ORGANIC
LETTERS
2
012
Vol. 14, No. 9
242–2245
Pyridine Is an Organocatalyst for the
Reductive Ozonolysis of Alkenes
2
†
Rachel Willand-Charnley, Thomas J. Fisher, Bradley M. Johnson, and
Patrick H. Dussault*
Department of Chemistry, University of NebraskaꢀLincoln, Lincoln,
Nebraska 68588-0304, United States
Received March 11, 2012
ABSTRACT
Whereas the cleavage of alkenes by ozone typically generates peroxide intermediates that must be decomposed in an accompanying step,
ozonolysis in the presence of pyridine directly generates ketones or aldehydes through a process that neither consumes pyridine nor generates
any detectable peroxides. The reaction is hypothesized to involve nucleophile-promoted fragmentation of carbonyl oxides via formation of
zwitterionic peroxyacetals.
The ozonolysis of alkenes, a widely used and environ-
mentally sustainable oxidative transformation, is nearly
always accompanied by a reaction to decompose the ozon-
upon trapping of carbonyl oxides by amine N-oxides or
5
water. However, the first of these requires basic conditions
while the latter generates hydrogen peroxide as a stoichio-
metric byproduct. We became interested in a handful of
reports describing the direct formation of carbonyl groups
1
ides or other peroxide intermediates. However, the pro-
clivity of ozonides toward exothermic and self-accelerating
decomposition reactions, combined with their low rate of
reaction with many reducing agents, can create serious
6,7
for ozonolyses conducted in the presence of pyridine. This
mechanistically unexplained process has received little syn-
2ꢀ4
8,9
thetic attention. We now report that ozonolysis in the
hazards.
An attractive alternative to a traditional step-
wise approach would involve in situ capture and decom-
position of the carbonyl oxide intermediates. We recently
described two approaches to “reductive” ozonolyses based
presence of pyridine involves an unprecedented organoca-
talyzed decomposition of carbonyl oxides via the formation
and fragmentation of zwitterionic peroxyacetals. The over-
all process offers a fast, general, and high-yielding route to
aldehydes and/or ketones.
†
Current address: 3M Abrasives System Division, St. Paul, MN 55144,
USA.
(
1) (a) Bailey, P. S. Ozonation in Organic Chemistry: Vol. 1: Olefinic
Compounds; Academic Press: New York, 1978. (b) McGuire, J.; Bond, G.;
Haslam, P. J. Ozonolysis in the Production of Chiral Fine Chemicals.
Handbook of Chiral Chemicals, 2nd ed.; Taylor & Francis: Boca Raton,
FL, 2006; pp 165ꢀ184. (c) Van Ornum, S. G.; Champeau, R. M.; Pariza, R.
Chem. Rev. 2006, 106, 2990.
(5) (a) Schwartz, C.; Raible, J.; Mott, K.; Dussault, P. H. Org. Lett.
2006, 8, 3199. (b) Tetrahedron 2006, 62, 10747. (c) Schiaffo, C. E.;
Dussault, P. H. J. Org. Chem. 2008, 73, 4688. See also: (d) Molander,
G. A.; Cooper, D. J. J. Org. Chem. 2007, 72, 3558.
(6) Slomp, G.; Johnson, J. L. J. Am. Chem. Soc. 1958, 80, 915.
(7) Lutidine has been employed as an additive for ozonolyses (Wang,
Y.-G.; Takeyama, R.; Kobayashi, Y. Angew. Chem., Int. Ed. 2006, 45,
3320), but the substrates in this study would be expected to generate
aldehydes regardless of conditions or additives.
(2) Kula, J. Chem. Health Safety 1999, 6, 21.
(3) (a) Gordon, P. M. Chem. Eng. News. 1990, 68, 2. (b) Lavallee, P;
Bouthillier, G. J. Org. Chem. 1986, 51, 1362–5; see note 27 and references
within. (c) Ferreira, J. T. B. Chem. Eng. News. 1990, 68, 4.
(4) (a) See: Hida, T.; Kikuchi, J.; Kakinuma, M.; Nogusa, H. Org.
(8) Griesbaum, K. Chem. Commun. 1966, 920.
Process Res. Dev. 2010, 14, 1485. For discussions of membrane- or flow-
through reactors, see: (b) O’Brien, M.; Baxendale, I. R.; Ley, S. V. Org.
Lett. 2010, 12, 1596. (c) Irfan, M.; Glasnov, T. N.; Kappe, C. O. Org.
Lett. 2010, 13, 984.
(9) Pyridine has been applied as an additive to enhance the chemo-
selectivity of ozonolysis within polyunsaturated systems. See ref 6 and:
Trost, B. M.; Machacek, M. R.; Tsui, H. C. J. Am. Chem. Soc. 2005, 127,
7014.
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0.1021/ol300617r r 2012 American Chemical Society
Published on Web 04/18/2012