12190
J. Am. Chem. Soc. 1999, 121, 12190-12191
Recently, the Kim group has reported that sulfonyl oxime
ethers, such as B and C, can serve as viable C1 radical acceptor
synthons, which serve as latent carbonyl groups, providing novel
free radical methods for acylation.8 The emergence of these
powerful C1 newcomers in radical chemistry led us to attempt a
series of unprecedented type of radical cascade reactions leading
to vicinal di- and tricarbonyl compounds based on multiple radical
C1 synthons: CO and sulfonyl oxime ethers. Herein we report
that this new strategy is indeed promising and permits the
synthesis of several types of vicinal singly and doubly acylated
oxime ethers, which would be precursors of vicinal di- and
tricarbonyl compounds.
New Radical Cascade Reactions Incorporating
Multiple One-Carbon Radical Synthons: A Versatile
Synthetic Methodology for Vicinal Singly and Doubly
Acylated Oxime Ethers
Ilhyong Ryu,*,† Hiroki Kuriyama,† Satoshi Minakata,†
Mitsuo Komatsu,† Joo-Yong Yoon,‡ and Sunggak Kim*,‡
Department of Applied Chemistry
Graduate School of Engineering, Osaka UniVersity
Suita, Osaka 565-0871, Japan
Center for Molecular Design and Synthesis
Department of Chemistry
In the event, the three-component coupling reaction comprised
of RX, CO, and phenylsulfonyl oxime ether B8a was successfully
achieved, providing the desired R-acyl-substituted aldoximes (eq
1). For example, when n-octyl iodide (1a) was treated with
phenylsulfonyl oxime ether B in the presence of allyltributyltin,
AIBN (catalytic) in a pressurized CO (autoclave) in benzene at
90 °C for 5 h, the anticipated product, O-benzyl nonanoyl
aldoxime 2a, was obtained in 80% isolated yield (Table 1, entry
1).9 Cyclohexyl iodide 1b and adamantyl iodide 1c were converted
to the corresponding 2-oxo aldoximes 2b and 2c, in 77 and 52%
yields, respectively (entries 2 and 3). In entry 4, 5-exo cyclization
preceded the consecutive addition to CO and B. As indicated in
eq 1, these radical reactions were generally conducted by initially
pressurizing the reaction vessel (autoclave) with carbon monoxide
to 65-80 atm, followed by heating to 90 °C for 5 h. The substrate
concentration was 0.025-0.05 M and AIBN was used as radical
initiator (20-40 mol%). Unlike simple oxime ethers which exist
as a mixture of syn and anti isomers, R-acylated aldoxime ethers
2 were obtained as a single stereoisomer of anti-geometry.10
Korea AdVanced Institute of Science and Technology
Taejon 305-701, Korea
ReceiVed June 22, 1999
Due largely to the extensive efforts of Wasserman and co-
workers, vicinal tricarbonyl compounds have found wide ap-
plicability as versatile synthetic intermediates for the synthesis
of numerous biologically active natural and unnatural compounds.1
Among many possible approaches for the synthesis of vicinal di-
and tricarbonyl compounds,2 the sequential coupling of multiple
molecules of carbon monoxide, while a direct and straightforward
method, has been difficult to achieve. Only restricted examples
of the synthesis of aromatic R-keto amides and R-keto esters have
been reported thus far in transition-metal catalyzed carbonylation
chemistry.3 Radical one-carbon (C1) approaches to di- and
tricarbonyl compounds also seem unlikely to provide a viable
alternative, since no evidence for double CO trapping was
observed during the radical copolymerization of ethylene and CO
even at extremely high CO pressures (>1000 atm, ethylene/CO
) 3/7).4,5 This observation suggests that the addition of an acyl
radical to CO occurs only with great difficulty.6 To our knowl-
edge, similar free radical transformations using isonitriles A,
another representative radical C1 synthon,4 are also unknown.
Thus, the synthesis of vicinal di- and tricarbonyl compounds based
on the coupling of multiple radical C1 synthons remains a
challenge among possible intermolecular radical cascade reaction
strategies.7
(1)
In this thermally induced radical chain reaction, allyltributyltin
serves as the radical chain carrier which traps benzenesulfonyl
radical and generates tributyltin radical. Fortunately, the competing
addition of acyl radicals to allyltin, leading to â,γ-unsaturated
ketones,11 was negligible, suggesting that the addition of acyl
radicals to sulfonyl oxime ether B is much more rapid than the
addition to allyltin.
n
n
n
Cascade reactions with carbon monoxide and bis-sulfonyl
oxime ether C8c are found to be useful for the synthesis of 2-oxo
and 2,2′-di-oxo ketoximes. Treatment of octyl iodide (1a) with
one mole equivalent of C under CO pressure gave a nonanoyl-
substituted sulfonyl oxime ether. Subsequent treatment of the
† Osaka University.
‡ KAIST.
(1) For selected references, see: (a) Wasserman, H. H.; Chen, J.-H.; Xia,
M. J. Am. Chem. Soc. 1999, 121, 1401. (b) Wasserman, H. H.; Shiraishi, M.;
Coats, S. J.; Cook, J. D. Tetrahedron Lett. 1995, 36, 6785. (c) Wasserman,
H. H.; Lee, G. M. Tetrahedron Lett. 1994, 35, 9783. (d) Wasserman, H. H.;
Blum, C. A. Tetrahedron Lett. 1994, 35, 9787. (e) Wasserman, H. H.; Vu, C.
B. Tetrahedron Lett. 1994, 35, 9779. (f) Wasserman, H. H.; Rotello, V. M.;
Krause, G. B. Tetrahedron Lett. 1992, 33, 5419. (g) Wasserman, H. H.; Duzer,
J. H.; Vu, C. B. Tetrahedron Lett. 1990, 31, 1609.
(7) For the retrosynthetic analysis of radical cascade reactions, see: Curran,
D. P. Synlett 1991, 63.
(8) (a) Kim, S.; Lee, I. Y.; Yoon, J.-Y.; Oh, D. H. J. Am. Chem. Soc. 1996,
118, 5138. (b) Kim, S.; Yoon, J.-Y.; Lee, I. Y. Synlett 1997, 475. (c) Kim, S.;
Yoon, J.-Y. J. Am. Chem. Soc. 1997, 119, 5982. (d) Kim, S.; Lee, I. Y.
Tetrahedron Lett. 1998, 39, 1587.
(2) For a review on vicinal polycarbonyl compounds, see: Rubin, M. B.
Chem. ReV. 1975, 75, 177.
(9) Typical procedure: A magnetic stir bar, AIBN (17 mg, 0.1 mmol), a
sulfonyl oxime ether B (207 mg, 0.7 mmol), allyltributyltin (199 mg, 0.6
mmol), an alkyl iodide 1a (123 mg, 0.5 mmol), and benzene (20 mL) were
placed in a 50-mL stainless steel autoclave lined with a glass liner. The
autoclave was purged with carbon monoxide, pressurized with 80 atm of CO,
and heated with stirring at 90 °C for 5 h. Excess CO was discharged at room
temperature. The crude mixture was washed with ether. After evaporation of
the solvent, the residue was subjected to silica gel flash column chromatog-
raphy (hexane/AcOEt ) 19/1) to give the R-keto oxime ether 2a which
contained a small amount of uncarbonylated product. Further purification by
recycling by HPLC with a GPC column gave 112 mg of pure 2a (80% yield).
(10) Recently Naito and co-workers reported that glycoxylic oxime ethers,
analogous to 2, act as alkyl radical acceptors, see: Miyabe, H.; Fujishima,
Y.; Naito, T. J. Org. Chem. 1999, 64, 2174 and references therein.
(11) Ryu, I.; Yamazaki, H.; Kusano, K.; Ogawa, A.; Sonoda, N. J. Am.
Chem. Soc. 1991, 113, 8558.
(3) For leading references of metal-catalyzed double vicinal carbonylations,
see: (a) Ozawa, F.; Kawasaki, N.; Okamoto, H.; Yamamoto, T.; Yamamoto,
A. Organometallics 1987, 6. 1640. (b) Urata, H.; Ishii, Y.; Fuchikami, T.
Tetrahedron Lett. 1989, 30, 4407. (c) Yamamoto, A. Bull. Chem. Soc. Jpn.
1995, 68. 433. (d) Kayaki, Y.; Yamamoto, A. J. Synth. Org. Chem., Jpn.
1998, 56, 96.
(4) For a review on C1 radical synthons, see: Ryu, I.; Sonoda, N.; Curran,
D. P. Chem. ReV. 1996, 96, 177.
(5) (a) Coffman, D. D.; Pinkney, P. S.; Wall, F. T.; Wood, W. H.; Young,
H. S. J. Am. Chem. Soc. 1952, 74, 3391. (b) Brubaker, M. M.; Coffman, D.
D.; Hoehn, H. H. J. Am. Chem. Soc. 1952, 74, 1509. Also see a review on
radical carbonylations: (c) Ryu, I.; Sonoda, N. Angew. Chem., Int. Ed. Engl.
1996, 35, 1050.
(6) To our knowledge, no kinetic information about carbonylation of acyl
radicals and the reverse process has been reported.
10.1021/ja992125d CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/15/1999