An expeditious synthesis of natural and unnatural disubstituted maleic anhydrides

Article abstract of DOI:10.1016/j.tetlet.2006.08.073

A facile entry to the synthesis of natural and unnatural substituted maleic anhydrides based on the Barton radical decarboxylation is described. The radicals, generated by the photolysis of N-hydroxy-2-thiopyridone esters derived from succinic and alkyl a

Full text of DOI:10.1016/j.tetlet.2006.08.073

Tetrahedron Letters 47 (2006) 7409–7411
An expeditious synthesis of natural and unnatural
disubstituted maleic anhydrides
Micka e¨ l Denanc e´ , Estelle Banaszak and Mohammad Samadi*
D e´ partement de Chimie, LIMBP, IPEM, Universit e´ Paul Verlaine de Metz, 1, bd Arago, Metz Technop oˆ le,
5
7078 Metz cedex 3, France
Received 29 June 2006; revised 14 August 2006; accepted 21 August 2006
Abstract—A facile entry to the synthesis of natural and unnatural substituted maleic anhydrides based on the Barton radical decar-
boxylation is described. The radicals, generated by the photolysis of N-hydroxy-2-thiopyridone esters derived from succinic and
alkyl acids reacted, respectively, with electron deficient olefin phenyl maleimide by a consecutive two-step radical addition, afforded
the corresponding disubstituted maleic anhydrides 1a–f.
Ó 2006 Elsevier Ltd. All rights reserved.
A number of natural products containing a substituted
O
maleic anhydride unit have been reported in the litera-
R
1
2
a R = CH (CH )
3 2 5
ture.1 They exhibit a range of biological activities,
O
b R = CH (CH )
2
3
3
2 7
including antibacterial activity, immunomodulating,
HOOC
3c R = CH (CH )
3
2 9
4
and plant growth promoting. Among them the un-
O
named dialkylsubstituted maleic anhydrides 1a and 1b
O
were isolated from the soil, Pseudomonas cepacia A-
HOOC
5
1
419 by Soda and co-workers, while 1c was prepared
O
chemically by the dehydration of natural spiculisporic
acid.6 Anhydride 2 and cordyanhydride A 3 have
recently been isolated as bioactive fungal natural prod-
O
O
O
O
HOOC
O
O
O
2
3
7
,8
ucts (Fig. 1).
Figure 1.
Two approaches for the synthesis of dialkylsubstituted
maleic anhydrides 1a–b based on ionic chemistry were
reported in the literature: copper mediated tandem
vicinal difunctionalization of dimethyl acetylenedicarb-
tion using thiohydroxamic esters as a source of carbon
1
2
radicals, seemed the method of choice. In this letter,
we report a further extension of this reaction towards
the total synthesis of anhydrides 1a–c and some ana-
logues using a double radical decarboxylation.
9
0
oxylate and chemoselective S 2/S 2 coupling of Grig-
N
N
1
0
nard reagents.
We reported previously that the carbon–carbon bond
formation using free radical reactions might be the most
suitable way to synthesize branched-chain maleic anhy-
Our strategy for the synthesis of 1 is based on a two-step
radical addition to phenyl maleimide. In the first step,
the readily available succinic acid monomethyl ester 4
was converted into its thiohydroxamic ester 5, by the
DCC coupling method in the presence of 1-hydroxypyri-
dine-2(1H)-thione. Irradiation in situ with a tungsten
light (500 W) of 5, in the presence of phenyl maleimide
1
1
dride. In this respect the Barton decarboxylation reac-
Keywords: Maleic anhydride; Barton decarboxylation; Thiohydr-
oxamic esters.
(5 equiv), gave the intermediate addition product 6 in
*
Corresponding author at present address: D e´ partement de Chimie,
LCA, IPEM, Universit e´ Paul Verlaine de Metz, 1, bd Arago, Metz
Technop oˆ le, 57078 Metz cedex 3, France. Tel.: +33 387547793; fax:
82% yield. The oxidation of 6 with m-CPBA, followed
by the elimination of the resulting sulfoxide produced
+33 387315801; e-mail: samadi@sciences.univ-metz.fr
an unsaturated 7 in 90% yield. The syn elimination of
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.08.073

7410
M. Denanc e´ et al. / Tetrahedron Letters 47 (2006) 7409–7411
Table 1.
HO N
COOH
O
Entry
Acid
% Product (yield)
S
1
2
3
4
5
6
8a
8b
8c
8d
8e
8f
1a (42)
1b (42)
1c (43)
1d (46)
1e (48)
1f (45)
H COOC
H COOC
O N
3
3
i
4
5
S
O
Spy: S
N
NPh
hν
O
O
O
Spy
double bond to give the disubstituted anhydride 1f.
The results are summarized in Table 1.
ii, iii
NPh
NPh
H COOC
H COOC
3
3
O
O
In summary, we have described an efficient and concise
synthesis of anhydride 1. The facile synthesis and excep-
tionally mild conditions of the reaction described herein
offer a rapid synthetic access to other analogues bearing
suitable functionalities on the alkyl side chain, and will
allow further biological evaluation.
7
6
Scheme 1. Reagents and conditions: (i) DCC, CH
phenyl maleimide (5 equiv) hm, 15 °C, 30 min (82%); (ii) m-CPBA,
CH Cl , 0 °C, 1 h; (iii) toluene, 110 °C, 1 h, (90% from 6).
2 2
Cl , rt, 2 h, then
2
2
the 2-pyridylthio group of the intermediate 6 established
the trans stereochemical relationship of the 2-pyridyl-
thio group and the alkyl substituents, which is the result
of a trans addition of the radical to phenyl maleimide
References and notes
1
. (a) Baldwin, J. E.; Adlington, R. M.; Roussi, F.; Bulger, P.
G.; Marquez, R.; Mayweg, A. V. W. Tetrahedron. 2001,
1
3
(
Scheme 1).
5
7, 7409–7416; (b) Singh, S. B.; Jayasuriya, H.; Silverman,
Having compound 7 in hand, it was subjected as the ole-
fin trap to a second step radical reaction. Thus acid 8
was converted to its thiohydroxamic ester 9 as was de-
scribed for 5, and irradiation in situ with tungsten light
K. C.; Bonfiglio, C. A.; Williamsons, J. M.; Lingham, R.
B. Bioorg. Med. Chem. 2000, 8, 571–580; (c) Nicolaou, K.
C.; Baran, P. S.; Zong, Y.-L.; Fong, K. C.; He, Y.; Yoon,
W. H.; Choi, H.-S. Angew. Chem., Int. Ed. 1999, 38, 1669–
1
675, and references cited therein; (d) Slade, R. M.;
(
500 W) in the presence of olefin 7 (5 equiv), produced
Branchaud, B. P. J. Org. Chem. 1998, 63, 3544–3549; (e)
Ratemi, E. S.; Dolence, J. M.; Poulter, C. D.; Vederas, J.
C. J. Org. Chem. 1996, 61, 6296–6301; (f) Bit, R. A.;
Davis, P. D.; Elliott, L. H.; Harris, W.; Hill, C. H.; Keech,
E.; Kumar, H.; Lawton, G.; Maw, A.; Nixon, J. S.; Vesey,
D. R.; Wadsworth, J.; Wilkinson, S. E. J. Med. Chem.
1993, 36, 21–29; (g) Pattenden, G.; Turvill, M. W.;
Chorlton, A. P. J. Chem. Soc., Perkin Trans. 1 1991,
2357–2361.
the intermediate addition product 10 as a mixture of iso-
1
4
mers, which was further treated with KOH in MeOH–
THF to furnish the desired dialkylsubstituted maleic
1
5
anhydride 1 as the sole isomer (Scheme 2). The natural
and unnatural anhydrides 1a–f were obtained in the
range of 42–48% yield over two steps from acids 8a–f.
Oleic acid 8f was successfully decarboxylated in the pres-
ence of olefin 7 without intramolecular addition to the
2
3
4
5
6
7
8
. Weidenmuller, H.-L.; Cavagna, F.; Fehlhaber, H.-W.;
Prave, P. Tetrahedron Lett. 1972, 13, 3519–3522.
. Weber, W.; Semar, M.; Anke, T.; Bross, M.; Steglich, W.
Planta Med. 1992, 58, 56–59.
. Mondal, G.; Dureja, P.; Sen, B. Indian J. Exp. Bio. 2000,
38, 84–87.
. Itoh, S.; Esaki, N.; Masaki, K.; Blank, W.; Soda, K. J.
Ferment. Bioeng. 1994, 77, 513–516.
. Gama, Y.; Yasumoto, M.; Suzuki, H.; Ishigami, Y.
Yukagaku 1989, 38, 292.
HO N
O
R C O N
S
RCOOH
8a-f
i
9
S
. Aldridge, D. C.; Carman, R. M.; Moore, R. B. J. Chem.
Soc., Perkin Trans. 1 1980, 2134–2135.
hν
7
. (a) Isaka, M.; Tanticharoen, M.; Thebtaranonth, Y.
Tetrahedron Lett. 2000, 41, 1657–1660; (b) Yamanishi,
R.; Okada, K.; Tamugi, N.; Iwashima, M.; Iguchi, K.
Bull. Chem. Soc. Jpn. 2000, 73, 2087–2091, and references
cited therein.
O
O
R
R
ii
H COOC
O
Spy
NPh
HOOC
3
O
O
9
. Adlington, R. M.; Baldwin, J. E.; Cox, R. J.; Pritchard, G.
J. Synlett 2002, 820–822, and references cited therein.
1
a-f
10
1
0. Kar, A.; Argade, N. P. Tetrahedron 2003, 59, 2991–2998.
a: R = CH (CH )
d: R = CH (CH )
11. (a) Poigny, S.; Guyot, M.; Samadi, M. J. Chem. Soc.,
Perkin Trans. 1 1997, 2175–2176; (b) Poigny, S.; Guyot,
M.; Samadi, M. J. Org. Chem. 1998, 63, 1342–1343.
3
2 5
3
2 8
b: R = CH (CH )
e: R = CH (CH )
2 10
3
2 7
3
c: R = CH (CH )
f : R = (Z)CH (CH ) CH=CH(CH )
3 2 7 2 7
3
2 9
1
2. (a) Barton, D. H. R.; Crich, D.; Motherwell, W. B.
Tetrahedron 1985, 41, 3901–3924; (b) Crich, D.; Quintero,
L. Chem. Rev. 1989, 89, 1413–1432.
Scheme 2. Reagents and conditions: (i) DCC, CH
equiv of 7, hm, 15 °C, 30 min; (ii) KOH, THF–MeOH, reflux, 3 h.
2
Cl
2
, rt, 2 h, then
5

M. Denanc e´ et al. / Tetrahedron Letters 47 (2006) 7409–7411
7411
1
1
3. For more detail of trans addition of radical to maleic
anhydride see: (a) Branchaud, B. P.; Slade, R. M.
Tetrahedron Lett. 1994, 35, 4071; (b) Barton, D. H. R.;
Gateau-Olesker, A.; Gero, S. D.; Lacher, B.; Tachdjian,
C.; Zard, S. M. J. Chem. Soc., Chem. Commun. 1987,
and extracted with ether. The aqueous phase layer was
acidified with diluted HCl and extracted with ether. The
organic layer was washed with water, brine, dried over
MgSO , and concentrated. The residue was purified by
4
column chromatography on silica gel using cyclohexane–
EtOAc as an eluent to yield compound 1.
1
790.
4. After irradiation, the reaction mixture was subjected to
column chromatography over silica gel. The excess of
olefin 7 was recovered along with compound 10, which was
used immediately in the next step without further charac-
terization. So the stereochemical relationships trans and
syn of the 2-pyridylthio group and the alkyl substituent of
compound 10 were not determined. For more detail on the
stereochemistry of radical addition to monosubstituted
maleic anhydride see: Giese, B.; Damm, W.; Witzel, H.;
Zeitz, H. G. Tetrahedron Lett. 1993, 34, 7053.
Spectral data of compounds 1a, 1b, and 1c are in
5
,6
agreement with the reported literature.
3-(4-Nonyl-2,5-dioxo-2,5-dihydrofuran-3-yl)propanoic acid
(1d). Oil; IR (neat) 2917, 2850, 1768, 1712, 1257,
ꢀ
1 1
910 cm ; H NMR (CDCl
3
, 250 MHz), d 2.76 (s, 4H),
2.49 (t, J = 7 Hz, 2H), 1.58 (m, 2H), 1.28 (m, 12H), 0.88 (t,
1
3
J = 6.5 Hz, 3H); C NMR (CDCl
3
, 62.5 MHz), d 176.2,
165.4, 165.2, 146.1, 141.2, 31.6, 30.8, 29.5, 29.4, 29.2, 29.0,
27.7, 24.4, 22.4, 19.4, 13.9; Anal. Calcd for C16
64.84, H, 8.16. Found: C, 64.65, H, 8.30.
3-(4-Undecyl-2,5-dioxo-2,5-dihydrofuran-3-yl)propanoic acid
24 5
H O : C,
1
5. General procedure for synthesis of disubstituted maleic
anhydrides 1. To a solution of acid 8 (1 mmol) and 1-
hydroxypyridine-2(1H)-thione (147 mg, 1.2 mmol) in dry
(1e). Mp 54–55 °C; IR (KBr) 2917, 2850, 1768, 1712, 1257,
ꢀ
1 1
3
910 cm ; H NMR (CDCl , 250 MHz), d: 2.76 (s, 4H),
CH
2
Cl
2
(10 mL) was added DCC (248 mg, 1.2 mmol)
2.49 (t, J = 7 Hz, 2H), 1.58 (m, 2H), 1.28 (m, 16H), 0.88 (t,
1
3
under argon. The mixture was stirred at room temperature
for 2 h. Olefin 7 (1.296 g, 5 mmol) was then added, and the
mixture irradiated with a tungsten lamp (500 W) at 10–
J = 6.5 Hz, 3H); C NMR (CDCl , 62.5 MHz), d 177.1,
3
165.6, 165.4, 146.3, 141.4, 31.9, 30.9, 29.6, 29.5, 29.4,
29.32, 29.28, 29.2, 27.9, 24.6, 22.7, 19.6, 14.1; HRMS m/z:
1
5 °C for 30 min. The solution was filtered to remove the
29 5
calcd for C18H O [MH] 325.2015, found 325.2022.
(Z)-3-(4-(Heptadec-8-enyl)-2,5-dioxo-2,5-dihydrofuran-3-
urea and the filtrate was washed with saturated NaHCO ,
3
water, brine, dried over MgSO
vacuo. The residue was purified over silica gel using
cyclohexane–EtOAc (80:20) as eluent to give compound
4
, and concentrated in
yl)propanoic acid (1f). Oil; IR (neat) 2927, 2856, 1768,
ꢀ
1
1
1714, 1274, 912 cm ; H NMR(CDCl , 250 MHz), d:
3
5.35 (m, 2H), 2.77 (s, 4H), 2.50 (t, J = 7 Hz, 2H), 2.01 (m,
4H), 1.57 (m, 2H), 1.26 (m, 20H), 0.88 (t, J = 6.5 Hz, 3H);
1
0, which was used in the next step without further
1
3
characterization. To a solution of imide 10 in THF–
MeOH (6 mL, 1:2) was added a solution of KOH (0.6 g) in
water (2 mL), and the reaction mixture was refluxed for
3
C NMR (CDCl , 62.5 MHz), d: 176.4, 165.6, 165.4,
146.3, 141.4, 130.1, 129.6, 31.9, 30.9, 30.3, 29.8, 29.7, 29.6,
29.5, 29.3, 29.1, 29.0, 27.9, 27.2, 27.1, 24.6, 22.7, 19.6, 14.1;
HRMS m/z: calcd for C H O [MH] 407.2797, found
3
h with stirring. The solvent mixture was removed under
2
4
39
5
reduced pressure, and the residue was dissolved in water,
407.2851.