Electron transfer-induced coupling of haloarenes to styrenes and 1,1-diphenylethenes triggered by diketopiperazines and potassium tert-butoxide

Article abstract of DOI:10.3390/molecules20021755

The coupling of haloarenes to styrenes and 1,1-diarylethenes has been achieved with potassium tert-butoxide in the presence of N,N'-dialkyldiketopiperazines. In contrast to previously reported reactions where phenanthroline has been used to mediate the reactions, the use of diketopiperazines can lead to either 1,1,2-triarylethenes or 1,1,2-triarylethanes, depending on the conditions used.

Full text of DOI:10.3390/molecules20021755

Molecules 2015, 20, 1755-1774; doi:10.3390/molecules20021755
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Communication
Electron Transfer-Induced Coupling of Haloarenes to Styrenes
and 1,1-Diphenylethenes Triggered by Diketopiperazines and
Potassium tert-Butoxide
Eswararao Doni, Shengze Zhou and John A. Murphy *
WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde,
295 Cathedral Street, Glasgow G1 1XL, UK; E-Mails: eswararao.doni@strath.ac.uk (E.D.);
shengze_zhou@hotmail.com (S.Z.)
*
Author to whom correspondence should be addressed; E-Mail: john.murphy@strath.ac.uk;
Tel.: +44-(0)141-548-4246.
Academic Editor: John Walton
Received: 22 December 2014 / Accepted: 6 January 2015 / Published: 22 January 2015
Abstract: The coupling of haloarenes to styrenes and 1,1-diarylethenes has been achieved
with potassium tert-butoxide in the presence of N,N'-dialkyldiketopiperazines. In contrast
to previously reported reactions where phenanthroline has been used to mediate the
reactions, the use of diketopiperazines can lead to either 1,1,2-triarylethenes or
1,1,2-triarylethanes, depending on the conditions used.
Keywords: electron transfer; coupling; haloarenes; potassium tert-butoxide; diketopiperazine
1
. Introduction
Stilbenes include a range of medicinally important molecules [1]. Traditionally, they can be formed
by coupling haloarenes to styrenes, catalyzed by palladium salts or complexes [2–5]. However, in
011, Shirakawa, Zhang and Hayashi [6] published a paper in which KOtBu (3 equiv) and EtOH
0.2 equiv) brought about coupling reactions between iodobenzenes and styrenes in DMF at 80 °C, to
2
(
afford the stilbene products in the absence of any palladium or other transition metal sources. Aryl
iodides worked well and some aryl chlorides and bromides were also effectively coupled, but only in
cases where the π-system extended beyond simple halobenzenes, e.g., halonaphthalenes. (this work
followed closely on the heels of the KOtBu-mediated coupling of halobenzenes to arenes [7–10]). This

Molecules 2015, 20
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paper [6] demonstrated the intermediacy of benzylic radicals, such as 4a, which resulted from addition
of an aryl radical to the styrene. A full mechanism was proposed that has since been adapted [11,12] to
the mechanism shown in Figure 1. The initiation of the reaction was proposed to occur by electron
transfer to the iodoarene 1a. Hayashi et al., suggested that the electron would be transferred from a
butoxide anion, thereby forming a butoxyl radical, but see below. The resulting aryl radical 2a adds to
1
,1-diphenylethene 3 to afford radical 4a. Deprotonation of this radical affords the stabilised radical
anion 5a. This then forms the stilbene product 6a by electron transfer to another molecule of
iodobenzene 1a that enters the chain reaction.
Ph
I
Ph
3
Ph
Ph
Ph
Ph
15a
initiation
I
H-atom
abstraction
1
a
2a
4a
I
KOtBu
1
a
Ph
Ph
Ph
Ph
6
a
5a
Figure 1. Mechanism of the coupling of iodoarenes to styrenes.
Two other research groups reported closely related findings in the same year. Shi et al., observed [13]
intermolecular and intramolecular couplings of iodoarenes to 1,1-diphenylethenes, mediated by KOtBu
in benzene as solvent at 110 °C., but in the presence of phenanthrolines as additives. Taking
phenanthroline itself in Figure 2 as an example, they proposed that the phenanthroline complex of
KOtBu 7 acted as an electron donor to the aryl halide to initiate the radical reactions. Rueping et al.,
likewise [14] used phenanthroline and KOtBu to bring about intramolecular coupling of iodoaryl
moieties with styryl and 1,1-diphenylethenyl groups. More recently, Rossi et al. [1] reported a new
version of the Hayashi process (i.e., in the absence of organic additives), using photostimulation to
enhance the initiation.
I
G = + 59.5
kcal mole-1
O
Pr
N
N
+
N
+
+
I
N
N
N
Pr
K
K
K
OtBu
OtBu
O
7
1a
8
9
2
14
H
K
N
N
N
N
N
N
N
N
N
N
N
K
OtBu
N
N
N
2
K
1
0
11
12
13
Figure 2. Species potentially involved in the electron-transfer initiation reactions.

Molecules 2015, 20
1757
The issue of electron transfer when KOtBu reacts in these reactions is of much current interest. For
a phenanthroline complex, 7, Tuttle, Murphy et al. [15] showed that electron transfer to iodobenzene
−1
would have a thermodynamic difference between starting materials and products ∆G = +59.5 kcal·mol ,
when calculated at the M06L/6-311G(d,p) level of theory using the CPCM continuum solvation
method to incorporate the polarizing effect of the benzene solvent. It is stressed that this is not the
kinetic barrier, which is likely to be considerably higher. The reaction is so endergonic as to make such
an electron transfer untenable in ground state chemistry. Moreover they isolated a single distinctive
product, 11, resulting from in situ dimerisation of phenanthroline and quenching by an electron
acceptor (in this case, iodine). This drove them to propose that the strong electron donors, anion 12
and/or dianion 13, are produced during these reactions and may play a crucial role in the electron
transfer steps.
Since then, Wilden et al., reported [16] evidence for decomposition products of tert-butoxyl radical
in coupling reactions, and therefore supporting the role of electron transfer from tert-butoxide anion.
In their case, they proposed that the electron transfer occurs to the phenanthroline to form the
phenanthroline radical anion that then acts as the electron donor. Very recently, Lei, Jutand et al.,
proposed [17] that the phenanthroline radical anion, resulting from electron transfer from butoxide to
phenanthroline, is the active electron donor although, surprisingly, they do not cite the Wilden
paper [16] that came to the same conclusion. Both of these papers cite the Tuttle and Murphy [15]
paper, but Wilden comments on our computational results and doesn’t discuss the experimental results
including the isolation of 11 and its implications, while Lei and Jutand mention the paper only in the
context that it reports that the “mechanism of action of 1,2-diamines” as organic additives in similar
reactions is not yet clarified (that was not studied in the paper) but don’t discuss the core findings of
the paper. A further paper has appeared from Yuan et al. [18] that uses a photoactivated complex of
KOtBu with phenanthroline, but cites none of these papers.
In the absence of phenanthroline additives, (i.e., the conditions used by Hayashi), Murphy and
Tuttle [15] proposed that traces of benzyne, formed from reaction of KOtBu with iodoarenes, can
initiate the reactions [1]. To date, phenanthrolines are the only organic additives to have triggered these
reactions. In exploring the scope of the coupling reactions and in understanding the roles of organic
additives, it would be helpful to explore alternative compounds that perform a similar role. That is the
task of this paper.
2
. Results and Discussion
Very recently, Tuttle and Murphy et al. reported [19] that the enolate 14 of
N,N'-dialkyldiketopiperazine 16 could act as an electron donor and trigger coupling reactions between
aryl halides and arenes. In coupling haloarenes to arenes, a number of authors had previously found
that aminoacids, in the presence of KOtBu, played a helpful role [9,20,21]. Moreover, it seemed that
N-monoalkyl aminoacids (i.e., secondary aminoacids) were more helpful than primary aminoacids. We
recently suggested that this might be explained if the secondary aminoacids underwent condensation
reactions in situ, that could lead to N,N'-dialkyldiketopiperazines [19]. In turn, these could be
deprotonated to form enolates that would act as electron donors. Regardless of whether that happens
for secondary amino acids, our interest in the possible role of enolates such as 14 was heightened. This

Molecules 2015, 20
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paper now investigates the coupling of iodoarenes with styrenes and 1,1-diphenylethenes in the
presence of KOtBu and N,N'-dialkyldiketopiperazines.
The prototype reaction used for the study was the coupling of iodobenzene (1a) to
1
,1-diphenylethene 3 (Table 1). In the presence of 16 (0.5 equiv), and heating in benzene for 16 h at
00 °C (entry 1) afforded products 6a (11%) and 15a (18%). Product 15a presumably arises from
1
coupling of the aryl radical to the alkene; hydrogen abstraction by this radical then occurs more rapidly
than deprotonation to form radical anion 5a, the precursor of 6a. Table 1 explores the optimisation of
this reaction, in which various solvents (DMSO, DMF, benzene), different temperatures and different
numbers of equivalents of butoxide, of the diketopiperazine and of the diphenylethene were used. The
most successful conditions for forming coupling products are shown in entries 10 and 11. In entry 10,
the number of equivalents of 16 is at a minimum (0.05), while the number of equivalents of KOtBu
(
10) is at a maximum. The latter helps to maximize the formation of 6a, since under these conditions,
the deprotonation of the benzylic radical 4a is most likely, thereby leading to the product 6a, following
electron transfer. On the other hand, conditions for entry 11 minimize the concentration of KOtBu, but
uses higher concentrations of the diketopiperazine 16 and this leads to 15 as the predominant product.
In this Table, Entry 8 shows the importance of using KOtBu, as potassium carbonate is not effective in
affording coupling. Entry 12 shows that the diketopiperazine 16 is required to afford the products; in
its absence, only a trace of product formed. This is in keeping with the proposed initiator role of
enolate 14 as an electron donor.
Table 1. Optimisation conditions for the coupling of iodobenzene 1a to 1,1-diphenylethene 3.
O
Pr
I
16
Ph
Ph
Ph
N
+
N
+
Ph Ph
Ph
Pr
Base
benzene (1 mL)
1
6
O
1a
3
6a
15a
Reaction
Entry 3 (Equiv.) 16 (Equiv.)
Base (Equiv.)
Solvent
T (°C)
6a (%) a 15a (%) a
Time (h)
16
1
2
3
4
5
6
7
8
9
1
1
1
1
3
3
5
5
5
5
5
5
0.5
0.1
0.1
0.1
0.1
0.3
0.1
0.1
0.2
0.05
0.3
-
KOtBu (3)
KOtBu (5)
KOtBu (5)
KOtBu (5)
KOtBu (5)
KOtBu (3)
KOtBu (6)
benzene
benzene
benzene
DMSO
100
110
160
160
160
110
110
110
110
110
110
110
11
22
25
-- b
6
18
13
8
-- b
13
43
26
0
16
16
16
DMF
16
benzene
benzene
benzene
benzene
benzene
benzene
benzene
36
25
36
0
36
K
2
CO
3
(6)
36
KOtBu (6)
KOtBu (10)
KOtBu (1.5)
KOtBu (6)
36
25
58
20
trace
42
14
63
trace
1
0
1
2
36
1
36
1
36
Notes: Reactions were carried out using 0.5 mmol of 1a in a sealed pressure tube and provided 1%–5% of
biphenyl product (except for Entries 5 and 8) along with 6a and 15a. a Isolated product yields. b Starting
material was decomposed.

Molecules 2015, 20
1759
These optimised conditions of entry 10 were then applied to the formation of coupled alkene
products 6. Figure 3 shows the outcomes. With the exception of the naphthalene cases arising from
1
-bromonaphthalene, in each case, a mixture of two products, the triarylethene 6 and triarylethane 15,
was formed. Where separation of the two products was possible, their isolated yields are quoted as the
percentages above. In some cases, separation of the two products was not possible and, there, an
overall yield is followed by a ratio of the two products. In each case, the alkene predominates, with the
ratios varying from 2.5:1 to more than 5.5:1. In the case of 1-bromonaphthalene, it appears that very
easy elimination to the corresponding benzyne occurred. Addition of tert-butoxide occurred selectively
at the 2-position, ultimately affording 2-t-butoxynaphthalene 17 [22]. Even allowing for that,
1
-naphthyl radicals were clearly also formed as shown by the formation of 6g and 15g. It is not clear
why the alkene product, 6g, was not isolated in greater yield in this case.
I
16 (0.05 equiv.)
Ph
Ph
Ph
+
+
Ph Ph
Ph
KOtBu (10 equiv.)
R
R
R
15
benzene (1 mL)
o
1
3 (5 equiv.)
6
1
10 C, 36 h
OMe
O
O
Ph
Ph
Ph
Ph
Ph
Ph
Pr
N
N
Me
MeO
Pr
16
6c + 15c, 43% (1 : 0.4)a
6d + 15d, 64% (1 : 0.18)a
6b 56% (15b, 18%)
Ph
Ph
Ph
Ph
Ph
Ph
O
Cl
6g, trace (15g, 12%)b
6e, 43% (15e, 11%)
6f, 53% (15f, 19%)
17, 46%
Reactions were carried out using 0.5 mmol of 1. All the yields are those of isolated products.
[
a] Reaction has provided inseparable mixture of both the products in the ratio as mentioned.
[
b] Reaction was carried out using the corresponding bromide (not iodide).
Figure 3. Scope of the formation of alkene products 6.
Returning to Table 1, entry 11 showed the optimised conditions for the formation of the
,1,2-triarylethanes 15. Here, far less KOtBu (1.5 equiv) was used, and the amount of diketopiperazine
6 was higher (0.3 equiv) than for entry 10. Figure 4 reports our studies on optimization of the yields
1
1
of 15. It should be noted that while the formation of the alkene product 6 leads to continuation of a
radical chain shown in Figure 1, the formation of 15 does not.
At the end of the addition sequence, hydrogen abstraction is required, and the most likely source of
that hydrogen is the molecule 16, since abstraction from one of its CH groups would afford a
2
stabilized captodative radical. However, there is a deficiency of this molecule (only 0.3 equiv), and
since more than 60% of product 15 is formed this suggests that each molecule of 16 provides more
than one hydrogen atom. This will be discussed further below (Figure 7). With 1-bromonaphthalene,
1
,1,2-triarylethane product 15g (46%) was formed in preference to 1,1,2-triarylethene 6g (trace
amounts), but 2-t-butoxynaphthalene 17 was again isolated (8%).

Molecules 2015, 20
1760
I
16 (0.3 equiv.)
Ph
Ph
Ph
+
+
Ph Ph
Ph
KOtBu (1.5 equiv.)
R
R
15
R
6
benzene (1 mL)
1
3 (5 equiv.)
o
1
10 C, 36 h
OMe
O
O
Ph
Ph
Ph
Ph
Ph
Ph
Pr
N
N
Me
MeO
Pr
1
6
15c + 6c, 52% (1 : 0.42)a
15d + 6d, 50% (1 : 0.33)a
1
5b, 66% (6b, 14%)
Ph
Ph
Ph
Ph
Ph
O
Ph
Cl
1
5e, 19% (6e, 23%)
15f, 54% (6f, 22%)
15g, 46%b (6g, trace)
17, 8%
Reactions were carried out using 0.5 mmol of 1. All the yields are those of isolated products.
[
[
a] Reaction has provided inseparable mixture of both the products in the ratio as mentioned.
b] Reaction was carried out using the corresponding bromide (not iodide).
Figure 4. Scope of the formation of triarylethane products 15.
Proceeding to test the reaction in coupling with styrenes (Figure 5), it is clear that the reaction
affords yields that are lower than for 1,1-diphenylethenes. Iodides work better than bromides, and the
higher temperature of 130 °C works better than lower temperatures.
X
16 (0.3 equiv.)
Ph
+
Ph
KOtBu (3 equiv.)
benzene (1 mL)
R
R
1
18 (5 equiv.)
19
Ph
Ph
O
Pr
Me
MeO
N
1
9b
19c
N
Pr
1
6
O
o
from 1c, X = I, 130 oC, 3 h, 36%
from 1b, X = I, 110 C, 16 h, 10%
from 1b, X = I, 80 oC, 3 h, 20%
o
from 1b, X = I, 130 C, 3 h, 35%
o
from 1b, X = Br, 130 C, 3 h, 10%
Reactions were carried out using 0.5 mmol of 1. All the yields are those of isolated products.
Figure 5. Formation of stilbene products from styrenes.
In reaching the unsaturated products, the importance of the acidity of the proton to be removed in
transforming benzylic radical 4 to the corresponding radical anion 5 (Figure 1) is key. This is seen in
comparing the cyclisations of substrates 20 and 23 (Figure 6). Cyclisation of the aryl radical derived
from iodoarene 20 onto the diphenylethene affords benzylic radical 26. Deprotonation of this radical
gives a radical anion 27 that can delocalize over the three aromatic rings. Hence the diphenylethene 28
can form in good yield, allowing the chain reaction to continue. Either during the reaction or on work
up, isomerisation of the stilbene central double-bond in 28 occurs to afford the benzofuran 21. In
contrast, deprotonation of the radical resulting from cyclisation of the aryl radical arising from 23 does
not lead to such a delocalized radical anion, and so the deprotonation is relatively inhibited, with
hydrogen atom abstraction occurring instead to form 24.

Molecules 2015, 20
1761
Ph
Ph
Ph
Ph
Ph
Ph
I
H
.Ph
Ph
+
Ph
Ph
O
O
O
O
O
O
2
0
21, 61%
22, (trace)
26
Pr
N
O
Me
Me
Me
Me
N
Ph
Me
Me
Pr
.Ph
28
I
16
+
O
O
O
O
2
3
24 20%
25, (trace)
27
o
Reaction conditions: 16 (0.3 eq.), KOtBu (3 eq.), benzene (2 mL) , 110 C, 24 h
Figure 6. The importance of acidity in forming alkene products.
The importance of the hydrogen abstraction step is revisited in Figure 7. Here two diketopiperazines
1
6 and 29 were compared, mindful of what was said above about hydrogen abstraction. The two
additives gave very different results. Compound 16 afforded significantly higher yield (66%) of the
reduced compound 15b, indicating that the additional CH group in 16 plays a major role in
2
determination of the pathways to product. Since 0.3 equiv of the N,N'-dialkyl diketopiperazine 16 was
used, and more than 60% of dihydrostilbene product 15b formed, it suggests that on average the
N,N'-dialkyl diketopiperazine, as the likely source for hydrogen atom abstraction, can be responsible
for providing two hydrogen atoms.
I
Ph
Ph
Ph
+
+
Ph Ph
Ph
Me
Me
Me
1
b
3, (5 equiv)
using 16: 6b, 14%
using 29: 6b, 28%
15b, 66%
15b, 26%
o
Reaction conditions: 16 / 29 (0.3 eq.), KOtBu (1.5 eq.), benzene (1 mL) , 110 C, 36 h
Me
I
Me
Ph
Ph
6h, 13%
Me
Ph
Ph
+
+
Ph Ph
1
h
3, (3 equiv)
using 16:
15h, 38%
using 30:
6h, 44%
15h, 17%
In lit:ref. 7
64%
n/a
o
Reaction conditions: 16/ 29 (0.3 eq.), KOtBu (3 eq.), benzene (1 mL) , 110 C, 36 h
O
O
Me
Me
Pr
Bu
N
N
N
N
N
N
Pr
Me
O
O
16
29
30
KOtBu
O
O
O
Pr
N
O
O
O
H
H
H
Pr
Pr
Pr
N
N
H
O
H
N
H
H
.
N
Pr
N
Ar
H
N
N
Pr
N
Pr
Pr
H
Pr
H
O
N
H
H
O
Pr
O
1
4
31
32
34
Figure 7. The importance of hydrogen atom abstraction.

Molecules 2015, 20
1762
If the diketopiperazine requires to be deprotonated to 14, and later transforms into radical 31
following electron transfer then, in either case, only a single hydrogen from the remaining methylene
group would be available for hydrogen atom abstraction. However, if dimerization of radical 31 to 32
should occur [23] (32 could also arise by combination of radical 31 with anion 14, followed by
electron transfer) or if combination of 31 with another radical (e.g., an aryl radical) to form 34 should
occur, then additional hydrogens come into play (shown in red in Figure 7), that can account for the
observed yields of products.
The results from the m-tolyl case 1h were less pronounced, but comparison with the experiment
using phenanthroline 30 shows that the yield of saturated product 15h is enhanced when the
diketopiperazine is used. The literature [13] reports a 64% yield of the stilbene, whereas our experiments
afford a 61% yield, (but as a 44% + 17% mixture of the stilbene and the dihydrostilbene product).
3. Experimental Section
3.1. General Information
All the reactions were performed in oven-dried or flame-dried apparatus and preparation of the
substrates was carried out under argon atmosphere using dry solvents. Diethyl ether, tetrahydrofuran,
dichloromethane and hexane were dried with a Pure-Solv 400 solvent purification system by
Innovative Technology Inc., Amesbury, MA, USA. A glove box (Innovative Technology Inc.,
Amesbury, MA, USA) was used to weigh out the super-electron-donor (SED) into the reaction flask.
All the reagents were bought from commercial suppliers and used without further purification unless
stated otherwise. A Büchi rotary evaporator was used to concentrate the reaction mixtures. Thin layer
chromatography (TLC) was performed using aluminum-backed sheets of silica gel and visualized
under a UV lamp (254 nm). The plates were developed using vanillin or KMnO solution. Column
4
chromatography was performed to purify compounds by using silica gel 60 (200–400 mesh).
1
Proton ( H) NMR spectra were recorded at 400 MHz on a Bruker DPX 400 spectrometer or at
1
3
5
00 MHz on a Bruker DRX 500 spectrometer. Carbon NMR ( C) spectra were recorded at 100 MHz
or 125 MHz respectively. The chemical shifts are quoted in parts per million (ppm) by taking
tetramethylsilane as a reference (δ = 0) but calibrated on the residual non-deuterated solvent signal.
Signal multiplicities are abbreviated as: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; bs,
broad singlet; coupling constants are given in Hertz (Hz).
Infra-Red spectra were recorded on a Perkin Elmer Spectrum One FT IR Spectrometer either
pressed as discs in KBr or as films applied on NaCl crystal plates or using Shimadzu FT-IR
Spectrophotometer (Model IRAffinity-1) with a MIRacle Single Reflection Horizontal ATR
Accessory. Melting points were determined on a Gallenkamp Melting point apparatus. High resolution
mass spectra were recorded at the EPSRC National Mass Spectrometry Service Centre, Swansea. The
spectra were recorded using electron ionization (EI), chemical ionization (CI), fast atom bombardment
(
FAB) or electrospray ionization (ESI) techniques as stated for each compound.

Molecules 2015, 20
1763
3
.2. Preparation of Piperazinediones
3
.2.1. Synthesis of Compound 16
Chloroacetyl chloride (5.60 g, 50 mmol) was added dropwise to a flask containing a solution of
n-propylamine (5.9 g, 100 mmol) in DCM (50 mL) cooled in an ice-water bath. The resulting reaction
mixture was stirred in the cooling ice bath for 1 h, diluted with ether (100 mL), and filtered. The
filtrate was then concentrated. The residue was again dissolved in ether (100 mL) and the solid was
filtered. Concentration of the filtrate provided 2-chloro-N-propylacetamide (6.73 g, 100%) as a pure
pale yellow oil. The product was used without further purification [19].
To a flask containing a suspension of NaH (1.80 g, 45 mmol) in dry THF (10 mL) was added
dropwise a solution of 2-chloro-N-propylacetamide (6.076 g, 45 mmol) in dry THF (30 mL) at 0 °C,
under argon gas flow. After the completion of the addition, the resulting reaction mixture was stirred at
room temperature for 3 h. Then the mixture was diluted with ether (70 mL) and filtered. The filtrate
was concentrated and purified by column chromatography (hexane/EtOAc = 50/50 → 100% EtOAc).
1
4
,4-Di-n-propylpiperazine-2,5-dione 16 [19] (723 mg, 73%) was obtained as a white solid. mp,
−1
0 °C–42 °C; νmax (neat)/cm 2965, 2934, 2874, 1653, 1482, 1336, 1310, 1279, 1206, 1057; [Found:
+
1
(
FTMS+) (M+H) 199.1439, C10
.93 (6H, t, J = 7.2 Hz, NCH
NCH CH CH ), 3.96 (4H, s, COCH
CH ), 50.1 (CH ), 163.6 (C).
H
19
N
2
O
2
(M+H) requires 199.1441]; H-NMR (400 MHz, CDCl
), 1.55–1.63 (4H, m, NCH CH CH ), 3.35–3.39 (4H, m,
): δ 11.2 (CH ), 20.1 (CH ), 47.7
3
): δ
0
2
CH
2
CH
3
2
2
3
1
3
2
2
3
2
N); C-NMR (100 MHz, CDCl
3
3
2
(
2
2
3
.2.2. Synthesis of Compound 29
To a suspension of 2-amino-2-methylpropanoic acid (5.25 g, 50.97 mmol) in MeOH (60 mL),
cooled in an ice-water bath, was added thionyl chloride (3.9 mL, 53.7 mmol) dropwise over about
0 min. The resulting solution was heated to 55–60 °C for 4 h, then cooled to room temperature, and
2

Molecules 2015, 20
1764
concentrated. More MeOH (50 mL) was added, and concentrated under vacuum. The white solid
obtained was used in the next reaction without purification.
Crude methyl 2-amino-2-methylpropanoate hydrogen chloride salt was dissolved in water. NaHCO
12.9 g, 153 mmol) was added, followed by chloroform (30 mL). The 2-chloroacetyl chloride (4.4 mL,
5 mmol) in chloroform (5 mL) was added dropwise. The mixture was stirred at room temperature
overnight. The organic layer was separated. The aqueous layer was extracted with chloroform (30 mL).
The combined organic layer was dried over Na SO , filtered and concentrated. Column purification
EtOAc) of the crude product provided methyl 2-(2-chloroacetamido)-2-methyl propanoate, (5.47 g,
3
(
5
2
4
(
5
6% over two steps) as a white solid that was used in the next step [19].
A solution of 2-(2-chloroacetamido)-2-methyl propanoate (850 mg, 4.41 mmol) and n-BuNH in
2
ethanol (15 mL) was heated at 55 °C for 3 h, and the mixture was cooled to room temperature. The
volatiles were removed on a rotary evaporator. The residue was dissolved in EtOAc and washed with
aqueous potassium carbonate solution (5 mL, containing K
2
CO (1.0 g). The organic layer was
3
separated and concentrated. The residue was dissolved in MeOH (5 mL) and THF (5 mL), sealed in a
pressure tube and heated to 150 °C overnight behind a shield. The mixture was cooled to room
temperature. The solvent was removed under vacuum, and the residue was purified by column
chromatography (EtOAc). 1-Butyl-3,3-dimethylpiperazine-2,5-dione [19] was obtained as a white
−1
solid, (645 mg, 74% over two steps). mp 78–80 °C; νmax (neat)/cm 3073, 2963, 2930, 2872, 1682,
+
1
645, 1450, 1427, 1298, 1196, 825, 785; [Found: (FTMS) (M+H) 199.1438, C10
H
19
N
2
O (M+H)
2
1
requires 199.1441]; H-NMR (400 MHz, CDCl
3
): δ 0.94 (3H, t, J = 7.3 Hz), 1.29–1.38 (2H, m), 1.49
(
(
6H, s), 1.50–1.58 (2H, m), 3.4 (2H, t, J = 7.4 Hz), 3.96 (2H, s), 7.55 (1H, broad); 13C-NMR
100 MHz, CDCl ): δ 13.2, 19.4, 27.3, 28.2, 45.8, 49.4, 55.5, 165.7, 168.6.
3
To a solution of 1-butyl-3,3-dimethylpiperazine-2,5-dione (220 mg, 1.11 mmol) in THF (8 mL)
cooled in an ice-water bath under argon was added n-BuLi (0.5 mL, 1.25 mmol) dropwise. The
mixture was stirred at room temperature for 10 min, then it was cooled in ice-water bath again.
Iodomethane (0.2 mL) was added and the mixture was stirred at room temperature overnight. The
reaction was quenched by water (30 mL). The mixture was extracted with EtOAc (2 × 30 mL). The

Molecules 2015, 20
1765
organic layer was dried over Na
2
SO
4
, filtered and concentrated. Purification by column
chromatography (EtOAc) gave 1-butyl-3,3,4-trimethylpiperazine-2,5-dione 29 [19] as a yellow oil
−
1
(
118 mg, 50%). νmax (neat)/cm 2959, 2932, 2875, 1651, 1456, 1429, 1400, 1379, 1308, 1211, 1153,
+
1
9
89, 752; [Found: (FTMS) (M+H) 213.1594, C11
H
21
N
2
O (M+H) requires 213.1598]; H-NMR
2
(
400 MHz, CDCl
3
): δ 0.85 (3H, t, J = 7.3 Hz), 1.25–1.29 (2H, m), 1.39–1.50 (2H, m), 1.43 (6H, s), 2.89
13
(3H, s), 3.13 (2H, t, J = 7.4 Hz), 3.89 (2H, s); C-NMR (100 MHz, CDCl
3
): δ 13.2, 19.3, 24.2, 27.2,
2
8.0, 45.7, 48.9, 60.1, 163.6, 168.0.
3
.3. Synthesis of (3-(2-Iodophenoxy)prop-1-ene-1,1-diyl)dibenzene (20)
To a flask equipped with condenser, magnesium turnings (0.583 g, 24 mmol), iodine (50 mg), and
dry THF (20 mL) were added and the flask was kept under argon gas flow. Vinyl bromide (1 M in
THF, 24 mL, 24 mmol) was added drop-wise into the flask while heating the reaction mixture
at 40 °C. Later, the resulting reaction mixture was stirred for 1 h at 50 °C before cooling it to room
temperature. This solution was then added dropwise using a cannula into another flask containing
benzophenone (3.644 g, 20 mmol) in THF (20 mL) at −78 °C. The resulting reaction mixture was then
warmed to room temperature and stirred for 16 h. Reaction contents were then quenched with ice and
extracted with diethyl ether (3 × 30 mL). The combined ether layers were washed with water (15 mL),
brine (15 mL), dried over anhydrous Na
2
SO , filtered and concentrated using rotary evaporator.
4
Purification of the crude product by column chromatography (15% EtOAc in hexane) afforded
1,1-diphenylprop-2-en-1-ol [13] (2.691 g, 64%).
A solution of phosphorus tribromide (2.7016 g, 10.0 mmol) was added drop-wise to a flask
containing 1,1-diphenylprop-2-en-1-ol (1.892 g, 9 mmol) and pyridine (0.711 g, 9 mmol) in dry
tetrahydrofuran (20 mL) at 0 °C under argon gas. The resulting solution was warmed to room
temperature and further stirred for 16 h. At this point, the reaction was quenched with water (10 mL)
and extracted with diethyl ether (3 × 10 mL). The combined ether layers were washed with water
(
10 mL), brine (10 mL), dried over anhy. Na
afforded (3-bromoprop-1-ene-1,1-diyl)dibenzene [13] (1.516 g, 62%).
To a flask containing K CO (0.691 g, 5 mmol) in acetone (20 mL) was added with 2-iodophenol
0.660 g, 3 mmol) in acetone (2 mL) and (3-bromoprop-1-ene-1,1-diyl)dibenzene (0.682 g, 2.5 mmol)
2
SO , filtered, concentrated using rotary evaporator and
4
2
3
(
in acetone (2 mL) at room temperature and the resulting reaction mixture was stirred at reflux
conditions for 16 h. At this point, the reaction was quenched with water (10 mL) and extracted with
diethyl ether (3 × 15 mL). The combined ether layers were washed with water (10 mL), brine (10 mL),
dried over anhydrous Na
2
SO , filtered, concentrated using rotary evaporator. The crude product was
4
then purified by column chromatography (2% diethyl ether in hexane) to afford desired
(
3-(2-iodophenoxy)prop-1-ene-1,1-diyl)dibenzene 19 [13] (0.746 g, 72%) as a viscous pale yellow oil.
−1
1
ν
max (neat)/cm 3057, 3023, 1580, 1470, 1441, 1377, 1241, 1020, 731; H-NMR (400 MHz, CDCl ) δ
3

Molecules 2015, 20
1766
4
.67 (2H, d, J = 6.8 Hz, ArOCH
2
), 6.38 (1H, t, J = 6.8 Hz, HC = CPh
2
), 6.66–6.72 (2H, m, ArH),
1
3
7
.20–7.31 (8H, m, ArH), 7.36–7.44 (3H, m, ArH), 7.79 (2H, dd, J = 7.6, 1.6 Hz, ArH); C-NMR
) δ 67.5 (CH ), 87.1 (C), 113.0 (CH), 122.8 (CH), 123.6 (CH), 127.9 (CH), 128.0
CH), 128.3 (CH), 128.5 (CH), 129.4 (CH), 129.9 (CH), 139.0 (C), 139.6 (CH), 141.6 (C), 146.0 (C),
(100 MHz, CDCl
3
2
(
1
57.4 (C). Spectral data of this compound were consistent with literature data [13].
3.4. Synthesis of 1-Iodo-2-((3-methylbut-2-en-1-yl)oxy)benzene (23)
To a flask containing K
2
CO (0.829 g, 6 mmol) in acetone (20 mL) was added with 2-iodophenol
3
(
(
0.968 g, 4.4 mmol) in acetone (2 mL) and 1-bromo-3-methylbut-2-ene (0.596 g, 4 mmol) in acetone
2 mL) at room temperature and the resulting reaction mixture was stirred at reflux conditions for 16 h.
At this point, the reaction was quenched with water (10 mL) and extracted with diethyl ether (3 × 15 mL).
The combined ether layers were washed with water (10 mL), brine (10 mL), dried over anhy. Na SO
2
4
,
filtered, concentrated using rotary evaporator. The crude product was then purified by column
chromatography (2% diethyl ether in hexane) to afford desired 1-iodo-2-((3-methylbut-2-en-1-
−1
yl)oxy)benzene (0.719 g, 62%) as a colourless oil. νmax (neat)/cm 3060, 2913, 2930, 1582, 1470,
1
1
439, 1383, 1275, 1230, 1050, 1018, 746; H-NMR (400 MHz, CDCl
3
) δ 1.76 (3H, s, CH
), 6.71 (1H, td, J = 7.6,
.6 Hz, ArH), 6.83 (1H, d, J = 8.0, 1.2 Hz, ArH), 7.26–7.31 (1H, m, ArH), 7.78 (1H, dd, J = 8.0, 1.6
3
), 1.80 (3H,
s, CH
3
), 4.59 (2H, d, J = 6.8 Hz, ArOCH
2
), 5.50–5.54 (1H, m, HC = C(CH
)
3 2
1
1
3
Hz, ArH); C-NMR (100 MHz, CDCl
3
) δ 18.5 (CH
3
), 25.9 (CH
3
), 66.4 (CH ), 87.1 (C), 112.8 (CH),
2
1
19.6 (CH), 122.5 (CH), 129.4 (CH), 138.0 (C), 139.6 (CH), 157.6 (C). Spectral data of this compound
were consistent with literature data [24].
3.5. General Reaction Procedure
t
Substrate (0.5 mmol) and additive were added to a pressure tube. KO Bu and benzene were added
into the tube in a glove box. The tube was then sealed properly before removing from the glove box
and reaction was done as described in the Tables (time and temperature). Later, the pressure tube was
cooled to room temperature. The reaction was quenched with water (10 mL) and extracted with diethyl
ether (3 × 15 mL). The combined ether layers were then washed with water (10 mL), brine (10 mL)
and dried over anhydrous sodium sulfate. The crude product was obtained after evaporation of solvent
under reduced pressure using a rotary evaporator. The crude product was then adsorbed onto silica and
purified by column chromatography (100% hexane), providing the corresponding coupling products.
3
.5.1. Data for Compound 6a

Molecules 2015, 20
1767
−1
White solid m.p. 70–72 °C (lit.: [25] 70 °C). νmax (neat)/cm 3057, 3023, 1601, 1493, 1446, 1078,
1
1
7
033, 908, 731; H-NMR (400 MHz, CDCl
3
) δ 6.98 (1H, s, ArCH = CPh ), 7.03–7.05 (2H, m, ArH),
2
1
3
.11–7.15 (3H, m, ArH), 7.21–7.23 (2H, m, ArH), 7.29–7.36 (8H, m, ArH); C-NMR (100 MHz,
) δ 126.9 (CH), 127.5 (CH), 127.6 (CH), 127.7 (CH), 128.1 (CH), 128.3 (CH), 128.34 (CH),
28.8 (CH), 129.7 (CH), 130.5 (CH), 137.5 (C), 140.5 (C), 142.7 (C), 143.6 (C). Spectral data of this
compound were consistent with literature data [26].
CDCl
3
1
3
.5.2. Data for Compound 15a
−1
White solid m.p. 50–52 °C (lit.: [20] 50–52 °C). νmax (neat)/cm 3062, 3027, 2935, 1601, 1495,
1
1
448, 1070, 1031, 694; H-NMR (400 MHz, CDCl
3
) δ 3.38 (2H, d, J = 7.6 Hz, ArCH CH), 4.24 (1H, t,
2
1
3
J = 7.6 Hz, ArCH
CDCl ) δ 42.2 (CH
C), 144.6 (2 × C). Spectral data of this compound were consistent with literature data [27].
2
CH), 7.00–7.02 (2H, m, ArH), 7.11–7.28 (3H, m, ArH); C-NMR (100 MHz,
3
2
), 53.2 (CH), 126.0 (CH), 126.3 (CH), 128.2 (CH), 128.5 (CH), 129.2 (CH), 140.4
(
3
.5.3. Data for Compound 6b
−1
White solid m.p. 70–72 °C (lit.: [26] 69–70 °C). νmax (neat)/cm 3079, 3055, 3023, 1599, 1495,
1
1
446, 1031, 908, 698; H-NMR (400 MHz, CDCl
3
) δ 2.28 (3H, s, CH
3
), 6.91–6.97 (5H, m,
) δ 21.3
), 127.4 (CH), 127.5 (CH), 127.6 (CH), 128.2 (CH), 128.3 (CH), 128.8 (CH), 128.9 (CH), 129.6
CH), 130.5 (CH), 134.7 (C), 136.7 (C), 140.7 (C), 141.8 (C), 143.7 (C). Spectral data of this
1
3
ArH + =CH), 7.21–7.24 (2H, m, ArH), 7.27–7.35 (8H, m, ArH); C-NMR (100 MHz, CDCl
3
(CH
3
(
compound were consistent with literature data [26].
3
.5.4. Data for Compound 15b
−1
White solid m.p. 78–80 °C (lit.: [28] 80 °C). νmax (neat)/cm 3084, 3025, 2917, 1601, 1493, 1452,
1
1
035, 1022, 700; H-NMR (400 MHz, CDCl
3
) δ 2.28 (3H, s, CH
3
), 3.34 (2H, d, J = 7.6 Hz,
ArCH
2
CH), 4.23 (1H, t, J = 7.6 Hz, ArCH
2
CH), 6.91 (2H, d, J = 7.2 Hz, ArH), 6.99 (2H, d, J = 8.0 Hz,
1
3
ArH), 7.15–7.19 (2H, m, ArH), 7.22–7.28 (8H, m, ArH); C-NMR (100 MHz, CDCl
3
) δ 21.1 (CH ),
3

Molecules 2015, 20
1768
4
1.8 (CH
2
), 53.3 (CH), 126.3 (CH), 128.2 (CH), 128.5 (CH), 128.9 (CH), 129.0 (CH), 135.4 (C), 137.3
(
C), 144.6 (2 × C). Spectral data of this compound were consistent with literature data [28].
3
.5.5. Data for Compound 6e
−1
Colourless viscous oil. νmax (neat)/cm 3057, 3023, 1493, 1444, 1053, 1037, 908, 731; [Found:
+
+
1
(
CI corona) (M+H) 291.0937 C20
H
16Cl (M+H) requires 291.0935]; H-NMR (400 MHz, CDCl )
3
δ 6.82–6.84 (1H, m, ArH), 6.87–6.91 (1H, m, ArH), 7.04–7.08 (1H, m, ArH), 7.10 (1H, s,
1
3
ArCH=CPh
2
), 7.14–7.16 (2H, m, ArH), 7.26–7.28 (3H, m, ArH), 7.32–7.38 (6H, m, ArH); C-NMR
100 MHz, CDCl ) δ 125.2 (CH), 126.1 (CH), 127.6 (CH), 128.0 (CH), 128.2 (CH), 128.4 (CH), 128.5
CH), 129.4 (CH), 130.8 (CH), 131.3 (CH), 134.7 (C), 136.4 (C), 139.9 (C), 143.1 (C), 144.8 (C); m/z
(
(
(
3
+
+
CI corona) 291 [(M+H) , 34%], 197 (22), 181 (100), 111 (14). Spectral data of this compound were
consistent with literature data [13].
3
.5.6. Data for Compound 15e
White solid m.p. 54–56 °C. νmax (neat)/cm−1 3062, 3027, 1603, 1496, 1450, 1053, 1040, 754;
+
)+ 310.1351. C20
1
[
Found: (CI corona) (M+NH
CDCl ) δ 3.49 (2H, d, J = 7.6 Hz, ArCH
.6 Hz, ArH), 6.97 (1H, td, J = 7.6, 1.6 Hz, ArH), 7.08 (1H, td, J = 7.6, 1.6 Hz, ArH), 7.16–7.29 (10H, m,
4
H
21NCl (M+NH
4
) requires 310.1357]; H-NMR (400 MHz,
3
2
), 4.40 (1H, t, J = 7.6 Hz, ArCH
2
CH), 6.81 (1H, dd, J = 7.6,
1
1
3
ArH), 7.33 (1H, dd, J = 8.0, 1.2 Hz, ArH) C-NMR (100 MHz, CDCl
3
) δ 39.9 (CH), 50.8 (CH ),
2
1
1
26.4 (CH), 126.42 (CH), 127.6 (CH), 128.3 (CH), 128.5 (CH), 129.5 (CH), 131.5 (CH), 134.4 (C),
+
)+, 9%], 215 (18), 167 (100), 149 (20).
37.8 (C), 144.2 (2 × C); m/z (CI corona) 310 [(M+NH
4
3
.5.7. Data for Compound 6f
White solid m.p. 110–112 °C (lit.: [29] 113–114 °C). νmax (neat)/cm−1 3053, 3023, 1601, 1493,
1
1
444, 1078, 735; H-NMR (500 MHz, CDCl
3
) δ 7.03 (1H, s, ArCH=CPh
2
), 7.12 (2H, d, J = 8.5 Hz,
) δ 126.7
CH), 127.0 (CH), 127.4 (CH), 127.6 (CH), 127.7 (CH), 127.74 (CH), 127.8 (CH), 128.4 (CH), 128.86
1
3
ArH), 7.26–7.43 (15H, m, ArH), 7.57 (2H, d, J = 8.0 Hz, ArH); C-NMR (100 MHz, CDCl
3
(

Molecules 2015, 20
1769
(
CH), 128.88 (CH), 130.1 (CH), 130.5 (CH), 136.6 (C), 139.5 (C), 140.6 (C), 140.7 (C), 142.8 (C),
1
43.6 (C). Spectral data of this compound were consistent with literature data [30].
3
.5.8. Data for Compound 15f
−1
White solid m.p. 128–130 °C. νmax (neat)/cm 3084, 3062, 3029, 1601, 1491, 1452, 1081, 1011,
+
)+ 352.2056. C26
1
7
65; [Found: (CI corona) (M+NH
) δ 3.42 (2H, d, J = 7.6 Hz, ArCH
J = 8.0 Hz, ArH), 7.16–7.20 (2H, m, ArH), 7.24–7.34 (9H, m, ArH), 7.39–7.43 (4H, m, ArH),
4
H
26N (M+NH
4
) requires 352.2060]; H-NMR
(
400 MHz, CDCl
3
2
CH), 4.29 (1H, t, J = 7.6 Hz, ArCH
2
CH), 7.09 (2H, d,
1
3
7
.55–7.57 (2H, m, ArH); C-NMR (100 MHz, CDCl
3
) δ 41.9 (CH ), 53.1 (CH), 126.4 (CH), 126.9
2
(
CH), 127.0 (CH), 127.1 (CH), 128.2 (CH), 128.5 (CH), 128.8 (CH), 129.6 (CH), 138.8 (C), 139.5 (C),
+
+
+
1
41.1 (C), 144.6 (2 × C); m/z (CI corona) 352 [(M+NH ) , 22%], 333 [(M−H) , 38%], 249 (11), 195
4
(
14), 171 (100), 149 (10).
3
.5.9. Data for Compound 17
−1
Colourless oil. νmax (neat)/cm 3057, 2976, 2932, 1632, 1597, 1508, 1467, 1366, 1251, 1154, 1122,
1
9
7
68, 867, 752; H-NMR (400 MHz, CDCl
3
) δ 1.43 (9H, s, CCH ), 7.20 (1H, dd, J = 8.8, 2.4 Hz, ArH),
3
1
3
.37–7.47 (3H, m, ArH), 7.66 (2H, d, J = 8.4 Hz, ArH), 7.81 (1H, d, J = 8.4 Hz, ArH); C-NMR
) δ 29.1 (CH ), 79.1 (C), 119.9 (CH), 124.6 (CH), 125.1 (CH), 126.1 (CH), 127.3
CH), 127.7 (CH), 128.7 (CH), 130.4 (C), 134.2 (C), 153.3 (C). Spectral data of this compound were
(
100 MHz, CDCl
3
3
(
consistent with literature data [31].
3.5.10. Data for Compound 15g
−1
White solid m.p. 90–92 °C. νmax (neat)/cm 3062, 3021, 2963, 1597, 1493, 1450, 1398, 1264, 1033,
+
)+ 326.1895. C24
) δ 3.84 (2H, d, J = 7.6 Hz, ArCH
CH), 6.92 (1H, d, J = 6.4 Hz, ArH), 7.18–7.30 (11H, m, ArH), 7.49–7.54 (2H, m, ArH), 7.69
1
018, 782; [Found: (CI corona) (M+NH
4
H
24N (M+NH
4
) requires 326.1903];
1H-NMR (400 MHz, CDCl
ArCH
1H, d, J = 8.4 Hz, ArH), 7.87–7.89 (1H, m, ArH), 8.06–8.09 (1H, m, ArH); C-NMR (100 MHz,
CH), 4.48 (1H, t, J = 7.6 Hz,
3
2
2
13
(

Molecules 2015, 20
CDCl ) δ 39.4 (CH
1770
3
2
), 51.8 (CH), 123.8 (CH), 125.3 (CH), 125.5 (CH), 126.0 (CH), 126.4 (CH), 126.9
(
(
CH), 127.4 (CH), 128.2 (CH), 128.5 (CH), 129.0 (CH), 132.1 (C), 134.0 (C), 136.0 (C), 144.8
+
+
+
2 × C); m/z (CI corona) 326 [(M+NH
4
) , 22%], 307 [(M−H) , 42%], 229 (100), 167 (50), 153 (25).
3
.5.11. Data for Compound 18b
White solid m.p. 116–118 °C (lit.: [25] 118–119 °C). νmax (neat)/cm−1 3051, 3027, 2921, 1599,
1
1
513, 1450, 966, 908, 731; H-NMR (400 MHz, CDCl
3
) δ 2.38 (3H, s, ArCH ), 7.07 (1H, d, J = 16.4
3
Hz, ArCH=CHPh), 7.12 (1H, d, J = 16.4 Hz, ArCH=CHPh), 7.18 (2H, d, J = 8.0 Hz, ArH), 7.24–7.28 (1H,
m, ArH), 7.37 (2H, t, J = 7.6 Hz, ArH), 7.43 (2H, d, J = 8.4 Hz, ArH), 7.52 (2H, d, J = 7.2 Hz, ArH);
13C-NMR (100 MHz, CDCl
CH), 129.5 (CH), 134.7 (C), 137.67 (C), 137.7 (C). Spectral data of this compound were consistent
with literature data [32].
) δ 21.4 (CH ), 126.5 (CH), 126.6 (CH), 127.5 (CH), 127.9 (CH), 128.8
3
3
(
3
.5.12. Data for Compound 18c
White solid m.p. 134–136 °C (lit.: [26] 136–137 °C). νmax (neat)/cm−1 3066, 3023, 2965, 2839,
1
1
6
603, 1595, 1513, 1448, 1249, 1180, 1031, 815; H-NMR (400 MHz, CDCl
3
) δ 3.84 (3H, s, ArCH ),
3
.91 (2H, d, J = 8.8 Hz, ArH), 6.98 (1H, d, J = 16.4 Hz, ArCH=CHPh), 7.08 (1H, d, J = 16.4 Hz,
ArCH=CHPh), 7.24–7.28 (1H, m, ArH), 7.36 (2H, t, J = 8.0 Hz, ArH), 7.46–7.51 (4H, m, ArH);
13C-NMR (100 MHz, CDCl
) δ 55.4 (CH ), 114.2 (CH), 126.4 (CH), 126.7 (CH), 127.3 (CH), 127.8
CH), 128.3 (CH), 128.8 (CH), 130.2 (C), 137.8 (C), 159.4 (C). Spectral data of this compound were
consistent with literature data [33].
3
3
(
3
.5.13. Data for Compound 20
−1
Pale yellow viscous oil. νmax (neat)/cm 3084, 3060, 3027, 1601, 1496, 1454, 1282, 1186, 1098,
1
8
7
60, 700; H-NMR (400 MHz, CDCl
3
) δ 5.54 (1H, s, CHPh ), 7.03 (1H, d, J = 1.6 Hz, OCH=C),
2
.08–7.15 (2H, m, ArH), 7.23–7.34 (11H, m, ArH), 7.48 (1H, d, J = 8.4 Hz, ArH); 13C-NMR
(100 MHz, CDCl
3
) δ 47.8 (CH), 111.6 (CH), 120.8 (CH), 122.5 (CH), 124.2 (C), 124.4 (CH), 126.9

Molecules 2015, 20
1771
(
CH), 127.7 (C), 128.7 (CH), 128.9 (CH), 142.4 (C), 144.1 (C), 156.0 (C). Spectral data of this
compound were consistent with literature data [13].
3
.5.14. Data for Compound 22
−1
1
Colourless oil. νmax (neat)/cm 3049, 2958, 2872, 1597, 1483, 1459, 1232, 1018, 748; H-NMR
400 MHz, CDCl ) δ 0.89 (3H, d, J = 7.2 Hz, CH ), 0.97 (3H, d, J = 6.8 Hz, CH ), 1.94–2.02 (1H, m,
), 3.31–3.36 (1H, m, ArCH), 4.39 (1H, dd, J = 9.2, 5.2 Hz, ArOCH ), 4.53 (1H, t,
), 6.78 (1H, d, J = 8.0 Hz, ArH), 6.86 (1H, td, J = 7.2, 0.8 Hz, ArH), 7.11–7.15
(
3
3
3
CH(CH
3
)
2
2
J = 9.2 Hz, ArOCH
2
1
3
(1H, m, ArH), 7.19 (1H, d, J = 7.6 Hz, ArH); C-NMR (100 MHz, CDCl
3
) δ 18.6 (CH
3
), 19.9 (CH ),
3
3
1.8 (CH), 48.3 (CH), 74.0 (CH
2
), 109.5 (CH), 120.2 (CH), 125.2 (CH), 128.3 (CH), 129.6 (C), 160.6
(
C). Spectral data of this compound were consistent with literature data [34].
3
.5.15. Data for Compound 6h
−
1
1
Colourless oil. νmax (neat)/cm 3055, 3021, 2921, 1603, 1493, 1446, 1076, 1031, 696; H-NMR
500 MHz, CDCl ) δ 2.20 (3H, s, CH ), 6.81 (1H, d, J = 8.0 Hz, ArH), 6.87 (1H, s, ArCH=), 6.94
1H, t, J = 7.5 Hz, ArH), 6.96 (1H, s, ArH), 7.02 (1H, t, J = 7.5 Hz, ArH), 7.21–7.23 (2H, m, ArH),
(
3
3
(
1
3
7
.28–7.36 (8H, m, ArH); C-NMR (100 MHz, CDCl
3
) δ 21.5 (CH ), 126.7 (CH), 127.5 (CH), 127.6
3
(
CH), 127.67 (CH), 127.7 (CH), 127.9 (CH), 128.3 (CH), 128.4 (CH), 128.7 (CH), 130.5 (CH), 130.6
CH), 137.4 (C), 137.5 (C), 140.6 (C), 142.5 (C), 143.6 (C). Spectral data of this compound were
(
consistent with literature data [13].
3
.5.16. Data for Compound 15h
Colourless oil. νmax (neat)/cm−1 3060, 3027, 2921, 1603, 1495, 1452, 1081, 1033, 698; [Found:
+
)+ 290.1899. C21
1
(
CI corona) (M+NH
CDCl ) δ 2.25 (3H, s, CH
.80 (1H, d, J = 7.5 Hz, ArH), 6.84 (1H, s, ArH), 6.95 (1H, d, J = 7.5 Hz, ArH), 7.06 (1H, t,
4
H
24N (M+NH
4
) requires 290.1903]; H-NMR (500 MHz,
3
3
), 3.34 (2H, d, J = 8.0 Hz, ArCH
2
CH), 4.24 (1H, t, J = 8.0 Hz, ArCH CH),
2
6
1
3
J = 7.5 Hz, ArH), 7.15–7.19 (2H, m, ArH), 7.21–7.28 (8H, m, ArH); C-NMR (100 MHz, CDCl
3
) δ
2
1.5 (CH ), 42.2 (CH ), 53.2 (CH), 126.2 (CH), 126.3 (CH), 126.7 (CH), 128.0 (CH), 128.2 (CH),
3
2

Molecules 2015, 20
1772
+
)+, 100%],
1
28.4 (CH), 130.1 (CH), 137.6 (C), 140.3 (C), 144.7 (2 × C); m/z (CI corona) 290 [(M+NH
4
+
271 [(M−H) , 28%], 195 (33), 167 (70), 111 (12).
4
. Conclusions
Coupling of iodoarenes to diphenylethenes and to styrenes can be triggered by N,N'-dialkyl
diketopiperazines in the presence of KOtBu. The reaction products can be largely determined by the
number of equivalents of KOtBu and of the N,N'-dialkyl diketopiperazine. Increasing the amount of
butoxide drives the products towards stilbene-type products, whereas increasing the number of
equivalents of the N,N'-dialkyl diketopiperazine while decreasing the number of equivalents of KOtBu
diverts the reaction towards dihydrostilbenes.
Supplementary Materials
Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/20/02/1755/s1.
Acknowledgments
We thank EPSRC (grant number EP/K033077/1) and University of Strathclyde for funding. High
resolution mass spectra were obtained at the EPSRC National Mass Spectrometry Centre, Swansea.
Author Contributions
The experimental work was principally carried out by E.D.; the diketopiperazine 29 was prepared
by S.Z. The paper was written by J.A.M. and E.D.
Conflicts of Interest
The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds are not available from the authors.
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2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
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(