Novel radical reaction of phenylsulfonyl oxime ethers. A free radical acylation approach

Article abstract of DOI:10.1021/ja9600993

Although acylation represents one of the most useful and thoroughly studied reactions in organic chemistry, a successful free radical mediated acylation is not presently available. free radical carbonylation has recently been reported. This reaction allow

Full text of DOI:10.1021/ja9600993

5138
J. Am. Chem. Soc. 1996, 118, 5138-5139
Scheme 1
Novel Radical Reaction of Phenylsulfonyl Oxime
Ethers. A Free Radical Acylation Approach
Sunggak Kim,* Ill Young Lee, Joo-Yong Yoon, and
Dong Hyun Oh
Department of Chemistry
Korea AdVanced Institute of Science and Technology
Taejon 305-701, Korea
ReceiVed January 12, 1996
Although acylation represents one of the most useful and
thoroughly studied reactions in organic chemistry,1 a successful
free radical-mediated acylation is not presently available. Only
a few examples, involving highly activated carbonyls such as
biacetyl2 and acyl aldoximes,3 have appeared to date.4 It is also
noteworthy that free radical carbonylation has recently been
reported.5 This reaction allows the introdution of carbonyl
groups to organic halides.
strengths of CdO bonds.10 Thus, a fundamentally new acylation
approach was sought, and we now report a conceptually simple
solution to this problem, wherein an oxime ether 4 can be used
as a carbonyl equivalent radical acceptor in addition reactions
of alkyl radicals. This concept is based on the fact that alkyl
radicals undergo facile additions to CdN bonds such as oxime
ethers11,12 and hydrazones.13 As shown in Scheme 1, our
approach involves additions of alkyl radicals to CdN bonds
and subsequent â-exclusion of phenyl thio radicals which react
with bis(trialkyl)tin to propagate a chain. However, initial
attempts to employ this strategy were disappointing, since the
use of 4a under the similar conditions afforded 5a in 20%
yield,14 whereas the use of 4b afforded only a small amount of
5b (<5%).
In order to examine the feasibility of radical-mediated
acylation reactions, we began our study with thiol esters as
radical acceptors (eq 1).6,7 When 4-phenoxybutyl iodide 1 was
We next examined phenylsulfonyl oxime ethers since the
phenylsulfonyl group would be expected to lower the energy
of the LUMO of a radical acceptor, thereby increasing the rate
of addition of alkyl radicals to 4c and 4d by reducing the
SOMO-LUMO difference.15 As predicted, the phenylsulfonyl
oxime ethers 4c and 4d appeared to be highly effective and
synthetically useful reagents for radical-mediated acylations
under mild conditions. Reagents 4c and 4d were prepared by
MCPBA oxidation of 4a and 4b, respectively, and obtained as
stable crystalline solids.16 When 1 was treated with Bu3SnSnBu3
(1.2 equiv), 4c (2.0 equiv), and acetone (5 equiv) as a sensitizer
in benzene (0.3 M in iodide) at 300 nm for 4 h, O-benzyl
aldoxime 5a was obtained in 94% yield. This product was
hydrolyzed to aldehyde 3a in 90% yield using a 30% HCHO
solution in THF (1:3) in the presence of a catalytic amount of
irradiated in the presence of S-phenyl thioformate 2a and bis-
(tributyltin) (1.2 equiv) in benzene (0.2M in iodide) using
Neumann’s method,8 aldehyde 3a was obtained in 15% yield.9
The use of S-phenyl thioacetate 2b did not give 3b, but the
selenol ester 2c gave 3b in 18% yield. We conceived that the
unsuccessful outcome might be due to the reversibility of the
additions of alkyl radicals to CdO bonds and the higher π bond
(1) (a) O’Neill, B. T. In ComprehensiVe Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 1, Chapter
1.13. (b) Davis, B. R.; Garratt, P. J. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 2,
Chapter 3.6.
(2) (a) Bentrude, W. G.; Darnall, K. R. J. Am. Chem. Soc. 1968, 90,
3588. (b) Oyama, M. J. Org. Chem. 1965, 30, 2429. (c) Minisci, F.; Galli,
R.; Cecere, M.; Malatesta, V.; Caronna, T. Tetrahedron Lett. 1968, 5609.
(3) Citterio, A.; Filippini, L. Synthesis 1986, 473. Homolytic C-alkylation
of unactivated aldoximes such as acetaldoxime and phenylaldoxime gave
ketoximes in very low yield (<20%).
(4) Indirect approaches for formylation include additions of alkyl radicals
to isonitriles and sulfonyl cyanides. (a) Stork, G.; Sher, P. M. J. Am. Chem.
Soc. 1983, 105, 6765. (b) Barton, D. H. R.; Ozbalik, N.; Vacher, B.
Tetrahedron 1988, 44, 3501. (c) Fang, J.-M.; Chen, M.-Y. Tetrahedron
Lett. 1987, 28, 2853. (d) Barton, D. H. R.; Jaszberenyi, J. C.; Theodorakis,
E. A. Tetrahedron Lett. 1991, 32, 3321. (e) Leopez, J. C.; Gomez, A. M.;
Fraser-Reid, B. J. Org. Chem. 1995, 60, 3871.
(5) (a) Ryu, I.; Kusano, K.; Ogawa, A.; Kambe, N.; Sonoda, N. J. Am.
Chem. Soc. 1990, 112, 1295. (b) Ryu, I.; Kusano, K.; Masumi, N.;
Yamazaki, H.; Ogawa, A.; Sonoda, N. Tetrahedron Lett. 1990, 31, 6887.
(c) Ryu, I.; Kusano, K.; Yamazaki, H.; Sonoda, N. J. Org. Chem. 1991,
56, 5003. (d) Ryu, I.; Yamazaki, H.; Kusano, K.; Ogawa, A.; Sonoda, N.
J. Am. Chem. Soc. 1991, 113, 8558. (e) Ryu, I.; Yamazaki, H.; Ogawa, A.;
Kambe, N.; Sonoda, N. J. Am. Chem. Soc. 1993, 115, 1187.
(6) (a) Scott, A. I.; Kang, K. J. Am. Chem. Soc. 1977, 99, 1997. (b)
Wollowitz, S.; Halpern, J. J. Am. Chem. Soc. 1984, 106, 8319. (c) Wollowitz,
S.; Halpern, J. J. Am. Chem. Soc. 1988, 110, 3112. (d) Dowd, P.; Wilk, B.;
Wilk, B. K. J. Am. Chem. Soc. 1992, 114, 7949.
(7) For selected examples on the use of thiol esters and selenol esters as
precursors of acyl radicals, see: (a) Pfenninger, J.; Heuberger, C.; Graf,
W. HelV. Chim. Acta 1980, 63, 2328. (b) Boger, D. L.; Mathvink, R. J. J.
Org. Chem. 1988, 53, 3377. (c) Boger, D. L.; Mathvink, R. L. J. Am. Chem.
Soc. 1990, 112, 4003. (d) Boger, D. L.; Mathvink, R. L. J. Am. Chem. Soc.
1990, 112, 4008. (e) Curran, D. P.; Liu, H. J. Org. Chem. 1991, 56, 3463.
(f) Batty, D.; Crich, D. Tetrahedron Lett. 1992, 33, 875. (g) Evans, P. A.;
Roseman, J. D. Tetrahedron Lett. 1995, 36, 31. (h) Chatgilialoglu, C.;
Lucarini, M. Tetrahedron Lett. 1995, 36, 1299.
(8) Harendza, M.; Junggebauer, J.; Lebmann, K.; Neuman, W. P.; Tews,
H. Synlett 1993, 286.
(9) In addition to 3a, S-phenyl 4-phenoxypentanethioate (6%) was
isolated along with recovery of 2a (40%).
(10) (a) Beckwith, A. L. J.; Hay, B. P. J. Am. Chem. Soc. 1989, 111,
230. (b) Beckwith, A. L. J.; Hay, B. P. J. Am. Chem. Soc. 1989, 111, 2674.
(c) Walton, R.; Fraser- Reid, B. J. Am. Chem. Soc. 1991, 113, 5791. (d)
Beckwith, A. L. J.; Raner, K. D. J. Org. Chem. 1992, 57, 4954.
(11) (a) Corey, E. J.; Pyne, S. G. Tetrahedron Lett. 1983, 24, 2821. (b)
Hart, D. J.; Seely, F. L. J. Am. Chem. Soc. 1988, 110, 1631. (c) Bartlett, P.
A.; Mclaren, K. L.; Ting, P. C. J. Am. Chem. Soc. 1988, 110, 1633. (d)
Parker, K. A.; Spero, D. M.; Epp, J. V. J. Org. Chem. 1988, 53, 4628. (e)
Enholm, E. J.; Burroff, J. A.; Jaramillo, L. M. Tetrahedron Lett. 1990, 31,
3727. (f) Booth, S. E.; Jenkins, P. R.; Swain, C. J. J. Chem. Soc., Chem.
Commun. 1991, 1248. (g) Barton, D. H. R.; Dalko, P. I.; Gero, S. D.
Tetrahedron Lett. 1991, 32, 4713. (h) Hatem, J.; Henriet-Bernard, C.;
Grimaldi, J.; Maurin, R. Tetrahedron Lett. 1992, 33, 1057. (i) Contelles, J.
M.; Ruiz, P.; Sanchez, B.; Jimeno, M. L. Tetrahedron Lett. 1992, 33, 5261.
(j) Hart, D. J.; Krishnamurthy, R.; Pook, L. M.; Seely, F. L. Tetrahedron
Lett. 1993, 34, 7819. (k) Naito, T.; Tajiri, K.; Harimoto, T.; Ninomiya, I.;
Kiguchi, T. Tetrahedron Lett. 1994, 35, 2205. (l) Kiguchi, T.; Tajiri, K.;
Ninomiya, I.; Naito, T.; Hiramatsu, H. Tetrahedron Lett. 1995, 36, 253.
(12) According to our kinetic and competition studies on the rate constant
for 5- exo and 6-exo cyclization of primary alkyl radicals to the O-benzyl
oxime ethers, CdN bonds in oxime ethers seem to be much better radical
acceptors than CdC and CdO bonds. Kim, Y. J. Unpublished results.
(13) (a) Kim, S.; Kee, I. S.; Lee, S. J. Am. Chem. Soc. 1991, 113, 9882.
(b) Kim, S.; Kee, I. S. Tetahedron Lett. 1993, 34, 4213. (c) Kim, S.; Cheong,
J. H.; Yoon, K. S. Tetrahedron Lett. 1995, 36, 6069. (d) Sturino, C. F.;
Fallis, A. G. J. Am. Chem. Soc. 1994, 116, 7447. (e) Sturino, C. F.; Fallis,
A. G. J. Org. Chem. 1994, 59, 6514.
(14) The use of the hydrazone (HC(SPh)dNNMe2) gave PhO(CH2)4-
CHdNNMe2 in 26% yield.
(15) (a) Giese, B. Radicals in Organic Synthesis: Formation of Carbon-
Carbon Bonds; Pergamon Press: New York, 1986; Chapter 2. (b) Fleming,
I. Frontier Orbitals and Organic Chemical Reactions; John Wiley &
Sons: London, 1976; Chapter 4 and 5.
S0002-7863(96)00099-6 CCC: $12.00 © 1996 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 118, No. 21, 1996 5139
Table 1. Preparation of Oxime Ethers from Alkyl Halides with 4c
and 4d21
yields were lower. In the reaction with benzylic bromide, the
desired oxime ether was obtained in low yield (40%) along with
the dimeric product (40%) because of the relatively low
reactivity of the stable benzylic radical. Acetal, ester, alcohol,
and carbamate moieties are all tolerated, as would be expected
from the nature of the radical reaction. The reaction was
successfully applied to a carbohydrate in which acylations were
achieved at the anomeric center, thus providing facile routes to
highly functionalized C-glycosyl derivatives.
Encouraged by the success of this acylation approach, we
have studied the feasibility of the cyclization-acylation se-
quence, which cannot be achieved using conventional synthetic
methods (eq 2). When a mixture of 27, Me3SnSnMe3 (1.2
equiv), 4c (2.0 equiv), and acetone (5 equiv) in benzene (0.3
M in the iodide) was irradiated at 300 nm for 4 h, 28a was
isolated in 88% yield.19
We have also studied three-component coupling reactions
involving an intermolecular addition, cyclization, and acylation
sequence (eq 3).20 Treatment of 29 with Me3SnSnMe3 (1.2
a All yield are uncorrected for recovery of starting material. b 14 was
used. c 16 (20%) was recovered. d The direct reduction product (20%)
was also isolated. e 4,4′-tert-butyldibenzyl (40%) was isolated.
HCl.17 In addition a small amount of O-benzyl n-pentanal-
doxime (12-20%) was isolated as a result of the homolytic
bond cleavage of the Sn-n-C4H9 bond under the photochemical
conditions used. The use of hexamethylditin obviates the
problem of the formation of aldoxime byproduct, and the
remaining reactions were carried out with this reagent (1.2
equiv).18 Thermal initiation with AIBN was also investigated
with 1 and 4c. However, the reaction was incomplete even after
12 h, and the yield was considerably lower (40%).
Table 1 summarizes the experimental results and illustrates
the efficiency and scope of the present method. For most of
the cases observed, the reaction was complete within 4 h with
alkyl iodides and afforded the O-benzyl oxime ethers in high
yield. However, sterically hindered tert-butyl iodide did not
work well with 4d. The reaction was successful with alkyl
bromides, although longer reaction times were required and
equiv), 4c (2.0 equiv), and acetone (5.0 equiv) in benzene (0.3
M in 29) and irradiation at 300 nm for 6 h, followed by
hydrolysis of the O-benzyl oxime ether group, afforded 30a in
82% yield, demonstrating the synthetic usefulness of the present
method. A similar result was also obtained with 4d, although
a lower yield was obtained.
In conclusion, we have discovered the first successful radical
acylation approach which we believe has great synthetic
potential because it succeeds in complex molecules, where more
conventional synthetic methods would be inappropriate. Further
studies on the synthetic utility of this method with several other
functionalized phenylsulfonyl oxime ethers are in progress, and
the results will be reported in the future.
Acknowledgment. We wish to thank the Ministry of Science and
Technology and OCRC(KOSEF) for financial support and Sang Yong
Jon for performing preliminary experiments. One of the authors (I.Y.L.)
is grateful to KRICT for financial support.
(16) The preparation of 4c (mp 51-52 oC) and 4d (mp 45-46 oC) is as
follows.
Supporting Information Available: Experimental procedures for
the preparation of 4c, 4d, and 5a as well as spectral data (1H NMR,
13C NMR, IR, and HRMS) for the reaction products (9 pages). Ordering
information is given on any current masthead page.
JA9600993
(19) The ratio of cis-/trans-isomer was determined by analysis of the
1H NMR spectrum of the corresponding ketones after deprotection of
O-benzyl oxime ether group.
(17) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis; John Wiley & Sons, Inc.: New York, 1991; p 214.
(18) The use of bis(tributyltin) gave similar yields in most cases.
However, separation of the product from O-benzyl pentanaldoxime was
difficult in several cases.
(20) Curran, D. P.; Chen, M.-H.; Spletzer, E.; Seong, C. M.; Chang,
C.-T. J. Am. Chem. Soc. 1989, 111, 8872.
(21) The reaction was carried out with Me3SnSnMe3 (1.2 equiv), 4c or
4d (2.0 equiv), and acetone (5.0 equiv) in benzene (0.3 M in substrate) at
300 nm for 4 h (alkyl iodides) and for 12 h (alkyl bromides).