Highly chemoselective oxidation of 1,5-diols to δ-lactones with TEMPO/BAIB

Article abstract of DOI:10.1016/S0040-4039(02)02489-9

The selective oxidative conversion of a variety of highly functionalized 1°,2°-1,5-diols into the corresponding δ-lactones has been effected simply and efficiently using a reagent system comprised of catalytic 2,2,6,6-tetramethylpiperidinooxy (TEMPO) and

Full text of DOI:10.1016/S0040-4039(02)02489-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 57–59
Highly chemoselective oxidation of 1,5-diols to d-lactones with
TEMPO/BAIB
T. Matthew Hansen,† Gordon J. Florence,‡ Priscilla Lugo-Mas, Jiehao Chen, Jason N. Abrams† and
Craig J. Forsyth*
Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, MN 55455, USA
Received 21 October 2002; accepted 6 November 2002
Abstract—The selective oxidative conversion of a variety of highly functionalized 1°,2°-1,5-diols into the corresponding d-lactones
has been effected simply and efficiently using a reagent system comprised of catalytic 2,2,6,6-tetramethylpiperidinooxy (TEMPO)
and excess bis-acetoxyiodobenzene (BAIB). © 2002 Elsevier Science Ltd. All rights reserved.
Substituted pyran and d-lactone moieties occur in a
wide array of natural products. In our recent studies
towards the synthesis of pyran containing targets phor-
boxazole A,1 okadaic acid2 and azaspiracid,3 we have
utilized nucleophilic additions to substituted lactones to
access these systems. Numerous conditions have been
reported to facilitate the oxidation of a 1,5-diol to the
corresponding d-lactone (Fig. 1), including TPAP,3,4
PCC,3,5 and TEMPO/co-oxidant.6 However, formation
of the undesired ketoaldehyde from 1°,2°-diols can be a
difficult side reaction to control resulting in lower con-
version to the lactone.
acetoxyiodobenzene (BAIB) as the co-oxidant was first
reported in 1997.7 Herein, we report the application of
this reagent system to the selective oxidation of 1°,2°-
1,5-diols to d-lactones.
As shown in Table 1, a variety of substituted lactones
were prepared from the corresponding diols. In general,
catalytic TEMPO (10–20 mol%) and 5 equiv. of BAIB
at room temperature in CH2Cl2 were used.8 Monitoring
of the reaction showed the initial formation of the
intermediate lactol species, which then undergoes fur-
ther oxidation to the lactone. Under these conditions
the monosubstituted diols 1 and 2 (entries 1 and 2) were
cleanly converted to 3 and 4.9 The oxidation of 1°
allylic diol 5 and 2° allylic diol 7 both proceeded
smoothly to provide lactones 6 and 9, respectively
(entries 3 and 4).
On this basis and with our continued interest in the use
of d-lactones as valuable synthetic intermediates, we
sought a chemoselective protocol capable of oxidizing a
range of 1°,2°-1,5-diols to highly functionalized d-lac-
tones. The selective oxidation of primary alcohols to
the corresponding aldehydes in the presence of sec-
ondary alcohols with catalytic TEMPO employing bis-
The oxidation of the highly substituted substrates 8 and
11 to the corresponding lactones was readily achieved
under the standard reaction conditions (entries 5 and
6). The application to the formation of fused ring
system 12 was demonstrated using tetrahydrofuran-diol
11 (entry 6).
The intermediacy of a hydroxy aldehyde species result-
ing from selective oxidation of the primary alcohol6b
was confirmed for substrate 8 by stopping the reaction
at shorter reaction times and isolating the corre-
sponding lactol. However, the partial oxidation was
difficult to control and provided variable amounts of
lactol and lactone. From 8, a 5:1 ratio was the highest
proportion of lactol:lactone that could be practically
isolated.
Figure 1. Oxidation of 1,5-diol to d-lactone.
* Corresponding author. Fax: 612-626-7541; e-mail: forsyth@
chem.umn.edu
† Current address: Abbott Laboratories, 200 Abbott Park Rd,
Abbott Park, IL 60064-6217, USA.
‡ Current address: University Chemical Laboratory, Lensfield Road,
Cambridge CB2 1EW, UK.
0040-4039/03/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02489-9

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T. M. Hansen et al. / Tetrahedron Letters 44 (2003) 57–59
Table 1. Oxidation of 1,5-diols with TEMPO/BAIB
In summary, the effectiveness of the TEMPO-BAIB
reagent system to selectively oxidize 1°,2°-1,5-diols to
the corresponding d-lactones has been demonstrated.
The generality and functional group compatibility of
this process has been highlighted through the formation
of several highly substituted systems.
2. (a) Dounay, A. B.; Urbanek, R. A.; Frydrychowski, V. A.;
Forsyth, C. J. J. Org. Chem. 2001, 66, 925; (b) Dounay, A.
B.; Forsyth, C. J. Org. Lett. 1999, 1, 451; (c) Dounay, A.
B.; Urbanek, R. A.; Sabes, S. F.; Forsyth, C. J. Angew.
Chem., Int. Ed. Engl. 1999, 38, 2258; (d) Sabes, S. F.;
Urbanek, R. A.; Forsyth, C. J. J. Am. Chem. Soc. 1998,
120, 2523.
3. Dounay, A. B.; Forsyth, C. J. Org. Lett. 2001, 3, 975.
4. Ley, S. V.; Norman, J.; Griffith, S. P.; Marsden, S. P.
Synthesis 1994, 639.
Acknowledgements
This research was partially supported by grants
ES10615 from the National Institute of Environmental
Health Sciences (NIEHS) and GM55756 from the
National Institute of General Medical Sciences, NIH.
Its contents are solely the responsibility of the authors
and do not necessarily represent the official views of the
NIEHS, NIH. P.L.M. was supported by the Research
Supplements for Underrepresented Minorities Program,
NIH. We thank Bristol-Myers Squibb for unrestricted
research grant support, and Dr. J. Hao for providing
compound 7.
5. Corey, E. J.; Suggs, J. W. Tetrahedron Lett. 1975, 16,
2647.
6. (a) TEMPO-NaBrO2: Inokuchi, T.; Matsumoto, S.;
Nishiyama, T.; Torii, S. J. Org. Chem. 1990, 55, 462; (b)
TEMPO-NaOCl, lactols: Siedlecka, R.; Skarzewski, J.;
Mlochowski, J. Tetrahedron Lett. 1990, 31, 2177; (c)
TEMPO-NaOCl, lactones: Anelli, P. L.; Banfi, S.; Monta-
nari, F.; Quici, S. J. Org. Chem. 1989, 54, 2970; (d) for a
recent review, see: Adam, W.; Saha-Mo¨ller, C. R.;
Ganeshpure, P. A. Chem. Rev. 2001, 101, 3499.
7. De Mico, A.; Margarita, R.; Parlanti, L.; Vescovi, A.;
Piancatelli, G. J. Org. Chem. 1997, 62, 6974.
8. All new compounds gave spectroscopic data in agreement
with the assigned structures. A typical procedure for oxi-
dation: To a stirred room temperature solution of triol 8
(1.9 g, 4.9 mmol) in CH2Cl2 (25 mL) was added sequen-
tially bis-acetoxyiodobenzene (BAIB, 5.00 g, 15.5 mmol)
References
1. Forsyth, C. J.; Ahmed, F.; Cink, R. D.; Lee, C. S. J. Am.
Chem. Soc. 1998, 120, 5597.

T. M. Hansen et al. / Tetrahedron Letters 44 (2003) 57–59
59
and 2,2,6,6-tetramethylpiperidinooxy (TEMPO, 0.15 g, 1.0
mmol). After stirring at rt for 3.5 h, saturated aqueous
Na2S2O3 and diethyl ether (50 mL) were added. The
separated organic phase was washed with saturated
aqueous NaHCO3 then H2O. The combined aqueous
washes were extracted with diethyl ether (3×25 mL) and
the combined organic fractions were washed with brine,
dried (NaSO4), filtered and concentrated by rotary evapo-
ration. The residue was purified by flash column chro-
matography (hexanes:ethyl acetate, 2:1“1:2, v/v) to
provide lactone 10 (1.76 g, 4.6 mmol, 94%) as a colorless
foam: Rf 0.45 (hexanes:ethyl acetate, 1:1, v/v); [h]2D3 −38.9
(c 2.65, CHCl3); IR (neat, cm−1) 3476, 2979, 2936, 2878,
1742, 1695, 1457, 1387, 1181; H NMR (300 MHz, C6D6,
1
70°C) l 5.39 (d, J=9.3 Hz, 1H), 4.4 (bs, 1H), 3.72, (m,
2H), 3.54 (d, J=1.5 Hz, 1H), 3.51 (d, J=1.2 Hz, 1H), 3.25
(s, 1H), 2.16 (m, 2H), 1.9–1.45 (m, 9H), 1.4 (s, 9H), 1.2 (d,
J=5.1 Hz, 3H), 0.74 (d, J=6.3 Hz, 3H); 13C NMR (75
MHz, C6D6, 70°C) l 173.4, 152.3, 128.9, 94.5, 87.5, 79.8,
75.5, 69.0, 68.9, 55.5, 40.2, 39.7, 28.9, 27.9, 25.0, 15.8, 11.8,
11.5; HRMS(CI) calcd for C20H34NO6[(M+H)+]: 384.2384;
found: 384.2385.
9. The prolonged reaction times indicated for entries 1 and 2
are generally not necessary.