An expedient procedure for the oxidative cleavage of olefinic bonds with PhI(OAc)2, NMO, and Catalytic OsO4

Article abstract of DOI:10.1021/ol100290a

(Figure Presented) PhI(OAc)₂ In the presence of OsO₄ (cat.) and 2,6-lutidine cleaves oleflnlc bonds to yield the corresponding carbonyl compounds, albeit, In some cases, with a-hydroxy ketones as byproduct. A more practical and clean protocol to effect oxidative cleavage of olefinic bonds involves NMO, OsO₄ (cat.), 2,6-lutidine, and PhI(OAc) ₂.

Full text of DOI:10.1021/ol100290a

ORGANIC
LETTERS
2010
Vol. 12, No. 7
1552-1555
An Expedient Procedure for the
Oxidative Cleavage of Olefinic Bonds
with PhI(OAc)2, NMO, and Catalytic
OsO4
K. C. Nicolaou,* Vikrant A. Adsool, and Christopher R. H. Hale
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps
Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, and
the Department of Chemistry and Biochemistry, UniVersity of California, San Diego,
9500 Gilman DriVe, La Jolla, California 92093
kcn@scripps.edu
Received February 3, 2010
ABSTRACT
PhI(OAc)2 in the presence of OsO4 (cat.) and 2,6-lutidine cleaves olefinic bonds to yield the corresponding carbonyl compounds, albeit, in
some cases, with r-hydroxy ketones as byproduct. A more practical and clean protocol to effect oxidative cleavage of olefinic bonds involves
NMO, OsO4 (cat.), 2,6-lutidine, and PhI(OAc)2.
The oxidative cleavage of olefinic bonds, either through their
ozonides or diols, is used widely in organic synthesis as a
useful method to truncate carbon chains or, more usefully,
to prepare carbonyl compounds. The most common methods
employed to carry out these operations involve ozonolysis
(Scheme 1a) or Johnson-Lemieux oxidation1 [NaIO4, OsO4
(cat.)] and its variants2 (Scheme 1b), including the recent
improvement (addition of 2,6-lutidine) introduced by Jin et
al.,3 all of which are one-step procedures. The disadvantages
involved with these methods (e.g., safety,4 drastic or
inconvenient conditions) led to the introduction of the two-
step procedure employing sequential Upjohn dihydroxyla-
tion5 [NMO, OsO4 (cat.)] and periodate cleavage of the
resulting 1,2-diol (Scheme 1c), which became as popular, if
not more, than the first two methods. More recent attempts
to improve upon these protocols led to the procedures of
Borhan et al.6 [oxone, OsO4 (cat.)] and Ochiai et al.7
[m-CPBA, HBF4, ArI (cat.)] that oxidatively cleave olefinic
bonds. The use of strong conditions, and the fact that both
(1) Pappo, R.; Allen, D. S., Jr.; Lemieux, R. U.; Johnson, W. S. J. Org.
Chem. 1956, 21, 478–479.
(2) (a) Okumoto, H.; Ohtsuko, K.; Banjoya, S. Synlett 2007, 3201–3205.
(b) Brooks, C. D.; Huang, L. C.; McCarron, M.; Johnstone, R. A. W. Chem.
Commun. 1999, 37–38. (c) Antonelli, E.; D’Aloisio, R.; Gambaro, M.;
Fiorani, T.; Venturello, C. J. Org. Chem. 1998, 63, 7190–7206. (d) Sato,
K.; Aoki, M.; Noyori, R. Science 1998, 281, 1646–1647. (e) Henry, J. R.;
Weinreb, S. M. J. Org. Chem. 1993, 58, 4745. (f) Ishii, Y.; Yamawaki, K.;
Ura, T.; Yamada, H.; Yoshida, T.; Ogawa, M. J. Org. Chem. 1988, 53,
3587–3593. (g) Lee, D. G.; Chang, V. S. J. Org. Chem. 1978, 43, 1532–
1536.
(3) Yu, W.; Mei, Y.; Kang, Y.; Hua, Z.; Jin, Z. Org. Lett. 2004, 6, 3217–
3219.
(4) (a) Dorofeev, S. B.; Eletskii, A. V.; Smirnov, B. M. Dokl. Akad.
Nauk SSSR 1981, 257, 592-596. (b) Koike, K.; Inoue, G.; Fukuda, T.
J. Chem. Eng. Jpn. 1999, 32, 295–299. (c) Ogle, R. A.; Schumacher, J. L.
Process Saf. Prog. 1998, 17, 127–133.
(5) VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976,
23, 1973–1976.
10.1021/ol100290a  2010 American Chemical Society
Published on Web 02/25/2010

recently, Arseniyadis et al. elegantly employed this reagent
to initiate cascade sequences that lead to novel heterocyclic
systems through transient dialdehydes.9a A polymer-
supported version of this reagent has also been reported,
but its use has been limited.10
Scheme 1. Common Methods for Cleaving Olefinic Bonds to
Carbonyl Compounds
The rarity of reports11 using PhI(OAc)2 to cleave 1,2-diols
can be attributed to the absence of a systematic study
demonstrating its capabilities in this regard. Thus, in order
to illustrate the generality and scope of PhI(OAc)2 as an
efficient 1,2-diol cleaving reagent, and as a prelude to our
a
Table 1. Cleavage of 1,2-Diols to Aldehydes by PhI(OAc)2
Scheme 2. Cleavage of 1,2-Diols to Aldehydes by PhI(OAc)2
of these procedures lead to carboxylic acids, also endows
them with certain limitations.
As part of a total synthesis program, we recently developed
practical and convenient protocols for cleaving 1,2-diols and
olefinic bonds to aldehydes and ketones employing hyper-
valent iodine reagents [e.g., PhI(OAc)2]8 as the main oxidant
(Scheme 2). In this paper, we highlight the practicality of
using PhI(OAc)2 to achieve a clean oxidative cleavage of
1,2-diols and demonstrate its compatibility and effectiveness
in oxidatively cleaving olefinic bonds into the corresponding
carbonyl compounds when coupled with dihydroxylation
conditions.
PhI(OAc)2 is an excellent reagent for the cleavage of
1,2-diols,9 and it is rather surprising that it is not
commonly employed in that capacity, despite a seven
decade old publication by Criegee and Beucker8 demon-
strating its ability to effect this transformation. More
a Reactions were carried out on 100 mg scale at 0.1 M concentration in
CH2Cl2 with 1.2 equiv of PhI(OAc)2 at ambient temperature. b Isolated yield.
c Competitive overoxidation observed.
(6) Travis, B. R.; Narayan, R. S.; Borhan, B. J. Am. Chem. Soc. 2002,
124, 3824–3825.
(7) Miyamoto, K.; Sei, Y.; Yamaguchi, K.; Ochiai, M. J. Am. Chem.
Soc. 2009, 131, 1382–1383.
(8) Criegee, R.; Beucker, H. Ann. Chem. 1939, 541, 218–238.
(9) (a) Lena, J. I. C.; Fernandez, E. M. S.; Ramani, A.; Birlirakis, N.;
Barrero, A. F.; Arseniyadis, S. E. Eur. J. Org. Chem. 2005, 683–700. (b)
Finet, L.; Lena, J. I. C.; Kaoudi, T.; Birlirakis, N.; Arseniyadis, S.
Chem.sEur. J. 2003, 9, 3813–3820. (c) Corbu, A.; Gauron, G.; Castro,
J. M.; Dakir, M.; Arseniyadis, S. Tetrahedron: Asymmetry 2008, 19, 1730–
1743. See also: Ohno, M.; Oguri, I.; Eguchi, S. J. Org. Chem. 1999, 64,
8995–9000. Hong, Z.; Liu, L.; Sugiyama, M.; Fu, Y.; Wong, C.-H. J. Am.
Chem. Soc. 2009, 131, 8352–8353.
subsequent investigations, we employed it to that effect on
a variety of diol substrates as shown in Table 1 (entries
(10) Chen, F.-E.; Xie, B.; Zhang, P.; Zhao, J.-F.; Wang, Hui.; Zhao, L.
Synlett 2007, 619–622.
(11) According to SciFinder Scholar v.2007, the original article (ref
8) was cited in only 17 publications at the time this manuscript was
prepared.
Org. Lett., Vol. 12, No. 7, 2010
1553

(Scheme 3b). On the other hand, addition of DIBAL-H to
the resulting mixture of the cleavage of diol substrate 2 led
to isolation of diol 14 in 60% overall yield for the one-pot
sequence (Scheme 3c). Finally, reductive amination14 (Scheme
3d) and dithiane protection (Scheme 3e) were also achieved
in high yields (94% and 85%, respectively) by adding the
indicated reagents to the aldehyde generated in situ from 1,2-
diol 3 according to the conditions of Table 1. Additional
such sequential reactions are envisioned, thus making this
technology potentially appealing for applications in a variety
of situations.
Scheme 3. One-Pot Applications of PhI(OAc)2 Cleavage of
1,2-Diols
We then proceeded to explore the usefulness of PhI(OAc)2
in cleaving olefinic bonds in the presence of catalytic
amounts of OsO4 and 2,6-lutidine. As shown in Scheme 4
and Table 2, this reaction works well in most instances (Table
2, entries 1-6), but fails to go to completion or leads to
byproduct, namely R-hydroxy ketones in certain cases (Table
2, entries 7-10). It should be noted that such byproducts
are also observed under Johnson-Lemieux conditions.3
From a more practical perspective, we discovered that a
one-pot combination of dihydroxylation using Upjohn condi-
Scheme 4. Oxidative Cleavage of Olefins to Aldehydes and/or
Ketones with PhI(OAc)2 and OsO4 (cat.) in the Presence of
2,6-Lutidine
tions followed by diol cleavage with PhI(OAc)2 was a
superior method to cleave olefins (Scheme 5 and Table 3,
entries 1-10). Thus, treating olefins with NMO and 2,6-
lutidine in the presence of catalytic OsO4 in acetone/water
(ca. 10:1) followed by the addition of PhI(OAc)2 effected
the cleavage of olefinic bonds in one pot to give the
corresponding carbonyl compounds. This process obviously
proceeds through the corresponding diol and liberates 2 molar
equiv of AcOH and 1 molar equiv of PhI, both of which
can be removed easily on workup and chromatography,
respectively.
1-10). In all the examples studied, a clean conversion of
the diol into the corresponding aldehydes/ketones was
observed. Experimentally, the procedure involves mixing of
the substrate and PhI(OAc)2 in CH2Cl2 at room temperature,
and upon completion, the product could conveniently be
isolated in pure form by removal of the solvent and
chromatography.12,13
Importantly, the PhI(OAc)2-based diol cleavage strategy
offers an opportunity for further reactions of the resulting
carbonyl compounds in the same pot. Thus, as shown in
Scheme 3a, addition of the stabilized phosphorane 11 to the
resulting mixture of the cleavage of diol substrate 1 led to
the isolation of conjugated ester 12 in high overall yield
(81%). Likewise, Grignard addition to the same aldehyde
produced propargylic alcohol 13 in 86% overall yield
The PhI(OAc)2-NMO-OsO4 protocol leads to alde-
hydes and ketones in high yields and admirably avoids
the formation of the R-hydroxy ketone side products
(compare Table 2, entries 9 and 10, with Table 3, entries
5 and 6). Notably, epoxides (entry 2, Table 3) survive
these oxidative cleavage conditions compared with condi-
tions that employ sodium periodate, which lead to
oxidative cleavage of the epoxide moiety.15 The reaction
accommodates both cyclic and acyclic olefins as well as
mono-, di-, and trisubstituted alkenes.
(12) The original report (ref 8) focused on the kinetics of the reaction
rather than its preparative usefulness and employed AcOH or benzene as
solvent.
(14) Abdel-Magid, A. F.; Carson, K. G.; Harris, B. D.; Maryanoff, C. A.;
Shah, R. D. J. Org. Chem. 1996, 61, 3849–3862.
(15) Binder, C. M.; Dixon, D. D.; Almaraz, E.; Tius, M. A.; Singaram,
B. Tetrahedron Lett. 2008, 49, 2764–2767.
(13) The only byproduct visible by TLC is iodobenzene.
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Org. Lett., Vol. 12, No. 7, 2010

Table 2. Oxidative Cleavage of Olefins to Aldehydes and/or
Ketones with PhI(OAc)2 and OsO4 (cat.) in the Presence of
2,6-Lutidinea
Scheme 5. Cleavage of Olefins to Aldehydes and/or Ketones by
NMO, OsO4 (cat.)/PhI(OAc)2 in the Presence of 2,6-Lutidine
Table 3. Cleavage of Olefins to Aldehydes and/or Ketones by
NMO, OsO4 (cat.)/PhI(OAc)2 in the Presence of 2,6-Lutidinea
a Reactions were carried out on 100 mg scale at 0.1 M concentration
in THF with 0.1 mL of H2O, 2.3 equiv of PhI(OAc)2, 2.5 equiv of
2,6-lutidine, and 0.02 equiv of OsO4 at ambient temperature. b Isolated
yield. c 67% yield based on 60% conversion. d 49% based on 93%
e
1
conversion. Inseparable mixture; ratio by H NMR.
a Reactions were carried out on 100 mg scale at 0.1 M concentration in
10:1 acetone/H2O with 2.0 equiv of 2,6-lutidine, 1.5 equiv of NMO, 0.02
equiv of OsO4, 1.5 equiv of PhI(OAc)2 at ambient temperature. b Isolated
yield. c 2.2 equiv of PhI(OAc)2 was used. d Carried out on 1 mmol scale.
The described synthetic methods offer a convenient,
robust, and economical16 alternative to the traditional olefin
cleavage methods for laboratory operations. In addition to
achieving high yields in most cases, all the protocols
described here involve essentially homogeneous media,
endowing them with certain advantages over the hetroge-
neous Johnson-Lemieux-type oxidations.
Institutes of Health (AI 055475) and the National Science
Foundation (CHE-0603217), as well an an NSF Graduate
Research Fellowship (to C.R.H.H.).
Supporting Information Available: Experimental pro-
cedures, characterization, and spectroscopic data for new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
Acknowledgment. Financial support for this work was
provided by A*STAR, Singapore, grants from the National
(16) NMO, NaIO4, and PhI(OAc)2 are all relatively inexpensive reagents
(∼$1-2/gram).
OL100290A
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