Alkoxy radical accelerated β-fragmentation of alcohols and lactols

Article abstract of DOI:10.1016/S0040-4039(01)00121-6

Treatment of alcohols and lactols with Pb(OAc)₄/Cu(OAc)₂ in refluxing benzene provides the corresponding δ-unsaturated carbonyl products.

Full text of DOI:10.1016/S0040-4039(01)00121-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2047–2049
Alkoxy radical accelerated b-fragmentation of alcohols and
lactols
James H. Rigby,* Anne Payen and Namal Warshakoon
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA
Received 6 December 2000; accepted 17 January 2001
Abstract—Treatment of alcohols and lactols with Pb(OAc) /Cu(OAc) in refluxing benzene provides the corresponding d-unsatu-
4
2
rated carbonyl products. © 2001 Elsevier Science Ltd. All rights reserved.
Radical-mediated fragmentation of hydroxyl group
based functionalities has been an area of considerable
activity over the years. In conjunction with a recent
An extensive examination of the scope and limitations of
this fragmentation process has been conducted and the
1
6
results of this study are detailed below. While, in general,
synthesis of (+)-estradiol, we required a fragmentation
simple alcohol substrates were found not to be viable
fragmentation participants, a range of strained alcohols
and lactols proved to be effective reactants.
method that would involve direct production of an
2
alkene during the bond-breaking step. After consider-
able experimentation, it was discovered that a combina-
tion of Pb(OAc) with a catalytic quantity of Cu(OAc)
7
In a typical example, cleavage of lactol 3 under the
4
2
3
efficiently converted compound 1 into 2, which was
subsequently transformed into the steroid via a novel
higher-order cycloaddition–Ramberg–B a¨ cklund sequen-
ce (Eq. (1)). Related conditions had been briefly exam-
mixed Pb(IV)/Cu(II) conditions afforded the corre-
sponding bicyclic alkene–formate 4 in serviceable yields
(Eq. (2)). In many cases mixtures of fragmentation
products were produced. For instance, (−)-borneol pro-
vided a mixture of isomeric fragmentation products 6 and
7 in good yield (Eq. (3)), and the closely related
substrate, fenchyl alcohol, gave a mixture of ring cleaved
3
4
ined previously for the cleavage of alcohols, and
8
Pb(OAc) is, of course, well known to effect decarboxyl-
4
5
ation of carboxylic acids.
(1)
(
(
2)
3)
Keywords: fragmentation reactions; radicals and radical reactions; alcohols; alkenes.
*
Corresponding author.
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00121-6

2
048
J. H. Rigby et al. / Tetrahedron Letters 42 (2001) 2047–2049
(
(
4)
5)
(
(
6)
7)
products comprised of all possible double bond isomers
in 50% yield.
(8)
In another illustration of the general nature of these
9
conditions, the fragmentation of bicyclic lactols 8a and
1
0
3
8b
gave the expected ring-cleaved lactones 9a and 9b
the ring-opened forms of 11a and 11b lead to 13a and
13b, respectively, via a hydrogen atom extraction–elec-
in good yield without incident (Eq. (4)).
14
tron transfer–trapping sequence.
Interestingly, the corresponding phenyl substituted lac-
1
1
tol 8c afforded the expected fragmentation product
In conclusion, a new and versatile method for alcohol
and lactol fragmentation has been developed using a
mixture of Pb(OAc) /Cu(OAc) in refluxing benzene.
4 2
3
9
c, accompanied by a moderate amount of the spiro-
3
lactone 10 (Eq. (5)). The latter compound is pre-
sumably derived from competitive homolytic
a
12
aromatic substitution process, or, alternatively, it may
be formed by trapping of a carbocation intermediate
produced during the bond breaking event. Efforts to
increase the proportion of 10 relative to 9c by adjusting
the ratio of Pb(OAc) :Cu(OAc) were not successful.
Acknowledgements
The authors wish to thank the National Institutes of
Health (GM-30771) for their generous support of this
research.
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2
Yet another intriguing side-reaction was observed dur-
ing attempted fragmentation of the bicyclic lactols 11a
and 11b. Each material led, on exposure to the standard
fragmentation conditions, to a moderate amount of the
desired lactone along with varying quantities of an
interesting spirocyclic ether by-product. Thus, lactol
References
1. For some leading references to other fragmentation pro-
cedures, see: (a) HgO/I : Suginome, H.; Yamada, S. J.
2
1
1a yielded cleavage product 12a as well as a small
Org. Chem. 1985, 50, 2489; Tetrahedron 1987, 43, 3371;
(b) Pb(OAc) /I : Fuhrer, H.; Lorenc, L.; Pavlovic, V.;
Rihs, G.; Rist, G.; Kalvoda, J.; Mihailovic, M. Lj. Helv.
1
3
quantity of ether 13a (Eq. (6)), while 11b gave a much
4
2
higher overall yield of products (Eq. (7)), now favoring
the production of ether 13b over the corresponding
lactone, 12b.
3
Chim. Acta 1981, 64, 703; (c) IBDA/I : Freire, R.; Mar-
2
3
rero, J. J.; Rodr ´ı guez, M. S.; Su a´ rez, E. Tetrahedron Lett.
1
986, 27, 383; (d) Iodosyl-benzene/I : Arrmas, P.; Fran-
2
In contrast, compound 14, which appears to exist exclu-
cisco, C. G.; Su a´ rez, E. Tetrahedron Lett. 1993, 34, 7331;
(e) FeSO /Cu(OAc) : Schreiber, S. L. J. Am. Chem. Soc.
1980, 102, 6163; (f) Pb(OAc)4 with g-hydroxyalkylstan-
nanes: Nakatani, K.; Isoe, S. Tetrahedron Lett. 1984, 25,
sively in the opened keto-alcohol form, gave only the
4
2
3
corresponding spiro-ether 13c in 34% yield (Eq. (8)).
This observation provides support for the notion that

J. H. Rigby et al. / Tetrahedron Letters 42 (2001) 2047–2049
2049
5
335; (g) Mn(OAc) /Cu(OAc) : Heiba, E. I.; Dessau, R. M.
mixture was heated to reflux while monitoring the progress
of the reaction by TLC (mixture turns blue-green when the
reaction is completed, ca. 20 min). At completion of the
reaction, the mixture was filtered through a thin pad of
Celite.
3
2
J. Am. Chem. Soc. 1971, 93, 524.
. Rigby, J. H.; Warshakoon, N. C.; Payen, A. J. J. Am.
Chem. Soc. 1999, 121, 8237.
. All new compounds exhibited spectral ( H NMR,
2
3
1
13
C
NMR, IR) and analytical (combustion analysis and/or
HRMS) data fully consistent with the assigned structures.
. (a) Kapustina, N. I.; Popkov, A. Y.; Gasanov, R. G.;
Nikishin, G. I. Izv. Akad. Nauk SSSR, Ser. Khim. 1988,
7. Suginome, H.; Yamada, S. Synthesis 1986, 741.
8. For a related result with Pb(OAc)4 in the absence of
4
Cu(OAc) , see: Partch, R. E. J. Org. Chem. 1963, 28, 276.
2
9. Sassaman, M. B.; Prakash, G. K. S.; Olah, G. A. Tetra-
2
327; (b) Kapustina, N. I.; Soejtirm, S. S.; Nikishin, G. I.
hedron 1988, 44, 3771.
Izv. Akad. Nauk SSSR, Ser. Khim. 1984, 2721; (c) Nikishin,
G. I.; Kapustina, N. I. Izv. Akad. Nauk SSSR, Ser. Khim.
10. Kobayashi, K.; Sasaki, A.; Kanno, Y.; Suginome, H.
Tetrahedron 1991, 47, 7245.
1
984, 1345.
11. Lyttle, M. H.; Streitwieser, A.; Miller, M. J. J. Org. Chem.
5
6
. Sheldon, R. A.; Kochi, J. K. Org. React. 1972, 19, 279.
. Typical experimental procedure: An oven dried flask
equipped with a water reflux condenser was charged with
a lactol (1 equiv.), lead tetraacetate (1.6 equiv.), copper(II)
acetate (0.18 equiv.), pyridine (1.2 equiv.) and benzene. The
1989, 54, 2331.
12. Harvey, D. R.; Norman, R. O. C. J. Chem. Soc. 1964, 4860.
13. Paquette, L. A.; Negri, J. T.; Rogers, R. D. J. Org. Chem.
1992, 57, 3947.
14. Mihailovic, M. Lj.; Cekovic, Z. Synthesis 1970, 209.
.