Ni-catalyzed asymmetric reductive allylation of aldehydes with allylic carbonates

Article abstract of DOI:10.1039/c3cc49859j

This work features first asymmetric Ni-catalyzed reductive coupling of allylic carbonates with aldehydes, which may proceed via allyl-Ni intermediates although Zn was used as the terminal reductant. Moderate to excellent enantiomeric excess was obtained with excellent functional group tolerance. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c3cc49859j

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ARTICLE TYPE
Ni-Catalyzed Asymmetric Reductive Allylation of Aldehydes with
Allylic Carbonates
Zhouzhen Tan, Xiaolong Wan, Zhenhua Zang, Qun Qian,* Wei Deng* and Hegui Gong,*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
This work features first asymmetric Ni-catalyzed reductive
coupling of allylic carbonates with aldehydes, which may
knowledge, this work features the first Niꢀcatalyzed asymmetric
reductive allylation of aldehydes with allylic carbonates. Our
proceed via allyl-Ni intermediates although Zn was used as 50 preliminary
mechanistic
studies
favored
that
the
the terminal reductant. Moderate to excellent enantiomeric
10 excess were obtained with excellent functional group
enantioselectivities should arise from addition of the weak
nucleophilic allylꢀNi to aldehydes.12
tolerance.
We first examined the coupling of methyl 2ꢀphenyl allylic
carbonate with 4ꢀanisaldehyde (Table 1). After extensive
55 screening of the reaction conditions, we identified that use of NiI2,
tridentate Pybox ligands and CuI in DMF was superior to other
nickel sources, ligands, additives and solvents (entries 1–8). With
a combination of NiI2/2c/CuI in the presence of zinc powder at 25
oC, 1 was generated in 92% yield and 73% ee (entry 4). The use
60 of Ni(COD)2 further boosted the ee to 77% (entry 9). Lowering
the temperature to 0 oC increased the ee to 86% (entry 10).
Ni(ClO4)2•6H2O proved to be more effective than Ni(COD)2,
which generated 1 in 91% ee even at 25 oC; slight increase of the
ee value was observed at 0 oC (entries 11–12). Interestingly,
65 replacement of CuI with CsI delivered equivalent yield and ee
(entry 13); without additives, 91% ee could still be attained (entry
Asymmetric carbonyl allylation represents one of the most
important reaction types in the current organic synthesis.1 In
particular, the reductive protocols that employ allylic and
15 carbonyl electrophiles without preꢀpreparation of allylic
nucleophiles has received significant advances.2ꢀ9 In addition to
the wellꢀestablished Niꢀcatalyzed NozakiꢀHiyamaꢀKishi (NHK)
method,2 Inꢀ, Znꢀ, Et3Bꢀ, and SnCl2ꢀmediated Barbier allylation
of aldehydes with allyl halides have also been well studied.
20 However, the catalytic asymmetric Barbier method appears to be
difficult, which generally requires stoichiometric amount of chiral
auxiliaries.3 The employment of more accessible and stable
allylic alcohols and their derivatives such as allylic acetates and
carbonates has drawn increasing attention in realizing highly
25 enantioselective allylation of carbonyl compounds.4ꢀ9 However,
the transition metals involved in these reductive umpolung
catalytic processes are primarily limited to palladium and iridium.
14). Moreover, 2ꢀphenyl allylic acetate is equally effective.
Table 1. Optimization of the reaction conditions for 1.a
5ꢀ8
For instance, Krische has developed an elegant Irꢀcatalyzed
transfer hydrogenation method allowing alcohols serving as the
30 substrates and reducing reagents, which sets a high bar in the
sense of green carbonyl allylation.6,7 Zanoni and Zhou have
demonstrated that catalytic Pd/phosphines in combination with
Et2Zn and Et3B generate homoallylic alcohols with high
enantioselectivities, respectively.8 Therefore, the development of
35 asymmetric reductive umpolung carbonyl allylation using less
expensive transition metals, e.g. nickel is still in need,9 although it
has been widely explored in the asymmetric carbonylation of
alkynes, dienes and allenes .10
In the course of our studies of Niꢀcatalyzed reductive coupling
40 of alkyl electrophiles with other electrophiles,11 we have noticed
that allylic acetates and carbonates react with aldehydes and
ketones in the presence of zinc powder. Herein we disclosed our
discovery of Niꢀcatalyzed asymmetric reductive coupling of
allylic carbonates with aldehydes using zinc as the terminal
45 reductant. Moderate to high levels of enantioselectivities were
observed, which appears to be significantly effected by the
substitution patterns on the allylic carbonates. To the best of
entry Ni
NiI2
ligand
additive
yield
(%)b
90
90
95
92
95
76
trace
38
98
95
95
95
95
95
ee
(%)
25
40
35
73
20
0
2a
2a
2b
2c
2d
2e
3
none
2
3
NiI2
NiI2
CuI (50%)
CuI (50%)
CuI (50%)
CuI (50%)
CuI (50%)
CuI (50%)
CuI (50%)
CuI (50%)
CuI (50%)
CuI (50%)
CuI (50%)
CsI (50%)
none
4
NiI2
5
NiI2
6
NiI2
7
NiI2
NAc
0
8
NiI2
4
9
Ni(COD)2
Ni(COD)2
Ni(ClO4)2•6H2O
Ni(ClO4)2•6H2O
Ni(ClO4)2•6H2O
Ni(ClO4)2•6H2O
2c
2c
2c
2c
2c
2c
77
86d
92d
91
91
91
10
11
12
13
14
a Reaction Conditions: aldehyde (100 mol%, 0.15 M in DMF), allylic carbonate
b
(150 mol %), Zn (300 mol %), Ni (10 mol%), Ligand (15 mol%), 25 ºC, 12 h.
Isolated yields. c Not available. d 0 ºC.
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DOI: 10.1039/C3CC49859J
diminished ees as evident in 26 and 27. The addition of CsI at ꢀ25
oC boosted the ee for 14 and 21 to 85% and 80%, respectively.
Likewise, the ee for 22 was enhanced to 81% at ꢀ15 oC. However,
lowering the temperatures for 6 8, 11 19, 21 22 and 25 did not
35 resulted in better ees.
Under the optimized reaction conditions (Table 1, entry 14),
the coupling of unsubstituted allylic carbonate with 4ꢀ
anisaldehyde delivered 5 in 49% ee albeit in high yield. Further
optimization indicated that the conditions in Table 1, entry 10
promoted the ee to 66% (Scheme 1). This result suggests that
optimal enantioselectivities for the allylic carbonates bearing
different substitution patterns may be achieved by modification of
the optimized conditions.
5
Using the optimized conditions (Table 1, entry 14) for the
reductive coupling of aromatic aldehydes with 1ꢀ and 3ꢀ
substituted allylic carbonates delivered the homoallylic products
28–30 in excellent yields (Table 3). Excellent anti/syn
40 selectivities were observed for arylꢀsubstituted allylic carbonates
(Table 3, entries 1–3), whereas poor anti/syn selectivities were
obtained for carbonates bearing methyl substituents (Table 3,
entries 4–5). In general, the ees were moderate even when the
10 Scheme 1. Optimized reaction conditions for 5.
Table 2. Coupling of 2ꢀaryl allylic carbonates with aldehydes.a,b
temperature was lowered to ꢀ25 oC (Table 3, entries 2 and 3).
OH
OH
OH
Me OH
45 Table 3. Carbonyl allylation of other allylic carbonates. a,b,c,d
Ph
Ph
Ph
Ph
entry
substrate
product
result
Me
N
OMe
6, yield: 96%
7, yield: 95%
8, yield: 95%
9, yield: 85%
ee: 88%
ee: 85%
ee: 88%
ee: 86%
HO
Ph
HO
H
OH
OH
O
Ph
Ph
Ph
12, yield: 94%
ee: 87%
13, yield: 95%
ee: 73%
11, yield: 95%
ee: 80%
10, yield: 48%
ee: 85%
OH
OH
Ph
Cl
OH
OH
Ph
Ph
Ph
Br
F3C
MeO2C
14, yield: 95% (77%)c
ee: 76% (85%)c
15, yield: 94%
ee: 77%
16, yield: 95%
ee: 71%
17, yield: 95%
ee: 69%
OH
OH
OH
OH
Ph
Ph
Ph
Me
Ph
Ph
Ph
OMe
R
22, yield: 95% (60%)d
21, yield: 95% (52%)c
19 (R = H), yield: 95%
18, yield: 91%
ee: 85%
c
a Reaction Conditions: as in Table 1, entry 14. b Isolated yields. The anti/syn ratios
ee: 72% (81%)d
ee: 68% (80%)c
ee: 85%
d
20 (R = Me), yield: 87%
were determined by 1H NMR analysis. The absolute stereochemistry is not
determined. e The reaction was run at ꢀ25 oC.
ee: 91%
OH
Me
OH
OH
It was interesing to note that coupling of 1ꢀphenyl allylic
carbonate with benzaldehdye gave 29 with equivalent results as
the 3ꢀphenyl analog (Table 3, entries 2–3). Likewise, similar
yields, drs and ees were observed for the coupling of 3ꢀmethylꢀ
50 and 1ꢀmethyl allylic carbonates (Table 3, entries 4–5), supporting
that the formation of Niꢀπꢀallyl complexes is one of the key steps
in the catalytic process. Low diastereoselectivities were observed
for 1ꢀ or 3ꢀmethylꢀsubsituted allylic carbonates (Table 3, entries
4–5), indicating that a possible equilibrium between η1ꢀ(E)ꢀallylꢀ
55 Ni and (Z)ꢀallylꢀNi when alkyl substituents are present at C1 or
H
HO
Ph
Ph
iPr
Ph
Me
Ph
R
23 (R = F), yield: 60%, ee: 81%
24 (R = CF3), yield: 90%, ee: 82%
25, yield: 96%
ee: 60%
26 yield: 53%
ee: 41%
27, yield: 45%
ee: 51%
a Reaction Conditions: as in Table 1, entry 14. b Isolated yields. c With CsI (50
mol%) at ꢀ25 oC. d With CsI (50 mol%) at ꢀ15 oC.
Application of the optimized conditions (Table 1, entry 14) to
the coupling of other 2ꢀaryl allylic acetates with a variety of
15 aldehydes was performed next (Table 2). The aromatic aldehydes
that do not bear electronꢀwithdrawing groups generally produced
high ees as in 6–12; this includes sterically hindered 2ꢀiPrꢀ
benzaldehyde. The naphthyl aldehyde produced 13 in 73% ee.
The Clꢀ and Brꢀsubstituted benzaldehydes gave similar ees
20 regardless of the substitution patterns as evident in 14 and 15. On
the other hand, the electronꢀwithdrawing groups appeared to
reduce the values of ees as evident in 16–17. Cinnamaldehyde
and (E)ꢀbutꢀ2ꢀenal also gave rise to the homoallylic alcohols 18–
20 in high ees. Aliphatic 3ꢀphenylpropanal delivered 21 in 68%
25 ee. The coupling of benzaldehyde with 2ꢀ(4ꢀmethoxy), 2ꢀ(4ꢀ
fluoro) and 2ꢀ(4ꢀtrifluoromethyl)phenyl allylic carbonates and 2ꢀ
methyl allylic carbonate produced 22 25 in 72%, 81%, 82% and
60% ees, suggesting that electronic nature of the allylic partners
is important in control of enantioselectivities. The sterically more
C3 positions of allylic carbonates.13
Table 4. Coupling of 4ꢀanisaldehyde with methyl 2ꢀphenyl allylic
carbonate generating 1 without Zn powder.
entry Ni(COD)2
ligand 2c
additive
yield/ee
1
2
3
4
5
150 mol %
150 mol %
150 mol%
150 mol %
150 mol %
none
none
none
90/0
150 mol %
15 mol %
15 mol %
15 mol %
90/35
93/91
90/91
90/30
Ni(ClO4)2 (10%)
Zn(ClO4)2 (10%)
CsI(100%)
Transformation of the weak nucleophilic allylꢀNi intermediate
60 into more reactive allylꢀZn is possible by reductive
transmetallation of allylꢀNi with Zn or by transmetallation of
allylꢀNi with Zn2+.9a,14 It is therefore important to identify
whether chiral allylꢀNi(II) was capable of adding to the
aldehydes.12 The coupling of 4ꢀanisaldehyde with 2ꢀphenyl
30 hindered 2ꢀ(2ꢀmethyl)phenyl and 2ꢀisopropyl allylic carbonates 65 allylcarbonate using 1.5 equiv of Ni(COD)2 in the absence of Zn
2
|
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DOI: 10.1039/C3CC49859J
60
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and ligand generated 1 in 90% yield (Table 4, entry 1). With 1.5
equiv of ligand 2c, 35% ee was obtained without eroding the
yield. Interestingly, addition of 10% of Ni(ClO4)2 or Zn(ClO4)2
drastically increased the ees to 91%, indicating the important role
of ClO4ꢀ (entries 3–4). The presence of 100% CsI also provided 1
with 30% ee (entry 5). These results suggest that transformation
of allylꢀNi to allylꢀZn is not necessary for this coupling event.14
In addition, treatment of 4ꢀanisaldehyde with allylbromide in
the presence or absence of Ni(ClO4)2•6H2O led to 5 in excellent
10 yields (Scheme 2). No enantioselectivities were observed in both
cases, owing to in situ formation of allylꢀzinc reagents that react
with aldehyde through a Barbier mechanism.15 As a result, we
reason that in our Niꢀcatalyzed reductive coupling process, the
enantioselectivity should not arise from allylꢀzinc reagents,
15 although their in situ formation cannot be excluded.
3
4
65
70
5
75
80
Conditions A: Ni(ClO4)2●6H2O (10 mol %), 2c (15 mol %), Zn (300 mol
%), DMF, rt. Conditions B: 2c (15 mol %), Zn (300 mol %), DMF, rt.
5
85
20 Scheme 2. Coupling of allylbromide with 4ꢀanisaldehyde
In summary, we have disclosed asymmetric Niꢀcatalyzed
reductive coupling of allylic carbonates with aldehydes utilizing
zinc powder as the terminal reductant. The reaction conditions are
25 particularly effective for the 2ꢀarylꢀallylic carbonates which
generate the homoallylic alcohols in good to excellent ees for
both aromatic and aliphatic aldehydes. The preliminary studies
suggest that the enantioselectivity arises from addition of allylꢀNi
to aldehydes rather than the more reactive allylꢀZn that may be
30 produced in the reactions.
We thank Ms. Yijing Dai for initial discovery of this reaction,
Prof. Yongjian Zhang (Shanghai Jiaotong University) for helpful
advices, and Dr Hongmei Deng (Shanghai University) for helping
use of the NMR facilities. Financial support was provided by the
35 Chinese NSF (Nos.21172140, 21372151, 21174081 and
21102088), and the Program for Professor of Special
Appointment at Shanghai Institutions of Higher Learning
Shanghai Education Committee.
90
6
7
95
100
105
110
8
9
Notes and references
40 a Department of Chemistry, Innovative Drug Research Center, and School
of Materials Science and Engineering, Shanghai University, 99 Shang-Da
Road, Shanghai 200444, China. E-mail: Hegui_gong@shu.edu.cn
† Electronic Supplementary Information (ESI) available: Charaterization
of all new compounds and HPLC data for ees. See
45 DOI: 10.1039/b000000x/
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50
55
2
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