formation of cyclised products should be improved by conduct-
ing the experiments with very low concentrations of both the
iodoacrylate and Bu3SnH, thus respectively decreasing of the
formation of oligomers and the rate of hydrogen atom transfer
to uncyclised radicals. Because such high dilution conditions
require the use of very large quantities of solvent for the
production of small amounts of products, they are of no interest
for preparative purposes. However, the same effect was
obtained by the separate slow addition with syringe pumps of
both Bu3SnH and iodoacrylate to a solution of AIBN in benzene
(method A). Under these conditions cyclised products were
isolated in modest to good yield (Table 2). In an alternative
procedure the precursors were heated with 1.1 molar equiva-
lents of Bu3SnH (0.01 mol dm23), AIBN and sodium tosylate
(method B). The role of the sodium tosylate is still uncertain but
it certainly promotes cyclisation. Each of these methods is
suitable for the convenient preparation of macrocyclic poly-
ethers on a gram scale.
Finally we examined the preparation of macrocycles that do
not contain a lactone group within the ring and hence should be
able to survive robust manipulation of the side chain. Thus
treatment of the ester 8 with Bu3SnH in the usual way gave 10
(64%) with a rate constant for cyclisation of kc = 2 3 104 s21
at 80 °C, while 9 gave 11 (87%). An advantage of products such
as 10 and 11 is that the side chain can be readily converted into
functionality suitable for tethering the macrocycle to other
ionophores or to fluorescent agents. Thus 11 readily underwent
hydrolysis with KOH in methanol to afford the acid 12 (84%)
while reduction with LAH in THF gave the alcohol 13 (79%).
In conclusion it appears that, as in the case of simple hexenyl
species, the introduction of oxygen atoms into suitable long
chain precursors enhances the rate of radical cyclisation
sufficiently to allow the preparation of substituted macrocyclic
polyethers in modest to good yield under convenient experi-
mental conditions. These results therefore complement those
describing other applications of radical macrocyclisation in
synthesis.10,11 Preliminary experiments indicate that some of
the macrocyclic polyethers described above may be useful as
complexing agents.
R
CO2Et
We gratefully acknowledge technical assistance from Mr
Robert Longmore and the award of a Commonwealth Post-
graduate Scholarship to K. D. and of a BDI Scholarship by
CNRS and Re´gion Aquitaine to A. P.
O
O
O
O
n
I
O
n
8 n = 1
9 n = 2
O
10 n = 1 R = CO2Et
11 n = 2 R = CO2Et
12 n = 2 R = CO2H
13 n = 2 R = CH2OH
References
1 A. L. J. Beckwith and S. A. Glover, Aust. J. Chem., 1987, 40, 157.
2 A. L. J. Beckwith, V. W. Bowry and G. Moad, J. Org. Chem., 1988, 53,
1632.
3 A. N. Abeywickrema and A. L. J. Beckwith, J. Chem. Soc., Chem.
Commun., 1986, 464.
4 A. L. J. Beckwith and C. H. Schiesser, Tetrahedron, 1985, 41, 3925.
5 The monotosylate was prepared by the general method previously used
for the preparation of the ditosylate: J. Dale and P. O. Kristiansen, Acta
Chem. Scand., 1972, 26, 1471.
6 A. L. J. Beckwith and G. Moad, J. Chem. Soc., Chem. Commun., 1974,
472.
7 C. Chatgilialoglu, K. U. Ingold and J. C. Scaiano, J. Am. Chem. Soc.,
1981, 103, 7739.
Table 1 Cylisation rate constants for polyether radicals in benzene at
80 °C
Radical
kc 3 1024/s21
Radical
kc 3 1024/s21
5b
5d
5f
15 ± 4
5.1 ± 0.8
3.0 ± 04
5c
5e
13 ± 1
10 ± 2
8 N. A. Porter and V. H.-T. Chang, J. Am. Chem. Soc., 1987, 109,
4976.
Table 2 Formation of macrocyclic polyethers by radical cyclisation
9 2j was obtained via DCC coupling of mono tert-butyl maleate with
tetraethylene glycol monotosylate. tert-Butyl maleate was prepared by
the same general method as that previously used for the preparation of
tert-butyl phthalate: W. A. Fessler and R. L. Schriner, J. Am. Chem.
Soc., 1936, 58, 1384.
10 N. A. Porter, D. R. Magnin and B. T. Wright, J. Am. Chem. Soc., 1986,
108, 2787; N. A. Porter, B. Lacher, V. H.-T. Chang and D. R. Magnin,
J. Am. Chem. Soc., 1989, 111, 8309.
11 For some recent examples see: J. Ullrich and D. P. Curran, Tetrahedron
Lett., 1995, 36, 8921; E. I. Troyansky, R. F. Ismagilov, V. V. Samoshin,
Y. A. Strelenko, D. V. Demchuk, G. I. Nikishin, S. V. Lindeman,
V. V. Khrustalyov and Y. T. Struchkov, Tetrahedron, 1995, 51, 11 431;
I. Ryu, K. Nagahara, H. Yamazaki, S. Tsunoi and N. Sonoda, Synlett,
1994, 643; M. J. Begley, G. Pattenden, A. J. Smithies and D. S. Walter,
Tetrahedron Lett., 1994, 35, 2417; K. S. Feldman, H. M. Berven,
A. L. Romanelli and M. Parvez, J. Org. Chem., 1993, 58, 6851.
Substrate
Ring size
Products [yield (%)]
2a
2b
2c
2d
2e
2f
2g
2h
2i
9
12
15
18
21
24
12/11
12/11
15/14
15/14
3a
3b (78a)
3c (72a, 78b)
3d (70a, 87b)
3e (63a, 90b)
3f (30a)
3g (37a 4g (21a)
3h (43a,c) 4h (57a,c
3i (36d) 4i (36d)
3j (29d) 4j (29d)
)
2j
a
b
Method A (see text); isolated yields. Method B (see text); yields
determined by GC with an internal reference. Relative yield; for this
reaction the absolute yield was not determined. Method B; total yield
c
d
determined by GC; relative yields by NMR.
Received, 19th December 1996; Com. 6/08494J
500
Chem. Commun., 1997