Terminal olefins to linear α,β-unsaturated ketones: Pd(II)/hypervalent iodine co-catalyzed wacker oxidation-dehydrogenation

Article abstract of DOI:10.1021/ja402651q

Development of a mild (35 C, no Bronsted acids) tandem Wacker oxidation-dehydrogenation of terminal olefins was accomplished using palladium(II) and hypervalent iodine co-catalysis. The reaction affords linear aryl and alkyl α,β-unsaturated ketones directly from readily available terminal olefins in good yields (average 75% per step) with excellent functional group tolerance and chemo- and stereoselectivities. The hypervalent iodine co-catalyst was found to be critical for dehydrogenation but was not effective as a stoichiometric oxidant.

Full text of DOI:10.1021/ja402651q

Subscriber access provided by UNIV OF REGINA
Communication
Terminal Olefins to Linear #,#-Unsaturated Ketones: Pd(II)/
Hypervalent Iodine Co-Catalyzed Wacker-Dehydrogenation
Marinus A. Bigi, and M. Christina White
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 14 May 2013
Downloaded from http://pubs.acs.org on May 15, 2013
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Terminal Olefins to Linear α,β-Unsaturated
Ketones: Pd(II)/Hypervalent Iodine Co-
Catalyzed Wacker-Dehydrogenation
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Marinus A. Bigi and M. Christina White*
Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801
KEYWORDS Dehydrogenation, Oxidation, C−H oxidation, Palladium, Hypervalent iodine, Tandem catalysis
Supporting Information Placeholder
ABSTRACT: Development of a mild (35oC, no Brönsted
acids) tandem Wacker-dehydrogenation of terminal olefins
Table 1. Reaction Development
OAc
Pd(II) cat. (10 mol%)
1,4-BQ (2 equiv.)
OAc
OAc
was accomplished using palladium(II) and hypervalent iodine
co-catalysis. The reaction affords linear aryl and alkyl α,β-
unsaturated ketones directly from readily available terminal
olefins in good yields (average 75% per step) with excellent
functional group tolerance, chemo- and stereoselectivities. The
hypervalent iodine co-catalyst was found to be critical for
dehydrogenation but was not effective as a stoichiometric oxi-
dant.
H
H
5
Additive
5
5
O
O
DMSO (0.67M)
H2O (1 equiv.)
35oC, 48h
H
H
> 20:1 E:Z
1
2
3
yield 3a
SM
entry
catalyst
additive
--
13% (68% 2)b
56%
1
2
3
1
1
1
1
1
Pd(CH3CN)4(BF4)2
Pd(CH3CN)4(BF4)2
Pd(CH3CN)4(BF4)2
Pd(CH3CN)4(BF4)2
Pd(CH3CN)4(BF4)2
100% PhI(OAc)2
25% PhI(OAc)2
10% PhI(OAc)2
59% (55%c)
38%
4
5
C—H functionalization reactions,1 due to their capacity for
directly installing valuable functionality onto readily available,
robust hydrocarbon skeletons, stand to significantly streamline
synthetic routes.2 In particular, terminal olefins are appealing
starting materials and synthetic intermediates because of their
abundance and tolerance of many standard acid-base organic
reactions. The ability to selectively transform terminal olefins
into ‘traditional’ polar functional groups, especially late in
synthetic sequences, continues to be a frontier challenge in
reaction development.3 As a classic example, the Wacker oxi-
dation transforms terminal olefins into methyl ketones in com-
plex molecule settings with outstanding selectivities.4 Addi-
tionally, Pd/sulfoxide-catalyzed C—H oxidation reactions
have emerged that introduce O, N, and C (including C—C
double bonds via dehydrogenation) functionality at the allylic
position of terminal olefins with high functional group toler-
100% PhI(OAc)2
1 equiv. BQ
25%
6
7
1
2
Pd(CH3CN)4(BF4)2
Pd(CH3CN)4(BF4)2
58%
23%
25% IBX
100% IBX
No BQ
8%
8
9
2
1
100% IBX
No BQ
--
Pd(OAc)2
Pd(TFA)2
25% PhI(OAc)2
25% PhI(OAc)2
25% PhI(OAc)2
3%
36%
35%
10
11
1
1
Pd(TFA)2
4,5-diazafluorenone
Pd(OAc)2
1,2-bis(benzylsulfinylethane)
12
1
1
1
trace
--
25% PhI(OAc)2
25% PhI(OAc)2
25% PhI(OAc)2
13d
14
Pd(TFA)2
DMSO
No Pd(II)
--
a
Determined by GC, average of two runs at 0.1 mmol, relative to standard
b
curve, external standard: nitrobenzene. Yield of Wacker product 2 shown
in parantheses. c Average isolated yield of 3 shown in parantheses (two runs
at 0.3 mmol). d 0.67 M in AcOH.
Figure 1.
ance and chemo- and regioselectivity.5 We herein report a
novel olefin/C—H oxidation reaction: Pd(II)/I(III)-catalyzed
tandem Wacker oxidation-dehydrogenation that directly and
selectively furnishes linear α,β-unsaturated ketones from ter-
minal olefins.
A. Palladium-catalyzed dehydrogenation of linear alkyl ketones
LnPd(X)2
cat.
O
O
O
R
R
2 80oC
R
O
R = aryl
ref. 11f
Pd(II)XLn
?
B. Hypervalent iodine carbonyl oxidation
α,β-Unsaturated ketones are a versatile class of synthetic
intermediates, readily engaging in Heck reactions, Michael
additions, and cycloadditions. Traditionally, these intermedi-
ates are prepared via multi-step routes (e.g., sulfoxide or sele-
noxide elimination,6 Saegusa oxidation7) or from preoxidized
starting materials (e.g., carbonyl olefination using stabilized
ylides,8 carbonyl dehydrogenation using stoichiometric rea-
gents).9 Alternatively, we envisioned that a direct route would
be possible from terminal olefins via a novel Pd(II)-catalyzed
tandem process: Wacker oxidation to form a methyl ketone
ArI(III)(X)2
stoich.
Nu
O
O
O
ArI(I)
R
R
R
X
ref. 15
Ph
Ph
Ph
IIII
Nu
Ar
C. Palladium/hypervalent iodine-catalyzed Wacker oxidation/dehydrogenation
LnPd(X)2 cat.
ArI(III)(X)2 cat.
O
O
R
H2O, BQ
R
R
R = alkyl and aryl
This Work
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 5
tones.11,12 Despite this, however, no general method has been
1
2
3
4
5
6
7
8
reported for linear ketone dehydrogenation, due to poor reac-
tivity and competitive overoxidation of aliphatic substrates
and their products.11f, 13, 14 To overcome these limitations, we
hypothesized that a hypervalent iodine(III) reagent would be
capable of generating an iodonium enolate from an intermedi-
ate methyl ketone (Figure 1). The iodine(III) reagent, well-
precedented to undergo nucleophilic displacement/reduction,15
could serve to activate the ketone for exchange with the palla-
dium (e.g. nucleophilic attack by the Pd(0) byproduct of
Pd(II)-catalyzed Wacker oxidation) to provide a Pd(II) eno-
late, thereby overcoming the low inherent reactivity of linear
ketones. Moreover, ketone activation via iodonium enolate
formation would hopefully obviate the need for external
Brönsted acids/high temperatures, and therefore limit unde-
sired overoxidation. Herein, we report the discovery and de-
velopment of a Pd(II)/hypervalent iodine-catalyzed tandem
Wacker-dehydrogenation reaction of terminal olefins.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
As shown in Table 1, Pd(II)-catalyzed oxidation of aliphatic
terminal olefin 1 under mild conditions [Pd(CH3CN)4(BF4)2,
0.67M DMSO, 1,4-benzoquinone, 35oC] led to 68% of the
Wacker product (2) with poor conversion to the α,β-
unsaturated ketone 3 (13% yield, Entry 1). In accord with our
hypothesis, addition of stoichiometric PhI(OAc)2 greatly im-
proved the yield of 3 to synthetically useful levels (56% yield,
Entry 2). Unexpectedly, however, lowering the amount of
PhI(OAc)2 to substoichiometric levels led to no diminishment
in reactivity, with 25 mol% proving optimal (Entries 3-4).
Consistent with this, replacing one equivalent of 1,4-
benzoquinone with PhI(OAc)2, to test if the I(III) reagent was
a competent terminal oxidant for the dehydrogenation step, led
to significantly reduced conversion to 3 (Entry 5). Other
common aryl iodonium(III) or iodonium(V) reagents led to
comparable results (Entry 6, also Supporting Information).
Notably, 2-iodoxybenzoic acid (IBX), an iodine(V) reagent
known to directly dehydrogenate ketones in DMSO at elevated
temperatures,9c is a competent catalytic additive but furnished
dehydrogenation product 3 from ketone 2 sluggishly under
these mild conditions, with or without palladium (Entries 6-8).
Finally, other previously reported palladium(II) dehydrogena-
tion catalysts5g, 11e, 11f as well as other common palladium salts
were inferior to Pd(CH3CN)4(BF4)2 for the tandem process
(Entries 9-13), while removing the palladium catalyst entirely
led to complete elimination of catalysis (Entry 14).
We next examined the scope of the tandem Wacker-
dehydrogenation reaction. As shown in Table 2, electron-rich
and electron-poor butenylated arenes delivered the desired
α,β-unsaturated ketones 4-7 in good yields (Entries 1-4). Or-
tho-substitution on the arene was tolerated (Entry 5) as was a
bioactive chromene functionality in benzopyran 9 (Entry 6).
Notably, non-activated, aliphatic substrates also underwent
tandem oxidation in good yields under these mild reaction
conditions (average 75% yield per step). It is significant to
note that these are the highest yields reported to date for direct,
catalytic dehydrogenation of this substrate class.14 A range of
oxygen and nitrogen functionality are well-tolerated in the α-
olefin substrates (i.e., benzoates, phthalimides, amides, esters,
benzyl ethers; Entries 7-12). Amides and esters did not under-
go competitive dehydrogenation, demonstrating that the dehy-
drogenation reaction is chemoselective for ketones over other
common carbonyl functionality (Entries 10-11). This lack of
reactivity has been attributed to the higher pKa value of the
followed by Pd-catalyzed dehydrogenation (Figure 1).10 Sig-
nificant progress has been made recently in the development
of Pd(II)-catalyzed dehydrogenation reactions of cyclic ke-
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
tively, this data supports the role of PhI(OAc)2 as a dehydro-
α−C—H bonds of esters and amides relative to ketone func-
tionality.11f A γ-stereocenter did not suffer epimerization in 15
despite its potential lability under enolizable reaction condi-
tions; similarly, 16 retained the trans stereochemistry found
within the olefin starting material (Entries 12-13). A disubsti-
tuted cyclohexene and an acetate enol ether were both well-
tolerated, highlighting the predictable selectivity of the Wack-
er reaction for terminal olefins (Entries 14-15). Estrone deriva-
tive 19 was isolated in 57% yield; the tandem reaction was
tolerant of a benzyl ether and an electron-rich aromatic and
proceeded next to the hindered D ring of the steroid core (En-
try 16). While some steric hindrance is tolerated, β-
disubstituted olefins, such as allylcyclohexane, underwent
facile Wacker oxidation (85% yield) but failed to undergo
significant dehydrogenation with only trace quantities of un-
saturated ketone 20 detected (Entry 17). Finally, the dehydro-
genation reaction proceeds with comparable efficiency starting
from the ketone intermediate and is not limited to linear sub-
strates (eq. 1). Taken together, our results demonstrate that
1
2
3
4
5
6
7
8
genation catalyst, not a terminal oxidant and therefore ex-
cludes mechanisms that generate PhI (e.g., Figure 1).17 Future
studies will seek to better understand the reaction mechanism
and the role of the hypervalent iodine catalyst.18
In summary, we herein report the development of a
Pd(II)/hypervalent
iodine-catalyzed
tandem
Wacker-
dehydrogenation reaction of terminal olefins. This reaction
provides for the expedient and selective synthesis of a broad
range of linear aryl and alkyl α,β-unsaturated ketones directly
from terminal olefins. Key to this reaction’s broad scope was
the discovery of an iodonium(III) co-catalyst that is critical for
facilitating dehydrogenation under mild conditions (35oC, no
Brönsted acids).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ASSOCIATED CONTENT
1
Experimental procedures, characterization data, and copies of H
and 13C NMR spectra for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org
the
Pd(II)/PhI(OAc)2-catalyzed
tandem
Wacker-
dehydrogenation readily converts a range of terminal olefins
directly into α,β-unsaturated ketones in good yields, with min-
imal overoxidation and good functional group tolerance.
AUTHOR INFORMATION
Corresponding Author
* white@scs.uiuc.edu
Funding Sources
Financial support was provided by the NIH/NIGMS (2R01 GM
076153B) and generous gifts from Novartis, Bristol-Myers
Squibb and Boehringer Ingelheim. We also thank Johnson
Matthey for generous gifts of palladium.
A critical question raised by these studies relates to the
mechanism by which catalytic hypervalent iodine reagents
promote the Pd(II)-Wacker/dehydration reaction. To probe
this, we monitored the reaction progress of terminal olefin 1
over time using GC analysis. Wacker oxidation occurred rap-
idly, with full conversion to methyl ketone 2 accomplished
within 3 hours, and was not influenced by the addition of
PhI(OAc)2. The overall kinetic profile of terminal olefin to
α,β-unsaturated ketone was monitored with and without
PhI(OAc)2 (Figure 2). A significant increase in the rate of de-
hydrogenation was observed in the presence of 25 mol%
PhI(OAc)2 and did not change significantly upon increasing to
stoichiometric PhI(OAc)2 (1 equiv.). Additionally, PhI was
never observed by 1H NMR during dehydrogenation.16 Collec-
ACKNOWLEDGMENT
We gratefully acknowledge Dr. Dustin J. Covell for preliminary
investigations of Pd(II)-catalyzed ketone dehydrogenation
reactions. We thank Iulia I. Strambeanu for checking the
experimental procedure in Table 2, Entry 3.
REFERENCES
(1) (a) Crabtree, R. H. J. Chem. Soc., Dalton Trans. 2001,
2437. (b) Labinger, J. A.; Bercaw, J. E. Nature 2002, 417,
507. (c) Dick, A. R.; Sanford, M. S. Tetrahedron 2006, 62,
2439. (d) Giri, R.; Shi, B.-F.; Engle, K. M.; Maugel, N.;
Yu, J.-Q. Chem. Soc. Rev. 2009, 38, 3242. (e) White, M. C.
Science 2012, 335, 807. (f) White, M. C. Synlett 2012, 23,
2746.
(2) For examples of synthetic streamlining using C—H func-
tionalization: (a) Hinman, A.; Du Bois, J. J. Am. Chem.
Soc. 2003, 125, 11510. (b) Wender, P. A.; Hilinski, M. K.;
Mayweg, A. V. W. Org. Lett. 2005, 7, 79. (c) Fraunhoffer,
K. J.; Bachovchin, D. A.; White, M. C. Org. Lett. 2005, 7,
223. (d) Covell, D. J.; Vermeulen, N. A.; Labenz, N. A.;
White, M. C. Angew. Chem. Int. Ed. 2006, 45, 8217. (e)
Stang, E. M.; White, M. C. Nat. Chem. 2009, 1, 547. (f)
Vermeulen, N. A.; Delcamp, J. H.; White, M. C. J. Am.
Chem. Soc. 2010, 132, 11323.
Figure 2. Overall kinetic profile
10% Pd(CH3CN)4(BF4)2,
H
O
1,4-BQ (2 equiv.)
AcO
AcO
H2O, DMSO, 35oC
H
PhI(OAc)2 (X mol%)
0%1&23#4/56'&#78#9*:#;<*:#5/#=99*#4.>)?@3+;#
(3) For recent examples, see: (a) Weiner, B.; Baeza, A.; Jer-
phagnon, T.; Feringa, B. L. J. Am. Chem. Soc. 2009, 131,
9473. (b) Michel, B. W.; McCombs, J. R.; Winkler, A.;
Sigman, M. S. Angew. Chem. Int. Ed. 2010, 131, 9473.
(4) Keith, J. A.; Henry, P. M. Angew. Chem. Int. Ed. 2009, 48,
9038.
*!"!!#
)!"!!#
(!"!!#
'!"!!#
&!"!!#
%!"!!#
$!"!!#
!"!!#
(5) (a) Chen, M. S.; White, M. C. J. Am. Chem. Soc. 2004,
126, 1346. (b) Vermeulen, N. A.; Delcamp, J. H. J. Am.
Chem. Soc. 2010, 132, 11323. (c) Gormisky, P. E.; White,
M. C. J. Am. Chem. Soc. 2011, 133, 12584. (d) Fraun-
hoffer, K. J. White, M. C. J. Am. Chem. Soc. 2007, 129,
7274. (e) Reed, S. A. White, M. C. J. Am. Chem. Soc.
2008, 130, 3316. (f) Young, A. J.; White, M. C. J. Am.
Chem. Soc. 2008, 130, 14090. (g) Stang, E. M.; White, M.
C. J. Am. Chem. Soc. 2011, 133, 14892.
A5#4.>)?@3+;#
;<*#4.>)?@3+;#
=99*#4.>)?@3+;#
(6) (a) Reich, H. J.; Wollowitz, S.; Org. React. 1993, 44, 1. (b)
Trost, B. M. Chem. Rev. 1978, 78, 363.
(7) (a) Ito, Y.; Hirao, T.; Saegusa, T. J. Org. Chem. 1978, 43,
1011. For a catalytic version of this reaction, see: (b)
Larock, R. C.; Hightower, T. R.; Kraus, G. A.; Hahn, P.;
!#
(#
$!#
$(#
%!#
%(#
&!#
&(#
'!#
,%-&#)./+#
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
Zheng, D. Tetrahedron Lett. 1995, 36, 2423. (c) Yu, J. Q.;
(15) (a) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108,
Wu, H. C.; Corey, E. J.; Org. Lett. 2005, 7, 1415.
(8) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863.
(9) (a) Walker, D.; Hiebert, J. D. Chem. Rev. 1967, 67, 153. (b)
Nicolaou, K. C.; Zhong, Y.-L.; Baran, P. S. J. Am. Chem.
Soc. 2000, 122, 7596. (c) Nicolaou, K. C.; Montagnon, T.;
Baran, P. S.; Zhong, Y.-L. J. Am. Chem. Soc. 2002, 124,
2245. (d) Nicolaou, K. C.; Montagnon, T.; Baran, P. S. An-
gew. Chem. Int. Ed. 2002, 41, 993. For a catalytic version
of this reaction for cyclic ketones using oxone as stoichio-
metric oxidant, see: (e) Uyanik, M.; Akakura, M.; Ishihara,
K. J. Am. Chem. Soc. 2009, 131, 251.
5299. (b) Moriarty, R. M.; Prakash, O. Org. React. 1999,
54, 273. (c) Koser, G. F. In Hypervalent Iodine Chemistry:
Modern Developments in Organic Synthesis; Wirth, T.,
Ed.; Springer, 2003; p 137. (d) Merritt, E. A.; Olofsson, B.
Synthesis 2011, 517.
1
2
3
4
5
6
7
8
(16) No products clearly derived from PhI were observed by 1H
NMR analysis of the crude reaction mixture (e.g., biaryls,
benzene, arylated BQ). If 1,4-benzoquinone were acting to
regenerate an I(III) reagent from PhI, thereby explaining
our inability to observe PhI, dehydrogenation should pro-
ceed similarly beginning from either PhI or PhI(OAc)2. As
expected, however, replacing 25 mol% PhI(OAc)2 with 25
mol% PhI and 100% AcOH led to only 15% yield of 3 (see
SI).
(17) Based on the well-precedented ability of hypervalent iodine
reagents to oxidize organopalladium(II) intermediates, we
considered the possibility of initial generation of a Pd(II)
enolate followed by oxidation with the I(III)-based oxidant
to provide a higher valent Pd(IV) enolate, with release of
PhI (for a review, see: Deprez, N. R.; Sanford, M. S. Inorg.
Chem. 2007, 46, 1924). Alternatively, as proposed in Fig-
ure 1, an iodonium(III) enolate might undergo reductive
displacement with Pd(0), affording a Pd(II) enolate and
PhI. In either case, β-hydride elimination from a Pd enolate
would release product and the I(III) reagent would function
as a terminal oxidant. We disfavor both pathways because
we have never observed PhI, the reaction requires stoichi-
ometric 1,4-BQ, and I(III) reagents can be used sub-
stoichiometrically.
(10) For two reviews of transition metal-catalyzed dehydrogena-
tion of alkanes: (a) Dobereiner, G. E.; Crabtree, R. H.
Chem. Rev. 2010, 110, 681. (b) Choi, J.; MacArthur, A. H.
R.; Brookhart, M.; Goldman, A. S. Chem. Rev. 2011, 111,
1761.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(11) For a review of Pd(II)-mediated carbonyl dehydrogenation:
(a) Muzart, J. Eur. J. Org. Chem. 2010, 3779. For early ex-
amples of this reactivity, see: (b) Theissen, R. J. J. Org.
Chem. 1971, 36, 752. (c) Muzart, J.; Pete, J. P. J. Mol.
Catal. 1982, 15, 373. For recent examples with greatly im-
proved scope, catalytic efficiency, and selectivity, see: (d)
Izawa, Y.; Pun, D.; Stahl, S. S. Science 2011, 333, 209. (e)
Diao, T.; Stahl, S. S. J. Am. Chem. Soc. 2011, 133, 14566.
(f) Diao, T.; Wadzinski, T. J.; Stahl, S. S. Chem. Sci. 2012,
3, 887. (g) Gao, W.; He, Z.; Qian, Y.; Zhao, J. Chem. Sci.
2012, 3, 883. (h) Tokunaga, M.; Harada, S.; Iwasawa, T.;
Obora, Y.; Tsuji, Y. Tetrahedron Lett. 2007, 48, 6860.
(12) For a rare example of Ir-catalyzed dehydrogenation of cy-
clic ketones, see: Zhang, X. W.; Wang, D. Y.; Emge, T. J.;
Goldman, A. S. Inorg. Chim. Acta 2011, 369, 253.
(18) A mechanism that cannot be excluded is iodonium(III) eno-
late formation (Figure 1) followed by a sigma-bond me-
tathesis with Pd(II) to furnish a Pd(II)-enolate with no
change in the oxidation state of the palladium or iodine.
Examples of sigma bond metathesis have been proposed
for silyl enol ethers with I(III) reagents: Chen, K.; Koser,
G. F. J. Org. Chem. 1991, 56, 5764.
(13) For examples of dehydrogenation of linear aliphatic alde-
hydes: (a) Zhu, J.; Liu, J.; Ma, R. Q.; Xie, H. X.; Li, J.;
Jiang, H. L.; Wang, W. Adv. Synth. Catal. 2009, 351, 1229.
(b) Liu, J.; Zhu, J.; Jiang, H. L.; Wang, W.; Li, J. Chem.—
Asian J. 2009, 4, 1712.
(14) The previous highest report described the convesion of 2-
octanone into oct-3-en-2-one in 17% yield using
Pd(TFA)2/ 4,5-diazafluorenone catalyst (ref. 11f).
a
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
Pd(II)/Hypervalent Iodine
Co-catalysis
OR
H
OR
O
10% Pd(II), 1,4-BQ
25% I(III)
H
H
H
7
H
57% yield
(75% per step)
H
8
9
RO
RO
>20:1 E:Z
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5
ACS Paragon Plus Environment