Aryl iodides from aryllithiums using an iodolactone as an iodine electrophile

Article abstract of DOI:10.1016/S0040-4039(01)01589-1

The paper describes the use of iodolactone 2 as an iodine electrophile for transforming aryllithiums into aryl iodides.

Full text of DOI:10.1016/S0040-4039(01)01589-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7501–7502
Aryl iodides from aryllithiums using an iodolactone as
an iodine electrophile
David C. Harrowven,a,* Michael I. T. Nunna and David R. Fenwickb
aDepartment of Chemistry, The University, Southampton S017 1BJ, UK
bDiscovery Chemistry, Pfizer Global Research and Development, Sandwich, Kent CT13 9NJ, UK
Received 30 March 2001; revised 7 August 2001; accepted 24 August 2001
Abstract—The paper describes the use of iodolactone 2 as an iodine electrophile for transforming aryllithiums into aryl iodides.
© 2001 Elsevier Science Ltd. All rights reserved.
The synthesis of aryl iodides from aryllithiums is usu-
ally accomplished using 1,2-diiodoethane or iodine as
the halogen electrophile.1,2 The fact that each method
has found widespread application bares testiment to
their utility and effectiveness. In this letter we report
our finding that iodolactone 23 also serves as an iodine
THF, -78°C → RT
+
+
CO2Li
I
ArLi
ArI
O
O
1
2
3
4
Scheme 1.
n-BuLi, THF,
-78°C, 30 min;
n-BuLi, THF,
-78°C, 30 min;
MeO
MeO
MeO
MeO
MeO
MeO
2, -78°C, 90 min
2, -78°C, 90 min
Br
I
Br
I
68%.
57%.
5
9
6
7
8
n-BuLi, THF,
-78°C, 30 min;
n-BuLi, THF
-78°C → RT, 1h;
Br
I
MeO
MeO
O
O
O
O
2, -78°C, 2h
2, -78°C, 2h;
to -10°C, 30 min,
49% (+ 11, 30%)
MeO
MeO
58%.
OTHP
OTHP
I
10
11
13
12
n-BuLi, THF,
-78°C → 0°C, 1h;
2, -78°C, 90 min
S
S
I
O
O
H
O
O
H
88%.
n-BuLi, THF,
-78°C, 30 min;
14
18
2, -78°C, 90 min;
O
O
n-BuLi, THF,
-78°C, 30 min;
45%.
Br
I
O
O
O
O
2, -78°C, 90 min
Br
I
MeO
MeO
70%.
15
16
17
Scheme 2.
Keywords: aryl halides; halogen–metal exchange; halogenation; lithium and compounds.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01589-1

7502
D. C. Harrow6en et al. / Tetrahedron Letters 42 (2001) 7501–7502
electrophile for the preparation of aryl iodides and
hetaryl iodides from the corresponding organolithiums
(Scheme 1). Notably, reactions are easily accomplished,
reliable for a wide range of substrates and yields com-
pare favourably with the aforementioned procedures.4
2. For recent examples using iodine, see: (a) Ogawa, T.;
Kishimoto, T.; Kobayashi, K.; Ono, N. J. Chem. Soc.,
Perkin Trans. 1 1998, 529; (b) Goldfinger, M. B.; Crawford,
K. B.; Swager, T. M. J. Org. Chem. 1998, 63, 1676; (c) Hirt,
U. H.; Spingler, B.; Wirth, T. J. Org. Chem. 1998, 63, 7674;
(d) Bailey, W. F.; Carson, M. W. J. Org. Chem. 1998, 63,
9960; (e) Stara, I. G.; Stary, I.; Kollarovic, A.; Teply, F.;
Saman, D.; Fiedler, P. Tetrahedron 1998, 54, 11209; (f)
Fukuyama, Y.; Yaso, H.; Nakamura, K.; Kodama, M.
Tetrahedron Lett. 1999, 44, 105; (g) Seki, M.; Furutani, T.;
Hatsuda, M.; Imashiro, R. Tetrahedron Lett. 2000, 41, 2149.
3. (a) van Tamelen, E. E.; Shamma, M. J. Am. Chem. Soc.
1954, 76, 2315; (b) Guenther, H. J.; Guntrum, E.; Jaeger,
V. Liebigs Ann. Chem. 1984, 15; (c) Wen, R.; Laronze, J.-Y.;
Levy, J. Heterocycles 1984, 22, 1061; (d) Detty, M. R.; Zhou,
F.; Friedman, A. E. J. Am. Chem. Soc. 1996, 118, 313.
4. All compounds gave satisfactory spectral and analytical
characteristics. At the request of a referee we have con-
ducted the following comparative studies using 1,2-
diiodoethane as the iodine electrophile. Thus, 5“6
proceeded in 69% yield; 7“8 proceeded in 55% yield; 15“16
proceeded in <35% yield; 17“18 proceeded in 60% yield.
The lithiation and iodination of 11 to 12 with iodine has
been reported to proceed in 90% yield (see: (a) Marti, T.;
Peterson, B. R.; Fuerer, A.; Mordasini-Denti, T.; Zarske, J.;
Jaun, B.; Diederich, F.; Gramlich, V. Helv. Chim. Acta 1998,
81, 109; (b) Essamkaoui, M.; Mayrargue, J.; Vierfond,
J.-M.; Reynet, A.; Moskowitz, H.; Thal, C. Synth. Commun.
1992, 22, 2723). The lithiation and iodination of 13 to 14
with iodine has been reported in yields ranging from 29 to
90% (see (c) Vallgarda, J.; Appelberg, U.; Arvidsson, L.-E.;
Hjorth, S.; Svensson, B. E.; Hacksell, U. J. Med. Chem.
1996, 39, 1485; (d) Gaertner, R. J. Am. Chem. Soc. 1952,
74, 4950; (e) Rossi, R.; Carpita, A.; Lezzi, A. Tetrahedron
1984, 40, 2773; (f) Ilagouma, A. T.; Dornand, J.; Liu, C. F.;
Zenone, F.; Mani, J. C.; Kamenka, J. M. Eur. J. Med. Chem.
1990, 25, 609.)
Several examples have been realised (Scheme 2) and in
each case products were formed in moderate to good
yield. Though this new procedure is primarily presented
as interesting curiosity, the ease with which it can be
effected makes it a worthwhile addition to existing
protocols.4 We are presently examining the reaction
with other readily available iodolactones in the hope of
suppressing the dominant side reaction, protonation.
Acknowledgements
The authors thank Pfizer Global Research and Devel-
opment and the EPSRC for their financial support
through an Industrial CASE award (to MITN).
References
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