Aldehyde-selective wacker-type oxidation of unbiased alkenes enabled by a nitrite co-catalyst

Article abstract of DOI:10.1002/anie.201306756

Breaking the rules: Reversal of the high Markovnikov selectivity of Wacker-type oxidations was accomplished using a nitrite co-catalyst. Unbiased aliphatic alkenes can be oxidized with high yield and aldehyde selectivity, and several functional groups are tolerated. ¹⁸O-labeling experiments indicate that the aldehydic O atom is derived from the nitrite salt. Copyright

Full text of DOI:10.1002/anie.201306756

Angewandte
Chemie
DOI: 10.1002/anie.201306756
Synthetic Methods Very Important Paper
Aldehyde-Selective Wacker-Type Oxidation of Unbiased Alkenes
Enabled by a Nitrite Co-Catalyst**
Zachary K. Wickens, Bill Morandi, and Robert H. Grubbs*
The Wacker oxidation is a premier reaction for the catalytic
oxidation of alkenes to carbonyls because of its efficiency and
high functional-group tolerance.[1] A recent renaissance of
Wacker chemistry has overcome several key limitations of the
methodology.[2–4] Despite this progress, the regioselectivity of
the Wacker oxidation remains substrate-controlled and thus
the majority of terminal alkenes produce predominately
methyl ketones, in accord with Markovnikovꢀs rule (Scheme
1A). Researchers have exploited specific biased alkenes to
ketone selectivity upon reaching synthetically relevant con-
versions. The inherent challenge of obtaining anti-Markovni-
kov regioselectivity has thus limited the development of
a synthetically viable aldehyde-selective Wacker oxidation
without reliance upon substrate control.
1-Dodecene was selected as a model for an unbiased
alkene for the development of a catalyst-controlled process,
as it contains no chemical handle to reverse the Markovnikov
selectivity. For example, although our previously reported
conditions oxidize styrene with 97% aldehyde selectivity in
90% yield,[8b] 1-dodecene provided only traces of oxidation
products with high ketone selectivity and considerable
isomerization under these conditions (Figure 1, entry 1).
Thus, these conditions are unable to provide aldehyde
selectivity without the powerful substrate control offered by
the aromatic moiety and a general catalyst-controlled solu-
tion remains to be developed.
Prior to our work, Feringa reported that [PdNO2Cl-
(MeCN)2], when combined with CuCl2 in tBuOH, provided
aldehyde in poor yield (< 20%) but with encouraging
selectivity for aldehyde over ketone formation (2.3:1).[12a]
Unfortunately, reactions that reach useful yields reverted to
Markovnikov selectivity (1:4.5; entry 2). However, it has been
suggested that under these conditions, the palladium nitrite
generates tert-butyl nitrite.[12b]
Scheme 1. A) Tsuji–Wacker conditions applied to unbiased alkenes.
B) Newly developed aldehyde-selective Wacker oxidation.
circumvent Markovnikovꢀs rule and produce aldehydes.[5–8]
Unfortunately, the utility of this approach is inherently
limited because the vast majority of alkenes are unbiased,
and thus mere traces of the anti-Markovnikov aldehyde
products are observed.[1d,5,9] A general aldehyde-selective
Wacker oxidation would be a key advance in the field of anti-
Markovnikov functionalization[10] because aldehydes are not
only sought after products but are also versatile synthetic
intermediates.[11] For example, anti-Markovnikov hydration
and hydroamination products can be accessed from aldehydes
through established catalytic processes.[11d,e]
Based upon this precedent and the possibility that the
poor aldehyde yield and selectivity could be due to inefficient
generation of a highly aldehyde-selective species from tert-
Despite many attempts to develop a catalyst-controlled,
aldehyde-selective Wacker oxidation, such a variant has
remained elusive.[5,12,13] Only moderate aldehyde selectivity
can be obtained from unbiased alkenes at low conversions
and all methods have universally reverted to the expected
[*] Z. K. Wickens, Dr. B. Morandi, Prof. Dr. R. H. Grubbs
Division of Chemistry and Chemical Engineering
California Institute of Technology
Pasadena, CA 91125 (USA)
E-mail: rhg@caltech.edu
[**] We thank Scott Virgil for technical assistance. We acknowledge
KAUST, KFUPM, and NSF for funding and the SNSF for a fellowship
to B.M.
Figure 1. Catalyst optimization. Entries 3–12: 1-dodecene (0.2 mmol),
[PdCl2(PhCN)2] (12 mol%), and CuCl2·2H2O (12 mol%) were used.
Entry 12: [PdCl2(PhCN)2] was replaced by [PdNO2Cl(MeCN)2].
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201306756.
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
Table 1: Aldehyde-selective Wacker-type oxidation of unbiased alkenes.[a]
butyl nitrite, we combined catalytic tert-butyl nitrite with
PdCl2 and CuCl2 co-catalysts and observed significantly
increased selectivity, for the first time providing modest
aldehyde selectivity above 50% conversion to oxidized
products (entry 3). However, an increase of the loading of
tert-butyl nitrite modestly increased the overall yield but
decreased selectivity (entry 4).
Entry
Substrate
Yield of oxidation
(aldehyde)[b] [%]
Sel.[c] [%]
1
2
80 (63)[d]
74 (61)
79
79
We reasoned that other nitrite sources could enable more
efficient access to the selective catalytic species. Of the nitrite
sources evaluated, each offered similar oxidation efficiency
with varying aldehyde selectivity (entries 3–9). Catalytic
AgNO2 provided a significant improvement, leading to good
anti-Markovnikov selectivity and synthetically useful yields.
Interestingly, no significant difference between 12 and
6 mol% AgNO2 was observed (entries 7 and 8). The com-
parable selectivity observed with NaNO2 (entry 9) suggests
that AgI most likely does not play a key co-catalytic role.[14]
Furthermore, replacement of the nitrite anion with nitrate
dramatically reduced oxidation yield and regioselectivity
(entry 10). Attempts to deviate from metal dichloride salts
or tBuOH[15] universally resulted in significantly decreased
yield and selectivity. MeNO2 was found to be the superior
cosolvent although its omission from the optimized conditions
3
4
5
6
7
78 (70)
72 (59)
68 (51)[e]
77 (65)
70 (59)
89
79
67
82
81
8
9
80 (45)
75 (60)[e]
57
80
10
11
77 (69)
89
90
71 (64)[e]
[a] Alkene (0.5 mmol) treated with [PdCl2(PhCN)2] (12 mol%),
CuCl2·2H2O (12 mol%), and AgNO2 (6 mol%) in tBuOH/MeNO2 (15:1,
8 mL) under O2 atmosphere (1 atm) at 20–258C. [b] Yield of isolated
aldehyde. Overall yield (of oxidation) calculated using selectivity.
[c] Selectivity determined by 1H NMR analysis. [d] Yield and selectivity
still provided
(entry 11).
a somewhat aldehyde-selective process
1
both determined by GC analysis. [e] Yield determined by H NMR
Importantly, when the palladium nitrite catalyst used by
Feringa[12a] was applied to the optimized conditions, the
process was much less selective (slightly ketone-selective)
than with other nitrite sources (entry 12). Thus, we suspect
that the nitrite anion does not simply undergo salt metathesis
to form PdNO2Cl in situ and that instead a more complex
synergistic interaction between the metals occurs.
analysis.
Having demonstrated aldehyde selectivity in unbiased
aliphatic alkenes, a set of three phthalimides, which upon
minor carbon skeleton changes range from aldehyde- to
ketone-selective under traditional substrate-controlled Tsuji–
Wacker conditions, were next subjected to the reaction
conditions (Scheme 3). For each substrate, products were
obtained with high yield and selectivity, regardless of the
innate selectivity. Beyond providing preliminary evidence
that this process could be a general catalyst-controlled
solution to aldehyde selectivity, these results illustrate the
efficacy of this process with proximal nitrogen functionality
without reliance upon the substrate-controlled regioselectiv-
ity.
Previous attempts to develop an aldehyde-selective
Wacker oxidation have been plagued by low yields and loss
of selectivity over the course of the reaction. Thus, we
examined the reaction profile to assess the behavior of the
aldehyde selectivity (Figure 2). Upon surpassing 5% con-
version, the selectivity stabilized and became relatively
independent of both yield and time. This behavior potentially
suggests that, once formed, the same catalytic species remains
active throughout the remainder of the reaction. The brief
induction period in aldehyde selectivity is particularly inter-
With optimized conditions in hand, the functional-group
tolerance of the transformation was explored (Table 1). To
avoid substrate-derived anti-Markovnikov selectivity, ali-
phatic substrates bearing only distal functionality were
selected.[16] These substrates provided products with yields
comparable to those expected under Tsuji–Wacker condi-
tions[1b] but with anti-Markovnikov selectivity. The reaction is
compatible with a diverse array of functional groups: alkyl
and aryl halides, esters, ethers, and nitro groups were all
tolerated. Despite the potential challenge of using unpro-
tected functional groups, carboxylic acids and alcohols still
provided synthetically viable yields of the corresponding
aldehyde products. The reduced selectivity in these cases
could be attributed to an intermolecular Markovnikov attack
by these nucleophilic functionalities, thus producing ketones.
Although alkene isomerization is a common problem in
Wacker-type oxidations, no significant isomerization was
observed with any of the substrates. All examples represent
the first instances of aldehyde-selective Wacker oxidations on
such substrates at synthetically relevant conversion.[5]
Next, the scalability of the process was assessed. Although
the palladium loading on a small scale was comparable to
Tsuji–Wacker conditions, it was reduced to 7 mol% to
accomodate a gram-scale process (Scheme 2). The success
of this large-scale reaction demonstrates that the process can
maintain high yield and aldehyde selectivity at an increased
scale, even with decreased catalyst loading.
Scheme 2. Aldehyde-selective Wacker oxidation on a 10 mmol scale
with reduced catalyst loading.
2
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Scheme 3. Comparison of innate selectivity (conditions A) to catalyst-
controlled selectivity (conditions B). Conditions A: (Ref. [4b]) PdCl2
(10–30 mol%), CuCl (1 equiv), DMF/H2O (7:1), RT, O2 (1 atm).
Conditions B: alkene (0.5 mmol), [PdCl2(PhCN)2] (12 mol%), CuCl2
(12 mol%), AgNO2 (6 mol%), tBuOH/MeNO2 (15:1), RT, O2 (1 atm).
Aldehyde yield determined after purification. Selectivity determined by
1H NMR analysis prior to purification.
Scheme 4. A) Stoichiometric 18O-labeling experiment. B) Plausible
mode of oxygen transfer. C) Radical model to explain anti-Markovnikov
selectivity.
esting, as previous systems have commonly demonstrated
moderate to high aldehyde selectivity only at very low
conversion.
atom should not be derived from nitrite after tBuOH attack.
On the other hand, definitive attack by nitrite salts has been
demonstrated only in systems that exhibit high Markovnikov
selectivity.[20] The 18O-labeling experiment presented herein
thus constitutes the first conclusive experimental illustration
that nitrite salts can indeed transfer an oxygen atom to the
terminal position of alkenes under palladium catalysis.
The unusual anti-Markovnikov regioselectivity of the
oxygen transfer from the nitrite salt combined with the
propensity of such salts to generate an NO2 radical in situ[21,22]
leads us to propose that the key mechanistic feature of this
reaction is a metal-mediated delivery of an NO2 radical
species across the alkene (Scheme 4C).[23] In traditional
Wacker-type oxidations, attack by water upon the coordi-
nated alkene is a polar addition and thus is controlled by
Markovnikovꢀs rule.[24] In contrast, radical-type addition to
alkenes proceeds selectively at the terminal position because
of the increased stability of the secondary radical intermedi-
ate.[25–27] Although vinylcyclopropane radical traps appeared
to open under the reaction conditions, our attempts to probe
radical intermediacy have been stymied by the difficulty to
distinguish between one- or two-electron ring-opening path-
ways.[28] However, we expect that the significant insight
provided by the 18O-labeling experiment will continue to
provide crucial guidance for further mechanistic study, aimed
to determine the ultimate origin of anti-Markovnikov selec-
tivity.
With the aim of providing key preliminary mechanistic
insight into this transformation, we sought to elucidate the
origin of the aldehydic oxygen atom in our system. To this
end, we treated 4-phenyl-1-butene with stoichiometric 18O-
labeled NaNO2 (NaNO2 provided comparable selectivity and
efficiency to AgNO2, see Figure 1) along with [PdCl2(PhCN)2]
and CuCl2·2H2O. We were delighted to find compelling
evidence that the oxygen atom is derived from the nitrite salt,
as the 18O label was effectively (81%) incorporated into the
aldehyde (Scheme 4A).[17] Incomplete incorporation is likely
due to exchange with adventitious water, however, a compet-
ing traditional Wacker-type nucleophilic attack cannot be
ruled out. Under our catalytic reaction conditions, NO
formed after oxygen transfer could be aerobically oxidized
back to NO2, enabling the catalytic use of the nitrite salt
(Scheme 4B).[18] Prior to this work, contradictory reports
have suggested that palladium nitrite complexes could oxidize
alkenes through attack of either tBuOH or the nitrite ligand.
Anti-Markovnikov attack by tBuOH has been substantiated
with specific substrates,[7,8b,12b,19] however it is unlikely to
occur under the present conditions, as the aldehydic oxygen
A Wacker-type oxidation of unbiased alkenes affording
the anti-Markovnikov aldehyde products has been developed.
The success of this system with challenging aliphatic sub-
strates combined with the lack of substrate-derived interfer-
ence by allylic and homoallylic functionality bodes well for
further development of the reaction into an efficient synthetic
tool. An informative 18O-labeling experiment suggests an
unusual mechanistic manifold, potentially involving the
metal-catalyzed attack at the terminal position of the alkene
by an NO2 radical.
Figure 2. Reaction profile of nitrite-modified Wacker oxidation to
assess stability of aldehyde-selective catalytically active species.
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
Schmidt, Chem. Rev. 1999, 99, 3329 – 3366; b) M. B. Smith, J.
March, Marchꢀs Advanced Organic Chemistry, 5th ed., Wiley,
New York, 2001; c) E. M. Carreira, L. Kvaerno, Classics in
Stereoselective Synthesis, 1st ed., Wiley-VCH, Weinheim, 2009;
d) C. Wang, A. Pettman, J. Basca, J. Xiao, Angew. Chem. 2010,
122, 7710 – 7714; Angew. Chem. Int. Ed. 2010, 49, 7548 – 7552;
e) B. L. Conley, M. K. Pennington-Boggio, E. Boz, T. J. Williams,
Chem. Rev. 2010, 110, 2294 – 2312.
Received: August 2, 2013
Published online: && &&, &&&&
Keywords: alkenes · anti-Markovnikov · oxidation · oxygen ·
.
palladium
[12] Attempts to obtain aldehyde selectivity in Wacker oxidations of
unbiased alkenes: a) B. L. Feringa, J. Chem. Soc. Chem.
Commun. 1986, 909; b) T. T. Wenzel, J. Chem. Soc. Chem.
Commun. 1993, 862 – 864; c) T. Ogura, R. Kamimura, A. Shiga,
T. Hosokawa, Bull. Chem. Soc. Jpn. 2005, 78, 1555 – 1557.
[13] Alternatively, an epoxidation/isomerization tandem process can
be used to oxidize alkenes to aldehydes: a) J. Chen, C.-M. Che,
Angew. Chem. 2004, 116, 5058 – 5062; Angew. Chem. Int. Ed.
2004, 43, 4950 – 4954; b) A. D. Chowdhury, R. Ray, G. K. Lahiri,
Chem. Commun. 2012, 48, 5497.
[14] Y. Lu, D.-H. Wang, K. M. Engle, J.-Q. Yu, J. Am. Chem. Soc.
2010, 132, 5916 – 5921.
[15] For example, if tBuOH is replaced by MeNO2, no conversion is
observed.
[16] Styrene was also evaluated and was oxidized in 47% yield to the
aldehyde (ꢀ 20:1 selectivity) and cleaved in 12% yield to the
benzaldehyde.
[17] Control experiments and further discussion can be found in the
Supporting Information.
[1] a) J. Smidt, W. Hafner, J. Sedlmeier, R. Jira, R. Rꢁttinger,
Angew. Chem. 1959, 71, 176 – 182; b) J. Tsuji, Synthesis 1984,
369 – 384; c) J. M. Takacs, J. Xt, Curr. Org. Chem. 2003, 7, 369 –
396; d) J. Tsuji, Palladium Reagents and Catalysts: New Perspec-
tives for the 21st Century, 2nd ed. Wiley, Hobken, 2004; e) R. Jira,
Angew. Chem. 2009, 121, 9196 – 9199; Angew. Chem. Int. Ed.
2009, 48, 9034 – 9037.
[2] Wacker oxidation of internal alkenes: a) T. Mitsudome, K.
Mizumoto, T. Mizugaki, K. Jitsukawa, K. Kaneda, Angew. Chem.
2010, 122, 1260 – 1262; Angew. Chem. Int. Ed. 2010, 49, 1238 –
1240; b) B. Morandi, Z. K. Wickens, R. H. Grubbs, Angew.
Chem. 2013, 125, 3016 – 3020; Angew. Chem. Int. Ed. 2013, 52,
2944 – 2948; c) R. J. DeLuca, J. L. Edwards, L. D. Steffens, B. W.
Michel, X. Qiao, C. Zhu, S. P. Cook, M. S. Sigman, J. Org. Chem.
2013, 78, 1682 – 1686; d) T. Mitsudome, S. Yoshida, T. Mizugaki,
K. Jitsukawa, K. Kaneda, Angew. Chem. 2013, 125, 6077 – 6080;
Angew. Chem. Int. Ed. 2013, 52, 5961 – 5964; e) T. Mitsudome, S.
Yoshida, Y. Tsubomoto, T. Mizugaki, K. Jitsukawa, K. Kaneda,
Tetrahedron Lett. 2013, 54, 1596; f) H. R. Darabi, M. Mirza-
khani, K. Aghapoor, K. Jadidi, L. Faraji, N. Sakhaee, J. Organo-
met. Chem. 2013, 740, 131; g) B. Morandi, Z. K. Wickens, R. H.
Grubbs, Angew. Chem. 2013, 125, 9933 – 9936; Angew. Chem.
Int. Ed. 2013, 52, 9751 – 9754.
[18] Selected examples of aerobic NO2 turnover in Pd catalysis:
a) T. T. Wenzel, J. Chem. Soc. Chem. Commun. 1989, 932 – 933;
b) K. J. Stowers, A. Kubota, M. S. Sanford, Chem. Sci. 2012, 3,
3192 – 3195.
[19] G. Dong, P. Teo, Z. K. Wickens, R. H. Grubbs, Science 2011, 333,
1609 – 1612.
[20] M. A. Andrews, K. P. Kelly, J. Am. Chem. Soc. 1981, 103, 2894 –
2896.
[3] Dioxygen as the sole oxidant: a) T. Mitsudome, T. Umetani, N.
Nosaka, K. Mori, T. Mizugaki, K. Ebitani, K. Kaneda, Angew.
Chem. 2006, 118, 495 – 499; Angew. Chem. Int. Ed. 2006, 45, 481 –
485; b) C. N. Cornell, M. S. Sigman, Inorg. Chem. 2007, 46,
1903 – 1909; c) K. M. Gligorich, M. S. Sigman, Chem. Commun.
2009, 3854 – 3867; d) A. N. Campbell, S. S. Stahl, Acc. Chem. Res.
2012, 45, 851 – 863.
[4] Catalyst-controlled Wacker oxidation with Markovnikov selec-
tivity: a) B. W. Michel, A. M. Camelio, C. N. Cornell, M. S.
Sigman, J. Am. Chem. Soc. 2009, 131, 6076 – 6077; b) B. W.
Michel, J. R. McCombs, A. Winkler, M. S. Sigman, Angew.
Chem. 2010, 122, 7470 – 7473; Angew. Chem. Int. Ed. 2010, 49,
7312 – 7315; c) M. S. Sigman, E. W. Werner, Acc. Chem. Res.
2012, 45, 874 – 884.
[21] a) “Nitric Acid, Nitrous Acid, and Nitrogen Oxides”: M.
Thiemann, E. Scheibler, K. W. Wiegand, Ullmannꢀs Encyclope-
dia of Industrial Chemistry, Wiley-VCH, Weinhei, 2012; b) for
a recent examples of nitrite salts serving as precursors to NO2: S.
Maity, S. Manna, S. Rana, T. Naveen, A. Mallick, D. Maiti, J. Am.
Chem. Soc. 2013, 135, 3355 – 3358.
[22] When the reaction is run in an unsealed vessel (exposed to air),
significantly lower yield and selectivity is observed relative to the
reaction run in a sealed vessel (under air atmosphere). This is
consistent with the formation of NO2, which is a gas at room
temperature.
[5] J. Muzart, Tetrahedron 2007, 63, 7505 – 7521.
[23] To probe whether Pd or Cu mediate NO2 delivery, a reviewer
suggested the stoichiometric reaction of CuCl2 and AgNO2 with
an alkene. No alkene conversion was observed under these
conditions, suggesting that Pd may mediate NO2 delivery.
[24] J. A. Keith, P. M. Henry, Angew. Chem. 2009, 121, 9200 – 9212;
Angew. Chem. Int. Ed. 2009, 48, 9038 – 9049.
[25] a) S. Z. Zard, Radical Reactions in Organic Synthesis, Oxford
University Press, New York, 2003; b) M. S. Kharasch, E. V.
Jensen, W. H. Urry, Science 1945, 102, 128.
[6] B. Weiner, A. Baeza, T. Jerphagnon, B. L. Feringa, J. Am. Chem.
Soc. 2009, 131, 9473 – 9474.
[7] J. J. Dong, M. FaÇanꢂs-Mastral, P. L. Alsters, W. R. Browne,
B. L. Feringa, Angew. Chem. 2013, 125, 5671 – 5675; Angew.
Chem. Int. Ed. 2013, 52, 5561 – 5565.
[8] a) J. A. Wright, M. J. Gaunt, J. B. Spencer, Chem. Eur. J. 2006,
12, 949 – 955; b) P. Teo, Z. K. Wickens, G. Dong, R. H. Grubbs,
Org. Lett. 2012, 14, 3237 – 3239; c) M. Yamamoto, S. Nakaoka, Y.
Ura, Y. Kataoka, Chem. Commun. 2012, 48, 1165 – 1167.
[9] J. Tsuji, H. Nagashima, H. Nemoto, Org. Synth. 1984, 62, 9.
[10] Reviews highlighting the need for catalyst-controlled anti-
Markovnikov functionalization reactions: a) M. Beller, J.
Seayad, A. Tillack, H. Jiao, Angew. Chem. 2004, 116, 3448 –
3479; Angew. Chem. Int. Ed. 2004, 43, 3368 – 3398; b) L.
Hintermann, Top. Organomet. Chem. 2010, 31, 123 – 155; c) J.
Mahatthananchai, A. M. Dumas, J. W. Bode, Angew. Chem.
2012, 124, 11114 – 11152; Angew. Chem. Int. Ed. 2012, 51, 10954 –
10990.
À
[26] For recent examples using a radical strategy to form carbon
nitrogen bonds, see: a) ref. [21b]; b) J. Guin, C. Mꢁck-Lichten-
feld, S. Grimme, A. Studer, J. Am. Chem. Soc. 2007, 129, 4498 –
4503.
[27] For a recent example using a radical cation strategy to form
À
carbon oxygen bonds, see: D. S. Hamilton, D. A. Nicewicz, J.
Am. Chem. Soc. 2012, 134, 18577 – 18580.
[28] W. Fischetti, R. F. Heck, J. Organomet. Chem. 1985, 293, 391 –
405.
[11] a) P. Eilbracht, L. Bꢃrfacker, C. Buss, C. Hollmann, B. E. Kitsos-
Rzychon, C. L. Kranemann, T. Rische, R. Roggenbuck, A.
4
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Synthetic Methods
Z. K. Wickens, B. Morandi,
R. H. Grubbs*
&&&& — &&&&
Aldehyde-Selective Wacker-Type
Oxidation of Unbiased Alkenes Enabled
by a Nitrite Co-Catalyst
Breaking the rules: Reversal of the high
Markovnikov selectivity of Wacker-type
oxidations was accomplished using a ni-
trite co-catalyst. Unbiased aliphatic
alkenes can be oxidized with high yield
and aldehyde selectivity, and several
functional groups are tolerated. 18O-
labeling experiments indicate that the
aldehydic O atom is derived from the
nitrite salt.
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!