Iridium-Catalyzed Asymmetric Allylic Amination Reactions with N-Aryl Phosphoramidite Ligands

Article abstract of DOI:10.1021/acs.organomet.6b00339

A series of N-aryl phosphoramidite ligands were synthesized, and the iridium complexes derived from these novel ligands were proven to be efficient catalysts for asymmetric intermolecular allylic amination reactions. This C-N bond forming process readily accommodates a diverse range of amines and allylic carbonates, especially for the previously challenging ortho-substituted cinnamyl substrates. Moreover, isolation and characterization of the corresponding (π-allyl)-iridium complex K1 reveal that the active iridacycle is generated through a C(sp²)-H bond insertion of tetrahydroquinoline of the ligand.

Full text of DOI:10.1021/acs.organomet.6b00339

Article
pubs.acs.org/Organometallics
Iridium-Catalyzed Asymmetric Allylic Amination Reactions with
N‑Aryl Phosphoramidite Ligands
Xiao Zhang, Wen-Bo Liu, Qiang Cheng, and Shu-Li You*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345
Lingling Lu, Shanghai 200032, People’s Republic of China
Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, People’s Republic of China
*
S Supporting Information
ABSTRACT: A series of N-aryl phosphoramidite ligands were
synthesized, and the iridium complexes derived from these
novel ligands were proven to be efficient catalysts for
asymmetric intermolecular allylic amination reactions. This
C−N bond forming process readily accommodates a diverse
range of amines and allylic carbonates, especially for the
previously challenging ortho-substituted cinnamyl substrates.
Moreover, isolation and characterization of the corresponding
(
π-allyl)−iridium complex K1 reveal that the active iridacycle is
2
generated through a C(sp )−H bond insertion of tetrahydroquinoline of the ligand.
INTRODUCTION
■
Iridium-catalyzed asymmetric allylic substitution reactions have
become a powerful tool to construct chiral centers in organic
1
synthesis. A literature survey shows that many catalytic
systems involving chiral ligands such as oxazolinyl-phosphine
1
h
2
ligands, binaphthol-derived phosphoramidites, phosphora-
3
4
midite-olefin ligands, and others have been successfully
demonstrated in this transformation.
In particular, Ir complexes derived from Feringa type ligands
usually provide excellent regio- and enantioselectivity for a
5
variety of substrates. Subsequent mechanistic studies by the
Hartwig group and the Helmchen group reveal that the active
iridacycle catalyst is generated by cyclometalation of a methyl
6
group of the ligand (Figures 1 and 2a). Although the
[
Ir(COD)Cl] /1a combination is widely appreciated for its
2
reactivity and selectivity, its sensitivity to steric hindrance
somehow limits its application. For example, ortho-substituted
phenyl allylic substrates were found to lead to a decrease in
Figure 2. Structures and CPK models of iridium cinnamyl complexes
(anions are omitted).
7
either yield or enantioselectivity in many cases (Scheme 1).
Recently, our group has developed a series of N-aryl
phosphoramidite ligands, which offer high regio- and
enantioselective control with a broad substrate scope involving
8
sterically congested nucleophiles. Moreover, these types of
ligands were found to be superior to previously established
systems in asymmetric allylic alkylation of ortho-substituted
8a,b
cinnamyl carbonates.
One possibility for the high reactivity
with sterically bulky substrates has been rationalized by the fact
2
that the iridacycle catalyst, formed through C(sp )−H
Received: April 26, 2016
Figure 1. Phosphoramidite ligands.
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.6b00339
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Article
Scheme 1. Ir-Catalyzed Allylic Amination with Ortho-
Substituted Substrates
applied in the allylic amination reactions. We herein wish to
report the results from this study.
RESULTS AND DISCUSSION
■
Optimization of the Reaction Conditions. We next
investigated the efficiency of these N-aryl phosphoramidite
10
ligands in iridium-catalyzed allylic amination reactions (Table
). The 2-phenyl-substituted ligand 1c led to a slightly
increased regioselectivity, but a decreased enantioselectivity
1
activation of Me-THQphos (1b) with [Ir(COD)Cl] , is less
8i
2
(
entry 3). To our delight, ligand 1d, by introducing double
sterically embraced in comparison with those derived from
Feringa type ligands (Figure 2b).
phenyl substituents at the 3,3′-positions of BINOL, was found
to be able to improve the branched selectivity dramatically (99/
We went on to apply Me-THQphos (1b) in asymmetric
allylic aminations, with the hope of overcoming the low yield
and enantioselectivity obtained from the reactions between
ortho-substituted cinnamyl substrates and nitrogen-containing
1
), meanwhile maintaining the excellent enantioselectivity
(
97% ee, entry 4). In comparison, linear product was formed
favorably when 3,3′-dibromo-substituted binaphthol derived
ligand 1e was used (4a/5a/6a = 22/78/0, entry 5). A sharp
decrease in the enantioselectivity (55% ee) was observed when
ligand 1f without a methyl group in the amine part was
employed (entry 6). Interestingly, employment of ligand 1g, a
diastereomer of 1d with an opposite configuration in the amine
part, provided results in terms of selectivity and yield identical
with those of the reaction with 1d (entry 4 vs entry 7). Given
the same reactivity and selectivity of the catalysts derived from
7b,h
nucleophiles in previous studies.
allylic carbonate and aniline as model substrates, Me-THQphos
1b) as a ligand resulted in a significantly increased
With 2-methoxylphenyl
(
enantioselectivity in comparison with 1a (from 36% to 97%
ee; Table 1, entries 1 and 2). To our surprise, the
Table 1. Investigation of Ligands in the Ir-Catalyzed Allylic
a
Amination Reaction
1d and 1g, we envisioned that it was not necessrary for the 2-
methyl-1,2,3,4-tetrahydroquinoline to be enantiopure in this
case. Further evidence was obtained by the use of a
combination of [Ir(COD)Cl] with a mixture of identical
2
amounts of 1d and 1g, affording the same yields and
selectivities as expected (4a/5a/6a = 99/1/0, 88% yield, 97%
ee, entry 8). Since the mixture of diastereomers is easily
accessed from readily available enantiopure BINOL and
racemic 2-methyltetrahydroquinoline directly, the utilization
of this diastereomeric ligand mixture will provide an economic
alternative for ligand 1d or 1g, especially for scale-up reactions.
Substrate Scope. With the optimized reaction conditions
in hand, our efforts were focused on expanding the reaction
substrate scope by exploring various nitrogen-containing
nucleophiles and ortho-substituted phenyl allylic carbonates
(Scheme 2). The results obtained with 1a as ligand for
comparison were adhered to (highlighted in blue). First, with
aniline as the nucleophile, the cinnamyl carbonate with an
electron-donating methyl group at the ortho position was
tested (1d as the ligand), affording the desired product 4b in
good yield and excellent enantioselectivity (80% yield, 93% ee).
In sharp contrast, only a moderate ee was obtained when 1a
was employed as the ligand (58% yield, 39% ee, 4b; Scheme 2).
It is worth noting that the reaction of 2-bromocinnamyl ethyl
carbonate with aniline catalyzed by the chiral Ir complex
derived from [Ir(COD)Cl] and (R,R,R )-1a form product 4c
b
c
d
entry
1
4a/5a/6a
yield of 4a (%)
ee of 4a (%)
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
99/1/0
83/14/3
90/10/0
99/1/0
22/78/0
99/1/0
99/1/0
99/1/0
60
61
64
88
20
87
88
88
36 (S)
97 (S)
85 (S)
97 (R)
91 (R)
55 (R)
97 (R)
97 (R)
1g
e
8
1d + 1g
a
Reaction conditions: [Ir(COD)Cl] (2.5 mol %), ligand 1 (5.0 mol
2
%
), 2a (100 mol %), PhNH (3a) (200 mol %) in THF at 50 °C
2
b
1
unless noted otherwise. Determined by H NMR of the crude
c
d
reaction mixture. Isolated yield. The ee of 4a was determined by
HPLC analysis. A mixture of 1d (2.5 mol %) and 1g (2.5 mol %) was
e
used.
corresponding regioselectivity (branched to linear) decreased
dramatically from 99/1 to 83/17. The C3 terminus of the allyl
fragment of Kb (Figure 2b) is more electrophilic than the C1
terminus, which principally drives the branched selectivity as we
2
a
7
i
in 26% yield and 29% ee. Pleasingly, with a catalyst derived
9
reported previously. However, by comparing the CPK models
from [Ir(COD)Cl] and ligand 1d, 2-bromocinnamyl methyl
2
(
Figure 2), we found that the C1 terminus of Kb is much less
carbonate was converted to its amination product 4c in 86%
yield and 96% ee. Moreover, non-ortho-substituted substrates
including heteroaryl allyl carbonate and para-substituted
cinnamyl carbonates proceeded smoothly, with ligand 1d
yielding 4d−f with satisfactory results (79−85% yields, 86−
90% ee) in comparison with those obtained from ligand 1a
(74−84% yields, 88−93% ee; Scheme 2), showcasing the
generality of the current catalytic system.
To further test the potential of this Ir-catalyzed allylic
amination reactions, we turned our attention toward other
nucleophiles such as indoline due to its prevalence in natural
products (4g−k, Scheme 2). While ligand 1a could only give
sterically surrounded than that of Ka. Thus, for the small but
highly reactive nucleophiles (i.e., amines), although the
branched product is still the major outcome, there are increased
chances to attack the C1 terminus to form a linear product. We
sought to improve the regioselectivity by engineering new
ligands to create a crowded environment close by the C1
terminus in order to prevent it from being attacked. With these
ideas in mind, several new N-aryl phosphoramidite ligands
(
1c−g), designed by the installment of substituents at the 3,3′-
positions of the BINOL scaffold or increase in the size of the 2-
substituent of tetrahydroquinoline, were synthesized and
B
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Scheme 2. Substrate Scope of the Ir-Catalyzed Allylic
Amination Reactions
Scheme 3. Gram-Scale Synthesis of 4a
−
a d
configuration of the branched products is opposite by using 1d
and 1a, although ligands 1d and 1a have the same chirality of
binaphthol. The same phenomenon is also observed in the
8
b
2
allylic alkylations. Consistent with C(sp )−H bond activation
for ligand 1b, it is likely that the active catalytic species of
2
iridium complex is generated through C(sp )−H bond
3
activation in ligand 1d rather than C(sp )−H bond activation.
To verify this hypothesis, π-allyl−iridium complex K1 was
6c,d
synthesized according to a one-pot procedure developed by
Helmchen and co-workers (Scheme 4). This complex was
Scheme 4. Preparation and X-ray Structure of the (π-Allyl)−
Ir−1d Complex K1
a
Reaction conditions: [Ir(COD)Cl] (2.5 mol %), ligand 1 (5.0 mol
2
%), 2 (100 mol %), and 3 (200 mol %) in THF at 50 °C unless noted
otherwise. The top results are from ligand 1d (black), while the
b
1
bottom results are from ligand 1a (blue). Determined by H NMR of
c
d
the crude reaction mixture. Isolated yield. ee of 4 was determined by
HPLC analysis. [Ir(COD)Cl] (5.0 mol %) and ligand 1 (10.0 mol
) were used. 2-Bromocinnamyl ethyl carbonate was used as the
substrate, and ent-1a was used as the ligand; see ref 7i. ent-1a was
e
2
f
%
g
obtained as a mixture of endo and exo isomers in a ratio of
2
used as the ligand; see ref 2c.
92:8. The C(sp )−H bond activation was confirmed
unambiguously by an X-ray crystallographic analysis of a crystal
10
of K1.
moderate ee values (8−60% ee) except for the non-ortho-
substituted 4g (95% ee), excellent enantioselectivity (90−
Synthetic Application. Plavix (7) is an antiplatelet
medication which is used in the prevention of blood clotting
as well as reducing the risk of heart attack and stroke.
Compound 8 displays antithrombotic and anti-blood-platelet-
99.9% ee) was obtained for the amination process with
11
cinnamyl carbonates having varying substituents (H, OMe, Me,
Cl, Br) at the ortho position of the phenyl group by ligand 1d.
In addition to the significant increase in enantioselectivity, the
yields of products could be improved in most cases.
Finally, benzylamine and 2-vinylaniline were also proven to
be suitable nucleophiles. The reactions with 2-methoxy
cinnamyl methyl carbonate proceeded smoothly, leading to
the desired products 4l,m in better yields (85 and 80%,
respectively) and ee value (97% and 88% ee, respectively) by
utilizing ligand 1d in comparison with ligand 1a (77% and 11%
yields and 76% and 29% ee, respectively; Scheme 2).
12
aggregating activities. As shown in Scheme 5, the reaction (or
allylic alkylation, since we are talking about 3b) of commercially
available 3b with 2-chloro cinnamyl methyl carbonate
proceeded smoothly under the optimized conditions, delivering
the desired product 4n in 86% yield and 98% ee. Attempts to
Scheme 5. Transformation
In order to demonstrate the robustness and practicality of the
current method, a gram-scale reaction was carried out. The
allylic amination reaction between aniline and 2-methoxy
cinnamyl methyl carbonate was performed on a 5.0 mmol scale
to give product 4a in 85% yield and 97% ee (Scheme 3).
Preparation of the π-Allyl−Iridium Complex. Evalua-
tion of the substrate scope led to the observation that the
C
DOI: 10.1021/acs.organomet.6b00339
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Organometallics
Article
convert 4n to Plavix under various oxidation conditions have
failed so far. Subjecting compound 4n (98% ee) to a
Compound (R)-4d. Yellow oil, 30.3 mg, 79% yield, 86% ee (Daicel
Chiralcel OJ-H (0.46 cm × 15 cm), n-hexane/2-propanol 80/20, v =
1
3
−1
0
.5 mL min , λ 230 nm, t(minor) = 22.04 min, t(major) = 25.13
Pd(OH) /C-catalyzed hydrogenation reaction afforded com-
2
20
1
min); [α]D = −64.9 (c = 1.0, CHCl ). H NMR (400 MHz, CDCl ):
3
3
pound 8 in 94% yield and 97% ee.
δ 4.05 (br s, 1H, NH), 5.21 (br s, 1H, CH), 5.25−5.38 (m, 2H, CH ),
2
3
3
3
6
.06 (ddd, J
= 6.0, J
H−H
= 10.4, J
= 17.2 Hz, 1H, CH), 6.65
H−H
H−H
H−H
4
3
CONCLUSION
(dd, J
= 1.2, J
= 8.8 Hz, 2H, Ar-H), 6.71−6.75 (m, 1H, Ar-
■
H−H
H), 6.96−7.01 (m, 2H, Ar-H), 7.14−7.18 (m, 2H, Ar-H), 7.22 (dd, J =
In conclusion, various N-aryl phosphoramidite ligands were
synthesized and demonstrated to be superior to the Feringa
ligands in Ir-catalyzed allylic amination reactions, especially
when ortho-substituted cinnamyl carbonates were used. High
to excellent regio- and enantioselectivities could be achieved for
several nitrogen-containing nucleophiles, including aniline,
indoline, benzylamine, and 2-vinylaniline. X-ray analysis of a
4
3
13
1
J
= 1.6, J
= 5.2 Hz, 1H, Ar-H). C{ H} NMR (100 MHz,
H−H
H−H
CDCl ): δ 56.3, 113.7, 116.5, 118.1, 124.6, 124.7, 126.9, 129.1, 138.2,
3
−1
1
1
6
46.3, 146.7. IR (thin film): νmax (cm ) 3663, 3401, 2969, 2903, 1599,
500, 1428, 1312, 1256, 1228, 1179, 1068, 1038, 991, 926, 795, 748,
+
+
90. MS-EI: 215 [M] . HRMS-EI: m/z [M] calcd for C H NS
1
3
13
+
(M ), 215.0769; found, 215.0772.
1
4
Compound (R)-4e. Yellow oil, 48.6 mg, 85% yield, 87% ee
(
π-allyl)−iridium complex revealed that the active Ir complex is
(Daicel Chiralpak AD-H (0.46 cm × 25 cm), n-hexane/2-propanol
−
1
2
9
8
8/2, v = 1.0 mL min , λ 230 nm, t(major) = 7.85 min, t(minor) =
formed via a C(sp )−H activation.
.36 min); [α]D20 = +1.5 (c = 1.0, CHCl ). H NMR (300 MHz,
CDCl ): δ 4.01 (br s, 1H, NH), 4.89 (d, J
5.22 (d, JH−H = 11.1 Hz, 1H, CH ), 5.23 (d, JH−H = 17.1 Hz, 1H,
1
3
3
= 5.7 Hz, 1H, CH),
3
H−H
EXPERIMENTAL SECTION
General Procedure for Ir-Catalyzed Allylic Amination
Reaction. In a dry Schlenk tube filled with argon, [Ir(COD)Cl]
3
3
■
2
3
3
3
CH
6.55 (d, J
H), 7.13 (t, J
Ar-H), 7.46 (d, J
), 6.00 (ddd, JH−H = 6.0, JH−H = 9.9, JH−H = 16.8 Hz, 1H, CH),
2
3
3
= 7.8 Hz, 2H, Ar-H), 6.70 (t, J
= 7.5 Hz, 1H, Ar-
= 8.1 Hz, 2H,
H−H
2
H−H
H−H
3
3
(
0
3.3 mg, 0.005 mmol, 2.5 mol %), phosphoramidite ligand 1d (6.1 mg,
.01 mmol, 5 mol %), and propylamine (0.5 mL) were dissolved in
= 7.8 Hz, 2H, Ar-H), 7.25 (d, J
H−H
3
= 8.4 Hz, 2H, Ar-H).
H−H
14
THF (0.5 mL). The reaction mixture was heated to 50 °C for 30 min
and then the volatile solvents were removed in vacuum to give a yellow
solid. In this tube, allylic carbonate 2 (0.20 mmol) and amine 3 (0.4
mmol, 2 equiv) were added and stirred at 50 °C until the reaction was
complete. The solvent was evaporated and the regioselectivity (4/5)
Compound (R)-4f. Yellow oil, 35.1 mg, 80% yield, 90% ee
(Daicel Chiralcel OD-H (0.46 cm × 25 cm), n-hexane/2-propanol
−1
100/1, v = 0.5 mL min , λ 214 nm, t(major) = 31.78 min, t(minor) =
37.58 min); [α]D20 = +18.1 (c = 1.0, CHCl ). H NMR (300 MHz,
1
3
3
CDCl ): δ 3.79 (s, 3H, OCH ), 3.98 (br s, 1H, NH), 4.88 (d, J
=
=
3
3
H−H
1
3
3
was determined by H NMR of the crude reaction mixture. The
5.1 Hz, 1H, CH), 5.21 (d, J
18.3 Hz, 1H, CH ), 6.01 (ddd, J
Hz, 1H, CH), 6.59 (d, J
Hz, 1H, Ar-H), 6.88 (d, J
= 11.4 Hz, 1H, CH ), 5.26 (d, J
H−H 2
H−H
3
3
3
residue was purified by silica gel column chromatography using PE/EA
as the eluent to give desired product 4.
Compound (R)-4a. Yellow oil, 37.7 mg, 88% yield, 97% ee (Daicel
= 6.0, J
= 10.2, J
= 16.8
= 7.2
H−H
2
H−H
H−H
H−H
3
3
= 8.1 Hz, 2H, Ar-H), 6.68 (t, J
= 8.7 Hz, 2H, Ar-H), 7.13 (d, J
= 9.0 Hz, 2H, Ar-H).
Compound (R)-4g. Yellow oil, 44.3 mg, 94% yield, 90% ee
H−H
3
3
=
H−H
H−H
3
Chiralcel OD-H (0.46 cm × 25 cm), n-hexane/2-propanol 98/2, v =
7.5 Hz, 2H, Ar-H), 7.29 (d, J
H−H
−
1
15
0
.8 mL min , λ 230 nm, t(major) = 7.64 min, t(minor) = 8.56 min);
1
[
(
α]D23 = +26.0 (c = 1.0, CHCl ). H NMR (400 MHz, CDCl ): δ 3.86
(Agilent 1260 Infinity Analytical SFC system, Daicel Chiralpak IC
3
3
−
1
s, 3H, OCH ), 4.20 (br s, 1H, NH), 5.14−5.24 (m, 2H, CH ), 5.33
(0.46 cm × 15 cm), CO /2-propanol 95/5, v = 1.3 mL min , λ 214
3
2
2
3
3
3
23
(
d, J
= 5.2 Hz, 1H, CH), 6.07 (ddd, J
= 5.6, J = 10.4,
= 10.0 Hz, 2H, Ar-H), 6.66
nm, t(major) = 6.56 min, t(minor) = 6.90 min); [α]D = +33.9 (c =
H−H
H−H
H−H
3
3
1
3
J
= 17.2 Hz, 1H, CH), 6.60 (d, J
= 8.4 Hz, 1H, Ar-H), 6.89−6.94 (m, 2H, Ar-H), 7.10−7.14
m, 2H, Ar-H), 7.24 (dt, J
1.0, CHCl ). H NMR (400 MHz, CDCl ): δ 2.95 (t, J
= 8.8 Hz,
H−H
H−H
3
3
H−H
3
3
(
(
(
t, J
2H, CH
2
), 3.30−3.40 (m, 2H, CH ), 4.96 (d, JH−H = 7.6 Hz, 1H,
2
H−H
4
3
= 2.0, J
= 7.6 Hz, 1H, Ar-H), 7.31
= 7.6 Hz, 1H, Ar-H). C{ H} NMR (75 MHz,
CH), 5.28−5.32 (m, 2H, CH ), 6.05−6.14 (m, 1H, CH), 6.30 (d,
2
H−H
H−H
4
3
13
1
3
3
dd, J
= 1.6, J
JH−H = 8.0 Hz, 1H, Ar-H), 6.62 (t, JH−H = 7.2 Hz, 1H, Ar-H), 6.95 (t,
H−H
H−H
3J
= 7.6 Hz, 1H, Ar-H), 7.06 (dd, J
4
= 0.8, J
3
= 7.2 Hz, 1H,
= 7.2 Hz, 2H, Ar-H),
CDCl ): δ 54.6, 55.4, 110.7, 113.4, 115.1, 117.3, 120.8, 127.7, 128.4,
3
H−H
H−H
H−H
−
1
3
1
3
1
+
29.0, 129.7, 138.6, 147.3, 156.8. IR (thin film): νmax (cm ) 3409,
050, 2836, 1599, 1500, 1462, 1436, 1314, 1238, 1179, 1089, 1049,
026, 992, 922, 870, 746, 691. HRMS (ESI): calcd for C H NO [M
Ar-H), 7.25−7.29 (m, 1H, Ar-H), 7.34 (t, J
H−H
3
7.42 (d, J
= 8.8 Hz, 2H, Ar-H).
H−H
16
18
Compound (R)-4h. Yellow oil, 52.0 mg, 98% yield, > 99.9% ee
+
H] , 240.1383; found, 240.1374.
Compound (R)-4b. Yellow oil, 37.2 mg, 80% yield, 93% ee (Daicel
Chiralpak AD-H (0.46 cm × 25 cm), n-hexane/2-propanol 100/1, v =
(Daicel Chiralcel OD-H (0.46 cm × 25 cm), n-hexane/2-propanol
−1
1000/1, v = 1.0 mL min , λ 230 nm, t(minor) = 18.35 min, t(major)
= 23.89 min); [α]D20 = +35.9 (c = 1.0, CHCl ). H NMR (300 MHz,
1
3
−
1
0
.5 mL min , λ 214 nm, t(major) = 15.53 min, t(minor) = 16.78
min); [α]D = −6.5 (c = 1.0, CHCl ). H NMR (300 MHz, CDCl ):
δ 2.38 (s, 3H, CH ), 3.95 (br s, 1H, NH), 5.09 (d, J
CH), 5.23 (d, J
CH), 6.04 (ddd, J
.55 (d, J
CDCl ): δ 2.88−2.94 (m, 2H, CH ), 3.23−3.42 (m, 2H, CH ), 3.79
3
2
2
2
0
1
3
3
3
(s, 3H, OCH ), 5.19−5.28 (m, 2H, CH ), 5.42 (d, J = 6.3 Hz, 1H,
H−H
CH), 6.05 (ddd, J
6.38 (d, J
H), 6.90 (t, J
Ar-H), 7.02 (d, J
7.38 (dd, J
3
2
3
3
3
3
= 4.8 Hz, 1H,
= 9.0 Hz, 1H,
= 16.2 Hz, 1H, CH),
= 6.6, J
= 10.2, J
= 7.8 Hz, 1H, Ar-H), 6.57 (t, J
= 17.1 Hz, 1H, CH),
= 7.2 Hz, 1H, Ar-
H−H
3
H−H
H−H
H−H
H−H
3
3
3
3
= 18.3 Hz, 1H, CH ), 5.25 (d, J
H−H
2
H−H
H−H
3
3
3
3
3
= 5.1, J
= 10.2, J
= 7.5 Hz, 2H, Ar-H), 6.68 (t, J
= 8.7 Hz, 2H, Ar-H), 6.95 (t, J
= 8.7 Hz, 1H,
H−H
H−H
H−H
H−H
H−H
3
3
3
6
= 7.2 Hz, 1H, Ar-
= 7.5 Hz, 1H, Ar-H), 7.20−7.27 (m, 1H, Ar-H),
H−H
3 13 1
H−H
H−H
1
3
1
4
H), 7.10−7.19 (m, 5H, Ar-H), 7.36−7.40 (m, 1H, Ar-H). C{ H}
NMR (75 MHz, CDCl ): δ 19.2, 56.9, 113.1, 116.4, 117.4, 126.4,
= 1.5, J
= 7.8 Hz, 1H, Ar-H). C{ H} NMR (75
H−H
H−H
3
MHz, CDCl ): δ 28.3, 50.2, 55.5, 57.1, 107.6, 110.7, 116.3, 116.8,
3
1
26.5, 127.3, 129.1, 130.6, 136.0, 137.8, 139.4, 147.3. IR (thin film):
120.4, 124.0, 127.0, 128.3, 128.6, 128.9, 129.9, 136.6, 151.8, 157.0. IR
−1
−1
νmax (cm ) 3410, 3051, 3020, 2962, 2920, 2852, 1602, 1502, 1461,
(thin film): νmax (cm ) 2836, 1677, 1603, 1488, 1460, 1242, 1159,
1
428, 1316, 1261, 1090, 1019, 926, 868, 799, 749, 727, 692. HRMS
1107, 1050, 1026, 922, 741, 685. HRMS (ESI): calcd for C H NO
1
8
20
+
+
(
ESI): calcd for C H N [M + H] , 224.1434; found, 224.1430.
[M + H] , 266.1539; found, 266.1541.
16
18
7
i
Compound (R)-4c. Yellow oil, 50.2 mg, 86% yield, 96% ee
Compound (R)-4i. Yellow oil, 44.1 mg, 75% yield, 94% ee (Daicel
(
9
6
Daicel Chiralpak AD-H (0.46 cm × 25 cm), n-hexane/2-propanol
Chiralcel OD-H (0.46 cm × 25 cm), n-hexane/2-propanol 98/2, v =
−1
−1
8/2, v = 1.0 mL min , λ 220 nm, t(major) = 5.64 min, t(minor) =
0.5 mL min , λ 214 nm, t(minor) = 12.70 min, t(major) = 13.88
.94 min); [α]D20 = −87.2 (c = 1.0, CHCl ). H NMR (400 MHz,
1
23
1
3
min); [α]D = +64.2 (c = 1.0, CHCl ). H NMR (300 MHz, CDCl ):
3
3
3
CDCl ): δ 3.23 (br s, 1H, NH), 5.19−5.26 (m, 2H, CH ), 5.40 (d,
δ 2.35 (s, 3H, CH ), 2.93 (t, J
1H, CH ), 3.29−3.38 (m, 1H, CH ), 5.07 (d, J = 6.6 Hz, 1H,
CH), 5.23 (d, J
1H, CH ), 6.05 (ddd, J
CH), 6.24 (d, J
= 8.7 Hz, 2H, CH ), 3.15−3.23 (m,
H−H
3
3
2
3
2
3
3
3
3
J
= 6.0 Hz, 1H, CH), 6.04 (ddd, J
= 5.6, J
= 10.4, J
= 9.6 Hz, 2H, Ar-H), 6.67−6.70
H−H
H−H
H−H
H−H
2
2
H−H
3
3
3
=
17.2 Hz, 1H, CH), 6.54 (d, J
= 17.1 Hz, 1H, CH ), 5.26 (d, J
= 10.2 Hz,
H−H
H−H
2
H−H
3
3
3
(
m, 1H, Ar-H), 7.10−7.14 (m, 2H, Ar-H), 7.19−7.23 (m, 2H, Ar-H),
= 6.9, J
= 10.2, J
= 17.1 Hz, 1H,
= 7.5 Hz, 1H,
2
H−H
H−H
H−H
3
3
7
.37−7.40 (m, 1H, Ar-H), 7.43−7.46 (m, 1H, Ar-H).
= 8.1 Hz, 1H, Ar-H), 6.60 (t, J
H−H H−H
D
DOI: 10.1021/acs.organomet.6b00339
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Ar-H), 6.95 (t, 3JH−H = 7.8 Hz, 1H, Ar-H), 7.04 (d, 3JH−H = 6.9 Hz,
1H, CH ), 3.69 (d, J
2
= 14.7 Hz, 1H, CH ), 4.48 (d, J
3
= 9.0
2
H−H
2
H−H
2
3
1
H, Ar-H), 7.18−7.19 (m, 3H, Ar-H), 7.41−7.44 (m, 1H, Ar-H).
Hz, 1H, CH), 5.10 (dd, J
(dd, JH−H = 0.6, JH−H = 17.1 Hz, 1H, CH ), 5.82 (ddd, JH−H = 9.0,
JH−H = 9.6, JH−H = 17.1 Hz, 1H, CH), 6.65 (d, JH−H = 5.1 Hz, 1H,
Ar-H), 7.01 (d, JH−H = 5.1 Hz, 1H, Ar-H), 7.12 (dt, JH−H = 1.5, JH−H
= 1.2, J
= 9.9 Hz, 1H, CH ), 5.39
H−H
H−H 2
1
3
1
2
3
3
C{ H} NMR (75 MHz, CDCl ): δ 19.3, 28.2, 50.0, 60.8, 107.2,
2
3
3
3
3
1
1
1
6
2
16.99, 117.03, 124.2, 126.0, 127.1, 127.2, 127.6, 130.0, 130.5, 135.4,
36.6, 138.6, 151.5. IR (thin film): νmax (cm ) 3022, 2845, 1748,
−
1
3
4
3
3
639, 1605, 1485, 1458, 1332, 1260, 1158, 1024, 996, 921, 873, 740,
= 7.5 Hz, 1H, Ar-H), 7.23 (t, JH−H = 7.5 Hz, 1H, Ar-H), 7.33 (dd,
+
4
3
4
3
40. HRMS (ESI): calcd for C H N [M + H] , 250.1590; found,
JH−H = 1.2, JH−H = 7.8 Hz, 1H, Ar-H), 7.65 (dd, JH−H = 1.5, JH−H =
18
20
1
3
1
50.1584.
Compound (R)-4j. Yellow oil, 49.2 mg, 94% yield, 97% ee (Daicel
Chiralcel OJ-H (0.46 cm × 25 cm), n-hexane/2-propanol 98/2, v = 0.5
7.8 Hz, 1H, Ar-H). C{ H} NMR (75 MHz, CDCl ): δ 25.4, 48.6,
3
51.5, 68.7, 116.7, 122.5, 125.3, 127.2, 127.9, 128.8, 129.6, 133.4, 133.6,
133.9, 138.9, 139.3. IR (thin film): νmax (cm ) 3065, 2962, 2922,
2843, 1638, 2808, 2760, 1592, 1469, 1435, 1369, 1341, 1320, 1299,
1260, 1172, 1096, 1080, 1048, 1033, 1013, 923, 799, 756, 734, 702,
673. HRMS (ESI): calcd for C16
290.0754.
−1
−1
mL min , λ 214 nm, t(major) = 17.54 min, t(minor) = 22.71 min);
2
0
1
[
(
(
α] = −22.0 (c = 1.0, CHCl ). H NMR (300 MHz, CDCl ): δ 2.96
D
3
3
3
+
t, J
= 8.1 Hz, 2H, CH ), 3.35−3.41 (m, 2H, CH ), 5.24−5.31
H
17ClNS [M + H] , 290.0765; found,
H−H
2
2
3
3
3
m, 3H, CH and CH ), 6.00 (ddd, J
= 6.9, J
= 10.2, J
= 8.1 Hz, 1H, Ar-H), 6.61 (t, J
=
2
H−H
H−H
H−H
3
3
1
=
7.4 Hz, 1H, CH), 6.22 (d, J
7.5 Hz, 1H, Ar-H), 6.94 (t, J
General Procedure for the Preparation of (π-Allyl)−Ir
H−H
H−H
3
Complex K1. In a flame-dried Schlenk tube were placed a solution
= 7.5 Hz, 1H, Ar-H), 7.05 (d,
H−H
3
of [Ir(COD)Cl] (203.8 mg, 0.3 mmol) and ligand 1d (378.9 mg, 0.6
JH−H = 6.9 Hz, 1H, Ar-H), 7.18−7.27 (m, 2H, Ar-H), 7.38−7.41 (m,
2
13
1
mmol) in dry THF (20 mL) under an argon atmosphere. After the
mixture was stirred for 30 min at room temperature, AgOTf (157.6
mg, 0.6 mmol) and allyl methyl carbonate (168.8 mg, 1.5 mmol) were
added subsequently, and the reaction mixture was stirred overnight to
afford a pale suspension. The precipitate was filtered, and the solvents
were removed under reduced pressure. The residue was washed with
diethyl ether (10 mL × 3) to give (π-allyl)−Ir complex K1 (284.8 mg,
1
H, Ar-H), 7.52−7.55 (m, 1H, Ar-H). C{ H} NMR (75 MHz,
CDCl ): δ 28.3, 50.9, 61.5, 107.7, 117.5, 117.7, 124.2, 127.0, 127.1,
3
1
28.5, 129.2, 129.8, 130.0, 133.7, 135.3, 138.3, 151.4. IR (thin film):
−1
νmax (cm ) 2962, 2847, 1606, 1486, 1441, 1261, 1089, 1025, 928, 871,
+
7
99, 745. HRMS (ESI): calcd for C H ClN [M + H] , 270.1044;
17 17
found, 270.1037.
Compound (R)-4k. Yellow oil, 67.5 mg, 91% yield, 93% ee (Daicel
8
5%) as a pale yellow powder, existing as two isomers in a ratio of 92/
Chiralcel OJ-H (0.46 cm × 25 cm), n-hexane/2-propanol 98/2, v = 0.5
3
1
−1
8 as determined by P NMR.
mL min , λ 214 nm, t(major) = 18.29 min, t(minor) = 22.71 min);
2
0
1
Full details can be found in the Supporting Information.
[
(
(
α] = −20.6 (c = 1.0, CHCl ). H NMR (300 MHz, CDCl ): δ 2.97
D
3
3
3
t, J
= 7.8 Hz, 2H, CH ), 3.35−3.42 (m, 2H, CH ), 5.24−5.33
H−H
2
2
3
3
3
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.6b00339.
m, 3H, CH and CH ), 5.99 (ddd, J
7.4 Hz, 1H, CH), 6.21 (d, J
7.5 Hz, 1H, Ar-H), 6.94 (t, J
= 7.2, J
= 10.5, J
= 7.8 Hz, 1H, Ar-H), 6.62 (t, J
=
■
2
H−H
H−H
H−H
3
3
1
*
S
H−H
H−H
3
=
= 8.1 Hz, 1H, Ar-H), 7.06 (d,
H−H
3
3
JH−H = 7.2 Hz, 1H, Ar-H), 7.11−7.17 (m, 1H, Ar-H), 7.29 (t, J
=
H−H
3
3
7
=
.5 Hz, 1H, Ar-H), 7.54 (d, J
= 7.8 Hz, 1H, Ar-H), 7.60 (d, J
H−H
H−H
8.1 Hz, 1H, Ar-H). 13C{ H} NMR (75 MHz, CDCl ): δ 28.3, 50.9,
1
3
Experimental procedures and analysis data for all new
compounds (PDF)
Crystallographic data (CIF)
6
1
2
8
3
1.5, 107.7, 117.5, 117.7, 124.2, 127.0, 127.1, 128.5, 129.2, 129.8,
30.0, 133.7, 135.3, 138.3, 151.4. IR (thin film): νmax (cm ) 3049,
−
1
843, 1639, 1605, 1566, 1485, 1437, 1333, 1259, 1158, 1022, 994, 925,
+
72, 807, 741, 643. HRMS (ESI): calcd for C H BrN [M + H] ,
17
17
14.0539; found, 314.0532.
AUTHOR INFORMATION
Corresponding Author
*E-mail for S.-L.Y.: slyou@sioc.ac.cn.
2
c
■
Compound (R)-4l. Yellow oil, 43.2 mg, 85% yield, 97% ee
(
Phenomenex Lu × 5u Amylose-2 (0.46 cm × 25 cm), n-hexane/2-
−1
propanol 85/15, v = 0.5 mL min , λ 230 nm, t(minor) = 9.63 min,
t(major) = 10.20 min); [α]D20 = −1.5 (c = 1.0, CHCl ). H NMR
1
Notes
3
(
3
300 MHz, CDCl ): δ 1.96 (br s, 1H, NH), 3.66−3.76 (m, 2H, CH ),
The authors declare no competing financial interest.
3
2
3
3
.80 (s, 3H, OCH ), 4.58 (d, J
= 6.6 Hz, 1H, CH), 5.11 (d, J
3
H−H H−H
3
=
9.6 Hz, 1H, CH ), 5.21 (d, J
= 17.1 Hz, 1H, CH ), 6.03 (ddd,
ACKNOWLEDGMENTS
We thank the National Basic Research Program of China
2016YFA0202900, 2015CB856600), the National Natural
Science Foundation of China (21332009, 21421091,
1572252), and the Chinese Academy of Sciences for generous
2
H−H
2
■
(
3
3
3
3
JH−H = 6.9, J
= 10.5, J
= 17.1 Hz, 1H, CH), 6.87 (d, J
=
H−H
H−H
H−H
3
7
7
.8 Hz, 1H, Ar-H), 6.95 (t, JH−H = 7.2 Hz, 1H, Ar-H), 7.21−7.36 (m,
H, Ar-H).
Compound (R)-4m. Yellow oil, 47.3 mg, 80% yield, 88% ee
2
(
5
Daicel Chiralcel OJ-H (0.46 cm × 25 cm), n-hexane/2-propanol 95/
−1
financial support.
, v = 1.0 mL min , λ 220 nm, t(minor) = 6.85 min, t(major) = 7.65
2
0
1
min); [α]D = −38.5 (c = 1.0, CHCl ). H NMR (300 MHz, CDCl ):
3
3
3
REFERENCES
δ 3.85 (s, 3H, OCH ), 4.43 (br s, 1H, NH), 5.15 (d, J
H, CH ), 5.20 (d, J
CH and CH ), 5.62 (d, J
= 10.2, J
H, Ar-H), 6.67 (t, J
H), 7.06 (t, J
= 10.5 Hz,
3
H−H
■
3
1
= 18.0 Hz, 1H, CH ), 5.30−5.37 (m, 2H,
= 17.1 Hz, 1H, CH ), 6.08 (ddd, J
= 16.8 Hz, 1H, CH), 6.55 (d, J
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2
H−H
2
̈
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3
3
=
2
H−H
2
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3
3
3
5
1
.4, J
= 8.1 Hz,
H−H
H−H
H−H
3
= 7.2 Hz, 1H, Ar-H), 6.77−6.94 (m, 3H, Ar-
= 7.5 Hz, 1H, Ar-H), 7.21−7.30 (m, 3H, Ar-H).
H−H
3
H−H
1
3
1
C{ H} NMR (75 MHz, CDCl ): δ 54.8, 55.4, 110.8, 112.1, 115.1,
3
1
1
1
16.1, 117.2, 120.9, 124.3, 127.3, 127.7, 128.4, 128.7, 129.6, 133.1,
38.6, 144.2, 156.8. IR (thin film): νmax (cm ) 2963, 1600, 1489,
−
1
456, 1261, 1095, 1023, 917, 799, 748. HRMS (ESI): calcd for
+
C H NO [M + H] , 266.1539; found, 266.1536.
1
8
20
Compound (R)-4n. Colorless oil, 499.3 mg, 86% yield, 98% ee
(
2
1
Daicel Chiralcel OJ-H (0.46 cm × 25 cm), n-hexane/2-propanol 98/
−1
, v = 0.5 mL min , λ 230 nm, t(minor) = 15.92 min, t(major) =
7.96 min); [α]D15 = −41.3 (c = 1.0, CHCl ). H NMR (300 MHz,
1
(2) For selected examples, see: (a) Bartels, B.; Helmchen, G. Chem.
Commun. 1999, 741−742. (b) Fuji, K.; Kinoshita, N.; Kawabata, T.;
3
2
CDCl ): δ 2.75−2.89 (m, 4H, CH CH ), 3.43 (d, J
= 14.7 Hz,
3
2
2
H−H
E
DOI: 10.1021/acs.organomet.6b00339
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
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(
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2
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(
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́
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́
(
4
(
(
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́
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DOI: 10.1021/acs.organomet.6b00339
Organometallics XXXX, XXX, XXX−XXX