Tandem homolytic addition/substitution sequences and their application to tin-free radical chemistry

Article abstract of DOI:10.1016/j.tetlet.2007.10.139

Alkyl pent-4-enyl selenides (3a, b, e and f), pent-4-enylseleno benzoate (3c) and phenyl (pent-4-enylseleno)formate (3d) act as precursors of alkyl, acyl and oxyacyl radicals by reaction with diethyl 2-phenylselenomalonate (1) under photochemical conditio

Full text of DOI:10.1016/j.tetlet.2007.10.139

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Tetrahedron Letters 48 (2007) 9077–9079
Tandem homolytic addition/substitution sequences
and their application to tin-free radical chemistry
a
Sofia Lobachevsky,a,b Carl H. Schiessera,b, and Vijay Gupta
*
aSchool of Chemistry, The University of Melbourne, Victoria 3010, Australia
bBio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia
Received 21 September 2007; revised 15 October 2007; accepted 25 October 2007
Available online 30 October 2007
Abstract—Alkyl pent-4-enyl selenides (3a, b, e and f), pent-4-enylseleno benzoate (3c) and phenyl (pent-4-enylseleno)formate (3d)
act as precursors of alkyl, acyl and oxyacyl radicals by reaction with diethyl 2-phenylselenomalonate (1) under photochemical
conditions in a process involving tandem homolytic addition/substitution to afford tetrahydroselenophenes (5, 11) and the
corresponding phenylselenides (6).
Ó 2007 Elsevier Ltd. All rights reserved.
There is a desire to remove stannane-based reagents
The product
EtO2C
EtO2C
R
from the chemical armoury available to the synthetic
chemist because these reagents and reaction byproducts
are toxic1 and are not readily removed from reaction
mixtures by chromatographic techniques.2,3 The reader
is referred to an excellent recent review by Walton in
which the ‘tyranny of tin’ is discussed in some detail.3
Stannanes, however, possess several features which are
desirable from the viewpoint of the free-radical chemist;
these include the ability to sustain chain reactions due to
well-matched rate constants for the transfer of a hydro-
gen atom to alkyl and other radicals,3 and for the reac-
tion of the ensuing stannyl radical with a wide variety of
radical precursors.3
Se
CO2Et
The radical
precursor
4
EtO2C
fast
Se
SeR
5
3
R
EtO2C
CO2Et
SePh
2
EtO2C
CO2Et
The chain-carrying
radical
1
RSePh
The reagent
6
The by-product
EtO2C
SeR
EtO2C
SePh
7
With our considerable experience in the use of intramo-
lecular homolytic substitution chemistry for the prepa-
ration of selenium-containing heterocycles,4 and with the
knowledge that radicals derived from diethyl 2-phenyl-
selenomalonate (1) undergo efficient intermolecular
addition chemistry,5 we began to explore the possibility
of sustaining the radical chain depicted in Scheme 1. The
use of intramolecular homolytic substitution chemistry
to trigger the formation of radicals is not new. Crich
reported that intramolecular attack of aryl radicals at
sulfur can be used to generate acyl radicals;6 however,
since homolytic substitution at sulfur is a relatively slow
process,7 this technique is limited to the use of reactive
Scheme 1.
aryl radicals and substituents on sulfur devoid of abst-
ractable hydrogens. In a preliminary experiment, a
solution of pent-4-enyl benzyl selenide (3a) (112 mg)
and 1 (5 equiv) in benzene (2 mL) was irradiated for
12 h with a 250 W sun lamp at a distance of about
10 cm. To our delight, tetrahydroselenophene 5 was iso-
lated in 88% yield after flash chromatography. This
transformation clearly demonstrates the viability of the
proposed radical chain (Scheme 1). The success of this
tandem homolytic addition/substitution protocol from
such simple precursors under stannane-free conditions
represents an important new procedure for the prepara-
tion of selenium-containing rings and for the generation
*
Corresponding author. Tel.: +61 3 8344 2432; fax: +61 3 9347
8189; e-mail: carlhs@unimelb.edu.au
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.10.139

9078
S. Lobachevsky et al. / Tetrahedron Letters 48 (2007) 9077–9079
of radicals which may be further manipulated to provide
interesting new synthetic targets. To demonstrate the
scope of this chemistry, we subjected a range of radical
precursors 3 to the reaction conditions listed in Table 1.
The yields of 5 ranged from 28% to 88%, while the alkyl
phenyl selenide product 6 was isolated in yields of 28–
61% after chromatography.8
CO2Et
1
EtO2C
Ph
12
Se
Se
CO2Et
hν
EtO2C
13
EtO2C
CO2Et
Scheme 3.
We also examined the synthetic utility of alkynes (8) as
radical precursors. The data listed in Table 1 demon-
strate clearly that 8 is less effective than 3 as a radical
precursor.
Se
SePh
1
+
5
hν
O
O
It should be noted that other than the reaction involving
3a, the remaining precursors failed to react to comple-
tion; varying amounts of starting material were always
observed by 1H NMR spectroscopy. Increasing the reac-
tion time did not appear to improve the outcome. We
speculate that the addition of the diethyl malonyl radical
(2) to alkene 3 or alkyne 8 is reversible and, as a conse-
quence, the success of the overall transformation relies
on the leaving ability of radical (R). When R is a poor
leaving group (R = Bu), we observed poorer yields as
well as the formation of the trapped (uncyclized) prod-
ucts 7 and 9 (Scheme 2).
16
17
Scheme 4.
In an attempt to increase the overall reaction rate, the
benzyl selenide 12, bearing geminyl ester substituents,
was prepared and subjected to similar reaction condi-
tions. The cyclized product 13 was isolated in 68% yield
after photolysis in toluene (0.125 M) for 5 h (Scheme 3).
A similar yield of 5 was obtained from 3a after 17 h
under identical reaction conditions.
It is also interesting to note that precursor 3c leading to
acyl radical 14 afforded the phenylseleno ester 6c in 54%
yield under the conditions described, while precursor 3d
leading to the oxyacy radical 15 afforded the analogous
phenylseleno formate 6d in considerably lower yield.
These results suggest that despite obvious structural
similarities, the oxyacyl radical 15 is less stable than
the analogous acyl radical 14. These observations are
consistent with our previous report9 that (phenyltell-
uro)formates are more stable than (phenyltelluro)esters
and are supported by ab initio calculations.10
Table 1. Yields of products arising from the photolysis of precursors 3
and 8 in the presence of diethyl 2-(phenylseleno)malonate (1)
Precursor
Conc. Solvent
(M)
Yield (%)
5 or 11
6
7 or 9
3a (R = benzyl)
3b (R = CH2CO2Et) 0.18
3c (R = COPh)
3c
0.18
PhH
PhH
PhH
PhMe
PhH
PhH
PhH
PhH
PhMe
PhH
PhH
PhH
PhH
PhH
88
74
55
80
32
56a
—
47a
—
60
28
39
51
59
Nd
61
—
—
—
0.18
0.125
0.18
0.07
0.18
0.07
0.07
0.18
54
70a
28
3d (R = CO2Ph)
3e (R = iso-propyl)
3f (R = n-butyl)
3f
40
47a 11a
O
O
—
55
Ph
14
PhO
15
Nd 20a
3g (R = Ph)
8a (R = benzyl)
8b (R = CH2CO2Et) 0.18
8b
8c (R = COPh)
8c
—
52
36a
37a
Nd
Nd
46
—
—
—
—
—
Finally, we examined the analogous reaction of precur-
sor 16. To our delight, when 16 (0.07 M in benzene) was
subjected to the previously described reaction condi-
tions, tetrahydrofuran (17) was isolated in 69% yield
(Scheme 4),11 demonstrating the synthetic potential of
this protocol.
0.07
0.18
0.07
Nd = yield not determined.
a Yield determined by 1H NMR spectroscopy of the crude reaction
mixture.
Acknowledgement
EtO2C
EtO2C
R
EtO2C
EtO2C
1
1
We thank the Australian Research Council through the
Centres of Excellence program for generous support.
SeR
Se
SeR
SePh
hν
10
9
8
References and notes
CO2Et
EtO2C
1
Se
1. Howe, P.; Watts, P. Conc. Int. Chem. Assess. Doc. 2005,
65, 1.
6
R
+
2. (a) Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188, and
references cited therein; (b) Chatgilialoglu, C.; Griller, D.;
Lesage, M. J. Org. Chem. 1988, 53, 3641; (c) Ballestri, M.;
11
Scheme 2.

S. Lobachevsky et al. / Tetrahedron Letters 48 (2007) 9077–9079
9079
Chatgilialoglu, C.; Clark, K. B.; Griller, D.; Giese, B.;
Kopping, B. J. Org. Chem. 1991, 56, 678; (d) Davies, A. G.
Organotin Chemistry; VCH: Weinheim, 1997; (e) Neu-
mann, W. P. Synthesis 1987, 665; (f) Curran, D. P.
Synthesis 1988, 417; (g) Curran, D. P. Synthesis 1988, 489;
(h) Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev.
1991, 91, 1237; (i) Crich, D.; Sun, S. J. Org. Chem. 1996,
61, 7200.
L. J.; Schiesser, C. H.; Sutej, K. Tetrahedron 1993, 49,
2557.
5. Byers, J. H.; Lane, G. C. J. Org. Chem. 1993, 58, 3355.
6. (a) Crich, D.; Yao, Q. J. Org. Chem. 1996, 61, 3566; (b)
Crich, D.; Hao, X. J. Org. Chem. 1997, 62, 5982.
7. Schiesser, C. H.; Wild, L. M. Tetrahedron 1996, 52, 13265.
8. In cases where it was not possible to fully separate the
reaction mixture, yields are estimated from 1H NMR
spectra of mixtures.
9. Schiesser, C. H.; Skidmore, M. A. J. Org. Chem. 1998, 63,
5713.
10. Morihovitis, T.; Schiesser, C. H.; Skidmore, M. A. J.
Chem. Soc., Perkin Trans. 2 1999, 2041.
3. Baguley, P. A.; Walton, J. C. Angew. Chem., Int. Ed. 1998,
37, 3073, and references cited therein.
4. (a) Schiesser, C. H. Chem. Commun. 2006, 4055; (b)
Fenner, T.; White, J. M.; Schiesser, C. H. Org. Biomol.
Chem. 2006, 4, 1067; (c) Carland, M. W.; Martin, R. L.;
Schiesser, C. H. Org. Biomol. Chem. 2004, 2, 2612; (d) Al-
Maharik, N.; Engman, L.; Malmstro¨m, J.; Schiesser, C. H.
J. Org. Chem. 2001, 66, 6286; (e) Lyons, J. E.; Schiesser, C.
H.; Sutej, K. J. Org. Chem. 1993, 58, 5632; (f) Benjamin,
11. This reaction failed to go to completion; yields are based
on the recovered starting material. Compound 17 was
accompanied by about 30% of the uncyclized (addition)
product 7.