Construction of tetrahydrofuran-3-ones from readily available organochalcogen precursors via radical carbonylation/reductive cyclization

Article abstract of DOI:10.1021/ol016127q

(matrix presented) β-Hydroxyalkyl aryl chalcogenides, readily available by regioselective ring-opening of epoxides with nucleophilic benzeneselenolate or tellurolate, were O-alkylated by treatment with ethyl propiolate or (E)-1,2-bis(phenylsulfonyl)ethyle

Full text of DOI:10.1021/ol016127q

ORGANIC
LETTERS
2002
Vol. 4, No. 1
3-6
Construction of Tetrahydrofuran-3-ones
from Readily Available Organochalcogen
Precursors via Radical Carbonylation/
Reductive Cyclization
Stefan Berlin, Cecilia Ericsson, and Lars Engman*
Uppsala UniVersity, Institute of Chemistry, Department of Organic Chemistry,
Box 531, S-751 21, Uppsala, Sweden
lars.engman@kemi.uu.se
Received May 15, 2001 (Revised Manuscript Received November 21, 2001)
ABSTRACT
â-Hydroxyalkyl aryl chalcogenides, readily available by regioselective ring-opening of epoxides with nucleophilic benzeneselenolate or tellurolate,
were O-alkylated by treatment with ethyl propiolate or (E)-1,2-bis(phenylsulfonyl)ethylene. Subsequent carbonylation/reductive cyclization in
the presence of AIBN/TTMSS and carbon monoxide (80 atm) afforded tetrahydrofuran-3-ones in moderate to good yields.
As a result of recent interest in radical-mediated synthesis,
acyl radical chemistry has also seen a renaissance.1 Acyl
radicals take part in a large variety of inter- and intramo-
lecular reactions and are therefore useful synthetic intermedi-
ates.2 These species are commonly generated by homolysis
of an acyl-X bond, where X could be hydrogen, halogen,
chalcogen, or a metal. Since most of these derivatives suffer
from certain shortcomings in radical processes, i.e., inef-
ficient chain-transfer, over-reduction, or poor reactivity
toward stannyl or silyl radicals, selenol esters have become
the most versatile precursors for acyl radicals.3 As demon-
strated by Ryu and co-workers, acyl radicals can also be
readily formed by reaction of alkyl radicals with carbon
monoxide.1,4,5 These carbonylation reactions are commonly
performed as one-pot reactions with 60-80 atm of CO,
conditions which can easily be obtained by using an ordinary
autoclave. Primary, secondary, and tertiary radicals can be
efficiently carbonylated and further transformed in more or
less elaborate ways into carbonyl derivatives such as alde-
hydes,6 ketones,7 esters,8 lactones,9 thiolactones,10 amides,11
(4) Ryu, I.; Sonoda, N. Angew. Chem., Int. Ed. Engl. 1996, 35, 1050.
Ryu, I.; Sonoda, N.; Curran, D. P. Chem. ReV. 1996, 96, 177.
(5) Ryu, I. Chem. Soc. ReV. 2001, 30, 16.
(6) Ryu, I.; Kusano, K.; Ogawa, A.; Kambe, N.; Sonoda, N. J. Am. Chem.
Soc. 1990, 112, 1295.
(7) Ryu, I.; Kusano, K.; Yamazaki, H.; Sonoda, N. J. Org. Chem. 1991,
56, 5003. Ryu, I. Yamazaki, H.; Kusano, K.; Ogawa, A.; Sonoda, N. J.
Am. Chem. Soc. 1991, 113, 8558. Ryu, I.; Yamazaki, H.; Ogawa, A.; Kambe,
N.; Sonoda, N. J. Am. Chem. Soc. 1993, 115, 1187. Brinza, I. M.; Fallis,
A. G. J. Org. Chem. 1996, 61, 3580. Nagahara, K.; Ryu, I.; Yamazaki, H.;
Kambe, N.; Komatsu, M.; Sonoda, N.; Baba, A. Tetrahedron 1997, 53,
14615.
(8) Nagahara, K.; Ryu, I.; Komatsu, M.; Sonoda, N. J. Am. Chem. Soc.
1997, 119, 5465.
(9) Tsunoi, S.; Ryu, I.; Okuda, T.; Tanaka, M.; Komatsu, M.; Sonoda,
N. J. Am. Chem. Soc. 1998, 120, 8692. Kreimerman, S.; Ryu, I.; Minakata,
S.; Komatsu, M. Org. Lett. 2000, 2, 389.
(10) Ryu, I.; Okuda, T.; Nagahara, K.; Kambe, N.; Komatsu, M.; Sonoda,
N. J. Org. Chem. 1997, 62, 7550.
(11) Ryu, I.; Nagahara, K.; Kambe, N.; Sonoda, N.; Kreimerman, S.;
Komatsu, M. J. Chem. Soc., Chem. Commun. 1998, 1953.
(1) Chatgilialoglu, C.; Crich, D.; Komatsu, M.; Ryu, I. Chem. ReV. 1999,
99, 1991.
(2) For representative examples of acyl radical cyclizations, see: Boger,
D. L.; Mathvink, R. J. J. Am. Chem. Soc. 1990, 112, 4003. Boger, D. L.;
Mathvink, R. J. J. Am. Chem. Soc. 1990, 112, 4008. Boger, D. L.; Mathvink,
R. J. J. Org. Chem. 1992, 57, 1429. Crich, D.; Chen, C.; Hwang, J.-T.;
Yuan, H.; Papadatos, A.; Walter, R. I. J. Am. Chem. Soc. 1994, 116, 8937.
Crich, D.; Yao, Q. J. Org. Chem. 1996, 61, 3566. Crich, D.; Hao, X. J.
Org. Chem. 1997, 62, 5982. Chen, L.; Gill, G. B.; Pattenden, G.; Simonian,
H.. J. Chem. Soc., Perkin Trans. 1 1996, 31. Batsanov, A.; Chen, L.; Gill,
G. B.; Pattenden, G. J. Chem. Soc., Perkin Trans. 1 1996, 45, Pattenden,
G.; Roberts, L.; Blake, A. J. J. Chem. Soc., Perkin Trans. 1 1998, 863.
(3) Renaud, P. In Topics in Current Chemistry; Wirth, T.; Ed.; Springer-
Verlag: Berlin Heidelberg, 2000; Vol 208, p 81.
10.1021/ol016127q CCC: $22.00 © 2002 American Chemical Society
Published on Web 12/14/2001

lactams,12 and acyl selenides.13 Atom or group transfer, inter-
or intramolecular radical addition, cascade reactions, radical
translocation, one-electron oxidation, or ionic chemistry are
noteworthy features of these transformations.
Scheme 2a
It occurred to us that radical carbonylation/reductive
cyclization could provide easy access to 2,5-disubstituted
tetrahydrofuran-3-ones from readily available organochal-
cogen precursors. Evans and co-workers have already shown
that cyclic ethers can be efficiently prepared by using
intramolecular acyl radical cyclizations (Scheme 1).14,15 By
a (i) (PhSe)2 or (ArTe)2, NaBH4; (ii) ethyl propiolate, NMM or
(E)-1,2-bis(phenylsulfonyl)ethylene, NaH; (iii) AlBN, TTMSS, CO
80 atm.
Scheme 1
The O-vinylation proceeded smoothly at room temperature
to give radical precursors 2a-k in 64-95% isolated yields
as pure E-isomers (Table 1). However, attempts to prepare
a tertiary alcohol radical precursor 2l failed (Table 1, entry
12).
Carbonylation/radical cyclization was conducted in an
autoclave equipped with a stirring rod. To find proper
reaction conditions, selenide 2a was carbonylated/cyclized
under various conditions (Table 2). The use of tri-n-butyltin
hydride as a hydrogen atom donor was found to cause
formation of substantial amounts of reduced product 4. Better
results were obtained using tris(trimethylsilyl)silane (TT-
MSS). With carbon monoxide at 80 atm, an 86% yield of
compound 3a as a 9:1 mixture of cis and trans isomers was
obtained. At lower pressures (60 atm), reduction of the
starting material again started to become a significant side
reaction. Tri-n-butylgermane was also tried as a hydrogen
atom donor, but found inferior to TTMSS. Thus, subsequent
carbonylation/reductive cyclizations were carried out using
TTMSS as a hydrogen atom donor and CO at 80 atm
(Table 1).
generating acyl radicals directly from alkyl radicals and
carbon monoxide (Scheme 1), one could approach these
systems in a different way, using more readily available
starting materials. Also, radical decarbonylation, a sometimes
unwanted side-reaction, could be suppressed.4,14a,b
Some time ago, we showed that epoxides can be regiose-
lectively ring-opened by benzeneselenolate or benzenetel-
lurolate to furnish â-hydroxyalkyl phenyl chalcogenides 1.16
For preparation of 2,5-disubstituted tetrahydrofuran-3-ones
by radical carbonylation/reductive cyclization, â-hydroxy-
alkyl phenyl selenides 1 were allowed to undergo hetero-
Michael addition14a-c,15b,17 to ethyl propiolate or to act as
nucleophiles in the vinylogous substitution of (E)-1,2-bis-
(phenylsulfonyl)ethylene14d,15a (Scheme 2).
As shown in Table 1 (entries 1-4), organotellurium
precursors 2b and 2d performed almost as well as their
organoselenium counterparts in the chemistry developed. The
unexpectedly low yield of compound 3c was a consequence
of a competing 1,5 hydrogen atom shift/6-exo-cyclization
(Scheme 3). This gave rise to byproduct 5 which was isolated
in 32% yield starting from compound 2c and 30% starting
from 2d. Only one diastereomer of dioxan 5 was isolated,
with all three substituents occupying equatorial positions.
In a separate experiment carried out in the absence of CO,
the dioxane derivative 5 was isolated in 82% yield along
with 3% reduced starting material.
(12) Ryu, I.; Matsu, K.; Minakata, S.; Komatsu, M. J. Am. Chem. Soc.
1998, 120, 5838.
(13) Ryu, I.; Muraoka, H.; Kambe, N.; Komatsu, M.; Sonoda, N. J. Org.
Chem. 1996, 61, 6396.
(14) (a) Evans, P. A.; Roseman, J. D. Tetrahedron Lett. 1995, 36, 31.
(b) Evans, P. A.; Roseman, J. D. J. Org. Chem. 1996, 61, 2252. (c) Evans,
P. A.; Murthy, V. S.; Roseman, J. D.; Rheingold, A. L. Angew. Chem., Int.
Ed. 1999, 38, 3175. (d) Evans, P. A.; Manangan, T. J. Org. Chem. 2000,
65, 4523.
(15) (a) Evans, P. A.; Roseman, J. D. Tetrahedron Lett. 1997, 38, 5249.
(b) Evans, P. A.; Roseman, J. D.; Garber, L. T. J. Org. Chem. 1996, 61,
4880.
(16) Engman, L.; Gupta, V. J. Org. Chem. 1997, 62, 157.
(17) Tiecco, M.; Testaferri, L.; Tingoli, M.; Marini, F. J. Org. Chem.
1993, 58, 1349. Mitsudera, H.; Kakehi, A.; Kamimura, A. Tetrahedron Lett.
1999, 40, 7389. Leeuwenburgh, M. A.; Litjens, R. E. J. N.; Code´e, J. D.
C.; Overkleeft, H. S.; van der Marel, G. A.; van Boom, J. H. Org. Lett.
2000, 2, 1275.
It is also noteworthy that the benzylic radical formed from
compound 2e (Table 1, entry 5) failed to undergo carbony-
lation/5-exo-cyclization. Only reduced starting material was
formed in 56% yield. However, this is in accord with
previous observations that carbonylated stabilized radicals
(benzylic, allylic, tertiary) decarbonylate more rapidly than
other acyl radicals.1 Carbonylation/cyclization of radical
precursors 2f-i afforded 2,5-disubstituted tetrahydrofuran-
3-ones in moderate to good yields. The â-hydroxyalkyl
phenyl selenides originating from 1,2-disubstituted epoxides
(Table 1, entries 10-11) furnished 2,4,5-trisubstituted tet-
4
Org. Lett., Vol. 4, No. 1, 2002

Table 1. Radical Precursors and Their Conversion to Tetrahydrofuran-3-ones
a Isolated yield in percent. b Inseparable mixture of diastereomers.
rahydrofuran-3-ones as inseparable mixtures of diastereo-
mers. It seems that carbonylation of the secondary alkyl
radical produces both of the possible (cis/trans) diastereo-
meric acyl radicals, which then undergo 5-exo-cycliza-
tion.
experiments. A 1,3 NOE was always seen for the cis isomer.
The selective formation of cis-2,5-disubstituted tetrahydro-
furan-3-ones follows from the Beckwith-Houk rules for ring
closure, assuming that the 2,5-substituents are both pseu-
doequatorial in the chairlike transition state.18 Some attempts
were also made to epimerise the diastereomeric mixture of
cis/trans 2,5-disubstituted tetrahydrofuran-3-ones. By treat-
The stereochemistry of the 2,5-disubstituted tetrahydro-
furan-3-ones prepared was assigned by using 2D NOESY
Org. Lett., Vol. 4, No. 1, 2002
5

Scheme 3
Table 2. Optimization of Carbonylation/Reductive Cyclization
cyclization. As compared with the cyclization of acyl radicals
as reported by Evans,14b,c cyclization yields were usually
somewhat lower. However, considering the availability of
the organoselenium radical precursors from epoxides, the
methodology reported herein would seem useful for the
construction of a variety of cyclic ethers.
a Isolated yield.
ment of compound 3a with 0.1 equiv of DBU in refluxing
benzene, the cis/trans ratio could not be improved more than
to 1:2.
In conclusion, we have shown that substituted tetrahydro-
furan-3-ones are easily prepared from O-vinylated-â-hy-
droxyalkyl phenyl chalcogenides via carbonylation/reductive
Acknowledgment. We thank the Swedish Natural Sci-
ence Research Council for financial support.
Supporting Information Available: Experimental pro-
cedures and characterization data for new compounds
prepared. This material is available free of charge via the
Internet at http://pubs.acs.org.
(18) Beckwith, A. L. J.; Easton, C. J.; Serelis, A. K. J. Chem. Soc., Chem.
Commun. 1980, 482. Beckwith, A. L. J.; Lawrence, T.; Serelis, A. K. J.
Chem. Soc., Chem. Commun. 1980, 484. Beckwith, A. L. J.; Schiesser, C.
H. Tetrahedron 1985, 41, 3925. Spellmeyer, D. C.; Houk, K. N. J. Org.
Chem. 1987, 52, 959.
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