcyclobu-
tanone. The best results are obtained by adding 1.5 equiv-
alents of Bu3SnH over 12 hours to a 0.01m solution of the
sulfoxide in refluxing benzene. Under these conditions, the
expected product of the two-carbon
Finally, we have tested our novel method for the generation
of the allyloxyl radical in a different reaction cascade, that is,
ring expansion, 2a, was isolated in
Table 1. Ring expansion of cyclobutanones according to Equation (1).
66% yield (Table 1, entry 1). As a
side product, 2-methyl-4-phenylcy-
clopentanone 3a, which results from
a final 5-exo cyclization, was isolated
in 19% yield.[15] Bicyclic sulfoxides
were also investigated. Sulfoxides 1b
and 1c give the desired products of
ring expansion 2b and 2c in 43% and
67% yield, respectively (Table 1, en-
tries 2 and 3). In these two examples,
the final product results from the
regioselective ring opening of the
cyclobutyloxyl radical followed by a
6-endo cyclization. Sulfoxide 1d gives
2d and 2d’ in 64% and 10% yields,
respectively (Table 1, entry 4). In this
case, the ring opening of the cyclo-
butane is not completely regioselec-
tive, and the major product results
from the fragmentation, which leads
to a secondary alkyl radical followed
by a 6-endo cyclization. The precur-
sor 1e affords the fused cyclohexa-
none 2e in 66% yield (Table 1, en-
try 5). The regioselectivity is ex-
plained by the formation of the more
stable 1-oxysubstituted radical. The
Entry
1
Substrate
Ring-expansion products[a]
1a
2a (66%)
3a (19%)
2
3
4
1b
1c
2b (43%)
2c (67%)
2d (64%)
1d
1e
2d’ (10%)
5
6
2e (66%)
1 f
2 f (36%)
2 f’ (36%)
1:1
[a] Bu3SnH (1.5 equiv) was added over 12 h to a solution of the sulfoxide 1 (0.01m) in refluxing benzene.
4324
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the radical oxy-Cope rearrangement.[17] For this purpose, the
sulfoxide 10 was prepared from norbornenone 8 via the allylic
alcohol 9 (the direct synthesis with the procedure of Evans
et al. does not work in this particular case). By treating the
sulfoxide 10 with Bu3SnH and azobisisobutyronitrile (AIBN)
in refluxing toluene, the desired rearranged compound 11 is
obtained in an unoptimized 46% yield (Scheme 3). This
reaction consists of a sequence of a [2,3]-sigmatropic rear-
rangement followed by generation of an allyloxyl radical,
regioselective fragmentation to an allyl radical, and finally a 6-
endo cyclization.[17]
[3] P. Dowd, S.-C. Choi, Tetrahedron 1989, 45, 77.
[4] A. L. J. Beckwith, D. M. O©Shea, S. W. Westwood, J. Am. Chem. Soc.
1988, 110, 2565.
[5] W. Zhang in Radicals in Organic Synthesis, Vol. 2 (Eds.: P. Renaud,
M. P. Sibi), Wiley-VCH, 2001, pp. 234.
[6] P. Galatsis, S. D. Millan, T. Faber, J. Org. Chem. 1993, 58, 1215.
[7] For a mechanistical study of this reaction, see: M. Afzal, J. C. Walton,
J. Chem. Soc. Perkin Trans. 2 1999, 937.
[8] S. Kim, S. Lee, Tetrahedron Lett. 1991, 32, 6575.
[9] M. Nagel, H.-J. Hansen, G. Frater, Synlett 2002, 275.
[10] M. Nagel, H.-J. Hansen, G. Frater, Synlett 2002, 280.
[11] E. G. Miller, D. R. Rayner, K. Mislow, J. Am. Chem. Soc. 1966, 88,
3139.
[12] S. Braverman, Y. Stabinsky, Chem. Commun. 1967, 270.
[13] D. A. Evans, G. C. Andrews, C. L. Sims, J. Am. Chem. Soc. 1971, 93,
4956.
1) (EtO)2POCH2COOEt
NaH (88%)
[14] D. A. Evans, C. L. Sims, G. C. Andrews, J. Am. Chem. Soc. 1977, 99,
5453.
2) AlH3 (79%)
O
[15] Experiments with tributyltin deuteride have demonstrated that the
cyclohexanone 2a results mainly from a 6-endo cyclization (deutera-
tion at C2) and that a 5-exo-cyclization process followed by a
Beckwith Dowd-type rearrangement (deuteration at C3) only con-
tributes marginally to the formation of 2a.
[16] A deuterium-labeling experiment with Bu3SnD proved that the
cycloheptanone derivative 7 results from a 7-endo cyclization and
not from a 6-exo cyclization followed by ring expansion.
[17] R. Chuard, A. Giraud, P. Renaud, Angew. Chem. 2002, 114, 4497;
Angew. Chem. Int. Ed. 2002, 41, 4321.
OH
8
9
1) BuLi, TsCl
2) PhSLi
3) MCPBA
H
O
Bu3SnH, AIBN
toluene, 110 °C
80%
H
S
Ph
46%
O
10
11
Scheme 3. Radical oxy-Cope rearrangement.[17] MCPBA ¼ meta-chloro-
perbenzoic acid.
In conclusion, we have demonstrated that allylsulfoxides,
which are easily available from ketones, are suitable precur-
sors for allyloxyl radicals. An unique method for the two-
carbon ring expansion of cyclobutanones has been developed
based on a sequential radical-chain reaction. To the best of
our knowledge, this is the first cascade process in which the
radical precursor is continuously generated in an equilibrium
reaction as a minor component of the reaction mixture. The
stability of the sulfoxide radical precursors and the mild
reaction conditions of the ring expansion renders this reaction
attractive for preparative purposes. The control of the
regioselectivity of the process requires a proper design of
the system. Extension of this reaction to other ring sizes and
more complexed systems is currently under investigation.
Low-Temperature Stopped-Flow Studies on the
Reactions of Copper(ii) Complexes and H2O2:
The First Detection of a Mononuclear
Copper(ii) Peroxo Intermediate**
Takao Osako, Shigenori Nagatomo,
Yoshimitsu Tachi, Teizo Kitagawa, and
Shinobu Itoh*
Mononuclear copper-active oxygen complexes are key
reactive intermediates in many biological and catalytic
4]
oxidation processes.[1 Aliphatic hydroxylation by O2 is
accomplished at the mononuclear copper-active sites in
dopamine b-hydroxylase (DbH) and peptidylglycine a-ami-
dating monooxygenase (PAM), and the oxidative modifica-
tions of tyrosine to 2,4,5-trihydroxyphenylalanine quinone
(TPQ) and lysine tyrosylquinone (LTQ) cofactors are per-
Experimental Section
General procedure for the radical ring expansion: A solution of Bu3SnH
(0.49 mL, 1.84 mmol) and AIBN (10 mg, 0.06 mmol) in C6H6 (3 mL) was
added over 12 h with a syringe pump to a refluxing solution of the allylic
sulfoxide (1.23 mmol) in C6H6 (123 mL, 0.01m). (For sulfoxide 1e, better
results were obtained when irradiation with
a 300-W sunlamp was
performed during the reaction.) The solvent was removed under reduced
pressure and the crude product was purified by flash chromatography.
[*] Prof. S. Itoh, T. Osako, Dr. Y. Tachi
Department of Chemistry
2c: From 1c (300 mg, 1.23 mmol), flash-column chromatography (EtOAc/
hexane) afforded 2c (112 mg, 67%) as a colorless oil. IR (film): n˜ ¼ 3050,
Graduate School of Science, Osaka City University
3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan)
Fax : (þ 81)6-6605-2564
1
2930, 2360, 1720, 1450, 1410, 1230 cmꢀ1, H NMR (360 MHz, CDCl3): d ¼
5.72 (m, 1H; CH ¼ CH), 5.54 (m, 1H; CH ¼ CH), 3.15 (m, 1H; 3a-H), 2.66
2.79 (m, 1H; 1-H), 2.49 2.65 (m, 2H; 7a-H, 4-H), 2.1 2.36 (m, 4H; 2 î 6-H,
1-H, 4-H), 1.93 2.03 (m, 1H; 7-H), 1.65 1.76 ppm (m, 1H; 7-H); 13C NMR
(90.5 MHz, CDCl3): d ¼ 213.7 (s), 133.3 (d), 130.2 (d), 43.2 (d), 42.4 (t), 39.6
(t), 37.5 (t), 33.6 (d), 27.1 (t). MS (EI): m/z (%): 136 (53) [Mþ], 79 (100);
HRMS (EI-MS) for C9H12O ([Mþ]): calcd 136.08826; found 136.08836.
E-mail: shinobu@sci.osaka-cu.ac.jp
S. Nagatomo, Prof. T. Kitagawa
Institute for Molecular Science
Myodaiji, Okazaki 444-8585 (Japan)
[**] This work was financially supported in part by Grants-in-Aid for
Scientific Research on Priority Area (No. 11228206) and Grants-in-
Aid for Scientific Research (No. 13480189) from the Ministry of
Education, Culture, Sports, Science, and Technology, Japan.
Received: July 17, 2002 [Z19750]
[1] M. Hesse, Ring Enlargement in Organic Chemistry, 1990.
[2] P. Dowd, W. Zhang, Chem. Rev. 1993, 93, 2091.
Supporting information for this article is available on the WWW under
http://www.angewandte.org or from the author.
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