Cobalt-Catalyzed Regio- and Enantioselective Allylic Amination

Article abstract of DOI:10.1021/jacs.9b06035

The first earth-abundant cobalt-catalyzed highly branched- and enantioselective allylic amination of racemic branched allylic carbonates bearing alkyl groups with both aromatic and aliphatic amines has been developed. The process allows rapid access of allylic amines in high yields with exclusively branched selectivity and excellent enantioselectivities (normally 99% ee) under mild reaction conditions.

Full text of DOI:10.1021/jacs.9b06035

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Communication
Cobalt-Catalyzed Regio- and Enantioselective Allylic Amination
Samir Ghorai, Sahadev Shrihari Chirke, Wen-Bin Xu, Jia-Feng Chen, and Changkun Li
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 05 Jul 2019
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Cobalt-Catalyzed Regio- and Enantioselective Allylic Amination
Samir Ghorai,† Sahadev Shrihari Chirke,† Wen-Bin Xu,† Jia-Feng Chen,† Changkun Li*,†‡
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†Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering
Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
‡Beijing National Laboratory of Molecular Sciences (BNLMS), Beijing 100871, China
Supporting Information Placeholder
protocol is effective for both racemic branched and linear (Z and E)
ABSTRACT: The first earth-abundant cobalt-catalyzed highly
allylic substrates under neutral conditions (Scheme 1, d).
branched- and enantioselective allylic amination of racemic
branched allylic carbonates bearing alkyl groups with both
Scheme 1. Earth-abundant Cobalt-Catalyzed Allylic
aromatic and aliphatic amines have been developed. The process
Substitutions
allows rapid access of allylic amines in high yields with exclusively
branched selectivity and excellent enantioselectivities (normally
a
Linear products or low regioselectivities
, regioselectivity:
99% ee) under mild reaction conditions.
Lg
Nu
Co
R
Nu
Nu-
R
+
or
R
R
Lg
main product
Challenging
Transition-metal-catalyzed asymmetric allylic substitution
reaction provides powerful methods for the enantioselective
construction of carbon-carbon and carbon-heteroatom bonds.1
However, several issues, such as regio/enantioseletive control and
substrate scope, are still challenging for this transformation. For
unsymmetrical allylic substrates, it is well known that Pd-catalyzed
allylic substitutions mostly give the products at the less-hindered
positions. Different from Pd, Ir-catalyzed asymmetric allylic
substitution of linear allylic substrates could afford branched
products with high regio- and enantioselectivities.2 Nevertheless,
the Ir-catalyzed reactions for the more readily accessible racemic
branched allylic substrates remain challenging. Although regio-
and enantioselective allylic substitution for certain substrates3,4 or
by other transition metals5 have been achieved in some cases, the
reaction of simple alkyl-substituted allylic donors is largely
unexplored. Highly regio- and enantioselective allylations of
aliphatic amines and indoles have only been recently reported by
Krische with their -allyliridium C,O-benzoate catalysts.4a,c
Therefore, the development of new efficient catalytic system to
achieve asymmetric allylic substitution of simple alkyl-substituted
allylic substrates is still highly desired.
b
, our previous work:
Branch-selective/Enantio-control on the nucleophile
cat. Co(BF4)2
cat. (S,S)-Ph-BPE
O
O
O
Me Me
CO2tBu
85% yield, 92% ee
OCO2Me
Me
t
+
O Bu
cat. Zn
Me
c
, Matsunaga and Kojima:
Branch-selective/Enantioselective version is not efficient
CoBr2, dppp
MeO2C
CO2Me
iPr2NEt, photocatalyst
OCO2Me
MeO2C
CO Me
+
2
Me
Me
90% yield, > 20 : 1 b/l
d
Branch- and enantioselective/Enantio-control on the electrophile
, this work:
5 mol% Co(BF4)2
OCO2R
R2
N
R3
R2
R1
R3
L*
6 mol%
+
N
R1
racemic
10 mol% Zn
H
R2 = Ar, Alkyl
R3 = alkyl, H
CH3CN
R1 = alkyl, Ar
R'
P
easily available tridentate ligands
exclusive branch-selectivity
Cobalt is an earth-abundant, lower-cost first-row transition
metal. The development of Co-catalyzed allylic substitution is
undoubtedly one of the ways to meet the criteria of sustainable and
green chemistry.6 Although Co-catalyzed allylic substitution has
sporadically been reported, the transformations normally produce
the linear products (Scheme 1, a).7 To the best of our knowledge,
highly branched- and enantioselective Co-catalyzed allylic
substitutions were unknown before our recent report on Co-
catalyzed enantioselective reverse prenylation of -ketoesters, in
which the enantioselectivity on the nucleophiles can be controlled
(Scheme 1, b). During we are preparing this manuscript,
Matsunaga and Kojima developed a Co-catalyzed allylation of
malonates and other derivatives with high branch-selectivity in
non-asymmetric variant (Scheme 1, c).9 Herein, we report the first
Co-catalyzed highly regio- and enantioselective allylic amination
with aniline and aliphatic amine derivatives, which allows rapid
access allylic amines10 in high yields with complete branch-
selectivities and excellent enantioselectivities. In addition, the
30 examples, normally 99% ee
novel complexation mode
neutral reaction condition
O
N
N
O
L*
Bisoxazolinephosphine
R'' R''
Inspired by the high stability and reactivity of base-metal/pincer
complexes,11 we initially conducted the reaction of racemic n-
propyl allylic carbonate 1a and aniline 2a as the model substrates
in the presence of Co-catalyst in situ formed by Co(BF4)2 and
tridentate chiral ligand (Table 1). However, the reaction with Pybox
ligand L1 barely took place (entry 1). To our delight, when the
reaction with bisoxazolinephosphine12 L2 in the presence of zinc
dust as a reductant was conducted at room temperature, the desired
allylic amine 3aa was obtained with exclusively branched
regioselectivity and excellent enantioselectivity (>99% ee),
whereas in moderate yield (entry 2). To further optimize the
catalytic reactivity, several NPN-type ligands with variations on the
oxazoline rings and the phosphine atom were synthesized (see
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Page 2 of 6
d
column. Co(BF4)2 (0.01 eq), L6 (0.0125 eq), Zn dust (0.02 eq) were
Supporting Information). It was found that the substitution on the
oxazoline rings for the ligand played important roles for the
reaction (entries 2-6). The reaction with ligand L3 bearing tert-
butyl group almost did not proceed (entry 3). It was delightedly
found that the reaction with ligand L6 with phenyl on the oxazoline
rings proceeded smoothly to give product 3aa in almost
quantitative yield with complete branch- and enantioselectivity
(entry 6). Next, the ligand with several different R1-substituents
were examined to evaluate the electronic and steric properties on
the phosphorus atom. The electronic and steric properties of P-atom
of the ligand also affected for the reaction efficiency (entries 7-11).
The ligand with the electron-rich and more bulky group is
beneficial for the reactivity, thus the reaction could be improved to
give 3aa in high yield when using the ligand L10 and L11 with 4-
MeO-3,5-tBu2C6H2 group (entries 10 and 11). Notably, although
the NPN-type ligands showed different reactivity for the reaction,
above 99% ees could be observed for all cases (entries 2-11). Next,
we examined the allylic amination reaction by using PN-type
ligand L12 and NPN-type ligand L13 without rigid phenyl ring.
However, the ligands are not effective for the reaction (entries 12
and 13). Full conversion of 2a was also obtained with 1 mol%
cobalt catalyst, although longer time (33 hours) is needed (entry
14).
used in 1.25 mmol scale and the reaction time is 33 hours.
1
2
3
4
5
6
7
8
Under the optimized condition (Table 1, entry 6), the reaction
scope was evaluated by using different substituted anilines
(Scheme 2). Various anilines with different electronic and steric
nature were tolerated under the reaction conditions to afford allylic
amines 3aa-3af in high yields with complete regioselectivities and
very high levels of enantioselectivities. In a 6 mmol scale reaction
with 2 mol % catalyst, 3ab could be obtained in 94% yield and 98%
ee, which indicates this transformation could be conducted in a
larger scale. High chemoselectivity was also observed with N-(4-
aminophenyl)acetamide and 5-aminoindole, thus allylic amines
3ag and 3ah as the only products were obtained with almost
quantitative yields and high enantioselectivities. Secondary amines
such as N-methylaniline and indoline were also suitable reaction
partners to give corresponding allylic amines 3ai and 3aj with high
selectivities. The phenylhydrazine 2k was also involved in this
reaction to afford the product 3ak, which could be transformed into
the N-allyl indole.10d The absolute configuration of 3ag was
assigned to be R by the single crystal X-ray diffraction analysis.
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Scheme 2. The scope of anilinesa
5 mol %Co(BF4)2
6
6 mol % L
Table 1. Optimization for Co-catalyzed Asymmetric Allylic
Aminationa
OCO2Me
NHAr
10 mol% Zn
Ar NH2
n-C3H7
1a
n-C3H7
Br
CH3CN, rt, 16 h
2
rac- (1.5 eq)
(1.0 eq)
5 mol% Co(BF4)2
L
6 mol%
OCO2Me
NHPh
MeO
10 mol% Zn
t-Bu
+
PhNH2
n-C3H7
n-C3H7
CH3CN, rt, 16 h
3aa
2a
1a
rac-
NH
NH
NH
NH
n-C3H7
3aa
n-C3H7
3ab
n-C3H7
3ac
n-C3H7
3ad
, R1 = Ph, R2 = iPr
, R1 = Ph, R2 = tBu
, R1 = Ph, R2 = Me
, R1 = Ph, R2 = Bn
, R1 = Ph, R2 = Ph
R1
P
L2
L3
L4
L5
L6
O
N
O
N
98% yield (94% yieldb)
99% yield
97% yield
95% yield
>99% ee
N
N
N
O
>99% ee (98% eeb)
>99% ee
>99% ee
O
iPr
iPr
L1
R2 R2
Me
NH
AcHN
Me
, R1 = 4-CF3C6H4, R2 = iPr
, R1 = 4-NMe2C6H4, R2 = iPr
, R1 = 4-OMeC6H4, R2 = iPr
, R1 = 4-OMe-3,5-tBu2C6H2, R2 = iPr
, R1 = 4-OMe-3,5-tBu2C6H2, R2 = Bn
Ph
P
L7
L8
L9
NH
NH
PPh2
O
n-C3H7
n-C3H7
3af
n-C3H7
O
N
N
O
O
N
3ag
3ae
L10
L11
91% yield
98% ee
99% yield
>99% ee
99% yield
>99% ee
iPr
iPr
L13
iPr
L12
3ag
H
N
yield (3aa, %)b
ee (%)c
--
Me
entry
1
catalyst
NH2
N
N
N
NH
Co(BF4)2/L1
Co(BF4)2/L2
Co(BF4)2/L3
Co(BF4)2/L4
Co(BF4)2/L5
Co(BF4)2/L6
Co(BF4)2/L7
Co(BF4)2/L8
Co(BF4)2/L9
< 5
57
< 5
84
68
99
38
70
63
89
96
< 5
< 5
99
n-C3H7
n-C3H7
n-C3H7
n-C3H7
3ah
3ai
66% yieldc
2
> 99
> 99
> 99
> 99
> 99
> 99
--
3aj
3ak
99% yield
98% ee
99% yield
99% ee
83% yield
>99% ee
3
99% ee
4
aConditions: 1a (0.38 mmol, 1.5 equiv), 2 (0.25 mmol, 1.0 equiv),
Co(BF4)2 (0.0125 mmol, 0.05 eq), L6 (0.015 mmol, 0.06 eq), Zn dust
(0.025 mmol, 0.1 eq) and CH3CN (2 mL). b2 mol% catalyst in a 6 mmol
5
6
c
scale. 10 mol% catalyst
7
8
The reaction scope was next examined by using various allylic
carbonates with p-anisidine 2b as model substrate (Scheme 3).
Importantly, the reaction is also effective for the allylic carbonate
derivatized from but-3-en-2-ol to afford allylic amine 3bb in 84%
yield with high enantioselectivity (97% ee). The allylic amine 3cb
with phenylethyl group could be synthesized in high yield and
above 99% ee. Sterically more hindered isopropyl, isobutyl and
cyclohexyl groups could be introduced by the allylic amination to
give corresponding allylic amines in high yields with excellent
enantioselectivities. Significantly, versatile cyclopropyl group, free
and protected hydroxyl groups could also be installed to afford
corresponding allylic amines with high yields with high levels of
enantioselectivities. Not only aliphatic racemic allylic carbonates,
9
> 99
> 99
> 99
--
10
11
12
13
14d
Co(BF4)2/L10
Co(BF4)2/L11
Co(BF4)2/L12
Co(BF4)2/L13
Co(BF4)2/L6
--
99
aConditions: 1a (0.38 mmol, 1.5 equiv), 2a (0.25 mmol, 1.0 equiv),
Co(BF4)2 (0.0125 mmol, 0.05 eq), ligand (0.015 mmol, 0.06 eq), Zn
b
c
dust (0.025 mmol, 0.1 eq) and CH3CN (2 mL). Isolate yield. The
enantiomeric excess of 3aa was determined by HPLC with a chiral
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phenyl substituted allylic carbonate 1h also participated in this
carbonates, when branched allyl hexafluoroisopropyl carbonate
1k was used in the presence of electron-rich L11 as ligand at 60
oC, full conversion of morpholine was realized to afford allylic
amine 7ka with 99% ee (Scheme 5). With this optimal conditions
in hand, the reaction with different aliphatic amines was
examined. The reactions with other cyclic secondary amines 6b,
6c and 6d gave corresponding allylic amines with good yields and
excellent enantioselectivities. Primary aliphatic amines were also
suitable reaction partners to produce allylic amines 7ke to 7kg in
good yields with high levels of enantioselectivities. The reactions
of both enantiomers of 1-phenylethanamine could also give the
1
2
3
4
5
6
7
8
reaction to produce allylic amine 3hb in 84% yield with 99% of ee
value when electron-rich L11 was used as a ligand under otherwise
identical conditions.
We next examined the Co-catalyzed allylic amination of linear
allylic carbonates. However, both Z- and E-linear allylic methyl
carbonates are not active under the optimal conditions. To
Scheme 3. The scope of allylic carbonatesa
9
5 mol %Co(BF4)2
c o r r e s p o n d i n g
7 k h
a n d
7 k i
L6
6 mol %
Ar
10
11
12
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OCO2Me
NH
10 mol% Zn
ArNH2
+
CH3CN, rt, 16 h
R
Scheme 5. The scope of aliphatic aminesa
Ar = 4-MeOC6H4
R
1
2b
3bb-3jb
rac- (1.5 eq)
(1.0 eq)
Ar
Ar
Ar
Ar
Ar
NH
NH
NH
NH
NH
Me
Me
Ph
Me
3db
3fb
3cb
3bb
3eb
88% yield
> 99% ee
98% yield
> 99% ee
84% yield
97% ee
89% yield
> 99% ee
81% yield
> 99% ee
Ar
Ar
Ar
Ar
NH
NH
NH
NH
HO
TBSO
Ph
3gb
3hb
84% yieldb
3ib
3jb
95% yield
>99% ee
89% yieldc
96% yield
>99% ee
99% ee
94% ee
aConditions: 1 (0.38 mmol, 1.5 equiv) and 2b (0.25 mmol, 1.0 equiv)
Co(BF4)2 (0.0125 mmol, 0.05 eq), L6 (0.015 mmol, 0.06 eq), Zn dust
(0.025 mmol, 0.1 eq) in CH3CN (2mL). L11 was used. 10 mol% of
b
c
catalyst was used.
accelerate the oxidative addition step, electron-withdrawing
hexafluoroisopropyl carbonates13 4 and 5 were synthesized. As
shown in Scheme 4, when using electron-riched L11 as a ligand at
60 oC, the allylic aminations of both E/Z isomers 4 and 5 proceeded
smoothly to afford same allylic product 3ab in acceptably high
yields with excellent enantioselectivities, albeit slightly less regio-
and enantioselectivity were observed for the reaction of Z-isomer
5.
aConditions: 1k (0.38 mmol, 1.5 equiv) and 6 (0.25 mmol, 1.0 equiv)
Co(BF4)2 (0.0125 mmol, 0.05 eq), L6 (0.015 mmol, 0.06 eq), Zn dust
(0.025 mmol, 0.1 eq) in CH3CN (2 mL). b1k (1.0 eq) and 6j (2.0 eq).
Scheme 4. The reactions of Z- and E-linear allylic
carbonates.
with high diastereoselectivities, which supports an excellent
catalyst control. As predicted, primary aliphatic amines with
electron-withdrawing CF3 group is more reactive, thus the allylic
amine 7kj bearing CF3 group was isolated in 84% yield.
MeO
5 mol %Co(BF4)2
10 mol% Zn
CF3
O
NH2
L11
6 mol%
F3C
O
O
NH
+
CH3CN, 60 oC, 16 h
MeO
2b
n-C3H7
n-C3H7
Scheme 6. The synthesis of Co(CH3CN)2(BF4)2-L8, Co(I)I-L4
and their reactivities
4
3ab
, 70%, 99% ee
B : L > 50 : 1
(1.5 eq)
(1.0 eq)
5 mol %Co(BF4)2
10 mol% Zn
MeO
NH2
n-C3H7
O
CF3
CF3
L11
6 mol%
+
NH
CH3CN, 60 oC, 16 h
O
O
MeO
2b
n-C3H7
(1.0 eq)
5
(1.5 eq)
3ab
, 70%, 95% ee
B : L = 13 : 1
To further expand the reaction scope of the Co-catalyzed
asymmetric allylic amination, we investigated the allylic
amination with aliphatic amines. Unfortunately, the reaction did
not proceed under the optimal conditions (Table 1, entry 6). More
basic aliphatic amines may lead to the deactivation of catalysts
because of the relative hard nature of cobalt metal. After further
optimization, we found that with 20 mol% Lewis acid La(OTf)3
under otherwise identical conditions, the allylic product 7ka could
be obtained in moderate yield. Inspired by the linear allylic
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NMe2
-
2BF4
AUTHOR INFORMATION
1
2
3
4
5
6
7
8
Corresponding Author
O
P
iPr
N
*E-mail: chkli@sjtu.edu.cn
Co(BF4)2
CH3CN
85%
O
N
P
N
Co
iPr
NMe2
N
N
O
N
O
Notes
H3C
CH3
The authors declare no competing financial interests.
iPr
iPr
L8
Co(CH3CN)2(BF4)2-
L8
ACKNOWLEDGMENT
This work is supported National Natural Science Foundation of
China (NSFC) (Grant 21602130) and the starting fund of Shanghai
Jiao Tong University. We thank Professor Yong Jian Zhang from
Shanghai Jiao Tong University for the helpful discussion.
9
Ph
P
1) CoI2
O
10
11
12
13
14
15
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60
P
N
Me
2) NaBH4
O
N
N
O
O
N
Me
Co
I
82%
Me Me
L4
L4
CoI-
REFERENCES
(1) (a) Trost, B. M.; Van Vranken, D. L. Asymmetric Transition Metal-
Catalyzed Allylic Alkylations. Chem. Rev. 1996, 96, 395-422. (b)
Trost, B. M.; Crawley, M. L. Asymmetric Transition-Metal-Catalyzed
Allylic Alkylations: Applications in Total Synthesis. Chem. Rev. 2003,
103, 2921-2943. (c) Lu, Z.; Ma, S. Metal-Catalyzed Enantioselective
Allylation in Asymmetric Synthesis. Angew. Chem. Int. Ed. 2008, 47,
258-297. For a recent book, see: (d) Transition Metal Catalyzed
Enantioselective Allylic Substitution in Organic Synthesis, U.
Kazmaier, Ed. Springer Verlag: Berlin and Heidelberg, Germany, 2012.
(2) For selected reviews, see: (a) Hartwig, J. F.; Stanley, L. M.
Mechanistically Driven Development of Iridium Catalysts for
Asymmetric Allylic Substitution. Acc. Chem. Res. 2010, 43, 1461-1475.
(b) Hethcox, J. C.; Shockley, S. E.; Stoltz, B. M. Iridium-Catalyzed
Diastereo-, Enantio-, and Regioselective Allylic Alkylation with
Prochiral Enolates. ACS Catal. 2016, 6, 6207-6213. (c) Qu, J.;
Helmchen, G. Applications of Iridium-Catalyzed Asymmetric Allylic
Substitution Reactions in Target-Oriented Synthesis. Acc. Chem. Res.
2017, 50, 2539-2555. (d) Iridium-Catalyzed Asymmetric Allylic
Substitution Reactions. Cheng, Q.; Tu, H.-F.; Zheng, C.; Qu, J.-P.;
Helmchen, G.; You, S.-L. Chem. Rev. 2019, 119, 1855-1969.
(3) For representative examples by Ir on the racemic aryl-substituted
allylic substrates, see: (a) Roggen, M.; Carreira, E. M. Enantioselective
Allylic Etherification: Selective Coupling of Two Unactivated
Alcohols. Angew. Chem. Int. Ed. 2011, 50, 5568-5571. (b) Lafrance,
M.; Roggen, M.; Carreira, E. M.; Direct, Enantioselective Iridium-
Catalyzed Allylic Amination of Racemic Allylic Alcohols. Angew.
Chem. Int. Ed. 2012, 51, 3470-3473. (c) Krautwald, S. ; Sarlah, D.;
Schafroth, M. A.; Carreira, E. M. Enantio- and Diastereodivergent Dual
Catalysis: α-Allylation of Branched Aldehydes. Science 2013, 340,
1065-1068. (d) Rössler, S. L.; Krautwald, S.; Carreira, E. M. Study of
5 mol%
Co(CH3CN)2(BF4)2-
L8
OCO2Me
NHPh
10 mol% Zn
+
PhNH2
n-C3H7
n-C3H7
3aa
CH3CN, rt, 16 h
2a
1a
98% yield, 99% ee
L4
5 mol% CoI-
10 mol% Zn(BF4)2
3aa
84% yield, 99% ee
CH3CN, rt, 16 h
L6
10 mol%
10 mol% Zn(BF4)2
3aa
no
was detected
CH3CN, rt, 16 h
To gain mechanistic insight of the Co-catalyzed asymmetric
allylic amination, the complex of Co(CH3CN)2(BF4)2-L8 was
synthesized by mixing L8 with Co(BF4)2 in acetonitrile (Scheme 6).
In the solid state, the complex adopts a distorted square pyramidal
geometry, with all of the three NPN atoms in ligand coordinated to
cobalt center. However, the complex of Co(CH3CN)2(BF4)2-L8 is
not able to catalyze the reaction. Upon reduction by 10 mol% Zn,
full conversion of aniline 2a was observed. These results indicated
that a low oxidative state Co is the active species.14 To demonstrate
whether the Co(I) is real active species, a complex of Co(I)-L4 was
synthesized. The complex of CoI-L4 adopts a distorted tetrahedral
geometry, and again the three NPN atoms in L4 coordinate with
cobalt center.15 Although CoI-L4 itself is not active for the reaction,
after the addition of 10 mol% Zn(BF4)2, the reaction proceeded
smoothly to afford 3aa in 84% yield with 99% ee. Control
experiment with 10 mol% Zn(BF4)2 and L6 excludes the possibility
of zinc-catalyzed allylation reaction. These results implied that a
cationic Co(I)/NPN complex is likely the active catalytic species in
this allylic amination reaction, and Zn(II) species may works as
Lewis acid to active allylic carbonate (see SI).
Intermediates
in
Iridium-(Phosphoramidite,Olefin)-Catalyzed
Enantioselective Allylic Substitution. J. Am. Chem. Soc. 2017, 139,
3603-3606.
(4) for the recent successful examples of racemic alkyl allylic substrates
by Ir, see: (a) Meza, A. T.; Wurm, T.; Smith, L.; Kim, S. W.; Zbieg, J.
R.; Stivala, C. E.; Krische, M. J. Amphiphilic π-Allyliridium
C,OBenzoates Enable Regio- and Enantioselective Amination of
Branched Allylic Acetates Bearing Linear Alkyl Groups. J. Am. Chem.
Soc. 2018, 140, 1275-1279. (b) Kim, S. W.; Schwartz, L. A.; Zbieg, J.
R.; Stivala, C. E.; Krische, M. J. Regio- and Enantioselective Iridium-
Catalyzed Amination of Racemic Branched Alkyl-Substituted Allylic
Acetates with Primary and Secondary Aromatic and Heteroaromatic
Amines. J. Am. Chem. Soc. 2019, 141, 671-676. (c) Kim, S. W.;
Schempp, T. T.; Zbieg, J. R.; Stivala, C. E.; Krische, M. J. Regio- and
Enantioselective Iridium-Catalyzed N-Allylation of Indoles and
Related Azoles with Racemic Branched Alkyl-Substituted Allylic
Acetates. Angew. Chem. Int. Ed. 2019, 58, 7792-7766.
(5) For a review on rhodium-catalyzed asymmetric allylations, see: (a)
Turnbull, B. W. H.; Evans, P. A. Asymmetric Rhodium-Catalyzed
Allylic Substitution Reactions: Discovery, Development and
Applications to Target-Directed Synthesis. J. Org. Chem. 2018, 83,
11463-11479. For examples, see: (b) Arnold, J. S.; Nguyen, H. M.
Rhodium-Catalyzed Dynamic Kinetic Asymmetric Transformations of
In
conclusion,
we
have
developed
a
cobalt/bisoxazolinephosphine catalyst system for the exclusively
branch-selective allylic substitutions. Chiral allylic amines were
prepared in excellent enantioselectivities (normally 99% ee) from
readily accessible racemic allylic carbonates bearing aliphatic
groups under mild reaction conditions. Bisoxazolinephosphine was
found to be unique in this transformation. Investigations on
reaction intermediate isolation, nucleophiles scope and more
challenging chiral quaternary carbon construction with this catalyst
system are on-going in our group.
ASSOCIATED CONTENT
Supporting Information. Detailed experimental procedures,
characterization data, copies of 1H, 13C NMR spectra, HPLC
spectra and X-ray crystal structure of Co(CH3CN)2(BF4)2-L8, CoI-
L4 and compound 3ag. This material is available free of charge via
the Internet at http://pubs.acs.org.
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Racemic Tertiary Allylic Trichloroacetimidates with Anilines. J. Am.
(b) Shu, C.; Leitner, A.; Hartwig, J. F. Enantioselective Allylation of
Aromatic Amines After in-situ Generation of an Activated
Cyclometalated Iridium Catalyst. Angew. Chem. Int. Ed. 2004, 43,
4797-4800. (c) Cooke, M. L.; Xu, K.; Breit, B. Enantioselective
Rhodium-Catalyzed Synthesis of Branched Allylic Amines by
Intermolecular Hydroamination of Terminal Allenes. Angew. Chem.
Int. Ed. 2012, 51, 10876-10879. (d) Xu, K.; Gilles, T.; Breit, B.
Asymmetric synthesis of N-allylic indoles via regio- and
enantioselective allylation of aryl hydrazines. Nat. Commun., 2015, 6,
7616. (e) Chen, Q.-A.; Chen, Z.; Dong, V. M. Rhodium-Catalyzed
Enantioselective Hydroamination of Alkynes with Indolines. J. Am.
Chem. Soc. 2015, 137, 8392-8395. (f) Guo, W.; Cai, A.; Xie, J.; Kleij,
A. W. Asymmetric Synthesis of α,α-Disubstituted Allylic Amines
through Palladium-Catalyzed Allylic Substitution. Angew. Chem. Int.
Ed. 2017, 56, 11797-11801.
(11) For selected reviews, see: (a) Chakraborty, S.; Bhattacharya, P.;
Dai, H.; Guan, H. Nickel and Iron Pincer Complexes as Catalysts for
the Reduction of Carbonyl Compounds. Acc. Chem. Res. 2015, 48,
1995-2003. (b) Wei, D.; Darcel, C. Iron Catalysis in Reduction and
Hydrometalation Reactions. Chem. Rev. 2019, 119, 2550-2610. (b)
Alig, L.; Fritz, M.; Schneider, S. First-Row Transition Metal (De)
Hydrogenation Catalysis Based On Functional Pincer Ligands. Chem.
Rev. 2019, 119, 2681-2751.
Chem. Soc. 2012, 134, 8380-8383. (c) Arnold, J. S.; Cizio, G. T.; Heitz,
D. R.; Nguyen, H. M. Rhodium-catalyzed regio- and enantioselective
amination of racemic secondary allylic trichloroacetimidates with N-
methyl anilines. Chem. Commun. 2012, 48, 11531-11533. (d) Arnold,
J. S.; Mwenda, E. T.; Nguyen, H. M. Rhodium-Catalyzed Sequential
Allylic Amination and Olefin Hydroacylation Reactions:
Enantioselective Synthesis of SevenMembered Nitrogen Heterocycles.
Angew. Chem. Int. Ed. 2014, 53, 3688-3692. (e) Zhang, Q.; Stockdale,
D. P.; Mixdorf, J. C.; Topczewski, J. J.; Nguyen, H. M. Iridium-
Catalyzed Enantioselective Fluorination of Racemic, Secondary
Allylic Trichloroacetimidates. J. Am. Chem. Soc. 2015, 137, 11912-
11915. (f) Li, C.; Breit, B. Rhodium-Catalyzed Dynamic Kinetic
Asymmetric Allylation of Phenols and 2-Hydroxypyridines. Chem. Eur.
J. 2016, 22, 14655–14663. (g) Liang, L.; Xie, M.-S.; Qin, T.; Zhu, M.;
Qu, G.-R.; Guo, H.-M. Regio- and Enantioselective Synthesis of Chiral
Pyrimidine Acyclic Nucleosides via Rhodium-Catalyzed Asymmetric
Allylation of Pyrimidines. Org. Lett. 2017, 19, 5212-5215. (h) Zhou,
Y.; Breit, B. Rhodium-Catalyzed Asymmetric N-H Functionalization
of Quinazolinoneswith Allenes and Allylic Carbonates: The First
Enantioselective Formal Total Synthesis of (-)-Chaetominine. Chem.
Eur. J. 2017, 23, 18156–18160. (i) Tang, S.-B.; Zhang, X.; Tu, H.-F.;
You, S.-L. Regio- and Enantioselective Rhodium-Catalyzed Allylic
Alkylation of Racemic Allylic Alcohols with 1,3-Diketones. J. Am.
Chem. Soc. 2018, 140, 7737-7742.
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60
(12) To the best of our knowledge, only two reactions with chiral NPN
ligands have been reported. Bisoxazolinephosphine was first
synthesized
(6) Anastas, P.; Eghbali, N. Green Chemistry: Principles and Practice.
Chem. Soc. Rev. 2010, 39, 301-312.
by Zhang, see: (a) Jiang, Y.; Jiang, Q.; Zhu, G.; Zhang, X. Highly
(7) For a review, see: (a) Begouin, J.-M.; Klein, J. E.M.N.; Weickmann,
D.; Plietker, B. Allylic Substitutions Catalyzed by Miscellaneous
Metals. Top. Organomet. Chem. 2012, 38, 269-320. For selected
examples of Co-catalyzed non-branch-selective allylations: see: (b)
Bhatia, B.; Reddy, M. M.; Iqbal, J. Cobalt (II) Catalysed Allylation of
1,3-Dicarbonyl Compounds with Allyl Acetates. Tetrahedron Lett.
1993, 34, 6301-6304. (c) Reddy, C. K.; Knochel, P. New Cobalt- and
Iron-Catalyzed Reactions of Organozinc compound. Angew. Chem. Int.
Ed. 1996, 35, 1700-1701. (d) Qian, X.; Auffrant, A.; Felouat, A.;
Gosmini, C. Cobalt-Catalyzed Reductive Allylation of Alkyl Halides
with Allylic Acetates or Carbonates. Angew. Chem. Int. Ed. 2011, 50,
10402-10405.
(8) Sun, M.; Chen, J.-F.; Chen, S.; Li, C. Construction of Vicinal
Quaternary Carbon Centers via Cobalt-Catalyzed Asymmetric Reverse
Prenylation. Org. Lett. 2019, 21, 1278-1282.
(9) Takizawa, K.; Sekino, T.; Sato, S.; Yoshino, T.; Kojima, M.;
Matsunaga, S. Cobalt Catalyzed Allylic Alkylation Enabled by
Organophotoredox Catalysis. Angew. Chem. Int. Ed. 2019, 58, 9919-
9203.
E
f
f
e
-
tive NPN type Tridentate Ligands for Asymmetric Transfer Hydrogen
tion of Ketones. Tetrahydron Lett. 1997, 38, 215-218. For a report in
which bisoxazolinephosphine acts as bidentate ligand, see: (b) Yama-
ishi, T.; Ohnuki, M.; Kiyooka, T.; Masui, D.; Sato, K.; Yamaguchi,
M
.
Construction of P-stereogenic Center by Selective Ligation of N-P-N
type Ligands and Application to Asymmetric Allylic Substitution
Reac-
tions. Tetrahedron: Asymmetry 2003, 14, 3275-3279.
(13) P. A. Evans, Uraguchi, D. Regio- and Enantiospecific Rhodium-
Catalyzed Arylation of Unsymmetrical Fluorinated Acyclic Allylic
Carbonates: Inversion of Absolute Configuration. J. Am. Chem. Soc.
2003, 125, 7158-7159.
(14) For a discussion about Co(0) or Co(I), see; Friedfeld, M. R.;
Zhong, H.; Ruck, R. T.; Shevlin, M.; Chirik, P. J. Cobalt-Catalyzed
Asymmetric Hydrogenation of Enamides Enabled by Single-Electron
Reduction. Science 2018, 360, 888-893.
(15) For an achiral bispyridylphosphine/CuI complex, see: Zeng, C.;
Wang, N.; Peng, T.; Wang, S. Copper(I) Complexes Bearing 1,2-
Phenyl-Bridged P ∧N, P ∧N ∧P, and N ∧P ∧N Chelate Ligands:
Structures and Phosphorescence. Inorg. Chem. 2017, 56, 1616-1625.
(10) For selected examples of asymmetric allylic aminations, see: (a)
Ohmura, T.; Hartwig, J. F. Regio- and Enantioselective Allylic
Amination of Achiral Allylic Esters Catalyzed by an Iridium-
Phosphoramidite Complex. J. Am. Chem. Soc. 2002, 124, 15164-15165.
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Page 6 of 6
1
2
3
4
5
5 mol% Co(BF4)2
R'
P
R2
R1
R3
L
*
6 mol%
OCO2R
R2
R3
N
10 mol% Zn
+
N
R1
racemic
R1 = alkyl, Ar R2 = Ar, Alkyl
R3 = alkyl, H
H
O
N
N
O
CH3CN
with/without LA
exclusive branched
normally 99% ee
L*
Bisoxazolinephosphine
R'' R''
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