Free-Radical Chemistry of Lactones Fragmentation of β-Lactones. The Beneficial Effect of Catalytic Benzeneselenol on Chain Propagation

Full text of DOI:10.1021/jo971712j

8624
J . Org. Chem. 1997, 62, 8624-8625
Sch em e 1
Sch em e 2
F r ee-Ra d ica l Ch em istr y of La cton es:
F r a gm en ta tion of â-La cton es. Th e
Ben eficia l Effect of Ca ta lytic
Ben zen eselen ol on Ch a in P r op a ga tion
David Crich* and Xue-Sheng Mo
Department of Chemistry, University of Illinois at Chicago,
845 West Taylor Street, Chicago, Illinois 60607-7061
Received September 15, 1997
It is widely appreciated that oxiranylcarbinyl radicals
undergo reversible1,2 ring opening some 2 or more orders
of magnitude more rapidly than the corresponding cy-
clopropylcarbinyl radicals.3-7 In these reactions, the
C-O bond is typically cleaved in preference to the C-C
bond (Scheme 1). Likewise, it is well-known that cy-
clobutylcarbinyl radicals undergo ring opening several
orders of magnitude more slowly than cyclopropylcarbinyl
radicals: as such they are rarely used in synthetic
schemes.8-10 Thus stimulated, we hypothesized that the
strategic inclusion of an oxygen in a cyclobutylcarbinyl
radical, as in a 2-oxetanylcarbinyl or 2-oxetanon-4-
ylcarbinyl radical, would lead to a substantial accelera-
tion in the rate of ring opening. We further reasoned
that ring opening would occur by preferential cleavage
of a C-O rather than a C-C bond. This line of reasoning
finds support in an isolated example of fragmentation of
a 2-oxetanylcarbinyl radical, with cleavage of the C-O
bond, described by the Kim group.11 Such ring openings
of â-lactones would stand in contrast to the ring contrac-
tions and/or expansions of similarly constituted higher
homologs12 and, more generally, with the chemistry of
â-(acyloxy)alkyl radicals, which is characterized by a
series of 1,2- and 2,3-shifts proceeding via polarized
three-electron-three-center and five-electron-five-center
cyclic transition states.13 The fragmentation of â-(acy-
loxy)alkyl radicals to alkenes and carboxyl radicals is an
extremely rare event and occurs only when an excep-
tional thermodynamic driving force is provided.14
Sch em e 3
carboxyl radical 3, which then decarboxylates to provide
4. A second electron transfer then gives the correspond-
ing triarylmethyl anion, which on workup, provides 5
(Scheme 2). However, we also recognize the possibility
that the second electron transfer could occur at the level
of 2 and that we might be observing an anionic fragmen-
tation and decarboxylation sequence.
To provide unambiguous evidence for the radical
fragmentation, we turned to the reaction of 6 with tri-
butyltin hydride, initiated by AIBN.16 When the reaction
was conducted at either reflux, or at room temperature
under irradiation from a sunlamp, diphenylmethane was
isolated typically in 60-65% yield. This suggests that
the initial radical (7) does indeed undergo rapid frag-
mentation, followed by decarboxylation (Scheme 3). The
product (10) must arise from oxidation either of 9 or of a
cyclohexadiene formed following chain transfer with Bu3-
SnH.
In a preliminary experiment, the known, spirocyclic
Hydrogenation of 6 over Pt/C provided the saturated
analogue 11 in 65% isolated yield. On irradiation with
a sunlamp at 60 °C, a mixture of 11, Bu3SnH, and AIBN
provided a 22% yield of an 88:12 mixture of the alkenes
12 and 13 and a 31% yield of their assorted dimers.
15
â-lactone 1 was exposed to SmI2 (2 equiv) in THF at
-78 °C resulting, after workup, in the isolation of 5 in
76% yield. We rationalize this result in terms of rapid
fragmentation of the initial Sm(III) ketyl 2 to give
(1) Marples, B. A.; Rudderham, J . A.; Slawin, A. Z.; Edwards, A. J .;
Hird, N. W. Tetrahedron Lett. 1997, 38, 3599-3602.
(2) Ziegler, F. E.; Petersen, A. K. J . Org. Chem. 1995, 60, 2666-
2667.
(3) Newcomb, M. Tetrahedron 1993, 49, 1151-1176.
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917-918.
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1573.
(7) Krosley, K. W.; Gleicher, G. J . J . Phys. Org. Chem. 1993, 6, 228-
232.
Clearly, the initial radical undergoes rapid cleavage of
the â-lactone C-O bond followed by decarboxylation. This
provides an allyl radical (14) that gives rise to 12 and
13, by chain transfer with Bu3SnH, and to the various
dimers. As in the reaction of 6, as much as 40 mol % of
AIBN was required to drive the reaction to completion.
We reasoned that, under the dilute conditions employed,
allyl radical 14 does not react efficiently with the stan-
nane, resulting in a breakdown of chain propagation. We
hypothesized that a catalytic quantity of PhSeSePh,
reduced in situ to PhSeH (and Bu3SnSePh)17-19 with its
(8) Crimmins, M. T.; Mascarella, S. W. Tetrahedron Lett. 1987, 28,
5063-5066.
(9) Crimmins, M. T.; Wang, Z.; McKerlie, L. A. Tetrahedron Lett.
1996, 37, 8703-8706.
(10) Boivin, J .; Fouquet, E.; Zard, S. Z. J . Am. Chem. Soc. 1991,
113, 1055-1057.
(11) Kim, S.; Lim, K. M. J . Chem. Soc., Chem. Commun. 1993,
1152-1153.
(12) Crich, D.; Beckwith, A. L. J .; Filzen, G. F.; Longmore, R. W. J .
Am. Chem. Soc. 1996, 118, 7422-7423.
(13) Beckwith, A. L. J .; Crich, D.; Duggan, P. J .; Yao, Q. Chem. Rev.
(Washington, D.C.) 1997, 97, in press.
(14) Barton, D. H. R.; Dowlatshahi, H. A.; Motherwell, W. B.;
Villemin, D. J . Chem. Soc., Chem. Commun. 1980, 732-733.
(15) Molander, G. A.; Harris, C. R. Chem. Rev. (Washington, D.C.)
1996, 96, 307-338.
(16) Blank experiments demonstrated that the various â-lactones
were thermally stable under the conditions employed for the radical
fragmentations.
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Communications
J . Org. Chem., Vol. 62, No. 25, 1997 8625
superior hydrogen-atom-donating capacity,20 would over-
come this problem. In the event, both at reflux and at
40 °C, the inclusion of 10 mol % of PhSeSePh in the
reaction mixture enabled the amount of AIBN to be
reduced to 10 mol % when smooth conversion of substrate
to alkene 12 (84% isolated yield) was still observed. It
is noteworthy that no dimers were formed in this PhSeH-
catalyzed reaction, indicating that the selenol is efficient
in the quenching of allyl radical 14. Moreover, quenching
of 14 was highly regioselective, providing only 12 (12:13
g 95:5).
It is noteworthy in the reaction of both 11 and 18 with
Bu3SnH and catalytic PhSeH, and in the reaction of 6
with Bu3SnH alone, that the products of simple reduction
(i.e., replacement of Br by H) were not observed (<5%).
This suggests that the key radical fragmentation reaction
is a relatively rapid process and that synthetic chemists
preparing â-lactones by a halolactonization/radical de-
halogenation sequence may encounter problems.
A
search of the literature revealed two such sequences.
Mead reported dehalogenation of 20 to occur with Bu3-
SnH, giving 21 in 72% yield for a reaction conducted at
-78 °C,22 and Shibata claimed an 89% yield of 23 on
treatment of 22 with Bu3SnH (0.5 M) at reflux in
benzene.23 The implication is that the fragmentation
A final example was provided by the halo lactone 18.
This was synthesized in a straightforward manner by
Wittig olefination of 15 to give 16, followed by saponifica-
tion to 17 and bromolactonization in the kinetic mode.21
may be prevented by working at a sufficiently low
temperature (Mead) or with a high concentration of Bu3-
SnH (Shibata). A full kinetic characterization of the
reactions of oxetanonylcarbinyl radicals, which we hope
will help to illuminate the situation, will be undertaken
and reported on in due course.
Treatment of 18 with Bu3SnH and AIBN alone was again
inefficient, owing to poor chain propagation by the
intermediate allyl radical. However, exposure of 18 to
Bu3SnH and 5 mol % of PhSeSePh, with initiation by only
5 mol % of di-tert-butyl peroxalate at room temperature,
resulted in the isolation of alkene 19 in 78% yield. This
again demonstrates the facile cleavage of the â-lactone
ring and the ability of PhSeH to transfer a hydrogen atom
to relatively unreactive radicals.
Ack n ow led gm en t . We thank the NSF (CHE
9625256) for support of this work.
Su ppor tin g In for m ation Available: Characterization data
(4 pages).
J O971712J
(17) Crich, D.; Yao, Q. J . Org. Chem. 1995, 60, 84-88.
(18) Crich, D.; J iao, X.-Y.; Yao, Q.; Harwood, J . S. J . Org. Chem.
1996, 61, 2368-2373.
(22) Mead, K. T.; Park, M. Tetrahedron Lett. 1995, 36, 1205-1208.
(23) Shibata, I.; Toyota, M.; Baba, A.; Matsuda, H. J . Org. Chem.
1990, 55, 2487-2491. Note that in this example the product of the
radical reaction would likely have gone unnoticed and that the yield
given in the text is not supported in the Experimental Section of the
paper.
(19) Crich, D.; Hwang, J .-T.; Liu, H. Tetrahedron Lett. 1996, 37,
3105-3108.
(20) Newcomb, M.; Varick, T. R.; Ha, C.; Manek, M. B.; Yue, X. J .
Am. Chem. Soc. 1992, 114, 8158-8163.
(21) Pommier, A.; Pons, J .-M. Synthesis 1993, 441-459.