Negishi Coupling for Highly Selective Syntheses of Allenes via Ligand Effect and Mechanistic Study via SAESI-MS/MS

Article abstract of DOI:10.1002/cjoc.201900322

β-H elimination is an intrinsic problem in transition metal-catalyzed reactions. We describe herein an interesting ligand effect for Et₂Zn acting as either ethyl provider or H provider, respectively: by applying SPhos or Gorlos-Phos as the liga

Full text of DOI:10.1002/cjoc.201900322

Chinese Journal
of Chemistry
CJC
中 国 化 学 - An International Journal
Accepted Article
Title: Negishi Coupling for Highly Selective Syntheses of Allenes via Ligand Effect
and Mechanistic Study via SAESI-MS/MS
Authors: Yangguangyan Zheng, Bukeyan Miao, Anni Qin, Junzhe Xiao, Qi Liu, Gen Li,
Li Zhang, Fang Zhang, Yinlong Guo,* and Shengming Ma*
This manuscript has been accepted and appears as an Accepted Article online.
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Negishi Coupling for Highly Selective Syntheses of Allenes via
Ligand Effect and Mechanistic Study via SAESI-MS/MS
Yangguangyan Zheng,a† Bukeyan Miao,a† Anni Qin,a Junzhe Xiao,b Qi Liu,b Gen Li, a Li Zhang,b,c Fang
Zhang,b,c Yinlong Guo, b,c* and Shengming Maa,b*
Abstract: β-H elimination is an intrinsic problem in transition metal-
catalyzed reactions. We describe herein an interesting ligand effect
for Et2Zn acting as either ethyl provider or H provider, respectively:
by applying SPhos or Gorlos-Phos as the ligand, β-H elimination has
been successfully controlled in the corresponding Negishi coupling
reaction affording different poly-substituted allenes in good yields
and excellent selectivities. SAESI-MS (Solvent Assisted
Electrospray Ionization Mass Spectrometry) has been applied to
successfully capture the highly reactive organometallic intermediates,
which show the different coordination behaviors of Pd with SPhos or
Gorlos-Phos as the ligand in the catalytic cycle. In addition, the
different reactivities of Int 1 and Int 2 towards the formation of the
final allene products have been demonstrated via SAESI-MS/MS
experiments. These MS studies visualized the whole catalytic cycle
for the Negishi coupling reaction while nicely explains the observed
reactivity and selectivity.
observed for Et2Zn as either ethyl provider or H provider,
manipulating the β-H elimination with an excellent selectivity (eq.
3).
Scheme 1. Negishi coupling for synthesis of multi-substituted allenes
Introduction
Results and Discussion
Allenes not only commonly exist in nature but also have been
developed as powerful chemicals in modern organic synthesis,
medicinal chemistry, and material science.[1-3] Among the
coupling reactions, Negishi coupling, in which organozinc
compounds are applied, is one of the most powerful and
convenient methodologies widely used in modern organic
chemistry for C-C bond formation.[4] The palladium-catalyzed
syntheses of allenes by using organozinc reagents with no β–H,
such as aryl zinc, [5] alkenyl zinc[6] or alkynyl zinc reagents[7] with
terminal propargylic bromides, propargylic acetates, or allenyl
In our initial attempt, 1-phenylhept-2-ynyl methyl carbonate 1a
and diethyl zinc were used as the substrates for optimization of
the reaction conditions. After some extensive screening of the
reaction parameters, as expected, a mixture of ethylation
product 2a and β-H elimination product 3a was usually afforded,
and some of the typical results with at least a decent selectivity
are shown in Table 1. Under the catalysis of 5 mol% of Pd(OAc)2,
different ligands were screened for the reaction in anhydrous
DMF at room temperature. Bidentate phosphine ligands such as
DPPE or DPPF did not give useful results (Table 1, entries 1
and 2), so we turned to the mono-dentate phosphine ligands.
After some screening, we observed the exclusive formation of
ethylation product allene 2a when SPhos[11] was used (Table 1,
entry 4). Other mono-phosphine ligands such as MePhos,
XPhos, or Zheda-Phos[12] (Table 1, entries 5, 6, 11) also
afforded a mixture of ethylation product 2a and β-H elimination
product 3a with a high selectivity while the reactions with
BrettPhos or t-BuXPhos gave rather poor results (Table 1,
entries 6 and 8). The loadings of SPhos and diethyl zinc could
be reduced to 7.5 mol% and 2.0 equiv. respectively (Table 1,
entry 13). Further screening led to the observation that with LB-
Phos or Gorlos-Phos[12] as the ligand, β-H elimination-based
allene product 3a was formed with a very high selectivity (Table
1, entries 9 and 10). After further optimization, we found
Pd(OCOCF3)2/Gorlos-Phos at 0 oC with 1.5 equiv. of diethyl zinc
[8]
halides have been reported (Scheme 1, eqs. 1 and 2).
However, allene syntheses via cross-coupling between
propargylic compounds with alkyl zincs bearing β–H, especially
diethyl zinc, are still a significant challenge due to the intrinsic
issue of β-H elimination. [9,10] In this paper, we wish to report our
recent observation on Pd-catalyzed coupling reaction of diethyl
zinc with differently substituted terminal or non-terminal 2-
alkynylic carbonates, in which a dramatic ligand effect was
[a]
[b]
Department of Chemistry, Fudan University, 220 Handan Lu,
Shanghai 200433, P. R. China
State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, 345
Lingling Lu, Shanghai 200032, P. R. China
[c]
National Center for Organic Mass Spectrometry in Shanghai,
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Lu, Shanghai 200032, P. R. China
† These two people contributed equally.
Supporting information for this article is given via a link at the end of
the document.
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differences between this version and the Version of Record. Please cite this article as doi:
10.1002/cjoc.201900322
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RESEARCH ARTICLE
Table 2. The scope of Pd/SPhos-catalyzed cross-coupling reaction[a]
was the best, where 3a could be afforded exclusively in NMP or
DMF (Table 1, entries 16 and 17).
Table 1. Optimization of conditions for the palladium-catalyzed highly selective
cross-coupling reaction of propargylic carbonate 1a with Et2Zn[a]
1
Yield of 2
(%)
Entry
R1
n-Bu
R2
Ph
R3
H (1a)
H (1b)
H (1c)
H (1d)
H (1e)
H (1f)
H (1g)
H (1h)
H (1i)
H (1j)
H (1k)
H (1l)
H (1m)
H (1n)
85 (2a)
81 (2b)
91 (2c)
80 (2d)
89 (2e)
86 (2f)
86 (2g)
80 (2h)
71 (2i)
81 (2j)
90 (2k)
81 (2l)
88 (2m)
52 (2n)
81 (2o)
78 (2p)
82 (2q)
83 (2r)
86 (2x)
78 (2y)
1
2
4-Cl(CH2)4
Cyclohexyl
Cyclopropyl
n-Bu
Ph
3
Ph
4
Ph
Ligand
(x mol%)
Reco
very
Entry
[Pd]
Yield (%)[b]
5
3-MeOC6H4
4-MeC6H4
4-ClC6H4
4-MeOOCC6H4
1-Naphthyl
Cyclohexyl
2-Phenylethyl
4-ClC6H4
Ph
(%)[b]
2a
3a
37
28
5
n-Bu
6
n-Bu
7
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OCOCF3)2
Pd(OCOCF3)2
Pd(OCOCF3)2
Pd(OCOCF3)2
DPPE (5)
DPPF (5)
-
9
2
-
-
59
-
-
7
-
-
-
-
21
-
n-Bu
8
-
n-Bu
9
SPhos (10)
MePhos (10)
BrettPhos (10)
XPhos (10)
83
74
14
50
1
-
4
5
1
n-Bu
10
11
12
13
14
15
16
17
18
19
20b
n-Bu
4-Cl(CH2)4
Ph
t-BuXPhos (10)
LB-Phos∙HBF4 (10)
Gorlos-Phos∙HBF4 (10)
Zheda-Phos (10)
rac-MOP (5)
2
9[c]
10[c]
11
11
2
52
-
59
59
4
H
4-ClC6H4
n-Bu
(CH2)5 (1o)
12
4
13[d]
14[c,e]
15[c]
16[c,e,f]
17[c,f]
SPhos (7.5)
84
-
-
-
-
-
n-Bu
n-Pr (1p)
Me (1q)
n-Hex (1r)
H (1y)
Me
Me
Me
Ph
Ph
Gorlos-Phos∙HBF4 (10)
Gorlos-Phos∙HBF4 (10)
Gorlos-Phos∙HBF4 (5)
Gorlos-Phos∙HBF4 (5)
1
1
-
-
71
67
83
84
Ph
Ph
-
(CH2)3COOMe
(CH2)5OTHP
H (1y)
[a] The reaction was conducted with 1.0 mmol of 1, Pd(OAc)2 (5 mol%),
SPhos (7.5 mol%), and 2 equiv. of Et2Zn (1.5 M in toluene) in 6 mL of
anhydrous DMF under Ar atmosphere. [b] The crude product was treated with
TsOH∙H2O before chromatography to remove the THP protecting group.
The scope of Pd/Gorlos-Phos-catalyzed reaction is shown in
Table 3. R1 may be alkyl such as n-butyl, 4-chloro-n-butyl,
cyclohexyl, cyclopropyl (entries 1-4) or aryl group (entry 10),
providing β-H elimination-based corresponding allenes in high
yields. For R2 group, in addition to alkyl group (entries 11 and
16), useful electron-donating methoxy group (entry 5) and
electron-withdrawing synthetic versatile group such as halogen
group Br, Cl and F (entries 7, 12 and 13), -COOMe, -NO2, -CN
(entries 8, 14 and 15) all may be installed to the phenyl group,
adding further potentiality to the current method. The reaction
also worked with R2 being 1-naphthyl (entry 9). Furthermore, the
reaction with tertiary carbonates could afford tri-substituted
allenes in high yields (entries 11 and 16). Functional groups
such as ester or OTHP was also tolerated (entries 17 and 18).
The gram-scale reactions with just 1 mol% of the catalyst may
also easily be achieved (Scheme 2). nBu2Zn and EtZnBr were
both tested, albeit in a lower selectivity. HCOONH4 or HCOONa
was also tested as a hydride donor, unfortunately no allene
product could be formed (Scheme 3).
[a] The reaction was conducted with 0.5 mmol of 1a, Pd catalyst (5 mol%),
Ligand (x mol%), and 3 equiv. of Et2Zn (1.5 M in toluene) in 3 mL of anhydrous
DMF under Ar atmosphere. [b] Determined by 1H NMR analysis. [c] x mol% of
K2CO3 (equal amount of the ligand) was added to in-situ generate the
phosphine ligand. [d] The reaction was conducted with 1.0 mmol of 1a,
Pd(OAc)2 (5 mol%), SPhos (7.5 mol%), and 2 equiv. of Et2Zn (1.5 M in
toluene) in 6 mL of anhydrous DMF under Ar atmosphere. [e] NMP was used
as the solvent. [f] 1.5 equiv. of Et2Zn (1.5 M in toluene) were used and the
reaction was conducted at 25 oC.
With two sets of the optimized conditions in hand, we
investigated the scope of these two reactions. In Pd/SPhos-
catalyzed reactions, different types of propargylic carbonates
were tested and the results are summarized in Table 2. With
secondary propargylic carbonates (R3 = H), R1 may be alkyl
such as n-butyl, 4-chloro-n-butyl, cyclohexyl, cyclopropyl, or
even ester, OTHP (entries 1-4, 12, 19 and 20), aryl group (entry
13). The reaction of terminal propargylic carbonate 1n also
proceeded smoothly, albeit in a somewhat lower yield of 2n
(entry 14). As for R2, both electron-donating group such as
methoxy or methyl and electron-withdrawing synthetically useful
group such as chloro or ester substituted aryl groups were well
tolerated (entries 5-8); R2 may also be naphthyl (entry 9) or alkyl
group such as cyclohexyl or 2-phenylethyl (entries 10 and 11).
The reaction may also be extended to tertiary propargylic
affording tetra-substituted allenes (entries 15-18).
8-Phenyl-6,7-octadien-1-ol 3y could also be prepared in high
yield and selectivity (eq. 9), which could be easily transformed
into acetate 3ya, bromide 3yb, benzyl ether 3yc, aldehyde 3yd,
acid 3ye, and nitrile 3yg (Scheme 4).
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RESEARCH ARTICLE
Table 3. The scope of Pd/Gorlos-Phos-catalyzed cross-coupling reaction[a]
1
Yield of 3
(%)
Entry
R1
n-Bu
R2
Ph
Ph
Ph
Ph
R3
H (1a)
H (1b)
H (1c)
H (1d)
H (1e)
H (1f)
1b
2
3b
80 (3a)
83 (3b)
85 (3c)
78 (3d)
96 (3e)
81 (3f)
85 (3g)
80 (3h)
58 (3i)
80 (3l)
70 (3r)
79 (3s)
80 (3t)
80 (3u)
83 (3v)
79 (3w)
88 (3x)
73 (3y)
4-Cl(CH2)4
Cyclohexyl
Cyclopropyl
n-Bu
4
Scheme 3. Scope of different zinc reagents and hydride donor
5
3-MeOC6H4
4-MeC6H4
4-ClC6H4
4-MeOOCC6H4
1-Naphthyl
4-ClC6H4
Me
n-Bu
6
n-Bu
H (1g)
H (1h)
H (1i)
7
n-Bu
8
9b
10
11
12
13b
14b
15
16
17
18c
n-Bu
H (1l)
4-Cl(CH2)4
Ph
n-Hex (1r)
H (1s)
H (1t)
n-Bu
4-BrC6H4
2-FC6H4
3-O2NC6H4
4-NCC6H4
Me
n-Bu
n-Bu
H (1u)
H (1v)
t-Bu (1w)
H (1x)
H (1y)
n-Bu
Ph
(CH2)3CO2Me
(CH2)5OTHP
Ph
Ph
[a] The reaction was conducted with 1.0 mmol of 1, Pd(OCOCF3)2 (5 mol%),
Gorlos-Phos∙HBF4 (5 mol%), K2CO3 (5 mol%) and 1.5 equiv. of Et2Zn (1.5 M in
toluene) in 6 mL of anhydrous DMF under Ar atmosphere. [b] The reaction
was conducted in 6 mL of anhydrous NMP under Ar atmosphere. [c] The
crude product was treated with TsOH∙H2O before chromatography to remove
the THP protecting group.
Scheme 4. Synthesis of allenes with synthetically useful functionalities
In order to unveil the nature controlling the selectivity, we
carried out three reactions and the resulting mixtures were
analyzed by SAESI-MS and SAESI-MS/MS.[13] The SAESI-MS
and SAESI-MS/MS spectra showed that the major Pd species
was Pd(SPhos)(OAc)+ (Figure S1 in SI and Figure 1) when
mixing Pd(OAc)2 with SPhos (eqn. 10). The transmetalated
product, allenyl ethyl mono-SPhos ligated palladium species Int
1, was detected (Figure S2 in SI and Figure 2) after propargylic
carbonate 1a and Et2Zn were added into the mixture of
Pd(OAc)2 and SPhos in sequence (eqn. 11). Interestingly,
SAESI-MS/MS experiment of Int 1 afforded ethylation product
allene 2a via reductive elimination (Fig. 2 and eqn. 12).
Scheme 2. Gram-scale synthesis of multiple-substituted allenes
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RESEARCH ARTICLE
Scheme 5. SAESI-MS/MS studies of Pd/SPhos and its catalyzed reaction
THF-02 #725-734 RT: 6.58-6.66 AV: 10 NL: 3.23E6
T: + c ESI Full ms2 575.000 [10.000-1200.000]
515
Scheme 6. SAESI-MS/MS Studies of Pd/Gorlos-Phos and its catalyzed
100
90
reaction
80
575
70
60
50
40
THF-07 #813 RT: 7.47 AV:
T: + c ESI Full ms2 886.000 [10.000-1200.000]
1 NL: 4.25E6
886
100
515
30
20
433
90
80
70
60
50
40
30
20
10
0
576
10
449
0
200
400
600
m/z
800
1000
1200
Figure 1. SASES-MS/MS experiment of Pd(SPhos)(OAc)+
496
500
885
THF-05 #522-564 RT: 4.76-5.15 AV: 43 NL: 1.73E5
T: + c ESI Full ms2 716.000 [10.000-1200.000]
100
200
300
400
600
700
800
900
1000
m/z
716
100
90
80
70
60
50
40
+
Figure 3. SAESI-MS/MS experiment of Pd(Gorlos-SPhos)2
THF-09 #1183 RT: 11.81 AV:
1 NL: 6.76E6
T: + c ESI Full ms2 668.000 [10.000-1200.000]
30
516
668
100
20
90
80
70
60
50
40
30
20
10
0
716
10
545
m/z
717
0
100
200
300
400
500
600
700
800
900
1000
Figure 2. SASES-MS/MS experiment of the ion at m/z 716
669
496
500
100
200
300
400
600
700
800
900
1000
As a comparison, when mixing Pd(OCOCF3)2 with Gorlos-
Phos, Pd(Gorlos-Phos)2 5A was detected as the only major Pd
m/z
+
species (Figure S3 in SI and Figure 3) (eq. 13). Allenyl mono-
Gorlos-Phos-ligated palladium hydride species Int 2 (Figure S4
in SI and Figure 4) was detected as the major Pd species when
mixing propargylic carbonate 1a, diethyl zinc with Pd(OCOCF3)2
and Gorlos-Phos, indicating that the transmetalated intermediate
went through β-H elimination readily (eq. 14). From these data it
is concluded that SPhos takes mono-ligation with Pd and
prevents the β-H elimination while Gorlos-Phos prefers bis-
ligation with Pd. Then the Gorlos-Phos-mono-ligated palladium
intermediate Int 2 would have the free coordination sphere
required by β-H elimination,[12] thus, facilitating β-H elimination
during the coupling reaction to afford the β-H elimination-based
coupling product allene 3a, as confirmed by SAESI-MS-MS
experiment of Int 2 (eq. 15).
Figure 4. SAESI-MS/MS experiment of the ion at m/z 668
Based on these data, a rationale for the observed selectivity is
proposed (Scheme 7)[14]. With SPhos, the coordination number n
for the catalytically active species is 1, [11b] thus, Pd(0)L was the
catalytically active species. After the SN2'-type anti-oxidative
addition of Pd(0)L with the propargylic carbonates, the tri-
coordinated allenylic palladium methoxide Int 3 (see Int 1 in
Scheme 4) would react with Et2Zn to afford transmetalated
intermediate, allenyl ethyl palladium Int 4, which would undergo
reductive elimination to afford the ethylation product 2. SPhos
prevents β-H elimination as well as promotes the reductive
elimination. When Gorlos-Phos was applied, bi-dentated Pd(0)L2
(n = 2) was the catalytically active species. Upon releasing one
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RESEARCH ARTICLE
201.9, 136.3, 128.5, 126.3, 110.6, 95.8, 32.5, 29.9, 25.8, 22.5, 14.0,
12.3; MS (70 ev, EI) m/z (%): 200 (M+, 2.60), 129 (100); IR (neat, cm-1)
2960, 2929, 1947, 1598, 1495, 1459, 1405, 1377, 1326, 1103, 1071,
1028; HRMS calcd. for C15H20 (M+): 200.1565; Found: 200.1567.
molecule of Gorlos-Phos, Int 4 may readily undergo β-H
elimination to form Int 5 (see Int 2 in Scheme 5), which
underwent reductive elimination to yield the β-H elimination-
based coupling product 3.
Acknowledgements
Financial supports from the National Natural Science Foundation
of China (Grant No. 21690063) and the National Basic Research
Program (2015CB856600) are greatly appreciated. We thank Mr
Yizhan Zhai in this group for reproducing the preparation of 2d,
2n, and 3s.
Keywords: Negishi Coupling • Palladium • SPhos • Gorlos-Phos
• SAESI-MS/MS
[1]
[2]
For a most recent monograph, see: Modern Allene Chemistry, ed. N.
Krause and A. S. K. Hashmi, Wiley-VCH, Weinheim, 2004, vols 1 and 2.
For selected reviews, see: a) S. Ma, Acc. Chem. Res. 2003, 36, 701. b)
S. Ma, Chem. Rev. 2005, 105, 2829. c) M. Brasholz, H. U. Reissig, R.
Zimmer, Acc. Chem. Res. 2009, 42, 45. d) S. Ma, Acc. Chem. Res.
2009, 42, 1679. e) S. Yu, S. Ma, Angew. Chem. Int. Ed. 2012, 51, 3074.
f) T. Lu, Z. Lu, Z. Ma, Y. Zhang, R. Hsung, Chem. Rev. 2013, 113,
4862. g) J. Ye, S. Ma, Acc. Chem. Res. 2014, 47, 989. h) F. López, J.
Mascareñas, Chem. Soc. Rev. 2014, 43, 2904.
Scheme 7. Proposed reaction pathway for ligand-controlled Negishi coupling
[3]
For reviews on the synthesis of allenes, see: a) K. Brummond, J.
DeForrest, Synthesis. 2007, 795. b) M. Ogasawara, Tetrahedron:
Asymmetry. 2009, 20, 259. c) S. Yu, S. Ma, Chem. Commun. 2011, 47,
5384. d) R. Neff, D. Frantz, ACS Catal. 2014, 4, 519. e) J. Ye, S. Ma,
Org. Chem. Front. 2014, 1, 1210.
Conclusion
In summary, as a general solution for capturing the reactive
organometallic intermediates, SAESI-MS/MS has been
successfully applied and the nature of the ligand effect has been
unveiled in the highly selective Negishi couplings of diethyl zinc
with propargylic carbonates affording different multiple-
substituted allenes: The selective formation of ethylation or β-H
elimination-based products could be achieved respectively
under mild conditions and different functional groups are well-
tolerated by applying SPhos or Gorlos-Phos as the ligand.
Currently, we are working on applying this protocol to dialkyl
zincs with an alkyl group beyond ethyl group. Further studies in
this area are being actively pursued in our laboratory.
[4] For some recent reviews on Negishi coupling, see: a) E. I. Negishi, Q. Hu,
Z. Huang, M. Qian, G. Wang, Aldrichim. Acta. 2005, 38, 71. b) C.
Valente, M. E. Belowich, N. Hadei, M. G. Organ, Chem. Eur. J. 2010,
16, 4343. c) M. Heravi, E. Hashemi, N. Nazari, Mol. Divers. 2014, 18,
441. d) S. Huo, R. Mroz, J. Carroll, Org. Chem. Front. 2015, 2, 416. e)
D. Haas, J. Hammann, R. Greiner, P. Knochel, ACS Catal. 2016, 6,
1540.
[5]
For synthesis of allenes via arylzinc compounds, see: a) E. Elsevier, P.
Stehouwer, H. Westmijze, P. Vermeer, J. Org. Chem. 1983, 48, 1103.
b) E. Elsevier, P. Vermeer, J. Org. Chem. 1985, 50, 3042. c) T. Konno,
M. Tanikawa, T. Ishihara, H. Yamanaka, Chem. Lett. 2000, 29, 1360. d)
J. Terao, F. Bando, N. Kambe, Chem. Commun. 2009, 7336.
For synthesis of allenes via alkenylzinc compounds, see: a) H. Kleijn, H.
Westmijze, J. Meijer, P. Vermeer, Recl. Trav. Chim. Pays-Bas, 1983,
102, 378. b) E. Keinan, E. Bosch, E. J. Org. Chem. 1986, 51, 4006. c)
C. Tucker, B. Greve, W. Klein, P. Knochel, Organometallics. 1994, 13,
94. d) S. Ma, G. Wang, Angew. Chem. Int. Ed. 2003, 42, 4215; Angew.
Chem. 2003, 113, 4347.
[6]
Experimental Section
To a 50 mL oven-dried Schlenk tube were added Pd(OAc)2 (11.4 mg,
0.05 mmol), SPhos (30.7 mg, 0.075 mmol), and 2 mL of anhydrous DMF
sequentially under Ar atmosphere. The resulting mixture was stirred at rt
for 30 minutes followed by the addition of 1a (246.6 mg, 1.0 mmol), 4 mL
of DMF, and Et2Zn (1.5 M in toluene, 1.35 mL, 2.0 mmol) sequentially.
After being stirred at 25 oC for 4 h, the resulting mixture was quenched
with 10 mL of an aqueous solution of 3 M HCl and extracted with ethyl
ether (10 mL × 3). The combined organic layer was washed with 30 mL
of brine, dried over anhydrous Na2SO4, filtrated, and concentrated. The
crude product was purified by column chromatography on silica gel
(eluent: petroleum ether) to afford 2a (170.7 mg, 85%) as a liquid: 1H
NMR (400 MHz, CDCl3) δ = 7.32-7.24 (m, 4 H, ArH), 7.19-7.13 (m, 1 H,
ArH), 6.15 (quint, J = 3.2 Hz, 1 H, =CH), 2.16-2.00 (m, 4 H, 2×CH2), 1.52-
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CH3), 0.88 (t, J = 7.4 Hz, 3 H, CH3); 13C NMR (100 MHz, CDCl3) δ =
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Entry for the Table of Contents
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Yangguangyan Zheng,a† Bukeyan
Miao,a† Anni Qin,a Junzhe Xiao,b Qi Liu,b
Gen Li, a Li Zhang,b,c Fang Zhang,b,c
Yinlong Guo, b,c* and Shengming Maa,b
*
Page No. – Page No.
1. SAESI-MS approach for capturing the highly reactive organometallic
intermediates and demonstrating reactivity towards final products
2. Ligand-controlled synthesis, high selectivity
Title
3. Wide functional group tolerance, decent yields
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