Palladium-catalyzed oxime assisted intramolecular dioxygenation of alkenes with 1 atm of air as the sole oxidant

Full text of DOI:10.1021/ja100716x

Published on Web 04/15/2010
Palladium-Catalyzed Oxime Assisted Intramolecular Dioxygenation of Alkenes
with 1 atm of Air as the Sole Oxidant
Ming-Kui Zhu, Jun-Feng Zhao, and Teck-Peng Loh*
DiVision of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang
Technological UniVersity, Singapore 637371
Received February 3, 2010; E-mail: teckpeng@ntu.edu.sg
Palladium-mediated organic transformations continue to be a
fascinating area in organic synthesis as well as organometallic
chemistry due to their versatility and ability to give unexpected
outcomes.1 Among them, palladium-catalyzed difunctionalization
of alkenes has attracted much attention.2,3 Recently, palladium-
catalyzed dioxygenation3 of alkenes has emerged as an alternative
approach to the synthesis of vicinal diols, which were previously
prepared by Sharpless dihydroxylations.4 While significant success
had been achieved, co-oxidants such as BQ, PhI(OAc)2, and Ag(I)
as well as Cu(II) salts are necessary for the catalytic cycle. Although
Jiang and co-workers employed molecular O2 as the sole oxidant,
high pressure and temperature are required.3d Atmospheric oxygen
should be an ideal source of oxygen in terms of environmental
benignity, offering both economical and practical advantages.
However, using atmospheric oxygen as the sole oxidant without
any other co-oxidants still remains a tremendous challenge in this
field.5 Herein, we present the first palladium-catalyzed oxime
assisted intramolecular dioxygenation of akenes with 1 atm of air
as the sole oxidant under very mild conditions.
oxime 1a containing a strategically positioned disubstituted terminal
alkene as the substrate for our model study.
To our delight, when 1a was treated with 20 mol % Pd(OAc)2,
24 mol % ligand A (1,10-phenanthroline), and 10 equiv of HOAc,
dioxygenation of olefin indeed proceeded readily under 1 atm of
molecular O2 at room temperature to give the dioxygenated products
2a and 3a in satisfactory yield (Table 1, entry 1). The ligand used
has a significant effect on the efficiency of this reaction and A was
found to be the best ligand (for details of ligands screening, see
Supporting Information). Other oxidants were also examined, and
it is notable that 1 atm of air proved to be the best choice in terms
of reaction efficiency, as well as practical and economical factors
(Table 1, entries 1-5). We also observed that a small amount of
water is favorable to this reaction (Table 1, entries 8, 10, and 11).
Finally, we found that, under 1 atm of air, 10 mol % Pd(OAc)2, 12
mol % ligand A, 10 equiv of HOAc, and 15 equiv of H2O afforded
the dioxygenated product with the highest yield (Table 1, entry
10). The catalyst loading of Pd(OAc)2 could be further lowered to
5 mol % to give the desired products with a slightly lower yield
(Table 1, entry 9).
Very recently, our group has embarked upon the palladium-
catalyzed functionalization of alkenes.6 Controlled ꢀ-hydride
elimination in transition-metal-catalyzed reactions is an efficient
strategy for further elaboration of the newly formed metal complex.
Based on our previous work together with inspiration from Sigman’s
Table 1. Optimization Studiesa
The presence of molecular oxygen is crucial for the reaction
(Table 1, entries 2-4). Control experiments showed that 2a and
3a are not interconvertible under the reaction conditions. To
investigate the origin of the hydroxyl group of 2a, isotopic labeling
studies with H218O and 18O2 were performed (eqs 1 and 2). The
isotopic labeling studies demonstrated clearly that the oxygen of
the hydroxyl group of 2a originated from molecular O2, hence
offering incorporation of the later into synthetically useful product
under mild conditions.
Next, we examined the generality of this methodology, and the
results are summarized in Table 2.9 With factors such as easy
removal of the acetyl group and practical convenience considered,
the initially formed mixtures of alcohol and ester were treated with
K2CO3 in methanol directly to give the alcohol exclusively. As
shown in Table 2, the substituents on the oxime moiety have no
significant influence on the efficiency of this reaction. Both aromatic
and aliphatic groups were tolerated and furnished the target products
in comparable yields. The introduction of heterocycles into this
system makes this methodology more useful for the preparation of
pharmaceuticals and agrochemicals (Table 2, 2e and 2f). Addition
of one methyl group to the tether CH2 has no detrimental effect on
the reaction efficiency (Table 2, 2j). However, two methyl groups
or a bulky phenyl group on the tether CH2 resulted in lower yields
(Table 2, 2m and 2n). Notably, the dioxygenation proceeded
smoothly even for the alkene conjugated with oxime (Table 2, 2o
entry
oxidant
T (°C)
time (h)
yield (2a/3a) (%)b
1
O2
25
25
25
25
25
25
40
40
40
40
40
8
24
24
24
18
24
18
24
48
24
24
70 (66:34)
35 (55:45)
trace
trace
73 (64:36)
trace
74 (60:40)
75 (55:45)
66 (58:42)
78 (53:47)
52 (56:44)
2
PhI(OAc)2
3
Cu(OAc)2
4
BQ
air
-
air
air
air
air
air
5
6
7
8c
9d
10c,e
11f
a Unless noted otherwise, the reactions were carried out on a 0.30
mmol scale of 1a with 10 equiv of HOAc (3 mmol), 24 mol % of
ligand A (0.072 mmol), and 20 mol % of Pd(OAc)2 (0.06 mmol) in
1,2-dichloroethane (DCE). b Isolated yield, the ratio of 2a/3a was
determined by crude 1H NMR. c 10 mol % of Pd(OAc)2 were used. d 5
mol % of Pd(OAc)2 were used. e 15 equiv of H2O were added. f 0.2 g of
4 Å MS was added.
work,3a,b we hypothesized that it may be possible to combine
intramolecular nucleopalladation and reductive elimination, while
retarding ꢀ-hydride elimination, to realize a palladium-catalyzed
dioxygenation of alkene by rational design of substrate.5c,7 Owing
to the coordinating ability and easy cleavage of the N-O bond
and the versatility of the resulting product,8 initially we chose (Z)-
9
6284 J. AM. CHEM. SOC. 2010, 132, 6284–6285
10.1021/ja100716x  2010 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Pd-Catalyzed Oxime Assisted Intramolecular
when 1a was treated with stoichiometric Pd(OAc)2 in the absence of
air or O2, a condition under which 3a should be formed exclusively
according to Wacker oxidation mechanism.12 Therefore, this reaction
is not a simple variant of the Wacker oxidation. When H2O2 was
used as oxidant, similar results with oxygen were observed (eq 5).
Furthermore, the reductive elimination of palladium-alkyl complex to
form a C-O bond is mainly observed in PdII/IV catalyzed organic
transformations.2b,d,f,3d,5f On the basis of these experimental results,
we assumed that the PdII/IV catalysis might be involved in this reaction.
In conclusion, we have developed a palladium-catalyzed oxime
assisted intramolecular dioxygenation of alkenes by using 1 atm
of air as the sole oxidant. This methodology incorporated atmo-
spheric O2 into synthetically useful compounds efficiently under
extremely mild conditions, which make it environmentally benign,
economical, and practical. Further study toward the mechanism and
development of an asymmetric version is in progress in our
laboratory.
Dioxygenation of Alkenes with 1 atm of Air as the Sole Oxidanta
Acknowledgment. We gratefully acknowledge the Nanyang
Technological University and Singapore Ministry of Education
Academic Research Fund Tier 2 (No. T207B1220RS) for the
funding of this research. We thank Profs. K. Narasaka, S. Chiba,
and J. (Steve) Zhou for their helpful discussions.
Supporting Information Available: Additional experimental pro-
cedures, all chromatograms, and spectral data for reactions products.
This material is available free of charge via the Internet at http://
pubs.acs.org.
a The reactions were carried out on a 0.3 mmol scale of 1 with 10 equiv
of HOAc (3 mmol), 10 mol % of Pd(OAc)2 (0.03 mmol), 12 mol % ligand
A (1,10-phenanthroline), and 15 equiv of water in 1,2-dichloroethane
(DCE), under 1 atm of air atmosphere. b The ratio of diastereomers was
References
(1) For reviews of palladium-catalyzed reactions, see: (a) Zeni, G.; Larock,
R. C. Chem. ReV. 2006, 106, 4644. (b) Sigman, M. S.; Jensen, D. R. Acc.
Chem. Res. 2006, 39, 221. (c) Beccalli, E. M.; Broggini, G.; Martinelli,
M.; Sottocornola, S. Chem. ReV. 2007, 107, 5318. (d) Chen, X.; Engle,
K. M.; Wang, D. H.; Yu, J. Q. Angew. Chem., Int. Ed. 2009, 48, 5094. (e)
Lyons, T. W.; Sanford, M. S. Chem. ReV. 2010, 110, 1147.
determined by crude H NMR. c 21% of E isomer of the starting material
1
was recovered (the E isomer is a very poor substrate for this reaction).
and 2p). In addition, the rigid alkene also could be used as a
substrate with good diastereoselectivity and yield (Table 2, 2k).
To probe the mechanism of this reaction, substrates 1q and 1r,
both of which contain a ꢀ-proton after hydroxyl-palladation, were
designed and subjected to the standard conditions. As expected,
no dioxygenated product was observed for 1q (eq 3). Only
ꢀ-hydride elimination product 4, accompanied by its double bond
isomer 5, was produced in 66% yield with a ratio of 47:53. This
indicates that the intramolecular cyclization was followed by
ꢀ-hydride elimination to give olefin 4 which isomerized to 5 easily
under the reaction conditions. To our surprise, a mixture of
dioxygenated products (6 and 7) from 1r was obtained while no
ꢀ-hydride elimination product was detected when 1r was subjected
to the reaction conditions (eq 4). We reasoned that the coordination
of oxygen to palladium in the metal complex 8 may have prohibited
the syn ꢀ-hydride elimination. These experiments demonstrated the
existence of a palladium-alkyl intermediate 8. The absence of
substituent at the 2-position of the terminal alkene led to allylic
isomerized product 6, which illustrates that the substituent at the
2-position of the terminal alkene is important to retard the 1,3-
isomerization of allylic palladium complex.11 There was no reaction
(2) (a) Bar, G. L. J.; Lloyd-Jones, G. C.; Booker-Milburn, K. I. J. Am. Chem.
Soc. 2005, 127, 7308. (b) Alexanian, E. J.; Lee, C.; Sorensen, E. J. J. Am.
Chem. Soc. 2005, 127, 7690. (c) Streuff, J.; Ho¨velmann, C. H.; Nieger,
M.; Mun˜iz, K. J. Am. Chem. Soc. 2005, 127, 14586. (d) Liu, G. S.; Stahl,
S. S. J. Am. Chem. Soc. 2006, 128, 7179. (e) Du, H. F.; Zhao, B. G.; Shi,
Y. A. J. Am. Chem. Soc. 2007, 129, 762. (f) Desai, L. V.; Sanford, M. S.
Angew. Chem., Int. Ed. 2007, 46, 5737. (g) Cochran, B. M.; Michael, F. E.
J. Am. Chem. Soc. 2008, 130, 2786.
(3) (a) Schultz, M. J.; Sigman, M. S. J. Am. Chem. Soc. 2006, 128, 1460. (b)
Zhang, Y.; Sigman, M. S. J. Am. Chem. Soc. 2007, 129, 3076. (c) Li, Y.;
Song, D. T.; Dong, V. M. J. Am. Chem. Soc. 2008, 130, 2962. (d) Wang,
A. Z.; Jiang, H. F.; Chen, H. J. J. Am. Chem. Soc. 2009, 131, 3846. (e)
Jensen, K. H.; Pathak, T. P.; Zhang, Y.; Sigman, M. S. J. Am. Chem. Soc.
2009, 131, 17074.
(4) Jacobsen, E. N.; Marko, I.; Mungall, W. S.; Schroeder, G.; Sharpless, K. B.
J. Am. Chem. Soc. 1988, 110, 1968.
(5) For examples for palladium-catalyzed reactions with oxygen, see: (a) Stahl,
S. S. Angew. Chem., Int. Ed. 2004, 43, 3400. (b) Gligorich, K. M.; Sigman,
M. S. Angew. Chem., Int. Ed. 2006, 45, 6612. (c) Trend, R. M.; Ramtohul,
Y. K.; Stoltz, B. M. J. Am. Chem. Soc. 2005, 127, 17778. (d) Liu, G. S.;
Yin, G. Y.; Wu, L. Angew. Chem., Int. Ed. 2008, 47, 4733. (e) Wang,
A. Z.; Jiang, H. F. J. Am. Chem. Soc. 2008, 130, 5030. (f) Zhang, Y. H.;
Yu, J. Q. J. Am. Chem. Soc. 2009, 131, 14654. (g) Zhang, J.; Khaskin, E.;
Anderson, N. P.; Zavalij, P. Y.; Vedernikov, A. N. Chem. Commun. 2008,
3625. (h) Vedernikov, A. N. Chem. Commun. 2009, 4781.
(6) (a) Xu, Y. H.; Lu, J.; Loh, T. P. J. Am. Chem. Soc. 2009, 131, 1372. (b)
Zhou, H.; Xu, Y. H.; Chung, W. J.; Loh, T. P. Angew. Chem., Int. Ed.
2009, 48, 5355. (c) Zhou, H.; Chung, W. J.; Xu, Y. H.; Loh, T. P. Chem.
Commun. 2009, 3472.
(7) Liu, G. S.; Stahl, S. S. J. Am. Chem. Soc. 2007, 129, 6328, and references
cited therein.
(8) (a) Jiang, D. H.; Peng, J. S.; Chen, Y. W. Org. Lett. 2008, 10, 1695. (b)
Chaminade, X.; Chiba, S.; Narasaka, K.; Dunach, E. Tetrahedron. Lett.
2008, 49, 2384. (c) One example of reduction and cleavage of N-O bond
was attached in the Supporting Information.
(9) So far, only five-membered rings were constructed. Attempts to construct
a six- or larger membered ring by this methodology were unsuccessful.
(10) CCDC 757318 contains the supplementary crystallographic data for this paper.
(11) (a) Chen, M. S.; White, M. S. C. J. Am. Chem. Soc. 2004, 126, 1346. (b)
Chen, M. S.; Prabagaran, N.; Labenz, N. A.; White, M. S. C. J. Am. Chem.
Soc. 2005, 127, 6970.
(12) (a) Smidt, J.; Hafner, W.; Jira, R.; Sedlmeier, J.; Sieber, R.; Ruttinger, R.;
Kojer, H. Angew. Chem., Int. Ed. Engl. 1959, 71, 176. (b) Keith, J. A.;
Oxgaard, J.; Goddard, W. A. J. Am. Chem. Soc. 2006, 128, 3132.
JA100716X
9
J. AM. CHEM. SOC. VOL. 132, NO. 18, 2010 6285