Rh-catalyzed C-C cleavage of benzyl/allylic alcohols to produce benzyl/allylic amines or other alcohols by nucleophilic addition of intermediate rhodacycles to aldehydes and imines

Article abstract of DOI:10.1002/chem.201201867

We report three transformations: 1) direct transformation from biarylmethanols into biarylmethylamines; 2) direct transformation from one biarylmethanol into another biarylmethanol; 3) direct transformation from allylic alcohols into allylic amines. These transformations are based on pyridyl-directed Rh-catalyzed C-C bond cleavage of secondary alcohols and subsequent addition to C=X (X=N or O) double bonds. The reaction conditions are simple and no additive is required. The driving force of C-C bond cleavage is the formation of the stable rhodacycle intermediate. Other directing groups, such as the pyrazolyl group, can also be used although it is not as efficient as the pyridyl group. We carried out in-depth investigations for transformation 1 and found that: 1) the substrate scope was broad and electron-rich alcohols and electron-deficient imines are more efficient; 2) as the leaving group, aldehyde had no significant impact on either the C-C bond cleavage or the whole transformation; 3) mechanistic studies (intermediate isolation, in situ NMR spectroscopic studies, competing reactions, isotopic labeling experiments) implied that: i) The C-C cleavage was very efficient under these conditions; ii) there is an equilibrium between the rhodacycle intermediate and the protonated byproduct phenylpyridine; iii) the addition step of the rhodacycle intermediate to imines was slower than the C-C cleavage and the equilibrium between the rhodacycle and phenylpyridine; iv) the whole transformation was a combination of two sequences of C-C cleavage/nucleophilic addition and C-C cleavage/protonation/C-H activation/nucleophilic addition, with the latter being perhaps the main pathway. We also demonstrated the first example of cleavage of an C(alkenyl)-C(benzyl) bond. These transformations showed the exchange (or substitution) of the alcohol group with either an amine or another alcohol group. Like the "group transplant", this method offers a new concept that can be used to directly synthesize the desired products from other chemicals through reorganization of carbon skeletons.

Full text of DOI:10.1002/chem.201201867

DOI: 10.1002/chem.201201867
À
Rh-Catalyzed C C Cleavage of Benzyl/Allylic Alcohols to Produce Benzyl/
Allylic Amines or other Alcohols by Nucleophilic Addition of Intermediate
Rhodacycles to Aldehydes and Imines
Xi-Sha Zhang,[a] Yang Li,[a] Hu Li,[a] Kang Chen,[a] Zhi-Quan Lei,[a, c] and
Zhang-Jie Shi*[a, b]
À
Abstract: We report three transforma-
tions: 1) direct transformation from
biarylmethanols into biarylmethyl-
1) the substrate scope was broad and
electron-rich alcohols and electron-de-
ficient imines are more efficient; 2) as
the leaving group, aldehyde had no sig-
imines was slower than the C C cleav-
age and the equilibrium between the
rhodacycle and phenylpyridine; iv) the
whole transformation was a combina-
ACHTUNGTRENNUNGamines; 2) direct transformation from
À
À
one biarylmethanol into another biaryl-
methanol; 3) direct transformation
from allylic alcohols into allylic amines.
These transformations are based on
nificant impact on either the C C bond
tion of two sequences of C C cleavage/
À
cleavage or the whole transformation;
3) mechanistic studies (intermediate
isolation, in situ NMR spectroscopic
studies, competing reactions, isotopic
labeling experiments) implied that:
nucleophilic addition and C C cleav-
À
age/protonation/C H activation/nucle-
ophilic addition, with the latter being
perhaps the main pathway. We also
demonstrated the first example of
À
À
pyridyl-directed Rh-catalyzed C C
bond cleavage of secondary alcohols
and subsequent addition to C=X (X=
N or O) double bonds. The reaction
conditions are simple and no additive
À
i) The C C cleavage was very efficient
cleavage of an CACTHNGUTRENNU(G alkenyl) CACHTUNGTRENNUNG(benzyl)
under these conditions; ii) there is an
equilibrium between the rhodacycle in-
termediate and the protonated byprod-
uct phenylpyridine; iii) the addition
step of the rhodacycle intermediate to
bond. These transformations showed
the exchange (or substitution) of the
alcohol group with either an amine or
another alcohol group. Like the “group
transplant”, this method offers a new
concept that can be used to directly
synthesize the desired products from
other chemicals through reorganization
of carbon skeletons.
À
is required. The driving force of C C
bond cleavage is the formation of the
stable rhodacycle intermediate. Other
directing groups, such as the pyrazolyl
group, can also be used although it is
not as efficient as the pyridyl group.
We carried out in-depth investigations
for transformation 1 and found that:
Keywords: allylic compounds
C C activation · rhodium · alco-
hols · synthetic methods
·
À
Introduction
be used to synthesize alcohols and amines, which are impor-
tant compounds in organic synthesis. For example, Grignard
reagents[1] and organolithium reagents[2] are widely used in
nucleophilic addition to C=X double bonds. However, these
reagents suffer from air- and moisture-sensitivity. Organo-
boron reagents can also be used as nucleophiles in the addi-
tion to C=X bonds in the presence of a metal catalyst, for
example Rh,[3] Pd,[4] Fe,[5] Ni,[6] Ru,[7] Co,[8] Cu,[9] and Pt.[10]
However, most of these organometallic reagents are pre-
pared from environmentally unfriendly and expensive orga-
nohalides. Organohalides can also be directly used as nucle-
ophiles in the addition to C=X bonds catalyzed by metal
species.[11] Recently, carboxylic acids have been shown to un-
dergo nucleophilic addition to C=X bonds through decar-
The nucleophilic addition of organometallic reagents to C=
X double bonds (X=O, N) is an important method that can
[a] X.-S. Zhang, Dr. Y. Li, H. Li, K. Chen, Z.-Q. Lei, Prof. Dr. Z.-J. Shi
Beijing National Laboratory of Molecular Sciences (BNLMS)
Key Laboratory of Bioorganic Chemistry
and Molecular Engineering of Ministry of Education
College of Chemistry and PKU Green Chemistry Center
Peking University, Beijing 100871 (P.R. China)
Fax: (+86)10-6276-0890
E-mail: zshi@pku.edu.cn
[b] Prof. Dr. Z.-J. Shi
State Key Laboratory of Organometallic Chemistry
Chinese Academy of Sciences
Shanghai 200032 (P.R. China)
boxylation.[12] Direct C H bond addition to the C=X bonds
À
has also been achieved and is more efficient and atom eco-
nomic.[13] Especially, Rh catalysis has played an important
role in this field.[14–20] In addition, Rh catalysts have also
[c] Z.-Q. Lei
Chengdu Institute of Biology
Chinese Academy of Sciences Chengdu
Sichuan 610068 (P.R. China)
À
been used in other types of C H functionalization reac-
tions.[21–23] These transformations are relatively benign to the
environment.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201201867.
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Chem. Eur. J. 2012, 18, 16214 – 16225

FULL PAPER
À
Another type of ubiquitous inert bond besides C H
direct group substitution (displacement) reaction through
[28]
À
À
À
bonds are C C bonds. Similar to the process of catalytic C
cleavage of a C C single bond (Scheme 1, c).
À
À
H addition to C=X bonds, in which an organometallic inter-
mediate (C M bond) was produced by C H activation, C
C bond activation can also produce the active organometal-
lic intermediate (C M bond) and proceed through subse-
quent addition reaction with the C=X bonds. Based on our
interest in C C bond activation, here we set out to inves-
tigate the reactivity of C C bonds towards addition to C=X
bonds. In contrast to C H addition to C=X bonds, the addi-
tion reaction by C C activation has been less extensively in-
vestigated. Oshima and Yorimitsu reported the allyl transfer
reaction from homoallyl alcohols to aldehydes through
retro-allylation, but the alcohol could not be obtained be-
cause of isomerization to the aldehyde.[25] Later, Oshima
Through the sequence of C C bond cleavage and C C
bond formation, the organic skeleton can be reorganized,
which may provide an efficient method to construct complex
molecules from widely existing organic compounds as start-
ing materials.[29] Despite the promising applications of this
À
À
À
À
[24]
À
À
À
sequence of C C bond cleavage and subsequent C C bond
À
À
formation, the C C cleavage faces several challenges: 1) the
[30]
À
À
high bond dissociation energy of C C bonds, 2) the diffi-
cult approach of the metal center to C C bonds,
[31]
À
À
and
[32]
À
3) the poor selectivity associated with C C activation.
Several strategies (release of ring strain,[33] formation of
stable metallacycle or p-allyl metal complex as intermedi-
ates in the assistance of coordination,[34] formation of stable
[35]
and Yorimitsu reported the Cu-catalyzed C C bond cleav-
C metal bonds, and others[36]) have been adopted to real-
À
À
À
age of tertiary alcohols and subsequent addition to alde-
ize the C C activation and subsequent organic transforma-
hydes and imines.[26] Herein, we report the Rh-catalyzed
tions.
À
À
À
C(aryl) C(benzyl) and C(alkenyl) C(benzyl) bond cleavage of sec
A
G
In contrast to tertiary alcohols, the C C bond cleavage of
secondary alcohols is much more challenging, resulting from
hydes (Scheme 1). First, we realized the transformation
the oxidation reaction to give ketones (b-H elimination)[37]
À
competing with the C C activation reaction (b-C elimina-
[24a]
tion).[38] In our previously developed C C activation
and
À
[15b]
À
C H addition,
we investigated the reaction mechanism
and identified the rhodacycle intermediate, which has a
À
transformable C Rh bond. Based on these analyses, we se-
À
lected secondary alcohol 1a as our model substrate. The C
C activation in this substrate was believed to be driven by
the pyridyl directing group.
Results and Discussion
Transformation from benzyl alcohol into benzyl amine:
Conditions: Secondary alcohol 1a and N-sulfonylimine 2a
were selected as model substrates to establish optimal condi-
tions to achieve this transformation (Table 1). Because of
À
the wide use of Rh catalysts in the C C activation reac-
tion,[39–46] Rh catalysts were first selected and investigated.
Although [Cp*RhCl2]2 showed good catalytic activity in the
[24a]
À
C C cleavage in our previous studies,
group substitution
leading to the desired product 3a was not observed (Table 1,
Scheme 1. Formal group substitution/displacement through Rh-catalyzed
À
entry 1). However, to our delight, when [Cp*Rh
AHCTUNGTRENNUNG
ACHTUGNERTN(NUNG CH3CN)3]-
C C cleavage.
obtained in 38% yield (Table 1, entry 2). Increasing the con-
centration of 1a from 0.05 to 0.20m resulted in a better
yield of 67% (Table 1, entry 4). The yield was clearly en-
hanced when 3.0 equivalent of 2a was presented (Table 1,
entry 5); further improvement could not be reached by fur-
ther increasing the amount of 2a or the concentration
(Table 1, entries 6 and 7). Reducing the reaction time gave a
similar result (Table 1, entry 8). Lower temperature sup-
pressed the efficiency, whereas higher temperature did not
lead to a better outcome (cf. Table 1, entries 8–10). Notably,
this transformation did not proceed in the presence of other
transition metal catalysts or in the absence of catalyst
(Table 1, entries 11–18). Among various solvents, tBuOH
from benzyl and allylic alcohol into amine by replacing the
À
aldehyde with an imine through Rh-catalyzed C C bond
cleavage/nucleophilic addition (Scheme 1, a). In general,
such a process requires multi-step redox transformations
(Scheme 1, a), although recent advances have realized the
alcohol–amine transformation by the hydrogen-borrowing-
lending strategy in one pot without scaffold reorganiza-
tion.[27] In addition, we expanded this strategy to the trans-
formation from benzyl alcohol into another benzyl alcohol
by replacing one aldehyde with another aldehyde through
À
Rh-catalyzed C C bond cleavage/nucleophilic addition
(Scheme 1, b). Formally, this kind of transformation is a
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Z.-J. Shi et al.
Table 1. Screening of RhIII-catalyzed C C bond cleavage/addition of secondary alco-
hol 1a with imine 2a.
À
biaryl methanols. In addition to secondary alcohols,
tertiary alcohol 1n was tested and we found that
group transfer also took place with good efficiency.
Remarkably, primary alcohol 1m showed partial re-
activity, with significant amounts of starting materi-
al remaining. The low efficiency probably results
À
from the thermodynamic stability of the C C bond
in this substrate and the difficulty in forming the
five-member rhodacycle. Moreover, substrates con-
taining two alcoholic structural units (1o, 1p and
1q) were further tested, and the results indicated
that the transformation for such substrates showed
high regio- and chemo-selectivity; only the alcohol
group adjacent to the pyridyl group showed good
reactivity and different alcohol groups (primary,
secondary, and tertiary) at the meta-position were
untouched. Secondary alcohol substitution resulted
in lower yield, possibly arising from oxidation of
this functional group (1p). In the presence of a ter-
tiary alcohol group (1q), the desired product 3qa
was obtained in 60% yield, accompanied by 28%
yield of 3qa’ formed from further dehydration of
the tertiary alcohol group.
Entry
Conc.
[m]
x
Cat.
A
T
[8C]
Solvent
[(1 mL)]
t
Yield
[%][a]
G
[h]
1[b]
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
0.05
0.05
0.10
0.20
0.20
0.20
0.25
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
2
2
2
2
3
4
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
E
90
90
90
90
90
90
90
90
60
120
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
EtOH
10
10
10
10
10
10
10
3
0
38
63
67
79
77
75
77
11
80
0
0
0
0
0
0
0
0
R
G
ACHTUNGTRENNUNG
N
E
ACHTUNGTRENNUNG
N
N
ACHTUNGTRENNUNG
R
R
ACHTUNGTRENNUNG
E
N
ACHTUNGTRENNUNG
N
R
ACHTUNGTRENNUNG
U
R
ACHTUNGTRENNUNG
E
R
G
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
N
N
A
R
E
N
R
N
U
Rh
No
A
E
G
N
60
55
64
46
52
48
53
Transformation from benzyl alcohol into benzyl
amine: Substrate scope of imines: A range of sulfo-
nylaldimines were further investigated (Table 3),
and it was found that the reaction was very sensi-
tive towards steric effects. For example, although
imines with methyl groups at the meta- and para-
positions of the phenyl group underwent this reac-
tion smoothly, those with an ortho-methyl substitu-
ent decreased the yield significantly (cf. 3bb and
N
N
R
tAmylOH
iPrOH
THF
dioxane
DCE
R
G
N
E
G
G
G
G
N
R
R
T
A
A
A
toluene
3
[a] Isolated yields are given unless otherwise noted. [b] 2.5 mol% of catalyst.
was found to be the most effective (Table 1, entries 19–25).
In general, protic solvents were better than nonprotic sol-
vents in terms of efficiency.
3bc with 3bd). The presence of electron-withdrawing
groups significantly improved the yields (3be, 3bf, 3bi, 3bj,
and 3bk), which can be rationalized by the higher electro-
philicity of the corresponding imines. In contrast, substrates
with an electron-donating group afforded the product in
much lower yield (3bl). It should be noted that halogen-con-
taining imines were tolerated well in this catalytic system,
making it possible for further orthogonal transformations
(3bg, 3bh). In addition, naphthyl, biphenyl, and heteroaro-
matic ring containing imines were also suitable electrophiles
for this transformation (3bm, 3bn, and 3bo). Finally, pro-
tecting groups of imines other than the tosyl group were
tested and both (4-fluorophenyl)sulfonyl (Fs) and methane-
sulfonyl (Ms) were found to be suitable for this transforma-
tion (3 bp, 3bq). The higher yield of 3 bp (than 3bq) results
from the stronger electrophilicity of 4-fluorophenylsulfonyl-
Transformation from benzyl alcohol into benzyl amine: Sub-
strate scope of alcohols: With these optimized conditions in
hand, we began to explore the substrate scope of different
alcohols (Table 2). To our delight, the para-methyl substitu-
ent was not necessary for promoting the efficiency and se-
lectivity. We found that nonsubstituted substrate 1b gave a
comparable yield to that obtained with 1a. Electron-donat-
ing and electron-withdrawing groups on the phenyl motif
(1c–f, and 1h) can be tolerated in this system, although elec-
tron-deficient substrates (1e and 1h) gave relatively lower
yield, which could be attributed to the lower nucleophilicity
of the rhodacycle intermediate towards addition to imine.
Halogen-containing substrates (1e) can also be tolerated, af-
fording the possibility for further transformations.[47]
AHCTUNGTREGiNNUN mine. We also assessed the use of the pyrazolyl group as
the directing group but found that, although the desired
Different functionalities on the phenyl ring of the leaving
group were also tested. Neither electron-rich nor electron-
deficient leaving groups (1i and 1j) affected the efficiency
dramatically. Alkyl alcohols 1k and 1l also successfully un-
product was obtained, its yield was low (3ra).
Transformation from benzyl alcohol into benzyl amine:
Mechanistic investigations: To gain insights into the mecha-
nism, we conducted this reaction in the absence of imine
À
derwent the desired C C cleavage/nucleophilic addition se-
À
quence, although the efficiency was not comparable with
partner 2 under standard conditions to investigate the C C
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Cleavage of Benzyl/Allylic Alcohols
FULL PAPER
À
cleavage step [Eq. (1)]. The C C bond cleavage indeed took
place and 2-phenylpyridine (5) was obtained in 87% yield
together with benzaldehyde (4) as leaving group in 60%
À
yield. This result proved that the C C bond was cleaved and
that 5 may result from further protonation of the five-mem-
bered rhodacycle 6. Therefore, further experiments were
conducted to determine whether the five-membered rhoda-
cycle 6 was involved in our system and acted as key inter-
mediate. Unfortunately, although the starting material was
consumed in the stoichiometric reaction between alcohol
and catalyst, pure compound 6 could not be separated due
to contamination by HSbF6 salts of the 2-phenylpyridine by-
product. However, intermediate 6 was identified by ESI-MS
analysis (see the Supporting Information). Fortunately, inter-
mediate 6, prepared by another method,[16b] was found to ef-
ficiently catalyze this reaction [Eq. (2)], indicating that this
Table 2. RhIII-catalyzed addition of secondary alcohols 1 with 2a through C C bond
À
five-membered rhodacycle intermediate was actual-
ly involved in our catalytic cycle.
cleavage.[a]
Next, we investigated the addition step from in-
termediate 6 to the final product. For this step,
there may be two different pathways: Path A, the
À
C C cleavage/direct addition sequence, and Path B,
À
À
the C C cleavage/protonation/C H activation cas-
cade sequence (Scheme 2).
First, we used in situ NMR experiments to detect
the trend of change in concentration (yields) of
starting material 1, desired product 3, and possible
intermediate 5 (Figure 1). At the initial stage of the
reaction, the concentration of alcohol 1b decreased
sharply, companying the formation of large amounts
of 2-phenylpyridine 5. After 1.5 h, most of the start-
ing material 1b was consumed and transformed
into the desired imine 3ba (ca. 10% yields) and the
protonated byproduct 5. With further time, the con-
centration of 5 gradually decreased and the yield of
product continued to increase. Complete conversion
was not achieved due to the lower concentration
under the NMR conditions (see the Supporting In-
formation). Several conclusions could be drawn
À
from this data: 1) The C C cleavage was very effi-
cient under these conditions; 2) There is an equili-
brium between the rhodacycle intermediate 6 and
the protonated byproduct 5; 3) The addition step of
the intermediate 6 to imine 2 was slower than the
À
C C cleavage and the equilibrium between 6 and 5,
so most of the starting material alcohol was trans-
formed into 5 during the reaction; 4) Path B was
the main pathway but Path A was also involved, be-
cause the rate of increase of the product was higher
at the initial stage than later.
We further conducted several other experiments
to support the conclusions mentioned above. A
competition experiment between 5 and 1a was car-
ried out. To our interest, 3ba and 3aa were ob-
tained in comparable yields, indicating that pathway
B was the main route to the desired product
[a] Reagents and conditions (0.2 mmol scale): alcohol 1, [Cp*RhACHTUNRTGENNUG(CH3CN)3]ACHUTGNTREN[NUGN SbF6]2
(5 mol%), imine (3 equiv), tBuOH (1.0 mL; conditions A) or toluene (1.0 mL; condi-
tions B), unless otherwise noted. Isolated yields are shown in the table. [b] 1.5 mL
tBuOH. [c] 0.5 mmol scale, 2.5 mL tBuOH. [d] With 59% 2-(2-methoxyphenyl)pyri-
dine formed as a byproduct. [e] 0.15 mmol scale, 1 mL tBuOH. [f] Reacted at 908C for
24 h, then at 1208C for 19 h; significant amounts of starting material remained; the
yield was determined by NMR spectroscopic analysis.
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Z.-J. Shi et al.
Table 3. RhIII-catalyzed addition of 1b with imines through C C bond cleava-
À
ge.[a]
Figure 1. In situ NMR spectroscopic analysis; the relationship between
the concentrations of the product, starting material alcohol, and phenyl-
pyridine 5 and reaction time.
To further clarify this issue, an isotopic labeling experi-
ment was carried out. We found that, other than the group
transplant to form amines, D/H scrambling took place at the
À
ortho-position, indicating that the C H cleavage was accom-
[a] Reagents and conditions (0.2 mmol scale): alcohol 1, [Cp*Rh
ACHTUNGTRENNUNG
ACHTUGNERTN(NUNG CH3CN)3]-
À
panied by C C cleavage under these conditions [Eq. (5)].
(1.0 mL; conditions B). Isolated yields are shown in the table.
À
Notably, the high value of the H/D ratio implied that C H
activation was reversible to some extent, which is in accord-
ance with our conclusion from the in situ NMR spectroscop-
ic study that there is an equilibrium between the rhodacycle
intermediate 6 and the protonated byproduct 2-phenylpyri-
À
dine 5. These observations suggested that both the C C
À
À
cleavage/direct C C formation and the sequence of C C
À
À
cleavage/protonation/C H activation/C C formation existed
under the reaction conditions and that Path B was the main
route to the resulting group substitution/displacement.
Scheme 2. Two different pathways.
À
[Eq. (3)]. Indeed, the addition of a C H bond to sulfonyl-
aldimine took place under exactly the same conditions
[(Eq. 4)].
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Cleavage of Benzyl/Allylic Alcohols
FULL PAPER
Based on these experimental results, we proposed that
this transformation proceeds through the pathway shown in
Scheme 3. First, the precatalyst coordinates with substrate
Scheme 4. Alcohol–amine exchange reaction.
peting reaction between two different aldehydes toward the
same nucleophilic metal intermediate. 4-Nitrobenzaldehyde
(11a) and 2-chloro-5-nitrobenzaldeyde (11c) showed better
efficiency than 3-nitrobenzaldehyde (11b). It was found that
dichloromethane was a better solvent than tBuOH for this
transformation. In summary, this reaction demonstrated the
À
versatility of the substitution reaction through C C cleav-
age.
Transformation from allylic alcohol into allylic amine:
Having realized the reaction between benzyl alcohols with
imines, we continued to investigate the reaction between al-
À
lylic alcohols and imines. Gratifyingly, the CACHTNUTRGNE(UNG alkenyl) C-
AHCTUNGTREG(NNUN benzyl) bond was cleaved and the desired allylic amine
product was obtained in moderate yields (Table 5). To the
best of our knowledge, this is the first report of the cleavage
À
of an C
G
(benzyl) bond. Longer reaction time and
Scheme 3. Proposed mechanism.
higher temperature had no effect on the yield (Table 5,
1b to form seven-membered rhodacycle intermedi-
Table 4. The substitution of one alcohol group with a second.[a]
ate I, releasing a proton to the reaction mixture.
Subsequent b-C elimination accompanied by re-
lease of benzaldehyde 4 gave five-membered rhoda-
cycle intermediate 6, which can either undergo
direct addition with imines (Path A) to give the de-
sired product or undergo the protonation process to
generate the 2-phenylpyridine derivative
5
Entry
Alcohol 11
Product 12
Solvent
A
Time
[h]
Yield
[%]
(Path B). The 2-phenylpyridine derivative 5 can
AHCTUNGTRENNUNG
À
also give the desired product through the C H acti-
vation process.[15b]
1
24
47
Formal intramolecular reaction: To make this reac-
tion a 100% atom economic reaction, one should
avoid the release of the benzaldehyde as a leaving
group. Based on this idea, we synthesized substrate
9 for an intramolecular reaction, which reacted effi-
ciently under these conditions to give the alcohol–
amine exchange product 10 in 34% NMR yield
(Scheme 4).
2[b]
11a
12a
B
B
20
24
61
24
3
Transformation between alcohol groups: Interest-
ingly, the alcohol group can not only be substituted
by amine groups, but also by other alcohol groups,
realizing the transformation from one alcohol into
another alcohol (Table 4).[18] Here, the electrophilic
partner aldehyde 11 should contain an electron-
withdrawing group and thus be more electrophilic
than benzaldehyde because, actually, this is a com-
4
5
A
B
3
57
71
11c
12c
24
[a] Reagents and conditions (0.2 mmol scale): alcohol 1b, [Cp*RhACHTUNTRGENNUG(CH3CN)3]ACHTUNGTRENNUNG[SbF6]2
(5 mol%), aldehyde 11 (3 equiv), tBuOH (1.0 mL; conditions A) or CH2Cl2 (1.0 mL;
conditions B), unless otherwise noted. Isolated yields are shown in the table. [b] Reac-
tion conducted on a 0.1 mmol scale in 0.5 mL CH2Cl2.
Chem. Eur. J. 2012, 18, 16214 – 16225
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16219

Z.-J. Shi et al.
Table 5. The reaction between allylic alcohols and imines to produce allylic amines.[a]
nated byproduct 2-phenylpyri-
dine 5; 3) the addition step of
the intermediate 6 to imine 2
À
was slower than the C C cleav-
age and the equilibrium be-
tween 6 and 5.
We also realized the direct
transformation from one sec-
ACHUTNGRENNUoG ndACHTUNTGRNEaNUGN ry benzyl alcohol into an-
Entry
Allylic alcohol 13
Product allylic amine 14
T
[8C]
t
Yield
[%]
[h]
other benzyl alcohol and the
first pyridylcyclopentenyl-group
transfer reaction, the direct
transformation from secondary
allylic alcohols into allylic
amines through RhIII-catalyzed
À
1
90
3
42[b]
2
3
13a
14a
14a
110
110
48
52
46
47
carbon carbon
cleavage/
À
carbon carbon formation se-
quence.
Through these reactions, we
investigated the reactivities of
À
C C bond addition to alde-
hydes and imines. In addition,
as a substitution reaction pro-
4
13a
13b
110
110
48
48
47
45
À
ceeding through C C bond
5[c]
14b
cleavage, this method offers a
concept that can be used to syn-
thesize the desired products
through direct reorganization of
carbon skeletons. These studies
are not only theoretically im-
portant to understand the new
[a] Reagents and conditions (0.2 mmol scale): substrate 13, [Cp*RhACTHUNRTGENNUG(CH3CN)3]AHCUTGNTRENN[GUN SbF6]2 (5 mol%), imine 2
(3 equiv), tBuOH (1.0 mL), unless otherwise noted. Isolated yields are shown in the table. [b] NMR yield with
21% starting material alkene remaining. [c] PivOH (20 mol%) was added and tBuOH (0.5 mL) and CH2Cl2
(0.5 mL) were used as the solvent.
entry 2), indicating that there was an equilibrium formed
during the reaction resulting from the competition between
imine 2a and the released aldehyde 15 to be nucleophilicly
attacked by the Rh intermediate (Table 5, entries 2 vs. 1). In
addition, different leaving groups (Table 5, entries 2 vs. 3)
and different imines (Table 5, entries 2 vs. 4) had no signifi-
cant impact on the yield.
reactivity of traditionally considered “inert” compounds, but
also potentially synthetically useful for the construction of
valuable chemicals from readily available and inexpensive
chemicals. Further investigations to explore new transforma-
À
tions using this substitution strategy through C C bond
cleavage is underway. Investigation of the application of this
strategy in the degradation of “white pollutants” is also our
goal.
Conclusion
Experimental Section
The pyridylphenyl-group transfer reaction, the direct trans-
formation from secondary alcohols, tertiary alcohols and
even primary alcohols into biarylmethylamines through a
General procedures: Synthesis of alcohols 1: The procedure for the syn-
thesis of the alcohols was the same as that reported by our group recent-
ly.[16] Alcohol substrates 1a–c, 1e, 1 f, 1k–n, 1p–r, and 7 were included in
the literature[16] and the characterization data are consistent with report-
ed data. Alcohol substrates 1d, 1g–j, and 1o were not reported and were
synthesized according to the literature method.[16]
III
À
À
Rh -catalyzed carbon carbon cleavage/carbon carbon for-
mation sequence, was developed. The reaction is straightfor-
ward to perform and no additive is required. The functional
group tolerance is good and electron-rich alcohols and elec-
tron-deficient imines are better in efficiency. The electronic
nature of the leaving group has no significant impact on the
Synthesis of 3: A 50 mL Schlenk tube was heated using a heat gun under
vacuum. After cooling to RT, catalyst [Cp*RhACHTNUTRGENN(UG CH3CN)3]ACHTUNGTRNE[NUGN SbF6]2 (8.3 mg,
0.01 mmol), alcohol derivative 1 (0.2 mmol), and aldimine derivative 2
(0.60 mmol) were added under air atmosphere. The reaction tube was
then evacuated and refilled with N2. After the addition of freshly distilled
tBuOH (1.0–2.5 mL) or toluene (1.0–2.5 mL) by using a syringe, the reac-
tion mixture was stirred in the sealed tube at 908C under N2 atmosphere
in a Wattecs Parallel Reactor for the time indicated (reaction monitored
by TLC to achieve full conversion of 1 and better yield of the product 3).
After cooling to RT, the solvent was removed in vacuo and the residue
À
yield. The mechanism is a combination of C C cleavage/ad-
À
À
dition (Path A) and C C cleavage/protonation/C H activa-
tion/addition (Path B), with the latter being the main route.
À
Mechanistic studies showed that: 1) the C C cleavage was
very efficient under these conditions; 2) there is an equilibri-
um between the rhodacycle intermediate 6 and the proto-
16220
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Chem. Eur. J. 2012, 18, 16214 – 16225

Cleavage of Benzyl/Allylic Alcohols
FULL PAPER
was purified by chromatography on silica gel (petroleum ether/EtOAc,
6:1 to 2:1, or petroleum ether/EtOAc/CH2Cl2, 6:1:1 to 3:1:1) to afford
compound 3 as a white solid.
124.4, 123.9 (d, J=17 Hz), 121.9, 117.7 (d, J=23.1 Hz), 60.7, 21.3, 14.0 (d,
J=2.9 Hz) ppm; HRMS (ESI): m/z calcd for C26H24FN2O2S: 447.15370
[M+H]+; found: 447.15489.
Compound 3aa (the same product as 3ia, 3ja, 3ka, and 3la): Obtained
as a white solid after column chromatography (petroleum ether/ethyl
acetate/CH2Cl2, 6:1:1). 1H NMR (400 MHz, CDCl3): d=8.75 (d, J=
8.8 Hz, 1H), 8.52–8.50 (m, 1H), 7.60 (d, J=8.8 Hz, 2H), 7.43 (dt, J=1.6,
7.6 Hz, 1H), 7.07–7.02 (m, 4H), 6.93–6.89 (m, 8H), 5.66 (d, J=9.2 Hz,
1H), 2.33 (s, 3H), 2.31 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=
160.0, 147.4, 142.2, 140.9, 139.2, 138.8, 137.4, 136.9, 136.8, 132.0, 131.1,
129.0, 128.7, 127.3, 126.9, 126.1, 126.0, 124.3, 121.8, 61.1, 21.3, 20.9 ppm;
HRMS (ESI): m/z calcd for C26H25N2O2S: 429.16313 [M+H]+; found:
429.16321.
Compound 3oa: Obtained as a white solid (with some colorless slabby
oil) by column chromatography (petroleum ether/ethyl acetate, 3:1 to 2:1
1
to 1:1). H NMR (400 MHz, CDCl3): d=8.58 (d, J=9.2 Hz, 1H), 8.51 (d,
J=4.4 Hz, 1H), 7.60 (d, J=8.0 Hz, 2H), 7.47 (dt, J=0.8, 7.6 Hz, 1H),
7.23 (s, 1H), 7.10–7.03 (m, 5H), 6.95–6.91 (m, 6H), 5.71 (d, J=9.2 Hz,
1H), 4.64 (s, 2H), 2.33 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=
159.5, 147.3, 142.4, 140.6, 140.5, 139.3, 139.1, 138.7, 137.2, 131.1, 129.8,
129.1, 127.4, 126.9, 126.6, 126.3, 126.0, 124.5, 122.0, 64.4, 60.8, 21.4 ppm;
HRMS (ESI): m/z calcd for C26H25N2O3S: 445.15804 [M+H]+; found:
445.15899.
Compound 3ca: Obtained as a white solid by column chromatography
(petroleum ether/ethyl acetate/CH2Cl2, 5:1:1). 1H NMR (300 MHz,
CDCl3): d=8.86 (d, J=12 Hz, 1H), 8.55–8.53 (m, 1H), 7.64–7.61 (m,
2H), 7.55–7.52 (m, 2H), 7.47–7.41 (m, 4H), 7.39–7.36 (m, 1H), 7.29–7.26
(m, 1H), 7.10–6.92 (m, 10H), 5.75 (d, J=12.0 Hz, 1H), 2.24 ppm (s, 3H);
13C NMR (100 MHz, CDCl3): d=159.8, 147.6, 142.3, 140.7, 140.6, 140.0,
139.8, 138.9, 138.7, 137.0, 131.6, 130.1, 129.0, 128.8, 127.6, 127.4, 126.9,
126.6, 126.3, 126.0, 124.5, 122.0, 61.2, 21.3 ppm; HRMS (ESI): m/z calcd
for C31H27N2O2S: 491.17878 [M+H]+; found: 491.17881.
Compound 3pa: A mixture of two diastereoisomers was obtained as a
white slabby solid by column chromatography (petroleum ether/ethyl
acetate/CH2Cl2, 5:1:1 then petroleum ether/ethyl acetate, 3:1). 1H NMR
(300 MHz, CDCl3): d=8.79 (d, J=9.6 Hz, 0.5H), 8.73 (d, J=9.3 Hz,
0.5H), 8.51–8.49 (m, 1H), 7.59–7.55 (m, 2H), 7.43 (dt, J=1.8, 7.8 Hz,
1H), 7.37–7.23 (m, 6H), 7.12–6.83 (m, 10H), 5.80–5.79 (m, 1H), 5.69 (d,
J=3.0 Hz, 0.5H), 5.66 (d, J=3.0 Hz, 0.5H), 2.34 (br, 1H), 2.28 (s, 1.5H),
2.22 ppm (s, 1.5H); 13C NMR (100 MHz, CDCl3): d=159.3, 159.3, 147.1,
143.5, 143.5, 143.4, 142.4, 140.4, 139.1, 139.0, 138.7, 137.5, 131.1, 131.0,
129.7, 129.3, 129.0, 128.6, 127.8, 127.8, 127.4, 126.9, 126.9, 126.6, 126.6,
126.6, 126.3, 126.3, 126.1, 124.7, 124.7, 122.2, 75.7, 75.66, 60.8, 60.8, 21.4,
21.3 ppm; HRMS (ESI): m/z calcd for C32H29N2O3S: 521.18934 [M+H]+;
found: 521.18984.
Compound 3da: Obtained as a white solid by column chromatography
(petroleum ether/ethyl acetate/CH2Cl2, 5:1:1). 1H NMR (300 MHz,
CDCl3): d=8.71 (d, J=12 Hz, 1H), 8.52–8.50 (m, 1H), 7.61 (d, J=
9.0 Hz, 2H), 7.44 (dt, J=3.0, 9.0 Hz, 1H), 7.09–7.05 (m, 3H), 7.01–6.89
(m, 7H), 6.75 (d, J=3.0 Hz, 1H), 6.57 (dd, J=3.0, 9.0 Hz, 1H), 5.64 (d,
J=12.0 Hz, 1H), 3.77 (s, 3H), 2.33 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=159.5, 158.8, 147.5, 142.2, 141.0, 140.6, 138.8, 137.0, 132.3,
132.2, 129.0, 127.3, 126.9, 126.0, 125.9, 124.3, 122.0, 117.4, 112.6, 60.7,
55.3, 21.3 ppm; HRMS (ESI): m/z calcd for C26H25N2O3S: 445.15804
[M+H]+; found: 445.15830.
Compound 3qa: A mixture of two diastereoisomers was obtained as a
white solid by column chromatography (petroleum ether/ethyl acetate/
CH2Cl2, 5:1:1 then petroleum ether/ethyl acetate, 3:1). 1H NMR
(400 MHz, CDCl3): d=8.79–8.74 (m, 1H), 8.49–8.46 (m, 1H), 7.57 (d, J=
8.0 Hz, 2H), 7.43–7.23 (m, 7H), 7.11–6.83 (m, 11H), 5.69 (d, J=4.0 Hz,
0.5H), 5.67 (d, J=4 Hz, 0.5H), 2.44 (br, 1H), 2.28–2.27 (m, 3H), 1.89 (s,
1.5H), 1.88 ppm (s, 1.5H); 13C NMR (100 MHz, CDCl3): d=159.8, 159.8,
147.6, 147.5, 147.4, 147.4, 142.2, 142.2, 140.6, 140.6, 139.2, 139.1, 138.7,
138.3, 136.9, 136.9, 130.8, 130.7, 129.0, 128.7, 128.2, 127.3, 127.1, 126.9,
126.9, 126.2, 126.0, 125.7, 125.6, 125.3, 124.5, 124.5, 121.9, 121.9, 75.8,
60.9, 60.9, 31.0, 30.8, 21.4, 21.3 ppm; HRMS (ESI): m/z calcd for
C33H31N2O3S: 535.20499 [M+H]+; found: 535.20495.
Compound 3ea: Obtained as a white solid (light-pink) by column chro-
matography (petroleum ether/ethyl acetate/CH2Cl2, 5:1:1). 1H NMR
(300 MHz, CDCl3): d=8.63 (d, J=9.6 Hz, 1H), 8.54–8.52 (m, 1H), 7.62–
7.59 (m, 2H), 7.47 (dt, J=1.8, 7.8 Hz, 1H), 7.20 (d, J=2.1 Hz, 1H), 7.13–
6.88 (m, 10H), 5.68 (d, J=9.3 Hz, 1H), 2.37 ppm (s, 3H); 13C NMR
(75 MHz, CDCl3): d=158.4, 147.7, 142.7, 140.9, 140.1, 138.5, 138.3, 137.2,
133.4, 132.3, 131.2, 129.2, 127.9, 127.5, 126.9, 126.4, 125.9, 124.3, 122.4,
60.6, 21.3 ppm; HRMS (ESI): m/z calcd for C25H22ClN2O2S: 449.10850
[M+H]+; found: 449.10879.
Compound 3qa’: Obtained as white solid by column chromatography
(petroleum ether/ethyl acetate/CH2Cl2, 5:1:1). 1H NMR (400 MHz,
CDCl3): d=8.82 (d, J=9.6 Hz, 1H), 8.52–8.51 (m, 1H), 7.64 (d, J=
8.0 Hz, 2H), 7.41 (dt, J=1.6, 7.6 Hz, 1H), 7.38–7.29 (m, 5H), 7.18 (d, J=
2.0 Hz, 1H), 7.09–7.03 (m, 4H), 7.00–6.92 (m, 6H), 6.87 (d, J=8.0 Hz,
1H), 5.73 (d, J=9.6 Hz, 1H), 5.47 (d, J=0.8 Hz, 1H), 5.44–5.43 (m, 1H),
2.33 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=159.8, 149.2, 147.6,
142.3, 141.0, 140.9, 140.6, 139.3, 139.3, 139.0, 137.0, 131.1, 131.1, 129.1,
128.3, 128.1, 127.9, 127.9, 127.4, 127.0, 126.3, 126.0, 124.5, 121.9, 114.8,
61.2, 21.4 ppm; HRMS (ESI): m/z calcd for C33H29N2O2S: 517.19443
[M+H]+; found: 517.19420.
Compound 3 fa: Obtained as a white solid by column chromatography
(petroleum ether/ethyl acetate/CH2Cl2, 6:1:1 to 5:1:1). 1H NMR
(300 MHz, CDCl3): d=9.13 (d, J=9.6 Hz, 1H), 8.52–8.50 (m, 1H), 7.63
(d, J=8.1 Hz, 2H), 7.43 (dt, J=1.8, 7.8 Hz, 1H), 7.17–7.03 (m, 5H),
6.97–6.83 (m, 7H), 5.77 (d, J=9.6 Hz, 1H), 2.78–2.68 (m, 1H), 2.31 (s,
3H), 1.16 (d, J=3.3 Hz, 3H), 1.14 ppm (d, J=3.3 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=159.9, 148.9, 147.3, 142.1, 140.8, 139.6, 139.0, 137.0,
136.9, 131.6, 129.7, 129.1, 127.2, 126.8, 126.0, 125.9, 125.5, 124.4, 121.7,
61.8, 33.4, 23.8, 23.4, 21.3 ppm; HRMS (ESI): m/z calcd for C28H29N2O2S:
457.19443 [M+H]+; found: 457.19458.
Compound 3bc: Obtained as white solid by column chromatography (pe-
troleum ether/ethyl acetate/CH2Cl2, 5:1:1). 1H NMR (300 MHz, CDCl3):
d=8.67 (d, J=9.6 Hz, 1H), 8.55–8.53 (m, 1H), 7.60 (d, J=8.4 Hz, 2H),
7.45 (dt, J=1.8, 7.8 Hz, 1H), 7.28–7.18 (m, 2H), 7.12–6.99 (m, 5H), 6.88
(d, J=8.1 Hz, 1H), 6.80 (t, J=7.5 Hz, 1H), 6.72–6.64 (m, 3H), 5.67 (d,
J=9.3 Hz, 1H), 2.33 (s, 3H), 2.05 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=160.0, 147.5, 142.3, 140.5, 140.0, 139.6, 138.8, 136.8, 136.8,
131.3, 130.9, 129.0, 128.1, 127.6, 127.3, 126.9, 126.9, 126.7, 124.5, 123.3,
121.8, 61.3, 21.4, 21.1 ppm; HRMS (ESI): m/z calcd for C26H25N2O2S:
429.16313 [M+H]+; found: 429.16305.
Compound 3ga: Obtained as a white solid (easily melted by warming) by
column chromatography (hexane/ethyl acetate, 3:1). 1H NMR (400 MHz,
CDCl3): d=8.59–8.58 (m, 1H), 7.90 (d, J=8.8 Hz, 1H), 7.64 (d, J=
8.4 Hz, 2H), 7.30–7.27 (m, 1H), 7.10–7.05 (m, 4H), 6.93–6.91 (m, 3H),
6.84–6.82 (m, 3H), 6.66 (t, J=8.0 Hz, 2H), 5.54 (d, J=9.2 Hz, 1H), 3.64
(s, 3H), 2.36 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=157.5, 155.8,
148.0, 142.4, 141.7, 140.7, 138.6, 135.4, 129.1, 129.0, 128.5, 127.4, 127.3,
127.0, 126.1, 125.7, 122.8, 121.8, 110.7, 60.9, 55.8, 21.4 ppm; HRMS (ESI):
m/z calcd for C26H25N2O3S: 445.15804 [M+H]+; found: 445.15797.
Compound 3be: Obtained as white slabby oil by column chromatography
(petroleum ether/ethyl acetate/CH2Cl2, 5:1:1). 1H NMR (300 MHz,
CDCl3): d=8.93 (d, J=9.6 Hz, 1H), 8.53 (dd, J=0.9, 4.8 Hz, 1H), 7.62
(d, J=8.4 Hz, 2H), 7.46 (dt, J=1.8, 7.8 Hz, 1H), 7.33–7.00 (m, 11H),
6.89 (d, J=7.8 Hz, 1H), 5.72 (d, J=9.3 Hz, 1H), 2.34 ppm (s, 3H);
13C NMR (75 MHz, CDCl3): d=159.4, 147.4, 145.0, 142.5, 139.2, 139.0,
138.5, 137.1, 131.4, 131.2, 129.1 (2C), 128.3, 128.3 (q, J=32.0 Hz), 128.0,
126.8 (2C), 126.3 (2C), 124.4, 124.1 (q, J=3.6 Hz, 2C), 123.9 (q, J=
Compound 3ha: Obtained as a white solid by column chromatography
(hexane/ethyl acetate, 5:1). 1H NMR (300 MHz, CDCl3): d=8.74 (d, J=
9.3 Hz, 1H), 8.51–8.49 (m, 1H), 7.63–7.59 (m, 2H), 7.44 (dt, J=1.8,
7.8 Hz, 1H), 7.09–7.04 (m, 3H), 7.02 (d, J=7.8 Hz, 1H), 6.93–6.86 (m,
6H), 6.59 (d, J=9.9 Hz, 1H), 5.58 (d, J=9.6 Hz, 1H), 2.35 (s, 3H),
2.22 ppm (d, J=1.5 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=160.4 (d,
J=246.6 Hz), 158.9, 147.5, 142.6, 140.1, 139.2 (d, J=6.9 Hz), 138.6, 137.0,
135.0 (d, J=3.5 Hz), 134.5 (d, J=5.7 Hz), 129.1, 127.4, 127.0, 126.4, 126.0,
Chem. Eur. J. 2012, 18, 16214 – 16225
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16221

Z.-J. Shi et al.
270.0 Hz), 122.1, 61.2, 21.3 ppm; HRMS (ESI): m/z calcd for
C26H22FN2O2S: 483.13486 [M+H]+; found: 483.13370.
for 24 h. Because the product 10 was difficult to isolate in pure form
from TsNH2, the yield was determined NMR spectroscopic analysis.
Upon completion of the reaction, the solvent was evaporated by rotary
evaporator, after which (methoxymethyl)benzene (4.0 mg, 0.03274 mmol)
was added as internal standard to determine the yield of the desired
product 10. After dissolving the residue in CDCl3, the mixture was de-
tected by 400MHz 1H NMR spectroscopic analysis. Comparison of the
1H NMR data of this system and the data of 10 identified the characteri-
zation peak and provided the NMR yield. The characteristic peaks are as
follows. 1H NMR (400 MHz, CDCl3): d=9.80 (s, 0.31H, CHO), 5.72 (d,
J=7.6 Hz, 0.35H, benzyl CH of product), 4.46 (s, 2H, CH2 of internal
standard), 3.39 ppm (s, 3H, CH3 of internal standard). The 1H NMR
yield was 34%. The characterization data of pure compound 10 obtained
Compound 3bf: Obtained as a yellow solid by column chromatography
(petroleum ether/ethyl acetate/CH2Cl2, 6:1:1 to 5:1:1). 1H NMR
(300 MHz, CDCl3): d=9.13 (d, J=9.6 Hz, 1H), 8.53–8.51 (m, 1H), 7.81–
7.76 (m, 2H), 7.62–7.59 (m, 2H), 7.48 (dt, J=1.8, 7.8 Hz, 1H), 7.34–7.24
(m, 2H), 7.19–7.06 (m, 6H), 7.01–6.98 (m, 1H), 6.96 (d, J=8.1 Hz, 1H),
5.73 (d, J=9.3 Hz, 1H), 2.34 ppm (s, 3H); 13C NMR (75 MHz, CDCl3):
d=159.2, 148.6, 147.4, 146.2, 142.7, 139.0, 138.4, 138.3, 137.4, 131.6, 131.3,
129.2, 128.5, 128.3, 126.8, 126.8, 124.4, 122.4, 122.3, 61.3, 21.3 ppm;
HRMS (ESI): m/z calcd for C25H22N3O4S: 460.13255 [M+H]+; found:
460.13291.
Compound 3bl: Obtained as a white solid by column chromatography
(petroleum ether/ethyl acetate/CH2Cl2, 5:1:1). 1H NMR (300 MHz,
CDCl3): d=8.70 (d, J=9.3 Hz, 1H), 8.54–8.52 (m, 1H), 7.60 (d, J=
8.4 Hz, 2H), 7.48 (dt, J=1.8, 7.8 Hz, 1H), 7.28–7.19 (m, 2H), 7.12–6.99
(m, 5H), 6.93 (d, J=8.1 Hz, 1H), 6.84 (d, J=8.4 Hz, 2H), 6.48–6.45 (m,
2H), 5.65 (d, J=9.3 Hz, 1H), 3.64 (s, 3H), 2.33 ppm (s, 3H); 13C NMR
(75 MHz, CDCl3): d=159.9, 157.9, 147.5, 142.3, 139.9, 139.5, 138.7, 137.0,
132.9, 131.4, 130.8, 129.0 (2C), 128.1, 127.6, 127.2 (2C), 126.9 (2C), 124.4,
121.9, 112.8 (2C), 60.9, 55.1, 21.4 ppm; HRMS (ESI): m/z calcd for
C26H25N2O3S: 445.1580 [M+H]+; found: 445.1579.
1
by preparative TLC was as follows: H NMR (400 MHz, CDCl3): d=9.80
(s, 1H), 9.07 (d, J=9.2 Hz, 1H), 8.52 (d, J=4.4 Hz, 1H), 7.62 (d, J=
8.0 Hz, 2H), 7.46–7.42 (m, 3H), 7.31–7.23 (m, 2H), 7.16 (d, J=8.0 Hz,
2H), 7.12–7.06 (m, 4H), 7.00 (d, J=7.6 Hz, 1H), 6.90 (d, J=8.0 Hz, 1H),
5.72 (d, J=9.2 Hz, 1H), 2.34 ppm (s, 3H); 13C NMR (100 MHz, CDCl3):
d=191.8, 159.5, 148.1, 147.5, 142.6, 139.2, 138.9, 138.6, 137.2, 134.5, 131.6,
131.4, 129.2, 128.8, 128.4, 128.1, 126.8, 126.6, 124.4, 122.2, 61.6, 21.4 ppm;
HRMS (ESI): m/z calcd for C26H23N2O3S: 443.14239 [M+H]+; found:
443.14301.
Competition experiment: The competition reaction was conducted with
2-phenylpyridine 5 and alcohol 1a with imine 2a. Catalyst [Cp*Rh-
ACHTUNERGN(UNG CH3CN)3]ACHUTGNTREN[NUNG SbF6]2 (8.3 mg, 0.01 mmol), alcohol 1a (55.1 mg, 0.20 mmol),
Compound 3bm: Obtained as a white solid by column chromatography
(petroleum ether/ethyl acetate/CH2Cl2, 5:1:1). 1H NMR (300 MHz,
CDCl3): d=8.90 (d, J=9.3 Hz, 1H), 8.55–8.53 (m, 1H), 7.65–7.59 (m,
3H), 7.50–7.19 (m, 8H), 7.14–7.03 (m, 6H), 6.82 (d, J=7.8 Hz, 1H), 5.85
(d, J=9.3 Hz, 1H), 2.33 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=
159.8, 147.5, 142.4, 139.7, 139.6, 138.8, 137.9, 136.8, 132.6, 131.9, 131.4,
131.1, 129.1, 128.3, 127.7, 127.2, 127.1, 127.0, 125.7, 125.4, 124.8, 124.6,
124.3, 121.9, 61.5, 21.3 ppm; HRMS (ESI): m/z calcd for C29H25N2O2S:
465.16313 [M+H]+; found: 465.16340.
and aldimine 2a (155.6 mg, 0.60 mmol) were added into a pre-dried
Schlenk tube under air atmosphere. The reaction tube was degassed
three times and the tube was filled with N2, then 2-phenylpyridine 5
(28.6 mL, 0.2 mmol) and freshly distilled tBuOH (1.0 mL) were added by
microinjector and syringe, respectively. The reaction mixture was stirred
in the sealed tube at 908C under N2 atmosphere in a Wattecs Parallel Re-
actor for 3 h. After cooling to RT, the solvent was removed in vacuo and
the yield was determined by NMR spectroscopic analysis. After evapora-
tion of the solvent, (methoxymethyl)benzene (5 mL, 0.1154 mmol) was
added as internal standard. 1H NMR (400 MHz, CDCl3): d=4.46 (s,
2.00H, CH2 of (methoxymethyl)benzene), 5.71 (d, J=5.6 Hz, 1.60H, CH
of 3ba), 5.66 ppm (s, 1.81H, CH of 3aa). The NMR yield of 3aa and 3ba
were 35 and 31%, respectively.
Compound 3bn: Obtained as a white solid by column chromatography
(petroleum ether/ethyl acetate/CH2Cl2, 5:1:1). 1H NMR (300 MHz,
CDCl3): d=8.81 (d, J=9.6 Hz, 1H), 8.56–8.54 (m, 1H), 7.63 (d, J=
8.1 Hz, 2H), 7.45–7.34 (m, 5H), 7.30–7.21 (m, 3H), 7.17–6.98 (m, 9H),
6.91–6.89 (m,1H), 5.74 (d, J=9.6 Hz, 1H), 2.34 ppm (s, 3H); 13C NMR
(75 MHz, CDCl3): d=159.8, 147.5, 142.3, 140.7, 139.9, 139.8, 139.5, 138.9,
138.7, 136.9, 131.4, 131.0, 129.1, 128.6, 128.2, 127.7, 127.1, 126.9, 126.8,
126.4, 126.0, 124.5, 121.9, 61.2, 21.4 ppm; HRMS (ESI): m/z calcd for
C31H27N2O2S: 491.17878 [M+H]+; found: 491.17860.
Deuterium Labeling Experiment: Catalyst [Cp*RhACHTNURTGENNUG(CH3CN)3]ACHTUNGTRENNUNG[SbF6]2
(4.2 mg, 0.005 mmol), 1-phenyl-[3,4,5,6–4D-2-(pyridine-2-yl)]benzyl alco-
hol 7 (26.5 mg, 0.10 mmol) and aldimine 2a (77.80 mg, 0.30 mmol) were
added into a pre-dried Schlenk tube under air atmosphere. The reaction
tube was then evacuated and refilled with N2. After the addition of fresh-
ly distilled tBuOH (1.0 mL) by using a syringe, the reaction mixture was
stirred in the sealed tube at 908C under N2 atmosphere in a Wattecs Par-
allel Reactor for 3 h. After cooling to RT, the solvent was removed in
vacuo and the residue was purified by column chromatography on silica
gel (petroleum ether/EtOAc/CH2Cl2, 5:1:1) to afford compound 8 as a
white solid (80%, 33.4 mg). 1H NMR (300 MHz, CDCl3): d=8.79 (d, J=
9.6 Hz, 1H), 8.54–8.52 (m, 0.95H), 7.62–7.59 (m, 2H), 7.47 (dt, J=1.8,
7.8 Hz, 1H), 7.21 (s, 1H), 7.12–7.03 (m, 3H), 7.00–6.86 (m, 6H), 5.71 (d,
J=9.6 Hz, 1H), 2.33 ppm (s, 3H). From this result, it can be concluded
that the H/D ratio of the product is approximately 95:5.
Compound 3bo: Obtained as a white solid (the solution in CDCl3 was
slightly blue) by column chromatography (petroleum ether/ethyl acetate/
CH2Cl2, 6:1:1). 1H NMR (300 MHz, CDCl3): d=8.61 (d, J=9.6 Hz, 1H),
8.58–8.56 (m, 1H), 7.63–7.58 (m, 3H), 7.32–7.10 (m, 5H), 7.06 (d, J=
7.8 Hz, 3H), 6.95–6.94 (m, 1H), 5.90 (q, J=1.8 Hz, 1H), 5.74–5.73 (m,
1H), 5.67 (d, J=9.3 Hz, 1H), 2.33 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=159.8, 153.1, 147.6, 142.5, 141.3, 139.7, 138.6, 137.5, 137.1,
131.1, 130.6, 129.1, 128.4, 128.1, 127.0, 124.1, 122.1, 109.9, 106.9, 56.9,
21.4 ppm; HRMS (ESI): m/z calcd for C23H21N2O3S: 405.12674 [M+H]+;
found: 405.12674.
Compound 3ra: Obtained as a white solid by column chromatography
(hexane/ethyl acetate, 5:1). 1H NMR (400 MHz, CDCl3): d=7.80 (d, J=
9.6 Hz, 1H), 7.63 (d, J=8.4 Hz, 2H), 7.58 (d, J=1.6 Hz, 1H), 7.30–7.27
(m, 1H), 7.17–7.12 (m, 2H), 7.09 (t, J=8.4 Hz, 3H), 7.03–7.01 (m, 3H),
6.99 (d, J=2.4 Hz, 1H), 6.92–6.90 (m, 2H), 6.08 (t, J=2.0 Hz, 1H), 5.69
(d, J=1.6 Hz, 1H), 2.33 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=
142.6, 140.3, 139.5, 138.8, 138.4, 136.9, 131.5, 130.9, 129.2, 128.5, 128.3,
127.7, 127.0, 126.7, 125.5, 106.8, 59.6, 21.4 ppm; HRMS (ESI): m/z calcd
for C23H22N3O2S: 404.14272 [M+H]+ and C23H21KN3O2S: 442.09861
[M+K]+; found: 404.14278 and 442.09893.
In situ NMR detection (Figure 1): This experiment was conducted in a
Young NMR tube on 0.025 mmol scale in 405 mL solvent (0.06173m),
which has lower concentration than in our standard reaction conditions.
This was because larger amounts of substrate did not dissolve well in the
NMR tube at RT, which affected the locking and shimming. Solutions
were prepared that contained 1b (65.33 mg, 0.25 mmol) and catalyst
(41.64 mg, 0.05 mmol) dissolved in freshly distilled [D8]toluene (1 mL,
0.025 mmol/100 mL) and distilled acetone (10 mL, 0.00125 mmol/250 mL)
in a volumetric flask. In addition (methoxymethyl)benzene (229.1 mg,
1.875 mmol) was dissolved in mesitylene (5 mL) as internal standard sol-
ution (0.001875 mmol/5 mL). To a pre-dried NMR tube, catalyst solution
(250 mL, 0.00125 mmol) was added by using a microinjector, and then the
solvent was removed under vacuum. Then [D8]toluene (100 mL) was then
added and vigorous shaking and slight heating were applied to dissolve
the catalyst. Imine 2a (19.6 mg, 0.075 mmol) was added to the NMR
N-{(4-Formylphenyl)[2-(pyridin-2-yl)phenyl]methyl}-4-methylbenzenesul-
fonamide (10): The reaction was carried out following the standard pro-
cedure. Catalyst [Cp*RhACHTUNGTRENNUN(G CH3CN)3]ACHUTGNTREN[NUNG SbF6]2 (4.2 mg, 0.005 mmol) and sub-
strate 9 (15.0 mg, 0.034 mmol) were added into a pre-dried Schlenk tube
under air atmosphere. The reaction tube was then evacuated and refilled
with N2. After the addition of freshly distilled tBuOH (0.5 mL) and tol-
uene (0.5 mL) by using a syringe, the reaction mixture was stirred in the
sealed tube at 908C under N2 atmosphere in a Wattecs Parallel Reactor
16222
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 16214 – 16225

Cleavage of Benzyl/Allylic Alcohols
FULL PAPER
tube, followed by further [D8]toluene (150 mL) to dissolve the imine. In-
ternal standard solution (5 mL, 0.001875 mmol, 7.5%), alcohol 1b solu-
tion (100 mL, 0.025 mmol), and [D8]toluene (50 mL) were then added se-
quentially. Finally, the NMR tube was filled with N2 and sealed. The
sample was first tested at RT to ensure that locking, shimming were satis-
factory, then the sample was heated to 908C before the data were collect-
ed (the experiment was conducted with a Bruker 500m NMR spectrome-
ter). For the first hour, data were collected every 5 min, and subsequent-
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1
ly, data were collected every 10 min. H NMR data were selected as con-
centration detection signals. The following characteristic peaks were used
to determine the concentration of the arious species: 1H NMR
(500 MHz, CDCl3): d=9.70 (s, CHO of benzaldehyde), 8.54 (d, 2-phenyl
pyridine), 6.02 (s, CH of product), 5.94 (s, CH of alcohol 1b), 4.26 (s,
CH2 of internal standard), 3.17 (s, CH3 of internal standard).
Transformation between alcohols: Typical procedure for 12 (Table 4): A
50 mL Schlenk tube was heated using a heat gun under vacuum to dry
the tube. After cooling to RT, catalyst [Cp*RhACHTNUTRGENN(UG CH3CN)3]ACHTUNGTRNE[NUGN SbF6]2 (8.3 mg,
[3] a) A. F. Trindade, P. M. P. Gois, M. T. Duarte, C. A. M. Afonso, S.
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0.01 mmol), alcohol 1b (0.2 mmol), and benzaldehyde derivative 11
(0.60 mmol) were added in sequence to the tube under air atmosphere.
The reaction tube was then evacuated and refilled with N2. After the ad-
dition of freshly distilled tBuOH (1.0 mL, condition A) or CH2Cl2
(1.0 mL, condition B), the reaction mixture was stirred in the sealed tube
at 908C under N2 atmosphere in a Wattecs Parallel Reactor for the time
indicated. After cooling to RT, the solvent was removed in vacuo and the
residue was purified by column chromatography on silica gel (petroleum
ether/EtOAc, 6:1 to 2:1, or petroleum ether/EtOAc/CH2Cl2, 6:1:1 to
3:1:1) to afford compound 12 as a white solid.
Compound 12a: Obtained by column chromatography (petroleum ether/
EtOAc/CH2Cl2, 4:1:1) as a white solid. 1H NMR (400 MHz, CDCl3): d=
8.55–8.54 (m, 1H), 8.02–8.00 (m, 2H), 7.72 (dt, J=1.6, 8.0 Hz, 1H), 7.51–
7.40 (m, 7H), 7.25–7.23 (m, 2H), 5.85 ppm (s, 1H); 13C NMR (100 MHz,
CDCl3): d=159.30, 151.21, 147.51, 146.65, 142.43, 139.64, 137.78, 131.13,
130.42, 129.33, 128.45, 127.05, 124.16, 122.78, 122.46, 74.58 ppm; HRMS
(ESI): m/z calcd for C18H15N2O3: 307.10772 [M+H]+; found: 307.10801.
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references therein.
Transformation from allylic alcohol into allylic amine: Typical procedure
for 14 (Table 5): A 50 mL Schlenk tube was heated using a heat gun
under vacuum to dry the tube. After cooling to RT, catalyst [Cp*Rh-
ACHTUNGTRENNUNG(CH3CN)3]ACHTUNGTRENNUNG[SbF6]2 (8.3 mg, 0.01 mmol), alcohol 13 (0.2 mmol), and aldi-
mine derivative 2 (0.60 mmol) were added in sequence to the tube under
air atmosphere. The reaction tube was then evacuated and refilled with
N2. After the addition of freshly distilled tBuOH (1.0 mL), the reaction
mixture was stirred in the sealed tube at 90 or 1108C under N2 atmos-
phere in a Wattecs Parallel Reactor for the time indicated. After cooling
to RT, the solvent was removed in vacuo and the residue was purified by
column chromatography on silica gel (petroleum ether/EtOAc, 6:1 to 2:1,
or petroleum ether/EtOAc/CH2Cl2, 6:1:1 to 3:1:1) to afford compound 14
as a white solid.
Compound 14b: Obtained by column chromatography (petroleum ether/
EtOAc/CH2Cl2, 5:1:1) as
a
light-yellow solid. 1H NMR (400 MHz,
CDCl3): d=9.20–9.17 (br, 1H), 8.54 (d, J=4.0 Hz, 1H), 7.67 (dt, J=1.2,
7.6 Hz, 1H), 7.49 (d, J=8.0 Hz, 2H), 7.16–7.01 (m, 7H), 6.86–6.82 (m,
1H), 5.56 (s, 1H), 2.74–2.69 (m, 1H), 2.54–3.48 (m, 2H), 2.36 (s, 3H),
2.30–2.22 (m, 1H), 1.77–1.73ACHTNUGRTNEUNG
(m, 1H), 1.62–1.57 ppm (m, 1H); 13C NMR
(100 MHz, CDCl3): d=162.7 (d, J=240.0 Hz), 154.1, 148.0, 142.8 (d, J=
71.0 Hz), 142.5, 138.3, 137.1, 135.8, 129.6 (d, J=100.0 Hz), 129.0, 126.9,
122.7 (d, J=3.0 Hz), 122.6, 121.77, 114.0 (d, J=20.0 Hz), 56.2, 39.2, 36.5,
21.4, 21.4 ppm; HRMS: m/z calcd for C24H24FN2O2S: 423.15370 [M+H]+;
found: 423.15386.
À
[13] For reviews on C H bond functionalization, see the following refer-
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Acknowledgements
Support of this work by a starter grant from Peking University and a
grant from the National Sciences of Foundation of China (No. 20821062,
20832002, 20925207, 20902006, 21002001) and the “973” Project from the
MOST of China (2009CB825300) is gratefully acknowledged.
Chem. Eur. J. 2012, 18, 16214 – 16225
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
16223

Z.-J. Shi et al.
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2+
[23] For cationic [Cp*RhIII
]
catalyzed C N bond formation, see: K.-H.
À
Ng, Z. Zhou, W.-Y. Yu, Org. Lett. 2012, 14, 272.
2+
[15] For cationic [Cp*RhIII
]
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À
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]
catalyzed C H addi-
2+
À
tion to imines, see: a) M. E. Tauchert, C. D. Incarvito, A. L. Rhein-
gold, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc. 2012, 134,
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catalyzed C H addition to isocyanates,
see: K. D. Hesp, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc.
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Angew. Chem. 2008, 120, 8789; Angew. Chem. Int. Ed. 2008, 47,
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Chem. Commun. 2010, 46, 1541. See also the Mitsunobu reaction.
2+
[17] For cationic [Cp*RhIII
]
À
2+
[18] For cationic [Cp*RhIII
]
catalyzed C H addition to aldehydes, see:
a) L. Yang, C. A. Correia, C.-J. Li, Adv. Synth. Catal. 2011, 353,
[28] Several examples of substitution/displacement reactions through C
À
À
C
single cleavage. Substitution reactions of propargylic amines
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Cleavage of Benzyl/Allylic Alcohols
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Received: May 28, 2012
Revised: August 9, 2012
Published online: October 18, 2012
Chem. Eur. J. 2012, 18, 16214 – 16225
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
16225