Iridium/ N-Heterocyclic Carbene Complex-Catalyzed Intermolecular Allylic Alkylation Reaction

Article abstract of DOI:10.1021/acs.organomet.8b00762

N-Heterocyclic carbenes (NHCs) were found to be suitable ligands in Ir-catalyzed intermolecular allylic alkylation reaction. In the presence of a catalyst derived from [Ir(dncot)Cl]₂ (dncot = dinaphthocyclooctatetraene) and triazolium salt L7,

Full text of DOI:10.1021/acs.organomet.8b00762

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Iridium/N‑Heterocyclic Carbene Complex-Catalyzed Intermolecular
Allylic Alkylation Reaction
Can-Can Bao,†,‡,# Dong-Song Zheng,†,# Xiao Zhang,*,† and Shu-Li You*,†,‡
†State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic
Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China
‡School of Physical Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China
S
* Supporting Information
ABSTRACT: N-Heterocyclic carbenes (NHCs) were found
to be suitable ligands in Ir-catalyzed intermolecular allylic
alkylation reaction. In the presence of a catalyst derived from
[Ir(dncot)Cl]2 (dncot = dinaphthocyclooctatetraene) and
triazolium salt L7, the alkylation products from the reaction of
aryl allyl carbonates with sodium dialkyl malonates could be
obtained in 85−99% yields favoring the formation of
branched products (90/10 → >99/1 b/l). In addition, chiral
dihydroisoquinoline-type NHC (DHIQ-NHC) (L8) is successfully applied in Ir-catalyzed asymmetric allylic alkylation
reactions. Excellent enantioselectivities and moderate regioselectivities were obtained for a wide range of substrates.
of copper catalysis.10 Recently, NHCs were found to be efficient
INTRODUCTION
■
ligands in Ir-catalyzed asymmetric allylic substitution reactions.
In the presence of Ir-catalyst derived from the Enders NHC11a
or D-camphor derived ones,11b intramolecular allylic amination
reaction of indoles and pyrroles could be realized, providing
facile access to the corresponding indolopiperazinones and
piperazinones (Scheme 1a).12 Interestingly, we found that the
C(sp2)−H activation mode is also occurring with NHC ligands,
in which an active five-membered cyclometalated complex is
generated through C−H activation at the ortho-position of N-
Since the first report introduced by the group of Takeuchi,
iridium-catalyzed allylic substitution reactions have developed
into a reliable method to construct C−C (or C−X) bonds.1−3
The emergence of privileged phosphoramidite ligands, such as
Feringa4 and Alexakis5 (P/C) ligands and Carreira’s bidentate
(P/olefin) coordination ligand (Figure 1),6 has contributed
Scheme 1. Ir/NHC-Catalyzed Allylic Substitution Reactions
Figure 1. Selected ligands for Ir-catalyzed asymmetric allylic
substitution reactions.
significantly to this field and allows numerous transformations in
a highly regio- and enantioselective fashion. Meanwhile, our
group developed a series of N-aryl phosphoramidites, in which
the active species is formed through an Ir-mediated C−H bond
insertion of the phenyl group. Further studies led to the
observation that this C(sp2)−H activation mode renders the
active iridacycle complex less sterically hindering in its three-
dimensional structure, thus accommodating a wide range of
substrates including those which were found to be challenging in
previous studies.7 Although great advances have been made
within this domain, the development of new ligand types
remains an important and challenging task.
N-Heterocyclic carbenes (NHCs) have been well-established
as organocatalysts8 and chiral ligands9 in the past years.
However, their applications in transition-metal-catalyzed allylic
substitution reaction have been less explored, with the exception
Received: October 20, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.8b00762
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Organometallics
Article
aryl group of the ligand. With these promising preliminary
results in hand, we went on to explore the feasibility of Ir/NHC-
catalyzed intermolecular variants (Scheme 1b). Control of
regioselectivity in metal-catalyzed allylic substitutions employ-
ing NHC ligand remains a significant challenge. Accordingly,
our efforts were devoted to the racemic versions at the very
beginning, with the goal to achieve the reactions in a highly
branched-selective fashion. Herein, we report our results from
this study.
Finally, the optimal conditions were confirmed as follows: The
catalyst derived from [Ir(dncot)Cl]2 (2.5 mol %) and L7 (5.0
mol %) was prepared via Et3N activation, followed by the
addition of substrates and CH2Cl2 under reflux.
Substrate Scope. With the optimal conditions in hand, the
reaction scope was then explored. Various allylic substrates were
allowed to react with sodium dimethyl malonate (2a). The
reactions of allylic carbonates bearing an electron-donating
group (−Me, −OMe, and −iBu) on different positions of the
aromatic ring, including previously unfavorable ortho-substi-
tuted cinnamyl carbonates (1b and 1e),7b,f all gave good
regioselectivity and yields (3/4 = 90/10 → 99/1, 90−99%
yields, entries 2−7, Table 2). Substrates bearing an electron-
withdrawing group, such as −Br or −CF3, at the para-position
on the phenyl ring (1h, 1i) were also compatible with this
protocol, leading to the desired products in 92/8 b/l, 99% yield,
and 90/10 b/l, 85% yield, respectively (entries 8−9, Table 2).
RESULTS AND DISCUSSION
■
Optimization of the Reaction Conditions. The initial
attempt was launched with the reaction between cinnamyl
carbonate (1a) and sodium dimethyl malonate (2a). With
[Ir(dncot)Cl]2 (dncot = dinaphthocyclooctatetraene)13 as the
iridium precursor and THF as the solvent, various NHCs
including those derived from imidazolium, benzothiazolium,
thiazolium, and triazolium salts were tested.14 It was found that
NHCs with different scaffolds have a profound effect on the
reaction outcome and that triazolium salt L7 gave the best
reactivity and promising regioselectivity (3aa/4aa = 94/6, 96%
yield, entry 7, Table 1). Switching the iridium precursor from
[Ir(dncot)Cl]2 to [Ir(cod)Cl]2 (cod = 1,5-cyclooctadiene) led
to a slight decrease in regioselectivity (3aa/4aa = 89/11, entry 8,
Table 1). Further investigation of the solvents such as toluene,
dioxane, CH3CN, and CH2Cl2 showed that CH2Cl2 is optimal in
terms of both yield and regioselectivity (entries 9−12, Table 1).
a
Table 2. Scope of the Allylic Substrates
yield
b
c
entry
1
1, R
t (h)
3/4
(3 + 4) (%)
1a, Ph
11 3aa/4aa,
98
96/4
2
1b, 2-MeC6H4
1c, 3-MeC6H4
12 3ba/4ba,
98
99
90
94
99
99
99
85
99
93
99
99
99
99
91
99
84
81
a
98/2
Table 1. Optimization of the Reaction Conditions
3
13 3ca/4ca,
95/5
4
1d, 4-MeC6H4
1e, 2-MeOC6H4
1f, 4-MeOC6H4
1g, 4-iBuC6H4
15 3da/4da,
96/4
5
15 3ea/4ea,
90/10
6
15 3fa/4fa, >
99/1
7
21 3ga/4ga,
99/1
8
1h, 4-BrC6H4
22 3ha/4ha,
92/8
9
1i, 4-CF3C6H4
1j, 2,4-(CH3)2C6H3
1k, 3,5-(CH3)2C6H3
1l, 3,4-(methylenedioxy)C6H3
1m, 3,4-(MeO)2C6H3
1n, 1-naphthyl
1o, 2-naphthyl
1p, 2-furanyl
15 3ia/4ia,
90/10
10
11
12
13
14
15
16
17
18
19
12 3ja/4ja, >
99/1
18 3ka/4ka,
b
c
entry
L
solvent
t (h) 3aa/4aa
yield (3aa + 4aa) (%)
96/4
17 3la/4la,
1
2
3
4
5
6
7
8
9
10
11
12
L1
L2
L3
L4
L5
L6
L7
L7
L7
L7
L7
L7
THF
THF
THF
THF
THF
THF
THF
THF
toluene
dioxane
CH3CN
CH2Cl2
11
12
11
16
11
11
12
12
14
14
14
11
59/41
57/43
84/16
72/28
40/60
52/48
94/6
89/11
91/9
92/8
10
57
26
63
4
5
100 (96)
97 (93)
100 (98)
100 (95)
100 (99)
100 (98)
95/5
14 3ma/4ma,
> 99/1
13 3na/4na,
96/4
16 3oa/4oa,
99/1
d
13 3pa/4pa,
94/6
1q, 2-thienyl
13 3qa/4qa,
98/2
94/6
96/4
1r, cyclohexyl
17 3ra/4ra,
e
18/82
1s, Et
13 3sa/4sa,
a
57/43
Reaction conditions: [Ir(dncot)Cl]2 (2.5 mol %), L (5.0 mol %), 1a
(0.4 mmol), and 2a (0.8 mmol) in solvent (2.0 mL) at 50 °C or
b
a
reflux. Catalyst was prepared via Et3N activation. Determined by 1H
Reaction conditions: [Ir(dncot)Cl]2 (2.5 mol %), L7 (5.0 mol %), 1
(0.4 mmol), and 2a (0.8 mmol) in CH2Cl2 (2.0 mL) under reflux.
c
NMR of the crude reaction mixture. 1H NMR yield with CH2Br2 as
b
1
an internal standard. Unless otherwise noted, the isolated yield was
Catalyst was prepared via Et3N activation. Determined by H NMR
of the crude reaction mixture. Isolated yield.
d
e
c
shown in parentheses. [Ir(cod)Cl]2 (2.5 mol %) was used. Reflux.
B
DOI: 10.1021/acs.organomet.8b00762
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Additionally, the reaction conditions display a good tolerance of
aromatic allylic carbonates bearing multi substituents [2,4-
(CH3)2C6H3−, 3,5-(CH3)2C6H3−, 3,4-(methylenedioxy)-
C6H3−, and 3,4-(MeO)2C6H3−] on the phenyl ring. In all
cases, good regioselectivity and yields were obtained (3/4 = 95/
5 → >99/1, 93−99% yields, entries 10−13, Table 2). Reactions
of naphthyl-, furanyl- and thienyl-substituted allylic carbonates
with sodium dimethyl malonate also proceeded smoothly,
resulting in the corresponding alkylation products in satisfying
results (3/4 = 94/6−99/1, 91−99% yields, entries 14−17,
Table 2). To our disappointment, only moderate regioselectivity
(3/4 = 18/82−57/43) was observed when aliphatic allylic
carbonates [cyclohexyl− (1r), Et− (1s)] were employed.
Moreover, various nucleophiles were investigated. In addition
to sodium dimethyl malonate, the corresponding sodium salt
derived from diethyl malonate (2b), diisopropyl malonate (2c),
β-ketoester (2d), and 1,3-diketone (2e) were also proved to be
suitable nucleophiles. Uniformly high levels of regioselectivity
and good yields were obtained (3/4 = 95/5−97/3, 95−99%
yields, entries 2−5, Table 3). Notably, the diastereoselectivity in
3ad was confirmed as about 1:1 when an additional stereocenter
was incorporated.
enantioselectivity (entry 5, Table 4). Amino-indanol-derived
triazolium salts L13−L15, camphor-derived triazolium salts
L16−L18, phenylalaninol-derived triazolium salt L19, trime-
thylalaninol-derived triazolium salt L20, and (1R,2R)-DPEN-
derived triazolium salt L21 (DPEN = 1,2-diphenylethylenedi-
amine) were subsequently tested, but none of them gave
improved results (entries 6−14, Table 4). Finally, Enders
triazolium salt L22 offered promising enantioselectivity albeit
with a low branched selectivity (95% ee, 3aa/4aa = 29/71, entry
15, Table 4). Other triazolium salts such as L23 and L24 also
gave satisfying results (entries 16 and 17, Table 4). However,
chiral imidazolium salts L25 and L26 afforded low asymmetric
induction (entries 18 and 19, Table 4). The utilization of other
16
iridium precursors including [Ir(cod)Cl]2 and [Ir(dbcot)Cl]2
(dbcot = dibenzocyclooctatetraene) led to poor results (entries
20 and 21, Table 4). Further investigations on solvents verified
that dichloromethane is the optimal solvent (3aa/4aa = 63/37,
90% yield, 95% ee, entry 24, Table 4).
Substrate Scope. Accordingly, our subsequent efforts were
devoted to the substrate scope for Ir/NHC-catalyzed asym-
metric allylic alkylation reactions. As shown in Table 5, the
cinnamyl derived carbonates containing an electron-donating
group at different positions of the phenyl ring (2-Me, 3-Me, 4-
Me, 2-MeO, 4-MeO, 4-iBu) gave excellent enantioselectivity for
the branched products (3aa−3ga, 91−98% ee, entries 1−7,
Table 5). Notably, these reactions typically proceeded with a
slight favoring of branched products (3/4 = 55/45−79/21)
except for ortho-methoxyl substituted substrate 1e (3ea/4ea =
34/66). When introducing an electron-withdrawing substituent
(4-Br, 4-CF3) on the phenyl ring of cinnamyl carbonates 1h and
1i, selectivity for the corresponding linear products was
observed (3/4 = 28/72−36/64). Moreover, the multisubsti-
tuted cinnamyl carbonates [(2,4-(CH3)2C6H3−, 3,5-
(CH3)2C6H3−, 3,4-(methylenedioxy)C6H3−, and 3,4-
(MeO)2C6H3−)] were also compatible with the reaction,
leading to the alkylated products in moderate to good
regioselectivity, excellent yields and enantioselectivity (3/4 =
59/41−84/16, 97−99% yields, 3ja-3ma: 95−98% ee, entries
10−13, Table 5). The allylic carbonates based on other aromatic
rings including 1-naphthyl-, 2-naphthyl-, 2-furanyl-, and 2-
thienyl proceeded smoothly under the optimized conditions. In
all cases, excellent enantioselectivity and moderate to good
regioselectivity were obtained for the branched products (3/4 =
58/42−91/9, 90−98% yields, 3na−3qa: 94−98% ee, entries
14−17, Table 5). In agreement with the previous racemic
reactions, the aliphatic allylic carbonates (1r and 1s)
predominantly formed linear products (3/4 = 21/79 to <1/99).
The asymmetric allylic alkylation reactions of diethyl
malonate (2b), diisopropyl malonate (2c), β-ketoester (2d),
and 1,3-diketone (2e) with cinnamyl carbonate 1a all gave the
desired products in reasonable to good regioselectivity, excellent
yields and ee values for the branched product (3/4 = 63/37−
74/26, 91−98% yields, 3ab−3ae: 95−98% ee, entries 2−5,
Table 6).
a
Table 3. Scope of the Nucleophiles
yield
(3 + 4) (%)
b
c
entry
2, NaNu
t (h)
3/4
1
2
3
2a, NaCH(CO2Me)2
2b, NaCH(CO2Et)2
2c, NaCH(CO2 Pr)2
2d, NaCH(COMe)
CO2Et
11 3aa/4aa, 96/4
18 3ab/4ab, 97/3
11 3ac/4ac, 97/3
10 3ad/4ad, 96/4
98
95
99
96
i
d
4
5
2e, NaCH(COMe)2
19 3ae/4ae, 95/5
99
a
Reaction conditions: [Ir(dncot)Cl]2 (2.5 mol %), L7 (5.0 mol %),
1a (0.4 mmol), and 2 (0.8 mmol) in CH2Cl2 (2.0 mL) under reflux.
b
1
Catalyst was prepared via Et3N activation. Determined by H NMR
c
d
of the crude reaction mixture. Isolated yield. The dr value for 3ad
1
was determined as 49/51 by H NMR.
IR/NHC-CATALYZED INTERMOLECULAR
ASYMMETRIC ALLYLIC ALKYLATION REACTION
■
Optimization of the Reaction Conditions. Next, we
switched our efforts to asymmetric Ir-catalyzed allylic alkylation
reactions with the introduction of chiral NHCs. The studies
commenced with the investigation of different chiral NHCs
derived from triazolium or imidazolium salts.15 As shown in
Table 4, the model reaction performed in the presence of
dihydroisoquinoline-type NHC (DHIQ-NHC) (L8) gave the
desired products with modest regioselectivity (3aa/4aa = 53/
47). Gratifyingly, the ee value for the branched product 3aa was
determined as 93% (entry 1, Table 4). Further examinations by
varying the aryl group on the triazolium core or deprotecting the
hydroxyl group in DHIQ-NHCs were conducted, merely
leading to a decreased regioselectivity or enantioselectivity for
3aa (entries 2−4, Table 4). It is worth noting that the reaction
gave poor yield without any asymmetric induction when L12
was used, further demonstrating NHC/C(sp2)−H bidentate
coordination mode is responsible for both reactivity and
Mechanistic Studies. [Ir(dncot)Cl]2 was subjected to L8 in
the presence of Et3N, which resulted in the formation of
iridium(I)-NHC complex Ir1, an air- and moisture-stable solid,
in 98% yield (Scheme 2a). Notably, the structure of its analog
Ir2, which was generated from [Ir(cod)Cl]2 and L8, has been
confirmed by X-ray crystallographic analyses.17 With complex
Ir1 as the catalyst, the model reaction proceeded smoothly with
the assistance of Et3N to afford the desired products in
comparable yield and selectivity to those obtained when using
C
DOI: 10.1021/acs.organomet.8b00762
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Article
a
Table 4. Optimization of the Reaction Conditions
b
c
d
entry
L
solvent
t (h)
3aa/4aa
yield (3aa + 4aa) (%)
ee (3aa) (%)
1
2
3
4
5
6
7
8
L8
L9
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
15
60
60
17
17
17
10
24
10
10
40
19
11.5
10
14
16
16
60
38
18
16
60
57
19
34.5
33
39
34
58
53/47
23/77
49/51
53/47
47
72
11
86
4
93
83
12
88
0
17
16
10
35
58
0
L10
L11
L12
L13
L14
L15
L16
L17
L18
L19
L20
L21
L22
L23
L24
L25
L26
L8
L8
L8
L8
L8
L8
L8
L8
L8
59/41
66/34
39/61
42/58
36/64
40/60
68/32
59/41
79/21
29/71
43/57
53/47
39/61
64/36
43/57
34/66
32/68
54/46
63/37
26/74
45/55
25/75
39/61
16/84
62
71
52
79
58
24
99
93
65
63
67
43
53
59
48
43
87
69
90
75
30
38
94
22
9
10
11
12
13
14
15
16
17
18
19
2
63
51
95
95
85
0
4
e
20
21
22
23
13
47
87
94
95
85
90
79
88
62
f
1,4-dioxane
Et2O
CH2Cl2
ClCH2CH2Cl
1,2-dichlorobenzene
toluene
g
g
24
25
26
27
28
29
MeCN
EtOAc
L8
a
Reaction conditions: [Ir(dncot)Cl]2 (2.5 mol %), L8 (5.0 mol %), 1a (0.4 mmol), and 2a (0.8 mmol) in solvent (2.0 mL) at 50 °C or reflux.
b
c
d
Catalyst was prepared via Et3N activation. Determined by 1H NMR of the crude reaction mixture. Isolated yield. Determined by HPLC analysis.
e
f
g
[Ir(cod)Cl]2 (2.5 mol %) was used. [Ir(dbcot)Cl]2 (2.5 mol %) was used. Reflux.
the in situ prepared catalyst. These results are consistent with our
previous studies (Scheme 2b).12a,b On the basis of these
observations, we proposed that the catalytically active iridium
complex might also involve C(sp2)−H activation of the N-aryl
group of the ligand.
CONCLUSION
■
In conclusion, we have developed an iridium/NHC complex-
catalyzed intermolecular allylic alkylation reaction. With [Ir-
(dncot)Cl]2 as the iridium precursor and triazolium salt L7 as
the NHC precursor, the alkylation reactions between aryl allyl
D
DOI: 10.1021/acs.organomet.8b00762
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Article
a
Table 5. Scope of the Allylic Substrates in Asymmetric Reaction
b
c
d
entry
1, R
t (h)
3/4
yield (3 + 4) (%)
ee (3) (%)
1
2
3
4
5
6
7
8
1a, Ph
19
12
13
35
15
16
43
21.5
39
12
42
17
13
47
15
47
47
41
68
3aa/4aa, 63/37
3ba/4ba, 55/45
3ca/4ca, 59/41
3da/4da, 67/33
3ea/4ea, 34/66
3fa/4fa, 79/21
3ga/4ga, 74/26
3ha/4ha, 36/64
3ia/4ia, 28/72
3ja/4ja, 84/16
3ka/4ka, 59/41
3la/4la, 66/34
3ma/4ma, 82/18
3na/4na, 85/15
3oa/4oa, 58/42
3pa/4pa, 74/26
3qa/4qa, 91/9
3ra/4ra, < 1/99
3sa/4sa, 21/79
90
93
99
94
98
93
91
94
95
99
99
97
98
97
95
90
98
94
49
95
97
98
98
96
97
91
95
84
98
95
96
97
97
94
98
96
1b, 2-MeC6H4
1c, 3-MeC6H4
1d, 4-MeC6H4
1e, 2-MeOC6H4
1f, 4-MeOC6H4
1g, 4-iBuC6H4
1h, 4-BrC6H4
9
1i, 4-CF3C6H4
1j, 2,4-(CH3)2C6H3
1k, 3,5-(CH3)2C6H3
1l, 3,4-(methylenedioxy)C6H3
1m, 3,4-(MeO)2C6H3
1n, 1-naphthyl
1o, 2-naphtyl
1p, 2-furanyl
1q, 2-thienyl
1r, cyclohexyl
1s, Et
10
11
12
13
14
15
16
17
18
19
a
Reaction conditions: [Ir(dncot)Cl]2 (2.5 mol %), L8 (5.0 mol %), 1 (0.4 mmol), and 2a (0.8 mmol) in CH2Cl2 (2.0 mL) under reflux. Catalyst
b
c
d
1
was prepared via Et3N activation. Determined by H NMR of the crude reaction mixture. Isolated yield. Determined by HPLC analysis.
a
Table 6. Scope of the Nucleophiles in Asymmetric Reaction
Scheme 2. (a) Synthesis of Iridium/NHC Complexes and (b)
Ir1-Catalyzed Asymmetric Allylic Alkylation Reaction
yield
ee (3)
d
b
c
entry
1
2, NaNu
t (h)
3/4
(3 + 4) (%)
(%)
2a,
NaCH(CO2Me)2
19 3aa/4aa,
90
92
96
98
91
95
63/37
2
3
2b, NaCH(CO2Et)2 19 3ab/4ab,
98
63/37
2c, NaCH(COiPr)2
19 3ac/4ac,
97
74/26
e
4
2d, NaCH(COMe)
CO2Et
62 3ad/4ad,
96, 96
95
72/28
5
2e, NaCH(COMe)2 21 3ae/4ae,
65/35
a
Reaction conditions: [Ir(dncot)Cl]2 (2.5 mol %), L8 (5.0 mol %),
1a (0.4 mmol), and 2 (0.8 mmol) in CH2Cl2 (2.0 mL) under reflux.
EXPERIMENTAL SECTION
■
b
1
Catalyst was prepared via Et3N activation. Determined by H NMR
General Methods. Unless stated otherwise, all reactions were
carried out in flame-dried glassware under a dry argon atmosphere. All
solvents were purified and dried according to standard methods prior to
use.
c
d
of the crude reaction mixture. Isolated yield. Determined by HPLC
e
analysis. The dr value for 3ad was determined as 49/51 by 1H NMR.
1H and 13C NMR spectra were recorded on an Agilent instrument
(400 and 100 MHz, respectively) or an Agilent instrument (600 and
150 MHz, respectively) and internally referenced to tetramethylsilane
signal or residual protio solvent signals. 19F NMR spectra were recorded
on an Agilent instrument (376 MHz) and referenced relative to CFCl3.
carbonates and sodium dialkyl malonates could be achieved in
high yields and excellent branched selectivity. Meanwhile, the
employment of dihydroisoquinoline-type chiral triazolium
NHC (DHIQ-NHC) (L8) could enable the corresponding
asymmetric reactions with excellent enantioselectivity and
moderate regioselectivity. Future studies will focus on the
development of NHCs with other novel scaffolds and their
applications in diverse asymmetric allylic substitution reactions.
1
Data for H NMR are recorded as follows: chemical shift (δ, ppm),
multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet or
unresolved, br = broad singlet, coupling constant(s) in Hz, integration).
Data for 13C NMR are reported in terms of chemical shift (δ, ppm).
General Procedure for Ir/L7(L8)-Catalyzed Allylic Alkylation
Reaction. A flame-dried 10 mL tube was cooled to room temperature
and charged with NaH (19.2 mg, 0.8 mmol, 2.0 equiv, without oil). The
E
DOI: 10.1021/acs.organomet.8b00762
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
tube was evacuated and backfilled with argon. To the flask were added
freshly distilled CH2Cl2 (1.0 mL) and malonate (0.8 mmol, 2.0 equiv),
and the resultant solution was stirred for 1 min to afford nucleophile 2.
A flame-dried 10 mL tube was cooled to room temperature and
charged with [Ir(dncot)Cl]2 (10.6 mg, 0.01 mmol, 2.5 mol %) and
NHC precursor L7 (5.5 mg, 0.02 mmol, 5 mol %) [or L8 (11.8 mg, 0.02
mmol, 5 mol %)]. The tube was evacuated and backfilled with argon. To
the flask were added freshly distilled THF (0.5 mL) and triethylamine
(80 μL), and the resultant solution was stirred for 30 min at 50 °C.
Then, the solvent was removed under reduced pressure to afford a
yellow solid. The freshly distilled CH2Cl2 (1.0 mL), allylic substrate 1
(0.4 mmol, 1.0 equiv), and the above prepared nucleophile 2 in 1.0 mL
CH2Cl2 were added. The resultant solution was stirred under reflux.
After the reaction was complete (monitored by TLC), the crude
reaction mixture was filtered through Celite and the filtrate was
concentrated by rotary evaporation. The ratio of 3/4 was determined
by 1H NMR of the crude reaction mixture. Then the combined crude
product was purified by silica gel column chromatography (PE/EtOAc
= 30/1−5/1) to afford desired product 3.
3ja. Pale yellow oil, 129.4 mg, 99% yield, 3ja/4ja > 99/1. 1H NMR
(400 MHz, CDCl3) δ 7.02−6.96 (m, 3H), 5.83 (ddd, J = 18.0, 10.0, 8.0
Hz, 1H), 5.07−5.00 (m. 2H), 4.34 (dd, J = 11.2, 8.0 Hz, 1H), 3.95 (d, J
= 11.2 Hz, 1H), 3.75 (s, 3H), 3.50 (s, 3H), 2.38 (s, 3H), 2.26 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 168.6, 167.9, 137.8, 136.3, 135.1,
131.6, 127.0, 126.0, 116.3, 56.9, 52.6, 52.5, 44.8, 21.0, 19.6. IR (thin
film): νmax (cm−1) = 3006, 2953, 2923, 1736, 1637, 1503, 14234, 1311,
1259, 1193, 1143, 1026, 990, 921, 813, 733, 662, 598, 559, 461. HRMS-
ESI calcd for C16H24NO4 [M + NH4]+: 294.1700. Found: 294.1699.
3ka. Pale yellow oil, 138.1 mg, 93% yield, 3ka/4ka = 96/4. 1H NMR
(400 MHz, CDCl3) δ 6.85−6.83 (m, 3H), 5.97 (ddd, J = 18.4, 12.0, 8.0
Hz, 1H), 5.14−5.04 (m, 2H), 4.02 (dd, J = 10.8, 8.4 Hz, 1H), 3.85 (d, J
= 10.8 Hz, 1H), 3.73 (s, 3H), 3.52 (s, 3H), 2.28 (s, 6H). 13C NMR (100
MHz, CDCl3) δ 168.5, 168.0, 140.0, 138.2, 138.1, 128.9, 125.7, 116.5,
57.4, 52.7, 52.5, 49.8, 21.4. IR (thin film): νmax (cm−1) = 3011, 2953,
2919, 1739, 1603, 1437, 1252, 1150, 1027, 992, 921, 849, 805, 705, 653.
HRMS-ESI calcd for C16H24NO4 [M + NH4]+: 294.1700. Found:
294.1698.
3la.22 Pale yellow oil, 115.2 mg, 99% yield, 3la/4la = 95/5. 1H NMR
(400 MHz, CDCl3) δ 6.74−6.67 (m, 3H), 5.98−5.90 (m, 3H), 5.13−
5.06 (m, 2H), 4.06−4.01 (m, 1H), 3.79 (d, J = 10.8 Hz, 1H), 3.74 (s,
3H), 3.55 (s, 3H).
3aa.18 Pale yellow oil, 109.4 mg, 98% yield, 3aa/4aa = 96/4. H
1
NMR (400 MHz, CDCl3) δ 7.31−7.28 (m, 2H), 7.23−7.21 (m, 3H),
5.99 (ddd, J = 18.0, 10.0, 8.8 Hz, 1H), 5.14−5.07 (m, 2H), 4.11 (dd, J =
10.8, 8.0 Hz, 1H), 3.87 (d, J = 10.8 Hz, 1H), 3.74 (s, 3H), 3.48 (s, 3H).
1
3ma. Pale yellow oil, 122.1 mg, 99% yield, 3ma/4ma > 99/1. H
3ba.7b Pale yellow oil, 122.1 mg, 98% yield, 3ba/4ba = 98/2. H
1
NMR (400 MHz, CDCl3) δ 6.81−6.74 (m, 3H), 5.98 (ddd, J = 17.2,
10.4, 8.8 Hz, 1H), 5.14−5.07 (m, 2H), 4.08−4.03 (m, 1H), 3.86 (s,
3H), 3.85−3.82 (m, 4H), 3.74 (s, 3H), 3.52 (s, 3H). 13C NMR (100
MHz, CDCl3) δ 168.2, 167.9, 148.8, 148.0, 137.9, 132.3, 119.8, 116.4,
111.2, 57.5, 55.84, 55.80, 52.6, 52.5, 49.3. IR (thin film): νmax (cm−1) =
3001, 2954, 2837, 1757, 1735, 1591, 1515, 1462, 1435, 1236, 1193,
1142, 1026, 923, 856, 809, 763, 673, 622. HRMS-ESI calcd for
C16H24NO6 [M + NH4]+: 326.1598. Found: 326.1596.
NMR (400 MHz, CDCl3) δ 7.18−7.09 (m, 4H), 5.89−5.81 (m, 1H),
5.08−5.03 (m, 2H), 4.39 (dd, J = 11.6, 8.4 Hz, 1H), 3.97 (d, J = 11.6 Hz,
1H), 3.76 (s, 3H), 3.48 (s, 3H), 2.42 (s, 3H).
3ca. Pale yellow oil, 104.2 mg, 99% yield, 3ca/4ca = 95/5. 1H NMR
(400 MHz, CDCl3) δ 7.20−7.16 (m, 1H), 7.03−7.01 (m, 3H), 6.02−
5.93 (m, 1H), 5.14−5.06 (m, 2H), 4.06 (dd, J = 12.0, 9.2 Hz, 1H), 3.86
(d, J = 10.8 Hz, 1H), 3.74 (s, 3H), 3.51 (s, 3H), 2.32 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 168.4, 167.9, 139.9, 138.3, 138.0, 128.7, 128.6,
128.0, 124.8, 116.6, 57.4, 52.7, 52.5, 49.8, 21.5. IR (thin film): νmax
(cm−1) = 3010, 2953, 2845, 1735, 1639, 1606, 1489, 1434, 1309, 1258,
1192, 1145, 1067, 1026, 994, 923, 785, 706, 673, 443. HRMS-ESI calcd
for C15H22NO4 [M + NH4]+: 280.1543. Found: 280.1545.
3na.18 Pale yellow oil, 118.7 mg, 99% yield, 3na/4na = 96/4. H
1
NMR (400 MHz, CDCl3) δ 8.24 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 8.0 Hz,
1H), 7.74 (d, J = 8.0 Hz, 1H), 7.58−7.54 (m, 1H), 7.51−7.47 (m, 1H),
7.45−7.41 (m, 1H), 7.38 (d, J = 7.2 Hz, 1H), 6.08 (ddd, J = 17.2, 10.0,
8.0 Hz, 1H), 5.19−5.09 (m, 2H), 5.03 (dd, J = 10.8, 8.0 Hz, 1H), 4.16
(d, J = 10.8 Hz, 1H), 3.78 (s, 3H), 3.39 (s, 3H).
3da.18 Pale yellow oil, 94.7 mg, 90% yield, 3da/4da = 96/4. H
1
3oa.19 Pale yellow oil, 117.9 mg, 99% yield, 3oa/4oa = 99/1. H
1
NMR (400 MHz, CDCl3) δ 7.11−7.10 (m, 4H), 6.02−5.93 (m, 1H),
5.13−5.05 (m, 2H), 4.10−4.05 (m, 1H), 3.85 (d, J = 11.2 Hz, 1H), 3.74
(s, 3H), 3.51 (s, 3H), 2.30 (s, 3H).
NMR (400 MHz, CDCl3) δ 7.81−7.78 (m, 3H), 7.69 (s, 1H), 7.48−
7.42 (m, 2H), 7.37 (d, J = 8.4 Hz, 1H), 6.12−6.03 (m, 1H), 5.19−5.11
(m, 2H), 4.29 (dd, J = 12.0, 9.6 Hz, 1H), 4.00 (d, J = 11.2 Hz, 1H), 3.77
(s, 3H), 3.45 (s, 3H).
3ea.19 Pale yellow oil, 126.0 mg, 94% yield, 3ea/4ea = 90/10. H
1
NMR (400 MHz, CDCl3) δ 7.22−7.15 (m, 2H), 6.90−6.84 (m, 2H),
6.18−6.09 (m, 1H), 5.14−5.03 (m, 2H), 4.34 (dd, J = 9.6, 9.2 Hz, 1H),
4.19 (d, J = 10.8 Hz, 1H), 3.85 (s, 3H), 3.72 (s, 3H), 3.49 (s, 3H).
3fa.18 Pale yellow oil, 106.3 mg, 99% yield, 3fa/4fa > 99/1. 1H NMR
(400 MHz, CDCl3) δ 7.14 (d, J = 8.4 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H),
5.98 (ddd, J = 18.4, 10.4, 8.0 Hz, 1H), 5.12−5.05 (m, 2H), 4.06 (dd, J =
11.2, 10.0 Hz, 1H), 3.82 (d, J = 11.2 Hz, 1H), 3.77 (s, 3H), 3.73 (s, 3H),
3.50 (s, 3H).
3pa.19 Pale yellow oil, 104.2 mg, 91% yield, 3pa/4pa = 94/6. H
1
NMR (400 MHz, CDCl3) δ 7.33−7.32 (m, 1H), 6.28−6.27 (m, 1H),
6.11−6.10 (m, 1H), 6.01−5.92 (m, 1H), 5.21−5.15 (m, 2H), 4.22 (dd,
J = 9.2, 8.8 Hz, 1H), 3.88 (d, J = 10.0 Hz, 1H), 3.72 (s, 3H), 3.64 (s,
3H).
3qa.18 Pale yellow oil, 147.5 mg, 99% yield, 3qa/4qa = 98/2. H
1
NMR (400 MHz, CDCl3) δ 7.18 (d, J = 5.2 Hz, 1H), 6.93−6.91 (m,
1H), 6.88−6.87 (m, 1H), 6.06−5.97 (m, 1H), 5.21−5.12 (m, 2H), 4.41
(dd, J = 9.6, 9.2 Hz, 1H), 3.84 (d, J = 10.0 Hz, 1H), 3.73 (s, 3H), 3.61 (s,
3H).
3ga. Pale yellow oil, 119.1 mg, 99% yield, 3ga/4ga = 99/1. 1H NMR
(400 MHz, CDCl3) δ 7.12 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 8.4 Hz, 2H),
5.99 (ddd, J = 18.0, 9.6, 7.6 Hz, 1H), 5.14−5.06 (m, 2H), 4.10−4.05
(m, 1H), 3.84 (d, J = 10.8 Hz, 1H), 3.74 (s, 3H), 3.47 (s, 3H), 2.42 (d, J
= 7.2 Hz, 2H), 1.87−1.77 (m, 1H), 0.87 (d, J = 6.4 Hz, 6H). 13C NMR
(100 MHz, CDCl3) δ 168.3, 168.0, 140.6, 138.0, 137.09, 137.07, 129.4,
127.7, 116.4, 57.5, 52.6, 52.4, 49.53, 49.46, 45.1, 30.2, 22.4. IR (thin
film): νmax (cm−1) = 3008, 2954, 2956, 2869, 2846, 2365, 1759, 1737,
1639, 1512, 1434, 1384, 1315, 1256, 1194, 1161, 1143, 1066, 1024, 990,
951, 921, 841, 793, 733, 667, 542, 416. HRMS-ESI calcd for
C18H28NO4 [M + NH4]+: 322.2013. Found: 322.2012.
3ra.22 Pale yellow oil, 102.2 mg, 84% yield, 3ra/4ra = 18/82. H
1
NMR (400 MHz, CDCl3, the peaks for 4ra were indicated by *) δ 5.72
(ddd, J = 17.2, 10.4, 6.8 Hz, 1H), 5.46 (dd, J = 15.6, 6.8 Hz, 1H*), 5.30
(dt, J = 14.4, 7.2 Hz, 1H*), 5.08−5.01(m, 2H), 3.73 (s, 6H*), 3.72 (s,
3H), 3.68 (s, 3H), 3.63 (d, J = 8.8 Hz, 1H), 3.40 (dd, J = 7.6, 7.6 Hz,
1H*), 2.68−2.62 (m, 1H), 2.57−2.54 (m, 2H*), 2.08−2.00 (m, 1H),
1.92−1.84 (m, 1H*), 1.71−0.87 (m, 10H), 1.71−0.87 (m, 10H*).
3sa. Pale yellow oil, 64.1 mg, 81% yield, 3sa/4sa = 57/43. 1H NMR
(400 MHz, CDCl3, the peaks for 4sa were indicated by *) δ 5.65−5.52
(m, 1H), 5.65−5.52 (m, 1H*), 5.32 (dt, J = 15.2, 6.8 Hz, 1H*), 5.10−
5.06 (m, 2H), 3.71 (s, 6H*), 3.71 (s, 3H), 3.67 (s, 3H), 3.41−3.37 (m,
1H), 3.41−3.37 (m, 1H*), 2.70−2.63 (m, 1H), 2.58−2.54 (m, 2H*),
2.00−1.93 (m, 2H*), 1.69−1.42 (m, 2H), 0.92 (t, J = 7.6 Hz, 3H*),
0.86 (t, J = 7.2 Hz, 3H).
3ha.20 Pale yellow oil, 129.4 mg, 99% yield, 3ha/4ha = 92/8. H
1
NMR (400 MHz, CDCl3) δ 7.44−7.41 (m, 2H), 7.12−7.09 (m, 2H),
5.99−5.90 (m, 1H), 5.13−5.08 (m, 2H), 4.08 (dd, J = 10.0, 9.2 Hz,
1H), 3.82 (d, J = 11.2 Hz, 1H), 3.74 (s, 3H), 3.52 (s, 3H).
3ia.21 Pale yellow oil, 106.9 mg, 85% yield, 3ia/4ia = 90/10. H
1
NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz,
2H), 5.96 (ddd, J = 18.4, 10.4, 8.4 Hz, 1H), 5.16−5.12 (m, 2H), 4.18
(dd, J = 10.8, 8.0 Hz, 1H), 3.88 (d, J = 11.2 Hz, 1H), 3.75 (s, 3H), 3.52
(s, 3H). 19F NMR (376 MHz, CDCl3) δ −62.6.
3ab.23 Pale yellow oil, 127.9 mg, 95% yield, 3ab/4ab = 97/3. H
1
NMR (400 MHz, CDCl3) δ 7.31−7.27 (m, 2H), 7.24−7.19 (m, 3H),
5.99 (ddd, J = 18.0, 10.0, 7.2 Hz, 1H), 5.14−5.06 (m, 2H), 4.21 (q, J =
F
DOI: 10.1021/acs.organomet.8b00762
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
7.8 Hz, 2H), 4.13−4.08 (m, 1H), 3.97−3.91 (m, 2H), 3.83 (d, J = 11.2
Hz, 1H), 1.27 (t, J = 7.2 H, 3H), 0.98 (t, J = 7.2 Hz, 3H).
propanol = 80/20, v = 1.0 mL/min, λ = 224 nm, t (minor) = 23.13 min, t
(major) = 30.19 min]; [α]2D6 + 21.3 (c = 1.0, CHCl3).
3ac. Pale yellow oil, 125.0 mg, 99% yield, 3ac/4ac = 97/3. 1H NMR
(400 MHz, CDCl3) δ 7.33−7.18 (m, 5H), 5.99 (ddd, J = 18.4, 10.4, 8.0
Hz, 1H), 5.13−5.04 (m, 3H), 4.83−4.74 (m, 1H), 4.09 (dd, J = 10.8,
8.0 Hz, 1H), 3.77 (d, J = 11.2 Hz, 1H), 1.27−1.23 (m, 6H), 1.03 (d, J =
6.4 Hz, 3H), 0.93 (d, J = 6.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ
167.5, 167.2, 140.3, 138.3, 128.6, 128.2, 127.1, 116.4, 69.2, 68.9, 57.7,
49.7, 21.8, 21.7, 21.5, 21.4. IR (thin film): νmax (cm−1) = 2981, 2937,
1726, 1455, 1260, 1174, 1099, 993, 912, 821, 761, 699, 523. HRMS-ESI
calcd for C18H28NO4 [M + NH4]+: 322.2013. Found: 322.2012.
3ad.24 Pale yellow oil, 99.3 mg, 96% yield, 3ad/4ad = 96/4, dr = 49/
51. 1H NMR (400 MHz, CDCl3) δ 7.31−7.28 (m, 4H), 7.23−7.19 (m,
6H), 6.00−5.86 (m, 2H), 5.13−5.06 (m, 4H), 4.20 (q, J = 7.2 Hz, 2H),
4.15−4.10 (m, 2H), 4.04−3.98 (m, 2H), 3.91 (q, J = 7.2 Hz, 2H), 2.30
(s, 3H), 1.99 (s, 3H), 1.27 (t, J = 6.8 Hz, 3H), 0.96 (t, J = 7.2 Hz, 3H).
3ae.25 Pale yellow oil, 97.5 mg, 99% yield, 3ae/4ae = 95/5. 1H NMR
(400 MHz, CDCl3) δ 7.32−7.28 (m, 2H), 7.24−7.18 (m, 3H), 5.87
(ddd, J = 18.0, 10.4, 8.0 Hz, 1H), 5.10−5.05 (m, 2H), 4.27 (d, J = 11.6
Hz, 1H), 4.17 (dd, J = 11.6, 7.6 Hz, 1H), 2.25 (s, 3H), 1.89 (s, 3H).
(R)-3aa.18 Pale yellow oil, 93.0 mg, 90% yield, (R)-3aa/4aa = 63/37,
95% ee [Daicel Chiralpak OJ-H (0.46 cm × 25 cm), hexane/2-propanol
= 90/10, v = 1.0 mL/min, λ = 224 nm, t (minor) = 15.85 min, t (major)
= 17.42 min]; [α]2D5 + 18.5 (c = 1.0, CHCl3).
(R)-3na.18 Pale yellow oil, 119.3 mg, 97% yield, (R)-3na/4na = 85/
15, 97% ee [Daicel Chiralpak OJ-H (0.46 cm × 25 cm), hexane/2-
propanol = 80/20, v = 1.0 mL/min, λ = 224 nm, t (minor) = 13.97 min, t
(major) = 19.84 min]; [α]2D5 + 36.6 (c = 1.0, CHCl3).
(R)-3oa.19 Pale yellow oil, 118.3 mg, 95% yield, (R)-3oa/4oa = 58/
42, 94% ee [Daicel Chiralpak OZ-H (0.46 cm × 25 cm), hexane/2-
propanol = 99/1, v = 0.8 mL/min, λ = 224 nm, t (major) = 20.95 min, t
(minor) = 22.36 min]; [α]2D7 + 31.4 (c = 1.0, CHCl3).
(R)-3pa.19 Pale yellow oil, 90.0 mg, 90% yield, (R)-3pa/4pa = 74/26,
98% ee [Daicel Chiralpak OJ-H (0.46 cm × 25 cm), hexane/2-propanol
= 97/3, v = 1.0 mL/min, λ = 224 nm, t (minor) = 21.74 min, t (major) =
23.54 min]; [α]3D0 + 23.5 (c = 1.0, CHCl3).
(R)-3qa.18 Pale yellow oil, 92.4 mg, 98% yield, (R)-3qa/4qa = 91/9,
96% ee [Daicel Chiralpak OJ-H (0.46 cm × 25 cm), hexane/2-propanol
= 98/2, v = 1.0 mL/min, λ = 224 nm, t (minor) = 31.53 min, t (major) =
33.72 min]; [α]2D6 + 36.6 (c = 1.0, CHCl3).
4ra.22 Pale yellow oil, 93.5 mg, 94% yield, (R)-3ra/4ra < 1/99. 1H
NMR (400 MHz, CDCl3) δ 4ra 5.48−5.43 (m, 1H), 5.33−5.26 (dt, J =
14.4, 6.8 Hz, 1H), 3.71 (s, 6H), 3.40 (t, J = 7.6 Hz, 1H), 2.56 (dd, J =
7.2, 7.2 Hz, 2H), 1.90−1.85 (m, 1H), 1.69−1.61 (m, 5H), 1.27−1.10
(m, 3H), 1.05−0.96 (m, 2H).
(R)-3sa. Pale yellow oil, 43.2 mg, 49% yield, (R)-3sa/4sa = 21/79.
(R)-3ab.23 Pale yellow oil, 119.0 mg, 92% yield, (R)-3ab/4ab = 63/
37, 98% ee [Daicel Chiralpak OJ-H (0.46 cm × 25 cm), hexane/2-
propanol = 99/1, v = 1.0 mL/min, λ = 224 nm, t (minor) = 24.98 min, t
(major) = 27.39 min]; [α]2D9 + 13.6 (c = 1.0, CHCl3).
(R)-3ba.7b Pale yellow oil, 123.4 mg, 93% yield, (R)-3ba/4ba = 55/
45, 97% ee [Daicel Chiralpak OD-H (0.46 cm × 25 cm), hexane/2-
propanol = 98/2, v = 1.0 mL/min, λ = 224 nm, t (major) = 5.90 min, t
(minor) = 6.67 min]; [α]3D0 + 37.3 (c = 1.0, CHCl3).
(R)-3ca. Pale yellow oil, 103.0 mg, 99% yield, (R)-3ca/4ca = 59/41,
98% ee [Daicel Chiralpak OZ-H (0.46 cm × 25 cm), hexane/2-
propanol = 99/1, v = 1.0 mL/min, λ = 224 nm, t (major) = 15.75 min, t
(minor) = 17.78 min]; [α]3D0 + 21.4 (c = 1.0, CHCl3).
(R)-3ac. Pale yellow oil, 120.4 mg, 96% yield, (R)-3ac/4ac = 74/26,
97% ee [Daicel Chiralpak IC (0.46 cm × 25 cm), hexane/2-propanol =
95/5, v = 1.0 mL/min, λ = 224 nm, t (minor) = 6.06 min, t (major) =
6.97 min]; [α]2D8 + 13.7 (c = 1.0, CHCl3).
(R)-3da.18 Pale yellow oil, 112.4 mg, 94% yield, (R)-3da/4da = 67/
33, 98% ee [Daicel Chiralpak OZ-H (0.46 cm × 25 cm), hexane/2-
propanol = 99/1, v = 1.0 mL/min, λ = 224 nm, t (major) = 10.29 min, t
(minor) = 11.52 min]; [α]3D0 + 23.6 (c = 1.0, CHCl3).
(R)-3ad.24 Pale yellow oil, 106.5 mg, 98% yield, (R)-3ad/4ad = 72/
28, 96% ee, 96% ee, 49/51 dr [Daicel Chiralpak AD-H (0.46 cm × 25
cm), hexane/2-propanol = 98/2, v = 1.0 mL/min, λ = 224 nm, t1
(minor) = 7.36 min, t1 (major) = 8.29 min; t2 (major) = 9.16 min, t2
(minor) = 10.12 min]; [α]2D9 + 14.7 (c = 1.0, CHCl3).
(R)-3ea.19 Pale yellow oil, 112.9 mg, 98% yield, (R)-3ea/4ea = 34/
66, 96% ee [Daicel Chiralpak OD-H (0.46 cm × 25 cm), hexane/2-
propanol = 98/2, v = 1.0 mL/min, λ = 224 nm, t (major) = 7.75 min, t
(minor) = 9.03 min]; [α]2D9 + 13.3 (c = 1.0, CHCl3).
(R)-3ae.25 Pale yellow oil, 81.7 mg, 91% yield, (R)-3ae/4ae = 65/35,
95% ee [Daicel Chiralpak OJ-H (0.46 cm × 25 cm), hexane/2-propanol
= 85/15, v = 1.0 mL/min, λ = 224 nm, t (minor) = 15.29 min, t (major)
= 20.07 min]; [α]2D4 + 22.7 (c = 1.0, CHCl3).
(R)-3fa.18 Pale yellow oil, 102.3 mg, 93% yield, (R)-3fa/4fa = 79/21,
97% ee [Daicel Chiralpak OD-H (0.46 cm × 25 cm), hexane/2-
propanol = 95/5, v = 1.0 mL/min, λ = 224 nm, t (major) = 12.84 min, t
(minor) = 14.92 min]; [α]2D6 + 19.8 (c = 1.0, CHCl3).
Procedure for the Synthesis of Iridium(I) Complex Ir1.12a
Et3N (227.7 mg, 2.25 mmol) was added in one portion to a mixture of
[Ir(dncot)Cl]2 (53.2 mg, 0.05 mmol) and chiral triazolium salt L8
(59.0 mg, 0.10 mmol) in THF (3 mL). The reaction mixture was stirred
at room temperature for 16 h, and then concentrated in vacuo. The
residue was purified by silica gel column chromatography (PE/EtOAc
= 5/1) to afford Ir1. Yellow solid, 101.2 mg, 98% yield, mp 213.9−
215.7 °C. 1H NMR (400 MHz, CDCl3) δ 8.28−8.26 (m, 2H), 7.90 (d, J
= 7.6 Hz, 1H), 7.75 (br s, 2H), 7.66−6.80 (m, 24H), 6.74 (s, 1H),
6.69−6.58 (m, 2H), 6.49 (d, J = 6.0 Hz, 1H), 5.93 (d, J = 8.8 Hz, 1H),
5.82 (d, J = 8.8 Hz, 1H), 3.61−3.41 (m, 1H), 3.31 (d, J = 16.4 Hz, 1H),
2.53 (d, J = 8.4 Hz, 1H), −0.36 and −0.54 (s, 9H). 13C NMR (100
MHz, CDCl3) δ 180.9, 151.6, 145.7, 145.3, 142.4, 142.2, 141.8, 141.03,
139.8, 138.7, 131.79, 131.76, 131.7, 131.6, 129.8, 18.8, 128.5, 128.2,
128.1, 127.8, 127.7, 127.4, 126.9, 126.5, 125.8, 125.3, 125.23, 125.17,
125.1, 125.0, 124.3, 123.7, 123.5, 123.1, 121.9, 86.3, 83.9, 83.2, 64.7,
57.0, 54.1, 31.0, 29.7, 1.4. Anal. Calcd for C56H47N3ClOSiIr: C, 65.06;
H, 4.58; N, 4.06. Found: C, 65.00; H, 4.80; N, 4.01. IR (thin film): νmax
(cm−1) = 3052, 2951, 2920, 2850, 2361, 1596, 1498, 1473, 1249, 1099,
1074, 992, 974, 874, 837, 739, 727, 704, 691, 575, 474, 454.
Procedure for the Synthesis of Iridium(I) Complex Ir2.12a
Et3N (489.7 mg, 4.84 mmol) was added in one portion to a mixture of
[Ir(cod)Cl]2 (72.2 mg, 0.108 mmol) and chiral triazolium salt L8
(126.7 mg, 0.215 mmol) in THF (6.5 mL). The reaction mixture was
stirred at room temperature for 16 h, and then concentrated in vacuo.
The residue was purified by silica gel column chromatography (PE/
EtOAc = 5/1) to afford Ir2. Yellow solid, 156.9 mg, 87% yield, mp
221.2−222.9 °C. 1H NMR (300 MHz, CDCl3) δ 8.20 (d, J = 9.0 Hz,
2H), 7.96 (d, J = 9.0 Hz, 3H), 7.66−7.19 (m, 10H), 7.09 (q, J = 9.0, 6.0
(R)-3ga. Pale yellow oil, 130.3 mg, 91% yield, (R)-3ga/4ga = 74/26,
91% ee [Daicel Chiralpak OJ-H (0.46 cm × 25 cm), hexane/2-propanol
= 99/1, v = 1.0 mL/min, λ = 224 nm, t (major) = 26.35 min, t (minor) =
29.76 min]; [α]2D6 + 19.1 (c = 1.0, CHCl3).
(R)-3ha.20 Pale yellow oil, 122.5 mg, 94% yield, (R)-3ha/4ha = 36/
64, 95% ee [Daicel Chiralpak OJ-H (0.46 cm × 25 cm), hexane/2-
propanol = 99/1, v = 1.0 mL/min, λ = 224 nm, t (major) = 31.15 min, t
(minor) = 38.43 min]; [α]3D0 + 5.7 (c = 1.0, CHCl3).
(R)-3ia.21 Pale yellow oil, 119.6 mg, 95% yield, (R)-3ia/4ia = 28/72,
84% ee. [Daicel Chiralpak ID-3, hexane/2-propanol = 96/4, v = 0.7
mL/min, λ = 214 nm, t (minor) = 5.47 min, t (major) = 6.21 min];
[α]2D5 + 5.45 (c = 1.0, CHCl3).
(R)-3ja. Pale yellow oil, 126.3 mg, 99% yield, (R)-3ja/4ja = 84/16,
98% ee [Daicel Chiralpak OJ-H (0.46 cm × 25 cm), hexane/2-propanol
= 98/2, v = 1.0 mL/min, λ = 224 nm, t (minor) = 13.85 min, t (major) =
17.61 min]; [α]3D0 + 56.0 (c = 1.0, CHCl3).
(R)-3ka. Pale yellow oil, 107.5 mg, 99% yield, (R)-3ka/4ka = 59/41,
95% ee [Daicel Chiralpak OZ-H (0.46 cm × 25 cm), hexane/2-
propanol = 99.5/0.5, v = 1.0 mL/min, λ = 224 nm, t (major) = 30.24
min, t (minor) = 34.23 min]; [α]2D9 + 21.2 (c = 1.0, CHCl3).
(R)-3la.22 Pale yellow oil, 115.9 mg, 97% yield, (R)-3la/4la = 66/34,
96% ee [Daicel Chiralpak OZ-H (0.46 cm × 25 cm), hexane/2-
propanol = 98/2, v = 1.0 mL/min, λ = 224 nm, t (major) = 14.89 min, t
(minor) = 16.71 min]; [α]2D6 + 16.5 (c = 1.0, CHCl3).
(R)-3ma. Pale yellow oil, 117.6 mg, 98% yield, (R)-3ma/4ma = 82/
18, 97% ee [Daicel Chiralpak IC (0.46 cm × 25 cm), hexane/2-
G
DOI: 10.1021/acs.organomet.8b00762
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Hz, 3H), 6.83−6.68 (m, 2H), 6.35 (d, J = 9.0 Hz, 1H), 4.75−4.63 (m,
2H), 3.42 (dd, J = 9.0, 6.0 Hz, 1H), 3.09 (d, J = 15.0 Hz, 1H), 2.29 (q, J
= 9.0, 6.0 Hz, 2H), 1.92−1.78 (m, 2H), 1.53−1.41 (m, 2H), 1.27 (dd, J
= 9.0, 9.0 Hz, 2H), 0.91−0.82 (m, 1H), −0.26 and −0.54 (s, 9H). 13C
NMR (75 MHz, CDCl3) δ 185.3, 151.6, 143.1, 142.7, 140.8, 139.5,
131.5, 129.9, 128.7, 128.6, 128.3, 128.2, 128.1, 127.8, 126.4, 126.1,
124.3, 122.4, 87.3, 85.8, 83.5, 64.7, 56.7, 51.9, 34.3, 32.2, 31.4, 30.0,
27.5, 1.6. Anal. Calcd for C40H43N3ClOSiIr: C, 57.36; H, 5.18; N, 5.02.
Found: C, 57.01; H, 4.93; N, 4.65. IR (thin film): νmax (cm−1) = 2955,
2912, 2883, 1589, 1564, 1471, 1418, 1327, 1249, 1080, 1040, 991, 973,
893, 835, 769, 728, 756, 739, 575.
Substitutions. Top. Organomet. Chem. 2011, 38, 155−207. (g) Tosatti,
P.; Nelson, A.; Marsden, S. P. Recent Advances and Applications of
Iridium-Catalysed Asymmetric Allylic Substitution. Org. Biomol. Chem.
2012, 10, 3147−3163. (h) Helmchen, G. In Molecular Catalysis; Gade,
L. H., Hofmann, P., Eds.; Wiley-VCH: Weinheim, 2014; pp 235−254.
(i) 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. (j) Qu, J.;
Helmchen, G. Applications of Iridium-Catalyzed Asymmetric Allylic
Substitution Reactions in Target-Oriented Synthesis. Acc. Chem. Res.
2017, 50, 2539−2555. (k) Zhang, X.; You, S.-L. THQphos in Ir-
Catalyzed Asymmetric Allylic Substitution Reactions. Chimia 2018, 72,
589−594.
(2) For early examples on Ir-catalyzed allylic substitution reactions,
see (a) Takeuchi, R.; Kashio, M. Iridium Complex-Catalyzed Allylic
Alkylation of Allylic Esters and Allylic Alcohols: Unique Regio- and
Stereoselectivity. J. Am. Chem. Soc. 1998, 120, 8647−8655. (b) Janssen,
J. P.; Helmchen, G. First Enantioselective Alkylations of Monosub-
stituted Allylic Acetates Catalyzed by Chiral Iridium Complexes.
Tetrahedron Lett. 1997, 38, 8025−8026.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.8b00762.
Experimental procedures and analysis data for all new
compounds (PDF)
(3) For selected recent examples, see (a) Qu, J.; Roßberg, L.;
Helmchen, G. Enantio- and Regioselective Iridium-Catalyzed Allylic
Esterification. J. Am. Chem. Soc. 2014, 136, 1272−1275. (b) Hamilton,
J. Y.; Sarlah, D.; Carreira, E. M. Iridium-Catalyzed Enantioselective
Allyl-Alkene Coupling. J. Am. Chem. Soc. 2014, 136, 3006−3009.
(c) Zhang, X.; Yang, Z.-P.; Huang, L.; You, S.-L. Highly Regio- and
Enantioselective Synthesis of N-Substituted 2-Pyridones: Iridium-
Catalyzed Intermolecular Asymmetric Allylic Amination. Angew. Chem.,
Int. Ed. 2015, 54, 1873−1876. (d) Breitler, S.; Carreira, E. M.
Formaldehyde N,N-Dialkylhydrazones as Neutral Formyl Anion
Equivalents in Iridium-Catalyzed Asymmetric Allylic Substitution. J.
Am. Chem. Soc. 2015, 137, 5296−5299. (e) Zhang, Q.; Stockdale, D. P.;
Mixdorf, J. C.; Topczewski, J. J.; Nguyen, H. M. Iridium-Catalyzed
Enantioselective Fluorination of Racemic, Secondary Allylic Trichlor-
oacetimidates. J. Am. Chem. Soc. 2015, 137, 11912−11915.
(f) Madrahimov, S. T.; Li, Q.; Sharma, A.; Hartwig, J. F. Origins of
Regioselectivity in Iridium Catalyzed Allylic Substitution. J. Am. Chem.
Soc. 2015, 137, 14968−14981. (g) Hamilton, J. Y.; Sarlah, D.; Carreira,
E. M. Iridium-Catalyzed Enantioselective Allylic Alkylation with
Functionalized Organozinc Bromides. Angew. Chem., Int. Ed. 2015,
54, 7644−7647. (h) Yuan, Q.; Yao, K.; Liu, D.; Zhang, W. Iridium-
Catalyzed Allyl−Allyl Cross-Coupling of Allylic Carbonates with (E)-
1,3-Diarylpropenes. Chem. Commun. 2015, 51, 11834−11836.
(i) Liang, X.; Wei, K.; Yang, Y.-R. Iridium-Catalyzed Enantioselective
Allylation of Silyl Enol Ethers Derived from Ketones and α,β-
Unsaturated Ketones. Chem. Commun. 2015, 51, 17471−17474.
(j) Zhan, M.; Li, R.-Z.; Mou, Z.-D.; Cao, C.-G.; Liu, J.; Chen, Y.-W.;
Niu, D. Silver-Assisted, Iridium-Catalyzed Allylation of Bis-
[(pinacolato)boryl]methane Allows the Synthesis of Enantioenriched
Homoallylic Organoboronic Esters. ACS Catal. 2016, 6, 3381−3386.
(k) Liu, W.-B.; Okamoto, N.; Alexy, E. J.; Hong, A. Y.; Tran, K.; Stoltz,
B. M. Enantioselective γ-Alkylation of α,β-Unsaturated Malonates and
Ketoesters by a Sequential Ir-Catalyzed Asymmetric Allylic Alkylation/
Cope Rearrangement. J. Am. Chem. Soc. 2016, 138, 5234−5237.
(l) Jiang, X.; Chen, W.; Hartwig, J. F. Iridium-Catalyzed Diaster-
eoselective and Enantioselective Allylic Substitutions with Acyclic α-
Alkoxy Ketones. Angew. Chem., Int. Ed. 2016, 55, 5819−5823.
(m) Jiang, X.; Beiger, J. J.; Hartwig, J. F. Stereodivergent Allylic
Substitutions with Aryl Acetic Acid Esters by Synergistic Iridium and
Lewis Base Catalysis. J. Am. Chem. Soc. 2017, 139, 87−90. (n) Liu, X.-J.;
You, S.-L. Enantioselective Iridium-Catalyzed Allylic Substitution with
2-Methylpyridines. Angew. Chem., Int. Ed. 2017, 56, 4002−4005.
Accession Codes
CCDC 1873681 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_
request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: zhangxiao@sioc.ac.cn.
*E-mail: slyou@sioc.ac.cn.
ORCID
Shu-Li You: 0000-0003-4586-8359
Author Contributions
#C.-C.B. and D.-S.Z. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Key Research and Development
Program of China (2016YFA0202900), the National Basic
Research Program of China (2015CB856600), the NSFC
(21572252 and 21332009), the Program of Shanghai Subject
Chief Scientist (16XD1404300), Shanghai Sailing Program
(18YF1428900), and the CAS (XDB20000000, QYZDY-SSW-
SLH012) for generous financial support. We thank Mr. James
Alexander Rossi-Ashton from University of York for helpful
discussion.
REFERENCES
■
(1) For reviews on Ir-catalyzed asymmetric allylic substitution
reactions, see (a) Miyabe, H.; Takemoto, Y. Regio- and Stereo-
controlled Palladium- or Iridium-Catalyzed Allylation. Synlett 2005,
1641−1655. (b) Takeuchi, R.; Kezuka, S. Iridium-Catalyzed Formation
of Carbon-Carbon and Carbon-Heteroatom Bonds. Synthesis 2006,
2006, 3349−3366. (c) Helmchen, G.; Dahnz, A.; Dubon, P.; Schelwies,
̈
̈
(o) Hamilton, J. Y.; Rossler, S. L.; Carreira, E. M. Enantio- and
M.; Weihofen, R. Iridium-Catalysed Asymmetric Allylic Substitutions.
Chem. Commun. 2007, 675−691. (d) Hartwig, J. F.; Stanley, L. M.
Mechanistically Driven Development of Iridium Catalysts for
Asymmetric Allylic Substitution. Acc. Chem. Res. 2010, 43, 1461−
1475. (e) Hartwig, J. F.; Pouy, M. J. Iridium-Catalyzed Allylic
Substitution. Top. Organomet. Chem. 2011, 34, 169−208. (f) Liu, W.-
B.; Xia, J.-B.; You, S.-L. Iridium-Catalyzed Asymmetric Allylic
Diastereoselective Spiroketalization Catalyzed by Chiral Iridium
Complex. J. Am. Chem. Soc. 2017, 139, 8082−8085. (p) Huang, L.;
Cai, Y.; Zheng, C.; Dai, L.-X.; You, S.-L. Iridium-Catalyzed
Enantioselective Synthesis of Pyrrole-Annulated Medium-Sized-Ring
Compounds. Angew. Chem., Int. Ed. 2017, 56, 10545−10548.
(q) Shockley, S. E.; Hethcox, J. C.; Stoltz, B. M. Enantioselective
H
DOI: 10.1021/acs.organomet.8b00762
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Synthesis of Acyclic α-Quaternary Carboxylic Acid Derivatives through
Iridium-Catalyzed Allylic Alkylation. Angew. Chem., Int. Ed. 2017, 56,
11545−11548. (r) Wang, Y.; Zheng, C.; You, S.-L. Iridium-Catalyzed
Asymmetric Allylic Dearomatization by a Desymmetrization Strategy.
Angew. Chem., Int. Ed. 2017, 56, 15093−15097. (s) Wei, L.; Zhu, Q.;
Xu, S.-M.; Chang, X.; Wang, C.-J. Stereodivergent Synthesis of α,α-
Disubstituted α-Amino Acids via Synergistic Cu/Ir Catalysis. J. Am.
Chem. Soc. 2018, 140, 1508−1513. (t) Hethcox, J. C.; Shockley, S. E.;
Stoltz, B. M. Enantioselective Synthesis of Vicinal All-Carbon
Quaternary Centersvia Iridium-Catalyzed Allylic Alkylation. Angew.
Chem., Int. Ed. 2018, 57, 8664−8667.
(4) For a review, see (a) Teichert, J. F.; Feringa, B. L.
Phosphoramidites: Privileged Ligands in Asymmetric Catalysis.
Angew. Chem., Int. Ed. 2010, 49, 2486−2528. For the first application
of Feringa ligand in Ir-catalyzed allylic substitution reaction, see
(b) 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.
9307−9387. (f) Cai, X.-H.; Xie, B. Stereoselective Reactions Catalyzed
by N-Heterocyclic Carbenes. Mini-Rev. Org. Chem. 2018, 15, 248−260.
́
(9) For selected reviews, see (a) Cesar, V.; Bellemin-Laponnaz, S.;
Gade, L. H. Chiral N-Heterocyclic Carbenes as Stereodirecting Ligands
in Asymmetric Catalysis. Chem. Soc. Rev. 2004, 33, 619−636. (b) Gade,
L. H.; Bellemin-Laponnaz, S. Chiral N-Heterocyclic Carbenes as
Stereodirecting Ligands in Asymmetric Catalysis. Top. Organomet.
Chem. 2006, 21, 117−157. (c) Hahn, F. E.; Jahnke, M. C. Heterocyclic
Carbenes: Synthesis and Coordination Chemistry. Angew. Chem., Int.
́
Ed. 2008, 47, 3122−3172. (d) Díez-Gonzalez, S.; Marion, N.; Nolan, S.
P. N-Heterocyclic Carbenes in Late Transition Metal Catalysis. Chem.
Rev. 2009, 109, 3612−3676. (e) Janssen-Muller, D.; Schlepphorst, C.;
̈
Glorius, F. Privileged Chiral N-Heterocyclic Carbene Ligands for
Asymmetric Transition-Metal Catalysis. Chem. Soc. Rev. 2017, 46,
4845−4854. For a book, see (f) Glorius, F., Ed. N-Heterocyclic Carbenes
in Transition Metal Catalysis; Springer: Heidelberg, 2007.
(10) For a selected review: Lazreg, F.; Nahra, F.; Cazin, C. S. J.
Copper-NHC Complexes in Catalysis. Coord. Chem. Rev. 2015, 293−
294, 48−79.
(11) (a) Enders, D.; Kallfass, U. An Efficient Nucleophilic Carbene
Catalyst for the Asymmetric Benzoin Condensation. Angew. Chem., Int.
Ed. 2002, 41, 1743−1745. (b) Li, Y.; Feng, Z.; You, S.-L. D-Camphor-
Derived Triazolium Salts for Catalytic Intramolecular Crossed
Aldehyde-Ketone Benzoin Reactions. Chem. Commun. 2008, 2263−
2265.
(12) (a) Ye, K.-Y.; Cheng, Q.; Zhuo, C.-X.; Dai, L.-X.; You, S.-L. An
Iridium(I) N-Heterocyclic Carbene Complex Catalyzes Asymmetric
Intramolecular Allylic Amination Reactions. Angew. Chem., Int. Ed.
2016, 55, 8113−8116. (b) Ye, K.-Y.; Wu, K.-J.; Li, G.-T.; Dai, L.-X.;
You, S.-L. Synthesis of Enantioenriched Indolopiperazinones via
Iridium(I) N-Heterocyclic Carbene Complex Catalyzed Asymmetric
Intramolecular Allylic Amination Reaction. Heterocycles 2017, 95, 304−
313. For a recent example on the application of Enders carbene in
iridium-catalyzed intramolecular asymmetric allylic alkylation of
hydroxyquinolines, see (c) Yang, Z.-P.; Jiang, R.; Zheng, C.; You, S.-
L. Iridium-Catalyzed Intramolecular Asymmetric Allylic Alkylation of
Hydroxyquinolines: Simultaneous Weakening of the Aromaticity of
Two Consecutive Aromatic Rings. J. Am. Chem. Soc. 2018, 140, 3114−
3119.
(5) For selected examples, see (a) Tissot-Croset, K.; Polet, D.;
Alexakis, A. A Highly Effective Phosphoramidite Ligand for
Asymmetric Allylic Substitution. Angew. Chem., Int. Ed. 2004, 43,
2426−2428. (b) Polet, D.; Alexakis, A. Kinetic Study of Various
Phosphoramidite Ligands in the Iridium-Catalyzed Allylic Substitution.
Org. Lett. 2005, 7, 1621−1624. (c) Polet, D.; Alexakis, A.; Tissot-
Croset, K.; Corminboeuf, C.; Ditrich, K. Phosphoramidite Ligands in
Iridium-Catalyzed Allylic Substitution. Chem. - Eur. J. 2006, 12, 3596−
3609.
(6) For selected examples, see (a) Defieber, C.; Grutzmacher, H.;
̈
Carreira, E. M. Chiral Olefins as Steering Ligands in Asymmetric
Catalysis. Angew. Chem., Int. Ed. 2008, 47, 4482−4502. (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) Rossler, S. L.; Krautwald, S.; Carreira,
E. M. Study of Intermediates in Iridium-(Phosphoramidite,Olefin)-
Catalyzed Enantioselective Allylic Substitution. J. Am. Chem. Soc. 2017,
139, 3603−3606.
(7) (a) Liu, W.-B.; He, H.; Dai, L.-X.; You, S.-L. Synthesis of 2-
Methylindoline- and 2-Methyl-1,2,3,4-tetrahydroquinoline-Derived
Phosphoramidites and Their Applications in Iridium-Catalyzed Allylic
Alkylation of Indoles. Synthesis 2009, 2009, 2076−2082. (b) Liu, W.-B.;
Zheng, C.; Zhuo, C.-X.; Dai, L.-X.; You, S.-L. Iridium-Catalyzed Allylic
Alkylation Reaction with N-Aryl Phosphoramidite Ligands: Scope and
Mechanistic Studies. J. Am. Chem. Soc. 2012, 134, 4812−4821. (c) Liu,
W.-B.; Reeves, C. M.; Virgil, S. C.; Stoltz, B. M. Construction of Vicinal
Tertiary and All-Carbon Quaternary Stereocenters via Ir-Catalyzed
Regio-, Diastereo-, and Enantioselective Allylic Alkylation and
Applications in Sequential Pd Catalysis. J. Am. Chem. Soc. 2013, 135,
10626−10629. (d) Liu, W.-B.; Reeves, C. M.; Stoltz, B. M. Enantio-,
Diastereo-, and Regioselective Iridium-Catalyzed Asymmetric Allylic
Alkylation of Acyclic β-Ketoesters. J. Am. Chem. Soc. 2013, 135, 17298−
17301. (e) Zhuo, C.-X.; Cheng, Q.; Liu, W.-B.; Zhao, Q.; You, S.-L.
Enantioselective Synthesis of Pyrrole-Based Spiro- and Polycyclic
Derivatives by Iridium-Catalyzed Asymmetric Allylic Dearomatization
and Controllable Migration Reactions. Angew. Chem., Int. Ed. 2015, 54,
8475−8479. (f) Zhang, X.; Liu, W.-B.; Cheng, Q.; You, S.-L. Iridium-
Catalyzed Asymmetric Allylic Amination Reactions with N-Aryl
Phosphoramidite Ligands. Organometallics 2016, 35, 2467−2472.
(8) For selected reviews, see (a) Enders, D.; Balensiefer, T.
Nucleophilic Carbenes in Asymmetric Organocatalysis. Acc. Chem.
Res. 2004, 37, 534−541. (b) Johnson, J. S. Catalyzed Reactions of Acyl
Anion Equivalents. Angew. Chem., Int. Ed. 2004, 43, 1326−1328.
(c) Enders, D.; Niemeier, O.; Henseler, A. Organocatalysis by N-
Heterocyclic Carbenes. Chem. Rev. 2007, 107, 5606−5655. (d) Hop-
kinson, M. N.; Richter, C.; Schedler, M.; Glorius, F. An Overview of N-
Heterocyclic Carbenes. Nature 2014, 510, 485−496. (e) Flanigan, D.
M.; Romanov-Michailidis, F.; White, N. A.; Rovis, T. Organocatalytic
Reactions Enabled by N-Heterocyclic Carbenes. Chem. Rev. 2015, 115,
(13) Ye, K.-Y.; Zhao, Z.-A.; Lai, Z.-W.; Dai, L.-X.; You, S.-L. Highly
Regioselective Allylic Substitution Reactions Catalyzed by an Air-Stable
(π-Allyl)iridium Complex Derived from Dinaphthocyclooctatetraene
and a Phosphoramidite Ligand. Synthesis 2013, 45, 2109−2114.
(14) For L1, see (a) Kingsbury, J. S.; Hoveyda, A. H. Regarding the
Mechanism of Olefin Metathesis with Sol-Gel-Supported Ru-Based
Complexes Bearing a Bidentate Carbene Ligand. Spectroscopic
Evidence for Return of the Propagating Ru Carbene. J. Am. Chem.
Soc. 2005, 127, 4510−4517. For L2, see (b) Kunz, D.; Deißler, C.;
Gierz, V.; Rominger, F.; Oeser, T. Reduction of Dipyrido Ureas via 6-
Alkyloxydipyrido[1,2-c,2,1-e]imidazolium Salts. Z. Naturforsch., B: J.
Chem. Sci. 2010, 65, 861−872. For L3, see (c) Matsumoto, T.;
Yamamoto, H.; Inoue, S. Selective Formation of Triose from
Formaldehyde Catalyzed by Thiazolium Salt. J. Am. Chem. Soc. 1984,
106, 4829−4832. For L4, see (d) Chow, K. Y.-K.; Bode, J. W. Catalytic
Generation of Activated Carboxylates: Direct, Stereoselective Synthesis
of β-Hydroxyesters from Epoxyaldehydes. J. Am. Chem. Soc. 2004, 126,
8126−8127. For L5, see (e) Becker, H. G. O.; Hoffmann, G.; Gwan, K.
M.; Knupfer, L. Azocoupling of Quaternary 1,2,4-Triazolium Salts to
̈
Form 5-p-N,N-Dimethylaminophenylazo-I,2,4-triazolium Salts. J.
Prakt. Chem. 1988, 330, 325−337. For L6, see (f) Ling, K. B.;
Smith, A. D. α-Aroyloxyaldehydes: Scope and Limitations as
Alternatives to α-Haloaldehydes for NHC-Catalysed Redox Trans-
formations. Chem. Commun. 2011, 47, 373−375. For L7, see
(g) Thomson, J. E.; Rix, K.; Smith, A. D. Efficient N-Heterocyclic
Carbene-Catalyzed O- to C-Acyl Transfer. Org. Lett. 2006, 8, 3785−
3788.
(15) For L8−L12, see (a) Li, G.-T.; Gu, Q.; You, S.-L.
Enantioselective Annulation of Enals with 2-Naphthols by Triazolium
Salts Derived from L-Phenylalanine. Chem. Sci. 2015, 6, 4273−4278.
I
DOI: 10.1021/acs.organomet.8b00762
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
́
For L13 and L19, see (b) Campbell, C. D.; Concellon, C.; Smith, A. D.
Catalytic enantioselective Steglich rearrangements using chiral N-
heterocyclic carbenes. Tetrahedron: Asymmetry 2011, 22, 797−811.
For L14, see (c) Kerr, M. S.; Read de Alaniz, J.; Rovis, T. An Efficient
Synthesis of Achiral and Chiral 1,2,4-Triazolium Salts: Bench Stable
Precursors for N-Heterocyclic Carbenes. J. Org. Chem. 2005, 70, 5725−
5728. For L15, see (d) Vora, H. U.; Rovis, T. N-Heterocyclic Carbene
Catalyzed Asymmetric Hydration: Direct Synthesis of α-Protio and α-
Deuterio α-Chloro and α-Fluoro Carboxylic Acids. J. Am. Chem. Soc.
2010, 132, 2860−2861. For L16−L18, see ref 11b. For L20, see (e) Li,
Z.; Li, X.; Cheng, J.-P. An Acidity Scale of Triazolium-Based NHC
Precursors in DMSO. J. Org. Chem. 2017, 82, 9675−9681. For L21, see
(f) Rong, Z.-Q.; Jia, M.-Q.; You, S.-L. (1R, 2R)-DPEN-Derived
Triazolium Salts for Enantioselective Oxodiene Dielse-Alder Reactions.
Tetrahedron 2011, 67, 9329−9333. For L22, see ref 11a. For L23 and
L24, see (g) Enders, D.; Han, J.-W. Synthesis of Enantiopure
Triazolium Salts from Pyroglutamic Acid and Their Evaluation in the
Benzoin Condensation. Tetrahedron: Asymmetry 2008, 19, 1367−1371.
For L25, see (h) Jia, Y.-X.; Katayev, D.; Bernardinelli, G.; Seidel, T. M.;
Kundig, E. P. New Chiral N-Heterocyclic Carbene Ligands in
̈
Palladium-Catalyzed α-Arylations of Amides: Conformational Locking
through Allylic Strain as a Device for Stereocontrol. Chem. - Eur. J.
2010, 16, 6300−6309. For L26, see (i) Zhu, S.; Wang, C.; Chen, L.;
Liang, R.; Yu, Y.; Jiang, H. Modular Approach for Synthesis of Vicinal
Diamines Containing Axial Chiral 1,10-Binaphthyl from 1,2-Diamino-
ethane by Pd-Catalyzed N-Arylation Reactions. Org. Lett. 2011, 13,
1146−1149.
(16) Spiess, S.; Welter, C.; Franck, G.; Taquet, J.-P.; Helmchen, G.
Iridium-Catalyzed Asymmetric Allylic Substitutions-Very High Re-
gioselectivity and Air Stability with a Catalyst Derived from
Dibenzo[a,e]cyclooctatetraene and a Phosphoramidite. Angew. Chem.,
Int. Ed. 2008, 47, 7652−7655.
(17) See the Supporting Information for more details.
(18) You, S.-L.; Zhu, X.-Z.; Luo, Y.-M.; Hou, X.-L.; Dai, L.-X. Highly
Regio- and Enantioselective Pd-Catalyzed Allylic Alkylation and
Amination of Monosubstituted Allylic Acetates with Novel Ferrocene
P,N-Ligands. J. Am. Chem. Soc. 2001, 123, 7471−7472.
(19) Nemoto, T.; Sakamoto, T.; Fukuyama, T.; Hamada, Y. Ir-
catalyzed asymmetric allylic alkylation using chiral diaminophosphine
oxides: DIAPHOXs. Formal enantioselective synthesis of (−)-parox-
etine. Tetrahedron Lett. 2007, 48, 4977−4981.
(20) Lai, Z.-W.; Yang, R.-F.; Ye, K.-Y.; Sun, H.; You, S.-L. Synthesis of
1-[Bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene Ligands and
Their Application in Regio- and Enantioselective Pd-Catalyzed Allylic
Alkylation of Monosubstituted Allyl Substrates. Beilstein J. Org. Chem.
2014, 10, 1261−1266.
(21) Hayashi, T.; Okada, A.; Suzuka, T.; Kawatsura, M. High
Enantioselectivity in Rhodium-Catalyzed Allylic Alkylation of 1-
Substituted 2-Propenyl Acetates. Org. Lett. 2003, 5, 1713−1715.
(22) Alexakis, A.; Polet, D. Very Efficient Phosphoramidite Ligand for
Asymmetric Iridium-Catalyzed Allylic Alkylation. Org. Lett. 2004, 6,
3529−3532.
(23) Onodera, G.; Watabe, K.; Matsubara, M.; Oda, K.; Kezuka, S.;
Takeuchi, R. Iridium-Catalyzed Enantioselective Allylic Alkylation
using Chiral Phosphoramidite Ligand Bearing an Amide Moiety. Adv.
Synth. Catal. 2008, 350, 2725−2732.
(24) Khafajeh, S.; Akhlaghinia, B.; Rezazadeh, S.; Eshghi, H.
Fe(HSO4)3: An Efficient, Heterogeneous and Reusable Catalyst for
C-Alkylation of β-Dicarbonyl Compounds. J. Chem. Sci. 2014, 126,
1903−1912.
(25) Beck, T. M.; Breit, B. Regio- and Enantioselective Rhodium-
Catalyzed Addition of 1,3-Diketones to Allenes: Construction of
Asymmetric Tertiary and Quaternary All Carbon Centers. Angew.
Chem., Int. Ed. 2017, 56, 1903−1907.
J
DOI: 10.1021/acs.organomet.8b00762
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