Palladium(II)-Catalyzed Deacylative Allylic C-H Alkylation

Article abstract of DOI:10.1021/acs.joc.7b00919

The first deacylative allylic C-H alkylation has been established by employing the palladium-catalyzed allylic C-H activation and decarboxylative nucleophile generation. A wide scope of nucleophiles are tolerated and densely functionalized alkylation products turn out to be furnished in moderate to good yield. More importantly, this strategy provides an alternative method for the allylic C-H alkylation with less stabilized carbon nucleophiles, and can be further expanded to the synthesis of unconjugated enynes.

Full text of DOI:10.1021/acs.joc.7b00919

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Note
Palladium(II)-Catalyzed Deacylative Allylic C-H Alkylation
Xiao-Le Zhou, Lei Ren, and Pu-Sheng Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b00919 • Publication Date (Web): 15 Aug 2017
Downloaded from http://pubs.acs.org on August 16, 2017
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The Journal of Organic Chemistry
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Palladium(II)-Catalyzed Deacylative Allylic C-H Alkylation
XiaoꢀLe Zhou†, Lei Ren‡, PuꢀSheng Wang*†
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† Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei,
China, 230026
‡ Anhui Therapy Pharmaceutical Co., LTD, China
Supporting Information
ABSTRACT: The first deacylative allylic C-H alkylation has been established by employing the palladium-catalyzed allylic C-H
activation and decarboxylative nucleophile generation. A wide scope of nucleophiles are tolerated and densely functionalized
alkylation products turn out to be furnished in moderate to good yield. More importantly, this strategy provides an alternative
method for the allylic C-H alkylation with less stabilized carbon nucleophiles, and can be further expanded to the synthesis of
unconjugated enynes.
Palladiumꢀcatalyzed allylic alkylation1 is one of the most
Scheme 1. Nucleophiles for allylic C-H alkylation.
widely applied transformations for the construction of carbonꢀ
carbon bonds, along with predictable high levels of chemoꢀ, regioꢀ,
and stereoselectivity.2 Over the past decades, allylic substrates
with a wide range of leaving groups, including acetates, halides,
carbonates, epoxides, phosphonates and alcohols, has been
introduced into the allylic alkylation.3 In recent years, the direct
palladiumꢀcatalyzed allylic CꢀH4 alkylation has emerged as a
more efficient synthetic approach, which can avoid the installation
of the allylic leaving groups. So far, the disubstituted methylene
carbon nucleophiles5 bearing electronꢀwithdrawing groups
(Scheme 1a) have been well developed.6 However, the scope of
tertiary carbon nucleophiles for the creation of quaternary carbon
centers are still restricted in the nucleophiles bearing two electronꢀ
withdrawing groups,5b,7 aldehyde enamines,8 and 3,3ꢀdisubstituted
indolines9 (Scheme 1b). Owing to the requirement of strong basic
condition for enolization, relatively less stabilized tertiary
nucleophiles, like nitronates,5b acylic ketones and esters, are rarely
In the proposed mechanism of the deacylative allylic CꢀH
alkylation (Scheme 2), the πꢀallyl palladium intermediate I was
formed from simple terminal olefin 1 in the presence of
palladium(0) and oxidant, while the nonstabilized tertiary
nucleophile II was generated in situ from the deacylative retroꢀ
Claisen condensation of functionalized ketones 2 with alkoxide
reported in the allylic C−H alkylation. Therefore, the emergence
of new efficient strategy for the allylic C−H alkylation with less
stabilized tertiary carbon nucleophiles is highly desired.
Since the last decade, decarboxylative10 and deacylative11
nucleophile generation strategy have emerged as a convenient
method for the in situ formation of less stabilized carbon
anion. Principally, nucleophile II could undergo either
nucleophiles, which can avoid the demand of stoichiometric
nucleophilic substitution or protonation, thus theoretically leading
to the formation of 3 and 4. Therefore, the control of reaction
conditions to selectively afford the alkylation product would be
organometallic reagents as strong base. In recent years, Tunge and
coꢀworkers developed a deacylative allylation reactions11bꢀd by
using readily functionalized ketones as the precursor of versatile
relatively less stabilized tertiary carbon nucleophiles, where the
intermolecular carbonꢀcarbon bond formation was facilitated by a
retroꢀClaisen condensation.12 Inspired by these leading findings,
we envision that the deacylative strategy might be compatible
with the oxidative allylic CꢀH condition.
one of the formidable challenges to the proposed reaction. Herein,
we will describe the first deacylative allylic CꢀH alkylation with
less stabilized carbon nucleophiles, enabled by combining
palladiumꢀcatalyzed allylic CꢀH activation and decarboxylative
nucleophile generation.
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Scheme 2. Proposed mechanism for the deacylative allylic C-H
alkylation.
turned out to be the best alcohol additive with balanced perforꢀ
1
2
3
4
5
6
7
8
mance to promote the deacylative nucleophile generation and
inhibit the allylic ether formation. When less hindered alcohol,
like MeOH, was used, the allylic ether was detected.14 Especially,
the yield was able to be greatly improved to 70% by the addition
of 1.0 equivalent H2O (entry 10), which might be caused by the
waterꢀassisted dispersion of Cs2CO3 in the solvent. Subsequently,
a brief screening of bases (entries 11−14) revealed that Cs2CO3
was clarified to be essential for the deacylative alkylation process.
The yield of 3a decreased dramatically when the other bases were
used.
9
With the optimized conditions in hand, various 1ꢀntroacetones
1 and allylarenes 2 were examined (Table 2). Generally, a wide
range of allylarenes bearing a phenyl group with substituents at
the paraꢀ and metaꢀ position (entries 1ꢀ6) were able to provide the
desired nitroꢀsubstituted 1,6ꢀdienes 3 in moderate yields. However,
the reactivity appeared to be greatly influenced by the orthoꢀ subꢀ
stitution of allylarenes. For instance, the reaction of 1a with or-
thoꢀmethyl allylbenzene gave a much lower yield (entry 7), where
the orthoꢀ substitution might inhibit the formation of πꢀallyl palꢀ
ladium intermediate. Moreover, 1ꢀntroacetone 1b with more steric
hindrance substituent could also give product 3i in 45% yield
(entry 8).
10
11
12
13
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Table 1. Optimization of reaction conditionsa
1a
3a
yield
(%)b
6
4a
yield
(%)b
23
entry
base
additive
oxidant
conv.
(%)b
99
Table 2. Scope of 1-nitroacetones and allylarenesa
1
2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
tBuOH
tBuOH
tBuOH
tBuOH
MeOH
iPrOH
2,6ꢀDMBQ
2,5ꢀDMBQ
2,6ꢀDTBQ
2,5ꢀDTBQ
2,5ꢀDTBQ
2,5ꢀDTBQ
2,5ꢀDTBQ
2,5ꢀDTBQ
2,5ꢀDTBQ
2,5ꢀDTBQ
2,5ꢀDTBQ
2,5ꢀDTBQ
2,5ꢀDTBQ
2,5ꢀDTBQ
99
82
99
99
99
99
99
99
99
85
26
59
98
6
trace
50
33
68
26
19
19
34
11
62
19
38
9
3
4
5
30
6
39
yield
R1
2
3
7
Cs2CO3 AdꢀOH
Cs2CO3 Ph3COH
Cs2CO3 Ph3SiOH
33
entry
R
H
1
(%)b
50
8
49
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1b
4ꢀMeꢀC6H4
4ꢀtBuꢀC6H4
2b
2c
2d
2e
2f
3b
3c
3d
3e
3f
9
45
70(60d)
H
50
40
56
53
57
25
45
10c
11c
Cs2CO3
tBuOH
tBuOH
H
4ꢀFꢀC6H4
K2CO3
28
H
3ꢀMeꢀC6H4
12c Na2CO3 tBuOH
13c
14c
18
H
3,4ꢀ(MeO)2ꢀC6H4
3,4,5ꢀ(MeO)3ꢀC6H4
2ꢀMeꢀC6H4
KOH
tBuOH
tBuOH
19
30
H
2g
2h
2e
3g
3h
3i
CsOH
11
45
H
aReaction conditions: 1a (0.125 mmol), 2a (0.5 mmol), Pd(OAc)2 (5 mol%),
PPh3 (20 mol%), base (1.2 equiv), oxidant (1.2 equiv), additive (2.0 equiv),
DCM/DCE=1:1 (0.8 mL), 80 oC, 22 h, under N2. bBased on GC analysis of
the crude reaction mixture using methyl benzoate as an internal standard.
cH2O (1.0 equiv) was added. dIsolated yield.
C6H5
3ꢀMeꢀC6H4
aReaction conditions: 1 (0.125 mmol), 2 (0.5 mmol), Pd(OAc)2 (5 mol%),
t
PPh3 (20 mol%), Cs2CO3 (1.2 equiv), 2,5ꢀDTBQ (1.2 equiv), BuOH (2.0
equiv), DCM/DCE=1:1 (0.8 mL), 80 oC, 22 h, under N2. bIsolated yield.
To our delight, the deacylative allylic CꢀH alkylation proceeded
smoothly with acetylacetone substrates (Table 3), which further
demonstrated the utility of this strategy to access alkylation
products with less stabilized carbon nucleophiles. After fineꢀ
tuning of the reaction conditions, the treatment of 3ꢀMethylꢀ3ꢀ(4ꢀ
nitrophenyl)pentaneꢀ2,4ꢀdione 5a with a wide range of allylarenes
2 bearing either electronꢀdonating or electronꢀwithdrawing groups
was nicely tolerated to furnish the alkylation products 6 in good to
excellent yield. (entries 1ꢀ7). However, allylarenes with orthoꢀ
electronꢀwithdrawing substitution (entry 8) was less reactive and
only resulted in 44% yield. Moreover, 2ꢀallylnaphthalene was
In the light of the previous works on allylic CꢀH alkylation5, 7ꢀ9
,
our initial investigation was conducted by the reaction of alꢀ
lylbenzene (2a) with 3ꢀmethylꢀ3ꢀnitrohexꢀ5ꢀenꢀ2ꢀone (1a) in the
presence of 5.0 mol% Pd(OAc)2, 20 mol% PPh3, 1.2 equivalent
2,6ꢀdimethylbenzoquinone (2,6ꢀDMBQ), 1.2 equivalent Cs2CO3,
and 2.5 equivalent tBuOH (Table 1, entry 1). Although the ketone
1a was converted completely, unfortunately only a small amount
of the desired alkylation product 3a was afforded, and the
undesired protonation product 4a was obtained in 23% yield. In
consideration of the possible side reaction between alkylquinone
oxidant and tertiary carbon nucleophile intermediate under basic
condition13, then a series of paraꢀbenzoquinones with more steric
hindrance substituents were examined. Using either 2,5ꢀDMBQ
(entry 2) or 2,6ꢀDTBQ (entry 3) as the oxidant gave nearly the
same performance as 2,6ꢀDMBQ. To our delight, the desired
alkylation product 3a was obtained in 50% yield, when 2,5ꢀDTBQ
was used as external oxidant for the reaction. Then a screen of
compatible with the optimal reaction condition
(entry
9),
delivering the desired product in moderate yield. Acetylacetone
substrate bearing more steric hindrance substituent (entry 10)
could successfully deliver the desired product in good yield. In
particular, the substituted acetoacetate (entry 11) was also suitable
deacylative nucleophile precursor to accomplish the αꢀallylic
alkylation of ester in synthetically useful yield.
t
alcohol additives was evaluated (entries 5ꢀ9), and BuOH was
2
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Table 3. Scope of alkenes and acetylacetonesa
1
2
3
4
5
6
7
8
9
entry
R1
R2
5
R3
2
6
yield (%)b
1
2
Ac Me 5a
Ac Me 5a
Ac Me 5a
Ac Me 5a
4ꢀMeꢀC6H4
4ꢀMeOꢀC6H5
4ꢀFꢀC6H4
2b 6a
2i 6b
2d 6c
2e 6d
90
73
92
78
89
90
71
44
67
77
58
3
10
11
12
13
14
15
16
17
18
19
20
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22
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4
3ꢀMeꢀC6H4
5
Ac Me 5a 3,4ꢀ(MeO)2ꢀC6H4 2f 6e
Ac Me 5a 3,4,5ꢀ(MeO)3ꢀC6H4 2g 6f
6
Moreover, the catalytic system of deacylative allylic CꢀH
alkylation was applicable for the combination of decarboxylative
process.15 For instance, when 3ꢀphenylpropiolic acid (15) was
treated with substituted allylbenzenes, the unconjugated enyne
products 16 could be generated in the presence of Pd(TFA)2, PPh3,
Cs2CO3 and 2,5ꢀDTBQ, albeit in the unsatisfying yields.
7
Ac Me 5a
Ac Me 5a
Ac Me 5a
2ꢀMeꢀC6H4
2ꢀFꢀC6H4
1ꢀnaphthyl
C6H5
2h 6g
2j 6h
2k 6i
2a 6j
2a 6k
8
9
10
Ac
Bn 5b
11 CO2Et Me 5c
aReaction conditions: 5 (0.125 mmol), 2 (0.5 mmol), Pd(OAc)2 (5 mol%),
C6H5
t
PPh3 (20 mol%), Cs2CO3 (1.2 equiv), 2,5ꢀDTBQ (1.2 equiv), BuOH (2.0
equiv), THF (0.8 mL), 80 oC, 22 h, under N2. bIsolated yield.
Particularly, the tertiary carbon centers were also accessible via
a oneꢀpot stepwise allylic CꢀH alkylation and deacylation under
the basic oxidation condition (Scheme 3). Various tertiary αꢀ
acetyl carbonyl compounds smoothly underwent the formal
deacylative allylic CꢀH alkylation in high conversion and gave the
tertiary carbon products with good yields. However, due to the
unstability of ethyl esters under the basic condition, the αꢀ
substituted ethyl acetylacetates would result in the formation of
aliphatic acids (8aꢀc). The αꢀmethyl acetylacetone was also suitaꢀ
ble substrate to afford aliphatic ketone (8d) in 70% yield with the
employment of Cs2CO3, as a relatively weaker base.
In conclusion, we have established a novel catalytic system for
the combination of allylic CꢀH activation and deacylation manner,
giving the αꢀallylic alkylation of nitroalkanes, ketones and esters
with tertiary or quaternary carbon center. This strategy not only
provides an alternative approach for the allylic CꢀH alkylation
with less stabilized carbon nucleophiles, but also can be used in a
tandem catalytic process with the Tsuji–Trost allylation to access
the unsymmetrical 1,6ꢀdiene through a threeꢀcomponent coupling.
Moreover, the catalytic system can be expanded to the
decarboxylative allylic CꢀH functionalization for the synthesis of
unconjugated enynes.
Scheme 3. Scope of tertiary carbon nucleophilesa
EXPERIMENTAL SECTION
General Information: NMR spectra were recorded on a Bruckerꢀ
400 MHz spectrometer. Mass spectra were recorded on a Thermo
LTQ Orbitrap XL (ESI+) or water XEVO G2 QꢀTOF (Waters
Corporation). Infrared spectra were recorded on a Nicolet MXꢀ1E
FTꢀIR spectrometer.
Materials: All starting materials, reagents and solvents were purꢀ
chased from commercial suppliers (Aldrich, Alfa, TCI, Adamas,
etc.) and used as supplied unless otherwise stated. The niꢀ
troketones11c and acetylacetones11b were prepared following the
procedures reported in literatures.
aReaction conditions: 7 (0.125 mmol), 2a (0.5 mmol), Pd(OAc)2 (5 mol%),
PPh3 (20 mol%), 20 M NaOH (4 equiv), 2,5ꢀDTBQ (1.2 equiv), THF (0.4 mL),
tBuOH (0.4 mL), 40 oC, 36 h, under N2, then 90 C, 36 h. bCs2CO3 (1.2 equiv)
o
was used as base, THF (0.8 mL), 40 oC, 24 h, under N2, then 80 oC, 24 h.
General procedure A for the deacylative allylation with ni-
troketones
Notably, a one pot tandem catalytic process involving Pdꢀ
catalyzed allylic alkylation7e and deacylative allylic CꢀH
alkylation was feasible to afford 1,6ꢀdienes. In the presence of
catalytic amount of Pd(PPh3)4 and OFBA (2ꢀfluorobenzoic acid),
αꢀaryl acetylacetone 9 could react smoothly with allyl methyl
carbonate 10 to give allylic alkylation intermediate 11, which
further underwent deacylative allylic CꢀH alkylation to give the
desired 1,6ꢀdiene 12 in 82% yield (eq. 1). Similarly, either αꢀ
acetyl ketone or ester 13 was also able to conduct the tandem
catalytic process, providing the 1,6ꢀdiene 14 in moderate to good
yield (eq. 2).
To a flameꢀdried schlenk tube (25 mL) were added nitroketone 1
(0.125 mmol), allylarene 2 (0.5 mmol), Pd(OAc)2 (5 mol%,
0.00625 mmol, 1.4 mg), PPh3 (20 mol%, 0.025 mmol, 6.5 mg),
Cs2CO3 (1.2 equiv, 0.15 mmol, 48.9 mg), 2,5ꢀDTBQ (1.2 equiv,
0.15 mmol, 33.1 mg), tBuOH (2.0 equiv, 0.25 mmol, 24 ꢁL), H2O
(1 equiv, 0.125 mmol, 2.3 ꢁL), DCM/DCE=1:1 (0.8 mL) and a
stir bar. The solution was stirred at 80 oC for 22 h, under N2. After
the vial was cooled down to room temperature, the reaction mixꢀ
ture was directly subjected on flash chromatography (SiO2, Petroꢀ
leum ether:EtOAc = 50:1) to provide the allylation product 3.
3
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6.04 – 5.91 (m, 1H), 5.70 (td, J = 17.0, 7.3 Hz, 1H), 5.20 (d, J =
General procedure B for the deacylative allylation with acety-
lacetones
1
2
3
4
5
6
7
8
6.8 Hz, 1H), 5.17 (d, J = 14.4 Hz, 1H), 2.88 (dd, J = 14.2, 7.1 Hz,
1H), 2.78 (dd, J = 14.1, 7.1 Hz, 1H), 2.69 (dd, J = 14.2, 7.8 Hz,
1H), 2.58 (dd, J = 14.1, 7.5 Hz, 1H), 2.33 (s, 3H), 1.57 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 138.2, 136.5, 135.5, 130.9, 128.6,
128.5, 127.0, 123.5, 121.8, 120.7, 90.9, 43.5, 42.7, 22.1, 21.4. IR
(KBr) γ 3462, 2922, 1538, 1513, 1456, 1387, 1352, 995, 971,
926, 853, 818, 795 cmꢀ1. HRMS (ESI) (m/z): [M+H]+ calcd for
C15H20NO2, 246.1494; found, 246.1492.
To a flameꢀdried schlenk tube (25 mL) were added acetylacetone
5 (0.125 mmol), allylarene 2 (0.5 mmol), Pd(OAc)2 (5 mol%,
0.00625 mmol, 1.4 mg), PPh3 (20 mol%, 0.025 mmol, 6.5 mg),
Cs2CO3 (1.2 equiv, 0.15 mmol, 48.9 mg), 2,5ꢀDTBQ (1.2 equiv,
0.15 mmol, 33.1 mg), tBuOH (2.0 equiv, 0.25 mmol, 24 ꢁL), THF
(0.8 mL) and a stir bar. The solution was stirred at 80 oC for 22 h,
under N2. After the vial was cooled down to room temperature,
the reaction mixture was directly subjected on flash chromatogꢀ
raphy (SiO2, Petroleum ether/EtOAc = 10:1) to provide the allylaꢀ
tion product 6.
(E)-1,2-dimethoxy-4-(4-methyl-4-nitrohepta-1,6-dien-1-
yl)benzene (3f)
9
1
Yield: 19.3 mg, 53%. H NMR (400 MHz, CDCl3) δ 6.88 (d, J =
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
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39
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43
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60
7.8 Hz, 2H), 6.81 (d, J = 8.0 Hz, 1H), 6.41 (d, J = 15.6 Hz, 1H),
5.88 (dt, J = 15.4, 7.5 Hz, 1H), 5.71 (td, J = 17.2, 7.5 Hz, 1H),
5.25 – 5.14 (m, 2H), 3.90 (s, 3H), 3.88 (s, 3H), 2.89 (dd, J = 14.2,
7.1 Hz, 1H), 2.80 (dd, J = 14.1, 7.0 Hz, 1H), 2.67 (dd, J = 14.2,
(E)-(4-methyl-4-nitrohepta-1,6-dien-1-yl)benzene (3a)
Yield: 17 mg, 60%. H NMR (400 MHz, CDCl3) δ 7.38 – 7.28
1
(m, 4H), 7.27 – 7.21 (m, 1H), 6.55 – 6.43 (m, 1H), 6.03 (dt, J =
15.4, 7.5 Hz, 1H), 5.70 (ddt, J = 17.4, 10.3, 7.3 Hz, 1H), 5.28 –
5.12 (m, 2H), 2.90 (dd, J = 14.2, 7.2 Hz, 1H), 2.79 (dd, J = 14.1,
7.1 Hz, 1H), 2.70 (dd, J = 14.2, 7.8 Hz, 1H), 2.59 (dd, J = 14.1,
7.5 Hz, 1H), 1.58 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 136.6,
135.4, 130.9, 128.6, 127.8, 126.3, 122.1, 120.7, 90.9, 43.5, 42.65,
22.11. IR (KBr) γ 3446, 1537, 1449, 1387, 1352, 969, 927, 748,
693 cmꢀ1. HRMS (ESI) (m/z): [M+H]+ calcd for C14H18NO2,
232.1332; found, 232.1335.
7.8 Hz, 1H), 2.59 (dd, J = 14.1, 7.6 Hz, 1H), 1.58 (s, 3H). 13
C
NMR (101 MHz, CDCl3) δ 149.1, 149.0, 135.1, 130.9, 129.8,
120.7, 120.0, 119.5, 111.1, 108.9, 91.0, 56.0, 55.9, 43.5, 42.8,
22.1. IR (KBr) γ 2938, 1602, 1538, 1515, 1464, 1266, 1140,
1027, 969, 857 cmꢀ1. HRMS (ESI) (m/z): [M+H]+ calcd for
C16H22NO4, 292.1543; found, 292.1560.
(E)-1,2,3-trimethoxy-5-(4-methyl-4-nitrohepta-1,6-dien-1-
yl)benzene (3g)
(E)-1-methyl-4-(4-methyl-4-nitrohepta-1,6-dien-1-yl)benzene
(3b)
Yield: 22.9 mg, 57%. 1H NMR (400 MHz, CDCl3) δ 6.55 (s, 2H),
6.40 (d, J = 15.7 Hz, 1H), 5.94 (dt, J = 15.3, 7.5 Hz, 1H), 5.71 (td,
J = 17.2, 7.5 Hz, 1H), 5.26 – 5.14 (m, 2H), 3.87 (s, 6H), 3.84 (s,
3H), 2.90 (dd, J = 14.1, 7.2 Hz, 1H), 2.80 (dd, J = 14.2, 7.1 Hz,
1H), 2.68 (dd, J = 14.3, 7.8 Hz, 1H), 2.59 (dd, J = 14.0, 7.6 Hz,
1H), 1.58 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 153.3, 138.0,
135.4, 132.3, 130.8, 121.4, 120.8, 103.4, 90.9, 60.9, 56.1, 43.6,
42.7, 22.0. IR (KBr) γ 3453, 2938, 1582, 1537, 1506, 1455, 1417,
1388, 1349, 1326, 1240, 1127, 1007, 969, 926, 854 cmꢀ1. HRMS
(ESI) (m/z): [M+H]+ calcd for C17H24NO5, 322.1802; found,
322.1805.
1
Yield: 15.4 mg, 50%. H NMR (400 MHz, CDCl3) δ 7.20 (t, J =
7.5 Hz, 1H), 7.15 (s, 1H), 7.13 (d, J = 8.1 Hz, 1H), 7.06 (d, J =
7.3 Hz, 1H), 6.45 (d, J = 15.7 Hz, 1H), 6.11 – 5.95 (m, 1H), 5.70
(td, J = 17.2, 7.4 Hz, 1H), 5.21 (d, J = 6.5 Hz, 1H), 5.18 (d, J =
13.7 Hz, 1H), 2.89 (dd, J = 14.3, 7.2 Hz, 1H), 2.79 (dd, J = 14.2,
7.0 Hz, 1H), 2.69 (dd, J = 14.1, 7.6 Hz, 1H), 2.59 (dd, J = 14.1,
7.6 Hz, 1H), 2.34 (s, 3H), 1.57 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 137.7, 135.3, 133.8, 130.9, 129.3, 126.2, 121.0, 120.7,
90.9, 43.5, 42.7, 22.1, 21.2. IR (KBr) γ 3456, 2921, 1642, 1538,
1455, 1387, 1352, 996, 969, 926, 775, 692 cmꢀ1. HRMS (ESI)
(m/z): [M+H]+ calcd for C15H20NO2, 246.1494; found, 246.1494.
(E)-1-(tert-butyl)-4-(4-methyl-4-nitrohepta-1,6-dien-1-
yl)benzene (3c)
(E)-1-methyl-2-(4-methyl-4-nitrohepta-1,6-dien-1-yl)benzene
(3h)
1
Yield: 7.7 mg, 25%. H NMR (400 MHz, CDCl3) δ 7.40 – 7.33
(m, 1H), 7.21 – 7.10 (m, 3H), 6.68 (d, J = 15.7 Hz, 1H), 5.97 –
5.84 (m, 1H), 5.71 (td, J = 17.2, 7.8 Hz, 1H), 5.21 (d, J = 5.4 Hz,
1H), 5.18 (d, J = 13.0 Hz, 1H), 2.91 (dd, J = 14.2, 7.4 Hz, 1H),
2.80 (dd, J = 14.1, 7.1 Hz, 1H), 2.73 (dd, J = 14.1, 7.6 Hz, 1H),
2.61 (dd, J = 14.2, 7.6 Hz, 1H), 2.32 (s, 3H), 1.59 (s, 3H). 13C
NMR (101 MHz, CDCl3) δ 136.0, 135.3, 133.6, 130.9, 130.3,
127.7, 126.1, 125.8, 123.6, 120.7, 91.0, 43.5, 42.9, 22.11, 19.80.
IR (KBr) γ 3463, 2921, 2852, 1642, 1538, 1386, 1352, 969, 927,
749 cmꢀ1. HRMS (ESI) (m/z): [M+H]+ calcd for C15H20NO2,
246.1494; found, 246.1466.
1
Yield: 18.0 mg, 50%. H NMR (400 MHz, CDCl3) δ 7.34 (d, J =
8.3 Hz, 2H), 7.28 (d, J = 8.3 Hz, 2H), 6.46 (d, J = 15.7 Hz, 1H),
6.07 – 5.93 (m, 1H), 5.70 (td, J = 17.2, 7.5 Hz, 1H), 5.25 – 5.12
(m, 2H), 2.88 (dd, J = 14.3, 7.2 Hz, 1H), 2.78 (dd, J = 14.2, 7.2
Hz, 1H), 2.70 (dd, J = 14.1, 7.9 Hz, 1H), 2.58 (dd, J = 14.1, 7.5
Hz, 1H), 1.57 (s, 3H), 1.31 (s, 9H). 13C NMR (101 MHz, CDCl3)
δ 151.0, 135.2, 133.9, 130.9, 126.1, 125.5, 121.2, 120.7, 90.9,
43.5, 42.7, 34.6, 31.3, 22.1. IR (KBr) γ 3465, 2963, 1540, 1460,
1387, 1352, 1269, 995, 971, 926, 855, 831, 553 cmꢀ1. HRMS
(ESI) (m/z): [M+H]+ calcd for C18H26NO2, 288.1958; found,
288.1972.
1-methyl-3-((1E,6E)-4-methyl-4-nitro-7-phenylhepta-1,6-dien-
1-yl)benzene (3i)
(E)-1-fluoro-4-(4-methyl-4-nitrohepta-1,6-dien-1-yl)benzene
(3d)
1
Yield: 18.1 mg, 45%. H NMR (400 MHz, CDCl3) δ 7.33 (q, J =
7.3 Hz, 4H), 7.25 (d, J = 3.9 Hz, 1H), 7.23 – 7.18 (m, 1H), 7.16
(s, 1H), 7.14 (d, J = 8.0 Hz, 1H), 7.06 (d, J = 7.4 Hz, 1H), 6.57 –
6.40 (m, 2H), 6.05 (dq, J = 14.9, 7.3 Hz, 2H), 2.99 – 2.89 (m,
2H), 2.74 (dd, J = 14.2, 7.8 Hz, 2H), 2.34 (s, 3H), 1.62 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 138.2, 136.6, 136.5, 135.6, 135.5,
128.6, 128.5, 127.8, 127.0, 126.4, 123.6, 122.1, 121.8, 91.19,
42.8, 42.8, 22.3, 21.4. IR (KBr) γ 3462, 3028, 2921, 1598, 1536,
1492, 1450, 1387, 1349, 969, 746, 692 cmꢀ1. HRMS (ESI) (m/z):
[M+H]+ calcd for C21H24NO2, 322.1802; found, 322.1805.
1
Yield: 12.5 mg, 50%. H NMR (400 MHz, CDCl3) δ 7.36 – 7.27
(m, 2H), 6.99 (t, J = 8.5 Hz, 2H), 6.44 (d, J = 15.7 Hz, 1H), 5.95
(dt, J = 15.5, 7.6 Hz, 1H), 5.70 (td, J = 17.2, 7.6 Hz, 1H), 5.27 –
5.12 (m, 2H), 2.89 (dd, J = 14.2, 7.2 Hz, 1H), 2.79 (dd, J = 13.9,
7.0 Hz, 1H), 2.68 (dd, J = 14.2, 7.8 Hz, 1H), 2.59 (dd, J = 14.0,
7.5 Hz, 1H), 1.58 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 162.4
(d, J = 247.2 Hz), 134.2, 132.8 (d, J = 3.4 Hz), 130.8, 127.86 (d, J
= 8.0 Hz), 121.79 (d, J = 2.2 Hz), 120.78, 115.5 (d, J = 21.6 Hz),
90.9, 43.5, 42.6, 22.1. IR (KBr) γ 3465, 2921, 1601, 1538, 1508,
1387, 1351, 1228, 1158, 970, 927 cmꢀ1. HRMS (ESI) (m/z):
[M+H]+ calcd for C14H17FNO2, 250.1238; found, 250.1254.
(E)-1-methyl-3-(4-methyl-4-nitrohepta-1,6-dien-1-yl)benzene
(3e)
(E)-3-methyl-3-(4-nitrophenyl)-6-(p-tolyl)hex-5-en-2-one (6a)
1
Yield: 36.4 mg, 90%. H NMR (400 MHz, CDCl3) δ 8.23 (d, J =
7.8 Hz, 2H), 7.43 (d, J = 7.9 Hz, 2H), 7.13 (d, J = 7.5 Hz, 2H),
7.07 (d, J = 7.7 Hz, 2H), 6.33 (d, J = 15.7 Hz, 1H), 5.87 – 5.69 (m,
1H), 2.94 – 2.70 (m, 2H), 2.31 (s, 3H), 1.98 (s, 3H), 1.58 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 208.7, 149.9, 147.0, 137.3, 134.2,
134.0, 129.2, 127.5, 126.0, 124.0, 123.4, 56.5, 41.8, 26.3, 21.3,
1
Yield: 17.2 mg, 56%. H NMR (400 MHz, CDCl3) δ 7.23 (d, J =
7.8 Hz, 2H), 7.12 (d, J = 7.8 Hz, 2H), 6.45 (d, J = 15.7 Hz, 1H),
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The Journal of Organic Chemistry
21.2. IR (KBr) γ 3025, 2975, 2922, 1710, 1604, 1519, 1457,
136.2, 135.0, 132.3, 130.2, 127.6, 127.4, 126.1, 125.9, 125.7,
1347, 1111, 1075, 970, 858, 793, 700, 505 cmꢀ1. HRMS (ESI)
(m/z): [M+H]+ calcd for C20H22NO3, 324.1594; found, 324.1621.
(E)-6-(4-methoxyphenyl)-3-methyl-3-(4-nitrophenyl)hex-5-en-
2-one (6b)
124.0, 56.5, 42.0, 26.3, 21.3, 19.7. IR (KBr) γ 3458, 2975, 1710,
1604, 1520, 1485, 1460, 1347, 1111, 969, 857, 749, 700 cmꢀ1.
HRMS (ESI) (m/z): [M+H]+ calcd for C20H22NO3, 324.1594;
found, 324.1616.
1
2
3
4
5
6
7
8
1
Yield: 30.8 mg, 73%. H NMR (400 MHz, CDCl3) δ 8.23 (d, J =
(E)-6-(2-fluorophenyl)-3-methyl-3-(4-nitrophenyl)hex-5-en-2-
one (6h)
8.8 Hz, 2H), 7.44 (d, J = 8.8 Hz, 2H), 7.17 (d, J = 8.6 Hz, 2H),
6.80 (d, J = 8.6 Hz, 2H), 6.31 (d, J = 15.6 Hz, 1H), 5.74 – 5.60
(m, 1H), 3.78 (s, 3H), 2.88 – 2.74 (m, 2H), 1.98 (s, 3H), 1.58 (s,
3H). 13C NMR (101 MHz, CDCl3) δ 208.7, 159.1, 149.9, 147.0,
133.5, 129.8, 127.5, 127.3, 124.0, 122.1, 113.9, 56.5, 55.3, 41.8,
26.3, 21.3. IR (KBr) γ 3443, 2935, 1709, 1605, 1511, 1463, 1346,
1246, 1112, 1037, 857, 750, 700 cmꢀ1. HRMS (ESI) (m/z):
[M+H]+ calcd for C20H22NO4, 340.1543; found, 340.1549.
(E)-6-(4-fluorophenyl)-3-methyl-3-(4-nitrophenyl)hex-5-en-2-
one (6c)
1
Yield: 17.8 mg, 44%. H NMR (400 MHz, CDCl3) δ 8.24 (d, J =
8.6 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H), 7.29 – 7.23 (m, 1H), 7.17
(dd, J = 13.4, 6.4 Hz, 1H), 7.09 – 6.93 (m, 2H), 6.51 (d, J = 15.9
Hz, 1H), 5.99 – 5.83 (m, 1H), 2.97 – 2.77 (m, 2H), 1.99 (s, 3H),
1.61 (s, 4H). 13C NMR (101 MHz, CDCl3) δ 208.5, 159.9 (d, J =
248.9 Hz), 149.6, 147.0, 128.7 (d, J = 8.3 Hz), 127.49, 127.36 (d,
J = 4.7 Hz), 127.17 (d, J = 3.8 Hz), 126.53 (d, J = 3.5 Hz), 124.69
(d, J = 12.3 Hz), 124.07, 124.03, 115.7 (d, J = 22.2 Hz), 56.4,
42.2, 26.2, 21.2. IR (KBr) γ 3452, 2927, 1710, 1604, 1520, 1487,
1456, 1347, 1229, 1110, 970, 856, 754, 700 cmꢀ1. HRMS (ESI)
(m/z): [M+H]+ calcd for C19H19FNO3, 328.1343; found, 328.1367.
(E)-3-methyl-6-(naphthalen-1-yl)-3-(4-nitrophenyl)hex-5-en-2-
one (6i)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
Yield: 37.7 mg, 92%. H NMR (400 MHz, CDCl3) δ 8.24 (d, J =
8.7 Hz, 2H), 7.44 (d, J = 8.7 Hz, 2H), 7.25 – 7.15 (m, 2H), 6.95 (t,
J = 8.6 Hz, 2H), 6.33 (d, J = 15.7 Hz, 1H), 5.82 – 5.68 (m, 1H),
2.91 – 2.73 (m, 2H), 1.98 (s, 3H), 1.60 (s, 3H). 13C NMR (101
MHz, CDCl3) δ 208.6, 162.2(d, 246.73), 149.7, 147.0, 133.1 (d, J
= 3.3 Hz), 132.9, 127.59 (d, J = 7.9 Hz), 127.48, 124.27 (d, J =
2.2 Hz), 124.02, 115.4 (d, J = 21.6 Hz)., 56.4, 41.8, 26.2, 21.2. IR
(KBr) γ 3446, 2979, 1710, 1602, 1520, 1509, 1348, 1227, 1158,
970, 858, 700, 514 cmꢀ1. HRMS (ESI) (m/z): [M+H]+ calcd for
C19H19FNO3, 328.1343; found, 328.1363.
1
Yield: 29.9 mg, 67%. H NMR (400 MHz, CDCl3) δ 8.25 (d, J =
8.8 Hz, 2H), 7.83 (dd, J = 9.3, 7.2 Hz, 2H), 7.74 (t, J = 4.7 Hz,
1H), 7.51 – 7.42 (m, 4H), 7.38 (d, J = 5.0 Hz, 2H), 7.04 (d, J =
15.5 Hz, 1H), 5.85 (dt, J = 15.3, 7.6 Hz, 1H), 2.95 (d, J = 7.5 Hz,
2H), 2.01 (s, 3H), 1.67 (s, 3H). 13C NMR (101 MHz, CDCl3) δ
208.6, 149.7, 147.0, 134.9, 133.5, 131.8, 130.9, 128.5, 127.9,
127.9, 127.6, 126.0, 125.8, 125.6, 124.0, 123.8, 123.6, 56.6, 42.2,
26.3, 21.3. IR (KBr) γ 3451, 1709, 1621, 1604, 1519, 1346, 1289,
1111, 1074, 1039, 970, 855, 777, 700 cmꢀ1. HRMS (ESI) (m/z):
[M+H]+ calcd for C23H22NO3, 360.1594; found, 360.1598.
(E)-3-methyl-3-(4-nitrophenyl)-6-(m-tolyl)hex-5-en-2-one (6d)
1
Yield: 31.5 mg, 78%. H NMR (400 MHz, CDCl3) δ 8.24 (d, J =
8.6 Hz, 2H), 7.44 (d, J = 8.6 Hz, 2H), 7.16 (t, J = 7.5 Hz, 1H),
7.09 – 6.97 (m, 3H), 6.34 (d, J = 15.8 Hz, 1H), 5.82 (dt, J = 15.2,
7.4 Hz, 1H), 2.97 – 2.73 (m, 2H), 2.31 (s, 3H), 1.98 (s, 3H), 1.59
(s, 3H). 13C NMR (101 MHz, CDCl3) δ 208.7, 149.8, 147.0,
138.2, 136.8, 134.3, 128.5, 128.3, 127.5, 126.8, 124.2, 124.0,
123.3, 56.5, 41.9, 26.3, 21.4, 21.3. IR (KBr) γ 3463, 2923, 1710,
1604, 1519, 1347, 1110, 968, 855, 776, 754, 698 cmꢀ1. HRMS
(ESI) (m/z): [M+H]+ calcd for C20H22NO3, 324.1594; found,
324.1616.
(E)-3-benzyl-3-(4-nitrophenyl)-6-phenylhex-5-en-2-one (6j)
1
Yield: 32.7 mg, 67%. H NMR (400 MHz, CDCl3) δ 8.21 (d, J =
8.7 Hz, 2H), 7.38 – 7.24 (m, 7H), 7.19 – 7.07 (m, 3H), 6.66 (d, J
= 6.9 Hz, 2H), 6.53 (d, J = 15.7 Hz, 1H), 6.12 – 5.99 (m, 1H),
3.38 (d, J = 14.1 Hz, 1H), 3.25 (d, J = 14.2 Hz, 1H), 2.99 – 2.80
(m, 2H), 2.03 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 207.9,
148.9, 147.1, 136.7, 136.1, 134.8, 130.2, 128.7, 128.2, 128.0,
127.8, 126.8, 126.3, 123., 123.3, 61.2, 40.6, 35.6, 27.1. IR (KBr)
γ 3462, 2959, 1737, 1521, 1403, 1386, 1370, 1348, 1208, 1176,
1121, 1020, 915, 855, 701 cmꢀ1. HRMS (ESI) (m/z): [M+H]+
calcd for C25H23NO3Na, 408.1570; found, 408.1579.
(E)-6-(3,4-dimethoxyphenyl)-3-methyl-3-(4-nitrophenyl)hex-5-
en-2-one (6e)
1
Yield: 41.1 mg, 89%. H NMR (400 MHz, CDCl3) δ 8.23 (d, J =
8.6 Hz, 2H), 7.44 (d, J = 8.6 Hz, 2H), 6.83 – 6.72 (m, 3H), 6.29
(d, J = 15.6 Hz, 1H), 5.78 – 5.63 (m, 1H), 3.85 (s, 6H), 2.85 (dd, J
= 14.2, 7.9 Hz, 1H), 2.76 (dd, J = 14.1, 6.9 Hz, 1H), 1.98 (s, 3H),
1.59 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 208.8, 149.9, 149.0,
148.7, 147.0, 133.9, 130.1, 127.5, 124.0, 122.4, 119.1, 111.1,
108.8, 56.5, 55.9, 55.9, 41.9, 26.3, 21.3. IR (KBr) γ 3452, 2935,
1709, 1603, 1516, 1464, 1347, 1265, 1158, 1139, 1026, 968, 857,
700 cmꢀ1. HRMS (ESI) (m/z): [M+H]+ calcd for C21H24NO5,
370.1649; found, 370.1661.
Ethyl (E)-2-methyl-2-(4-nitrophenyl)-5-phenylpent-4-enoate
(6k)
1
Yield: 24.5 mg, 58%. H NMR (400 MHz, CDCl3) δ 8.20 (d, J =
8.7 Hz, 2H), 7.51 (d, J = 8.7 Hz, 2H), 7.38 – 7.14 (m, 5H), 6.42
(d, J = 15.7 Hz, 1H), 6.04 – 5.88 (m, 1H), 4.17 (q, J = 7.1 Hz,
2H), 2.98 (dd, J = 13.8, 7.7 Hz, 1H), 2.83 (dd, J = 13.8, 7.2 Hz,
1H), 1.63 (s, 3H), 1.20 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz,
CDCl3) δ 174.6, 150.8, 146.8, 137.0, 134.4, 128.6, 127.5, 127.3,
126.2, 124.4, 123.6, 61.4, 50.9, 43.0, 22.8, 14.1. IR (KBr) γ 2981,
1728, 1604, 1521, 1496, 1449, 1348, 1229, 1114, 1015, 969, 856,
742, 694 cmꢀ1. HRMS (ESI) (m/z): [M+H]+ calcd for C20H22NO4,
340.1543; found, 340.1563.
(E)-3-methyl-3-(4-nitrophenyl)-6-(3,4,5-
trimethoxyphenyl)hex-5-en-2-one (6f)
1
Yield: 45.0 mg, 90%. H NMR (400 MHz, CDCl3) δ 8.26 – 8.20
(m, 2H), 7.49 – 7.40 (m, 2H), 6.45 (s, 2H), 6.27 (d, J = 15.7 Hz,
1H), 5.84 – 5.68 (m, 1H), 3.83 (s, 6H), 3.81 (s, 3H), 2.86 (dd, J =
14.2, 7.7 Hz, 1H), 2.74 (dd, J = 14.1, 7.2 Hz, 1H), 1.98 (s, 3H),
1.60 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 208.7, 153.3, 149.8,
147.0, 137.7, 134.2, 132.7, 127.5, 124.02, 123.95, 103.2, 60.9,
56.5, 56.1, 41.9, 26.3, 21.3. IR (KBr) γ 3459, 2939, 1581, 1519,
1456, 1418, 1347, 1239, 1158, 1127, 1009, 967, 857, 700 cmꢀ1.
HRMS (ESI) (m/z): [M+H]+ calcd for C22H26NO6, 400.1755;
found, 400.1761.
General procedure C for the deacylative allylation with alkyl
acetylacetates
To a flameꢀdried schlenk tube (25 mL) were added alkyl acetyꢀ
lacetate 7 (0.125 mmol), allylarene 2 (0.5 mmol), Pd(OAc)2 (5
mol%, 0.00625 mmol, 1.4 mg), PPh3 (20 mol%, 0.025 mmol, 6.5
mg), NaOH solution (4.0 equiv, 0.5 mmol, 20 M, 25 ꢁL), 2,5ꢀ
t
DTBQ (1.2 equiv, 0.15 mmol, 33.1 mg), BuOH (0.4 mL), THF
(0.4 mL) and a stir bar. The solution was stirred at 40 oC for 36 h,
(E)-3-methyl-3-(4-nitrophenyl)-6-(o-tolyl)hex-5-en-2-one (6g)
1
o
Yield: 28.8 mg, 71%. H NMR (400 MHz, CDCl3) δ 8.23 (d, J =
under N2. The solution was warmed up to 90 C and stirred for
8.5 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H), 7.22 (d, J = 6.7 Hz, 1H),
7.15 – 7.06 (m, 3H), 6.55 (d, J = 15.6 Hz, 1H), 5.70 (dt, J = 15.2,
7.4 Hz, 1H), 2.94 – 2.77 (m, 2H), 2.23 (s, 3H), 1.99 (s, 3H), 1.61
(s, 3H). 13C NMR (101 MHz, CDCl3) δ 208.6, 149.8, 147.0,
another 36 h. Then the vial was cooled down to room temperature,
the reaction mixture was directly subjected on flash chromatogꢀ
raphy (SiO2, EtOAc/EtOH = 1:1) to provide the allylation product
8.
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Page 6 of 7
(E)-2-methyl-5-phenylpent-4-enoic acid (8a)
General procedure E for the deacylative allylation with Di-
carbonyl compounds to construct tertiary center under tan-
dem catalysis process
1
1
2
3
4
5
6
7
8
Yield: 19.5 mg, 82%. H NMR (400 MHz, CDCl3) δ 7.37 – 7.27
(m, 4H), 7.23 – 7.17 (m, 1H), 6.45 (d, J = 15.8 Hz, 1H), 6.21 –
6.11 (m, 1H), 2.78 – 2.54 (m, 2H), 2.45 – 2.29 (m, 1H), 1.24 (d, J
= 6.9 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 181.3, 137.3,
132.4, 128.5, 127.2, 126.8, 126.2, 39.3, 36.7, 16.5. IR (KBr) γ
3461, 3027, 2976, 2930, 1706, 1494, 1461, 1416, 1285, 1238,
965, 741, 693 cmꢀ1. HRMS (ESI) (m/z): [MꢀH]ꢀ calcd for
C12H13O2, 189.0910; found, 189.0931.
To a flameꢀdried schlenk tube (25 mL) were added dicarbonyl
compounds 13 (0.125 mmol), allylarene 2a (0.5 mmol), Pd(OAc)2
(5 mol%, 0.00625 mmol, 1.4 mg), PPh3 (20 mol%, 0.025 mmol,
6.5 mg), allyl methyl carbonate (1.0 equiv., 14 ꢁL), THF (0.4 mL)
and a stir bar. The solution was stirred at room temperature for 1
h, under N2. After that time, base, 2,5ꢀDTBQ (1.2 equiv, 0.15
t
mmol, 33.1 mg) and BuOH (0.4 mL) were added. The solution
(E)-2-cinnamylhexanoic acid (8b)
9
Yield: 22.2 mg, 77 %. 1H NMR (400 MHz, CDCl3) δ 7.39 – 7.24
(m, 4H), 7.20 (t, J = 7.0 Hz, 1H), 6.44 (d, J = 15.8 Hz, 1H), 6.23 –
6.08 (m, 1H), 2.62 – 2.47 (m, 2H), 2.46 – 2.34 (m, 1H), 1.79 –
1.48 (m, 2H), 1.43 – 1.27 (m, 4H), 0.89 (s, 3H). 13C NMR (101
MHz, CDCl3) δ 181.5, 137.4, 132.2, 128.5, 127.2, 127.0, 126.2,
45.4, 35.3, 31.3, 29.4, 22.6, 13.9. IR (KBr) γ 3027, 2957, 2930,
2859, 1705, 1494, 1452, 1417, 1285, 1239, 964, 740, 692 cmꢀ1.
HRMS (ESI) (m/z): [MꢀH]ꢀ calcd for C15H19O2, 231.1380; found,
231.1402.
was stirred at 40 oC for 24 h, under N2. The solution was warmed
o
up to 80 or 90 C and stirred for another 24 h. Then the vial was
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12
13
14
15
16
17
18
19
20
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23
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27
28
29
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31
32
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34
35
36
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48
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cooled down to room temperature, the reaction mixture was diꢀ
rectly subjected on flash chromatography (SiO2, PE/DCM = 2:1)
to provide the allylation product 14.
(E)-3-allyl-6-phenylhex-5-en-2-one (14a)
Yield: 12.2 mg, 47 %. 1H NMR (400 MHz, CDCl3) δ 7.36 – 7.27
(m, 4H), 7.23 – 7.16 (m, 1H), 6.41 (d, J = 15.8 Hz, 1H), 6.10 (dt,
J = 15.7, 7.3 Hz, 1H), 5.74 (ddt, J = 17.1, 10.2, 7.0 Hz, 1H), 5.11
– 5.01 (m, 2H), 2.77 – 2.68 (m, 1H), 2.51 (dtd, J = 8.7, 7.4, 1.3
Hz, 1H), 2.45 – 2.32 (m, 2H), 2.30 – 2.21 (m, 1H), 2.15 (s, 3H),
1.56 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 211.1, 137.2, 135.2,
132.3, 128.5, 127.3, 126.9, 126.1, 117.2, 52.4, 35.3, 34.39, 29.78.
IR (KBr) γ 3462, 3079, 3026, 2925, 2852, 1711, 1641, 1493,
1442, 1356, 1162, 1026, 966, 916, 743, 693 cmꢀ1. HRMS (ESI)
(m/z): [M+H]+ calcd for C15H19O, 215.1430; found, 215.1429.
tert-butyl (E)-2-allyl-5-phenylpent-4-enoate (14b)
(E)-2-cinnamylheptanoic acid (8c)
Yield: 19.5 mg, 63 %. 1H NMR (400 MHz, CDCl3) δ 7.38 – 7.24
(m, 4H), 7.20 (t, J = 7.2 Hz, 1H), 6.44 (d, J = 15.8 Hz, 1H), 6.24 –
6.07 (m, 1H), 2.61 – 2.47 (m, 2H), 2.47 – 2.34 (m, 1H), 1.74 –
1.61 (m, 1H), 1.60 – 1.48 (m, 1H), 1.40 – 1.19 (m, 6H), 0.88 (t, J
= 6.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 181.1, 137.4,
132.2, 128.5, 127.2, 127.0, 126.1, 45.4, 35.3, 31.7, 31.6, 26.9,
22.5, 14.0. IR (KBr) γ 3457, 3027, 2955, 2928, 2857, 1706, 1447,
1411, 1280, 1240, 964, 740, 692 cmꢀ1. HRMS (ESI) (m/z): [Mꢀ
H]ꢀ calcd for C16H21O2, 245.1536; found, 245.1559.
1
Yield: 23.5 mg, 69%. H NMR (400 MHz, CDCl3) δ 7.35 – 7.26
(m, 4H), 7.23 – 7.17 (m, 1H), 6.41 (d, J = 15.6 Hz, 1H), 6.15 (dt,
J = 15.7, 6.9 Hz, 1H), 5.78 (ddt, J = 17.0, 10.2, 6.9 Hz, 1H), 5.15
– 4.97 (m, 2H), 2.54 – 2.43 (m, 2H), 2.43 – 2.32 (m, 2H), 2.30 –
2.21 (m, 1H), 1.42 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 174.2,
137.5, 135.5, 131.9, 128.5, 127.3, 127.1, 126.1, 116.7, 80.4, 46.0,
36.1, 35.3, 28.2. IR (KBr) γ 3445, 3027, 2977, 2930, 1727, 1643,
1441, 1368, 1237, 1151, 965, 916, 847, 741, 693 cmꢀ1. HRMS
(ESI) (m/z): [M+H]+ calcd for C18H25O2, 273.1849; found,
273.1847.
(E)-3-methyl-6-phenylhex-5-en-2-one (8d)
1
Yield: 16.5 mg, 70 %. H NMR (400 MHz, CDCl3) δ 7.35 – 7.26
(m, 4H), 7.23 – 7.18 (m, 1H), 6.41 (d, J = 15.8 Hz, 1H), 6.12 (dt,
J = 15.7, 7.2 Hz, 1H), 2.76 – 2.61 (m, 1H), 2.56 (dtd, J = 8.0, 6.8,
1.3 Hz, 1H), 2.32 – 2.20 (m, 1H), 2.17 (s, 3H), 1.15 (d, J = 7.0
Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 211.9, 137.3, 132.1,
128.5, 127.3, 127.2, 126.1, 47.1, 36.2, 28.5, 16.1. IR (KBr) γ
3461, 3199, 2923, 2852, 1712, 1657, 1632, 1454, 1405, 1359,
966, 742, 693 cmꢀ1. HRMS (ESI) (m/z): [M+H]+ calcd for
C13H17O, 189.1274; found, 189.1271.
General procedure F for the decarboxylative allylation with
alkynyl acids
To a flameꢀdried schlenk tube (25 mL) were added alkynyl acids
11 (0.25 mmol), Pd(TFA)2 (10 mol%, 0.025 mmol, 8.3 mg), PPh3
(40 mol%, 0.10 mmol, 26.2 mg), Cs2CO3 (2 equiv, 0.5 mmol,
163.0 mg), 2,5ꢀDTBQ (2 equiv, 0.5 mmol, 110.2 mg), 2 (4.0
equiv, 1.0 mmol), oꢀFBA (1 equiv, 0.25mmol, 35.0 mg), toluene
(3.0 mL) and a stir bar. The solution was subjected to three
freezeꢀpumpꢀthaw cycles using liquid nitrogen to degas, then the
General procedure D for the deacylative allylation with acety-
lacetones under tandem catalysis process
To a flameꢀdried schlenk tube (25 mL) were added acetylacetone
9 (0.125 mmol), oꢀFBA (10% mol), Pd(PPh3)4 (5% mol), allyl
methyl carbonate (1.0 equiv., 14ꢁL), THF (0.4 mL) and a stir bar.
The solution was stirred at room temperature for 1 h, under N2.
After that time, Cs2CO3 (1.2 equiv, 0.15 mmol, 48.9 mg), 2,5ꢀ
DTBQ (1.2 equiv, 0.15 mmol, 33.1 mg), 2a (4.0 equiv, 0.5
mmol), and another 0.4 mL THF was added into the solution. And
o
mixture was stirred at 75 C for 22 h. After the vial was cooled
down to room temperature, the reaction mixture was subjected
directly on flash chromatography (SiO2, Petroleum ether/EtOAc =
100:1) to provide the allylation product 12.
o
the mixture was stirred at 80 C for 18 hours. After the vial was
cooled down to room temperature, the reaction mixture was subꢀ
jected directly on flash chromatography (SiO2, Petroleum
ether/EtOAc = 10:1) to provide the allylation product 9.
(E)-pent-1-en-4-yne-1,5-diyldibenzene (16a)
1
Yield: 22.0 mg, 40%. H NMR (400 MHz, CDCl3) δ 7.45 (d, J =
3.7 Hz, 2H), 7.39 (d, J = 7.4 Hz, 2H), 7.35 – 7.27 (m, 5H), 7.27 –
7.19 (m, 1H), 6.71 (d, J = 15.7 Hz, 1H), 6.25 (dt, J = 15.7, 5.6 Hz,
1H), 3.36 (d, J = 5.5 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ
137.1, 131.65, 131.43, 128.56, 128.27, 127.85, 127.4, 126.29,
124.26, 123.65, 86.8, 82.9, 23.0. IR (KBr) γ 3080, 3028, 2878,
1750, 1653, 1598, 1574, 1490, 1444, 1414, 1341, 1310, 1269,
1177, 1070, 1027, 964, 840, 795, 755, 690 cmꢀ1. HRMS (ESI)
(m/z): [M+H]+ calcd for C17H15, 219.1168; found, 219.1171.
(E)-1-methyl-4-(5-phenylpent-1-en-4-yn-1-yl)benzene (16b)
(E)-3-allyl-3-(4-nitrophenyl)-6-phenylhex-5-en-2-one (12)
1
Yield: 34.4 mg, 82%. H NMR (400 MHz, CDCl3) δ 8.25 (d, J =
8.9 Hz, 2H), 7.41 (d, J = 8.9 Hz, 2H), 7.32 – 7.17 (m, 5H), 6.40
(d, J = 15.8 Hz, 1H), 5.80 – 5.68 (m, 1H), 5.50 (dt, J = 16.2, 7.3
Hz, 1H), 5.18 – 5.08 (m, 2H), 2.92 (d, J = 7.5 Hz, 2H), 2.83 (d, J
= 7.2 Hz, 2H), 1.97 (s, 3H). 13C NMR (101 MHz, CDCl3) δ
207.7, 148.8, 147.1, 136.8, 134.5, 132.0, 128.6, 127.8, 127.6,
126.1, 124.0, 123.5, 119.7, 59.9, 37.7, 37.1, 26.6. IR (KBr) γ
3081, 3027, 2925, 2854, 1709, 1597, 1495, 1447, 1347, 1188,
1165, 1111, 1014, 968, 924, 857, 746, 695 cmꢀ1. HRMS (ESI)
(m/z): [M+H]+ calcd for C21H22NO3, 336.1594; found, 336.1618.
1
Yield: 14.2 mg, 24%. H NMR (400 MHz, CDCl3) δ 7.45 (d, J =
4.0 Hz, 2H), 7.34 – 7.26 (m, 5H), 7.12 (d, J = 7.7 Hz, 2H), 6.68
(d, J = 15.7 Hz, 1H), 6.20 (dt, J = 15.6, 5.6 Hz, 1H), 3.35 (d, J =
5.4 Hz, 2H), 2.33 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 137.1,
134.3, 131.6, 131.3, 129.2, 128.3, 127.8, 126.2, 123.7, 123.2,
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The Journal of Organic Chemistry
86.9, 82.5, 23.0, 21.2. IR (KBr) γ 3454, 2962, 2924, 1621, 1512,
M. C. J. Am. Chem. Soc. 2008, 130, 14090. (c) Young, A. J.;
1490, 1412, 1384, 1261, 1096, 1027, 869, 799, 755, 691 cmꢀ1.
HRMS (ESI) (m/z): [M+H]+ calcd for C18H17, 233.1325; found,
233.1315.
White, M. C. Angew. Chem., Int. Ed. 2011, 50, 6824. (d)
Trost, B. M.; Hansmann, M. M.; Thaisrivongs, D. A. Angew.
Chem., Int. Ed. 2012, 51, 4950. (e) Tang, S.; Wu, X.; Liao,
W.; Liu, K.; Liu, C.; Luo, S.; Lei, A. Org. Lett. 2014, 16,
3584.
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2
3
4
(E)-1-methyl-3-(5-phenylpent-1-en-4-yn-1-yl)benzene (16c)
1
Yield: 16.4 mg, 28%. H NMR (400 MHz, CDCl3) δ 7.51 – 7.40
5
6
7
8
(m, 2H), 7.36 – 7.27 (m, 3H), 7.24 – 7.16 (m, 3H), 7.10 – 6.99 (m,
1H), 6.68 (dt, J = 15.7, 1.6 Hz, 1H), 6.29 – 6.19 (m, 1H), 3.36
(dd, J = 5.6, 1.7 Hz, 2H), 2.34 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 138.1, 137.0, 131.7, 131.5, 128.5, 128.2, 128.2, 127.8,
127.1, 124.0, 123.7, 123.4, 86.8, 82.8, 23.0, 21.4. IR (KBr) γ
3465, 3031, 2920, 1599, 1489, 1442, 1415, 1274, 1070, 964, 775,
755, 690 cmꢀ1. HRMS (ESI) (m/z): [M+H]+ calcd for C18H17,
233.1325; found, 233.1345.
(6) (a) Tao, Z. L.; Zhang, W. Q.; Chen, D. F.; Adele, A.; Gong, L.
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L.; Han, Z. Y.; Gong, L. Z. Org. Lett. 2016.
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Angew. Chem., Int. Ed. 2012, 51, 11522. (b) Li, L.; Chen, Q.
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White, M. C. J. Am. Chem. Soc. 2014, 136, 5750. (e) Lin, H.
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(14)30% yield of cinnamyl methyl ether was obtained when
MeOH was used.
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(E)-1-fluoro-4-(5-phenylpent-1-en-4-yn-1-yl)benzene (16d)
1
Yield: 24.6 mg, 42%. H NMR (400 MHz, CDCl3) δ 7.49 – 7.39
(m, 2H), 7.39 – 7.27 (m, 5H), 7.06 – 6.93 (m, 2H), 6.67 (d, J =
15.7 Hz, 1H), 6.16 (dt, J = 15.7, 5.6 Hz, 1H), 3.35 (dd, J = 5.6,
1.6 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ162.2 (d, J = 246.2
Hz), 133.3 (d, J = 3.3 Hz), 131.7, 130.3, 128.3, 127.9, 127.8 (d, J
= 7.9 Hz), 124.00 (d, J = 2.2 Hz), 123.58, 115.4 (d, J = 21.6 Hz),
86.6, 83.0, 23.0. IR (KBr) γ 3455, 3036, 1600, 1508, 1499, 1229,
1158, 1070, 965, 840, 756, 691 cmꢀ1. HRMS (ESI) (m/z):
[M+H]+ calcd for C17H14F, 237.1074; found, 237.1079.
AUTHOR INFORMATION
Corresponding Author
pusher@ustc.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We are grateful for financial support from NSFC (21602214), and
the China Postdoctoral Science Foundation (No. 2015M580534).
SUPPORTING INFORMATION
The Supporting Information is available free of charge on the
ACS Publications website.
1H and 13C NMR spectra for compounds 3, 6, 8, 12, 14,
16.
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