1, 4-addition of terminal alkynes to conjugated enones in water using green catalyst bis[(l)prolinato-N,O]Zn-An environmentally benign protocol

Article abstract of DOI:10.1007/s10562-010-0451-8

An easy, low cost, and green procedure is proposed for the 1, 4-addition of terminal alkynes to conjugated enones in water as a sole medium using easily accessible Zn[(l)Proline]₂. This protocol has advantages of high yield, mild reaction condi

Full text of DOI:10.1007/s10562-010-0451-8

Catal Lett (2011) 141:183–190
DOI 10.1007/s10562-010-0451-8
1, 4-Addition of Terminal Alkynes to Conjugated Enones
in Water Using Green Catalyst Bis[(L)prolinato-N,O]Zn—An
Environmentally Benign Protocol
•
Mazaahir Kidwai Arti Jain Saurav Bhardwaj
•
Published online: 29 October 2010
Ó Springer Science+Business Media, LLC 2010
Abstract An easy, low cost, and green procedure is
proposed for the 1, 4-addition of terminal alkynes to con-
jugated enones in water as a sole medium using easily
accessible Zn[(L)Proline]2. This protocol has advantages of
high yield, mild reaction conditions, no environmental
pollution and simple work up procedure.
have emerged that have been catalyzed by transition metals
[15–20]. These methods take advantage of the facile C–H
insertion chemistry of alkynes to generate the acetylide,
which then adds to the enone. However they often suffer
from the drawbacks of long reaction time, harsh reaction
conditions, less atom efficiency of the catalyst, toxicity and
difficulty in product separation, non recyclability and
tedious procedure for the formation of the catalyst, which
limit their use in the synthesis of complex molecules. Less
work has been done where 1, 4-addition of alkynes have
occurred in mild conditions [21]. Moreover only one
method has been explored, which employs zinc catalyst for
the alkynylation of the enones [22]. This is very unfortu-
nate for the researchers as c, d-acetylenic ketones are
valuable synthetic intermediates, since they are easily
converted to a variety of important structural classes such
as 1,4-diketones [23], 1,5-dienes [24], furans [25], pyrroles
[26], synthesis of prostaglandin analogs [27, 28]. In case of
benzalacetophenone as a reactant synthesis of jasmone can
also be achieved [29, 30].
Keywords Bis[(L)prolinato-N,O]Zn Á c, d-Acetylenic
ketones Á 1,4-Addition Á Water as a solvent Á Recyclability Á
TEM Á Powder XRD
1 Introduction
Conjugate addition of carbon nucleophiles to acceptors
constitutes an important strategy for the construction of
C–C bonds in chemical syntheses [1, 2]. Conceptually
direct approach for their synthesis involves a Michael-type
reaction between an acetylenic unit and a conjugated
enone. The most common cuprate chemistry and dilithium
trialkynylcuprate complexes fail to effect the conjugate
addition of an alkynyl group to a conjugated enone [3, 4].
Numerous attempts have been made to bridge this gap in
synthetic methodology [5–14]. In each of these cases,
acetylides must be generated by deprotonation, which
requires stoichiometric quantities of at least one metal.
Recently, several examples of the 1, 4-addition of alkynes
Hence development of a synthetic protocol which is
nature friendly, simple, efficient and cost effective remains
one of the ever challenging objectives. Therefore the first
goal of our program is to find a catalyst that does not
require very sensitive ligands. The second is to find the
catalyst which is cheap, recyclable and easy to handle. And
the third, which is most important goal is to use milder and
greener reaction conditions.
The reactivity of metal complexes in water is limited
because water can compete with the substrate for metal
coordination. Criteria for metal-compatible catalyst have
been developed based on correlation between the catalyst
activity and two parameters, namely the hydrolysis constant
and water exchange constant [31]. Among several metals
that could be considered suitable for catalysis in water, zinc
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-010-0451-8) contains supplementary
material, which is available to authorized users.
M. Kidwai (&) Á A. Jain Á S. Bhardwaj
Green Research Laboratory, Department of Chemistry,
University of Delhi, Delhi 110007, India
e-mail: kidwai.chemistry@gmail.com
123

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M. Kidwai et al.
looks most appealing as it is not redox active because it
could accommodate several coordination geometries and it
could form stable complexes with nitrogen containing
ligands, and also it is found in abundance in the nature. Until
now Zn[(L)Proline]2 has been explored as a powerful cata-
lyst for the few organic reactions, such as aldol reaction
[32, 33], Hantzsch reaction [34], etc.
volume of 3 mL water as a solvent, 2 mol% Zn[(L)Pro-
line]2 and two drops of triethylamine were added in it and
stirred at 50 °C. The reaction was monitored by TLC, after
cooling at room temperature, ethyl ether (2 9 4 mL) was
added to the mixture to extract the product. The combined
organic layers were washed with water and brine, dried
with MgSO4 and evaporated under reduced pressure. The
residue was finally purified by flash chromatography on
silica gel using 15% ethyl acetate, 5% methanol and 80%
petroleum ether as an eluent to give the desired product.
The structures of all the products were unambiguously
As part of our ongoing program to device the greener
methodologies [35–37], we have tried to reveal the catalytic
properties of Zn–proline complex for the synthesis of c,
d-acetylenicketonesupto 85% yield undermildconditionsby
the coupling of enones with terminal alkynes in the presence
of Zn[(L)Proline]2, as a catalyst and Et3N as an additive.
1
established on the basis of their spectral analysis (IR, H
NMR and GC/MS mass spectral data). All the products are
known compounds.
2 Experimental
2.4 Procedure to Recover Zn[(L)proline]2
2.1 General
After completion of reaction the product was extracted
using ethylacetate and dried over anhydrous sodium sul-
phate. Solvent was evaporated under reduced pressure and
water extract was further used for consecutive runs.
Some chemicals were purchased from Sigma–Aldrich and
Lancaster and were used as such. The chalcone was pre-
pared according to the literature procedure [38, 39]. All
reactions and purity of terminal alkynes and enones were
monitored by thin layer chromatography (TLC) using
aluminium plates coated with silica gel (Merck) employing
ethylacetate and hexane (3:7). The isolated products were
further purified by column chromatography using silica gel
(Sigma–Aldrich 24, 217- 9, 70, 35-70, mesh 40 Ao surface
area 675 m2/g). IR spectra were recorded on Perkin–Elmer
FTIR-1710 spectrophotometer using Nujol film and KBr
pellet. 1H NMR spectra were recorded on a Bruker Avance
Spectrospin (300 MHz) using TMS as internal standard
and chemical shifts are in d. HR–MS mass spectra were
recorded on a Waters LCT Micromass. The melting point
of the compounds was measured through a Thomas–Hoo-
ver melting point apparatus and is uncorrected. Powder
XRD was done on Bruker D8 Discover at 1600 W. TEM
images were taken on Technai G2 30 U-TWIN at 300 KV.
2.4.1 Spectroscopic Data of Synthesized 1, 3, 5-Triphenyl-
4-pentyn-1-one (3a)
IR (neat): 1,689 cm-1 1H NMR (300 MHz, d, CDCl3):
7.75–7.95 (2H, m), 7.38–7.55 (ArH, 13H, m), 4.93 (1H,
dd), 3.67, 3.40 (2H, dd), 13C NMR (75 MHz, CDCl3, d
ppm):198.6, 141, 137.71, 132.3, 131, 127, 128.2, 127, 126,
123, 93, 80, 49.8, 33. m/z (HR-MS): 310 (M?, C23H18O)
calculated for C23H18O: C, 89; H, 5.84; Found C, 89.96; H,
5.91.
2.4.2 1, 3-Diphenyl-4-undecyn-1-one (3b)
IR (neat): 1,684 cm-1 1H NMR (300 MHz, d, CDCl3):
7.95–8.05 (10H, m), 7.15–7.70 (8H, m), 4.41 (1H, dd),
3.34(dd, 1H), 3.59 (dd, 1H), 2.24 (m, 2H), 1.12–1.46
((CH2)4, 8H, m), 0.90 (CH3, 3H, t) 13C NMR (75 MHz,
CDCl3, d ppm):198.4, 141.5, 135.2, 131.2, 127.3, 127,
126.4, 126.1, 83, 80, 47.8, 33.1, 28, 22.9, 17.7, 13.0 m/z
(HR-MS): 318.412 (M?, C23H26O) calculated for
C23H26O: C, 86.75; H, 8.23; Found C, 86.88; H, 8.61.
2.2 Synthesis and Characterization of Zn[(L)proline]2
The zinc amino complex was prepared by adding Et3N
(0.6 mL) to the amino acid (4.34 mmol) in MeOH
(10 mL), followed, after 10 min by zinc acetate
(2.17 mmol) after stirring for 45 min a white precipitate
was collected by filtration (25–95% yield). Complex were
2.4.3 4, 6-Diphenyl-hex-5-yn-2-one (3c)
1
characterized by H-NMR, IR, and ESI–MS [32, 33].
IR (neat): 1,726 cm-1 1H NMR (300 MHz, d, CDCl3):
7.35–7.65 (5 H, m), 7.15–7.23 (5H, m), 4.21–4.33 (1H, m),
2.44(dd, 1H), 2.69 (dd, 1H), 0.90 (CH3, 3H, t) 13C NMR
(75 MHz, CDCl3, d ppm):204.4, 141.7, 128.3, 127, 126.4,
126, 123, 123, 121, 49.8, 33.9, 28, 22.9, 18.7 m/z (HR-
MS): 248.112 (M?, C18H16O) calculated for C23H16O: C,
87.06; H, 6.49; Found C, 87.98; H, 6.61.
2.3 General Procedure for the Three-Component
Reactions
An appropriate terminal alkyne (1.1 mmol) and enone
(1.1 mmol) were added in the round bottom flask. A
123

Addition of Terminal Alkynes to Conjugated Enones in Water
185
2.4.4 4-Phenyl-5-dodecyn-2-one (3d)
2.4.9 1-Phenyl-3-phenylethynyl-nonan-1-one (3i)
IR (neat): 1,726 cm-1 1H NMR (300 MHz, d, CDCl3):
7.15–7.35 (5H, m), 4.11–4.23 (1H, m), 2.34 (dd, 1H), 2.59
(dd, 1H), 2.14 (m, 2H), 2.09 (3H, s), 1.2–1.54 (8H, m), 0.90
(CH3, 3H, t) 13C NMR (75 MHz, CDCl3, d ppm): 204.4,
141.7, 128.3, 127, 126.4, 83, 80, 49.8, 33.9, 28, 22.9, 18.7,
14.0 m/z (HR-MS): 256.112 (M?, C18H24O) calculated for
C23H26O: C, 84.32; H, 9.44; Found C, 84.98; H, 9.61.
IR (neat): 1,669 cm-1 1H NMR (300 MHz, d, CDCl3):
7.75–7.95 (2 H, m), 7.38–7.55 (ArH, 3 H, m), 7.25–7.35
(m, 5H), 2.61–2.93 (1H, m), 1.20–1.71 (m, 2H), 1.2–1.54
(8H, m), 0.65–0.95 (3H, m), 13C NMR (75 MHz, CDCl3, d
ppm): 198.6, 137.7, 132.3, 127, 128.2, 127, 126, 126.2,
123, 122 83, 80, 49.8, 27.7, 27.4, 22.9, 21, 18.7, 14.0 m/z
(HR-MS): 318.45 (M?, C23H26O) calculated for C23H26O:
C, 86.75; H, 8.23; Found C, 86.96; H, 8.91.
2.4.5 3-(1-Methylethyl)-1, 5-diphenyl-pent-4-yn-1-one (3e)
2.4.10 3-Hexyl-1-phenyl-4-undecyn-1-one (3j)
IR (neat): 1,686 cm-1 1H NMR (300 MHz, d, CDCl3):
7.75–7.95 (2 H, m), 7.35–7.55 (3H, m), 7.05–7.25(5H, m),
3.05 (1H, m), 2.59 (m, 2H), 1.09 (6 H, d), 1.2–1.54 (1H,
m), 13C NMR (75 MHz, CDCl3, d ppm): 197.6, 132.7,
128.3, 127, 126, 125, 124.3, 123, 121, 120, 83, 80, 28.4, 28,
22.9, 21, m/z (HR-MS): 276.15 (M?, C20H20O) calculated
for C20H20O: C, 86.92; H, 7.29; Found C, 86.98; H, 7.61.
IR (neat): 1,649 cm-1 1H NMR (300 MHz, d, CDCl3):
7.75–7.95 (2 H, m), 7.38–7.55 (ArH, 3 H, m), 2.61–2.93
(3H, m), 1.20–1.71 (m, 2H), 1.2–1.54 (18H, m), 0.65–0.95
(6H, m), 13C NMR (75 MHz, CDCl3, d ppm): 198.6, 137.7,
132.3, 127, 128.2, 83, 80, 49.8, 33.9, 31.2, 31, 28.4, 28,
27.7, 27.4, 22.9, 21, 18.7, 14.0 m/z (HR-MS): 326 (M?,
C23H34O) calculated for C23H34O: C, 84.60; H, 10.50;
Found C, 84.96; H, 9.91.
2.4.6 3-(1-Methylethyl)-1-phenyl-4-undecyn-1-one (3f)
IR (neat): 1,626 cm-1 1H NMR (300 MHz, d, CDCl3):
7.75–7.95 (2 H, m), 7.35–7.55 (3 H, m), 2.11–2.23 (3H, m),
1.80–2.11(m, 2H), 2.59 (m, 1H), 2.14 (m, 2H), 2.09 (3 H,
s), 1.2–1.54 (1H, m), 0.9–1.45 (8H, m), 0.94 (CH3, 3H, t)
13C NMR (75 MHz, CDCl3, d ppm):197.6, 132.7, 128.3,
127, 83, 80, 49.8, 33.9, 31.2, 31, 28.4, 28, 22.9, 21, 18.7,
18.1, 14.0 m/z (HR-MS): 284.113 (M?, C20H28O) calcu-
lated for C23H26O: C, 84.45; H, 9.92; Found C, 84.98; H,
9.61.
2.4.11 3-(2-Furyl)-1,5-diphenyl-pent-4-yn-1-one (3k)
IR (neat): 1,690 cm-1 1H NMR (300 MHz, d, CDCl3):
8.05–8.25 (5H, m), 7.24–7.95 (5H, m), 7.35–7.55 (3 H, m),
7.31 (1H, dd), 6.66(1H, dd), 6.59 (1H,dd), 4.64–4.94 (1H,
m), 13C NMR (75 MHz, CDCl3, d ppm): 197.6, 154, 141,
137, 130, 128.3, 127, 126, 126, 123, 121, 116, 105, 83, 80,
78, 45, 31.2, 28.4, 28, 27, m/z (HR-MS): 304 (M?,
C21H20O2) calculated for C21H20O2: C, 82.86; H, 6.62;
Found C, 81.98; H, 6.61.
2.4.7 1, 3-Di (4-bromophenyl)-5-phenyl-4-pentyn-1-one
(3g)
2.4.12 3-(2-Furyl)-1-phenyl-4-undecyn-1-one (3l)
IR (neat): 1,680 cm-1 1H NMR (300 MHz, d, CDCl3):
7.92–7.95 (13 H, m), 4.58 (1H, m), 5.66–5.89 (2H, m), 3.64
(2H,dd), 13C NMR (75 MHz, CDCl3, d ppm):196.6, 140,
135.7, 131, 130, 130, 129, 128.6, 128.3, 127, 126, 120, 89,
80, 45, 33.2 m/z (HR-MS): 282 (M?, C23H16Br2O) calcu-
lated for C23H16Br2O: C, 59; H, 3.44; Found C, 58.98; H,
3.61.
IR (neat): 1,696 cm-1 1H NMR (300 MHz, d, CDCl3):
7.24–7.95 (5H, m), 7.35–7.55 (3H, m), 7.31 (1H, dd),
6.66(1H, dd), 6.59 (1H,dd), 4.64–4.94 (1H, m), 3.49 (d,
2H), 2.14 (m, 2H), 1.3–1.54 (8H, m), 0.87 (CH3, 3H, t) 13
C
NMR (75 MHz, CDCl3, d ppm): 197.6, 154, 141, 137, 130,
128.3, 127, 116, 105, 83, 80, 78, 45, 31.2, 28.4, 28, 27,
22.9, 21, 18.7, 14.0 m/z (HR-MS): 308 (M?, C21H24O2)
calculated for C21H24O2: C, 81.78; H, 7.84; Found C,
81.98; H, 7.61.
2.4.8 1, 3-Di (4-bromophenyl)-4-undecyn-1-one (3h)
IR (neat): 1,696 cm-1 1H NMR (d, CDCl3): 7.92–7.95 (8
H, m), 4.55 (1H, m), 5.66–5.89 (2H, m), 3.64 (2H,dd), 3.49
(dd, 2H), 2.14 (m, 2H), 1.1–1.64 (8H, m), 0.87 (CH3, 3H, t)
13C NMR (75 MHz, CDCl3, d ppm): 196.6, 140, 135.7,
131, 130, 128.3, 127, 126, 120, 83, 80, 45, 31.2, 31, 28.4,
28, 22.9, 18.7, 14.0 m/z (HR-MS): 282 (M?, C23H24Br2O)
calculated for C23H24Br2O: C, 58; H, 5.08; Found C,58.98;
H, 5.61.
2.4.13 3-(1-Naphthyl)-1,5-diphenyl-4-pentyn-1-one (3m)
IR (neat): 1,686 cm-1 1H NMR (300 MHz, d, CDCl3):
8.22–8.42 (17H, m), 5.42 (1H, dd), 3.67 (2H, dd), 3.49 (dd,
2H), 13C NMR (75 MHz, CDCl3, d ppm): 197.6, 137.7,
137, 134, 133, 130, 130, 128.9, 128.6, 128.3, 127, 126.4,
126, 125, 124, 83, 80, 45, 31.2 m/z (HR-MS): 360
123

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M. Kidwai et al.
(M?,C27H20O) calculated for C27H20O: C, 89.97; H, 5.59;
Found C, 88.98; H, 5.61.
21, 18.7, 14.0 m/z (HR-MS): 180 (M?, C12H20O) calcu-
lated for C12H20O: C, 79.94; H,11.18; Found C, 78.98; H,
11.61.
2.4.14 3-(1-Naphthyl)-1-phenyl-4-undecyn-1-one (3n)
IR (neat): 1,686 cm-1 1H NMR (300 MHz, d, CDCl3):
8.22-8.42 (1H, m), 7.64-7.95 (5 H, m), 7.35-7.55 (6 H, m),
5.12- 5.23(1H, m), 3.67(2H, dd), 3.49 (dd, 2H), 2.14 (m,
2H), 1.05-1.54 (8H, m), 0.84 (CH3, 3H, t) 13C NMR
(75 MHz, CDCl3, d ppm):197.6, 137.7, 137,134, 133, 130,
128.3, 127,126.4, 126, 125, 124, 83, 80, 45, 31.2, 28.4, 28,
27, 22.9, 21, 18.7, 14.0 m/z (HR-MS): 368 (M?,C27H28O)
Calcd for C27H28O: C, 88; H, 7.66; Found C, 88.98; H,
7.61.
3 Results and Discussions
In an initial endeavour, efforts were made towards the
catalytic evaluation of Zn[(L)Proline]2, we have taken the
synthesis of 3a from phenylacetylene and benzalacetoph-
enone as model reaction. A blank reaction was carried out
using equivalent each of phenylacetylene and benzalace-
tophenone in water at 50 °C. Even after 24 h no product
was obtained and then the same reaction was tried with
Zn[(L)Proline]2 as a catalyst and Et3N as an additive
(Scheme 1). Surprisingly, under same reaction conditions,
yield of desirable product reached up to 85%. To evaluate
the role of Et3N in the reaction, we have experimented the
same reaction without Et3N. It was found that only 40% of
desirable product had been obtained. It shows that Et3N is
relevant for the abstraction of hydrogen atom to form
alkynyl species (activation of alkyne).
2.4.15 3-(1, 1-Dimethylethyl)-1,5-diphenyl-pent-4-yn-1-
one (3o)
IR (neat): 1,686 cm-1 1H NMR (300 MHz, d, CDCl3):
7.85–7.95 (2H, m), 7.35–7.55 (3H, m), 7.05–7.23 (m, 5H),
3.11 (2H, dd), 2.94 (1H, dd), 2.89 (m, 1H), 0.9 (9H, s) 13C
NMR (75 MHz, CDCl3, d ppm): 199.6, 137, 132.7, 128.3,
127, 123, 122, 122.2, 121, 120, 83, 80, 39, 39.2, 31, 31, 31,
m/z (HR-MS): 290 (M?, C21H22O) calculated for C21H22O:
C, 86.85; H, 7.64; Found C, 86.98; H, 7.61.
Ph
O
O
NH
O
O
O
NH
O
Ph
Ph
2.4.16 3-(1, 1-Dimethylethyl)-1-phenyl-4-undecyn-1-one
(3p)
+
Ph
Ph
Ph
Et3N, water
Scheme 1 Synthesis of c, d-acetylenic ketones using benzalacetoph-
enone and phenylacetylene at 50 °C with Zn[(L)Proline]2 in water
IR (neat): 1,686 cm-1 1H NMR (300 MHz, d, CDCl3):
7.85–7.95 (2H, m), 7.35–7.55 (3H, m), 3.11 (2H,dd), 2.94
(1H, dd), 2.89 (m, 1H), 2.14 (m, 2H), 1.3–1.54 (8H, m), 0.9
(9H, s), 0.84 (CH3, 3H, t) 13C NMR (75 MHz, CDCl3, d
ppm): 199.6, 137, 132.7, 128.3, 127, 83, 80, 39, 39.2, 33.9,
31.2, 31, 28.4, 28, 22.9, 21, 18.7, 18.1, 14.0 m/z (HR-MS):
298 (M?,C21H30O) calculated for C21H30O: C, 84.51; H,
10.13; Found C, 84.98; H, 9.61.
Table 1 Various catalyst catalyzed model reaction in watera
S. No.
Catalyst
Time
Yieldb (%)
1
2
3
4
5
a
Zn(CH3COO)2
Zn(Lys)2
5
10
6
40
30
50
40
85
Zn(Arg)2
Zn(His)2
10
2
2.4.17 6-Phenyl-hex-5-yn-2-one (3q)
Zn(L-Pro)2
IR (neat): 1,689 cm-1 1H NMR (d, CDCl3): 7.75–7.95 (5
H, m), 2.93 (2H, m), 2.67 (2H, m), 2.09 (3H, s) 13C NMR
(75 MHz, CDCl3, d ppm): 203.6, 127, 128.2, 127, 126,
123, 123, 93, 80, 49.8, 23, 12 m/z (HR-MS): 172 (M?,
C12H12O) calculated for C12H12O: C, 83.69; H, 7.02;
Found C, 83.96; H, 7.01.
Reactions were performed with the phenylacetylene (0.01 mol),
benzalacetophenone (0.01 mol) and various catalyst (2 mol%) in
water by stirring the mixture for 12 h at 50 °C
b
Reaction progress monitored by TLC
R1
O
O
NH
O
O
O
2.4.18 Dodec-5-yn-2-one (3r)
NH
O
H
R1
+
R3
R2
R3
R2
IR (neat): 1,680 cm-1 1H NMR (300 MHz, d, CDCl3):
2.64 (m, 2H), 2.30 (m, 2H), 2.09 (3H, s), 1.98 (2H, t),
1.05–1.54 (8H, m), 0.84 (CH3, 3H, t) 13C NMR (75 MHz,
CDCl3, d ppm): 207.6, 83, 80, 45, 31.2, 28.4, 28, 27, 22.9,
1(a-b)
Et3N, water
2(a-i)
3(a-r)
Scheme 2 Synthesis of c, d-acetylenic ketones using substituted
enones and terminal alkynes at 50 °C with Zn[(L)Proline]2 in water
123

Addition of Terminal Alkynes to Conjugated Enones in Water
187
The success of the reaction depends critically on the
proper selection of ligand associated with the central metal of
the catalyst. So we have screened various ligands around zinc
for carrying out the same model reaction, results are reported
in Table 1. Trial experiments indicates that only Zn[(L)pro-
line]2 is capable to act as an efficient catalyst for the synthesis
Table 2 Synthesis of various c,
S. No.
Enone
R3
Terminal
alkyne
Product
Yieldb
(%)
Time
(h)
d-acetylenic ketones using
Zn[(L)Proline]a2
R2
1
Ph
Ph
Ph
3a
3b
3c
3d
3e
3f
85
85
88
81
80
82
80
80
81
80
80
82
78
78
80
85
85
88
12
12
10
14
14
10
12
12
11
12
12
12
12
12
10
12
12
11
2
Ph
Ph
C6H13
Ph
3
Ph
CH3
CH3
Ph
4
Ph
C6H13
Ph
5
(CH3)2CH
(CH3)2CH
C6H4Br
C6H4Br
C6H13
C6H13
2-furyl
2-furyl
1-naphthyl
1-naphthyl
(CH3)3C
(CH3)3C
H
6
Ph
C6H13
Ph
7
C6H4Br
C6H4Br
Ph
3g
3h
3i
8
C6H13
Ph
9
10
11
12
13
14
15
16
17
18
Ph
C6H13
Ph
3j
Ph
3k
3l
Ph
C6H13
Ph
a
Reactions were performed
Ph
3m
3n
3o
3p
3q
3r
with the terminal alkyne
(0.01 mol), enone (0.01 mol)
and Zn[(L)Proline]2 (2 mol%) in
water by stirring the mixture for
12 h at 50 °C
Ph
C6H13
Ph
Ph
Ph
C6H13
Ph
CH3
CH3
b
Reaction progress monitored
H
C6H13
by TLC
Fig. 1 A tentative mechanism
for the Zn catalysed 1,4-
addition of terminal alkynes
Ph
Et3N
Et3N+H
H
O
Ph
Ph
O
O
NH
O
C
Ph
Et3N
Et3N+H
Ph
NH
O
Ph
Ph
Ph
O
O
NH
Ph
O
NH
O
O
O
O
NH
O
O
NH
O
Ph
Ph
O
O
NH
O
NH
O
O
C
Ph
Ph
Ph
A
123

188
M. Kidwai et al.
c, d-acetylenic ketones. Zinc acetatae is not able to catalyze
the reaction efficiently, as four membered ring formed by
acetate group on chelation with zinc is not as stable as five
membered ring formed by proline group. Moreover only in
Zn[(L)proline]2, amino acid contains secondary amine which
ultimately enhances the catalytic efficiency of Zn[(L)Pro-
line]2. Other catalysts do not contain any secondary amine.
To define the full scope of the new reaction conditions,
synthesis of small library of 1, 4-alkynylation products was
carried out (Scheme 2, Table 2). With good results in hand,
the substrate tolerance of the reaction with respect to
functionality on the alkyne and the enone was explored
(Table 2). Both aromatic and alkyl substituted alkynes
showed good reactivity in the 1, 4-addition reaction.
The use of zinc reagent to effect the 1,4- addition of an
alkynyl group to an a, b- unsaturated ketone can be
explained by the tendency, with which zinc binds alkyne
ligand [40]. It suggests that highly water soluble catalyst
could coordinate with the alkyne easily and could be
transformed it into product via intermediate. A tentative
mechanism for the zinc catalyzed 1, 4-addition of terminal
alkyne to conjugated enone has been illustrated in Fig. 1. A
plausible pathway involves the intramolecular delivery of
an alkynyl group through a six membered transition state,
which has been depicted in the idealized form by ‘‘A’’.
This on further rearrangement gives desirable product.
Mechanism illustrates that there is no scope for the for-
mation of side product. Furthermore it is also shown that
Triethylamine is added in fractional amount to deprotonate
the terminal alkyne and could be recovered back in the
aqueous layer, when product was extracted.
3.1 Characterization of the Catalyst Powder X-Ray
Diffraction
Fig. 2 a Powder XRD of fresh Zn[(L)Proline]2. b Powder XRD of
Zn[(L)Proline]2 after third run
X-ray patterns of the Zn[(L)proline]2 complex recorded at
2h = 0–100 range were shown in Fig. 2. Complex has
specific d values, which can be used for its characterization
and peaks obtained from powder XRD are matched with
data card [41] 47-1919JCDPS. These interpreted peaks
revealed that the crystal is orthorhombic in shape. The
powder XRD patterns exhibited identical peaks for both
fresh and recovered Zn[(L)proline]2 complex. It shows that
there is no change in geometry as well as stability of the
catalyst after recovering it from aqueous reaction media.
Moreover our catalyst is water soluble hence it would be
difficult to make highly resolved single crystal.
Table 3 Catalyst recycling studiesa
Catalyst recycle
Time (h)
Yieldb (%)
1
2
3
4
5
a
12
12
12
14
14
85
80
77
75
70
Reactions were performed with the terminal alkyne (0.01 mol),
enone (0.01 mol) and Zn [(L)Proline]2 (2 mol%) in water by stirring
the mixture for 2 h
To check the crystalline nature of the catalyst, TEM
images of the catalyst are taken on carbon coated grid. By
these images it is found that compound is crystalline in
nature. Furthermore both recycled and fresh catalyst has
same TEM images. TEM images have been given in Fig. 3.
To the best of our knowledge, until now, no information
b
Reaction progress monitored by TLC
regarding the shape and crystalline nature of the catalyst
has been reported using XRD and TEM characterization.
Catalyst recycling ability was also checked under the same
123

Addition of Terminal Alkynes to Conjugated Enones in Water
189
Fig. 3 a TEM images of fresh
Zn[(L)Proline]2. b TEM images
of Zn[(L)Proline]2 after third run
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123