Generation of 5- and 6-membered ring radicals by deoxygenation of alkoxy radicals

Article abstract of DOI:10.1055/s-1998-1712

A new approach, based on deoxygenation of alkoxyl radicals with triphenylphosphine, for the formation of 5- and 6-membered ring radicals from acyclic radical precursors is described.

Full text of DOI:10.1055/s-1998-1712

May 1998
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525
Generation of 5- and 6-Membered Ring Radicals by Deoxygenation of Alkoxy Radicals
Sunggak Kim* and Dong Hyun Oh
Department of Chemistry, Korea Advanced Institute of Science and Technology, Taejon 305-701, Korea
E-mail:skim@sorak.kaist.ac.kr
Received 27 January 1998
Abstract: A new approach, based on deoxygenation of alkoxyl radicals
with triphenylphosphine, for the formation of 5- and 6-membered ring
radicals from acyclic radical precursors is described.
and the direct reduction product 7 (6%). There was no indication of the
presence of β-fragmentation product 9. Among several phosphorous
compounds tested in deoxygenation of alkoxy radicals, triphenyl-
phosphine gave the best result and triethylphosphite was similarly
effective as shown in Table 1. However, tri-n-butylphosphine was
totally ineffective, although tri-n-butylphosphine would be more
reactive than triphenylphosphine toward alkoxy radicals. Apparently, α-
fragmentation must occur exclusively because the ejection of an alkyl
Synthetic importance of radical cyclizations has been well recognized in
1
recent years. However, the cyclization pathway is mainly limited to 5-
exo ring closure along with somewhat less efficient 6-exo ring closure
2
due to stereoelectronic and geometric reasons. Furthermore, it is well-
7
radical from phosphine would be a facile process. Furthermore, it is
known that the formation of 5-membered ring radicals from acyclic
noteworthy that the addition of an excess amount of phosphine (5 equiv)
did not improve the yield and the remaining reactions were carried out
radical precursors involving 5-endo ring closure is a disfavored
3
process. To solve this problem, we previously reported a reliable
8
with 2 equiv of triphenylphosphine.
4
method using N-aziridinyl imines as radical acceptors. We wish to
report an alternative method which is operationally simple because it
does not require the conversion of the carbonyl groups into the N-
aziridinyl imines. Our approach is based on the previously known
deoxygenation of alkoxy radicals with organophosphorous(III)
5
compounds (eq 1) and involves an intramolecular addition of an alkyl
radical onto the carbonyl group and the subsequent deoxygenation of an
alkoxy radical with the phosphorous compound as shown in Scheme 1.
In this approach, the phosphorous compound should trap the cyclic
alkoxy radical 3 before it would undergo quenching 3 with n-Bu SnH
3
6
and/or well-known β-fragmentation reaction to lead to 9.
Table 2 summarizes some experimental results and illustrates the
efficiency and the scope of the present method. Radical reactions with
10 and 11 under the similar conditions gave somewhat lower yields. In
the case of 12a and 12b, somewhat surprisingly, only the desired
cyclopentane and cyclohexane derivatives were isolated without the
formation of any side products. Vinyl bromide could be utilized as a
radical precursor. When vinyl bromide 13a was subjected to the
standard radical condition, a mixture of cyclopentene derivatives was
obtained in 68% yield in a ratio of 10:1 along with an alcohol (7%). A
similar result was also obtained with 13b. However, we found that the
use of a ketone as a radical acceptor was unsuccessful in the present
approach. Thus, treatment of iodoketone 14 with n-Bu SnH (1.2 equiv)
3
and triphenylphosphine (2 equiv) in benzene (0.05M) at 350 nm for 1.5
h afforded the direct reduction product (70%) as a major product along
with a small amount of the desired methylcyclopentane (17%).
Tandem radical cyclizations were briefly studied under the similar
conditions. When 15 was subjected to the standard condition, 16 was
isolated in 72% yield after two consecutive radical cyclizations and the
subsequent deoxygenation (eq 2). Similar results were also obtained
with 17 and 18, demonstrating the efficiency of deoxygenation reaction
by triphenylphosphine (eq 3 and 4). We also examined the feasibility of
the cyclization-deoxygenation-intermolecular addition approach which
would demonstrate the formation of two carbon-carbon bonds in
Scheme 1
We first examined an alkyl radical addition onto the aldehyde and the
subsequent deoxygenation of an alkoxy radical with triphenyl -
phosphine to generate a 5-membered ring radical. Since triphenyl-
phosphine reacts with alkyl iodides at an elevated temperature to form
alkyltriphenylphosphonium salts, the reaction was carried out at room
9
temperature under photochemically initiated conditions. When
a
succession at the same carbon. When iodoaldehyde 19 was treated with
solution of iodoaldehyde 1 with n-Bu SnH and triphenylphosphine in
acrylonitrile (5 equiv) and Bu SnH in the presence of
3
3
degassed benzene (0.05M) was irradiated at 350 nm for 1 h,
triphenylphosphine (2 equiv) in benzene at 350 nm, the desired product
cyclopentane 6 was isolated in 75% yield along with alcohol 8 (17%)
20 was obtained in 55% yield along with cyclization and deoxygenation

526
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SYNLETT
product 21 (33%) (eq 5). The present reaction demonstrates two
consecutive carbon-carbon bond formations although the efficiency of
this approach is not very high.
Acknowledgement: We thank the Organic Chemistry Research Center
for financial support of this work.
References and Notes
(1) For recent reviews see : (a) Curran, D. P. Synthesis 1988, 417,
489. (b) Thebtaranonth, C.; Thebtaranonth, Y. Tetrahedron 1990,
46, 1385. (c) Curran, D. P. In Comprehensive Organic Synthesis;
Trost, B. M.; Flemming, I., Eds; Pergamon: Oxford, 1991; Vol. 4,
p 715-831. (d) Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem.
Rev. 1991, 91, 1237.
(2) (a) Beckwith, A. L. J.; Moad G. J. Chem. Soc., Chem. Commun.
1974, 472 (b) Mayo, F. R. J. Chem. Educ. 1986, 63, 97. (c)
Walling, C. J. Chem. Educ. 1986, 63, 99.
(3) (a) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734. (b)
Beckwith, A. L. J.; Schiesser, C. H. Tetrahedron Lett. 1985, 26,
373. (c) Beckwith, A. L. J.; Schiesser, C. H. Tetrahedron 1985,
41, 3925. (d) Spellmeyer, D. C.; Houk, K. N. J. Org. Chem. 1987,
52, 959.
(4) (a) Kim, S.; Kee, I. S.; Lee, S. J. Am. Chem. Soc. 1991, 113, 9882.
(b) Kim, S.; Kee, I. S. Tetrahedron Lett. 1993, 34, 4213. (c) Kim,
S.; Cheong, J. H.; Yoon, K. S. Tetrahedron Lett. 1995, 36, 6069.
(5) Walling, C. J. Am. Chem. Soc. 1960, 82, 2181.
(6) (a) Tsang, R.; Fraser-Reid, B. J. Am. Chem. Soc. 1986, 108, 8102.
(b) Beckwith, A. L. J.; Hay, B. P. J. Am. Chem. Soc. 1989, 111,
230.
(7) (a) Buckler, S. A. J. Am. Chem. Soc. 1962, 84, 3093. (b) Dockery,
K. P.; Bentrude, W. G. J. Am. Chem. Soc. 1994, 116, 10332.
(8) A benzene solution (4.8 ml, 0.05 M) of iodide 1 (117 mg, 0.24
mmol), 1.2 equiv of n-Bu SnH (71 mg, 0.25 mmol), and
3

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527
triphenylphosphine (188 mg, 0.48 mmol) was degassed for 20
(200MHz, CDCl ) δ 0.77(t, J=7.3 Hz, 3H), 2.10(m, 5H), 3.11(s,
2H), 5.10(s, 4H), 7.28-39(m, 10H), 9.64(s, 1H). 8: H NMR
3
1
min, and irradiated at 350 nm for 1 h. Then, the reaction mixture
was washed with aqueous KF solution (5 ml) and the aqueous
layer was extracted with diethyl ether. The resulting solution was
(200MHz, CDCl ) δ 1.77-2.02(m, 4H), 2.27-2.47(m, 4H),
3
4.37(broad s, 1H), 5.08 (s, 2H), 5.11 (s, 2H), 7.28-40(m, 10H)
dried over anhydrous MgSO , filtered and concentrated in vacuo.
(9) (a) Nagai, M.; Lazor, J. and Wilkox, C. S. J. Org. Chem. 1990, 55,
3440. (b) Curran, D. P. and Liu, H. J. Am. Chem. Soc. 1991, 113,
2127. (c) Ryu, I.; Yamazaki, H.; Kusano, K.; Ogawa, A. and
Sonoda, N. J. Am. Chem. Soc. 1991, 113, 8558. (d) Lee, H. Y.;
Kim, D.-I.; Kim, S. J. Chem. Soc., Chem. Commun. 1996, 1539.
(e) Kim, S.; Cheong, J. H. Synlett 1997, 947. (f) Curran, D. P.;
Diederichsen, U.; Palovich, M. J. Am. Chem. Soc. 1997, 119,
4797.
4
The crude product was subjected to silica gel column
chromatography (EtOAc/hexane = 1/30) to afford 6 (61 mg, 75%)
1
along with 7 (5 mg, 6%) and 8 (15 mg, 17%). 6: H NMR
(200MHz, CDCl ) δ 1.63-1.70 (m, 4H), 2.17-2.24 (m, 4H), 5.09
3
13
(s, 4H), 7.26-35 (m, 10H); C NMR (50.32MHz, CDCl ) δ 25.41,
3
34.55, 60.44, 66.92, 127.88, 128.12, 128.45, 135.64, 172.29; IR:
-1
1
3033, 2958, 2874, 1731, 1455, 1263, 1155 cm . 7: H NMR