I2/Li2CO3-promoted cyanation of diarylalcohols through a dual activation process

Article abstract of DOI:10.1016/j.tet.2018.11.069

One-step base promoted strategy for cyanation of α,α-diaryl alcohols has been developed under mild and transition metal-free conditions. This method provides a straightforward and facile way towards the synthesis of β,γ-unsaturated nitriles and α-phenylnitiriles from α-vinyl carbinols and α,α-diaryl methanols, respectively, up to 99% yield. Moreover, various azides and ethers could also be accessed from their respective nucleophiles under standard reaction conditions.

Full text of DOI:10.1016/j.tet.2018.11.069

Accepted Manuscript
I /Li CO -promoted cyanation of diarylalcohols through a dual activation process
2
2
3
Liangzhen Hu, Muhammad Ijaz Hussain, Qingfu Deng, Qing Liu, Yangyang Feng,
Xiaohui Zhang, Yan Xiong
PII:
S0040-4020(18)31459-5
https://doi.org/10.1016/j.tet.2018.11.069
TET 29980
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 26 September 2018
Revised Date: 28 November 2018
Accepted Date: 30 November 2018
Please cite this article as: Hu L, Hussain MI, Deng Q, Liu Q, Feng Y, Zhang X, Xiong Y, I /Li CO -
2
2
3
promoted cyanation of diarylalcohols through a dual activation process, Tetrahedron (2018), doi: https://
doi.org/10.1016/j.tet.2018.11.069.
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Graphical Abstract
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I2/Li2CO3-Promoted Cyanation of Diarylalcohols
through a Dual Activation Process
Liangzhen Hu,a Muhammad Ijaz Hussain,a Qingfu Deng,a Qing Liu,a Yangyang Feng,a Xiaohui Zhanga,* and
Yan Xionga,b,*
aSchool of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, China
b State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China.
.

ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
I2/Li2CO3-Promoted Cyanation of Diarylalcohols through a Dual Activation Process
Liangzhen Hu,a Muhammad Ijaz Hussain,a Qingfu Deng,a Qing Liu,a Yangyang Feng,a Xiaohui Zhanga,*
and Yan Xionga,b,*
aSchool of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, China
b State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
One-step base promoted strategy for cyanation of α,α-diaryl alcohols has been developed under
mild and transition metal-free conditions. This method provides a straightforward and facile way
towards the synthesis of β,γ-unsaturated nitriles and α-phenylnitiriles from α-vinyl carbinols and α,α-
diaryl methanols, respectively, up to 99% yield. Moreover, various azides and ethers could also be
accessed from their respective nucleophiles under standard reaction conditions.
Available online
2018 Elsevier Ltd. All rights reserved
.
.
Keywords:
Cyanation
Diarylalcohols
Dual activity
1. Introduction
iodine and hypervalent iodines to promote intramolecular
aminocyanation, aminothiocyanation and other cyanations.16
Allylic alcohols were used to form C-C, C-O, C-N bonds
through nucleophilic substitution procedure in the last two
decades.17 Meanwhile, diarylalkanes are crucial fragment as
pharmacologically active compounds.18 Therefore, in the
continuation of our ongoing interest, we envisioned a procedure
using α,α-diaryl alcohols as substrates via carbocation
intermediate direct into nitriles promoted by iodine could be
achieved. As expected, a series of both β,γ-unsaturated nitriles
and α-phenylnitiriles from α-vinyl carbinols and α,α-diaryl
methanols were approached successively. Herein, we would like
to report iodine-promoted transition metal-free cyanation of
diaryl alcohols towards synthesis of versatile nitriles.
β,γ-Unsaturated nitriles are not only important compounds in
dyes and perfumes but also notably important fragments in
natural products and various potential medicinal drugs, for
instance, HIV-1 cytopathic drug.1 Common cyanation methods to
synthesize cyanides started from halides2 and other allylic
substituted compounds, such as carbonates and acetates, have
been well reported.3 Except for these common strategies, quite
limited publications were reported to achieve β,γ-unsaturated
nitriles.4 Whereas, in the last few decades, the direct access to
nitriles from relatively easily available alcohols, which are key
substrates in carbon chain elongation, attracted much attention.
Based on the concept of the Mitsunobu reaction,5 various one-pot
cyanation strategies from alcohols have been developed by
utilizing either inorganic nitrile sources, for instance, HCN,
NaCN, KCN or using n-Bu4NCN reagent as organic cyanide
source.6 Meanwhile, both metal-free and metal-catalyzed
nucleophilic carbocation cyanation of alcohols have also been
developed, such as, utilizing B(C6F5)3,7 In(III),8 montmorillonite,9
2. Results and discussion
The feasibility of the intended transformation was appraised
using 1,1-diphenylprop-2-en-1-ol as a model substrate and
TMSCN with lower toxicity as cyanide source in the presence of
iodine in DCM and results are shown in Table 1. To our delight,
the transformation of test substrate proceeds selectively to allylic
.
11
FeCl3 6H2O,10 and Zn(OTf)2 as catalysts. Takemoto et al.
developed a strategy by using the combined halogen bond donor
with trimethylsilyl halide as Lewis acid co-catalyst to achieve the
direct dehydroxylative coupling of alcohols with organosilanes.12
As important as metal Lewis acids, iodine as Lewis acid has
extensive applications in organic synthesis especially the
functionalization of alcohols as well as alkenes.13 Iodine-
promoted reactions have a great advantage due to the mild
reaction conditions, safe handling, easy operation and clean
mixture.14 In the recent years, introduction of cyano motifs to
provide useful nitrile complexity in the compounds utilizing both
metal and metal-free reagents attracts most of our attention.15 In
this regards, we have successfully employed both elemental
o
cyanide 2a at 35 C in 35% yield and no rearranged benzyl
cyanated product was observed (entry 1, Table 1). The benzyl
carbocation, more stable and sterically hindered, is harder to be
attacked by nucleophile, therefore, it undergoes a rearrangement
to less sterically hindered allylic carbocation which is easier to be
attacked by cyanide anion, as depicted in Figure 1. Encouraged
by this primary result, the efficiencies of several solvents were
examined. Firstly, the reaction seems to be sensitive to solvents
and only DCE and DCM afforded the desired product 2a in 20%
and 35% yields, respectively (entries 2-6, Table 1). Next, the
effect of various amounts of I2 was investigated and the

2
Tetrahedron
ACCEPTED MANUSCRIPT
decreased yield was observed no matter increasing or
54% (entry 1, Table 2). Next, various inorganic bases were
decreasing its dosage (entries 7-8, Table 1). After the
concentration effect of TMSCN was examined and the best
outcome was obtained in 47% yield when 4.5 equivalents of
TMSCN was added (entries 9-12, Table 1). In the study of
temperature effect, decreased yields of the targeted product were
observed in both cases of raising and lowering of temperature
(entries 13-14, Table 1). In the end, effects of concentration and
reaction time were tested, and it proved to be detrimental to this
reaction when the two factors were changed (entries 15-18, Table
1).
analyzed and weak base were found to be capable to increase the
reaction yield (entries 2-6, Table 2). The best yield of 80% was
provided when 0.2 equivalent of Li2CO3 was loaded along with
optimized conditions (entry 6, Table 2). In cases of increasing
and decreasing the amount of Li2CO3, decreased yield of desired
product was observed (entries 6-8, Table 2). When the reaction
was performed in the dark which excluded the light promoting
reaction pathway the yield kept the same with in light (entry 6).
Eventually, after detailed experimentation, we were successful to
gain optimal dual-activation reaction conditions where iodine
activates alcohol substrate to generate carbocation and Li2CO3
activates TMSCN to release free cyanide anion.
Table 1. Optimization of reaction conditions.a
Table 2. Optimization of Additives.a
Yieldb
(% )
35
Entry
Solvent
TMSCN
(eq.)
3.0
I2
(eq.)
1.8
T
(°C)
35
1
2
DCM
THF
Entry
Additives
Equiv. (eq.)
Yieldb (% )
3.0
3.0
3.0
3.0
3.0
3.0
3.0
2.0
4.0
4.5
5.0
4.5
4.5
4.5
4.5
4.5
4.5
1.8
1.8
1.8
1.8
1.8
1.5
2.0
1.8
1.8
1.8
1.8
1.8
1.8
1.8
1.8
1.8
1.8
35
35
35
35
35
35
35
35
35
35
35
25
40
35
35
35
35
trace
0
3
CH3OH
EA
1
2
3
4
5
t-BuOK
NaHCO3
Na2CO3
K2CO3
0.2
0.2
0.2
0.2
0.2
54
63
50
62
63
4
trace
20
5
DCE
6
DMF
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
0
7
30
Mn2CO3
8
27
6
7
8
Li2CO3
Li2CO3
Li2CO3
0.2
0.1
0.3
80 (80)c
63
9
trace
40
10
11
12
13
14
15
16
17
18
70
47
a
39
Conditions: 1a (0.3 mmol), TMSCN (4.5 eq.), I2 (1.8 eq.) and base
(specified) in solvent (5 mL) at 35oC for 5 h.
b Yield determined by 1H-NMR using anisole as an internal standard.
c The reaction was performed in dark condition.
13
25
31c
32d
22e
18f
With the optimized conditions in hand, first we turned our
attention to explore the scope of diarylallylic alcohols and the
results were summarized in Table 3. Several allylic alcohols
bearing one or two electron-withdrawing groups were evaluated
to study this metal-free transformation and the desired cyanation
products under standard conditions were afforded in good to
excellent yields with some interesting conversions (2b-i). At the
outset, electronic effect of various halogens was investigated, as a
result, good to excellent outcome was obtained (2b-f). Among
these, substrates with electronegative substituents gave better
yields and a gradual decrease of yield is observed with the
increase of size and decrease of electronegativity. After that,
space orientation effect of halo-substituted substrates at ortho-
and meta-position was analyzed. As a result, lower yield of meta-
chloro substrate comparing to para- substituted was obtained. It
is important to note that ortho-chloro substrates responded to this
transformation under standard conditions in completely different
fashion and gave the rearranged iodinated products 3i in 81%
isolated yields. These results imply the prominent steric influence
of same counterparts at different positions on aromatic phenyl
ring. Furthermore, the remarkable transformation generality and
efficacy was demonstrated in the case of alcohol having an
electron donating functional group at para-position and 2j was
obtained in 78% yield. However, a decreased yield of targeted
product 2k was found due to the significant steric effect of ortho-
substitutent. For both electron-donating and electron-
withdrawing groups, para-substituents seemed to more
a
Conditions: 1a (0.3 mmol), TMSCN (specified), I2 (specified) in solvent (5
mL) at 35 oC for 5 h.
b Yield determined by 1H-NMR using anisole as an internal standard.
c 4 mL of DCM.
d 6 mL of DCM.
e 4 h.
f 6 h. n.d. = not detected.
Figure 1. Cyanation favoured rearrangement of carbocation from
benzyl to allylic site.
It is well-known that bases are capable of enhancing the
reactivity of TMSCN through ionization of TMSCN.19
Accordingly, diverse bases were subjected under standard
reaction conditions and as a result, the expected improvements in
yield was noticed (Table 2). A strong organic base such as t-
BuOK facilitated the transformation and gave a better yield of

favourable than ortho- and meta- counterparts. Besides mono-
ACCEPTED MANUSCRIPT
substituted substrates, 3,4-dimethyl substituted alcohol also
readily gave the desired product 2l in moderate yield. Quite low
stereoselectivity of desired products was observed, with the
exception of the strong steric hindrance substrate 1k. To test the
flexibility of the reaction, substrates with substitution at the
double bond were tested under the standard conditions, but only
2m was provided with lower yield of 28% and internal alkene
failed to give desired product 2n. Next, 1o and 1p were examined.
Only rigid allylic alcohol 1o provided product 2o in 33% yield
because of conjugation in the cations. Next, α-arylallylic alcohols
were tested but neither cinnamyl alcohol nor 1-phenylprop-2-en-
1-ol works well. Common substrates 1s and 1t were employed 2s
and 2t were obtained in the yields of 55% and 84%, respectively.
Following above results, we investigated cyanation of phenyl
substituted methanols (Scheme 2). As depicted in Scheme 1,
several phenyl commuted methanols such as diphenyl or
triphenyl could be transformed into cyanation products (2aa-ad)
up to 99% yield. Para-substituted substrates provided the
cyanation products in moderate to good yields (2ab-ac) and
better reactivity of electron-donating substituted derivatives was
observed as compared to electron-withdrawing substituted one.
Table 3. Scope of cyanation of allylic alcohol.a
Scheme 2. Cyanation of di- or tri-phenylmethanols.
To extend nucleophilic dual activation generality, other
trimethylsilyl based nucleophile such as TMS-N3, -OTf, -CF3 and -
C≡CH were utilized under standard conditions. Among these
trimethylsilyl reagents, the only azidation (Scheme 3) of the model
substrate was successful and product 2ba was isolated in 61% while
other counterparts found to be ineffectual to give the responding
products. Likewisely, the azidated product 2bb from
diphenylmethanol was obtained in a good yield of 79%. Moreover,
β,γ-unsaturated ethers were assembled when alcohols such as methyl
and benzyl alcohol were been chosen as a nucleophilic reagents, in
excellent yields of 98% and 89%, respectively.
2a,
2b, 79%
E:Z=1:1
2c, 69%
2d, 66%
E:Z = 1.23:1
80%,(77%)b
2e, 59%
2f, 62%
2g, 80%
2h, 28%
E:Z ≈ 1:1
E:Z ≈ 1:1
E:Z = 1.5:1
E:Z = 1.24:1
Scheme 3. Azidation and etherification under the optimal
conditions.
3i, 81%
E:Z≈1:1
2j,78%
E:Z = 1.75:1
2k, 43%
E:Z > 20:1
2l, 33%
E:Z = 5.98:1
CN
2m, 28%
2q, trace
2n, complex
2r, trace
2p, trace
2o, 33%
2s, 55%
In an effort to glean insights into the mechanism, some
control experiments were conducted. In the absence of either
TMSCN or I2, neither iodide nor cyanide was observed (Scheme
4 (a) and (b)). In the former case, the cyanation did not proceed,
even the time was prolonged to 24 h. However, in the later case,
TLC analysis showed a complex reaction then TMSCN was
added to react for another 5 h and no cyanided product was
detected. This suggested that elemental iodine plays a role of
Lewis acid to activate the oxygen and as such the C-O bond
became readily cleavable meanwhile there was no iodinated
intermediates formed. When diphenylmethanol was subjected to
this standard conditions only in the absence of I2,
(benzhydryloxy)trimethylsilane was captured and isolated in 74%
yield (Scheme 4 (c)), which shows the existence of ether
intermediate.
2t, 84%
a Conditions: 1 (0.3 mmol), TMSCN (1.35 mmol), I2 (0.54 mmol) and Li2CO3
(0.06 mmol) in DCM (5 mL) at 35 °C for 5 h in sealed reaction test tube.
:Z
b E ratio of products was determined by 1H NMR or 13C NMR, and E-
and Z- isomers was confirmed by 2D NOESY. c Isolated yields.
The synthetic utility of this method is amply demonstrated in
the alternative formal synthesis of well-known mental disorder
drug amitriptyline. The compound 1o obtained from
dibenzosuberone was subjected to this β,γ-unsaturated cyanation
gave 2o and followed by a reduction20 and a substitution to
access amitriptyline (Scheme 1).
Scheme 1. Synthetic utility of I2/Li2CO3-promoted cyanation of
diarylalcohols protocol in the synthesis ofamitriptyline.

4
Tetrahedron
To a two-necked flask under argon atmosphere loaded with a
ACCEPTED MANUSCRIPT
Scheme 4. Control experiments.
solution of ketone (5 mmol) in anhydrous THF (5 mL) then
under vigorous stirring Grignard reagent (1.0 M in THF, 5.5 mL,
5.5 mmol, 1.1 equiv.) was dropwise added via syringe in ice-bath.
The mixture was stirred for 0.5 h in ice bath, then warmed to
room temperature and stirred for 2-5 h. After detected by TLC,
aqueous NH4Cl (6 mL) was added to quench the reaction, then
the mixture was extracted with EtOAc (5 mL×3). The combined
organic layers were dried over anhydrous magnesium. The
solvent was removed in vacuo by ratory evaporator. And the
crude was purified by chromatography on silica gel to obtain
desired allylic alcohols.
Ph
OH
I2, Li2CO3
Ph
Ph
TMSCN
a
complex
Ph
not detected
CN
DCM, 35 oC, 5 h
OH
OH
TMSCN, Li2CO3
DCM, 35 oC, 5 h
Ph
b
n.r
Ph
OTMS
TMSCN, Li2CO3
DCM, 35 oC, 5 h
c
Ph
Ph
Ph
Ph
4, 74%
Based on the above experiments, a plausible mechanistic
pathway is proposed (Figure 3). Initially, substrate reacts with
TMSCN to form an intermediate A which interacted with iodine
to afford intermediate B. Subsequent removal of iodine and
trimethylsilyl alcohol could give carbocation intermediates which
changed to its steady state and coupled with the formed cyanide
anion to generate the desired product.
4.3. General procedure for the synthesis of aryl methanols 22
To ice-cold solution of ketone (5 mmol) in methanol (10 mL),
sodium borohydride (7 mmol) was slowly added under stirring.
o
Then, the mixture was further stirred for 1-3 h at 0 C. After
completion of the reaction monitored by TLC, evaporation of the
solvent and purified by a short chromatography on silica gel to
give alcohols.
4.4. General procedure of this method for synthesizing the
desired products (2 and 3)
To a round-bottom flask was charged with compounds 1 (0.3
mmol) in DCM (5 mL), Li2CO3 (0.06 mmol), TMSCN (or
TMSN3, or RO-H) (1.35 mmol), and I2 (0.54 mmol) in sequence
successively. Then the resulting mixture was stirred under closed
conditions at 35 oC (water bath temperature) for 5h. The reaction
was quenched with saturated solution of Na2S2O3. The organic
phase was separated, and the aqueous layer was extracted with
DCM (5 mL × 3). The combined organic solution was dried with
Mg2SO4 and concentrated in vacuo. The resulting residue was
purified by a column chromatography to give the corresponding
products.
Figure 3. Proposed reaction mechanism.
3. Conclusion
In summary, a straightforward transition metal-free dually
activated cyanation for preparation of diaryl substituted β,γ-
unsaturated nitriles, and α-phenylnitiriles from alcohols has been
developed. The mechanistic study revealed that elemental iodine
plays a role of Lewis acid to activate the oxygen and a possible
mechanism has been proposed: iodine activates alcohol and
lithium carbonate activates TMSCN. This protocol has
successfully been utilized in the concise synthesis of
amitriptyline. The easy operation and mild condition make this
protocol feasible and practical
4.4.1 4,4-diphenylbut-3-enenitrile (2a). White solid; m.p.
o
1
92.0-94.0 C; 77% yield, 50.7 mg; H NMR (500 MHz,
CDCl3) δ 7.45-7.36 (m, 3H), 7.29 (t, = 4.5 Hz, 3H), 7.23 (t,
= 4.0 Hz, 2H), 7.18 (d, = 8.0 Hz, 2H), 6.04 (t, = 7.5 Hz,
1H), 3.15 (d,
= 7.5Hz, 2H); 13C NMR (125 MHz, CDCl3) δ
J
J
J
J
J
147.7, 140.9, 138.1, 129.5, 129.0, 128.5, 128.4, 128.3,
127.6, 118.3, 115.6, 18.5; HRMS (m/z) calcd for C16H13NH+
220.1121, found 220.1130.
4.4.2 4-(4-fluorophenyl)-4-phenylbut-3-enenitrile (2b). E/Z=
1
o
4. Experimental section
1:1 White solid; m.p. 91-92 C; 79% yield, 56.2 mg; H
NMR (500 MHz, CDCl3) δ 7.44-7.29 (m, 3H), 7.20-7.10 (m,
4.1. General Information
5H), 6.97 (t,
3.12 d,
δ 163.9, 163.6, 161.9, 161.6, 146.8, 146.7, 140.7, 137.9,
137.0 (d, = 3.12 Hz), 134.0 (d, = 3.25 Hz), 131.3 (d,
8.05 Hz), 129.3 (d, = 7.12 Hz), 129.2 (d, = 50.38 Hz),
128.6, 128.5 (d, = 7.13 Hz), 127.5, 118.1, 118.0, , 116.03,
J
J
= 8.0 Hz, 1H), 6.00 (dt,
J = 29.5, 7.0 Hz, 1H)
. 13C NMR (125 MHz, CDCl3)
The 1H and 13C NMR spectra were recorded in CDCl3
，
（
= 7.5 Hz, 2H
）
o
1
solution at 500 (125) MHz spectrometer at 20-25 C. H NMR
spectra were reported in parts per million using TMS (δ = 0.00
ppm) as an internal standard. 13C NMR spectra were reported in
parts per million using solvent CDCl3 (δ = 77.2 ppm) as an
internal standard. High-resolution mass spectra (HRMS)
electrospray ionization (ESI) was carried out on a UPLC-Q-ToF
MS spectrometer. All reagents were purchased from commercial
suppliers and used as received. Common experiments were
conducted in the atmosphere, while the reactions with Grignard
reagent were developed in argon. Column chromatography and
thin-layer chromatography (TLC) which was used to monitor the
reactions were performed on silica gel.
J
J
J =
J
J
J
116.02 (d,
J = 21.38 Hz), 115.5, 115.4 (d, J = 21.50 Hz),
18.48, 18.46; HRMS (m/z) calcd for C16H12FNH+ 238.1027,
found 238.1027.
4.4.3 4,4-bis(4-fluorophenyl)but-3-enenitrile (2c). Light
1
yellow solid; m.p. 76-78 oC; 69%, 53.1 mg; H NMR (500
MHz, CDCl3) δ 7.18-7.11 (m, 6H), 6.99 (t,
5.99 (t, = 7.0 Hz, 1H), 3.13 (d, = 7.0 Hz, 2H); C NMR
(125 MHz, CDCl3) δ 163.8 (d, = 31.38 Hz), 161.8 (d,
31.25 Hz), 145.7, 136.8 (d, J = 3.25 Hz), 133.8 (d, J = 3.38
J = 8.0 Hz, 3H),
13
J
J
J
J =
4.2. General procedure for preparation of cyclic, acyclic
Hz), 130.29 (d,
J
= 250 Hz), 130.23 (d,
J
= 250 Hz), 118.0,
allylic
alcohols,
furan-2-yl(phenyl)methanol
and
phenyl(thiophen-2-yl)methanol.21
116.1 (d,
J
= 21.37 Hz), 115.9, 115.5 (d, J = 21.50 Hz), 18.5;
HRMS (m/z) calcd for C16H11F2NH+ 256.0933, found
256.0936.

2d). E/ =
18.4; HRMS (m/z) calcd for C17H15NH+ 234.1277, found
234.1285.
4.4.4 4-(4-chlorophenyl)-4-phenylbut-3-eneAnitCrilCe E( PTEZD MANUSCRIPT
1
1.23:1; White solid; m.p. 69-71 oC; 66% yield, 50.2 mg; H
NMR (500 MHz, CDCl3) δ 7.36-7.16 (m, 5H), 7.11 (d,
1.5 Hz, 1H), 7.07-7.03 (m, 3H), 5.95 (dt, = 12.5, 7.5 Hz,
1H), 3.05 (t,
= 4.0 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ
J
=
4.4.10 4-phenyl-4-(o-tolyl)but-3-enenitrile (2k
White liquid; 43% yield, 30.1 mg; H NMR (500 MHz,
)
.
E
/
Z
> 20:1
J
1
J
CDCl3) δ 7.30-7.25 (m, 6H), 7.24-7.20 (m, 2H), 7.11-7.08
146.59, 146.57, 140.4, 139.3, 137.6, 136.5, 134.35, 134.28,
130.9, 129.4, 129.2, 129.1, 128.8, 128.7, 128.59, 128.55,
128.50, 127.5, 118.05, 117.97, 116.14, 116.10, 18.50, 18.46;
HRMS (m/z) calcd for C16H12ClNH+ 254.0731, found
254.0731.
(m, 1H), 6.16 (t,
J = 7.5 Hz, 1H), 2.97(t, J = 5.5 Hz, 2H),
2.06 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 146.8, 139.3,
137.1, 136.4, 130.8, 129.5, 128.6, 128.4, 128.3, 126.6, 126.4,
118.0, 115.6, 19.6, 18.2; HRMS (m/z) calcd for
C16H12ClNH+ 234.1277, found 234.1273.
4.4.5 4-(4-bromophenyl)-4-phenylbut-3-enenitrile (2e). E/Z
1
4.4.11 4-(3,4-dimethylphenyl)-4-phenylbut-3-enenitrile (2l).
o
≈ 1:1 White solid; m.p. 59-60 C; 59% yield, 52.7 mg; H
NMR (500 MHz, CDCl3) δ 7.55 (d, = 2.5 Hz, 1H), 7.44-
7.38 (m, 3H), 7.29 (s, 1H), 7.20 (s, 1H), 7.14 (d, = 7.0 Hz,
1H), 7.07 (dd, = 11.5, 8.5 Hz, 2H), 6.03 (dd, = 16.0, 9.0
Hz, 1H), 3.12 (d,
= 6.5 Hz, 2H); 13C NMR (125 MHz,
1
E
/
Z
= 5.98:1 White liquid; 33% yield, 24.3 mg; H NMR
J
(500 MHz, CDCl3) δ 7.42-7.34 (m, 2H), 7.29-7.15 (m, 3H),
7.06-6.89 (m, 3H), 5.98 (td, = 7.5, 3.5Hz, 6H), 3.13 (dd,
= 20.0, 7.5 Hz, 2H), 2.24 (dd,
= 27.0, 17.0 Hz, 2H); 13C
J
J
J
J
J
J
J
NMR (125 MHz, CDCl3) δ 147.7, 147.6, 141.1, 138.5, 138.4,
137.2, 137.0, 136.7, 136.6, 135.6, 130.5, 130.0, 129.7, 129.5,
128.8, 128.7, 128.4, 128.2, 128.1, 127.6, 126.9, 125.1, 118.4,
115.2, 114.6, 19.94, 19.93, 19.7, 19.6, 18.5, 18.4; HRMS
(m/z) calcd for C18H17NH+ 248.1434, found 248.1442.
CDCl3) δ 146.56, 146.53, 140.3, 139.7, 137.5, 137.0, 132.1,
131.6, 131.2, 129.4, 129.1, 129.0, 128.55, 128.52, 128.47,
127.5, 122.5, 117.96, 117.90, 116.17, 116.11, 18.47, 18.42;
HRMS (m/z) calcd for C16H12BrNH+ 298.0226, found
298.0226.
4.4.12 3-methyl-4,4-diphenylbut-3-enenitrile (2m). White
4.4.6 4-(4-iodophenyl)-4-phenylbut-3-enenitrile (2f). E/Z ≈
1
o
1
solid; m.p. 71-73 C; 28% yield, 16.1 mg; H NMR (500
MHz, CDCl3) δ 7.35-7.21 (m, 6H), 7.16-7.12 (m, 4H), 3.16
(s, 2H), 1.97 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 143.0,
141.42, 141.36, 129.4, 129.2, 128.7, 128.3, 127.6, 127.3,
123.5, 118.4, 24.6, 19.9.
o
1:1 White solid; m.p. 66-68 C; 62% yield, 63.9 mg; H
NMR (500 MHz, CDCl3) δ 7.76 (d, = 8.5 Hz, 1H), 7.62 (d,
J
J = 8.5 Hz, 1H), 7.45-7.37 (m, 2H), 7.31-7.28 (m, 1H), 7.21-
7.17 (m, 1H), 7.16-7.13 (m, 1H), 6.97-6.92 (m, 2H), 6.06-
6.01 (m, 1H), 3.13 (d, J
= 7.0 Hz, 3H); 13C NMR (125 MHz,
CDCl3) δ 146.7, 146.6, 140.3, 140.2, 138.1, 137.54, 137.50,
137.4, 131.3, 129.4, 129.3, 129.0, 128.53, 128.50, 128.4,
127.5, 117.93, 117.88, 116.1, 116.0, 94.18, 94.15, 18.5, 18.4;
HRMS (m/z) calcd for C16H12INH+ 346.0087, found
346.0086.
4.4.13
3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-
ylidene)propanenitrile (2o). White solid; m.p. 136-137 oC;
1
33% yield, 24.2 mg; H NMR (500 MHz, CDCl3) δ 7.29-
7.27 (m, 1H), 7.25-7.14 (m, 5H), 7.10 (d,
7.05 (d, J = 7.0 Hz, 1H), 6.85 (t, J = 7.5 Hz, 1H), 3.32 (dd,
= 24.5, 13.5 Hz, 1H), 3.20-3.06 (m, 2H), 2.95 (t, J = 13.0 Hz,
1H), 2.78 (d,
= 12.5 Hz, 1H); 13C NMR (125 MHz, CDCl3)
δ 148.9, 139.44, 139.40, 138.2, 137.4, 130.4, 128.7, 128.6,
128.4, 128.1, 127.51, 126.46, 118.2, 117.6, 33.6, 31.9, 18.1.
J = 7.5 Hz, 1H),
J
4.4.7 4-phenyl-4-(p-tolyl)but-3-enenitrile (2g). E
Light yellow solid; m.p. 152-154 oC; 80% yield, 56.1 mg; 1H
NMR (500 MHz, CDCl3) δ 7.63 (t, = 9.0 Hz 2H) 7.54 (dd,
= 24.5, 7.5 Hz, 2H), 7.47-7.33 (m, 4H), 7.30-7.19 (m, 6H),
/Z = 1.5:1
J
J
J
23
6.06 (td,
J = 14.5, 7.5 Hz, 1H), 3.16 (dd, J = 25.0, 7.5 Hz,
4.4.14 (E)-2-methyl-4-phenylbut-3-enenitrile
(2s).
2H); 13C NMR (125 MHz, CDCl3) δ 147.4, 147.3, 141.17,
141.15, 140.9, 140.56, 140.52, 139.7, 138.1, 137.1, 130.0,
129.6, 129.05, 129.02, 128.98, 128.6, 128.4, 128.3, 128.0,
127.8, 127.66, 127.60, 127.22, 127.20, 127.15, 118.3, 118.2,
115.8, 115.6, 18.6, 18.5; HRMS (m/z) calcd for C22H17NH+
296.1434, found 296.1440.
1
Colorless oil; 55% yield, 26.1 mg; H NMR (500 MHz,
CDCl3) δ 7.41-7.34 (m, 4H), 7.32-7.27 (m, 1H), 6.73 (d,
15.5 Hz, 1H), 6.09 (dd, = 15.5, 6.0 Hz, 1H), 3.52-3.48 (m,
1H), 1.52 (d, = 7.5 Hz, 3H); C NMR (125 MHz, CDCl3)
J
=
J
13
J
δ 135.8, 132.6, 128.8, 128.3, 126.6, 124.4, 121.0, 28.4, 19.1.
8
4.4.15 (E)-2,4-diphenylbut-3-enenitrile (2t). White solid;
m.p. 62-64 C; 84% yield, 55.0 mg; H NMR (500 MHz,
CDCl3) δ 7.41-7.21 (m, 10H), 6.79 (d, = 15.5 Hz, 1H),
o
1
4.4.8 4-(3-chlorophenyl)-4-phenylbut-3-enenitrile
= 1.24:1; Light yellow liquid; 28% yield, 21.2 mg; H
NMR (500 MHz, CDCl3) δ 7.46-7.30 (m, 4H), 7.27-7.09 (m,
(2h).
1
E/Z
J
6.17 (dd,
J = 15.5, 6.0 Hz, 1H), 4.66 (dd, J = 6.5, 1.5 Hz,
1H); 13C NMR (125 MHz, CDCl3) δ 135.6, 134.7, 133.4,
5H), 6.05 (dd, J = 4.5, 2.5 Hz, 1H), 3.14 (d, J = 7.0 Hz, 2H);
13C NMR (125 MHz, CDCl3) δ 146.6, 146.4, 142.7, 140.1,
139.9, 137.4, 135.0, 134.5, 130.3, 129.7, 129.47, 129.43,
129.1, 128.64, 128.61, 128.59, 128.55, 128.4, 127.74,
127.66, 127.5, 125.8, 118.0, 117.9, 116.9, 116.4, 18.50,
18.48; HRMS (m/z) calcd for C16H12ClNH+ 254.0731, found
254.0723.
129.4, 128.8, 128.6, 127.7, 126.8, 123.4, 118.9, 40.1.
4.4.16 2,2-diphenylacetonitrile (2aa). White solid; m.p. 67-
69 oC; 98% yield, 55.7 mg; H NMR (500 MHz, CDCl3) δ
1
7.39-7.29 (m, 10H), 5.13 (s, 1H); 13C NMR (125 MHz,
CDCl3) δ 136.0, 129.3, 128.4, 127.8, 119.8, 42.7.
4.4.17 2-phenyl-2-(p-tolyl)acetonitrile (2ab). White solid;
m.p. 52-54 C; 98% yield, 55.7 mg; H NMR (500 MHz,
4.4.9 4-phenyl-4-(p-tolyl)but-3-enenitrile (2j). E
/
Z
= 1.75:1;
Yellow liquid; 78% yield, 56.3 mg; H NMR (500 MHz,
CDCl3) δ 7.43-7.36 (m, 2H), 7.27 (s, 1H), 7.22 (d, = 5.5
Hz, 2H), 7.16 (d, = 7.0 Hz, 1H),7.10 (s, 2H), 7.05 (d,
7.0 Hz, 1H), 5.99 (t, = 7.0 Hz, 1H), 3.12 (dd, = 15.5, 7.0
Hz, 2H), 2.36 (d,
= 30.5 Hz, 3H); 13C NMR (125 MHz,
o
1
1
CDCl3) δ 7.39-7.29 (m, 5H), 7.24-7.22 (m, 2H), 7.17 (d,
J =
J
9.0 Hz, 2H), 5.10 (s, 1H), 2.34 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 144.2, 136.8, 128.9, 128.4, 127.2, 126.3, 123.8,
122.0, 120.1, 119.8, 119.4, 111.2, 40.3.
J
J =
J
J
J
CDCl3) δ 147.6, 147.5, 141.1, 138.3, 138.2, 138.1, 138.0,
135.1, 129.6, 129.5, 129.4, 129.2, 128.9, 128.4, 128.23,
128.17, 127.6, 127.4, 118.4, 115.4, 114.7, 21.4, 21.2, 18.5,
4.4.18
2-(4-chlorophenyl)-2-phenylacetonitrile
(2ac).
1
Colorless liquid; 60% yield, 41.2 mg; H NMR (500 MHz,
CDCl3) δ 7.39-7.30 (m, 7H), 7.29-7.24 (m, 2H), 5.11 (s, 1H);

6
Tetrahedron
ACCEPTED MANUSCRIPT
13C NMR (125 MHz, CDCl3) δ 135.5, 134.6, 134.4, 129.5,
and Parekh, H. H. J. Sci. Islamic Repub. Iran 2004, 15, 135-138; e)
Guillemont J.; Pasquier E.; Palandjian P.; Vernier D.; Gaurrand S.;
129.4, 129.2, 128.6, 127.8, 119.4, 42.1.
Lewi P. J.; Heeres J.; De Jonge M. R.; Koymans L. M. H.;
Daeyaert F. F. D.; Vinkers M. H.; Arnold E.; Das K.; Pauwels R.;
Andries K.; De Béthune M.-P.; Bettens E.; Hertogs K.; Wigerinck
P.; Timmerman P. and Janssen P. a. J. J. Med. Chem. 2005, 48,
2072-2079.
4.4.19 2,2,2-triphenylacetonitrile (2ad). White solid; m.p.
o
1
124-126 C; > 99% yield, 80.3 mg; H NMR (500 MHz,
CDCl3) δ 7.44-7.39 (m, 9H), 7.31-7.28 (m, 6H); 13C NMR
(125 MHz, CDCl3) δ 140.3, 128.9, 128.7, 128.2, 123.6, 57.5.
2. a) Kanai, T.; Kanagawa, Y.; Ishii, Y. J. Org. Chem. 1990, 55,
3274-3277; b) Patel, D. V.; Schmidt, R. J. Synth. Commun. 1995,
25, 413-421; c) Singh, V.; Pathak, R.; Batra, S. Catal. Comm.
2007, 8, 2048-2052.
4.4.20 (3-azidoprop-1-ene-1,1-diyl)dibenzene (2ba). Light
yellow liquid; 61% yield, 43 mg; H NMR (500 MHz,
1
3. a) Tsuji, Y.; Yamada, N.; Tanaka, S. Org. Chem. 1993, 58, 16-17;
b) Tsuji, Y.; Kusui, T.; Kojima, T.; Sugiura, Y.; Yamada, N.; Tanaka,
S.; Ebihara, M.; Kawamura, T. Organometallics 1998, 17, 4835-4841;
c) Munemori, D.; Tsuji, H.; Uchida, K.; Suzuki, T.; Isa, K.;
Minakawa, M.; Kawatsura, M. Synthesis 2014, 46, 2747-2750.
4. a) Concellon, J. M.; Rodrıguez-Solla, H.; Simal, C.; Santos, D.
and Paz, N. R. Org. Lett. 2008, 10, 4549-4552; b) Tang, S.; Liu,
C.; Lei, A. Chem. Commun. 2013, 49, 2442-2444.
CDCl3) δ 7.41-7.33 (m, 3H), 7.29-7.23 (m, 5H), 7.17 (d,
J =
7.0 Hz, 2H), 6.17 (t,
J = 7.5 Hz, 1H), 3.85 (d, J = 7.5 Hz,
2H); 13C NMR (125 MHz, CDCl3) δ 147.3, 141.3, 138.5,
129.9, 128.6, 128.4, 128.2, 128.0, 127.8, 49.9; IR (KBr):
2093 cm–1.
4.4.21 (azidomethylene)dibenzene (2bb). Light yellow liquid;
1
79% yield, 49.3 mg; H NMR (500 MHz, CDCl3) δ 7.38-
5. Mitsunobu, O. Synthesis 1981, 1, 1-28.
7.34 (m, 4H), 7.38-7.34 (m, 6H), 5.71 (s, 1H); 13C NMR
6.
a) Aesa, M. C.; Baan, G.; Novak, L.; Szantay, C. Synth. Commun.
1995, 25, 2575-2578; b) Brett, D.; Dowine, I. M.; Lee, J. B. J.
Org. Chem. 1967, 32, 855-856; c) Mizuno, A.; Hamada, Y.;
Shioiri, T. Synthesis 1980, 12, 1007-1009; d) Iranpoor, N.;
Firouzabadi, H.; Akhlaghinia, B.; Nowrouzi, N. J. Org. Chem.
2004, 69, 2562-2564; e) Aerelie, T.-M.; Florence, P.; Eric, D. Syn.
Commun. 2010, 40, 1646-1648.
(125 MHz, CDCl3) δ 139.7, 128.8, 128.2, 127.5, 68.6.
4.4.22 2,2-bis(4-methoxyphenyl)-2-phenylacetonitrile (2bc).
White solid; m.p. 67.2-69 OC; 99% yield, 97.6 mg; 1H NMR
(500 MHz, CDCl3) δ 7.37-7.30 (m, 3H), 7.23-7.21 (m, 2H),
7.13-7.10 (m, 4H), 6.88-6.84 (m, 4H), 3.80 (s, 6H); 13C
NMR (125 MHz, CDCl3) δ 159.4, 141.0, 132.7, 130.1,
128.80, 128.76, 128.2, 123.9, 114.1, 56.2, 55.5.
7. Rajagopal, G.; Kim, S. S. Tetrahedron 2009, 65, 4351-4355.
8. Chen, G.; Wang, Z.; Wu, J.; Ding, K. Org. Lett. 2008, 10, 4573-
4576.
9. Wang, J.; Masui, Y.; Onaka, M. ACS Cata. 2011, 1, 446-454.
10. Trill, P.; Baeza, A.; Najera, C. ChemCatChem 2013, 5, 1538-1542.
11. Theerthagiri, P.; Lalitha, A. Tetrahedron Lett. 2012, 53, 5535-
5538.
4.4.23 (3-methoxyprop-1-ene-1,1-diyl)dibenzene
(
2ca).
Colorless liquid; 98% yield, 65.8 mg; H NMR (500 MHz,
CDCl3) δ 7.49-7.43 (m, 3H), 7.39-7.34 (m, 5H), 7.29 (d,
1
J
=
12. Saito, M., Tsuji, N., Kobayashi, Y., Taakemoto, Y. Org. Lett.
2015, 17, 3000-3003.
7.0 Hz, 2H), 6.34 (t,
J = 6.5 Hz, 1H), 4.10 (d, J = 6.5 Hz,
2H), 3.42 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 144.8,
142.0, 139.3, 129.9, 128.3, 127.7, 127.63, 127.60, 125.6,
70.3, 58.2.
13. a) Karimi, B.; Golshani, B. J. Org. Chem. 2000, 65, 7228-7230; b)
Chu, C.-M.; Huang, W.-J.; Liu, J.-T.; Yao, C.-F. Tetrahedron Lett.
2007, 48, 6881-6885; c) Liu, Z.; Liu, L.; Shafiq, Z.; Wu, Y.-C.;
Wang, D.; Chen,Y.-J. Tetrahedron Lett. 2007, 48, 3963-3967; d)
Rao, W.; Tay, A. H. L.; Goh, P. J.; Choy, J. M. L.; Ke, J. K.; Chan,
P. W. H. Tetrahedron Lett. 2008, 49, 122-126.
4.4.24 (3-methoxyprop-1-ene-1,1-diyl)dibenzene
(
2cb).
Colorless liquid; 89% yield, 80.2 mg; H NMR (500 MHz,
CDCl3) δ 7.36-7.29 (m, 7H), 7.27-7.22 (m, 6H), 7.17 (d,
1.5 Hz, 2H), 7.15 (s, 1H), 6.27 (t, = 2.0 Hz, 2H), 4.46 (s,
= 7.0 Hz, 2H); C NMR (125 MHz, CDCl3)
1
14. Zhou, Y.; Yan, P.; Li, G.; Chen, Z. Chin. J. Org. Chem. 2009, 29,
1719-1727.
J
=
J
15. a) Shen, H.; Zhang, X.; Liu, Q.; Pan, J.; Hu, W.; Xiong, Y.; Zhu,
X. Tetrohedron Lett. 2015, 56, 5628-5631; b) Shen, H.; Li, J.; Liu,
Q.; Pan, J.; Huang, R.; Xiong, Y. J. Org. Chem. 2015, 80, 7212-
7218; c) Shen, H.; Hu, L.; Liu, Q.; Hussain, M. I.; Pan, J.; Huang,
M.; Xiong, Y. Chem. Commun. 2016, 52, 2776-2779; d) Hussain,
M. I.; Feng, Y.; Hu, L.; Deng, Q.; Zhang, X.; Xiong, Y. J. Org.
Chem. 2018, 83, 7852-7859.
16. a) Shen, H.; Deng, Q.; Liu, R.; Feng, Y.; Zheng, C.; Xiong, Y.
Org. Chem. Front. 2017, 4, 1806-1811; b) Feng, Y.; Hussain, M.
I.; Zhang, X.; Shi, J.; Hu, W.; Xiong, Y., Tetrahedron 2018, 74,
2669-2676.
17. a) Shibuya, M.; Ito, S.; Takahashi. M.; Iwbuchi, Y. Org. Lett.
2004, 6, 4303-4306; b) Vatele, J.-M. Tetrahedron 2010, 66, 904-
912; c) Li, J.; Tan, C.; Gong, J.; Yang, Z. Org. Lett. 2014, 16,
5370-5373; d) Tamaru, Y. Eur. J. Org. Chem. 2005, 13, 2647-
2656; e) Trost, B. M.; Quancard, J. J. Am. Chem. Soc. 2006, 128,
13
2H), 4.10 (d,
J
δ 145.0, 142.0, 139.4, 138.5, 129.9, 128.5, 128.3, 128.0,
127.8, 127.73, 127.67, 127.61, 125.7, 72.5, 68.1.
4.4.25 1-chloro-2-(3-iodo-1-phenylprop-1-en-1-yl)benzene
1
(3i). E/Z ≈ 1:1 Light yellow liquid ; 81% yield, 78 mg; H
NMR (500 MHz, CDCl3) δ 7.47 (d,
7.31 (m, 3H), 7.28-7.24 (m, 3H), 7.21 (d,
J
= 7.5 Hz, 1H), 7.37-
= 7.5 Hz, 2H),
= 8.0 Hz, 1H), 3.71 (t, J =
J
6.54 (t,
J
= 9.0 Hz, 1H), 3.93 (t,
J
9.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 141.7, 139.2,
136.7, 134.0, 130.5, 130.2, 129.5, 128.6, 128.2, 127.1, 126.6,
126.3, 4.2; HRMS (m/z) calcd for C15H12ClINa+ 376.9564,
found 376.9553.
6314-6315; f) Mohr, J. T.; Stoltz, B. M. Chem. Asian J. 2007, 2,
4.4.26 (benzhydryloxy)trimethylsilane (
4
). Colorless liquid;
74% yield, 57.2 mg; H NMR (500 MHz, CDCl3) δ 7.38 (d,
= 7.0 Hz, 4H), 7.33 (t, = 8.0 Hz, 4H), 7.25 (t, = 7.5 Hz,
1
1476-1491; g) Utsunomiya, M.; Miyamoto, Y.; Ipposhi, J.;
Ohshima, T.; Mashima, K. Org. Lett. 2007, 9, 3371-3374; h) Mora,
G.; Piechaczyk, O.; Houdard, R.; Mezailles, N.; Le, Goff, X.-F.;
Le Floch, P. Chem. Eur. J. 2008, 14,10047-10057; i) Banerjee, D.;
Jagadeesh, R. V.; Junge, K.; Junge, H.; Beller, M. ChemSusChem
2012, 5, 2039-2044.
J
J
J
13
2H), 5.81 (s, 1H), 2.20 (s, 2H), 0.12 (s, 9H); C NMR (125
MHz, CDCl3) δ 145.0, 128.3, 127.2, 126.7, 76.6, 0.28.
Acknowledgments
18. a) Kim, J. S.; Quang, D. T. Chem. Rev. 2007, 107, 3780-3799; b)
Brotin, T.; Dutasta, J.-P. Chem. Rev. 2009, 109, 88-130; c) Xue,
M.; Yang, Y.; Chi, X.; Zhang, Z.; Huang, F. Acc. Chem. Res. 2012,
45, 1294-1308; d) Vanjari, R.; Singh, K. N. Chem. Soc. Rev. 2015,
44, 8062-8096.
19. a) Deng, H.; Isler, M. P.; Snapper, M. L.; Hoveyda, A. H. Angew.
Chem. Int. Ed. 2002, 41, 1009-1012; b) Shen, Y.; Feng, X.; Li, Y.;
Zhang, G.; Jiang, Y. Synlett 2002, 5, 793-795; c) Shen, Y.; Feng,
X.; Li, Y.; Zhang, G.; Jiang, Y. Tetrahedron 2003, 59, 5667-5675;
d) Tian, S.-K.; Hong, R.; Deng, L. J. Am. Chem. Soc. 2003, 125,
9900-9901; e) Fuerst, D. E. and Jacobsen, E. N. J. Am. Chem. Soc.
We gratefully acknowledge funding from the National
Natural Science Foundation of China (No. 21372265) and
the Natural Science Foundation Project of CQ CSTC
(cstc2018jcyjAX0155).
References and notes
1. a) Takashi, M. JP. Patent 04089869, 1992; b) Granier, T. JP.
Patent 02306954, 1990. c) Granier, T. U.S. Patent 20110207835,
2011; d) Hirpara, K. V.; atel, S. P.; arikh, K. A.; A. S. Bhimani

2005, 127, 8964-8965; f) Xiong, Y.; Huang, X.; Gou, S.; Huang,
22. Li, J.; Liu, Q.; Shen, H.; Huang, R.; Zhang, X.; Xiong, Y.; Chen,
C. RSC Adv. 2015, 5, 85291-85295.
23. Sawama, Y.; Goto, R.; Nagata, S.; Shishido, Y.; Monguchi, Y.;
Sajiki, H. Chem. Eur. J. 2014, 20, 2631-2636.
ACCEPTED MANUSCRIPT
J.; Wen, Y.; Feng, X. Adv. Synth. Catal.2006, 348, 538-544.
20. a) Mahesh, K. WO 2013168008, 2013; (b) Bryson, H. M.; Wilde,
M. I. Drugs & Aging 1996, 8, 459-476.
21. Zhang J.-J.; Yan C.-S.; Peng Y.; Luo Z.-B.; Xu X.-B. and Wang
Y.-W. Org. Biomol. Chem. 2013, 11, 2498-2513.