Tin-free radical acylation reactions with methanesulfonyl oxime ether

Article abstract of DOI:10.1002/1521-3773(20010702)40:13<2524::AID-ANIE2524>3.0.CO;2-4

A simple strategy involving thermal decomposition of the methanesulfonyl radical into the methyl radical and the subsequent transfer of an iodine atom or phenyl telluride group was used to develop a tin-free radical acylation reaction (see scheme; V-40 = 1,1′-azobis(cyclohexane-1-carbonitrile). The key was finding reaction conditions under which the I or PhTe transfer is faster than the direct addition of the alkyl radical to the methanesulfonyl ether.

Full text of DOI:10.1002/1521-3773(20010702)40:13<2524::AID-ANIE2524>3.0.CO;2-4

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[13] The calculations were carried out with the Gaussian 98 suite of
programs: Gaussian98 (RevisionA.7), M. J. Frisch, G. W. Trucks,
H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, V. G.
Zakrzewski, J. A. Montgomery, R. E. Stratmann, J. C. Burant, S.
Dapprich, J. M. Millam, A. D. Daniels, K. N. Kudin, M. C. Strain, O.
Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci, C.
Pomelli, C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson, P. Y.
Ayala, Q. Cui, K. Morokuma, D. K. Malick, A. D. Rabuck, K.
Raghavachari, J. B. Foresman, J. Cioslowski, J. V. Ortiz, B. B. Stefanov,
G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R. L.
Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A.
Nanayakkara, C. Gonzalez, M. Challacombe, P. M. W. Gill, B. G.
Johnson, W. Chen, M. W. Wong, J. L. Andres, M. Head-Gordon, E. S.
Replogle, J. A. Pople, Gaussian, Inc., Pittsburgh, PA, 1998. Pd was
represented with the Hay-Wadt relativistic core potential (ECP) for
the 28 innermost electrons and its associated double-z basis set.[14] Cl
was also described with the Los Alamos ECPs and their associated
double-z basis set augmented by a d polarization function.[15, 16] A 6 ±
31G(d,p) basis set was used for H atoms.[17] Full optimizations without
symmetry constraints have been carried out at the B3LYP level.[18, 19]
[14] P. J. Hay, W. R. Wadt, J. Chem. Phys. 1985, 82, 299.
OBn
R
OBn
H+
O
(Me3Sn)2
300 nm
N
N
RI+
(1)
H
R
H
SO2Ph
H
radical acylation reactions. Our approach is largely based on
the tin-free radical allylation reaction of Zard et al. [Eq. (2)][2]
AIBN
SO2Et
+
RI
(2)
R
and involves thermal decomposition of an alkylsulfonyl
radical (path a) and subsequent transfer of an iodine atom
(path b),[6] as outlined in Scheme 1. The problem with tin-free
b
a
R1SO2
AIBN
_
_
R
1 I
R1
+
+
R
R I
[15] W. R. Wadt, P. J. Hay, J. Chem. Phys. 1985, 82, 284.
–SO2
1
1
[16] A. Hölwarth, M. Böhme, S. Dapprich, A. W. Ehlers, A. Gobbi, V.
Jonas, K. Köhler, R. Stegmann, A. Veldkamp, G. Frenking, Chem.
Phys. Lett. 1993, 208, 237.
d
c
R1SO2
R1SO2
1
2
3
[17] P. C. Hariharan, J. A. Pople, Theor. Chim. Acta 1973, 28, 213.
[18] A. D. Becke, J. Chem. Phys. 1993, 98, 5648.
[19] C. Lee, W. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785.
OBn
OBn
OBn
R
N
N
N
R1
H
H
SO2R1
H
1
2
3
Scheme 1. Pathways for the radical reaction of an alkyl iodide with 1.
radical acylation arises from the fast addition of an alkyl
radical to sulfonyl oxime ether 1 to afford oxime ether 2.[7]
Since the direct addition of the alkyl radical to sulfonyl oxime
ether 1 (path c) would compete with transfer of an iodine
atom (path b) in the radical acylation approach, efficient
iodine transfer is a key factor for the success of this approach.
We first studied the efficiency of iodine-atom transfer from
a secondary alkyl iodide to an ethyl radical relative to the
addition of the ethyl radical to ethanesulfonyl oxime ether 4
[Eq. (3)]. Treatment of cyclohexyl iodide with an equimolar
Tin-Free Radical Acylation Reactions with
Methanesulfonyl Oxime Ether**
Sunggak Kim,* Hyun-Ji Song, Tae-Lim Choi, and
Joo-Yong Yoon
Recent advances in radical reactions have greatly benefited
from the efficiency of organotin reagents as mediators.
However, organotin reagents are highly toxic, and it is
difficult to remove their residues from the products. These
disadvantages have proved to be a serious barrier to industrial
applications. To solve the problems associated with toxic
organotin reagents, several alternative approaches, including
the use of polymer-supported organotin reagents and organo-
silanes, have been utilized with some success.[1] Recently, a
few tin-free carbon ± carbon bond-forming reactions were
reported; they include organosulfone-mediated radical allyla-
tion, alkenylation, alkynylation, and azidation reactions.[2±4]
Recently, we reported highly efficient tin-mediated radical
acylation reactions with sulfonyl oxime ethers [Eq. (1)].[5] We
then studied the possibility of environmentally benign tin-free
OBn
N
OBn
OBn
I
N
AIBN
N
H
(3)
+
+
R
H
H
SO2R
6: 25%
6:
7:
60%
4 : R = Et
5 : R = Me
8:
62%
< 3%
amount of 4 and azobisisobutyronitrile (AIBN; 0.1 equiv) in
refluxing heptane for 24 h resulted in a 25:60 mixture of two
oxime ethers 6 and 7. Evidently, addition of the ethyl radical to
4 is more than two times faster than the transfer of the iodine
atom from cyclohexyl iodide to the ethyl radical. Although
the yield of 6 was increased to 48% along with 21% of 7 by
using a large excess of cyclohexyl iodide (5 equiv), the serious
problem of the formation of 7 could not be solved, and this
indicates that 4 is not suitable for tin-free radical acylation
with secondary alkyl iodides.
[*] Prof. Dr. S. Kim, H.-J. Song, T.-L. Choi, Dr. J.-Y. Yoon
Center for Molecular Design and Synthesis
and Department of Chemistry
School of Molecular Science
Korea Advanced Institute of Science and Technology
Taejon 305-701 (Korea)
Fax : (‡82)42-869-8370
E-mail: skim@mail.kaist.ac.kr
We next turned our attention to methanesulfonyl oxime
ether 5. Although it was reported that the methanesulfonyl
[**] We thank the CMDS and the BK21 project for financial support.
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radical hardly decomposes into SO2 and a methyl radical,[8] we
found that decomposition of the methanesulfonyl radical
occurred at 1208C. When cyclohexyl iodide was treated with 5
in refluxing heptane in the presence of AIBN for 40 h,
cyclohexyl oxime ether 6 was isolated in 62% yield along with
a trace of methyl oxime ether 8, that is, transfer of the iodine
atom was much faster than the direct addition process. Thus, 5
solved the problem we faced with secondary alkyl iodides.
Since the use of AIBN in heptane required 40 h at reflux, the
reaction was carried out in octane at 1208C with V-40
(azobis(cyclohexanecarbonitrile)) as initiator, and this short-
ened the reaction time to 6 h. As shown in Table 1, the results
OBn
OBn
+
OBn
V-40
N
N
N
_
(4)
+
R I
EtO2C
Me
EtO2C
10
R
EtO2C
SO2Me
11
9
The reaction was carried out under the same conditions and
afforded 10 in good yields (64 to 75%) without formation of
11 (Table 1).
Primary alkyl iodides did not work well with 5 and 9. Due to
the small energy difference between the methyl radical and a
primary alkyl radical, iodine-atom transfer competed with the
direct addition of the methyl radical to 5 [Eq. (5)]. Treatment
of 4-phenoxybutyl iodide (12) with an equimolar amount of 5
in tert-butylbenzene at 1408C for 30 h, which gave a 45:25
mixture of the desired oxime ether 15 and 8, demonstrates the
inefficiency of 5 with primary alkyl iodides.
Table 1. Synthesis of oxime ethers from alkyl iodides and tellurides by
using 5 and 9.
Substrate[a]
Product
Yield [%]
X ˆ H
80
73
X ˆ CO2Et
OBn
+
OBn
Me
OBn
V-40
tBuC6H5, 140 o
N
N
N
(5)
RCH2X
+
C
H
R
H
H
SO2Me
X ˆ H
78
75
8
5
15
X ˆ CO2Et
R = PhO(CH2)3
25%
12 : X = I
45%
13 : X = S(C=S)OEt
14 : X = TePh
20%
0%
65%
78%
X ˆ H
71
64
X ˆ CO2Et
X ˆ H
70
70
To solve the problem of slow iodine-atom transfer associ-
ated with primary alkyl iodides, we searched for better
radical-accepting systems than alkyl iodides, and xanthates
were our initial choice.[10] The reaction of xanthate 13 with 5
and V-40 under the same conditions afforded a 65:20 mixture
of 15 and 8 and indicated that transfer of the xanthate group is
slightly faster than that of the iodine atom.
Since the xanthate could not solve the present problem
associated with the direct addition of the methyl radical to 5,
we turned our attention to organic tellurides, which have been
utilized to generate alkyl and acyl radicals.[11, 12] Gratifyingly,
reaction of phenyl telluride 14 with 5 and V-40 in tert-
butylbenzene at 1408C for 24 h gave 15 in 78% yield without
any indication of the formation of 8. This result is somewhat
surprising, because tansfer of an iodine atom and of a phenyl
telluride group are known to proceed approximately at the
same rate,[13] although there was a previous report that vinyl
radicals abstract a phenyl telluride group about ten times
faster than an iodine atom.[14] Therefore, we performed a
competition experiment [Eq. (6)]. Reaction of an equimolar
X ˆ CO2Et
X ˆ H
67
64
X ˆ CO2Et
X ˆ H
72[b]
63[c]
X ˆ CO2Et
Yˆ I, X ˆ H
67
77
Yˆ TePh, X ˆ H
FG ˆ OPh[d]
78
77
FG ˆ OTBS[d]
FG ˆ OCOPh[d]
R ˆ Me, n ˆ 1
72
71
R ˆ Et, n ˆ 2
71
76
OBn
5, V-40
N
(6)
+
HO(CH2)3I
TBSO(CH2)4TePh
tBuC6H5, 140 o
C
[a] For iodides, in octane at 1208C for 6 h. For tellurides, in tBuC6H5 at
1408C for 24 h. [b] exo:endo ˆ 4.5:1. [c] exo:endo ˆ 1.8:1. [d] FG ˆ func-
tional group.
R
H
16
17
18 : R = TBSO(CH2)4 (65%)
19 : R = HO(CH2)3 (< 4%)
obtained with 5 were quite satisfactory; the corresponding
oxime ethers were obtained in good yields (65 ± 80%). The
present approach was further extended to the synthesis of a-
oxime ester 10, a synthetic equivalent of an a-keto ester, by
mixture of phenyl telluride 16, iodide 17, and 5 with V-40
(0.2 equiv) in tert-butylbenzene at 1408C for 20 h afforded 18
in 65% yield along with a small amount of 19 (<4%), and this
clearly indicates the higher efficiency of transfer of a phenyl
using ethoxycarbonyl oxime ether
9
[Eq. (4)].[9]
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telluride group relative to that of an iodine atom.[15] Some
experimental results are included in Table 1 and demonstrate
the efficiency of the phenyl telluride approach. The reaction
was successful with secondary and primary alkyl tellurides.
We briefly examined a sequential radical reaction involving a
cyclization and acylation sequence [Eq. (7)]. Reaction of 21
1988, pp. 1089 ± 1113; c) M. Bertrand, Org. Prep. Proced. Int. 1994, 26,
257 ± 290.
[9] S. Kim, J.-Y. Yoon, I. Y. Lee, Synlett 1997, 475 ± 476.
[10] a) D. Crich, L. Quintero, Chem. Rev. 1989, 89, 1413 ± 1432; b) J.
Boivin, J. Camara, S. Z. Zard, J. Am. Chem. Soc. 1992, 114, 7909 ±
7910; c) B. Quiclet-Sire, S. Z. Zard, J. Am. Chem. Soc. 1996, 118,
9190 ± 9191; d) S. Z. Zard, Angew. Chem. 1997, 109, 724 ± 737; Angew.
Chem. Int. Ed. Engl. 1997, 36, 672 ± 685; e) B. Quiclet-Sire, S. Seguin,
S. Z. Zard, Angew. Chem. 1998, 110, 3056 ± 3058; Angew. Chem. Int.
Ed. 1998, 37, 2864 ± 2866.
[11] a) D. H. R. Barton, J. C. Jaszberenyi, E. A. Theodorakis, J. Am. Chem.
Soc. 1992, 114, 5904 ± 5905; b) M. A. Lucas, C. H. Schiesser, J. Org.
Chem. 1996, 61, 5754 ± 5761.
[12] a) C. Chen, D. Crich, A. Papadatos, J. Am. Chem. Soc. 1992, 114,
8313 ± 8314; b) C. Chen, D. Crich, Tetrahedron Lett. 1993, 34, 1545 ±
1548; c) D. Crich, C. Chen, J.-T. Hwang, H. Yuan, A. Papadatos, R. I.
Walter, J. Am. Chem. Soc. 1994, 116, 8937 ± 8951.
E
E
OBn
Me
E
E
5, V-40
tBuC6H5, 140 o
N
OBn
+
(7)
N
C
H
X
H
8
22
20:
21:
31%
67%
X = I
55%
0%
X = TePh
[13] D. P. Curran, A. A. Martin-Esker, S.-B. Ko, M. Newcomb, J. Org.
Chem. 1993, 58, 4691 ± 4695.
[14] L.-B. Han, K.-I. Ishihara, N. Kambe, A. Ogawa, I. Ryu, N. Sonoda, J.
Am. Chem. Soc. 1992, 114, 7591 ± 7592.
[15] We thank the referees for suggesting a competition experiment and
for drawing our attention to ref. [13].
with 5 under the same conditions afforded the desired oxime
ether 22 in 67% yield, whereas the use of iodide 20 gave 22 in
31% yield along with 8 (55%); this demonstrates the
efficiency of the phenyl telluride group as a radical precursor.
Experimental Section
Typical procedure: A degassed solution of 1-bromo-4-iodomethyl-benzene
(118 mg, 0.40 mmol), O-benzyl-1-(methanesulfonyl)formaldoxime (5,
128 mg, 0.60 mmol) and V-40 (20 mg, 0.08 mmol) in freshly distilled octane
(2 mL) was heated to reflux under N2 for 8 h. The solvent was evaporated
under reduced pressure, and the residue was purified by chromatography
on a silica gel column (n-hexane: ethyl acetate 1:15) to yield O-benzyl-1-(4-
bromobenzyl)formaldehyde (98 mg, 0.32 mmol, 80% yield, E:Z ˆ 1.1:1).
1H NMR (CDCl3, 200 MHz): E isomer: d ˆ 3.45 (d, J ˆ 6.4 Hz, 2H), 5.08 (s,
2H), 7.06 (d, J ˆ 2.2 Hz, 2H), 7.32 ± 7.43 (m, 7H), 7.49 (t, J ˆ 6.4 Hz, 1H); Z
isomer: d ˆ 3.65 (d, J ˆ 5.4 Hz, 2H), 5.15 (s, 2H), 6.80 (t, J ˆ 5.4 Hz, 1H),
7.02 (d, J ˆ 2.2 Hz, 2H), 7.32 ± 7.43 (m, 7H); 13C NMR (CDCl3, 100 MHz):
d ˆ 31.9, 35.3, 75.8, 76.1, 120.5, 120.8, 127.8, 127.9, 128.2, 128.4, 128.6, 128.8,
130.4, 130.5, 131.7, 131.8, 135.3, 135.8, 137.6, 137.7, 149.0, 149.3; IR (NaCl):
nÄ ˆ 3031, 2928, 1656, 1586, 1488, 1454, 1367, 1276, 1072, 1012 cm 1; HR-MS:
Cyclodextrin Cavities as Probes for Ligand-
Exchange Processes
Eric Engeldinger, Dominique Armspach,* and
Dominique Matt*
Cyclodextrins (CDs) have attracted a lot of attention as
chiral building blocks for the construction of enzyme mimics
because of their ability to bind a wide range of organic
substrates in water.[1±4] Combining CDs with transition metals
has proven a very attractive goal in terms of achieving highly
selective and efficient catalysis.[5±11] One of the challenges, so
far not met, is to force a metal that is covalently linked to a
CD framework to be confined in the cavity where maximum
interaction between the first coordination sphere of the metal
and the CD walls is expected to take place so as to stabilize
unusual coordination modes. In addition, cavities with intro-
verted[12] functionalities could provide new catalysts where a
metal center operates inside a spatially restricted environ-
ment.[13±15] We report here the first a-CD-based multitopic
ligand (2) capable of hosting metal ± organic fragments. As
shown by NMR investigations, the complexes derived from
this ligand display unique intra- and intermolecular ligand-
exchange phenomena at the included metal center.
‡
[M ] calcd for C15H14BrNO: 303.0259; found: 303.0257.
Received: February 5, 2001 [Z16557]
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5983.
We anticipated that an easy way to ensure metal encapsu-
lation in a cavity would be to use an a-CD derivative bearing
[6] a) D. P. Curran, M.-H. Chen, D. Kim, J. Am. Chem. Soc. 1986, 108,
2489 ± 2490; b) D. P. Curran, D. Kim, Tetrahedron Lett. 1986, 27,
5821 ± 5814; c) D. P. Curran, D. Kim, Tetrahedron 1991, 47, 6171 ±
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6189 ± 6196.
[7] S. Kim, I. Y. Lee, Tetrahedron Lett. 1998, 39, 1587 ± 1590.
[8] a) A. Horowitz, L. A. Rajbenbach, J. Am. Chem. Soc. 1975, 97, 10 ± 13;
b) C. Chatgilialoglu in The Chemistry of Sulfones and Sulfoxides
(Eds.: S. Patai, Z. Rappoport, C. J. M. Stirling), Wiley, Chichester,
[*] Dr. D. Armspach, Dr. D. Matt, E. Engeldinger
Â
Laboratoire de Chimie Inorganique Moleculaire, UMR 7513 CNRS
Â
Universite Louis Pasteur
1, rue Blaise Pascal, 67008 Strasbourg Cedex (France)
Fax : (‡33)3-90-240-722
E-mail: dmatt@chimie.u-strasbg.fr
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
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