Highly regioselective allylic substitution reactions catalyzed by an air-stable (π-Allyl)iridium complex derived from dinaphthocyclooctatetraene and a phosphoramidite ligand

Article abstract of DOI:10.1055/s-0033-1339187

An air-stable (π-allyl)iridium complex derived from dinaphthocyclooctatetraene and a phosphoramidite ligand has been synthesized and found to be highly efficient in iridium-catalyzed allylic substitution reactions. This catalyst features excellent regiose

Full text of DOI:10.1055/s-0033-1339187

SPECIAL TOPIC
▌2109
special topic
Highly Regioselective Allylic Substitution Reactions Catalyzed by an
Air-Stable (π-Allyl)iridium Complex Derived from Dinaphthocyclooctatetraene
and a Phosphoramidite Ligand
Iridium-Catalyzed Allylic Substitution Reactions
Ke-Yin Ye, Zhuo-An Zhao, Zeng-Wei Lai, Li-Xin Dai, Shu-Li You*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu,
Shanghai 200032, P. R. of China
Fax +86(21)54925087; E-mail: slyou@sioc.ac.cn
Received: 28.04.2013; Accepted after revision: 16.05.2013
By taking the advantage of strong binding affinity to irid-
Abstract: An air-stable (π-allyl)iridium complex derived from di-
ium of dibenzo[a,e]cyclooctatetraene (dbcot),5 Helmchen
naphthocyclooctatetraene and a phosphoramidite ligand has been
and co-workers developed a modified catalyst derived
from [Ir(dbcot)Cl]2 and a phosphoramidite ligand and
synthesized and found to be highly efficient in iridium-catalyzed al-
lylic substitution reactions. This catalyst features excellent regiose-
lectivity and high stability. When NaCH(CO2Me)2 was used as the found the resulting catalyst could enable the reaction be-
ing run under air or in the presence of water.6,7 As part of
nucleophile, the catalyst loading in allylic alkylation reactions can
be as low as 0.01 mol%.
our ongoing research interest on Ir-catalyzed allylic sub-
stitution reactions,8 we envisaged that [Ir(dncot)Cl]2, pre-
Key words: (π-allyl)iridium complex, allylic substitution, enantio-
selectivity, regioselectivity, dinaphthocyclooctatetraene
pared from dinaphthocyclooctatetraene (dncot), might be
a good precursor given the strong binding of dncot with
iridium. Herein, we report our results on allylic substitu-
Transition metal-catalyzed allylic substitution reactions tion reactions using a well-defined (π-allyl)Ir complex de-
represent one of the most powerful methods to construct rived from [Ir(dncot)Cl]2 and a phosphoramidite ligand.
C–C and C–X (X = N, O, S, etc.) bonds.1 Among the var-
Catalyst preparation is of crucial importance for Ir-cata-
ious metals used, iridium catalyst features invariably high
lyzed allylic substitution reaction for ligands that undergo
regio- and enantioselectivity control with a broad scope of
C–H activation at the Me or aryl group generating the cy-
monosubstituted substrates.2,3 The bulk of the work on Ir-
clometalated iridium intermediate. Certain additives
catalyzed allylic substitution reactions focused on cata-
lysts derived from [Ir(cod)Cl]2 and a phosphoramidite li-
(such as TBD,9 n-propylamine,10 DABCO,10 DBU,11 etc.)
have been used to induce the formation of the active cata-
gand, which consists of a cyclometalated iridium-
lyst by C–H activation. The air-sensitive character of this
phosphoramidite core chelated by cycloocta-1,5-diene
intermediate makes the preactivation process inconve-
(cod). In general, the reaction catalyzed by these air-sen-
nient. The mechanistic studies revealed that the cyclo-
sitive iridium intermediates should be performed under an
metalated iridium-phosphoramidite complex is the active
inert atmosphere in anhydrous solvents. In addition, the
catalytic species in Ir-catalyzed allylic substitution reac-
catalyst loading of the known Ir-catalytic system is far
tions.12 Helmchen and co-workers have demonstrated that
from satisfactory in the industrial viewpoint as generally
the corresponding isolated (π-allyl)Ir complex exhibited
much higher catalytic activity than the catalyst prepared in
more than 4 mol% Ir precatalyst was employed. This cat-
alyst system also suffers from low regioselectivity with
situ in Ir-catalyzed allylic hydroxylation reaction.7d The
certain allylic substrates such as 1f–i (Scheme 1).4
direct use of (π-allyl)Ir complex as catalyst precursor
would greatly simplify the operation procedure.
BnNH2 (2a)
NaCH(CO2Me)2 (2b)
Nu
OCO2Me
+
R
Nu
1a, R = Ph
R
[Ir(diene)Cl]2/L
R
1b, R = 4-MeOC6H4
1c, R = 3-MeOC6H4
1d, R = 4-BrC6H4
1e, R = 4-ClC6H4
1
3
4
1f, R = CH2CH2Ph
1g, R = CH2OSiPh2t-Bu
1h, R = CH2OCPh3
1i, R = CH2CH2OCPh3
cod
dbcot
dncot
Scheme 1 Ir-catalyzed allylic substitutions
SYNTHESIS 2013, 45, 2109–2114
Advanced online publication: 24.06.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1339187; Art ID: SS-2013-C0317-ST
© Georg Thieme Verlag Stuttgart · New York

2110
K.-Y. Ye et al.
SPECIAL TOPIC
+
OTf–
1
/2 [Ir(dncot)Cl]2
AgOTf
+
O
OCO2Me
THF, r.t.
Ir
O
P
N
Ar
O
P
N
R
R
O
Ar
(S,S,Sa)-L1, Ar = Ph
(S,S,Sa)-L2, Ar = 2-MeOC6H4
C1, R = H, 85%
C2, R = OMe, 87%
Scheme 2 Preparation of (π-allyl)Ir complexes
The dncot ligand can be conveniently synthesized in with NaCH(CO2Me)2 prompted us to further explore the
gram-scale via a [2+2+2+2] cycloaddition of diynes de- lower catalyst loading. It was found that good results
veloped by Wender and co-workers.13 The preparation of could also be obtained with 0.1 mol% catalyst in four
[Ir(dncot)Cl]2 is also straightforward following the known hours (Table 1, entry 11). No deleterious effect of regio-
procedure.13c The (π-allyl)Ir complexes C1 and C2 can be and enantioselectivities was observed even with 0.01
directly synthesized using a one-pot procedure developed mol% catalyst although a longer reaction time was needed
by Helmchen and co-workers,12b as depicted in Scheme 2. and a lower yield resulted (entry 12).
Similar to [Ir(dbcot)Cl]2, the (π-allyl)Ir complexes de-
rived from [Ir(dncot)Cl]2 could be subjected to silica gel
Table 1 Ir-Catalyzed Allylic Substitution Reactionsa
column chromatography for purification. These complex-
Entry Cat.
1
2
Temp Time Product Ratio of ee
(°C) (h)
es are not sensitive to oxygen and moisture. They could be
stored under ambient atmosphere for more than six
months without detectable loss of catalytic activity.
Yield (%)b 3/4c
(%)d
1e C1
1e C2
1a
1a
1a
1a
1a
1b
1c
1d
1e
1a
1a
1a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
r.t.
r.t.
r.t.
50
50
50
50
50
50
50
50
50
24
24
48
24
24
24
24
24
24
1
3aa 82
3aa 90
3aa 86
3aa 90
3aa 89
3ab 88
3ac 93
3ad 95
3ae 81
3ba 91
3ba 86
3ba 52
>97:3
94
98
98
98
98
96
96
97
95
98
98
97
With these (π-allyl)Ir complexes in hand, their catalytic
performance in allylic substitution reactions was exam-
ined next. With 2 mol% catalyst loading, the reaction of
BnNH2 with cinnamyl methyl carbonate occurred
smoothly at room temperature furnishing the allylic ami-
nation products with excellent regio- and enantioselectiv-
ities (Table 1, entries 1, 2). The reaction with (π-allyl)Ir
complex C2 provided higher yield and ee (90% yield,
3aa/4aa >97:3, 98% ee for 3aa). Prolonged reaction time
was needed in the presence of 1 mol% catalyst and the re-
action time could be shortened by running the reaction at
50 °C without decrease of enantioselectivity (entries 3, 4).
The reaction with the new catalyst was generally slower
than those with [Ir(cod)Cl]2 and [Ir(dbcot)Cl]2 probably
due to the steric hindrance and strong binding affinity to
iridium of dncot. Allylic substitution reactions with the
new catalyst proceeded smoothly under aerobic condi-
tions as a proof of its air-insensitive character (entry 5).
The allylic amination reactions catalyzed by (π-allyl)Ir
complex C2 are general for substituted cinnamyl methyl
carbonates bearing either an electron-donating (1b, 1c) or
an electron-withdrawing group (1d, 1e). In all cases, ex-
cellent regio- and enantioselectivities were obtained (en-
tries 6–9). When NaCH(CO2Me)2 was used as a
nucleophile, the allylic alkylation reaction proceeded
much faster than the allylic amination reaction and the de-
sired alkylation product was obtained with excellent re-
sults (91% yield, 3ba/4ba >97:3, 98% ee for 3ba, entry
10). The high catalytic activity of (π-allyl)Ir complex C2
>97:3
>97:3
>97:3
>97:3
>97:3
>97:3
>97:3
>97:3
>97:3
>97:3
>97:3
3
4
C2
C2
5f C2
6
7
8
9
C2
C2
C2
C2
10 C2
11g C2
12h C2
4
48
a Reaction conditions: 1/2/cat. = 1:2:0.01, 0.4 mmol of 1 in 1.0 mL
THF.
b Isolated yield.
c Determined by 1H NMR analysis of the crude reaction mixture.
d Determined by HPLC analysis.
e Catalyst used: 2 mol%.
f Under air.
g Conditions: 0.8 mmol of 1a, 0.1 mol% of C2 in 2 mL THF.
h Conditions: 8 mmol of 1a, 0.01 mol% of C2 in 20 mL THF.
Despite the generally high regioselectivity control in Ir-
catalyzed allylic substitution reactions, low regioselectiv-
ity was observed with certain allylic substrates. The re-
Synthesis 2013, 45, 2109–2114
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Iridium-Catalyzed Allylic Substitution Reactions
2111
Table 2 Allylic Substitution Reactions of Challenging Substrates with Catalyst Derived from L2a
Entry
1
Product 3
Diene
Temp (°C)
Time (h)
Yield (%)b
3/4c
73:27
>95:5
>97:3
ee (%)d
NHBn
cod
dbcot
dncot
r.t.
50
50
2
2
24
68
87
89
97
90
82
t-BuPh2SiO
3ag
CH(CO2Me)2
cod
dbcot
dncot
r.t.
50
50
8
4
4
85
91
79
76:24
94:6
93:7
98.5
92
84
t-BuPh2SiO
2
3
3bg
CH(CO2Me)2
cod
dbcot
dncot
r.t.
50
50
18
2
4
90
88
89
82:18
94:6
94:6
99
94
84
Ph3CO
3bh
CH(CO2Me)2
cod
dbcot
dncot
r.t.
50
50
18
1
2
90
93
82
74:26
93:7
>97:3
92
96
95
Ph3CO
4
5
2
3bi
NHBn
cod
dbcot
dncot
r.t.
r.t.
50
2
3.5
24
65
79
68
85:15
96:4
>97:3
95
94
96
Ph
3af
a Reaction conditions: 1/2/C2 = 1:2:0.01, 0.4 mmol of 1 in 1.0 mL THF. The data for [Ir(cod)Cl]2 and [Ir(dbcot)Cl]2 are taken from the literature.6
b Isolated yield.
c Determined by 1H NMR analysis of the crude reaction mixture.
d Determined by HPLC analysis.
Unless stated otherwise, all reactions were carried out in flame-
dried glassware under argon atmosphere. All solvents were purified
and dried according to standard methods prior to use. 1H NMR spec-
tra were obtained at 300 MHz or 400 MHz and recorded relative to
TMS signal (0 ppm) or residual protio-solvent. 13C NMR spectra
were obtained at 75 MHz or 100 MHz, and chemical shifts were re-
corded relative to the solvent resonance (CDCl3, 77.0 ppm). Data
for 1H NMR are recorded as follows: chemical shift (δ, ppm), mul-
tiplicity (standard abbreviations were used to denote the signal mul-
tiplicities), coupling constant(s) in Hz, integration. Data for 13C
NMR are reported in terms of chemical shift (δ, ppm). The phos-
phoramidite ligands14 and the substituted allylic carbonates4c,d,15
were prepared according to the known procedures.
gioselectivity could be improved by utilizing [Ir(dbcot)Cl]2
as shown previously by Helmchen et al.6 When the new
catalyst C2 was used, regioselectivity of all reactions with
those challenging substrates was considerably improved
compared with that of the cod complex and slightly im-
proved even when compared with that of the dbcot com-
plex (Table 2). There is a general trend that the
enantioselectivity was decreased while the regioselectivi-
ty was improved (3ag, 3bg, 3bh). We reasoned that the
bulky substrates might retard the rate of nucleophilic at-
tack at the (π-allyl)Ir center, which provided longer time
for epimerization of the diastereomeric (π-allyl)Ir com-
plexes leading to decreased enantioselectivity.12d It is
worth noting that in the allylic alkylation of 1i and allylic
amination of 1f, excellent regioselectivity and enantiose-
lectivity could be obtained in both cases (Table 2, entries
4, 5).
Catalyst C1
In a flame-dried Schlenk tube under an argon atmosphere, a solution
of [Ir(dncot)Cl]2 (211.2 mg, 191 μmol) and (S,S,Sa)-L1 (215.7 mg,
400 μmol) in anhyd THF (10 mL) was stirred at r.t. for 1 h. (E)-But-
2-en-1-yl methyl carbonate (104.0 mg, 800 μmol) and AgOTf
(102.4 mg, 400 μmol) were added and the resulting suspension was
stirred for 24 h at r.t. The resultant white precipitate was removed
by filtration, and the solution was concentrated in vacuo. The resi-
due was subjected to silica gel column chromatography (CH2Cl2–
i-PrOH, 100:0 → 97:3) to yield C1 (400.6 mg, 85%) as a light
yellow powder; mp 195 °C (dec.).
In summary, well-defined catalysts derived from [Ir(dn-
cot)Cl]2 and phosphoramidite ligands have been synthe-
sized and applied in allylic substitution reactions. These
(π-allyl)Ir complexes have the following features: 1) They
are air-stable and can be stored under ambient atmosphere
over six months without loss of catalytic activity; 2) Very
high regioselectivity was obtained even with some chal-
lenging substrates, and 3) The catalytic loading can be as
low as 0.01 mol%. Further studies on extending the sub-
strate scope are currently under way in our laboratory.
1H NMR (400 MHz, THF-d8): δ = 0.59 (d, J = 7.2 Hz, 3 H), 1.21 (t,
J = 12.0 Hz, 1 H), 1.60 (dd, J = 8.4, 6.4 Hz, 3 H), 2.24 (dd, J = 11.0,
5.6 Hz, 1 H), 2.98 (d, J = 11.2 Hz, 2 H), 3.31 (t, J = 7.6 Hz, 1 H),
3.94 (dd, J = 16.4, 7.2 Hz, 1 H), 4.02 (dd, J = 11.6, 5.6 Hz, 1 H),
4.48 (dd, J = 9.2, 2.8 Hz, 1 H), 4.50–4.59 (m, 1 H), 4.71–4.82 (m, 1
H), 4.85 (d, J = 9.2 Hz, 1 H), 5.21 (dd, J = 8.8, 6.4 Hz, 1 H), 5.58
(br, 1 H), 6.32 (dd, J = 9.6, 7.2 Hz, 1 H), 6.39 (d, J = 8.0 Hz, 1 H),
6.49 (d, J = 8.8 Hz, 1 H), 6.85 (t, J = 6.8 Hz, 1 H), 6.97 (t, J = 7.2
Hz, 1 H), 7.00 (t, J = 8.4 Hz, 1 H), 7.08–7.13 (m, 1 H), 7.18–7.22
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2109–2114

2112
K.-Y. Ye et al.
SPECIAL TOPIC
(m, 4 H), 7.22–7.25 (m, 2 H), 7.29–7.33 (m, 4 H), 7.36–7.40 (m, 2
H), 7.43–7.49 (m, 3 H), 7.52–7.57 (m, 4 H), 7.59 (d, J = 7.6 Hz, 1
H), 7.65 (t, J = 7.2 Hz, 1 H), 7.79 (d, J = 8.8 Hz, 1 H), 7.90 (d, J =
8.0 Hz, 1 H), 8.11 (d, J = 8.8 Hz, 1 H), 8.15 (d, J = 8.8 Hz, 1 H),
8.30 (d, J = 8.0 Hz, 1 H), 8.57 (d, J = 8.8 Hz, 1 H).
13C NMR (100 MHz, THF-d8): δ = 15.1 (d, J = 4.1 Hz, 1 C), 19.6,
21.3 (d, J = 4.9 Hz, 1 C), 50.0, 61.1 (d, J = 5.3 Hz, 1 C), 66.6, 82.0
(d, J = 7.1 Hz, 1 C), 85.5 (d, J = 24.5 Hz, 1 C), 90.8 (d, J = 5.7 Hz,
1 C), 95.4, 104.6, 108.6, 121.8, 122.5, 122.8, 123.6, 125.3, 126.0,
126.6, 126.7, 126.8, 127.1, 127.3, 127.4, 127.6, 127.7, 127.8, 127.9,
128.0, 128.1, 128.2, 128.6, 128.7, 128.8, 129.1, 129.2, 129.4, 129.5,
129.8, 129.9, 130.0, 132.2, 132.3, 132.8, 133.2, 133.3, 133.4, 133.7,
134.2, 136.7, 139.7, 141.0, 141.6, 142.1, 143.7, 143.8, 148.4, 148.5,
149.7, 149.8.
HPLC: Daicel Chiralcel OD-H, hexane–i-PrOH (98:2), v = 0.5
mL·min–1, λ = 230 nm, tR (minor) = 9.31 min, tR (major) = 10.25
min; 98% ee.
1H NMR (400 MHz, CDCl3): δ = 1.66 (br, 1 H), 3.70 (AB, JAB
=
13.2 Hz, 1 H), 3.74 (BA, JBA = 13.2 Hz, 1 H), 4.22 (d, J = 7.2 Hz, 1
H), 5.11 (d, J = 10.0 Hz, 1 H), 5.22 (d, J = 17.2 Hz, 1 H), 5.94 (ddd,
J = 17.2, 10.4, 7.2 Hz, 1 H), 7.19–7.27 (m, 2 H), 7.29–7.39 (m, 8 H).
3ab16
Yield: 89.1 mg (88%); colorless oil; [α]D20.4 +0.8 (c 1.00, CHCl3).
HPLC: Daicel Chiralcel OD-H, hexane–i-PrOH (98:2), v = 0.5
mL·min–1, λ = 230 nm, tR (minor) = 12.63 min, tR (major) = 16.40
min; 96% ee.
1H NMR (300 MHz, CDCl3): δ = 1.62 (br, 1 H), 3.70 (s, 2 H), 3.77
(s, 3 H), 4.17 (d, J = 7.2 Hz, 1 H), 5.11 (d, J = 9.6 Hz, 1 H), 5.19 (d,
J = 17.1 Hz, 1 H), 5.92 (ddd, J = 17.1, 9.9, 7.2 Hz, 1 H), 6.81–6.91
(m, 2 H), 7.18–7.35 (m, 7 H).
31P NMR (162 MHz, THF-d8): δ = 115.2.
HRMS (ESI+): m/z calcd for [Ir(dncot)(C,P-L1)(crotyl)]
=
C64H52IrNO2P: 1090.3365; found: 1090.3356.
3ac17
Catalyst C2
Yield: 90.5 mg (93%); colorless oil; [α]D22.4 +3.8 (c 1.00, CHCl3).
In a flame-dried Schlenk tube under an argon atmosphere, a solution
of [Ir(dncot)Cl]2 (106.2 mg, 96 μmol) and (S,S,Sa)-L2 (123.5 mg,
206 μmol) in anhyd THF (5 mL) was stirred at r.t. for 1 h. (E)-But-
2-en-1-yl methyl carbonate (48.7 mg, 374 μmol) and AgOTf (63.9
mg, 250 μmol) were added and the resulting suspension was stirred
for 24 h at r.t. The resultant white precipitate was removed by filtra-
tion, and the solution was concentrated in vacuo. The residue was
subjected to silica gel column chromatography (CH2Cl2–i-PrOH,
100:0 → 97:3) to yield C2 (226.5 mg, 87%) as a light yellow pow-
der; mp 205 °C (dec.).
1H NMR (300 MHz, THF-d8): δ = 0.46 (d, J = 7.5 Hz, 3 H), 0.97 (t,
J = 11.1 Hz, 1 H), 1.64 (dd, J = 8.1, 5.7 Hz, 3 H), 2.38 (dd, J = 11.1,
4.5 Hz, 1 H), 2.94 (d, J = 10.5 Hz, 1 H), 3.24 (t, J = 6.9 Hz, 1 H),
3.55 (s, 3 H), 3.89 (s, 3 H), 4.40–4.67 (m, 5 H), 4.85 (d, J = 9.3 Hz,
1 H), 5.03 (t, J = 6.3 Hz, 1 H), 5.74 (br, 1 H), 6.37 (d, J = 8.1 Hz, 1
H), 6.43 (d, J = 8.7 Hz, 1 H), 6.49 (t, J = 8.4 Hz, 1 H), 6.80 (t, J =
6.9 Hz, 1 H), 6.85–6.99 (m, 4 H), 7.04 (t, J = 7.5 Hz, 1 H), 7.08–
7.16 (m, 2 H), 7.16–7.19 (m, 1 H), 7.20–7.26 (m, 4 H), 7.26–7.31
(m, 2 H), 7.31–7.36 (m, 2 H), 7.40 (t, J = 7.2 Hz, 1 H), 7.51–7.63
(m, 6 H), 7.73 (d, J = 8.7 Hz, 1 H), 7.94 (d, J = 8.4 Hz, 1 H), 8.12
(d, J = 9.0 Hz, 1 H), 8.17 (d, J = 8.7 Hz, 1 H), 8.28 (d, J = 8.1 Hz, 1
H), 8.54 (d, J = 8.4 Hz, 1 H).
13C NMR (100 MHz, THF-d8): δ = 15.3, 18.6, 19.6, 49.7, 53.3, 55.4,
56.0, 60.7 (d, J = 34.8 Hz, 1 C), 82.2 (d, J = 7.6 Hz, 1 C), 84.6 (d,
J = 26.7 Hz, 1 C), 91.2, 94.7, 104.0, 108.8, 111.4, 111.8, 121.6,
121.8, 121.9, 122.3, 123.1, 123.6, 124.2, 125.1, 125.3, 125.9, 126.5,
126.6, 126.7, 127.0, 127.2, 127.3, 127.4, 127.6, 127.7, 127.8, 128.0,
128.2, 128.4, 128.5, 128.6, 128.8, 129.2, 129.4, 129.6, 130.0, 130.1,
130.3, 131.6, 131.7, 132.2, 132.8, 133.2, 133.3, 133.4, 133.6, 133.7,
134.0, 136.9, 139.7, 141.0, 142.2, 148.2, 148.3, 149.6, 149.8, 158.0,
158.1.
HPLC: Daicel Chiralcel OD-H, hexane–i-PrOH (98:2), v = 0.5
mL·min–1, λ = 230 nm, tR (minor) = 13.30 min, tR (major) = 17.83
min; 96% ee.
1H NMR (300 MHz, CDCl3): δ = 1.62 (br, 1 H), 3.71 (s, 2 H), 3.77
(s, 3 H), 4.18 (d, J = 7.2 Hz, 1 H), 5.10 (d, J = 9.9 Hz, 1 H), 5.22 (d,
J = 17.1 Hz, 1 H), 5.92 (ddd, J = 17.7, 10.2, 7.2 Hz, 1 H), 6.94–6.82
(m, 1 H), 6.91–6.98 (m, 2 H), 7.16–7.34 (m, 6 H).
3ad18
Yield: 117.8 mg (95%); colorless oil; [α]D24.1 –1.5 (c 1.00, CHCl3).
HPLC: Daicel Chiralcel OD-H, hexane–i-PrOH (98:2), v = 0.5
mL·min–1, λ = 230 nm, tR (minor) = 10.50 min, tR (major) = 11.92
min; 97% ee.
1H NMR (300 MHz, CDCl3): δ = 1.59 (br, 1 H), 3.66 (AB, JAB
=
13.8 Hz, 1 H), 3.71 (BA, JBA = 13.5 Hz, 1 H), 4.17 (d, J = 7.2 Hz, 1
H), 5.11 (d, J = 9.3 Hz, 1 H), 5.20 (d, J = 17.1 Hz, 1 H), 5.87 (ddd,
J = 16.8, 9.6, 6.9 Hz, 1 H), 7.19–7.36 (m, 7 H), 7.40–7.50 (m, 2 H).
3ae17
Yield: 83.2 mg (81%); colorless oil; [α]D23.3 +0.1 (c 1.00, CHCl3).
HPLC: Daicel Chiralcel OD-H, hexane–i-PrOH (98:2), v = 0.5
mL·min–1, λ = 230 nm, tR (minor) = 10.27 min, tR (major) = 11.55
min; 95% ee.
1H NMR (300 MHz, CDCl3): δ = 1.60 (br, 1 H), 3.67 (AB, JAB
=
13.8 Hz, 1 H), 3.72 (BA, JBA = 13.8 Hz, 1 H), 4.19 (d, J = 7.2 Hz, 1
H), 5.12 (d, J = 9.9 Hz, 1 H), 5.20 (d, J = 17.1 Hz, 1 H), 5.88 (ddd,
J = 17.1, 9.9, 6.9 Hz, 1 H), 7.20–7.36 (m, 9 H).
3af17
Yield: 69.2 mg (68%); colorless oil; [α]D23.4 +2.8 (c 1.00, CHCl3).
31P NMR (162 MHz, THF-d8): δ = 115.4.
HPLC: Daicel Chiralcel OD-H, hexane–i-PrOH (98:2), v = 0.5
mL·min–1, λ = 230 nm, tR (minor) = 17.97 min, tR (major) = 19.74
min; 96% ee.
HRMS (ESI+): m/z calcd for [Ir(dncot)(C,P-L2)(crotyl)]
=
C66H56IrNO4P: 1150.3576; found: 1150.3569.
1H NMR (300 MHz, CDCl3): δ = 1.35 (br, 1 H), 1.63–1.92 (m, 2 H),
2.50–2.73 (m, 2 H), 2.99–3.11 (m, 1 H), 3.62 (AB, JAB = 13.5 Hz, 1
H), 3.82 (BA, JBA = 13.2 Hz, 1 H), 5.14 (d, J = 18.0 Hz, 1 H), 5.19
(d, J = 12.0 Hz, 1 H), 5.57–5.77 (m, 1 H), 7.09–7.19 (m, 3 H), 7.20–
7.35 (m, 7 H).
Ir-Catalyzed Allylic Amination Reaction; General Procedure
A suspension of C2 (5.2 mg, 1 mol%), allylic carbonate 1 (0.4
mmol), and BnNH2 (85.6 mg, 0.8 mmol) in THF (1 mL) was stirred
at 50 °C until TLC monitoring (eluent: PE–EtOAc, 20:1) showed
complete conversion. The solvent was removed in vacuo and the
residue was subjected to silica gel column chromatography (eluent:
eluent: PE–EtOAc, 20:1) to yield the amination products. The ratio
of regioisomers was determined by 1H NMR analysis of the crude
product, and the enantiomeric excess was determined by HPLC on
a chiral column.
3ag4d
Yield: 168.0 mg (89%); colorless oil; [α]D22.0 +34.2 (c 1.00, CHCl3).
HPLC: Daicel Chiralpak AD-H, hexane–i-PrOH (90:10), v = 0.5
mL·min–1, λ = 210 nm, tR (minor) = 7.20 min, tR (major) = 8.85 min;
82% ee.
1H NMR (300 MHz, CDCl3): δ = 1.04 (s, 9 H), 2.18 (br, 1 H), 2.50–
2.73 (m, 1 H), 3.63 (d, J = 6.0 Hz, 2 H), 3.66 (d, J = 14.7 Hz, 1 H),
3aa16
Yield: 83.2 mg (90%); colorless oil; [α]D18.2 +6.2 (c 1.00, CHCl3).
Synthesis 2013, 45, 2109–2114
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Iridium-Catalyzed Allylic Substitution Reactions
2113
3.89 (d, J = 13.8 Hz, 1 H), 5.15 (d, J = 9.9 Hz, 1 H), 5.16 (d, J = 18.6
Hz, 1 H), 5.62 (ddd, J = 18.0, 9.9, 7.8 Hz, 1 H), 7.19–7.46 (m, 11
H), 7.57–7.68 (m, 4 H).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
Ir-Catalyzed Allylic Alkylation Reaction; General Procedure
A suspension of C2 (5.2 mg, 1 mol%), allylic carbonate 1 (0.4
mmol), and NaCH(CO2Me)2 (0.8 mmol) in THF (1 mL) was stirred
at 50 °C until TLC monitoring (eluent: eluent: PE–EtOAc, 10:1)
showed complete conversion. The reaction was quenched by sat. aq
NH4Cl (2.0 mL) and diluted with EtOAc (2.0 mL). The organic lay-
er was separated, washed with brine (2.0 mL), dried (MgSO4), and
concentrated under reduced pressure. The residue was subjected to
flash chromatography over silica gel (eluent: eluent: PE–EtOAc,
20:1) to yield the products. The ratio of regioisomers was deter-
Primary Data for this article are available online at
http://www.thieme-connect.com/ejournals/toc/synthesis and can be
cited using the following DOI: 10.4125/pd0048th.PmriDyramPatrPiDiyrp
m
4hd1a4.285./0tyraDaZteanh1l01
C
hemrysti
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1
mined by H NMR of the crude product, the enantiomeric excess
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3ba4c
Yield: 94.1 mg (91%); colorless oil; [α]D23.1 +31.1 (c 1.00, CHCl3).
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HPLC: Daicel Chiralcel OJ-H, hexane–i-PrOH (95:5), v = 1.0
mL·min–1, λ = 230 nm, tR (minor) = 24.71 min, tR (major) = 27.16
min; 98% ee.
1H NMR (300 MHz, CDCl3): δ = 3.48 (s, 3 H), 3.73 (s, 3 H), 3.87
(d, J = 11.1 Hz, 1 H), 4.10 (dd, J = 10.5, 8.7 Hz, 1 H), 5.08 (d, J =
9.6 Hz, 1 H), 5.12 (d, J = 16.5 Hz, 1 H), 5.99 (ddd, J = 18.0, 9.3, 8.1
Hz, 1 H), 7.15–7.24 (m, 3 H), 7.25–7.33 (m, 2 H).
3bg4c
Yield: 148.7 mg (79%); colorless oil; [α]D18.0 +42.5 (c 1.00, CHCl3).
HPLC: Daicel Chiralpak AD-H, hexane–i-PrOH (98:2), v = 0.5
mL·min–1, λ = 230 nm, tR (major) = 10.15 min, tR (minor) = 11.17
min; 84% ee.
1H NMR (300 MHz, CDCl3): δ = 1.05 (s, 9 H), 2.96–3.10 (m, 1 H),
3.67 (s, 3 H), 3.69 (s, 3 H), 3.69–3.76 (m, 2 H), 3.88 (d, J = 8.1 Hz,
1 H), 5.10 (d, J = 10.2 Hz, 1 H), 5.11 (d, J = 17.7 Hz, 1 H), 5.90 (dt,
J = 16.8, 9.3 Hz, 1 H), 7.32–7.46 (m, 6 H), 7.57–7.66 (m, 4 H).
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3bh4c
Yield: 168.8 mg (89%); colorless oil; [α]D23.3 +29.4 (c 1.00, CHCl3).
HPLC: Daicel Chiralpak AD-H, hexane–i-PrOH (98:2), v = 0.5
mL·min–1, λ = 230 nm, tR (major) = 14.79 min, tR (minor) = 17.21
min; 84% ee.
1H NMR (300 MHz, CDCl3): δ = 3.03–3.15 (m, 1 H), 3.15–3.24 (m,
2 H), 3.56 (s, 3 H), 3.62 (s, 3 H), 3.82 (d, J = 8.1 Hz, 1 H), 5.10 (d,
J = 9.9 Hz, 1 H), 5.11 (d, J = 18.9 Hz, 1 H), 5.91 (dt, J = 17.1, 9.9
Hz, 1 H), 7.15–7.32 (m, 9 H), 7.35–7.47 (m, 6 H).
3bi4c
Yield: 180.8 mg (82%); colorless oil; [α]D22.2 –2.3 (c 1.00, CHCl3).
HPLC: Daicel Chiralpak AD-H, hexane–i-PrOH (98:2), v = 0.5
mL·min–1, λ = 230 nm, tR (major) = 12.72 min, tR (minor) = 13.61
min; 95% ee.
1H NMR (300 MHz, CDCl3): δ = 1.51–3.68 (m, 1 H), 1.78–1.92 (m,
1 H), 2.92–3.06 (m, 2 H), 3.07–3.17 (m, 1 H), 3.42 (d, J = 8.4 Hz, 1
H), 3.66 (s, 3 H), 3.72 (s, 3 H), 4.92 (d, J = 9.0 Hz, 1 H), 4.94 (d, J =
17.1 Hz, 1 H), 5.55 (dt, J = 17.1, 9.6 Hz, 1 H), 7.15–7.31 (m, 9 H),
7.38–7.46 (m, 6 H).
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Acknowledgment
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by [Ir(dbcot)Cl]2: (a) Franck, G.; Brödner, K.; Helmchen, G.
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We thank the National Basic Research Program of China (973 Pro-
gram 2010CB833300) and the National Natural Science Foundati-
on of China (20932008, 21025209, 2112106) for generous financial
support.
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2109–2114

2114
K.-Y. Ye et al.
SPECIAL TOPIC
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Synthesis 2013, 45, 2109–2114
© Georg Thieme Verlag Stuttgart · New York