Highly efficient, regioselective, and stereospecific oxidation of aliphatic C-H groups with H2O2, catalyzed by aminopyridine manganese complexes

Article abstract of DOI:10.1021/ol3015122

Aminopyridine manganese complexes [LMn^II(OTf)₂] having a similar coordination topology catalyze the oxidation of unactivated aliphatic C-H groups with H₂O₂, demonstrating excellent efficiency (up to TON = 970), site selectivity, and stereospecificity (up to >99%).

Full text of DOI:10.1021/ol3015122

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
Highly Efficient, Regioselective, and
Stereospecific Oxidation of Aliphatic CꢀH
Groups with H O , Catalyzed by
000–000
2
2
Aminopyridine Manganese Complexes
†
Roman V. Ottenbacher, Denis G. Samsonenko, Evgenii P. Talsi, and
‡
§
,§
Konstantin P. Bryliakov*
Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russian Federation,
Nikolaev Institute of Inorganic Chemistry, Pr. Lavrentieva 9, Novosibirsk 630090,
Russian Federation, and Boreskov Institute of Catalysis, Pr. Lavrentieva 5,
Novosibirsk 630090, Russian Federation
bryliako@catalysis.ru
Received May 3, 2012
ABSTRACT
II
Aminopyridine manganese complexes [LMn (OTf)
2
] having a similar coordination topology catalyze the oxidation of unactivated aliphatic CꢀH
groups with H O , demonstrating excellent efficiency (up to TON = 970), site selectivity, and stereospecificity (up to >99%).
2
2
Direct CꢀH transformations have attracted particular
interest as valuable tools for the synthesis of natural and
unnatural compounds, as well as mechanistic probes for
Major drawbacks, opposing their wide synthetic applica-
tion, are the modest turnover numbers sustained by non-
2
heme Fe systems, and the lack of predictable selectivity in
1
the understanding of the properties of CꢀH groups.
the catalytic oxidation of inactivated aliphatic CꢀH
3
While the oxidations of CꢀH bonds, catalyzed by en-
zymes, are widely present in nature, selective, efficient, and
environmentally benign CꢀH oxidation catalyzed by syn-
thetic low-molecular weight compounds remains a great
groups.
Nonheme Mn catalyzed CꢀH oxidations with H O
2
2
have been less represented in the literature, with known
examples mainly focusing on Mn complexes with 1,4,7-
1
4
contemporary challenge in synthetic chemistry. To date, a
vast number of nonheme iron based catalysts have been
trimethyl-1,4,7-triazacyclononane (Me tacn) or its derivatives.
3
developed; some of those can conduct CꢀH oxidations
(
3) (a) Chen, M. S.; White, M. K. Science 2007, 318, 783. (b) Chen,
1
with H O with high selectivity and stereospecificity.
2
M. S.; White, M. K. Science 2010, 327, 566. (c) Company, A.; G oꢀ mez, L.;
G u€ ell, M.; Ribas, X.; Luis, J. M.; Que, L., Jr.; Costas, M. J. Am. Chem.
Soc. 2007, 129, 15766. (d) Company, A.; G oꢀ mez, L.; Fontrodona, X.;
2
ꢀ
Ribas, X.; Costas, M. Chem.;Eur. J. 2008, 14, 5727. (e) Gοmez, L.;
†
‡
§
Novosibirsk State University.
Nikolaev Institute of Inorganic Chemistry.
Boreskov Institute of Catalysis.
Garcia-Bosch, I.; Company, A.; Benet-Buchholz, J.; Polo, A.; Sala, X.;
Ribas, X.; Costas, M. Angew. Chem., Int. Ed. 2009, 48, 5720. (f) Bigi,
M. A.; Reed, S. A.; White, M. C. Nat. Chem. 2011, 3, 216. (g) Hitomi, Y.;
Arakawa, K.; Funabiki, T.; Kodera, M. Angew. Chem., Int. Ed. 2012, 51,
3448. Nonheme iron based catalyst systems for CꢀH oxidations have
been recently overviewed: (h) Costas, M.; Mehn, M. P.; Jensen, M. P.;
Que, L., Jr. Chem. Rev. 2004, 104, 939. (i) Correa, A.; Manche n~ o, O. G.;
Bolm, C. Chem. Soc. Rev. 2008, 37, 1108. (j) Shteinman, A. Russ. Chem.
Rev. 2008, 77, 945. (k) Talsi, E. P.; Bryliakov, K. P. Coord. Chem. Rev.
2012, 256, 1418.
(1) (a) Christmann, M. Angew. Chem., Int. Ed. 2008, 47, 2740. (b)
Que, L., Jr.; Tolman, W. Nature 2008, 455, 333. (c) Shul’pin, G. B. Mini-
Rev. Org. Chem. 2009, 6, 95. (d) Sun, C.-L.; Li, B.-J.; Shi, Z.-J. Chem.
Rev. 2011, 111, 1293.
(
derivatized triazacyclononane ligands or with bulky pinene groups
2) A notable exception is the Fe complexes with methylpyridine
3d,e
(>50ꢀ100 turnovers).
1
0.1021/ol3015122 r XXXX American Chemical Society

Importantly, in many cases Mn catalysts demonstrated higher
efficiencies than Fe ones (up to hundreds of turnovers), albeit
3k,4
with lower selectivity.
8
Figure 2. Ball-and-stick plot showing the X-ray structure of
complex [((S)-pmpp)Mn(CF SO ) ] (3). Hydrogen atoms ex-
3 3 2
cluded for clarity.
3
3ꢀ
SO .
Figure 1. Manganese(II) complexes considered; X = CF
Recently, Costas with co-workers reported that com-
H,Me
plex [(
turnovers in the oxidation of cis-1,2-dimethylcyclo-
Pytacn)Mn(CF SO ) ] performed eight catalytic
3 3 2
Scheme 1. Catalytic Oxidation of Various Aliphatic Alkanes
3
e
hexane. We have found that chiral complexes [((S,S)-
bpmcn)Mn(CF SO ) ] (1) and [((S,S)-pdp)Mn(CF SO ) ]
3
3 2
3
3 2
(
olefins with AcOOH and H O /AcOH with high efficiency
2) catalyze the enantioselective epoxidation of various
2
2
5
up to 1000 TON); the structure of the aminopyridine
(
ligand and a properadjustmentofreactionconditionswere
crucial for attaining high efficiency and predictable selec-
tivity. In this work, we present the CꢀH oxidation reac-
tivity of Mn complexes 1ꢀ3 (Figure 1): under appropriate
conditions, they demonstrate previously unachievable
high site selectivities and high efficiencies at the same time.
3
e,5a,6
7
8
Complexes 1,
3, Figure 2) feature a similar cis-R-coordination topology,
which was earlier shown to be crucial for achieving good
2, and [((S)-pmpp)Mn(CF SO ) ]
3 3 2
(
(4) (a) Lindsay Smith, J. R.; Shul’pin, G. B. Tetrahedron Lett. 1998,
9, 4909. (b) Shul’pin, G. B.; Lindsay Smith, J. R. Russ. Chem. Bull.
3
1
998, 47, 2379. (c) Shul’pin, G. B.; S u€ ss-Fink, G.; Lindsay Smith, J. R.
Tetrahedron 1999, 55, 5345. (d) Shul’pin, G. B.; S u€ ss-Fink, G.; Shul’pina,
L. S. J. Mol. Catal. A: Chem. 2001, 170, 17. (e) Shul’pin, G. B.; Nizova,
G. V.; Kozlov, Y. N.; Pechenkina, I. G. New J. Chem. 2002, 26, 1238.
(
f) Shul’pin, G. B. J. Mol. Catal. A: Chem. 2002, 189, 39. (g) Nizova, G. V.;
Bolm, C.; Ceccarelli, S.; Pavan, C.; Shul’pin, G. B. Adv. Synth. Catal. 2002,
44, 899. (h) Bennur, T. H.; Sabne, S.; Desphande, S. S.; Srinivas, D.;
3
Sivasanker, S. J. Mol. Catal. A: Chem. 2002, 185, 71. (i) Ryu, J. Y.; Kim,
S. O.; Nam, W.; Heo, S.; Kim, J. Bull. Korean Chem. Soc. 2003, 24, 1835.
(j) Shul’pin, G. B.; Nizova, G. V.; Kozlov, Y. N.; Arutyunov, V. S.; dos
Santos, A. C. M.; Ferreira, A. C. T.; Mandelli, D. J. Organomet. Chem.
2005, 690, 4498. (k) Nizova, G. V.; Shul’pin, G. B. Tetrahedron 2007, 63,
7997. (l) Shul’pin, G. B.; Matthes, M. G.; Romakh, V. B.; Barbosa, M. I. F.;
Aoyagi, J. L. T.; Mandelli, D. Tetrahedron 2008, 64, 2143. (m) Romakh,
V. B.; Rherrien, B.; S u€ ss-Fink, G.; Shul’pin, G. B. Inorg. Chem. 2007, 46,
1315.
(
5) (a) Ottenbacher, R. V.; Bryliakov, K. P.; Talsi, E. P. Inorg. Chem.
2010, 49, 8620. (b) Ottenbacher, R. V.; Bryliakov, K. P.; Talsi, E. P. Adv.
Synth Catal. 2011, 353, 558. (c) Lyakin, O. Yu.; Ottenbacher, R. V.;
Bryliakov, K. P.; Talsi, E. P. ACS Catalysis 2012, 2, 1196.
(6) X-ray structure of the (R,R)-enantiomer of complex 1 was
reported in: Murphy, A.; Dubois, G.; Stack, T. D. P. J. Am. Chem.
Soc. 2003, 125, 5250.
(
7) X-ray structure of [((S,S)-pdp)Mn(CF
the Supporting Information for ref 5b.
8) CCDC 877672 (Λ-R-[((S)-pmpp)Mn(CF
3
SO
3
)
2
] (2) was reported in
], complex 3) con-
catalytic efficiency and high alcohol/ketone selectivity in
9
nonheme iron systems.
(
3
SO
3
)
2
tains the supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Additional
X-ray data are provided in the Supporting Information.
(9) (a) Chen, K.; Que, L., Jr. J. Am. Chem. Soc. 2001, 123, 6327.
(b) Costas, M.; Que, L., Jr. Angew. Chem., Int. Ed. 2002, 41, 2179.
B
Org. Lett., Vol. XX, No. XX, XXXX

At high oxidant/substrate ratios, the reaction yields
mainly cyclohexanone (apparently via further oxidation
of the initially formed cyclohexanol), which requires two
molecules of H O per one substrate molecule.
Table 1. Cyclohexane Oxidation with H O in the Presence of
2
2
a
1ꢀ3
2
2
1
2
3
Adamantane oxidation occurs predominately at more
b
electron-rich tertiary CꢀH groups (3°/2° values of
conversion, %
84
68
72
1
1
c
A/K
5.0
144
4.9
116
5.1
124
40ꢀ49), despite a 3-fold statistical prevalence of second-
ary CꢀH groups, yielding 1-adamantanol as the main
product (2-adamantanol and 2-adamantanone are the
major and minor byproduct, respectively).
d
TN
a
Reaction conditions: solvent: 0.4 mL of CH
AcOH, [cyclohexane]/[H O ]/[catalyst] = 400:20:0.1 μmol; 0 °C, oxi-
2 2
dant added by syringe pump over 1 h, and reaction mixture stirred for
3
CN þ 0.08 mL of
To probe the electronic effects on the oxidation site
selectivity, in particular the influence of electron-with-
drawing groups, the oxidation of substrates 4ꢀ6 contain-
ing different substituents at the same position has been
performed (Table 3). While the oxidation of 2,6-dimethy-
loctane yields an equimolar mixture of ‘remote’ and ‘prox-
imal’ oxidation products, introduction of electron accep-
tors substantially deactivates the proximal tertiary CꢀH
group. In the case of 6, the observed remote/proximal ratio
varies from 34:1 up to 97:1; to the best of our knowledge,
these values are the highest reported for nonheme metal
b
additional 1 h. Based on the oxidant, calculated as 100% ꢁ (alcohol þ 2
c
d
2 2 0
ketone)/[H O ] . Alcohol/ketone ratio. Turnover number, mol of
products (A þ K) per mol of catalyst.
Table 2. Catalytic Oxidation of Cyclohexane and Adamantane
with H
a
2
O
2
in the Presence of 1ꢀ3
yield of products, %
conversion,
3°d/
2°
ketone/
alcohol
3
b,c
catalysts. The oxidation of tertiary CꢀH groups in the
substrate
catalyst
%
presence of catalysts 1ꢀ3 is highly sensitive to the steric
environment: (ꢀ)-acetoxy-p-menthane 7 yields predomi-
nately product 8 with all catalysts (Table 4). Complex 2
demonstrates an unprecedented selectivity for 8 over 9
cyclohexane
cyclohexane
cyclohexane
1
2
3
77.8 (778)
87.0 (870)
80.0 (800)
ꢀ
ꢀ
ꢀ
71.7:6.1
84.2:2.8
75.0:5.0
conversion,
3°d/
2°
1-ol/2-ol/
2-one
(
57:1 at 0 °C; at ꢀ10 °C, 8 is formed as the only detectable
b,c
substrate
catalyst
%
product).
To test the scalability of the CꢀH oxidations, larger-
adamantane
adamantane
adamantane
1
2
3
10.3 (103)
70.6 (706)
36.2 (362)
48
40
49
9.7:0.6:ꢀ
65.7:3.2:1.7
34.1:2.1:ꢀ
scale oxidation of substrates 5, 6, and 7 in the presence of
e
a
Reaction conditions: [Cyclohexane]/[H
CN þ 0.08 mL of AcOH, oxidant added
by syringe pump over 1 h, and reaction mixture stirred for additional 1 h.
Adamantane]/[H
]/[catalyst] = 100:130:0.1 μmol, 0 °C, solvent: 0.8 mL of
CH Cl þ 0.16 mL of AcOH, oxidant added by syringe
CN þ 0.6 mL of CH
2 2
O ]/[catalyst] = 100:250:0.1
μmol, 0 °C, solvent: 0.4 mL of CH
3
a
Table 3. Catalytic Oxidation of Substrates 4ꢀ6
[
2 2
O
yield of products, %
3
2
2
pump over 30 min, and reaction mixture stirred for additional 5.5 h.
b
c
Conversion based on the substrate. Turnover number given in parentheses,
remote/
b,c
d
substrate catalyst conversion, %
remote proximal proximal
in mol of products per mol of catalyst. 3°/2° = 3 ꢁ [1-adamantanol]/
e
(
[2-adamantanol] þ [2-adamantanone]). Oxidant added over 2 h.
4
4
4
1
2
3
63.5 (635)
68.8 (688)
57.8 (578)
31.8
34.4
28.9
31.8
34.4
28.9
1:1
1:1
1:1
Cyclohexane is one of the most widely used ‘test sub-
strates’ for catalyzed CꢀH oxidations, since it enables free-
radical-driven oxidation to be readily distinguished from
the metal-based one: in the former case, the observed cyclo-
hexanol/cyclohexanone ratio is expected to be close to 1.0,
while, in the latter one, it should be substantially higher than
5
5
5
1
2
3
49.1 (491)
53.4 (534)
44.0 (440)
43.1
46.6
37.6
6.0
6.9
6.4
7:1
7:1
6:1
6
6
6
1
2
3
67.7 (677)
74.1 (741)
44.5 (445)
56.2
67.6
43.5
1.5
37:1
34:1
97:1
10
2.0
1. The results of the cyclohexane oxidation (Scheme 1) are
0.45
presented in Table 1. For all catalysts, the A/K ≈ 5 (clearly
indicative of metal-based oxidant) values are the highest ever
reported for nonheme manganese catalyzed cyclohexane
a
Reaction conditions: solvent: 0.4 mL of CH
AcOH, oxidant added by syringe pump over 30 min, and reaction
mixture stirred for additional 2.5 h, [alkane]/[H O ]/[catalyst] =
100:130:0.1 μmol, 0 °C. Conversion based on the substrate. Turnover
number given in parentheses, in mol of products per mol of catalyst.
3
CN þ 0.08 mL of
3
k
2
2
oxidations with H O . Under these model conditions
2
2
b
c
(
catalytic turnovers, which is already higher than that for most
[H O ] , [substrate], Table 1), 1ꢀ3 performed 115ꢀ144
2
2
3
,9
of the related iron-based catalysts. Under practical condi-
tions ([H O ] g [substrate]), the catalytic efficiencies are even
more impressive, up to a TON of 870 (Table 2).
catalyst 2 were carried out (Supporting Information); after
column chromatography separation, the isolated yields of
major oxidation products were 49, 52, and 66%, which is
2
2
(
10) (a) Tanase, S.; Bowman, E. In Advances in Inorganic Chemistry,
Vol. 58; van Eldik, R., Reedijk, J., Eds.; Academic Press: 2006; p 29.
b) Costas, M.; Chen, K.; Que, L., Jr. Coord. Chem. Rev. 2000, 200ꢀ202, 517.
(11) These 3°/2° selectivities are among the highest reported for
nonheme Fe and Mn catalysts (up to 48); see refs 10a, 10b.
(
Org. Lett., Vol. XX, No. XX, XXXX
C

manganese complexes 1ꢀ3, in the presence of acetic acid.
All three catalysts demonstrate unprecedented high selec-
tivity and stereospecificity, and high efficiency (up to 970
turnovers) and good oxidant economy at the same time.
The reactivity of catalysts 1ꢀ3 is sufficient to complete the
reaction within an acceptable time (2ꢀ4 h) at low catalyst
loadings (0.1 mol %). The most plausible origin of the
much higher efficiency of manganese systems (as com-
pared with iron ones) is their higher reactivity, which
allows lower catalyst loadings (0.1 mol % for Mn vs
Table 4. Oxidation of (ꢀ)-Acetoxy-p-menthane (7) and cis-1,2-
a
Dimethylcyclohexane (10) with H
2
O
2
in the Presence of 1ꢀ3
yield of products
b,c
substrate
catalyst
conversion, %
8:9, %
8:9
7
7
7
7
1
2
3
58.2 (582)
69.5 (695)
64.0 (640)
27.9 (279)
51.5:3.3
68.3:1.2
56.0:4.3
27.9:ꢀ
16:1
57:1
13:1
ꢀ
d
2
1
.0ꢀ15.0 mol % for Fe), thus reducing the catalyst degra-
b,c
e
substrate
catalyst
conversion, %
11:12:13, %
RC, %
dation via bimolecular collisions. We believe that the
predictable site selectivity and excellent efficiency of ami-
nopyridine manganese complexes will appreciably elevate
the area of transition metal catalyzed sustainable regio-
10
10
10
1
2
3
89.4 (894)
97.0 (970)
84.6 (846)
79.7:4.9:4.9
92.9:1.7:2.3
75.6:4.5:4.5
>99
>99
>99
5
b,c
and stereoselective CꢀH oxidations and epoxidations.
a
Reaction conditions: solvent: 0.4 mL of CH
AcOH, oxidant added by syringe pump over 30 min, and reaction
mixture stirred for additional 3.5 h, [alkane]/[H ]/[catalyst] =
3
CN þ 0.08 mL of
Further studies will be aimed at the elucidation of the
nature of catalytically active species and at the application
of the novel catalyst systems for preparative catalytic
syntheses of complex molecular structures.
2
O
2
b
c
1
00:130:0.1 μmol, 0 °C. Conversion based on the substrate. Turnover
d
number given in parentheses, in mol of products per mol of catalyst. At
e
ꢀ
10 °C. RC = 100% ꢁ [((1R,2R)-11 þ (1S,2S)-11) ꢀ ((1R,2S)-11 þ
(
1S,2R)-11)]/[((1R,2R)-11 þ (1S,2S)-11) þ ((1R,2S)-11 þ (1S,2R)-11)].
Acknowledgment. This work was supported by the
Russian Foundation for Basic Research, Grant 12-03-
comparable or only a few percent lower than those under
model conditions (cf. Tables 3 and 4).
00782. We thank Dr. O. Yu. Lyakin (Boreskov Institute
ofCatalysis) for the donation of the (S,S)-pdp chiralligand
which was used for the synthesis of complex 2.
Finally, the stereospecificity of catalysts 1ꢀ3 was probed
using cis-1,2-dimethylcyclohexane as the test substrate
(
Table 4). The oxidations yield mainly the tertiary alcohol
1 in good to high yields and with excellent (>99%)
Supporting Information Available. Experimental pro-
1
13
1
cedures, copies of H and C NMR spectra, and the
X-ray data for complex 3. This material is available free of
charge via the Internet at http://pubs.acs.org.
retention of the cis-configuration, ketones 12 and 13 being
minor byproducts
In summary, the oxidation of aliphatic CꢀH groups
with H O is efficiently catalyzed by cis-R-aminopyridine
The authors declare no competing financial interest.
2
2
D
Org. Lett., Vol. XX, No. XX, XXXX