Enantio- and regioselective iridium-catalyzed allylic esterification

Article abstract of DOI:10.1021/ja411869r

A highly enantioselective and regioselective Ir-catalyzed allylic esterification is described, in which branched allylic esters are synthesized directly. Carboxylates were used as nucleophiles and linear allylic phosphates as electrophiles. In some cases the allylic substitution reaction was found to be accompanied by a kinetic resolution process, which causes a change of the enantiomeric excess.

Full text of DOI:10.1021/ja411869r

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Communication
Enantio- and Regioselective Iridium-Catalyzed Allylic Esterification
Jianping Qu, Lydia Roßberg, and Guenter Helmchen
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja411869r • Publication Date (Web): 14 Jan 2014
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Enantio- and Regioselective Iridium-Catalyzed Allylic Esterification
Jianping Qu, Lydia Roßberg and Günter Helmchen*
Organisch-Chemisches Institut der Ruprecht-Karls-Universität Heidelberg,
Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany
RECEIVED DATE (automatically inserted by publisher); Email: g.helmchen@oci.uni-heidelberg.de
arylallyl chlorides.9 The catalyst requires an elaborate synthesis
Abstract: A highly enantioselective and regioselective
involving approximately 10 linear steps, which is a serious im-
pediment to applications.10 Overman, Kirsch et al. accomplished
asymmetric Pd-catalyzed allylic esterifications with (Z)-allylic
trichloroacetimidates, albeit with a narrow substrate scope ex-
cluding sp2 bound substituents, i. e. aryl and alkenyl groups.11
Thus, the development of a generally applicable allylic esteri-
fication appeared as a true challenge, which we have accepted.
Herein we are pleased to report the first transition metal cataly-
zed asymmetric esterification with linear allylic substrates with
broad substrate scope and catalyst loading as low as 0.2 mol %.
Exploratory experiments were carried out with carboxylates
containing a double bond, for example crotonates, in order to
ensure synthetic applications via ring closing metathesis.12
Ir-catalyzed allylic esterification is described, in which
branched allylic esters are synthesized directly. Carboxyl-
ates were used as nucleophiles and linear allylic phos-
phates as electrophiles. In some cases the allylic substi-
tution reaction was found to be accompanied by a kinetic
resolution process, which causes a change of the enantio-
meric excess.
14
15
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Asymmetric allylic substitution has found numerous applica-
tions in organic synthesis.1 After years of predominance by Pd-
catalysis, catalysts based on other metals have been gaining
importance, particularly for reactions of monosubstituted allylic
substrates to give branched products (eq. 1).
Ar
R
O
P
N
aR
O
R
Ar
Among these, the iridium-catalyzed asymmetric allylic substi-
tution offers a very broad scope, particularly with respect to the
range of possible nucleophiles. 2 As catalysts, (allyl)Ir-com-
plexes derived in situ from [Ir(cod)Cl]2 and a phosphoramidite
by treatment with base have most often been used (Figure 1).
More recently, pure (π-allyl)Ir complexes C have become rea-
dily available,3 which are air stable and are now often used as
single component catalysts.2c-e
Regioselectivity can be low with allylic substrates carrying an
sp3 bound substituent R. In such cases, replacement of cod by
dbcot (dbcot = dibenzocyclooctatetraene) generally gives im-
proved results.4 In addition, reactions catalyzed by dbcot com-
plexes can be run under air, tolerate a wide variety of solvents
and can be run at higher temperatures than reactions catalyzed
by cod complexes.
Over the last few years, allylic substitutions with O-nucleo-
philes have received considerable attention. While good results
were obtained for reactions with phenolates and alkoxides,5
water and carboxylates turned out to be problematic nucleophi-
les, necessitating the use of water surrogates, such as silanoates.6
We were able to solve the “water problem” by using bicarbonate
as the nucleophile in conjunction with allylic carbonates as elec-
trophiles and catalysts C2 or C3 in an aqueous reaction medi-
um.7 Concerning allylic esterification with Ir-catalysts, only kin-
etic resolutions with branched allylic esters as substrates have
been reported (Carreira8a and Hartwig’s8b group). Hartwig et al.
observed a remarkably high selectivity factor for kinetic resolu-
tions with branched allylic benzoates.8b More, but still limited
success was obtained with other transition metal catalysts.
Onitsuka et al. developed Ru-catalyzed reactions of (E)-allylic
chlorides; however, high ee was only achieved in the case of
L1
:
L2
:
Ar = Ph
Ar = 2-MeOC6H4
cod
dbcot
+
OTf
O
O
P
O
Ir
P
N
O
Ir
R
CH2
CH2
H3C
H3C
N
C
C'
Ar
Ar
Ar
Ar
C1, C1': diene = cod, Ar = 2-MeOC6H4, R = CH3
C2, C2': diene = dbcot, Ar = Ph, R = CH3
C3: C3': diene = dbcot, Ar = 2-MeOC6H4, R = CH3
Figure 1. Ligands and (π-allyl)Ir-complexes used in this work.
We initially used cinnamyl derivatives 1a-1e as substrates
(Table 1), because it was known that esters of branched arylal-
lylic alcohols can undergo an Ir-catalyzed rearrangement, via (π-
allyl)Ir complexes, to the linear esters.8b This process could lead
to reduced yield and ee of the branched product. (E)-Crotonate
was employed as the standard nucleophile. Using ent-C1 as cat-
alyst, the phosphate 1d gave promising results, whereas the car-
bonate 1a, the chloride 1b and the trichloroacetimidate 1c were
found to be unsuitable substrates (Table 1, entries 1-6). Signifi-
cant improvement of enantio- as well as regioselectivity and rate
were obtained with the dbcot complexes ent-C2 and ent-C3 as
catalysts (entries 7, 8). The branched/linear (b/l) ratio (ent-3/4)
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Table 1. Optimization of Reaction Variables Using 3-Phenylallylic Substrates a
1
2
3
4
5
O
O
O
O
MO
catalyst
+
Ph
X
Ph
O
Ph
1
3a
4a
6
temp
time
(h)
24
2
24
2
24
24
2
0.5
1
2
5
6
0.5
1.0
1.0
4.0
ent-
yield
(%)c
n.d.
61
<10
n.d.
40
28
n.d.
80
80
63
80
68
60
65
63
60
ee
(%)d
13
43
n.d.
75
84
88
80
88
92
91
91
92
90
89
89
94
7
8
9
entry
X
1
M
1/2
catalyst
(°C)
45
45
45
45
rt
3a/4ab
1:5
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
OCO2Me
Cl
1a
1b
1c
1d
K
K
K
K
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
1.05:1
1:1.5
1.05:1
ent-C1
ent-C1
ent-C1
ent-C1
ent-C1
ent-C1
ent-C2
ent-C3
ent-C3
ent-C3
ent-C3
ent-C3
ent-C3
ent-C3
ent-C3
ent-C3
>20:1
n.d.
>10:1
6:1
OCNHCCl3
OP(O)(OEt)2
OP(O)(OEt)2
OP(O)(OEt)2
OP(O)(OEt)2
OP(O)(OEt)2
OP(O)(OEt)2
OP(O)(OEt)2
OP(O)(OEt)2
OP(O)(OEt)2
OP(O)(OEt)2
OP(O)(OEt)2
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
1d Na
1d
1d
1d
1d Cs
1d
1d Na
1d
1d
1d
Li
K
K
rt
6:1
45
45
rt
rt
rt
rt
0
0
0
>10:1
>20:1
>10:1
>10:1
>10:1
>10:1
>20:1
8:1
K
Li
K
K
K
K
OP(O)(OEt)2e 1d
6:1
>20:1
OP(O)(OEH)2 1e
0
a Conditions: argon atmosphere, 1 (2.0 equiv.), crotonic acid salt (1.0 equiv.), catalyst (4 mol %), THF (10 mL/mmol of
2). b Determined by 1H NMR analysis of the crude product. c Isolated yield of branched product; n.d. = not determined. d
Determined by HPLC on a chiral column. e (EH = 2-ethylhexyl).
was high, when the allylic component 1 was used in excess (cf.
entries 13-15); we used a 5% excess of 1 in all further reactions.
Under these conditions an allyl complex C is expected to be the
resting state3 of the reaction (see below). Further investigation
of the reaction conditions revealed that the reaction selectivity is
insensitive to temperature in the range 0-30°C. However, selec-
tivity and rate are fairly sensitive to the counter ion of the car-
boxylate; faster reactions were obtained with Cs+ and K+ than
Na+ and Li+ (entries 4-6 and 9-12). Potassium salts were hence-
forth used.
high selectivities. Initial experiments with substrate 1f, R = n-
heptyl, and potassium crotonate were disappointing; while re-
gioselectivity was high, the ee was low (Table 2, entry 1). The
b/l ratio and ee were improved by increasing the size of the leav-
ing group (entries 1-4). The readily available di-(2-ethylhexyl)-
phosphates showed high reactivity (entry 6), gave optimal selec-
tivity and were henceforth generally employed.13 An improve-
ment was also found for the corresponding cinnamyl derivative
(Table 1, entry 16). Solvent tests demonstrated that toluene and
ethers give rise to high ees, while polar solvents give rise to low
ees (see Supporting Information). Commercial dry grade t-
Substrates with aryl substituents often give rise to particularly
Table 2. Optimization of Reaction Conditions for 3-Heptyl-allyl phosphates and the Crotonate 2a as Substrates
(EH = 2-Ethylhexyl)a
O
O
O
O
KO
2a
+
n-C7H15
O
n-C7H15
OP(O)(OR')2
n-C7H15
Ir-catalyst (C)
3b
4b
1
entry
X (substrate)
1
catalyst
(mol %)
solvent
temp
(°C)
0
0
0
0
-20
rt
rt
rt
rt
35
rt
rt
rt
rt
rt
rt
time
3/4b
yieldc
ee
(h)
0.5
1
(conv d) (%)
(%)e
70
1
2
3
4
5
6
7
8
OP(O)(OEt)2
OP(O)(OiPr)2
OP(O)(OtBu)2
OP(O)(OEH)2
OP(O)(OEH)2
OP(O)(OEH)2
OP(O)(OEH)2
OP(O)(OEH)2
OP(O)(OEH)2
OP(O)(OEH)2
OP(O)(OEH)2
OP(O)(OEH)2
OP(O)(OEH)2
OP(O)(OEH)2
OP(O)(OEH)2
OP(O)(OEH)2
1f
1g
1h
1i
1i
1i
1i
1i
1i
1i
1i
1i
1i
1i
1i
1i
ent-C3 (4)
ent-C3 (4)
ent-C3 (4)
ent-C3 (4)
ent-C3 (4)
ent-C3 (1)
C3 (1)
C3 (0.5)
C3 (0.5)
C3 (0.2)
C3 (0.5)
C3 (0.5)i
C3 (0.5)i
C3 (0.5)i
C3 (0.5)i
C3 (0.5)i,l
THF
THF
THF
THF
THF
THF
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
20:1
20:1
n.d. (95)
n.d.
n.d.
n.d.
54 (70)
77
79
79
85
75
92.5
93
93
95.5
94.5
77
1
5
8
2
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
0.5
2
89
80
75
60
90
70
70
73
9f
3
10f
11g
12
13h
14j
15k
16
12
0.5
3
98
99
96
95
3
1.5
3.5
2.5
71
70
98
a Conditions: argon atmosphere, phosphate 1 (1.05 equiv.), nucleophile 2a (1.0 equiv.), catalyst ent-C3 or C3 (4-0.2 mol %), dry
solvent (10 mL/mmol of 2a). Regioselectivity was determined by 1H NMR analysis of the crude product. Isolated yield of
b
c
branched product. d Conversion of 1 was determined by 1H NMR of the crude product. e Determined by GC on a chiral column.
f
The reaction mixture was subjected to freeze-pump-thaw degassing. g 2.8 equiv of water were added. h MS 4Å was added (200
i
mg/mmol). A mixture of C3 and 2a was kept under oil pump vacuum for 10 min, then argon was introduced and further
components were added. j c = 0.2 M. k c = 0.5 M. l Reaction in air.
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Scheme 1. Mechanistic rationale of a combined allylic substitution/ kin-
etic resolution.
BuOMe was chosen as a standard solvent (entry 7). Rearrange-
1
2
3
4
5
6
7
8
ment of the branched to the linear product, even with an excess
of the nucleophile, was not observed with substrate 1f. The
catalyst loading could be reduced to 0.2 mol % without substan-
tial decrease in yield or ee (entries 8-10). In view of previous
results with aqueous reaction media,7a,14 it was a surprise that
water as an additive led to a marked decrease of the enan-
tiomeric excess (entry 11). As a consequence, catalyst C3 and
salt 2a were dried prior to the reaction; this led to a distinct
increase of enantioselectivity (entry 12). Addition of MS 4Å
further improved the ee to 99 % (entry 13). In order to get a
value of the reaction time not biased by low solubility of the salt
2a, a rather low standard concentration of 0.1 M was chosen.
However, the reaction could be run at higher concentration, with
a small accompanied decrease of the ee (entries 14, 15). Finally,
it was possible to carry out reactions in air (entry 16).
As mentioned above, the rearrangement of the branched to
the linear isomers is potentially accompanied by a decrease of
the ee. Therefore, time dependence of the ee was investigated in
detail with representative substrates using THF as the solvent
(Fig. 2). A marked decrease in ee was found for arylallyl sub-
strates and a crotyl derivative (R = CH3), while the ee was con-
stant for another alkylallyl compound (R = n-heptyl). Generally,
the effect is small during the reaction time.
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
The scope of the esterification reaction was explored using
the optimal conditions (Table 2, entry 12) in conjunction with
catalyst C3. The results presented in Table 3 demonstrate that
even with substrates containing an sp2 substituent (R) the ee is
generally high, if the reaction is stopped at 62-85% conversion
in order to prevent further rearrangement. We also reexamined
the phosphate leaving group. For the formation of 3a, diethyl
phosphate 1d was as well suited as the more complicated phos-
phate 1e.
Absolute configurations of the products with known configu-
ration were as expected on the basis of a general rule, which was
found to be valid for all allylic substitutions catalyzed by cyc-
lometallated Ir-complexes.2a
In summary, we have developed the first direct Ir-catalyzed
enantioselective allylic esterification, which allows for syntheti-
cally valuable branched allylic esters to be generated. A wide
variety of solvents and reaction conditions as well as air are
tolerated. Excellent regioselectivities and enantioselectivities
have been achieved with a representative set of substrates.
A rationale for the decrease of the ee over time is represented
in Scheme 1. The allylic substitution promoted by catalysts of
type C via the standard catalytic cycle3 (see Supporting Informa-
tion) yields the ester 3 as the major and ent-3 as the minor bran-
ched product and the linear isomer 4. As already observed by
Hartwig et al.,8b branched allylic esters can undergo kinetic
resolution with a high selectivity factor.15 In the present case,
kinetic resolution involves reaction of the branched isomer 3
-
with the 16 e complex C' (Figure 1). C' is formed in the
catalytic cycle, at a rate k2 < k1 but k2 > k2' to give the linear
isomer 4 in a practically irreversible step because k-3 << k1. As
the major branched product is both formed faster and removed
more rapidly than the minor one, the mixture is depleted of the
major enantiomer and the ee slowly decreases.16
ASSOCIATED CONTENT
Supporting Information
O
O
OP(O)(OR')2
KO
O
2a
Experimental procedures, results of catalyst screening experi-
ments, characterization of compounds, determination of regio- and
enantioselectivities. This material is available free of charge via the
Internet at http://pubs.acs.org.
R
conditions:
Table 2, entry 6
3
R
R = CH3, R' = EH
R = Ph, R' = Et
R = n-C7H12, R' = EH
R = 4-F3CC6H4, R' = EH
100
95
90
85
80
75
70
AUTHOR INFORMATION
Corresponding Author
g.helmchen@oci.uni-heidelberg.de
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
0
100
200
300
400
500
This work was supported by the Deutsche Forschungsgemein-
schaft (SFB 623) and the Fonds der Chemischen Industrie. J. Qu
thanks the Alexander von Humboldt foundation for a scholar-
ship. We thank Mascha Jäkel for samples of the catalysts and
Prof. K. Ditrich (BASF SE) for enantiomerically pure 1-aryl-
ethylamines, and Dr. S. C. E. Stieber for linguistic polishing of
the manuscript.
time (min)
Figure 2. Dependence of enantioselectivity on time for allylic esterifica-
tions of arylallyl and alkylallyl substrates. The arrows mark work-up of
the substitution reactions (EH = 2-ethylhexyl).
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Table 3. Branched Allylic Esters Prepared by Ir-Catalyzed Allylic Substitution (Conditions According to Table
2, Entry 12). For Definition of Substrates and Linear Esters See the Supporting Information
1
2
3
4
5
6
7
8
9
O
O
O
R''
O
2a
KO
R''
+
R
OP(O)(OEH)2
R
R
O
R''
Ir-catalyst (C)
1
3
4
O
O
O
O
O
O
O
O
O
O
C7H15
H3C
Ph
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
F3C
H3C
3a
3b
3c
3d
3e
4 h, 62% yield
5 h, 74% yielda
3 h, 70% yield
7.5 h, 60% yield (63% conv)b
6 h, 55% yield
8.5 h, 80% yield
97% ee, b/l = 14:1 96% ee, b/l = 16:1 98% ee, b/l >20:1
93% ee, b/l = 9:1
97% ee, b/l >20:1
97% ee, b/l = 14:1
O
O
O
O
O
O
O
O
O
O
O
Ph
C3H7
C7H15
Ph
Ph
Ph
3f
3g
3h
3i
3j
2 h, 68% yield
3 h, 60% yield
94% ee, b/l >20:1
2.5 h, 72% yield
96% ee, b/l >20:1
3.5 h, 73% yield
24 h, 57% yield (62% conv)
96% ee, b/l = 12:1
98% ee, b/l >20:1
>99% ee, b/l >20:1
O
O
O
CH3
Ph
O
O
NH
O
O
O
O
O
C7H15
OMe
C7H15
C7H15
C7H15
C7H15
3k
3l
3h, 81% yield
93% ee, b/l >20:1
3m
3n
3o
3 h, 79% yield
4.5 h, 62% yieldc
94% ee, b/l >20:1
5 h, 57% yieldc
24 h, 52% yield
87% ee, b/l >20:1
3 h, 52% yieldc
95% ee, b/l >20:1
96% ee, b/l >20:1
87% ee, b/l >20:1
a Diethyl phosphate 1d was used instead of 1e. b 1 mol% of C3. c 2 mol% of C3.
Dodo, N.; Onitsuka, K.; Uno, M.; Takahashi S. Bull. Chem. Soc. Jpn.
2001, 73, 527-537. (e) A simplified version of the Onitsuka catalyst
and a few examples of esterification with arylallyl substrates, which
gave 88-93% ee, were recently reported: Trost, B. M.; Rao, M.;
Dieskau, A. P. J. Am. Chem. Soc. 2013, 135, 18697-18704.
(11) (a) Kirsch, S. F.; Overman, L. E. J. Am. Chem. Soc. 2005, 127, 2866-
2867. (b) Cannon, J. S.; Kirsch, S. F.; Overman, L. E. J. Am. Chem.
Soc. 2010, 132, 15185-15191.
(12) (a) Kirsch, S. F.; Klahn, P.; Menz, H. Synthesis 2011, 3592-3603. (b)
Takii, K.; Kanbayashi, N; Onitsuka, K. Chem. Comm. 2012, 48, 3872-
3874.
(13) Phosphates are routinely used as substrates for allylic substitutions.
However, allylic di-(2-ethylhexyl) phosphates have only once been
employed to the best of our knowledge: Zhong, C.; Kunii, S; Kosaka,
Y.; Sawamura, M.; Ito, H. J. Am. Chem. Soc. 2010, 133, 11441-11442.
(14) Ueda, M.; Hartwig, J. F. Org. Lett. 2010, 12, 92-94.
(15) We have determined the selectivity factor of the kinetic resolution of
racemic 3c (cf Table 3) with potassium crotonate (2a) as s = 42 (see
Supporting Information). The determination was carried out according
to a method described in Kagan, H. G; Fiaud, J. C. Topics in Stereo-
chemistry; Wiley: New York, 1988; Vol. 18, p. 249.
(16) This effect can be used for improvement of the ee of the branched re-
action product by subjecting it to a kinetic resolution using the enan-
tiomer of the catalyst that was employed in its preparation. For an
example see the Supporting Information.
REFERENCES
(1) Reviews covering the whole field of allylic substitutions: (a) Trost, B.
M.; Lee, C. In Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.;
Wiley-VCH: New York, 2010, pp 593-649. (b) Lu, Z.; Ma, S. Angew.
Chem. Int. Ed. 2008, 47, 258-297. (c) Helmchen, G.; Kazmaier, U.;
Förster, S. In Catalytic Asymmetric Synthesis, 3rd ed.; Ojima, I., Ed.;
Wiley-VCH: New York, 2010, pp 497-461.
(2) (a) Helmchen, G.; Dahnz, A.; Dübon, P.; Schelwies, M.; Weihofen, R.
Chem. Comm. 2007, 675-691. (b) Helmchen, G. In Iridium Complexes
in Organic Synthesis; Oro, L. A., Claver, C., Eds.; Wiley-VCH: Wein-
heim, 2009, pp 211-250. (c) Hartwig, J. F.; Stanley, L. M. Acc. Chem.
Res. 2010, 43, 1461-1475. (d) Liu, W.-B.; Xia, J.-B.: You, S.-L. Top.
Organomet. Chem. 2012, 38, 155-208. (e) Tosatti, P.; Nelson, A.;
Marsden, S. P. Org. Biomol. Chem. 2012, 10, 3147-3163.
(3) (a) Spiess, S.; Raskatov, J. A.; Gnamm, C.; Brödner, K.; Helmchen, G.
Chem. Eur. J. 2009, 15, 11087-11090. (b) Raskatov, J. A.; Spiess, S.;
Gnamm, C.; Brödner, K.; Rominger, F.; Helmchen, G. Chem. Eur. J.
2010, 16, 6601-6615. (c) For an alternative preparation see:
Madrahimov, S. T.; Markovic, D.; Hartwig, J. F. J. Am. Chem. Soc.
2009, 131, 7228-7229.
(4) (a) Spiess, S.; Welter, C.; Franck, G.; Taquet, J.-P.; Helmchen, G. An-
gew. Chem., Int. Ed. 2008, 47, 7652-7655. (b) Raskatov, J. A.; Jäkel,
M.; Straub, B. F.; Rominger, F.; Helmchen, G. Chem. Eur. J. 2012,
18, 14314-14328.
(5) (a) Lopez, F.; Ohmura, T.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125,
3426-3427. (b) Welter, C.; Dahnz, A.; Brunner, B.; Streiff, S.; Dübon,
P.; Helmchen, G. Org. Lett. 2005, 7, 1239-1242. (c) A. Leitner, C.
Shu, J. F. Hartwig, Org. Lett. 2005, 7, 1093-1096.
(6) Lyothier, I.; Defieber, C.; Carreira, E. M. Angew. Chem., Int. Ed.
2006, 45, 6204-6207.
(7) (a) Gärtner, M.; Mader, S.; Seehafer, K.; Helmchen, G. J. Am. Chem.
Soc. 2011, 133, 2072–2075. (b) Slightly later the allylic hydroxylation
was successfully accomplished with a Ru-catalyst: Kanbayashi, N.;
Onitsuka, K. Angew. Chem., Int. Ed. 2011, 50, 5197-5199.
(8) (a) Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E. M. J. Am. Chem.
Soc. 2004, 126, 1628-1629. (b) Stanley, L. M.; Bai, C.; Ueda, M.;
Hartwig, J. F. J. Am. Chem. Soc. 2010, 132, 8918-8920.
(9) Kanbayashi, N; Onitsuka, K. J. Am. Chem. Soc. 2010, 132, 1206-
1207.
(10) Synthesis of the Ru-catalyst: (a) Hatanaka, M.; Himeda, Y.; Ueda, I. J.
Chem. Soc., Perkin Trans. 1, 1993, 2269-2274. (b) Komatsuzaki, N.;
Uno, M.; Kikuchi, H.; Takahashi, S. Chem. Lett. 1996, 677-678. (c)
Dodo, N.; Matsushima, Y.; Uno, M.; Onitsuka, K.; Takahashi, S. J.
Chem. Soc., Dalton Trans. 2000, 35-41. (d) Matsushima, Y.;
Komatsuzaki, N.; Ajioka, Y.; Yamamoto, M.; Kikuchi, H.; Takata, Y.;
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Graphical Abstract
OTf
+
O
P
O
O
(R''O)2
R
O
O
R'
O
O
R'
Ir
O
P
N
C
R
R
CH2
H3C
C
Ar
Ar
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