Nickel-catalyzed reductive allylation of ketones with allylic carbonates

Article abstract of DOI:10.1055/s-0033-1339111

Nickel-catalyzed efficient umpolung allylation of ketones with allylic carbonates in the presence of zinc powder is developed, which accommodates a variety of allylic and ketone substrates. Although chiral ligand is necessary for the transformation, no enantioselectivity was observed. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1339111

SPECIAL TOPIC
▌1901
sNpeiccialktoeplic-Catalyzed Reductive Allylation of Ketones with Allylic Carbonates
Allylation of Ketones with Allylic Carbonates
Chenglong Zhao,a Zhuozhen Tan,a Zhuye Liang,b Wei Deng,*a Hegui Gong*a
a
Department of Chemistry, Shanghai University, 99 Shang-Da Road, Shanghai 200444, P. R. of China
Fax +86(21)66132410; E-mail: wdeng@shu.edu.cn; E-mail: Hegui_gong@shu.edu.cn
b
College of Chemistry and Molecular Engineering, Zhengzhou University, 100 Science Road, Zhengzhou 450001, P. R. of China
Received: 12.03.2014; Accepted after revision: 13.04.2014
moallylic alcohols in high yields and up to 91%
Abstract: Nickel-catalyzed efficient umpolung allylation of ke-
enantioselectivities.16 Herein we extend the same strategy
tones with allylic carbonates in the presence of zinc powder is de-
to ketones, and disclose our systematic results for genera-
veloped, which accommodates a variety of allylic and ketone
tion of homoallylic quaternary alcohols. Our initial stud-
ies indicate that the catalytic reactions may involve
addition of allylnickel to ketone, which may be promoted
by in situ generated zinc(II).
substrates. Although chiral ligand is necessary for the transforma-
tion, no enantioselectivity was observed.
Key words: nickel, catalysis, allylation, umpolung, ketones
To begin with, the coupling of cyclohexanone with meth-
yl (2-phenylallyl)carbonate (1) using Ni(cod)2/(S)-i-Pr-
Pybox (2)/MgCl2 in DMA in the presence of zinc powder
was examined, but this generated only a trace amount of
product 6a (Table 1, entry 1). Replacement of MgCl2 with
CuI gave the product in 93% yield (Table 1, entry 2). In-
vestigation of other Ni sources suggests only NiI2 to be ef-
ficient to produce the quaternary alcohol 6a in 73% yield
(Table 1, entry 3 vs 4–6). With NiI2 as the precatalyst, oth-
er ligands such 3 and 4 (Figure 1) were less efficient (Ta-
ble 1, entries 7, 8). When DMF was used as the solvent,
the yield was boosted to 90% (Table 1, entry 9). CuSO4
was equally effective (Table 1, entry 10). However, the
catalyst and ligand loading can be reduced to half without
eroding the yields (Table 1, entry 11). Interestingly, with-
out Cu additives, the reaction remains effective even
when 1.5 equivalents of allylic carbonates were used (Ta-
ble 1, entries 12, 13). The unsubstituted Pybox 5 reduced
the yield to 80% (Table 1, entry 14). A control experiment
without ligand or NiI2 gave poor result (Table 1, entries 15
and 16).
Direct coupling of allylic electrophiles with carbonyl de-
rivatives that avoids pre-preparation of allylic nucleo-
philes has become one of the most notable protocols for
generating homoallylic alcohols.1–15 For instance, the use
of allylic halides in the Nozaki–Hiyama–Kishi and Barbier
allylation reactions,2,3 has led to successful asymmetric al-
lylation of ketones as reported by Sigman,3 although the
Barbier-type reactions require stoichiometric chiral auxil-
iaries to produce chiral homoallylic alcohols.4 In contrast,
the employment of more stable and accessible allylic al-
cohols and their derivatives has also been extensively
studied under rhodium-,5 ruthenium-,6 iridium-,7,8 palladi-
um-,9,10 cobalt-,11 iron-,12 titanium-,13 and nickel-
catalyzed14,15 conditions, which generally entail reducing
reagents such as indium, zinc, tin, alcohol, and boron, etc.
The asymmetric version includes Krische’s iridium-cata-
lyzed transfer hydrogenation method,8 Zanonni and
Zhou’s palladium-catalyzed allylation of aldehydes with
allylic alcohols and their derivatives.10
However, in contrast to aldehydes, allylation of ketones
with allylic alcohols and their derivatives has received
much less attention. The rhodium-,5 cobalt-11 and iron-
catalyzed12 allylation of ketones have been disclosed un-
der (Bpin)2, manganese, zinc, and electrochemical reduc-
ing conditions. These studies are restricted to limited
allylic and ketone substrates. Although nickel and palladi-
um catalysts have been used for ketone allylation, the re-
actions require activation reagents such as InI, Et2Zn, and
diboron, which proceed through addition of allyl–M
(M = In, Zn, and B) to ketones. The use of less atomic
economic reductants renders these methods less practi-
cal.9a,c,14a
With the optimized conditions in hand (Table 1, entry 13),
we studied the coupling of cyclohexanone with a variety
of allylic carbonates (Table 2). The 2-(4-fluoro)- and 2-(4-
methyl)phenyl- and 2-methylallylic carbonates were effi-
O
O
N
N
N
N
N
N
N
N
R
R
4
R = H: (S)-i-Pr-Pybox (2)
R = Me: (S)-t-Bu-Pybox (3)
Recently, we disclosed that under Ni/Pybox-catalyzed
conditions, asymmetric allylation of aldehydes can be re-
alized in the presence of zinc powder, generating the ho-
O
O
N
N
N
SYNTHESIS 2014, 46, 1901–1907
Advanced online publication: 28.05.2014
5
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1339111; Art ID: ss-2014-c0174-st
© Georg Thieme Verlag Stuttgart · New York
Figure 1 Structures of ligands

1902
C. Zhao et al.
SPECIAL TOPIC
cient, giving 6b–d in high yields (Table 2, entries 1–3).
While 3-phenylallylic carbonate delivered the product 6e
in good yield, the 1-phenyl analogue was not successful
due to dimerization of the allylic carbonate (Table 2, en-
tries 4, 5). The unsubstituted allylic carbonate also provid-
ed the quaternary alcohol 6f in 65% yield (Table 2, entry
6). The 3- and 1-methylallylic carbonates provided 6g in
moderate or only trace amounts, respectively (Table 2, en-
tries 7, 8). The 3,3-dimethylallylic carbonate produced the
homoallylic alcohol 6h in poor yield (Table 2, entry 9). Fi-
nally, the allylic acetate appears to be less effective than
its carbonate analogue, as evident in entry 10 (cf. Table 1,
entry 13).
Table 1 Optimization of the Reaction Conditions
‘standard conditions’
Ph
O
HO
NiI2 (5 mol%)
(S)-i-Pr-Pybox (2) (7 mol%)
Ph
OCO2Me
+
Zn (300 mol%), DMF
6a, 95%
1 (1.5 equiv)
0.3 mmol
Entry 1
Ni source
Ligand Additive Solvent Yield
(equiv) (mol%)
(mol%) (50 mol%)
(%)
1
2
2
Ni(cod)2 (10) 2 (15)
MgCl2
DMA trace
DMA 93
2
Ni(cod)2 (10) 2 (15)
CuI
Next, we studied the compatibility of ketones by coupling
with unsubstituted allyl methyl carbonate (Table 3, entries
1–14). As anticipated, 4-phenylcyclohexanone gave simi-
lar result to cyclohexanone (Table 3, entry 1). The aryl ke-
tones generally gave the quaternary alcohols 8–16 in good
to excellent yields (Table 3, entries 2–10), regardless of
the electronic properties of the benzene rings as evident in
4-fluoro- and 4-methoxyphenylethanone (Table 3, entries
7, 8). The naphthylethanone and 1-methylindoline-2,3-di-
one generated the coupling products 15 and 16 in 94% and
69% yields, respectively (Table 3, entries 9, 10). The re-
action conditions were also highly effective for dialkyl ke-
tones including 4-phenylbutan-2-one and nonan-5-one
(Table 3, entries 11, 12). However, sterically more con-
gested ketones such as dicyclohexylmethanone and 2-
methyl-1-phenylpropan-1-one, failed to give the coupling
products 19 and 21 (Table 3, entries 13 and 15). The con-
jugated 3-methylcyclohex-2-enone gave 20 in 57% yield
(Table 3, entry 14). Finally, coupling of 2-phenylallylic
carbonate with cyclopentanone and Cbz-protected piperi-
din-4-one, and 2-methylallylic carbonate with dihydro-
2H-pyran-4(3H)-one gave the products 22–24 in moder-
ate to good yields (Table 3, entries 16–18).
3
2
NiI2 (10)
2 (15)
2 (15)
2 (15)
CuI
DMA 73
4
2
NiBr2 (10)
NiCl2 (10)
CuI
DMA trace
DMA trace
DMA trace
5
2
CuI
6
2
Ni(acac)2 (10) 2 (15)
CuI
7
2
NiI2 (10)
NiI2 (10)
NiI2 (10)
NiI2 (10)
NiI2 (5)
3 (15)
4 (15)
2 (15)
2 (15)
2 (7)
CuI
DMA
DMA
DMF
DMF
DMF
DMF
DMF
DMF
51
36
90
92
70
95
95
80
8
2
CuI
9
2
CuI
10
11
12
13
14
15
16
2
CuSO4
CuSO4
none
none
none
none
none
2
2
NiI2 (5)
2 (7)
NiI2 (5)
1.5
1.5
1.5
1.5
2 (7)
NiI2 (5)
NiI2 (5)
none
5 (7)
none
2 (7)
DMF <10
DMF trace
Table 2 Allylation of Cyclohexanone with a Variety of Allylic Carbonates and Acetates
R4
OH
O
NiI2 (5 mol%)
(S)-i-Pr-Pybox (2) (7 mol%)
R2
R2
R1
OCO2Me
+
Zn (300 mol%), DMF
R3
R
1 = H, R3 = R4
R3 = H, R1 = R4
0.3 mmol
1.5 equiv
Entry
Allylic substrate
Product
Yield (%)a
F
F
OH
1
2
90
OCO2Me
6b
OH
89
OCO2Me
6c
Synthesis 2014, 46, 1901–1907
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Allylation of Ketones with Allylic Carbonates
1903
Table 2 Allylation of Cyclohexanone with a Variety of Allylic Carbonates and Acetates (continued)
R4
OH
O
NiI2 (5 mol%)
(S)-i-Pr-Pybox (2) (7 mol%)
R2
R2
R1
OCO2Me
+
Zn (300 mol%), DMF
R3
R
1 = H, R3 = R4
R3 = H, R1 = R4
0.3 mmol
1.5 equiv
Entry
Allylic substrate
Product
Yield (%)a
OH
3
4
81
OCO2Me
6d
OH
Ph
Ph
OCO2Me
60
6e
OH
Ph
OCO2Me
5
6
7
trace
65
Ph
6e
OH
OCO2Me
6f
OH
OCO2Me
38
6g
OH
OCO2Me
8
9
trace
n.d.b
85
6g
OH
OCO2Me
6h
OH
10
OAc
6a
a Isolated yields.
b Not detected.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1901–1907

1904
C. Zhao et al.
SPECIAL TOPIC
Table 3 Scope of Ketones
Table 3 Scope of Ketones (continued)
O
O
NiI2 (5 mol%)
(S)-i-Pr-Pybox (2) (7 mol%)
NiI2 (5 mol%)
(S)-i-Pr-Pybox (2) (7 mol%)
OH
R2
OH
R1
R3
R3
R1
R1
R2
+
R1
R2
+
OCO2Me
OCO2Me
Zn (300 mol%), DMF
R3
Zn (300 mol%), DMF
R2
R3
1 equiv
1.5 equiv
1 equiv
1.5 equiv
Entry Allylic substrate
Product
Yield (%)a
Entry Allylic substrate
Product
Yield (%)a
OH
HO
OCO2Me
O
N
1
59
10
69
Ph
Me
7
16
HO
HO
2
3
4
52
93
95
11
12
13
81
83
5
8
17
HO
HO
9
18
HO
HO
10
19
OH
HO
14
57
5
6
73
96
20
11
HO i-Pr
Ph
Ph
HO
15
n.d.b
OCO2Me
21
HO
Ph
12
16
17
52
72
76
HO
22
7
8
95
95
94
OH
Ph
F
13
N
Cbz
HO
23
OH
MeO
18
OCO2Me
O
14
24
HO
a Isolated yields.
b Not detected.
9
15
Synthesis 2014, 46, 1901–1907
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Allylation of Ketones with Allylic Carbonates
1905
O
HO
Ni(cod)2 (150 mol%)
(S)-i-Pr-Pybox 2a (150 mol%)
OCO2Me
+
DMF
MeO
MeO
14
1 equiv
1.5 equiv
with ZnI2 (100 mol%): 72%
without ZnI2: 11%
with Bu4NI (100 mol%): 10%
Scheme 1 Ketone allylation for the production of 14 in the presence of stoichiometric amount of Ni(cod)2 and ligand 2, with and without ZnI2
Two possible mechanisms may be involved for the forma- 1),19 although transmetalation of allyl–nickel with zinc(II)
tion of homoallylic alcohols. The first one is through di- that leads to allyl–zinc has been suggested.18b The collec-
rect addition of allylnickel, which is formed by the tive results appear to support that addition of allyl–nickel
reaction of nickel(0) with allylic carbonate to the ke- to ketone is responsible for the catalytic allylation pro-
tone.16,17 The second one is through the addition of allyl- cess, which may be activated by in situ generated zinc(II).
zinc, which is generated by transmetalation of allylnickel
Finally, we also tested chiral ligand 3 for asymmetric pro-
duction under the ketone allylation conditions (Scheme
3). Again, no enantioselectivity was observed for 14, al-
though the ligand has proven to be essential for the reac-
with zinc to the ketone.18 The coupling of 4-methoxy-
phenylethanone and allyl methyl carbonate in the pres-
ence of 1.5 equivalents of Ni(cod)2/2 in DMF only
provided the homoallylic alcohol 14 in 11% yield
(Scheme 1). However, addition of 1 equivalent of ZnI2
tivity of nickel, as evident from Table 1, entry 15.
In conclusion, we have developed a nickel-catalyzed re-
ductive coupling method for allylation of ketones which
produced 14 in 72% yield (Scheme 1). Control experi-
ment using 1 equivalent of Bu4NI gave 14 only in 10%
produces quaternary homoallylic alcohols. The reaction
yield. This observation indicates that zinc(II) plays an im-
conditions accommodate a variety of allylic carbonates
portant role in the activation of ketone allylation.
and ketones with good to excellent coupling efficiency
On the other hand, a comparison of the nickel-catalyzed
and excellent functional group tolerance. Although chiral
reductive allylation conditions (Scheme 2, equation 1)
ligand is necessary for the catalytic process, no enantiose-
with a Barbier-type procedure (Scheme 2, equation 2) for
lectivity was observed. The preliminary mechanistic stud-
the coupling of dicyclohexylmethanone with allyl methyl
ies suggest addition of ketone by allyl–nickel may be
carbonate and allyl bromide was carried out. The signifi-
responsible for the alcohol production, although zinc(II)
cant difference in coupling efficiency suggests that gener-
may play an important role in regulating the addition effi-
ation of more reactive allyl–zinc as evident in the Barbier-
ciency.
type allylation (Scheme 2, equation 2) may not be appli-
cable to this reductive coupling event (Scheme 2, equation
O
NiI2 (5 mol%)
(S)-i-Pr-Pybox (2) (7 mol%)
HO
OCO2Me
(1)
+
Zn (300 mol%), DMF
1 equiv
O
1.5 equiv
5%
HO
(S)-i-Pr-Pybox (2) (7 mol%)
Zn (300 mol%)
Br
(2)
+
DMF
1 equiv
1.5 equiv
20 47%
Scheme 2 Comparison of the Ni-catalyzed reductive allylation conditions with a Barbier-type procedure
O
HO
NiI2 (5 mol%)
(S)-t-Bu-Pybox (3) (7 mol%)
OCO2Me
+
Zn (300 mol%), DMF
MeO
MeO
1 equiv
1.5 equiv
14 85%, 0% ee
Scheme 3 Ketone allylation for the production of 14 using chiral ligand 3
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1901–1907

1906
C. Zhao et al.
SPECIAL TOPIC
All manipulations were carried out under an atmosphere of N2 using
standard Schlenk or glove box techniques. Column chromatography
was performed using silica gel 300–400 mesh (purchased from
Qingdao-Haiyang Co., China) as the solid support. All NMR spec-
tra were recorded on Bruker Avance 500 MHz spectrometer at STP
unless otherwise indicated. 1H NMR and 13C NMR chemical shifts
are reported in δ units, parts per million (ppm) relative to the chem-
ical shift of residual solvent. For a more detailed description of the
general remarks section to the experimental, see the Supporting In-
formation.
IR (KBr): 3302, 3093, 2986, 2926, 1690, 1616, 1472, 993, 925, 760
cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.41 (d, J = 7.3 Hz, 1 H), 7.38–
7.31 (td, J = 7.8, 1.1 Hz, 1 H), 7.12 (t, J = 7.4 Hz, 1 H), 6.85 (d, J =
7.8 Hz, 1 H), 5.71–5.58 (m, 1 H), 5.18–5.04 (m, 1 H), 3.56 (br s, 0.4
H), 3.47 (br s, 0.6 H), 3.19 (d, J = 1.6 Hz, 3 H), 2.77 (dd, J = 13.5,
6.4 Hz, 1 H), 2.64 (dd, J = 13.5, 8.3 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 177.9, 177.9, 143.3, 130.5, 129.7,
129.7, 124.1, 123.1, 120.3, 108.4, 75.9, 75.9, 42.9, 26.2.
HRMS (EI): m/z [M + Na]+ calcd for C12H13NNaO2: 226.0844;
Nickel-Catalyzed Allylation of Ketones; General Procedure
A flame-dried Schlenk tube was charged with ligand 2 (6.3 mg,
0.021 mmol, 7 mol%) and activated Zn powder (59.2 mg, 0.900
mmol, 300 mol%). The tube was capped with a rubber septum and
moved into a glove box, at which point NiI2 (4.7 mg, 0.015 mmol,
5 mol%) was added. DMF (0.5 mL), the respective ketone (0.300
mmol, 100 mol%), and the allylic carbonate (0.450 mmol, 150
mol%) were added via syringe. The reaction mixture was allowed
to stir overnight under an N2 atmosphere at r.t. The mixture was di-
rectly loaded onto a silica column without workup. The residue in
the reaction vessel was rinsed with a small amount of CH2Cl2 or el-
uent. Flash column chromatography (eluent: 5–40% EtOAc in PE)
provided the product.
found 226.0845.
1,1-Dicyclohexylbut-3-en-1-ol (19)
Yield: 3.5 mg (5%); colorless liquid.
IR (KBr): 3488, 3074, 2927, 2851, 2668, 1636, 1447, 984, 911 cm–1.
1H NMR (500 MHz, CDCl3): δ = 5.90–5.77 (m, 1 H), 5.14–5.02 (m,
2 H), 2.32 (d, J = 7.4 Hz, 2 H), 1.84–1.62 (m, 10 H), 1.55–1.48 (m,
2 H), 1.23–1.08 (m, 11 H).
13C NMR (125 MHz, CDCl3): δ = 153.1, 117.6, 76.6, 44.7, 38.9,
27.4, 27.1, 27.1, 26.7.
HRMS (EI): m/z [M]+ calcd for C16H28O: 236.2140; found:
218.2032 (M+ – H2O).
1-[2-(4-Fluorophenyl)allyl]cyclohexanol (6b)
1-(2-Phenylallyl)cyclopentanol (22)
Yield: 63.2 mg (90%); colorless liquid.
Yield: 31.5 mg (52%); colorless liquid.
IR (neat): 3461, 3081, 2932, 2858, 1622, 1602, 1509, 1447, 1232,
840, 820 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.42–7.35 (m, 2 H), 7.05–6.96 (m,
2 H), 5.33 (d, J = 1.7 Hz, 1 H), 5.12 (s, 1 H), 2.69 (s, 2 H), 1.60–1.10
(m, 11 H).
13C NMR (125 MHz, CDCl3): δ = 163.2, 161.2, 144.2, 138.7, 138.6,
128.1, 128.0, 117.2, 115.3, 115.1, 71.3, 47.8, 37.8, 25.6, 22.1.
IR (KBr): 3448, 3080, 3056, 3023, 2958, 2870, 1623, 1493, 1444,
1009, 900, 779, 669 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.45–7.38 (m, 2 H), 7.37–7.30 (m,
2 H), 7.30–7.24 (m, 1 H), 5.36 (d, J = 1.6 Hz, 1 H), 5.18 (s, 1 H),
2.86 (s, 2 H), 1.79–1.68 (m, 2 H), 1.61–1.41 (m, 7 H).
13C NMR (125 MHz, CDCl3): δ = 146.3, 142.4, 128.4, 127.5, 126.6,
116.8, 81.6, 46.4, 39.8, 23.5.
HRMS (EI): m/z [M]+ calcd for C15H19FO: 234.1420; found:
234.1425.
HRMS (EI): m/z [M]+ calcd for C14H18O: 202.1358; found
202.1355.
1-[2-(p-Tolyl)allyl]cyclohexanol (6c)
1-[2-(p-Tolyl)allyl]cyclohexanol (23)
Yield: 61.5 mg (89%); colorless liquid.
Yield: 75.9 mg (72%); colorless liquid.
IR (KBr): 3431, 3082, 3025, 2931, 2858, 1717, 1670, 1606, 1447,
1182, 901, 825 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.33 (d, J = 8.2 Hz, 2 H), 7.14 (d,
J = 8.0 Hz, 2 H), 5.36 (d, J = 1.9, 1 H), 5.14–5.08 (m, 1 H), 2.72 (s,
2 H), 2.35 (s, 3 H), 1.61–1.12 (m, 11 H).
13C NMR (125 MHz, CDCl3): δ = 145.1, 139.6, 137.2, 129.1, 126.3,
116.5, 72.3, 47.6, 37.8, 25.7, 22.1, 21.0.
IR (KBr): 3450, 3059, 3031, 2948, 1697, 1623, 1435, 1276, 1243,
1150, 1088, 698 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.44–7.22 (m, 10 H), 5.42 (d, J =
1.6 Hz, 1 H), 5.16 (m, 1 H), 5.10 (m, 2 H), 3.97–3.76 (m, 2 H), 3.11
(br s, 2 H), 2.74 (s, 2 H), 1.54–1.36 (m, 5 H).
13C NMR (125 MHz, CDCl3): δ = 155.2, 144.3, 141.9, 136.8, 128.6,
128.4, 127.9, 127.8, 127.8, 126.4, 117.9, 69.4, 66.9, 48.1, 39.9.
HRMS (EI): m/z [M]+ calcd for C16H22O: 230.1671; found
230.1675.
HRMS (EI): m/z [M + Na]+ calcd for C22H25NNaO3: 374.1732;
found 374.1727.
4-Phenylhept-1-en-4-ol (12)
Yield: 54.8 mg (96%); colorless liquid.
Acknowledgment
IR (KBr): 3475, 3060, 2958, 1639, 1602, 1494, 1446, 999, 917, 765,
702 cm–1.
We thank Ms. Yijing Dai and Mr. Zhenhua Zang for the initial dis-
covery of this reaction, Dr. Hongmei Deng (Shanghai University)
for help with the use of the NMR facilities. Financial support was
provided by the Chinese NSF (No. 21172140, 21372151,
21174081, and 21102088), and the Program for Professor of Special
Appointment at Shanghai Institutions of Higher Learning Shanghai
Education Committee.
1H NMR (500 MHz, CDCl3): δ = 7.43–7.38 (m, 2 H), 7.37–7.32 (m,
2 H), 7.27–7.21 (m, 1 H), 5.64–5.53 (m, 1 H), 5.19–5.09 (m, 1 H),
2.74 (ddt, J = 13.5, 6.0, 1.1 Hz, 1 H), 2.51 (dd, J = 13.8, 8.7 Hz, 1
H), 2.09 (br s, 1 H), 1.87–1.73 (m, 2 H), 1.41–1.26 (m, 1 H), 1.15–
1.03 (m, 1 H), 0.86 (t, J = 7.3 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 146.1, 133.5, 128.0, 126.3, 125.2,
119.5, 75.8, 47.3, 45.0, 16.7, 14.3.
HRMS (EI): m/z [M]+ calcd for C13H18O: 190.1358; found
190.1362.
Supporting Information for this article is available online
at
http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000084.SunogIpimrfiantoSuIpg
n
fonirtat
ori
3-Allyl-3-hydroxy-1-methylindolin-2-one (16)
Yield: 42.1 mg (69%); white solid; mp 149–150 °C.
Synthesis 2014, 46, 1901–1907
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
References
Allylation of Ketones with Allylic Carbonates
1907
(b) Kimura, M.; Shimizu, M.; Shibata, K.; Tazoe, M.;
Tamaru, Y. Angew. Chem. Int. Ed. 2003, 42, 3392.
(1) For reviews on enantioselective carbonyl allylation, see:
(a) Yus, M.; González-Gómez, J. C.; Foubelo, F. Chem. Rev.
2011, 111, 7774. (b) Marek, I.; Sklute, G. Chem. Commun.
2007, 1683. (c) Hall, D. G. Synlett 2007, 1644. (d) Denmark,
S. E.; Fu, J. Chem. Rev. 2003, 103, 2763. (e) Kennedy, J. W.
J.; Hall, D. G. Angew. Chem. Int. Ed. 2003, 42, 4732.
(f) Ramachandran, P. V. Aldrichimica Acta 2002, 35, 23.
(2) For selected examples of asymmetric NHK reactions, see:
(a) Xia, G.; Yamamoto, H. J. Am. Chem. Soc. 2006, 128,
2554. (b) Deng, Q.-H.; Wadepohl, H.; Gade, L. H. Chem.
Eur. J. 2011, 17, 14922. (c) Bandini, M.; Cozzi, P. G.;
Melchiorre, P.; Umani-Ronchi, A. Angew. Chem. Int. Ed.
1999, 38, 3357. (d) Zhang, Z.; Aubry, S.; Kishi, Y. Org. Lett.
2011, 13, 3077. (e) Guo, H.; Dong, C.-G.; Kim, D.-S.;
Urabe, D.; Wang, J.; Kim, J. T.; Liu, X.; Sasaki, T.; Kishi,
Y. J. Am. Chem. Soc. 2009, 131, 15387. (f) Berkessel, A.;
Menche, D.; Sklorz, C. A.; Schroder, M.; Paterson, I. Angew.
Chem. Int. Ed. 2003, 42, 1032.
(3) (a) Harper, K. C.; Sigman, M. S. Science 2011, 333, 1875.
(b) Miller, J. J.; Sigman, M. S. J. Am. Chem. Soc. 2007, 129,
2752.
(4) For selected examples of asymmetric Barbier reactions, see:
(a) Haddad, T. D.; Hirayama, L. C.; Singaram, B. J. Org.
Chem. 2010, 75, 642. (b) Hirayama, L. C.; Gamsey, S.;
Knueppel, D.; Steiner, D.; Dela Torre, K.; Singaram, B.
Tetrahedron Lett. 2005, 46, 2315.
(5) For nonasymmetric coupling of allylic alcohol/thioether
with carbonyl compounds using Rh/B, see: (a) Williams, F.
J.; Grote, R. E.; Jarvo, E. R. Chem. Commun. 2012, 48, 1496.
Rh/CO: (b) Vasylyev, M.; Alper, H. J. Org. Chem. 2010, 75,
2710.
(6) For Ru/CO, see: (a) Denmark, S. E.; Nguyen, S. T. Org. Lett.
2009, 11, 781. For Ru-catalzyed reactions involving
secondary alcohols, see: (b) McInturff, E. L.; Nguyen, K. D.;
Krische, M. J. Angew. Chem. Int. Ed. 2014, 53, 3232.
(c) McInturff, E. L.; Mowat, J.; Waldeck, A. R.; Krische, M.
J. J. Am. Chem. Soc. 2013, 135, 17230. (d) Park, B. Y.;
Montgomery, T. P.; Garza, V.; Krische, M. J. J. Am. Chem.
Soc. 2013, 135, 16320. (e) Yamaguchi, E.; Mowat, J.;
Luong, T.; Krische, M. J. Angew. Chem. Int. Ed. 2013, 52,
8428.
(7) For nonasymmetric allylation using [Ir(cod)Cl]2/SnCl2, see:
Roy, S.; Banerjee, M. J. Mol. Catal. A 2006, 246, 231.
(8) For iridium-catalyzed transfer hydrogenation, see:
(a) Dechert-Schmitt, A.-M. R.; Schmitt, D. C.; Krische, M.
J. Angew. Chem. Int. Ed. 2013, 52, 3195. (b) Kim, I.-S.;
Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc. 2008, 130,
6340. (c) Kim, I. S.; Ngai, M-Y.; Krische, M. J. J. Am.
Chem. Soc. 2008, 130, 14891. Allyliridium/alcohol:
(d) Bower, J. F.; Skucas, E.; Patman, R. L.; Krische, M. J.
J. Am. Chem. Soc. 2007, 129, 15134.
Pd(OAc)2/Et3B: (c) Kimura, M.; Tomizawa, T.; Horino, Y.;
Tanaka, S.; Tamaru, Y. Tetrahedron Lett. 2000, 41, 3627.
Pd/diboron via allyl–B: (d) Selander, N.; Kipke, A.;
Sebelius, S.; Szabó, K. J. J. Am. Chem. Soc. 2007, 129,
13723. Pd/SmI2: (e) Jacquet, O.; Bergholz, T.; Magnier-
Bouvier, C.; Mellah, M.; Guillot, R.; Fiaud, J.-C.
Tetrahedron 2010, 66, 222.
(10) Palladium-catalyzed asymmetric umpolung using Pd/Et2Zn:
(a) Zanoni, G.; Gladiali, S.; Marchetti, A.; Piccinini, P.;
Tredici, I.; Vidari, G. Angew. Chem. Int. Ed. 2004, 43, 846.
Pd/B: (b) Zhu, S.-F.; Qiao, X.-C.; Zhang, Y.-Z.; Wang, L.-
X.; Zhou, Q.-L. Chem. Sci. 2011, 2, 1135. (c) Zhu, S. F.;
Yang, Y.; Wang, L.-X.; Liu, B.; Zhou, Q.-L. Org. Lett. 2005,
7, 2333.
(11) Co/Zn: Gomes, P.; Gosmini, C.; Périchon, J. Synthesis 2003,
1909.
(12) Iron-electrochemical reduction: (a) Durandetti, M.;
Meignein, C.; Périchon, J. J. Org. Chem. 2003, 68, 3121.
Fe/Mn: (b) Muriel, D. M.; Périchon, J. Tetrahedron Lett.
2006, 47, 6255.
(13) For nonasymmetric coupling of allylic alcohol/thioether
with carbonyl compounds using titanium-mediated
protocols modulated by nickel or palladium, see:
(a) Campaa, A. G.; Bazdi, B.; Fuentes, N.; Robles, R.;
Cuerva, J. M.; Oltra, J. E.; Porcel, S.; Echavarren, A. M.
Angew. Chem. Int. Ed. 2008, 47, 7515. Ti: (b) Takeda, T.;
Yamamoto, M.; Yoshida, S.; Tsubouchi, M. Angew. Chem.
Int. Ed. 2012, 51, 7263.
(14) For nonasymmetric carbonyl allylation with allyl-OR under
Ni/InI, see: (a) Hirashita, T.; Kambe, S.; Tsuji, H.; Omori,
H.; Araki, S. J. Org. Chem. 2004, 69, 5054. Intramolecular
coupling of allyl ether with aldehyde: (b) Franco, D.;
Wenger, K.; Antonczak, S.; Cabrol-Bass, D.; Dunach, E.;
Rocamora, M.; Gomez, M.; Muller, G. Chem. Eur. J. 2002,
8, 664.
(15) (a) Montgomery, J. Angew. Chem. Int. Ed. 2004, 43, 3890.
(b) Köpfer, A.; Sam, B.; Breit, B.; Krische, M. J. Chem. Sci.
2013, 4, 1876.
(16) (a) Dai, Y.; Wu, F.; Zang, Z.; You, H.; Gong, H. Chem. Eur.
J. 2012, 16, 808. (b) Tan, Z.; Wan, X.; Zang, Z.; Qian, Q.;
Deng, W.; Gong, H. Chem. Commun. 2014, 50, 3827.
(17) For stoichiometric addition of allyl–Ni(I) to carbonyl, see:
(a) Corey, E. J.; Semmelhack, M. F. J. Am. Chem. Soc. 1967,
89, 2755. (b) Hegedus, L. S.; Stiverson, R. K. J. Am. Chem.
Soc. 1974, 96, 3250.
(18) (a) For reductive transmetalation of allylpalladium with
indium, see: Fontana, G.; Lubineau, A.; Scherrmann, M.-C.
Org. Biomol. Chem. 2005, 3, 1375. Possible transmetalation
of allylnickel with zinc: (b) Durandetti, S.; Sibille, S.;
Perichon, J. J. Org. Chem. 1989, 54, 2198.
(19) For Barbier-type allylation involving addition of allylzinc to
carbonyl, see: Berton, B. W.; Shugart, J. H.; Hughey, C. A.;
Conrad, B. P.; Perala, S. M. Molecules 2001, 6, 655.
(9) For selected examples of palladium-catalyzed
nonasymmetric carbonyl allylation with allylic alcohols and
acetates, see: Pd/Et2Zn: (a) Flahaut, A.; Toutah, K.;
Mangeney, P.; Roland, S. Eur. J. Inorg. Chem. 2009, 5422.
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Synthesis 2014, 46, 1901–1907