Barium manganate in microwave-assisted oxidation reactions: synthesis of lactones by oxidative cyclization of diols

Article abstract of DOI:10.1016/j.tetlet.2009.09.117

Microwave irradiation of a range of diols at 150 °C in acetonitrile in the presence of three equivalents of barium manganate facilitates a novel tandem oxidation/heterocyclocondensation to give the corresponding lactone, including both small and medium ring lactones, in only one hour and in high yield without the need for chromatographic purification.

Full text of DOI:10.1016/j.tetlet.2009.09.117

Tetrahedron Letters 50 (2009) 6823–6825
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Barium manganate in microwave-assisted oxidation reactions: synthesis
of lactones by oxidative cyclization of diols
*
*
Mark C. Bagley , Zhifan Lin, David J. Phillips, Andrew E. Graham
School of Chemistry, Main Building, Cardiff University, Park Place, Cardiff CF10 3AT, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 July 2009
Accepted 21 September 2009
Available online 24 September 2009
Microwave irradiation of a range of diols at 150 °C in acetonitrile in the presence of three equivalents of
barium manganate facilitates a novel tandem oxidation/heterocyclocondensation to give the correspond-
ing lactone, including both small and medium ring lactones, in only one hour and in high yield without
the need for chromatographic purification.
Ó 2009 Elsevier Ltd. All rights reserved.
The oxidative cyclization of diols to lactones is an effective
route to valuable targets of broad applicability that has seen use
in natural product synthesis1 and in the preparation of synthetic
building blocks for fine chemical production.2 Despite the potential
for broad utility of this methodology, current procedures3 employ
expensive reagents or metal-based catalysts, which often require
prior preparation, very high temperatures, co-oxidants or hydro-
gen acceptors, protracted reaction times, inert conditions, special-
ist equipment, for example, in electrochemical processes,4 or
rigorous chromatographic purification of the products.
our previous findings that MnO2 can mediate the rapid oxidation
of heterocyclic precursors under microwave dielectric heating,11
and the precedent that MnO2 is an effective reagent for the oxida-
tion of lactols to lactones,12 we set out to investigate the desym-
metrization of diols using this reagent.
The manganese dioxide-mediated oxidative cyclization of 1,5-
pentanediol was studied initially under conductive heating (Table
1). Reactions were carried out with a large excess of oxidant
(20 equiv) in dichloromethane at room temperature which pro-
ceeded to give moderate amounts of d-valerolactone in addition to
considerable quantities of the corresponding lactol. It was found
that it was most efficient to carry out these reactions in chloroform
under reflux conditions to maximize the yield, although consider-
able quantities of the desired product were obtained at room tem-
perature after extended reaction times. Surprisingly, reactions
employing activated manganese dioxide produced no lactone prod-
uct at all with only starting material isolated, providing another
example of the importance in choosing the correct grade of oxidant.5
The cyclization reactions of a range of unactivated diols were
investigated under these conditions to assess the utility of the con-
We recently reported the desymmetrization of unactivated
diols by reaction with stabilized Wittig reagents in the presence
of an excess of manganese dioxide to give
a,b-unsaturated
hydroxyesters in a highly efficient one-pot procedure.5 It was
noted during these studies that in the case of 1,4- and 1,5-diols,
the yields of
a,b-unsaturated hydroxyesters were reduced by a
competing oxidative cyclization which produced the correspond-
ing lactones.6 Tandem oxidation processes involving manganese
dioxide are of particular current interest, especially those which in-
volve the formation of reactive carbonyl intermediates, and a num-
ber of transformations have been described.7 Our own studies8
have shown that a tandem oxidation/heterocyclocondensation
approach provides direct access to pyridines and pyrimidines from
propargylic alcohols. However, given the considerable attention
afforded to the desymmetrization of symmetrical diols, and the
lack of convenient methods by which this transformation can be
carried out,9 we set out to realize a new procedure for the desym-
metrization of diols by oxidative cyclization that was effective and
efficient in short reaction times, used commercially available and
cheap reagents, exhibited broad substrate scope, and provided
the lactone product without the need for lengthy purification re-
gimes. Given previous successes in realizing rapid methods to
functionalized heterocyclic targets using microwave irradiation,10
Table 1
Comparing conversions for the oxidative cyclization of pentane-1,5-diol using MnO2
(10
l
m) under conductive heating
OH
O
MnO2 (20 equiv.)
conductive heating
OH
O
Entry
Conditionsa
Conversionb (%)
1
2
3
4
CH2Cl2, rt, 20 h
CHCl3, rt, 20 h
CHCl3, reflux, 4 h
CHCl3, reflux, 20 h
30c
57c
29c
91
a
b
c
rt = room temperature.
Determined by 1H NMR spectroscopic analysis of the crude reaction mixture.
* Corresponding authors.
E-mail address: bagleymc@cardiff.ac.uk (M.C. Bagley).
Contained ꢀ40% lactol.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.09.117

6824
M. C. Bagley et al. / Tetrahedron Letters 50 (2009) 6823–6825
Table 2
Table 3
Comparing the isolated yield of d-valerolactone from the BaMnO4- and MnO2-
mediated oxidative cyclization under microwave irradiation with or without a SiC
passive heating element
Comparing the microwave-assisted oxidative cyclization of diols using BaMnO4 with
a MnO2-mediated conductive heating reaction
Entry Diola
Lactone productb
Yield%c Yield%d
Entry
Conditionsa
Yieldb (%)
MnO2/D BaMnO4/lx
1
2
3
4
MnO2 (10
BaMnO4, lx
MnO2 (10
l
m),
, MeCN, 150 °C, 1 h
m), , SiC PHE, MeCN, 150 °C, 1 h
BaMnO4, lx, SiC PHE, MeCN, 150 °C, 1 h
l
x
, MeCN, 150 °C, 1 h
60b
88c
84b
86c
OH
O
O
1
0e
76
70
60
l
lx
OH
a
Reaction was carried out under microwave irradiation (
lx
) at 150 °C for 1 h
with 3 equiv of oxidant in MeCN in a sealed tube (10 mL) using a CEM DiscoverÒ
microwave synthesizer by moderating the initial microwave power (150 W). SiC
PHE refers to the addition of a silicon carbide passive heating element (as supplied
from Anton Paar).
2
3
72
44
OH
O
O
OH
b
Yield% refers to isolated yield of lactone after purification by column chroma-
tography on silica gel.
Yield% refers to isolated yield of lactone after only a simple filtration through
Celite.
c
OH
O
O
OH
O
H
ductive heating reaction (see later in Table 3). Gratifyingly, diols
containing either primary, or both primary and secondary, alcohol
functionality underwent efficient oxidative cyclization to produce
lactone products in good to high yields. Interestingly, the oxidation
of 1,4-pentanediol and 1,5-hexanediol produced quantities of the
corresponding acyclic dicarbonyl compound (10 and 25%, respec-
tively) produced by oxidation of both the primary and the second-
ary alcohol functions. The method was effective for activated
alcohols which are much more readily oxidized and so shorter
reaction times could be employed. Thus, reaction of 1,2-benzenedi-
methanol at room temperature for 8 h produced the corresponding
lactone, but also gave quantities of the corresponding dialdehyde.
Disappointingly, however, reactions involving either 2-butene-
1,4-diol or diols containing heteroatoms in the chain gave only a
trace of the desired lactone product and were accompanied by con-
siderable amounts of degradation. Thus, although the method ap-
peared to offer promise, its somewhat limited substrate scope,
long reaction time, requirement for a large excess of oxidant, reli-
ance upon chlorinated solvents, and requirement for chromato-
graphic purification identified formidable challenges to overcome.
In order to reduce the large excess of oxidant that was needed
and simultaneously accelerate the process, the transformation
was next studied at elevated temperatures in a sealed vessel under
microwave irradiation. The oxidative cyclization of 1,5-pentane-
diol at 150 °C in an alternative non-chlorinated solvent, acetoni-
trile, using only three equivalents of MnO2 did provide the
d-valerolactone product; however the heating profile (Fig. 1) of
reaction demonstrated that at an initial power of 150 W the set
temperature was not attained and the yield of the product was
compromised as a consequence (Table 2, entry 1). By switching
H
H
OH
OH
4
5
6
7
87
64
74
81
80
80
88
87
O
H
O
O
OH
OH
OH OH
O
O
O
O
OH OH
8
9
62f
80
84
OH OH
O
O
0e
OH
O
O
OH
160
140
120
100
80
10
0e
78
OH
O
OH
O
a
b
c
All diols were used as supplied.
All products gave satisfactory spectroscopic and spectrometric data.
Reactions carried out in CHCl3 at reflux using 20 equiv of MnO2 (10
60
l
m). Yield%
refers to isolated yield of lactone after purification by column chromatography on
silica gel.
40
20
d
Reaction was carried out under microwave irradiation (lx) at 150 °C for 1 h
with 3 equiv of BaMnO4 in MeCN in a sealed tube (10 mL) using a CEM DiscoverÒ
microwave synthesizer by moderating the initial microwave power (150 W). Yield%
refers to isolated yield of lactone after only a simple filtration through Celite.
0
0
500
1000 1500 2000 2500 3000 3500 4000
Time / s
e
The reaction failed to give any more than a trace (<10%) of the desired lactone
product.
Figure 1. Heating profile under microwave irradiation with MnO2 (purple) and
BaMnO4 (black) without a SiC passive heating element.
f
The reaction was heated at reflux for 48 h.

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140
120
100
80
References and notes
1. (a) Suzuki, T.; Ohmori, K.; Suzuki, K. Org. Lett. 2001, 3, 1741–1744; (b) Zhu, X.;
Yu, B.; Hui, Y.; Higuchi, R.; Kusano, T.; Miyamoto, T. Tetrahedron Lett. 2000, 41,
717–719; (c) Amaike, M.; Mori, K. Liebigs Ann. 1995, 1451–1454; (d) Ley, S. V.;
Norman, J.; Pinel, C. Tetrahedron Lett. 1994, 35, 2095–2098; (e) Appendio, G.;
Valle, M. G.; Gariboldi, P. J. Chem. Soc., Perkin Trans. 1 1986, 1363–1372; (f)
Moret, E.; Schlosser, M. Tetrahedron Lett. 1984, 25, 4491–4494; (g) Imamura, P.
M.; Sierra, M. G.; Ruveda, E. A. Chem. Commun. 1981, 734–735.
60
40
2. (a) Gräfje, H.; Körnig, W.; Weitz, H.; Reiss, W. Ullmann’s Encyclopedia of
Industrial Chemistry, 6th ed.; Wiley-VCH: Weinheim, 2000; (b) Zhu, Y.-L.; Xiang,
H.-W.; Wu, G.-S.; Bai, L.; Li, Y.-W. Chem. Commun. 2002, 254–255.
3. (a) Shvo, Y.; Blum, Y.; Reshef, D.; Menzin, M. J. Organomet. Chem. 1982, 226,
C21–C25; (b) Tamaru, Y.; Yamada, Y.; Inoue, K.; Yamamoto, Y.; Yoshida, Z. J.
Org. Chem. 1983, 48, 1286–1292; (c) Ishii, Y.; Suzuki, K.; Ikariya, T.; Saburi, M.;
Yoshikawa, S. J. Org. Chem. 1986, 51, 2822–2824; (d) Ishii, Y.; Osakada, K.;
Ikariya, T.; Saburi, M.; Yoshikawa, S. J. Org. Chem. 1986, 51, 2034–2039; (e)
Murahashi, S.-I.; Naota, T.; Ito, K.; Maeda, Y.; Taki, H. J. Org. Chem. 1987, 52,
4319–4327; (f) Minami, I.; Tsuji, J. Tetrahedron 1987, 43, 3903–3915; (g) Lin, Y.;
Zhu, X.; Zhou J. Organomet. Chem. 1992, 429, 269–274; (h) Suzuki, T.; Morita, K.;
Tsuchida, M.; Hiroi, K. Org. Lett. 2002, 4, 2361–2363; (i) Zhao, J.; Hartwig, J. F.
Organometallics 2005, 24, 2441–2446.
4. (a) Kyrides, L. P.; Zienty, F. B. J. Am. Chem. Soc. 1946, 68, 1385; (b) Bloch, R.;
Brillet, C. Synlett 1991, 829–830; (c) Inokuchi, T.; Matsumoto, S.; Torii, S. J. Org.
Chem. 1991, 56, 2416–2421; (d) Nozaki, K.; Yoshida, M.; Takaya, H. J.
Organomet. Chem. 1994, 473, 253–256; (e) Tanaka, H.; Kawakami, Y.; Goto,
K.; Kuroboshi, M. Tetrahedron Lett. 2001, 42, 445–448; (f) Miyata, A.; Furukawa,
M.; Irie, R.; Katsuki, T. Tetrahedron Lett. 2002, 43, 3481–3484; (g) Barluenga, J.;
González-Bobes, F.; Murguía, M. C.; Ananthoju, S. R.; González, J. M. Chem. Eur.
J. 2004, 10, 4206–4213.
20
0
0
500
1000 1500 2000 2500 3000 3500 4000
Time / s
Figure 2. Heating profile under microwave irradiation with MnO2 (purple) and
BaMnO4 (black) in the presence of a SiC passive heating element.
oxidant from MnO2 to BaMnO4 (3 equiv), difficulties in coupling
with the microwave irradiation were overcome (Fig. 1) and this
was reflected in an increase in the isolated yield (Table 2, entry
2). The BaMnO4-mediated reaction was more efficient, both in
terms of energy transfer under microwave irradiation, presumably
as a consequence of its ionic character, and isolated yield and pro-
vided the product without the need for chromatographic purifica-
tion, thus achieving many of the goals we had set out to reach. In
order to verify that it was the heating profile that was the signifi-
cant factor, reactions using MnO2 and BaMnO4 were repeated un-
der microwave irradiation with a SiC passive heating element
present.13 Under these conditions, the heating profiles (Fig. 2)
and isolated yield of product (Table 2, entries 3 and 4) were near
identical, thus verifying that the higher temperature of the micro-
wave-assisted BaMnO4-mediated reaction in MeCN had caused the
increase in yield.
5. Phillips, D. J.; Pillinger, K. S.; Wei, L.; Taylor, A. E.; Graham, A. E. Chem. Commun.
2006, 2280–2282.
6. (a) Phillips, D. J.; Pillinger, K. S.; Wei, L.; Taylor, A. E.; Graham, A. E. Tetrahedron
2007, 63, 10528–10533; (b) Phillips, D. J.; Graham, A. E. Synlett 2008, 649–652.
7. (a) Taylor, R. J. K.; Reid, M.; Foot, J.; Raw, S. A. Acc. Chem. Res. 2005, 38, 851–869;
(b) Smith, B. M.; Graham, A. E. Tetrahedron Lett. 2007, 48, 4891–4894.
8. Bagley, M. C.; Hughes, D. D.; Sabo, H. M.; Taylor, P. H.; Xiong, X. Synlett 2003,
1443–1446.
9. (a) Nishiguchi, T.; Taya, H. J. Am. Chem. Soc. 1989, 111, 9102–9103; (b)
Nishiguchi, T.; Fujisaki, S.; Ishii, Y.; Yano, Y.; Nishida, A. J. Org. Chem. 1994, 59,
1191–1195; (c) Ogawa, H.; Amano, M.; Chihara, T. Chem. Commun. 1998, 495–
496; (d) Bianco, A.; Brufani, M.; Melchioni, C.; Romagnoli, P. Tetrahedron Lett.
1997, 38, 651–652; (e) Zhu, P. C.; Lin, J.; Pittman, C. U., Jr. J. Org. Chem. 1995, 60,
5729–5731.
10. (a) Bagley, M. C.; Dix, M. C.; Fusillo, V. Tetrahedron Lett. 2009, 50, 3661–3664;
(b) Torborg, C.; Hughes, D. D.; Buckle, R.; Robinson, M. W. C.; Bagley, M. C.;
Graham, A. E. Synth. Commun. 2008, 38, 205–211; (c) Bagley, M. C.; Davis, T.;
Dix, M. C.; Murziani, P. G. S.; Rokicki, M. J.; Kipling, D. Bioorg. Med. Chem. Lett.
2008, 18, 3745–3748; (d) Davis, T.; Bagley, M. C.; Dix, M. C.; Murziani, P. G. S.;
Rokicki, M. J.; Widdowson, C. S.; Zayed, J. M.; Bachler, M. A.; Kipling, D. Bioorg.
Med. Chem. Lett. 2007, 17, 6832–6835; (e) Bagley, M. C.; Davis, T.; Dix, M. C.;
Rokicki, M. J.; Kipling, D. Bioorg. Med. Chem. Lett. 2007, 17, 5107–5110; (f)
Bagley, M. C.; Lubinu, M. C.; Mason, C. Synlett 2007, 704–708; (g) Bagley, M. C.;
Davis, T.; Dix, M. C.; Widdowson, C. S.; Kipling, D. Org. Biomol. Chem. 2006, 4,
4158–4164; (h) Bagley, M. C.; Lubinu, M. C. In Topics in Heterocyclic Chemistry;
Van der Eycken, J. J., Kappe, C. O., Eds.; Springer: Heidelberg, 2006; Vol. 1, pp
31–58; (i) Bagley, M. C.; Jenkins, R. L.; Lubinu, M. C.; Mason, C.; Wood, R. J. Org.
Chem. 2005, 70, 7003–7006; (j) Bagley, M. C.; Hughes, D. D.; Lubinu, M. C.;
Merritt, E. A.; Taylor, P. H.; Tomkinson, N. C. O. QSAR Comb. Sci. 2004, 23, 859–
867; (k) Bagley, M. C.; Hughes, D. D.; Taylor, P. H. Synlett 2003, 259–261; (l)
Bagley, M. C.; Lunn, R.; Xiong, X. Tetrahedron Lett. 2002, 43, 8331–8334; (m)
Bagley, M. C.; Singh, N. Synlett 2002, 1718–1720.
With successful conditions established14 using microwave irra-
diation, the scope of the BaMnO4-mediated method was reviewed
using the same range of diols (Table 3), for convenience in the ab-
sence of the SiC heating element. It was apparent that the effi-
ciency of the microwave-assisted method was comparable if not
improved over the conductive heating procedure (Table 3), as well
as offering considerable advantages in terms of convenience, speed
and facility. Furthermore, most surprisingly, it enabled the synthe-
sis of both small and medium ring lactones where the conductive
heating method failed, providing for example, b-butyrolactone (en-
try 1) in 76% yield and the 13-membered
astonishing 78% isolated yield (entry 10) without the need for
chromatographic purification.
x-dodecanolactone in an
In conclusion, we have shown that the BaMnO4-mediated oxi-
dative cyclization of unactivated diols proceeds rapidly and effi-
ciently under microwave irradiation to give high yields of the
corresponding lactone products. The benign nature of the oxidant,
in addition to its low cost and ease of use, the simple experimental
and work-up procedures, and the fact that no chromatographic
purification is required demonstrate that BaMnO4 is an attractive
replacement for MnO2 in microwave-mediated tandem oxidation
processes.
11. Bagley, M. C.; Lubinu, M. C. Synthesis 2006, 1283–1288.
12. Highet, R. J.; Wildman, W. C. J. Am. Chem. Soc. 1955, 77, 4399–4401.
13. For the use of passive heating elements in microwave-assisted organic
synthesis, see: (a) Hoogenboom, R.; Wilms, T. F. A.; Erdmenger, T.; Schubert,
U. S. Aust. J. Chem. 2009, 62, 236–243; (b) Razzaq, T.; Kremsner, J. M.; Kappe, C.
O. J. Org. Chem. 2008, 73, 6321–6329; (c) Kremsner, J. M.; Kappe, C. O. J. Org.
Chem. 2006, 71, 4651–4658.
14. In a typical experimental procedure, a mixture of 1,5-pentanediol (0.58 mmol,
1 equiv) and BaMnO4 (1.74 mmol, 3 equiv) in MeCN (5 mL) was irradiated at
150 °C, at an initial power of 150 W, using a self-tuned single mode CEM
DiscoverÒ Focused Synthesizer for 1 h in a pressure-rated Pyrex reaction tube
(10 mL). The mixture was then cooled rapidly to room temperature, by passing
compressed air through the microwave cavity for 5 min, and then filtered
through Celite and washed with MeCN, to give d-valerolactone (50 mg, 88%),
with spectroscopic and spectrometric characterization data that agreed with
literature values.
Acknowledgments
We thank the EPSRC for funding together with Cardiff University,
Professor C. Oliver Kappe for helpful discussions and Steve Singh at
Anton Paar Ltd (Hertford, UK) for the provision of the SiC heating
elements.