Decarboxylative acylation approach of thiohydroxamate esters

Article abstract of DOI:10.1039/b104025c

A decarboxylative acylation approach is achieved with thiohydroxamate ester 6, which is less reactive and more stable than Barton's ester 1.

Full text of DOI:10.1039/b104025c

Decarboxylative acylation approach of thiohydroxamate esters
Sunggak Kim,*a Chae Jo Lim,a Sang-Eun Songb and Han-Young Kangb
a 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.
E-mail: skim@mail.kaist.ac.kr
b Department of Chemistry, Chungbuk National University, Cheongju 361-763, Korea
Received (in Cambridge, UK) 4th May 2001, Accepted 20th June 2001
First published as an Advance Article on the web 12th July 2001
A decarboxylative acylation approach is achieved with
thiohydroxamate ester 6, which is less reactive and more
stable than Barton’s ester 1.
Since O-acyl thiohydroxamates were introduced in radical
chemistry by Barton,1 they have attracted a great deal of
attention among synthetic chemists as useful radical precursors
of alkyl2 and aminyl radicals.3 Radical chemistry of O-acyl
thiohydroxamates 1 were further applied not only to the
introduction of synthetically useful functional groups such as a
halide4 and a nitrile5 but also to the formation of carbon-carbon
bonds.6 However, a highly reactive trapping agent is normally
required because the alkyl radical could attack the thiocarbonyl
group of 1 concurrently.
In connection with our recent interest in tin-free radical
reactions,7,8 we have studied the feasibility of decarboxylative
acylation approaches of carboxylic acids via O-acyl thiohydrox-
amates 1 using phenylsulfonyl oxime ether 2a as an acylating
trapping agent (eqn. (1)).9 Irradiation of a solution of 1 and 2a
(3)
Furthermore, it is evident that a methyl radical, generated from
thermal decomposition of a methanesulfonyl radical, attacked
2b to some extent to yield 7.8 Thus, we performed the same
reaction with 2a and it was gratifying to find that thermal
reaction of 6 with 2a and V-40 in refluxing heptane afforded 3
in 78% yield without the formation of 7 and 8. Furthermore, the
decarboxylative acylation approach could be performed under
photochemically initiated conditions. Unlike Barton’s ester 1, 6
required irradiation at 300 nm. Irradiation of a benzene solution
of 6 with 2a at 300 nm for 9 h afforded 3 in 65% yield. Thus, the
remaining reactions were carried out with 2a in refluxing
heptane (0.25 M) for 12 h. Table 1 summarizes some
experimental results and illustrates the efficiency of the
decarboxylative acylation approaches. Primary and secondary
aliphatic carboxylic acids worked well, yielding the correspond-
ing oxime ethers in high yields. Sterically hindered tertiary
(1)
in benzene with a tungsten sun lamp (300 W) for 12 h gave a
mixture of oxime ether 3 (32%) and pyridyl sulfide 4 (36%) in
a roughly equal ratio, which was anticipated from the previously
reported kinetic data.10 Thus, the key feature for the success of
the decarboxylative acylation approach is to reduce the rate of
the alkyl radical additions onto the thiocarbonyl group to
suppress the formation of 4.
Table 1 Preparation of oxime ethers from thiohydroxamate esters
Substrate
X = (CO2–NMe-
Yielda
(%)
(CNS)SMe)
Product
R = H
R = COOMe
76 (64)
62
Our attention was given to somewhat less reactive thiohy-
droxamate esters that would not undergo aromatization upon
radical-mediated fragmentation.11 In this regard, we expected
that a thiohydroxamate ester 6 would be well suited for our
purpose. It is noteworthy that a very similar type of the reagent
(RCO2–NMe(CNS)SPh) was previously reported and would
have similar properties.2b Thiohydroxamate ester 6 was ob-
tained in high yield by treatment of a carboxylic acid with N-
methylhydroxydithiocarbamate 5, diethyl azodicarboxylate,
and triphenylphosphine in THF and was stable thermally and
hydrolytically (eqn. (2)). When 6 was treated with 2b using 1,1A-
R = H
R = COOMe
75 (68)
68
R = H
R = COOMe
82
68
R = H
R = COOMe
88 (76)
70
(2)
R = H
R = COOMe
87
74
azobis(cyclohexanecarbonitrile) (V-40) as an initiator in octane
at 120 °C for 10 h, a 71+16 mixture of oxime ether 3 and 7 was
obtained, indicating the addition of the alkyl radical onto 2b was
much faster than the rearrangement to afford 8 (eqn. (3)).
R = H
R = COOMe
84
71
a The numbers in parentheses indicate the yields at 300 nm.
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Chem. Commun., 2001, 1410–1411
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b104025c

In conclusion, we have developed a new thiohydroxamate
ester, which is much less reactive and more stable than Barton’s
ester and demonstrated the first examples of decarboxylative
acylation approaches under tin-free conditions.
We thank the Center for Molecular Design and Synthesis
(CMDS) and BK21 project for financial support.
carboxylic acids underwent the decarboxylative acylation
cleanly.
Thermal conditions gave somewhat higher yields than
photochemical conditions and required 12 h for completion of
the reaction. The major advantage of the present method is a
sequential cyclization and acylation approach, which was
demonstrated successfully in the present study (eqn. (4)).
Notes and references
1 For reviews, see: D. Crich and L. Quintero, Chem. Rev., 1989, 89, 1413;
D. H. R. Barton, Tetrahedron, 1992, 48, 2529; S. Z. Zard, Angew.
Chem., Int. Ed. Engl., 1997, 36, 672.
(4)
2 (a) D. H. R. Barton, D. Crich and W. B. Motherwell, Chem. Commun.,
1983, 939; (b) D. H. R. Barton, D. Crich and P. Potier, Tetrahedron
Lett., 1985, 26, 5943.
3 M. Newcomb, S.-U. Park, J. Kaplan and D. J. Marquardt, Tetrahedron
Lett., 1985, 26, 5651; M. Newcomb and T. M. Deeb, J. Am. Chem. Soc.,
1987, 109, 3163; M. Newcomb, T. M. Deeb and D. J. Marquardt,
Tetrahedron, 1990, 46, 2317; J. Esker and M. Newcomb, Tetrahedron
Lett., 1992, 33, 5913.
To obtain an oxime ester, a synthetic equivalent of a a-keto
ester,12 when we repeated the reaction with methoxycarbonyl
oxime ether 9 in refluxing heptane for 12 h, the desired oxime
ester 10 was isolated in 54% yield along with a significant
amount of the rearranged product 8 (31%) (eqn. (5)). Appar-
ently,
4 D. H. R. Barton, D. Crich and W. B. Motherwell, Tetrahedron, 1985, 41,
3901.
5 D. H. R. Barton, J. S. Jaszberenyi and E. A. Theodorakis, Tetrahedron,
1992, 48, 2613.
6 D. H. R. Barton, H. T. Togo and S. Z. Zard, Tetrahedron Lett., 1985, 26,
6349; D. H. R. Barton, D. Crich and G. Kretzschmar, Tetrahedron Lett.,
1984, 25, 1055.
(5)
7 S. Kim, C. J. Lim, S.-E. Song and H.-Y. Kang, Synlett, 2001, 688.
8 S. Kim, H.-J. Song, T.-L. Choi and Y.-J. Yoon, Angew. Chem., Int. Ed.
Engl., 2001, 40, 2524.
9 S. Kim, I. Y. Lee, J.-Y. Yoon and D. H. Oh, J. Am. Chem. Soc., 1996,
118, 5138.
the addition of the alkyl radical onto 9 was slowed down to
some extent, thereby allowing the alkyl radical to attack 6. The
problem of the formation of the rearranged product was solved
by the addition of 6 into 9 with a syringe pump. Thus, the
addition of a 0.05 M chlorobenzene solution of 6 to a 0.1 M
chlorobenzene solution of 9 at 120 °C by a syringe pump over
8 h with additional stirring for 2 h afforded the desired 10 in
65% yield without the formation of 8. Similarly, the formation
of several oxime esters worked equally well under highly
diluted conditions as shown in Table 1.
10 S. Kim and I. Y. Lee, Tetrahedron Lett., 1998, 39, 1587; M. Newcomb
and S. U. Park, J. Am. Chem. Soc., 1986, 108, 4132; M. Newcomb and
J. Kaplan, Tetrahedron Lett., 1987, 28, 1615; D. P. Curran, A. A.
Martin-Esker, S.-B. Ko and M. Newcomb, J. Org. Chem., 1993, 58,
4691.
11 D. H. R. Barton and G. Kretzschmar, Tetrahedron Lett., 1983, 24, 5889;
D. H. R. Barton, D. Crich and G. Kretzschmar, J. Chem. Soc., Perkin
Trans. 1, 1986, 39; D. H. R. Barton, P. Blundell and J. C. Jaszberenyi,
Tetrahedron, 1992, 48, 7121.
12 S. Kim, J.-Y. Yoon and I. Y. Lee, Synlett, 1997, 475.
Chem. Commun., 2001, 1410–1411
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