N-Heterocyclic Carbene/Potassium Ion Cooperatively Catalyzed Phenylation Reactions of α,β-Unsaturated Acylazoliums

Article abstract of DOI:10.1002/ejoc.201600838

A catalytic phenylation reaction of α,β-unsaturated acylazoliums with in-situ-generated phenolates was developed. A combination of N-heterocyclic carbene and potassium ion cooperatively catalyzed the generation of α,β-unsaturated acylazoliums and phenolates from α,β-unsaturated phenolic esters for the efficient [3+3] annulation, which involves a dearomatization–rearomatization process. The approach gives good yields and excellent regioselectivities, and the products could be easily converted into high-value polycyclic derivatives. Mechanistic studies demonstrated that the potassium ion plays a vital role in this reaction.

Full text of DOI:10.1002/ejoc.201600838

DOI: 10.1002/ejoc.201600838
Full Paper
1
Phenylation Reaction
N-Heterocyclic Carbene/Potassium Ion Cooperatively Catalyzed
Phenylation Reactions of α,ꢀ-Unsaturated Acylazoliums
Jinhua Zheng,[a] Kejie Zhu,[a] Yaofeng Yuan,*[a] and Jiajia Cheng*[a]
Abstract: A catalytic phenylation reaction of α,ꢀ-unsaturated matization–rearomatization process. The approach gives good 11
6 acylazoliums with in-situ-generated phenolates was developed. yields and excellent regioselectivities, and the products could
A combination of N-heterocyclic carbene and potassium ion be easily converted into high-value polycyclic derivatives.
cooperatively catalyzed the generation of α,ꢀ-unsaturated Mechanistic studies demonstrated that the potassium ion plays
acylazoliums and phenolates from α,ꢀ-unsaturated phenolic es- a vital role in this reaction.
ters for the efficient [3+3] annulation, which involves a dearo-
16 Introduction
ety of carbon–carbon and carbon–heteroatom bond-forming
reactions.[1,2] The NHC-catalyzed generation of α,ꢀ-unsaturated
N-Heterocyclic-carbene (NHC) catalysis of α,ꢀ-unsaturated carb- acylazoliums from various α,ꢀ-unsaturated carbonyl com- 21
onyl compounds has emerged as a powerful strategy for a vari- pounds is now well established.[1a] As an important 1,3-biselec
Scheme 1. Carbene/Lewis-acid-cocatalyzed phenylation reaction.
trophilic intermediate, α,ꢀ-unsaturated acylazoliums enable
bond formation with nucleophiles both at the ꢀ-carbon atom
and at the acyl position (Scheme 1, a).[3] The nucleophiles that
have been most well investigated are reactive enol or enamine 26
substrates, such as enolizable ketones and aldehydes,[4] silyl
enol ethers,[5] sulfur ylides,[6] imines, and vinylogous amides.[7]
[a] College of Chemistry, Fuzhou University,
2 Xueyuan Road, Fuzhou 350116, P. R. of China
E-mail: jjcheng@fzu.edu.cn
Yaofeng_yuan@fzu.edu.cn
http://chem.fzu.edu.cn/szdw/teacherinfo.aspx?id=403
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under http://dx.doi.org/10.1002/ejoc.201600838.
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On the other hand, relatively unreactive nucleophiles, such as to 65 % when KCl was used as the cocatalyst (Table 1, entry 8).
aromatic compounds, have been much less extensively investi- We then found that using tBuOK instead of the combination of
31 gated. In 2009, Bode and coworkers published an elegant paper tBuONa and KCl gave a similar result (Table 1, entry 9). To evalu- 86
on the NHC-catalyzed Claisen rearrangement of α,ꢀ-unsatu- ate the effect of the potassium ion on the reaction, the macro-
rated acylazoliums with 2-naphthols as the nucleophile.[8a,8b] cyclic polyether 18-crown-6 was added to form a stable com-
Later, Biju and coworkers reported a similar NHC-catalyzed an- plex with K+. The dramatic drop in yield shows that the potas-
nulation reaction with 2-bromoenals and ꢀ-naphthols as sub- sium ion plays a vital role in this annulation reaction (Table 1,
36 strates.[8c] Recently, You and coworkers found that the asym- entry 10). The use of other potassium salts, such as K3PO4 and 91
metric annulation of enals and 2-naphthols could be effectively K2CO3, also gave moderate yields of the product (Table 1, en-
achieved under oxidative conditions using new triazolium salts tries 11 and 12). This observation further confirms our hypothe-
derived from L
-phenylalanine.[8d] Phenols have proved to be sis on the NHC/K+ cooperative catalysis. We then tested other
more challenging motifs than naphthols due to the fact that NHC catalysts, but these gave results no better than that ob-
41 the energy barrier for breaking the aromaticity of phenols is tained with the IMes catalyst (Table 1, entries 13–16). No prod- 96
significantly higher than that of naphthol compounds.[9] Thus, uct was observed in the absence of an NHC catalyst (Table 1,
the direct NHC-catalyzed reaction of α,ꢀ-unsaturated acyl- entry 17). Elevating the reaction temperature did not improve
azoliums with simple phenols is of great value, but remains the result (Table 1, entry 18), but increasing the catalyst loading
underdeveloped.
to 20 mol-% gave a 71 % yield of 2a after 48 h at 120 °C
(Table 1, entry 19). Finally, we found that by using NHC catalyst 101
A (20 mol-%) and tBuOK (30 mol-%) at 130 °C for only 24 h, a
quantitative conversion of α,ꢀ-unsaturated phenolic ester 1a
46
The 3,4-dihydrocoumarin core is widely found in a variety of
biologically active molecules and natural products that show
anti-inflammatory, antioxidant, anticoagulant, antibiotic, and
antiviral properties (Scheme 1, b).[10] In this paper, we report a
new carbene/potassium-ion-cocatalyzed annulation reaction of
Table 1. Optimization of the reaction conditions.[a]
51 an α,ꢀ-unsaturated acylazolium with a phenolate as a nucleo-
phile (Scheme 1, c). The key step involves the dearomatiza-
tion[11] and 1,4-addition of phenolate II to α,ꢀ-unsaturated
acylazolium intermediate I, which is generated by the addition
of the NHC catalyst to α,ꢀ-unsaturated phenolic ester 1.[12] The
56 issue of dearomatization of the phenyl ring was addressed by
invoking the synergy of the NHC organocatalysis and the potas-
sium ion. The potassium ion may behave as a Lewis acid to
both activate the phenolate and increase the electrophilicity
of the α,ꢀ-unsaturated acylazolium.[13,14,4b,4f] Notably, although
61 potassium salts have been widely used in NHC catalysis, to the
best of our knowledge, the cocatalysis effect of the potassium
ion has not been reported before. In addition to demonstrating
a new nucleophilic phenylation reaction of the α,ꢀ-unsaturated
acylazolium intermediate, this study opens a concise route to
66 clinically significant 3,4-dihydrocoumarin derivatives.
Entry
NHC
Base
Additive
Yield [%][b]
1
2
3
4
A
A
A
A
A
A
A
A
A
A
A
A
B
tBuONa
MeONa
Cs2CO3
DBU
–
–
–
–
6
n.d.
n.d.
n.d.
n.d.
<5
61
65
68
<5
54
21
17
n.d.
n.d.
n.d.
n.d.
66
5
NEt3
–
Results and Discussion
6[c]
7[c]
8[d]
9
tBuONa
tBuONa
tBuONa
tBuOK
tBuOK
K2CO3
K3PO4
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
Sc(OTf)3
LiCl
KCl
–
18-crown-6
–
–
We started by using α,ꢀ-unsaturated phenolic ester 1a, derived
from sesamol, as the model substrate (Table 1). tBuONa and
toluene were chosen as the base and reaction solvent, respec-
71 tively. When exposed to imidazolium catalyst IMes (A), the ex-
pected annulation product (i.e., 2a) was formed in a low but
encouraging 6 % yield (Table 1, entry 1). This proof-of-principle
result clearly revealed that activation and dearomatization of
the phenyl group using the NHC organocatalyst was feasible.
76 Cs2CO3, MeONa, DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), and
NEt3 were also tested as bases, but none of these led to any
formation of 2a (Table 1, entries 2–5). Inspired by the work
of Scheidt[13,14a–14e] on Lewis acid cooperative catalysis, several
Lewis acids were investigated to improve the reactivity. Sc(OTf)3
81 showed only a small effect on the reaction yield (Table 1, en-
try 6), but LiCl was found to have a dramatic influence on the
reaction outcome (Table 1, entry 7). The reaction yield increased
10[c]
11
12
13
14
15
16
17
18[e]
19[f]
20[g]
C
–
–
–
–
–
–
–
D1
D2
–
A
A
A
71
72
[a] Reaction conditions: 1a (0.1 mmol), NHC catalyst (10 mol-%), base (15 mol-
%), solvent (1 mL) at 120 °C for 48 h. [b] Isolated yield. [c] 30 mol-% of
additive was added. [d] 15 mol-% of KCl was added. [e] The reaction was
stirred at 130 °C. [f] NHC A (20 mol-%), tBuOK (30 mol-%) at 120 °C. [g] NHC
A (20 mol-%), tBuOK (30 mol-%) at 130 °C for 24 h; n.d.: not determined.
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could be achieved, with the formation of 2a in 72 % yield as a creasing the electrophilicity of the alkene moiety, was well tol- 116
single regioisomer (Table 1, entry 20).
erated, and gave the desired annulation products in good
yields. Replacement of the ꢀ-phenyl substituent with a hetero-
aryl (2k, 2l) unit had little effect on the reaction outcome. How-
ever, methyl-substituted α,ꢀ-unsaturated phenolic esters did
not give the annulation products under the optimal reaction 121
conditions. Most of the starting materials remained intact when
the reaction was carried out at 130 °C for 24 h.
106
Having established acceptable reaction conditions, the sub-
strate scope of the α,ꢀ-unsaturated phenolic ester component
was evaluated (Table 2). First, we explored a series of α,ꢀ-unsat-
urated esters in which R2 was a 3,4-methylenedioxy group. A
substrate beating an electron-withdrawing group (2b) on the
111 ꢀ-phenyl moiety worked well in this reaction. The fact that the
reaction tolerates the presence of functional groups [e.g., halo-
Next, we investigated the scope of the reaction in terms of
gen (2c–2e) and alkyl (2f) groups] could be useful for struc- varying the R2 group (with R1 = H, Table 2). When the α,ꢀ-
ture–activity relationship (SAR) studies.[15] The presence of an unsaturated phenolic ester was replaced by another electron- 126
electron-rich substituent on the aryl ring (2g–2j), although de- donating group, such as m-N(CH3)2 or m-N(CH2)4, a high yield
Table 2. Scope of the reaction in terms of α,ꢀ-unsaturated phenolic esters.[a]
[a] Reaction conditions: 1 (0.1 mmol), NHC catalyst A (20 mol-%), tBuOK (30 mol-%), toluene (1 mL) at 130 °C for 24 h; yields refer to products isolated by
column chromatography.
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and excellent regiocontrol were still observed (2m, 2n). Addi-
tionally, the reaction could also be applied to other multi-sub-
stituted phenolic esters (2o, 2p).
131
α,ꢀ-Unsaturated naphtholic esters 1 were then examined to
further expand the scope of this arylation reaction. Under the
standard conditions, substrates containing substituted fused
aromatic groups led to the corresponding products (i.e., 2q–2u)
in high yields and with excellent regioselectivities (Scheme 2).
136 Notably, in contrast to the study by Bode, Biju, and You,[8] 1-
naphthol worked well to give the desired annulation product
(i.e., 2q).
Scheme 3. Preliminary enantioselective studies of the reaction. [a] The abso-
lute configuration of the major enantiomer was assigned based on a compar-
ison of optical rotation data with literature values.[16]
tion probably takes place through the 1,4-addition of the α,ꢀ-
unsaturated acylazoliums with the in-situ-generated phenol-
ates.
Scheme 2. Scope of the reaction in terms of α,ꢀ-unsaturated naphtholic es-
ters. Reaction conditions: 1 (0.1 mmol), NHC catalyst A (20 mol-%), tBuOK
(30 mol-%), toluene (1 mL) at 130 °C for 24 h; isolated yields by column
chromatography.
Substrate 1v reacted smoothly under the standard condi-
tions [Equation (1)] to give polymethoxy substituted product
141 2v. In addition, a larger-scale reaction was carried out. This gave
the desired product without any loss of efficiency, as shown by
the gram-scale preparation of 2a [Equation (2)].
A preliminary enantioselective study of this method was car-
ried out using several triazolium salts (see the Supporting Infor-
146 mation for details). We were delighted to find that when E was
used as the chiral carbene precursor, annulation product (S)-2a
was obtained in 19 % yield with a promising 43 % ee
(Scheme 3).
To investigate the effect of potassium ion on the reaction,
A crossover study was carried out to gain a deeper insight the following control experiments were designed (Scheme 4). 161
151 into the reaction mechanism [Equation (3)].[17] A mixture of sub- Free carbene A′ was prepared[18] and was subjected to the reac-
strates 1i and 1p was subjected to the standard conditions. tion conditions, but no product was observed when the reac-
Besides the expected products 2i and 2p, crossover products tion was carried out at 130 °C for 24 h. However, when the
2a and 2v were observed in 23 and 19 % yields. These results reaction was run in the presence of KCl (15 mol-%) under other-
suggest that an α,ꢀ-unsaturated acylazolium intermediate is di- wise identical conditions, the desired product was obtained in 166
156 rectly generated from the ester with the NHC catalyst; the reac- 35 % yield.
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Scheme 6. Synthetic transformation of the product. [a] The relative configura-
tion of 3 was assigned on the basis of its NOESY spectrum (see the Support-
ing Information).
Scheme 4. Control experiments.
Conclusions
In conclusion, we have developed an effective phenylation reac-
tion of α,ꢀ-unsaturated acylazoliums with in-situ-generated
phenolates as the nucleophiles. The challenge associated with 191
the dearomatization of the phenolates was overcome by using
an NHC/potassium ion cooperative catalytic strategy. Addition-
ally, α,ꢀ-unsaturated naphtholic esters were well tolerated, and
derivatization of the resulting cyclic products provided high-
value polycyclic structures. Mechanistic studies were also car- 196
ried out to demonstrate that the presence of the potassium ion
was essential for this reaction. The exploration of other related
NHC-catalyzed arylation reactions is currently underway in our
lab.
Based on the results described above, a reaction mechanism
is proposed in Scheme 5. Deprotonation of the imidazolium
precatalyst salt with tBuOK gives the carbene catalyst and the
171 potassium ion. Addition of the NHC catalyst to ester 1 then
leads to the formation of α,ꢀ-unsaturated acylazolium I and
phenolate II. The potassium ion and the NHC cooperatively acti-
vate the α,ꢀ-unsaturated acylazolium to allow the addition of
the relatively unreactive nucleophile. Dearomatization and 1,4-
176 addition of phenolate II with I gives intermediate III, which un-
dergoes tautomerization, rearomatization, and lactone forma-
tion to give product 2 and regenerate the NHC catalyst. In the
overall hypothesized process, only a catalytic amount of base is
needed, and the stability of the product may be the driving
181 force for the reaction.
Experimental Section
201
General Information: Commercially available materials purchased
from Alfa Aesar or Aldrich was used as received. Proton nuclear
magnetic resonance (1H NMR) spectra were recorded with a
400 MHz spectrometer. Chemical shifts are reported in parts per
million (ppm, δ) relative to tetramethylsilane (δ = 0.00 ppm). 1H 206
NMR splitting patterns are designated as singlet (s), doublet (d),
triplet (t), quartet (q), dd (doublet of doublets), m (multiplet), etc.
All first-order splitting patterns were assigned on the basis of the
appearance of the multiplet. Splitting patterns that could not be
easily interpreted are designated as multiplet (m) or broad (br). 211
Carbon nuclear magnetic resonance (13C NMR) spectra were re-
corded with a 100 MHz spectrometer. Mass spectral analysis (ESI-
MS) was carried out with a mass spectrometer. The determination
of ee was carried out by chiral phase HPLC analysis. Optical rotations
were measured with a polarimeter using a 1 mL cell with a 1 cm 216
path length, and are reported as follows: [α]2D0. Analytical thin-layer
chromatography (TLC) was carried out on precoated silica gel plates
(0.2 mm thickness), which were visualized using a UV lamp.
Typical Procedure for the Catalytic Reactions: NHC
A
(0.02 mmol), tBuOK (0.03 mmol), α,ꢀ-unsaturated phenolic ester 1a 221
(0.1 mmol) and toluene (1 mL) were put into a dry sealed tube
equipped with a magnetic stirrer bar. The mixture was stirred in the
sealed tube at 130 °C for about 24 h under a nitrogen atmosphere
until 1a was completely consumed (monitored by TLC). The mixture
was then concentrated under reduced pressure. The resulting crude 226
residue was purified by column chromatography on silica gel (hex-
anes/EtOAc, 5:1) to give the desired product (i.e., 2a).
Scheme 5. Postulated reaction pathway.
Naphthalene-fused polycyclic structure 3 is the core skeleton
of a variety of natural products and biologically active mol-
ecules.[19] Using our method, 2w could easily be prepared from
readily available substrates (Scheme 6), which further gave
186 fused tetracyclic compound 3 in excellent yield and with excel-
lent stereoselectivity.
8-Phenyl-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-6-one
(2a): White solid (19.4 mg, 72 %), m.p. 133.0–134.0 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.44–7.22 (m, 3 H), 7.15 (d, J = 8.1 Hz, 2 H), 231
6.65 (s, 1 H), 6.39 (s, 1 H), 5.94 (s, 2 H), 4.22 (t, J = 6.8 Hz, 1 H), 3.06–
2.93 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.5, 147.5,
146.2, 144.4, 140.4, 129.1, 127.7, 127.4, 117.9, 107.3, 101.7, 99.1, 40.6,
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37.0 ppm. MS (ESI): m/z =C16H13O4 [M + H] 269.1; found 269.1.
236 HRMS (ESI): calcd. for C16H13O4 [M + H] 269.0808; found 269.0794.
128.2, 127.7, 119.1, 112.9, 107.3, 101.6, 99.0, 40.5, 39.7, 37.2 ppm. 296
MS (ESI): m/z = 312.2 [M + H]. HRMS (ESI): calcd. for C18H18NO4 [M
+ H] 312.1230; found 312.1218.
8-(4-Fluorophenyl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-
6-one (2b): White solid (22.3 mg, 78 %), m.p. 144.0–145.0 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.17–7.09 (m, 2 H), 7.08–6.96 (m, 2 H),
6.65 (s, 1 H), 6.38 (s, 1 H), 5.95 (s, 2 H), 4.21 (t, J = 6.7 Hz, 1 H), 3.10–
241 2.83 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.3, 162.1 (d,
8-(3,4,5-Trimethoxyphenyl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]-
chromen-6-one (2i): White solid (22.9 mg, 64 %), m.p. 192.0–
1
193.0 °C. H NMR (400 MHz, CDCl3): δ = 6.65 (s, 1 H), 6.44 (s, 1 H), 301
6.35 (s, 2 H), 5.96 (s, 2 H), 4.15 (t, J = 8.0 Hz, 1 H), 3.83 (s, 3 H), 3.81
J = 245.0 Hz), 147.6, 146.1, 144.5, 136.2 (d, J = 4.0 Hz), 129.0 (d, J = (s, 6 H), 3.10–2.87 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
8.0 Hz), 117.6, 116.0 (d, J = 21.0 Hz), 107.1, 101.7, 99.2, 39.9,
37.1 ppm. 19F NMR (376 MHz, CDCl3): δ = –114.6 ppm. MS (ESI):
m/z = 287.1 [M + H]. HRMS (ESI): calcd. for C16H12FO4 [M + H]
246 287.0714; found 287.0698.
167.5, 153.6, 147.5, 146.1, 144.4, 137.4, 136.1, 117.8, 107.2, 104.4,
101.7, 99.0, 60.8, 56.1, 40.9, 37.0 ppm. MS (ESI): m/z = 358.9 [M + H].
HRMS (ESI): calcd. for C19H19O7 [M + H] 359.1125; found 359.1114. 306
8-(Benzo[d][1,3]dioxol-5-yl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]-
chromen-6-one (2j): Pale yellow solid (18.4 mg, 59 %), m.p. 140.0–
141.0 °C. 1H NMR (400 MHz, CDCl3): δ = 6.76 (d, J = 8.5 Hz, 1 H),
6.64 (s, 1 H), 6.62–6.57 (m, 2 H), 6.41 (s, 1 H), 5.95 (s, 4 H), 4.14 (t,
8-(4-Chlorophenyl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-
6-one (2c): White solid (22.0 mg, 73 %), m.p. 134.0–135.0 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.32 (d, J = 8.4 Hz, 2 H), 7.08 (d, J =
8.3 Hz, 2 H), 6.65 (s, 1 H), 6.38 (s, 1 H), 5.96 (s, 2 H), 4.20 (t, J = J = 8.0 Hz, 1 H), 3.15–2.70 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): 311
251 6.4 Hz, 1 H), 3.12–2.82 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.5, 148.3, 147.5, 147.0, 146.1, 144.4, 134.2, 120.8, 118.0, 108.6,
δ = 167.1, 147.7, 146.2, 144.5, 139.0, 133.6, 129.3, 128.8, 117.2, 107.1,
101.8, 99.2, 40.1, 36.9 ppm. MS (ESI): m/z = 303.1 [M + H]. HRMS
(ESI): calcd. for C16H12ClO4 [M + H] 303.0419; found 303.0412.
107.6, 107.2, 101.7, 101.2, 99.1, 40.3, 37.2 ppm. MS (ESI): m/z = 313.0
[M + H]. HRMS (ESI): calcd. for C17H13O6 [M + H] 313.0707; found
313.0692.
8-(3-Chlorophenyl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-
256 6-one (2d): White solid (22.3 mg, 74 %), m.p. 101.0–102.0 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.35–7.18 (m, 2 H), 7.12 (s, 1 H), 7.07–
8-(Thiophen-2-yl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen- 316
6-one (2k): White solid (15.8 mg, 58 %), m.p. 115.0–116.0 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.22 (dd, J = 5.1, 1.2 Hz, 1 H), 6.94 (dd,
6.98 (m, 1 H), 6.65 (s, 1 H), 6.39 (s, 1 H), 5.96 (s, 2 H), 4.20 (t, J = J = 5.1, 3.5 Hz, 1 H), 6.88–6.79 (m, 1 H), 6.66–6.62 (m, 1 H), 6.57 (s,
6.6 Hz, 1 H), 3.18–2.76 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): 1 H), 5.96 (dd, J = 3.3, 1.3 Hz, 2 H), 4.47 (t, J = 6.1 Hz, 1 H), 3.07 (d,
δ = 167.0, 147.7, 146.1, 144.5, 142.5, 134.9, 130.4, 127.9, 127.6, 125.6,
261 116.8, 107.1, 101.8, 99.2, 40.3, 36.8 ppm. MS (ESI): m/z = 302.9 [M
+ H]. HRMS (ESI): calcd. for C16H12ClO4 [M + H] 303.0419; found
303.0386.
J = 6.1 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.0, 147.7, 321
145.7, 144.4, 143.7, 127.1, 125.1, 125.0, 117.6, 106.9, 101.7, 99.2, 37.3,
36.0 ppm. MS (ESI): m/z = 274.5 [M + H]. HRMS (ESI): calcd. for
C14H11O4S [M + H] 275.0373; found 275.0364.
8-(4-Bromophenyl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-
6-one (2e): White solid (24.6 mg, 71 %), m.p. 167.0–168.0 °C. 1H
266 NMR (400 MHz, CDCl3): δ = 7.46 (d, J = 8.4 Hz, 2 H), 7.02 (d, J =
8-(Furan-2-yl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-6-
one (2l): Colorless solid, m.p. 121.0–122.0 °C (15.3 mg, 56 %). 1H 326
NMR (400 MHz, CDCl3): δ = 7.36 (d, J = 1.2 Hz, 1 H), 6.61 (s, 1 H),
8.3 Hz, 2 H), 6.65 (s, 1 H), 6.38 (s, 1 H), 5.95 (s, 2 H), 4.18 (t, J = 6.57 (s, 1 H), 6.30 (dd, J = 3.2, 1.9 Hz, 1 H), 6.06 (d, J = 3.2 Hz, 1 H),
6.7 Hz, 1 H), 3.11–2.79 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): 5.96 (dd, J = 6.1, 1.3 Hz, 2 H), 4.27 (t, J = 5.9 Hz, 1 H), 3.19–2.90 (m,
δ = 167.1, 147.7, 146.2, 144.5, 139.5, 132.2, 129.1, 121.6, 117.1, 107.1,
101.8, 99.2, 40.1, 36.8 ppm. MS (ESI): m/z = 347.0 [M + H]. HRMS
271 (ESI): calcd. for C16H12BrO4 [M + H] 346.9913; found 346.9906.
2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.2, 152.9, 147.8, 146.0,
144.4, 142.6, 115.4, 110.4, 107.0, 106.8, 101.7, 99.3, 34.6, 33.8 ppm. 331
MS (ESI): m/z = 259.0 [M + H]. HRMS (ESI): calcd. for C14H11O5 [M +
H] 259.0601; found 259.0583.
8-(p-Tolyl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-6-one
(2f): White solid (19.0 mg, 67 %), m.p. 131.0–132.0 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.15 (d, J = 7.9 Hz, 2 H), 7.03 (d, J = 8.0 Hz,
2 H), 6.65 (s, 1 H), 6.39 (s, 1 H), 5.94 (d, J = 1.7 Hz, 2 H), 4.18 (t, J =
276 8.0 Hz, 1 H), 3.13–2.78 (m, 2 H), 2.33 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 167.7, 147.4, 146.2, 144.4, 137.4, 129.8, 127.3, 118.2,
6-(Dimethylamino)-4-phenylchroman-2-one (2m): White solid
(15.5 mg, 58 %), m.p. 115.0–116.0 °C. 1H NMR (400 MHz, CDCl3): δ =
7.36–7.30 (m, 2 H), 7.29–7.23 (m, 1 H), 7.20–7.12 (m, 2 H), 6.80 (d, 336
J = 8.6 Hz, 1 H), 6.52–6.33 (m, 2 H), 4.25 (t, J = 6.2 Hz, 1 H), 3.14–
2.86 (m, 8 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 168.2, 152.6,
107.3, 101.7, 99.1, 40.3, 37.0, 21.0 ppm. MS (ESI): m/z = 283.2 [M + 151.1, 141.4, 129.0, 128.6, 127.5, 127.3, 112.8, 108.6, 100.5, 40.4, 40.0,
H]. HRMS (ESI): calcd. for C17H15O4 [M + H] 283.0965; found
283.0978.
37.7 ppm. MS (ESI): m/z = 268.3 [M + H]. HRMS (ESI): calcd. for
C17H18NO2 [M + H] 268.1332; found 268.1319.
341
281 8-(4-Methoxyphenyl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]-
chromen-6-one (2g): White solid (18.5 mg, 59 %), m.p. 134.0–
4-Phenyl-6-(pyrrolidin-1-yl)chroman-2-one (2n): White solid
(17.9 mg, 61 %), m.p. 173.0–174.0 °C. 1H NMR (400 MHz, CDCl3): δ =
135.0 °C. 1H NMR (400 MHz, CDCl3): δ = 7.06 (d, J = 8.6 Hz, 2 H), 7.36–7.29 (m, 2 H), 7.28–7.22 (m, 1 H), 7.15 (d, J = 7.1 Hz, 2 H), 6.78
6.87 (d, J = 8.7 Hz, 2 H), 6.64 (s, 1 H), 6.39 (s, 1 H), 5.94 (s, 2 H), 4.17
(t, J = 8.0 Hz, 1 H), 3.79 (s, 3 H), 3.13–2.76 (m, 2 H) ppm. 13C NMR
286 (100 MHz, CDCl3): δ = 167.7, 159.0, 147.4, 146.1, 144.4, 132.3, 128.5,
118.4, 114.5, 107.2, 101.6, 99.1, 55.3, 39.8, 37.1 ppm. MS (ESI): m/z =
299.0 [M + H]. HRMS (ESI): calcd. for C17H15O5 [M + H] 299.0914;
found 299.0906.
(d, J = 8.4 Hz, 1 H), 6.35–6.22 (m, 2 H), 4.24 (t, J = 6.7 Hz, 1 H), 3.26
(t, J = 6.5 Hz, 4 H), 3.09–2.92 (m, 2 H), 2.00 (t, J = 6.6 Hz, 4 H) ppm. 346
13C NMR (100 MHz, CDCl3): δ = 168.3, 152.6, 148.4, 141.6, 128.9,
128.7, 127.5, 127.3, 111.7, 108.0, 99.6, 47.7, 40.0, 37.8, 25.4 ppm. MS
(ESI): m/z = 294.3 [M + H]. HRMS (ESI): calcd. for C19H20NO2 [M + H]
294.1489; found 294.1495.
8-[4-(Dimethylamino)phenyl]-7,8-dihydro-6H-[1,3]dioxolo-
291 [4,5-g]chromen-6-one (2h): Yellow solid (16.8 mg, 54 %), m.p.
6,7-dimethoxy-4-phenylchroman-2-one (2o): White solid 351
(19.1 mg, 67 %), m.p. 154.0–155.0 °C. 1H NMR (400 MHz, CDCl3): δ =
7.39–7.31 (m, 2 H), 7.31–7.25 (m, 1 H), 7.22–7.08 (m, 2 H), 6.69 (s, 1
H), 6.46 (s, 1 H), 4.27 (t, J = 6.6 Hz, 1 H), 3.88 (s, 3 H), 3.73 (s, 3 H),
3.11–2.93 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.6, 149.2,
145.8, 145.5, 140.8, 129.1, 127.6, 127.4, 116.1, 110.6, 101.2, 56.2, 56.1, 356
1
122.0–123.0 °C. H NMR (400 MHz, CDCl3): δ = 7.00 (d, J = 8.7 Hz, 2
H), 6.69 (d, J = 8.8 Hz, 2 H), 6.63 (s, 1 H), 6.39 (s, 1 H), 5.93 (dd, J =
2.9, 1.3 Hz, 1 H), 4.10 (t, J = 8.0 Hz, 1 H), 3.04–2.84 (m, 8 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 168.1, 150.0, 147.2, 146.1, 144.3,
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40.5, 37.4 ppm. MS (ESI): m/z = 285.2 [M + H]. HRMS (ESI): calcd. for
C17H17O4 [M + H] 285.1121; found 285.1109.
δ = 167.4, 153.6, 153.4, 150.4, 147.5, 138.9, 137.4, 137.0, 110.7, 103.7,
96.6, 61.1, 60.9, 60.7, 56.01, 59.97, 37.0, 35.5 ppm. MS (ESI): m/z =
405.0 [M + H]. HRMS (ESI): calcd. for C21H25O8 [M + H] 405.1544;
found 405.1532.
5,6,7-Trimethoxy-4-phenylchroman-2-one (2p): White solid
(22.9 mg, 73 %), m.p. 146.0–147.0 °C. 1H NMR (400 MHz, CDCl3): δ =
361 7.31–7.24 (m, 2 H), 7.24–7.17 (m, 1 H), 7.14–7.07 (m, 2 H), 6.51 (s, 1
H), 4.57 (dd, J = 5.3, 3.7 Hz, 1 H), 3.87 (s, 3 H), 3.82 (s, 3 H), 3.65 (s,
3 H), 3.05–2.95 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.4,
153.7, 150.5, 147.7, 141.7, 139.0, 128.9, 127.2, 126.7, 110.9, 96.8, 61.0,
60.9, 56.1, 37.1, 35.4 ppm. MS (ESI): m/z = 315.1 [M + H]. HRMS (ESI):
366 calcd. for C18H19O5 [M + H] 315.1227; found 315.1216.
421
Procedure for the Enantioselectivity Study of the Catalytic Re-
action: NHC E (0.02 mmol), tBuOK (0.03 mmol), α,ꢀ-unsaturated
phenolic ester 1a (0.1 mmol), and toluene (1 mL) were put into a
dry sealed tube equipped with a magnetic stirrer bar. The mixture
was stirred in the sealed tube at 130 °C for about 24 h under a 426
nitrogen atmosphere until 1a was completely consumed (moni-
tored by TLC). The resulting crude residue was purified by column
chromatography on silica gel (hexanes/EtOAc, 5:1) to give the de-
sired product (S)-2a (5.2 mg, 19 %) as a white solid. [α]2D0 = +1.3
(c = 0.8, CHCl3); 43 % ee as determined by HPLC (IA, 75:25 hexanes/ 431
iPrOH, 0.5 mL/min, λ = 220 nm), tmajor = 20.8 min, tminor = 21.4 min.
6-Chloro-4-phenyl-3,4-dihydro-2H-benzo[h]chromen-2-one
1
(2q): Pale green solid, m.p.(18.8 mg, 61 %), m.p. 127.0–128.0 °C. H
NMR (400 MHz, CDCl3): δ = 8.36–8.28 (m, 1 H), 8.24–8.17 (m, 1 H),
7.75–7.50 (m, 2 H), 7.40–7.26 (m, 3 H), 7.21–7.13 (m, 3 H), 4.43 (t,
371 J = 6.6 Hz, 1 H), 3.28–3.01 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 166.7, 145.7, 140.0, 130.7, 129.3, 127.9, 127.51, 127.48, 127.4,
125.1, 124.7, 124.4, 121.7, 120.2, 40.9, 37.0 ppm. MS (ESI): m/z =
309.1 [M + H]. HRMS (ESI): calcd. for C19H14ClO2 [M + H] 309.0677;
found 309.0658.
Acknowledgments
We gratefully acknowledge the National Natural Science Foun-
dation of China (grant numbers 21502019, 21402027), the Sci-
entific Research Foundation for Returned Overseas Chinese 436
Scholars, State Education Ministry, the Science Foundation of
the Fujian Province, China (grant numbers 2015J05021,
2015J05046), the Education Foundation of Fujian Province, P. R.
China (grant number JA15095), and Fuzhou University for finan-
376 1-Phenyl-1H-benzo[f]chromen-3(2H)-one (2r): White solid
(24.2 mg, 88 %), m.p. 164–165 °C. 1H NMR (400 MHz, CDCl3): δ =
7.86 (d, J = 8.6 Hz, 2 H), 7.79 (d, J = 8.1 Hz, 1 H), 7.52–7.40 (m, 2 H),
7.35 (d, J = 8.9 Hz, 1 H), 7.28–7.16 (m, 3 H), 7.12 (d, J = 7.7 Hz, 2 H),
4.95 (d, J = 6.4 Hz, 1 H), 3.31–3.07 (m, 2 H) ppm. 13C NMR (100 MHz,
381 CDCl3): δ = 167.1, 149.8, 140.6, 131.1, 131.0, 129.9, 129.2, 128.8,
127.6, 127.5, 126.9, 125.3, 123.1, 117.61, 117.56, 37.7, 37.5 ppm. MS
(ESI): m/z = 275.2 [M + H]. HRMS (ESI): calcd. for C19H15O2 [M + H]
275.1067; found 275.1054.
cial support.
441
Keywords: Organocatalysis · Cyclization · Carbenes ·
8-Bromo-1-phenyl-1H-benzo[f]chromen-3(2H)-one (2s): White
386 solid (28.9 mg, 82 %), m.p. 120.0–121.0 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.95 (s, 1 H), 7.71 (d, J = 8.9 Hz, 1 H), 7.61 (d, J = 9.0 Hz,
1 H), 7.46 (d, J = 8.9 Hz, 1 H), 7.32 (d, J = 8.9 Hz, 1 H), 7.26–7.12 (m,
3 H), 7.07 (d, J = 7.2 Hz, 2 H), 4.87 (d, J = 4.0 Hz, 1 H), 3.50–2.70 (m,
2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.6, 150.0, 140.2, 132.2,
391 130.8, 130.7, 129.6, 129.3, 129.0, 127.7, 126.8, 124.8, 119.2, 118.8,
117.9, 37.7, 37.3 ppm. MS (ESI): m/z = 352.9 [M + H]. HRMS (ESI):
calcd. for C19H14BrO2 [M + H] 353.0172; found 353.0161.
Nitrogen heterocycles · Oxygen heterocycles · Potassium
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9-Bromo-1-phenyl-1H-benzo[f]chromen-3(2H)-one (2t): White
solid (27.9 mg, 79 %), m.p. 173.0–174.0 °C. 1H NMR (400 MHz,
396 CDCl3): δ = 7.92 (s, 1 H), 7.82 (d, J = 8.9 Hz, 1 H), 7.71 (d, J = 8.7 Hz,
1 H), 7.50 (dd, J = 8.7, 1.7 Hz, 1 H), 7.35 (d, J = 8.9 Hz, 1 H), 7.31–
7.17 (m, 3 H), 7.14–7.07 (m, 2 H), 4.90–4.83 (m, 1 H), 3.30–2.98 (m,
2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.6, 150.4, 140.0, 132.3,
130.3, 129.8, 129.4, 129.3, 128.7, 127.7, 126.8, 125.4, 122.1, 118.0,
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3(2H)-one (2u): Yellow solid (30.1 mg, 76 %), m.p. 145.0–146.0 °C.
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396.0583.
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(2v): White solid (28.3 mg, 70 %), m.p. 168.0–169.0 °C. 1H NMR
(400 MHz, CDCl3): δ = 6.51 (s, 1 H), 6.33 (s, 2 H), 4.51 (dd, J = 5.3,
416 3.5 Hz, 1 H), 3.88 (s, 3 H), 3.84 (s, 3 H), 3.79 (s, 3 H), 3.78 (s, 6 H),
3.74 (s, 3 H), 3.05–2.92 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
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Received: July 8, 2016
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Phenylation Reaction
571 J. Zheng, K. Zhu, Y. Yuan,*
J. Cheng* .............................................. 1–9
N-Heterocyclic Carbene/Potassium
Ion Cooperatively Catalyzed Phenyl-
ation Reactions of α,ꢀ-Unsaturated
576 Acylazoliums
A catalytic phenylation reaction of α,ꢀ- ates, which are directly generated from
unsaturated acylazoliums was devel- α,ꢀ-unsaturated
phenolic
esters.
oped. A combination of N-heterocyclic Mechanistic studies demonstrated that
carbene and potassium ion coopera- the potassium ion plays a vital role in
tively catalyzed the cyclization of α,ꢀ- this reaction.
581
unsaturated acylazoliums with phenol
Authors: Please check that the ORCID identifiers listed below are correct. We encourage all authors to provide an ORCID
identifier for each coauthor. ORCID is a registry that provides researchers with a unique digital identifier. Some funding
agencies recommend or even require the inclusion of ORCID IDs in all published articles, and authors should consult their
586 funding agency guidelines for details. Registration is easy and free; for further information, see http://orcid.org/.
Jinhua Zheng
Kejie Zhu
Yaofeng Yuan*
and Jiajia Cheng http://orcid.org/0000-0002-0878-7069*
591
DOI: 10.1002/ejoc.201600838
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
9
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim