Synthesis, characterization of active Sn(0), and its application in selective propargylation of aldehyde at room temperature in water

Article abstract of DOI:10.1139/cjc-2017-0745

Active Sn(0) particles are synthesized in high yields by the chemical reduction of the blue-black stannous oxide using freshly prepared sodium stannite solution as reducing agent at 40 °C and 60 °C. The Sn(0) particles are characterized using powder XRD, SEM, and DSC. The as-synthesized Sn(0) particles are applied as reagent for the regioselective synthesis of homopropargyl alcohols from propargyl bromide and aldehydes in distilled water at room temperature (in 50%-84% yields). No assistance of heat, microwave, ultrasound, organic co-solvent, co-reagent, or inert atmosphere is required for this reaction. The propargylation reaction is highly chemoselective towards aldehyde over other less electrophilic carbonyl functional groups such as ketone, amide, and carboxylic acid. Our in-house synthesized homopropargyl alcohols can be used to synthesize conjugated 1,3-diynes.

Full text of DOI:10.1139/cjc-2017-0745

Page 1 of 32
Synthesis, characterization of active Sn(0) and its application in selective
propargylation of aldehyde at room temperature in water
Paresh Nath Chatterjee,*,a Dipankar Paul,a Micky Lanster Sawkmie,a Arun Kumar Sinha,b and
Snehadrinarayan Khatuac
a
Department of Chemistry, National Institute of Technology Meghalaya, Bijni Complex,
Laitumkhrah, Shillong 793003, Meghalaya, India.
b
Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, West Bengal,
India.
c Centre for Advance Studies, Department of Chemistry, North Eastern Hill University, Shillong
793022, India.
*Corresponding author:
Email: paresh.chatterjee@nitm.ac.in / chemparesh83@gmail.com
Tel.: +91-364-2501294; Fax: +91-364-2501113
Dipankar Paul: imdpaul91@gmail.com
Micky Lanster Sawkmie: mick_sawkmie@yahoo.co.in
Arun Kumar Sinha: hiaksinha@gmail.com
Snehadrinarayan Khatua: snehadri@gmail.com
1

Page 2 of 32
Abstract
Active Sn(0) particles are synthesized in high yields by the chemical reduction of the
blue-black stannous oxide using freshly prepared sodium stannite solution as reducing agent at
40 °C and 60 °C. The Sn(0) particles are characterized using powder XRD, SEM and DSC. The
as-synthesized Sn(0) particles are applied as reagent for the regioselective synthesis of
homopropargyl alcohols from propargyl bromide and aldehydes in distilled water at room
temperature (in 50-84% yields). No assistance of heat, microwave, ultrasound, organic co-
solvent, co-reagent or inert atmosphere is required for this reaction. The propargylation reaction
is highly chemoselective towards aldehyde over other less electrophilic carbonyl functional
groups such as ketone, amide and carboxylic acid. Our in-house synthesized homopropargyl
alcohols can be used to synthesize conjugated 1,3-diynes.
Keywords: Active Sn(0), selective propargylation, aldehyde, homopropargyl alcohol, 1,3-diyne.
2

Page 3 of 32
Introduction
Tin containing materials are known for their wide applications in the domains of gas
sensing,1 superconductors,2 solar cells,3 lithium-ion storage batteries,4 soldering agents,5
photocatalysis6 and Barbier-type allylation of carbonyl functionalities.7 Some research groups
synthesized Sn(0) species by using strong reducing agents,8 γ-ray irradiation,7l soft template
polyemrs9 and hard template carbon nanotubes.10 In a recent report, Sn(0) materials are
synthesized by the reduction of SnO by sodium stannite (Na2SnO2) solution at room temperature
or under hydrothermal conditions albeit in very poor yields.11 As tin has tremendous potential for
mediating several organic transformations, we decided to develop a synthetic process of active
Sn(0) in higher yields and shorter reaction time. Herein, we report the synthesis of active Sn(0)
from the blue-black SnO using freshly prepared Na2SnO2 solution as the reducing agent at 40 °C
and 60 °C in excellent yields within few hours. The synthesized Sn(0) particles in two different
temperatures are characterized by various analytical techniques for measuring the particle sizes
and checking the phase purity. These in-house synthesized Sn(0) particles are much more
efficient than commercial tin powder for mediating the coupling between propargyl bromide and
aldehydes to produce homopropargyl alcohols, regioselectively, in distilled water at room
temperature. No assistance of heat, microwave, ultrasound, organic co-solvent, co-reagent or
inert atmosphere is required for this reaction. The use of water as a solvent has considerable
advantages because it is not only environmentally benign but also readily available and non-toxic
solvent.12
The propargylation of carbonyl compounds, to produce homopropargyl alcohols, is a very
important C–C bond forming reaction in organic synthesis.13 The homopropargyl alcohols can
host versatile modifications in both the hydroxyl and alkyne functional groups for the synthesis
3

Page 4 of 32
of valuable organic moieties.14 Various research groups reported the synthesis of homopropargyl
alcohols using ex situ and in situ generated allenyl and propargyl metal reagents.15 But the
ambident nucleophilic character of the allenyl and propargyl organometallic reagents, via
metallotropic rearrangement, often produces a mixture of the allenyl and homopropargyl
alcohols. Development of a practical method for the selective synthesis of homopropargyl
alcohols using readily available starting materials is of great value to the synthetic organic
chemists. The coupling between propargyl halides and carbonyl compounds directly mediated by
metals like indium,16 zinc,7e,17 tin,18 gallium,19 and dysprosium20 have been reported. Tin(II) salts
are also known to promote the reaction between propargyl halides and carbonyl compounds to
21
give homopropargyl alcohols.15a,
Tokuda et al. reported regioselective propargylation of
carbonyls by electrochemical reaction using Zn or Al anodes and Pt cathodes.22 But in the earlier
reports on metallic tin mediated coupling reactions between propargyl bromide and carbonyl
compounds, the uses of different additives, volatile and toxic organic solvents, microwave
irradiation etc., in addition to the metallic tin based reagent, make them less user friendly
(Scheme 1).18 It is needless to mention that from a practical viewpoint, the metal promoted
selective propargylation of aldehydes or ketones is always a desirable methodology for the
synthesis of homopropargyl alcohols. A safe and simple experimental methodology for the
selective propargylation of aldehydes using cheap and efficient reagents incorporating a green
solvent under mild reaction conditions is always advantageous. Taking this in account, we
developed a new method for the coupling between propargyl bromide and aldehydes, mediated
by our in-house prepared highly active Sn(0) particles, in distilled water at room temperature to
give the homopropargyl alcohols in moderate to high yields. The reaction does not require the
assistance of any additive, organic solvent, heat, ultrasound, microwave or inert atmosphere. The
4

Page 5 of 32
organic solvent free, green methodology qualifies as a cost effective and environment friendly
process. The present work illustrates a straightforward technique for the synthesis of active Sn(0)
particles, in excellent yields, which acts as an efficient reagent for the selective propargylation of
aldehydes at room temperature in water.
<SCHEME 1>
Results and discussion
Our investigation started with the synthesis of active Sn(0) particles, at two different
temperatures, namely 40 °C and 60 °C [these two Sn(0) samples are here after represented as
Sn40°C and Sn60°C, respectively]. The synthesis of Sn40°C and Sn60°C samples proceeded by a wet
chemical reaction between the blue-black SnO (10 mmol) and freshly prepared Na2SnO2 solution
(45 mL) with an isolated yield of 95% and 92% in 16 h and 10 h, respectively (Scheme 2). We
were happy to reproduce this unique route to synthesize active Sn(0) particles in 5 g scale of SnO
at 40 °C with an isolated yield of 94% (here after represented as Sn40°C*).
<SCHEME 2>
The synthesized Sn(0) particles were characterized using powder XRD, SEM and DSC.
The X-ray diffraction patterns of the Sn40°C and Sn60°C particles are in good agreement with the
diffraction pattern of crystalline tin with JCPDS Card No. 04-673 (Figure 1a and 1b).11, 23 The
diffraction peaks of Sn(0) materials appear at about (2θ) 31°, 32°, 44°, 45°, 55°, 62°, 64°, 65°,
72°, 73° and 80° which are indexed to the (200), (101), (220), (211), (301), (112), (400), (321),
(420), (411) and (312) crystal facets. The resultant Sn40°C and Sn60°C particles are phase pure.
The crystal structure of the as-synthesized Sn(0) particles are indexed to be body centered
tetragonal phase. The size of the Sn40°C and Sn60°C particles were studied by SEM analysis.
Figure 2a and 2b represent the SEM images of Sn40°C and Sn60°C particles, respectively, clearly
5

Page 6 of 32
reflecting that the size of the synthesized Sn(0) particles increase with the increase in reaction
temperature from 40 °C to 60 °C. The thermal profiles of the micron sized Sn40°C and Sn60°C
particles, obtained from DSC analysis, show size-dependent slight melting temperature
depression (Figure 3).24 We found that the melting point of Sn40°C particles is 233.7 °C (Figure
3a) which is 0.5 °C less than that of Sn60°C particles (Figure 3b).
<FIGURE 1>
<FIGURE 2>
<FIGURE 3>
The synthesized Sn(0) particles are applied in the proposed propargylation of carbonyl
compounds. In this mission, we took 4-chlorobenzaldehyde 1a as a representative electrophile
and propargyl bromide 2a as the propargylating agent in the presence of various tin reagents at
room temperature for model studies. Initial solvent screening included both aqueous and non-
aqueous solvents, e.g. ethanol and THF, in air, using Sn40°C particles as the metal reagent (Table
1). We observed that the propargylation of aldehyde 1a was promoted by the controlled addition
of water in the organic solvents to give the desired homopropargyl alcohol 3a (Table 1; entries 1-
6). We were pleased to find that the highest yield of homopropargyl alcohol 3a was obtained
when only water was used as solvent at room temperature (Table 1; entry 7). The Sn60°C particles
gave slightly lower yield of the desired homopropargyl alcohol 3a, with respect to Sn40°C
particles, in the same reaction conditions (Table 1; entries 8). The small change in reactivity of
Sn60°C particles might be due to the larger particle size than the Sn40°C particles. We were
delighted to find that our in-house synthesized active Sn40°C particles are equally efficient as the
active Sn(0) particles synthesized by Pal et al. at room temperature for 5 days (represented as
6

Page 7 of 32
SnRT) to promote the propargylation reaction (Table 1; entry 9).11 The Sn(0) particles synthesized
in 5 g scale, i.e. Sn40°C*, is also equally reactive to mediate the propargylation of aldehyde 1a
(Table 1; entry 10). Although the Sn40°C particles mediated propargylation reaction of aldehyde
progresses faster at higher temperature, there is no noticeable change in the yield of the
homopropargyl alcohol 3a (Table 1; entry 11). Our in-house synthesized Sn40°C particles showed
much superior reactivity over commercially available tin powder and granulated tin (Table 1;
entries 12 and 13). No propargylation of aldehyde 1a was observed without Sn(0) reagent (Table
1; entry 14). However, propargylation of aldehyde 1a using SnCl2.2H2O and SnO furnished
desired homopropargyl alcohol 3a but only in poor yields after longer reaction time (Table 1;
entries 15 and 16). In our reaction conditions, when propargyl alcohol 2b and propargyl chloride
2c were employed instead of propargyl bromide 2a, the expected product 3a did not form at all
(Table 1; entries 17 and 18).
<TABLE 1>
The optimized reaction conditions, namely aldehyde 1 (1.0 mmol), propargyl bromide 2a
(1.2 mmol), active Sn40°C particles (1.2 mmol), water as solvent (5 mL) at room temperature in
air, were then applied in the selective propargylation of aldehydes 1, containing wide range of
functional groups, to synthesize the desired homopropargyl alcohols 3 (Table 2).25 We found that
the electron donating and electron withdrawing substituents, present at variable positions in the
phenyl ring of the aromatic aldehydes, are well tolerated during the reaction, albeit at different
rates, to produce the desired homopropargyl alcohol 3 regioselectively (Table 2; entries 1-5 and
7-9). Most of the aldehydes did not provide significant amount of allenic alcohols in our reaction
conditions. However, during the reaction of 2,4-dichlorobenzaldehyde 1c and 2-
7

Page 8 of 32
nitrobenzaldehyde 1e with propargyl bromide 2a, very small amount of the corresponding allenic
alcohols were detected (Table 2; entries 3 and 5).26 Our methodology worked well for 9-
anthraldehyde 1j and heterocyclic aldehydes, e.g. 2-thiophenecarboxaldehyde 1k and furfural 1l
(Table 2; entries 10-12). Propargylation occurs at both formyl groups of terephthalaldehyde 1m
with moderate yield (Table 2; entry 13). When cinnamaldehyde 1n was used as α,β-unsaturated
aldehyde, only 1,2-addition product 3n was obtained regioselectively (Table 2; entry 14).
Aliphatic aldehydes 1o-1p also generated the corresponding homopropargyl alcohol 3o-3p
regioselectively in good yields (Table 2; entries 15-16). However, propargylation of aliphatic
aldehydes 1q and 1r in the optimized reaction conditions led to the formation of a small amount
of allenic alcohols26 in addition to the desired homopropargyl alcohols 3q and 3r (Table 2;
entries 17-18). As aldehyde 1q contains a stereogenic center, the reaction yielded a mixture of
1
diastereomers of the homopropargyl alcohol 3q in the ratio 1.92:1 (calculated from H NMR).
We have also tested the reusability of the tin reagent after the completion of the reaction by using
the resulting tin residue as potential reagent for mediating proaprgylation of aldehydes. In this
regard we have isolated the tin residue from a batch of propargylation reaction after its
completion by centrifugation (Table 2, entry 18). The isolated tin residue was washed several
times with ethanol and water and subsequently reused as the reagent, instead of fresh Sn40°C
material, for mediating the propargylation reaction of aldehyde 1r (See supporting information
for experimental details). We observed that the reaction proceeds sluggishly to produce lower
yields of the desired homopropargyl alcohol 3r with unreacted aldehyde remaining after 10 h
(Table 2, entries 19-20). Significant decline in the yield of the desired product may render the
Sn40°C material impractical for reuse after third run. Notably, we also applied our methodology
toward the large scale synthesis of homopropargyl alcohol 3f using 10 mmol of benzaldehyde 1f,
8

Page 9 of 32
12 mmol of propargyl bromide 2a and 12 mmol of Sn40°C particles in water at room temperature
with 80% isolated yield.
<TABLE 2>
Under the same reaction conditions, no propargylation took place when ketone, amide
and carboxylic acid were employed as substrates, instead of aldehyde, which makes our
methodology highly chemoselective towards aldehydes over other less electrophilic carbonyl
functional groups. We successfully applied the chemoselective nature of the present
methodology, to discriminate 4-chlorobenzaldehyde 1a from acetophenone 4a, benzamide 4b
and benzoic acid 4c using Sn40°C reagent as mentioned in Scheme 3. In all the cases the desired
homopropargyl alcohol 3a was formed in high yields from aldehyde 1a while the unreacted
acetophenone 4a, benzamide 4b and benzoic acid 4c were recovered from their respective
reaction mixtures (Scheme 3).
<SCHEME 3>
To have an understanding of the mechanistic pathway that the reaction may follow, we
have performed a control experiment in presence of TEMPO as radical scavenger (See
supporting information for details). Although the reaction proceeded sluggishly in presence of
TEMPO but a comparable isolated yield of the corresponding homopropargyl alcohol opposes
the involvement of radical mechanism in our reaction. Literature suggests that the reaction of
propargyl bromide 2a with tin(0) (Sn40°C material in our case) may generate a propargyl
organotin species A via oxidative addition which may further lead to species B by reacting with
another molecule of 2a (Scheme 4). The allenyl organotin species C and D could easily be
generated from propargyl organotin species A and B respectively through metallotropic
9

Page 10 of 32
rearrangement.27,15l Although the hydrolysis of tin(II) and tin(IV) organometallics cannot be
ruled out, the hydrolyzed tin organometallics are established to be more reactive by virtue of
electron donation from the hydroxy pendant to the vacant d-orbital of tin.28 Both the allenyl
organotin species C and D can react with aldehyde in SE2′ pathway to yield the homopropargyl
alcohol 3.27,15l
<SCHEME 4>
As the major product obtained in our reaction conditions is the homopropargyl alcohols, the
most probable intermediate in this case is expected to be the allenyl organotin species
considering the SE2′ mechanism.27,15l Consequently, we attempted to trace the formation of the
1
1
allenyl organotin species using in-situ H NMR studies (Figure 4). The H NMR spectrum of
propargyl bromide 2a (80% solution in toluene) in D2O showed the peaks of methylene protons
at δ = 3.87 (t, J = 2.4 Hz, 2H) and the alkyne proton at δ = 1.96 (br, 1H) in addition to the peak
for the methyl protons of toluene at 2.21 ppm and other unidentifiable impurities Figure 4(A).
The proton signals of the allenyl organotin species formed after stirring propargyl bromide 2a
1
with Sn40°C material in D2O for 30 min are clearly visible in Figure 4(B). In the H NMR, the
signals for the allenyl organotin species appear at δ = 5.21 (t, J = 6.8 Hz, 1H), 4.64 (d, J = 6.8
Hz, 1H), 4.52 (d, J = 7.2 Hz, 1H) which match well with literature report,18a thereby establishing
its formation in the reaction medium (Full spectra is given in the supporting information). No
1
trace of propargyl organotin species (A and B) was found in the in-situ H NMR study.18a The
allenyl organotin species reacts readily with electrophilic aldehydes, resulting in the formation of
homopropargyl alcohol 3 as evident from the results presented in Table 2.
<FIGURE 4>
10

Page 11 of 32
We perceived that there remains a great applicability of the present methodology toward the
synthesis of the conjugated 1,3-diyne derivatives, which are very important skeletons in the fields
of biology and material sciences.29 Herein, we successfully explored the CuI/TMEDA
(N,N,N′,N′-tetramethylethane-1,2-diamine) catalyzed homocoupling reaction of the terminal
alkynes of the synthesized homopropargyl alcohols 3 to produce the symmetrical conjugated 1,3-
diynes 5 in excellent yields (Scheme 5).30
<SCHEME 5>
Conclusion
In summary, we have synthesized active Sn(0) particles from blue-black SnO using
freshly prepared Na2SnO2 solution as the reducing agent, at 40 °C and 60 °C, in excellent yields
and shorter reaction time. We have also applied our method for the preparation of active Sn(0)
particles at 40 °C in a large scale (5 g). The as-synthesized active Sn40°C particles have been
found to act as an efficient reagent for the regio- and chemoselective propargylation of aldehydes
in water at room temperature, without inert atmosphere, producing homopropargyl alcohols in
moderate to high yields. This methodology does not require any assistance of heat, microwave,
ultrasound, organic co-solvent or co-reagent. Hence, the present method is more convenient and
more useful than the previously reported methods as it is a cost effective, time economical,
energy efficient and greener method for the synthesis of homopropargyl alcohols from easily
available starting materials. Providing practical simplicity, yet not compromising on the
selectivity, the methodology presented in this paper could be a meaningful addition to the
existing methods of propargylic functionalization of aldehydes.
Supplementary data
11

Page 12 of 32
Supplementary information including experimental procedures, characterization data, and
NMR spectra and spectral data are available with the article through the journal Web site at
http://
Acknowledgements
Scientific and Engineering Research Board (SERB) is gratefully acknowledged for financial
support to P.N.C (sanction order no. SB/FT/CS-115/2014; dated 24/08/2015). We thank NIT
Meghalaya (for financial support to D.P.). P.N.C thanks Dr. M. Chopkar, NIT Raipur, Dr. M.
Pradhan and Dr. N. K. Nath, NIT Meghalaya for useful discussion and many help. SAIF, NEHU
is also acknowledged for analytical facilities.
References
1.
2.
Wang, B.; Zhu, L.; Yang, Y.; Xu, N.; Yang, G. J. Phys. Chem. C 2008, 112, 6643.
Jankovic, L.; Gournis, D.; Trikalitis, P. N.; Arfaoui, I.; Cren, T.; Rudolf, P.; Sage, M.-H.;
Palstra, T. T.; Kooi, B.; De Hosson, J. Nano Lett. 2006, 6, 1131.
3.
Kim, J.; Hong, A. J.; Nah, J.-W.; Shin, B.; Ross, F. M.; Sadana, D. K. ACS nano 2011, 6,
265.
4.
5.
Wang, Y.; Zeng, H. C.; Lee, J. Y. Adv. Mater. 2006, 18, 645.
Cui, Q.; Rajathurai, K.; Jia, W.; Li, X.; Gao, F.; Lei, Y.; Gu, Z. J. Phys. Chem. C 2010,
114, 21938.
6.
7.
Sinha, A. K.; Pradhan, M.; Sarkar, S.; Pal, T. Environ. Sci. Technol. 2013, 47, 2339.
(a) Nokami, J.; Otera, J.; Sudo, T.; Okawara, R. Organometallics 1983, 2, 191; (b)
Uneyama, K.; Matsuda, H.; Torii, S. Tetrahedron Lett. 1984, 25, 6017; (c) Einhorn, C.; Luche,
J.-L. J. Organomet. Chem. 1987, 322, 177; (d) Imai, T.; Nishida, S. Synthesis 1993, 395; (e)
12

Page 13 of 32
Marton, D.; Stivanello, D.; Tagliavini, G. J. Org. Chem. 1996, 61, 2731; (f) Cokley, T. M.;
Harvey, P. J.; Marshall, R. L.; McCluskey, A.; Young, D. J. J. Org. Chem. 1997, 62, 1961; (g)
Chan, T. H.; Yang, Y.; Li, C. J. J. Org. Chem. 1999, 64, 4452; (h) Alcaide, B.; Almendros, P.;
Aragoncillo, C.; Rodríguez-Acebes, R. J. Org. Chem. 2001, 66, 5208; (i) Law, M. C.; Wong, K.-
Y.; Chan, T. H. Green Chem. 2002, 4, 161; (j) Zha, Z.; Wang, Y.; Yang, G.; Zhang, L.; Wang, Z.
Green Chem. 2002, 4, 578; (k) Andrews, P. C.; Peatt, A. C.; Raston, C. L. Tetrahedron Lett.
2002, 43, 7541; (l) Wang, Z.; Zha, Z.; Zhou, C. Org. Lett. 2002, 4, 1683; (m) Tan, K.-T.; Chng,
S.-S.; Cheng, H.-S.; Loh, T.-P. J. Am. Chem. Soc. 2003, 125, 2958; (n) Zha, Z.; Xie, Z.; Zhou,
C.; Chang, M.; Wang, Z. New J. Chem. 2003, 27, 1297; (o) Zhang, J.; Blazecka, P. G.; Berven,
H.; Belmont, D. Tetrahedron Lett. 2003, 44, 5579; (p) Alcaide, B.; Almendros, P.; Rodriguez-
Acebes, R. J. Org. Chem. 2005, 70, 3198; (q) Zha, Z.; Qiao, S.; Jiang, J.; Wang, Y.; Miao, Q.;
Wang, Z. Tetrahedron 2005, 61, 2521; (r) Guimarães, R. L.; Lima, D. J.; Barros, M. E. S.;
Cavalcanti, L. N.; Hallwass, F.; Navarro, M.; Bieber, L. W.; Malvestiti, I. Molecules 2007, 12,
2089; (s) Manchanayakage, R.; Handy, S. T. Tetrahedron Lett. 2007, 48, 3819; (t) Roy, U. K.;
Roy, S. Tetrahedron Lett. 2007, 48, 7177; (u) Dam, J. H.; Fristrup, P.; Madsen, R. J. Org. Chem.
2008, 73, 3228.
8.
Balan, L.; Schneider, R.; Billaud, D.; Ghanbaja, J. Nanotechnology 2005, 16, 1153.
Zhou, Q.; Liu, X.; Zhao, Y.; Jia, N.; Liu, L.; Yan, M.; Jiang, Z. Chem. Commun. 2005,
9.
4941.
10.
(a) Li, R.; Sun, X.; Zhou, X.; Cai, M.; Sun, X. J. Phys. Chem. C 2007, 111, 9130; (b)
Tombros, N.; Buit, L.; Arfaoui, I.; Tsoufis, T.; Gournis, D.; Trikalitis, P. N.; van der Molen, S. J.;
Rudolf, P.; van Wees, B. J. Nano Lett. 2008, 8, 3060.
11.
Sinha, A. K.; Sil, A.; Sasmal, A. K.; Pradhan, M.; Pal, T. New J. Chem. 2015, 39, 1685.
13

Page 14 of 32
12.
(a) Li, C. J. Chem. Rev. 1993, 93, 2023; (b) Chan, T.; Li, C.; Lee, M.; Wei, Z. Can. J.
Chem. 1994, 72, 1181; (c) Lubineau, A.; Augé, J.; Queneau, Y. Synthesis 1994, 741; (d) Li, C.-J.
Tetrahedron 1996, 52, 5643; (e) Chan, T. Pure Appl. Chem. 1996, 68, 919; (f) Li, C. J.; Chan, T.
H. Organic Reactions in Aqueous Media; John Wiley & Sons, Inc.; New York, 1993.
13.
14.
Yus, M.; González-Gómez, J. C.; Foubelo, F. Chem. Rev. 2011, 111, 7774.
(a) Nicolaou, K.; Skokotas, G.; Furuya, S.; Suemune, H.; Nicolaou, D. C. Angew. Chem.
Int. Ed. 1990, 29, 1064; (b) An, Z.; She, Y.; Yang, X.; Pang, X.; Yan, R. Org. Chem. Front.
2016, 3, 1746; (c) Hosseyni, S.; Wojtas, L.; Li, M.; Shi, X. J. Am. Chem. Soc. 2016, 138, 3994;
(d) Sarkar, D.; Rout, N.; Ghosh, M. K.; Giri, S.; Neue, K.; Reuter, H. J. Org. Chem. 2017, 82,
9012.
15.
(a) Minowa, N.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 1987, 60, 3697; (b) Zhang, L.-J.;
Mo, X.; Huang, Y.-Z. J. Organomet. Chem. 1994, 471, 77; (c) Kanda, T.; Ando, Y.; Kato, S.;
Kambe, N.; Sonoda, N. Synlett 1995, 745; (d) Nakagawa, T.; Kasatkin, A.; Sato, F. Tetrahedron
Lett. 1995, 36, 3207; (e) Tamaru, Y.; Goto, S.; Tanaka, A.; Shimizu, M.; Kimura, M. Angew.
Chem. Int. Ed. 1996, 35, 878; (f) Cabezas, J. A.; Alvarez, L. X. Tetrahedron Lett. 1998, 39,
3935; (g) Guillemin, J.-C.; Malagu, K. Organometallics 1999, 18, 5259; (h) Cabezas, J. A.;
Pereira, A. R.; Amey, A. Tetrahedron Lett. 2001, 42, 6819; (i) Nakajima, M.; Saito, M.;
Hashimoto, S. Tetrahedron: Asymmetry 2002, 13, 2449; (j) Banerjee, M.; Roy, S. Chem.
Commun. 2003, 534; (k) Konishi, S.; Hanawa, H.; Maruoka, K. Tetrahedron: Asymmetry 2003,
14, 1603; (l) Banerjee, M.; Roy, S. Org. Lett. 2004, 6, 2137; (m) Brown, H. C.; Khire, U. R.;
Racherla, U. S. Tetrahedron Lett. 1993, 34, 15; (n) Inoue, M.; Nakada, M. Org. Lett. 2004, 6,
2977; (o) Maddess, M. L.; Lautens, M. Org. Lett. 2005, 7, 3557; (p) Schneider, U.; Sugiura, M.;
Kobayashi, S. Tetrahedron 2006, 62, 496; (q) Ito, H.; Sasaki, Y.; Sawamura, M. J. Am. Chem.
14

Page 15 of 32
Soc. 2008, 130, 15774; (r) Naodovic, M.; Xia, G.; Yamamoto, H. Org. Lett. 2008, 10, 4053; (s)
Liu, S.; Kim, J. T.; Dong, C.-G.; Kishi, Y. Org. Lett. 2009, 11, 4520; (t) Usanov, D. L.;
Yamamoto, H. Angew. Chem. Int. Ed. 2010, 49, 8169; (u) Guo, L. N.; Gao, H.; Mayer, P.;
Knochel, P. Chem. Eur. J. 2010, 16, 9829; (v) Chen, J.; Captain, B.; Takenaka, N. Org. Lett.
2011, 13, 1654; (w) Jain, P.; Wang, H.; Houk, K. N.; Antilla, J. C. Angew. Chem. 2012, 124,
1420; (x) Hirashita, T.; Suzuki, Y.; Tsuji, H.; Sato, Y.; Naito, K.; Araki, S. Eur. J. Org. Chem.
2012, 5668; (y) Reddy, L. R. Org. Lett. 2012, 14, 1142; (z) Couto, T. R.; Freitas, J. J.; Freitas, J.
C.; Cavalcanti, I. H.; Menezes, P. H.; Oliveira, R. A. Synthesis 2015, 47, 71.
16.
(a) Alcaide, B.; Almendros, P.; Aragoncillo, C.; Rodriguez-Acebes, R. J. Org. Chem.
2001, 66, 5208; (b) Miao, W.; Chan, T. H. Synthesis 2003, 0785; (c) Loh, T.-P.; Lin, M.-J.; Tan,
K.-L. Tetrahedron Lett. 2003, 44, 507; (d) Lin, M.-J.; Loh, T.-P. J. Am. Chem. Soc. 2003, 125,
13042; (e) Miao, W.; Chung, L. W.; Wu, Y.-D.; Chan, T. H. J. Am. Chem. Soc. 2004, 126,
13326; (f) Lee, P. H.; Kim, H.; Lee, K. Adv. Synth. Catal. 2005, 347, 1219; (g) Hirayama, L. C.;
Dunham, K. K.; Singaram, B. Tetrahedron Lett. 2006, 47, 5173; (h) Arimitsu, S.; Hammond, G.
B. J. Org. Chem. 2006, 71, 8665; (i) Hirayama, L. C.; Haddad, T. D.; Oliver, A. G.; Singaram, B.
J. Org. Chem. 2012, 77, 4342; (j) Haddad, T. D.; Hirayama, L. C.; Buckley, J. J.; Singaram, B. J.
Org. Chem. 2012, 77, 889.
17.
(a) Chen, C.; Crich, D. J. Chem. Soc., Chem. Commun. 1991, 1289; (b) Bieber, L. W.; da
Silva, M. F.; da Costa, R. C.; Silva, L. O. Tetrahedron Lett. 1998, 39, 3655; (c) Ma, X.; Wang, J.
-X.; Li, S.; Wang, K. –H.; Huang, D. Tettrahedron 2009, 8683; (d) Ghosh, P.; Chattopadhyay, A.
Tetrahedron Lett. 2012, 53, 5202.
15

Page 16 of 32
18.
(a) Nokami, J.; Tamaoka, T.; Koguchi, T.; Okawara, R. Chem. Lett. 1984, 13, 1939; (b)
Wu, S.; Huang, B.; Gao, X. Synth. Commun. 1990, 20, 1279; (c) Li, Q. R.; Gu, C. Z.; Yin, H.
Chin. J. Chem. 2006, 24, 72.
19.
20.
21.
Han, Y.; Chi, Z.; Huang, Y.-Z. Synth. Commun. 1999, 29, 1287.
Li, Z.; Jia, Y.; Zhou, J. Synth. Commun. 2000, 30, 2515.
(a) Mukaiyama, T.; Harada, T. Chem. Lett. 1981, 10, 621; (b) Houllemare, D.; Outurquin,
F.; Paulmier, C. J. Chem. Soc., Perkin Trans. 1 1997, 1629; (c) Masuyama, Y.; Ito, A.;
Fukuzawa, M.; Terada, K.; Kurusu, Y. Chem. Commun. 1998, 2025; (d) Wang, J.; Miao, X.-P.;
Yuan, G. Aust. J. Chem. 2005, 58, 611.
22.
23.
Kurono, N.; Sugita, K.; Tokuda, M. Tetrahedron 2000, 56, 847.
(a) Qiu, L.; Pol, V. G.; Wei, Y.; Gedanken, A. New J. Chem. 2004, 28, 1056; (b) Qiu, L.;
Pol, V. G.; Calderon-Moreno, J.; Gedanken, A. Ultrason. Sonochem. 2005, 12, 243.
24. (a) Jiang, H.; Moon, K. -S.; Dong, H.; Hua, F.; Wong, C. Chem. Phys. Lett. 2006, 429,
492; (b) Jo, Y. H.; Jung, I.; Choi, C. S.; Kim, I.; Lee, H. M. Nanotechnology 2011, 22, 225701.
25. General procedure for the synthesis of homopropargyl aclcohol (3a) by the Sn40°C
particles mediated coupling between propargyl bromide (2a) and 4-chlorobenzaldehyde
(1a) in water at room temperature: A 25 mL round bottomed flask equipped with a magnetic
bar was charged with Sn40°C particles (1.2 mmol), propargyl bromide 2a (1.2 mmol) and distilled
water (5 mL) and allowed to stir vigorously for 30 min at room temperature in air. After that, 4-
chlorobenzaldehyde 1a (1.0 mmol) was added and the reaction mixture was allowed to continue
at room temperature. The progress of the reaction was monitored by TLC (eluent: petroleum
ether 60-80 °C/ethyl acetate 19:1 v/v). Following completion of the reaction, the reaction mixture
16

Page 17 of 32
was filtered through a celite bed and the bed was washed with ethyl acetate (2 x 5 mL). The
filtrate was extracted with ethyl acetate (3 x 10 mL), washed with water (2 x 10 mL), brine
solution (2 x 10 mL) and dried over anhydrous sodium sulphate. The organic solvent was
removed under reduced pressure, and the mixture was subjected to column chromatography over
silica gel (100-200 mesh, eluent: petroleum ether 60-80 °C/ethyl acetate 49:1 v/v) to afford a
corresponding homopropargyl alcohol 3a as a yellow oil in 80% isolated yield. Compound 3a:
1H NMR (400 MHz, CDCl3): δ (ppm) 7.34-7029 (m, 4H), 4.83 (t, J = 5.8 Hz, 1H), 2.74 (s, 1H),
13
2.60 (dd, J = 6.4 Hz and 2.4 Hz, 2H), 2.08 (t, J = 2.4 Hz, 1H). C NMR (100 MHz, CDCl3): δ
(ppm) 140.9, 133.7, 128.6, 127.2, 80.3, 71.6, 71.3, 29.4.
26.
The following allenic alcohols were detected in our reaction conditions in very small
amount and characterized by 1H and 13C NMR. See the supporting information for details.
27. (a) Kundu, A.; Prabhakar, S.; Vairamani, M.; Roy, S. Organometallics 1999, 18, 2782. (b)
McCluskey, A.; Muderawan, I. W.; David J. Young, D. J. J. Org. Chem. 2001, 66, 7811.
28. Huang, T.; Meng, Y.; Venkatraman, S.; Wang, D.; Li, C. -J. J. Am. Chem. Soc. 2001, 123,
7451.
29. (a) Tour, J. M. Chem. Rev. 1996, 96, 537; (b) Martin, R. E.; Diederich, F. Angew. Chem. Int.
Ed. 1999, 38, 1350; (c) De Meijere, A.; Kozhushkov, S.; Haumann, T.; Boese, R.; Puls, C.;
Cooney, M. Chem. Eur. J. 1995, 1, 124; (d) Bohlmann, F.; Zdero, C. Naturally occurring
acetylenes; Academic Press, 1973; (e) Hansen, L.; Boll, P. M. Phytochemistry 1986, 25, 285; (f)
17

Page 18 of 32
Matsunaga, H.; Katano, M.; Yamamoto, H.; Fujito, H.; Mori, M.; Takata, K. Chem. Pharm. Bull.
1990, 38, 3480.
30. Zhang, S.; Liu, X.; Wang, T. Adv. Synth. Catal. 2011, 353, 1463.
18

Page 19 of 32
Table 1: Optimization of reaction conditions for the propargylation of aldehyde 1aa
O
OH
X
Tin reagent
+
Solvent
Cl
Cl
Temperture
1a
2a
2
3a
2b
X= Br, ; X= OH, ; X= Cl,
2c
Entry Tin reagents
X
Solvent
EtOH
Time (h)
Yield of 3a (%)b
1
2
Sn40°C
Sn40°C
Sn40°C
Sn40°C
Sn40°C
Sn40°C
Sn40°C
Sn60°C
SnRT
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
6
6
10
15
30
43
54
68
80
72
80
79
80
30
12
-
THF
3
EtOH:H2O (1:1)
THF:H2O (1:1)
THF:H2O (1:2)
THF:H2O (1:3)
H2O
6
4
6
5
6
6
6
7
6
8
H2O
6
9c
10
11d
12
13
14e
15
16
17e
H2O
6
Sn40°C
*
H2O
6
Sn40°C
H2O
4
Commercial tin powder
Granulated tin
No Sn(0) reagent
SnCl2.2H2O
SnO
H2O
6
H2O
24
24
24
24
12
12
H2O
H2O
21
10
-
H2O
Sn40°C
OH H2O
Cl H2O
18e
Sn40°C
-
a
Reaction conditions: 4-chlorobenzaldehyde 1a (1.0 mmol), compound 2 (1.2 mmol), tin reagents (1.2 mmol),
b
c
solvent (5 mL), RT = room temperature. Isolated yields. SnRT = active Sn(0) prepared at room temperature by
d
e
Pal et al.11 Temperature = 60 °C. Unreacted 4-chlorobenzaldehyde 1a was recovered.
19

Page 20 of 32
Table 2: Substrate scope of Sn40°C particles mediated propargylation of aldehydes 1 in water at
room temperature a
Entry
1, R
Product
3a
Time (h)
Yield of 3 (%)b
1
2
1a, 4-ClC6H4
1b, 4-BrC6H4
6
7
80
78
3b
3c
4
1c, 2,4-Cl2C6H4
1d, 2,6-Cl2C6H4
1e, 2-O2NC6H4
1f, C6H5
3c
3d
3e
3f
6
6
70
75
50
81
82
65
70
84
72
75
55
70
52
70
5c
6
11
8
7
1g, 4-MeC6H4
1h, 4-MeOC6H4
1i, 3-Br-6-HOC6H3
1j, 9-anthracenyl
1k, 2-thienyl
3g
3h
3i
8
8
8
9
6
10
11
12
13d
14
15
16
3j
8
3k
3l
7
1l, 2-furyl
7
1m, 4-(OHC)C6H4
1n, C6H5CH=CH
1o, n-Bu
3m
3n
3o
3p
12
8
10
6
1p, C6H5CH2CH2
17c
18c
1q, C6H5CH(CH3)
1r, C6H5CH2
6
6
68
74
3q
3r
20

Page 21 of 32
19e
20f
1r, C6H5CH2
1r, C6H5CH2
10
10
58
31
3r
3r
a
Reaction conditions: Aldehyde 1 (1.0 mmol), propargyl bromide 2a (1.2 mmol), Sn40°C particles (1.2 mmol), water
b
c
as solvent (5 mL), RT = room temperature. Isolated yields. See reference no. 26 and the supporting information
d
for more details about the corresponding allenic alcohols. Reaction conditions: Aldehyde 1m (1.0 mmol),
e
propargyl bromide 2a (2.4 mmol), Sn40°C particles (2.4 mmol), water as solvent (6 mL), RT = room temperature.
f
Tin residue formed after the first batch (entry 18) used as reagent instead of fresh Sn40°C particles. Tin residue
formed after the second batch (entry 19) used as reagent instead of fresh Sn40°C particles.
21

Page 22 of 32
LIST OF FIGURES/SCHEMES
Figure 1: XRD pattern of (a) Sn40°C and (b) Sn60°C particles.
Figure 2: SEM images of (a) Sn40°C and (b) Sn60°C particles.
Figure 3: Size-dependent melting temperature depression measured by DSC (a) Sn40°C and (b)
Sn60°C particles.
Figure 4: Partial 1H NMR spectra of (A) propargyl bromide 2a (80% solution in toluene) and (B)
propargyl bromide 2a treated with Sn40°C material in D2O for 30 min. *Peak for the
#
methyl protons of toluene. Peaks for impurities present in propargyl bromide;
€Unidentifiable peak in the reaction mixture.
Scheme 1: Sn(0) mediated synthesis of homopropargyl alcohols from propargyl bromide and
carbonyl compounds.
Scheme 2: Synthesis of active Sn(0) particles from blue-black SnO.
Scheme 3: Chemoselective propargylation of aldehyde 1a in presence of other less electrophilic
carbonyls 4.
Scheme 4: Plausible mechanism for active Sn(0) mediated propargylation of aldehydes in water.
Scheme 5: CuI/TMEDA promoted synthesis of conjugated 1,3-diynes 5.a
a Reaction conditions: compound 3 (1.0 mmol), CuI (5 mol%), TMEDA (10 mol%),
Et3N (3.0 mmol), acetone (5 mL), RT = room temperature, 20 h.
22

Page 23 of 32
Figure 1: XRD pattern of (a) Sn
and (b) Sn
particles
40°C
60°C

Page 24 of 32
Figure 2: SEM images of (a) Sn
and (b) Sn
particles
40°C
60°C

Page 25 of 32
Figure 3: Size-dependent melting temperature depression measured by DSC (a) Sn
and (b) Sn
60°C
40°C
particles

Page 26 of 32
1
Figure 4: Partial H NMR spectra of (A) propargyl bromide 2a (80% solution in toluene) and (B) propargyl
bromide 2a treated with Sn
material in D O for 30 min. *Peak for the methyl protons of toluene.
40°C
2
#
€
Peaks for impurities present in propargyl bromide; Unidentifiable peak in the reaction mixture.
112x100mm (300 x 300 DPI)

Page 27 of 32
Scheme 1: Sn(0) mediated synthesis of homopropargyl alcohols from propargyl bromide and carbonyl
compounds
82x104mm (300 x 300 DPI)

Page 28 of 32
Scheme 2: Synthesis of active Sn(0) particles from blue-black SnO
89x27mm (300 x 300 DPI)

Page 29 of 32
Scheme 3: Chemoselective propargylation of aldehyde 1a in presence of other less electrophilic carbonyls 4
148x30mm (300 x 300 DPI)

Page 30 of 32
Scheme 4: Plausible mechanism for active Sn(0) mediated propargylation of aldehydes in water
112x67mm (300 x 300 DPI)