Silver-catalyzed carbon-selenium cross-coupling using N-(phenylseleno)phthalimide: An alternate approach to the synthesis of organoselenides

Article abstract of DOI:10.1139/cjc-2016-0427

Silver(I) catalyzed phenylselenylation of terminal alkynes and organoboronic acids has been demonstrated using N-(phenylseleno)phthalimide as an electrophilic SePh donor. A wide variety of terminal alkynes and organoboronic acids are selenylated efficiently to produce the corresponding alkynyl and diaryl selenides, respectively, in good yields. Silver(I) acts as a Lewis acid in this process.

Full text of DOI:10.1139/cjc-2016-0427

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Silverꢀcatalyzed carbonꢀselenium cross coupling using Nꢀ
(phenylseleno)phthalimide: an alternate approach to the synthesis of
organoselenides
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Nirmalya Mukherjee,a Subhajit Pal,a Amit Saha*b and Brindaban C. Ranu*a
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N. Mukherjee, S. Pal, Prof. Dr. B. C. Ranu. Department of Organic Chemistry,
Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India.
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Dr. A. Saha. Department of Chemistry, Achhruram Memorial College, Jhalda, Purulia 723202,
West Bengal, India.
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aCorresponding author (Fax: +91ꢀ33ꢀ24732805; Tel: +91 33 24734971; Eꢀmail:
ocbcr@iacs.res.in)
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bCorresponding author (Eꢀmail: amitsahaiacs@yahoo.co.in)
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ABSTRACT
Silver(I) catalyzed phenylselenylation of terminal alkynes and organoboronic acids has been
demonstrated using Nꢀ(phenylseleno)phthalimide as electrophilic SePh donor. A wide variety of
terminal alkynes and organoboronic acids are selenylated efficiently to produce the
corresponding alkynyl and diaryl selenides respectively in good yields. Silver(I) acts as a Lewis
acid in this process.
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Keywords: silver catalysis, selenylation, Nꢀ(phenylseleno)phthalimide, alkynyl selenide, diaryl
selenide.
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41 Graphical abstract
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Silverꢀcatalyzed carbonꢀselenium cross coupling using Nꢀ
43 (phenylseleno)phthalimide: an alternate approach to the synthesis of
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organoselenides
Nirmalya Mukherjee,a Subhajit Pal,a Amit Saha*b and Brindaban C. Ranu*a
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Introduction
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Organoselenium compounds are of immense importance due to their occurrence in many
micronutrients,1 biologically active molecules2 and natural products.3 They have potential
applications in the field of pharmaceutical chemistry,4 organic synthesis5 and material science.6
One of the efficient tools for the synthesis of organoselenium compounds is cross coupling with
suitable selenylating reagents in the presence of a transition metal (Cu,7 Pd,8 Ni,9 Ru,10 Rh11)
catalyst. The commonly used selenylating reagents include PhSeSePh,7aꢀe,8a,10ꢀ12 PhSeCl,11,13
PhSeBr,7f,14 PhSeCN.7g,15 However, these selenylating reagents are associated with one or more
drawbacks, such as lower stability, generation of toxic vapour and reactive byproducts.16 A better
alternative selenium source is the less explored Nꢀ(phenylseleno)phthalimide (NPSP)17 which
exists as odourless and colourless stable crystalline solid.
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Thus we are interested to investigate selenylation using Nꢀ(phenylseleno)phthalimide (NPSP) as
the benign source of SePh in presence of a suitable metal catalyst. Palladium, copper and nickel
catalysts being considerably active have been widely used for cross coupling reactions.18 On the
other hand, among the noble metals silver catalyst is moderately active and has been used for
coupling reaction in a limited way.19 Earlier, NPSP was involved in the enantioselective
selenylation of aldehydes using different organocatalysts such as Lꢀproline,20 TMSꢀprotected
α,αꢀdiphenylꢀ2ꢀpyrrolidinemethanol,21 and diphenylprolinol silyl ether,22 enantioselective
selenoloactonization using (DHQD)2PHAL
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(1,4ꢀbis[(S)ꢀ[(2R,4S,5R)ꢀ5ꢀethylquinuclidinꢀ2ꢀyl]ꢀ(6ꢀethoxyꢀ4ꢀquinolyl)methoxy]phthalazine)23a
and selenylation of olefins under the catalysis of pꢀTsOH.23b As NPSP releases an electrophilic
SePh species we consider it appropriate to involve a nucleophilic coupling partner such as
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terminal alkyne and organoboronic acid under the catalysis of moderately active metal for an
effective selenylation. With this concept we report here a simple and general method for
phenylsenylation of alkynes/organoboronic acids using NPSP and silver catalyst in THF
(Scheme 1).
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Scheme 1.
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Reports of CꢀSe crossꢀcoupling reaction usually invoke the formation of the CꢀSe bond by
reductive elimination from an intermediate transition metal complex A of Cu/Pd/Ru/Rh (Scheme
2).7,8,10,11 It is anticipated that in the present reaction Ag(I) catalyst having moderate Lewis acid
activity19d is likely to increase the electrophilicity of SePh moiety which will then readily interact
with the nucleophilic aryl/alkynyl counterpart.
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Scheme 2.
Results and Discussion
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To optimize the reaction conditions a series of experiments were conducted with 4ꢀ
methoxyphenylacetylene as a model substrate for selenylation using NPSP in the presence of
Ag(I) catalyst with variation of reaction parameters such as catalyst, solvent, reaction
temperature and time (Table 1). The selenylation was not observed using 10 mol% of Ag2CO3 in
o
THF at room temperature (25 C) (Table 1, entry 1). However the increase of reaction
o
temperature to 66 C in THF at reflux for12 h made a remarkable improvement (Table 1, entry
2).
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Table 1.
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Lowering of catalyst loading to 5 mol% and reducing the reaction time to 10 h decreased the
yield (Table 1, entries 3 and 4). Use of other solvents, Nꢀmethylpyrrolidinone (NMP) and toluene
at similar conditions did not give better results (Table 1, entries 5 and 6). The involvement of
other silver salts such as AgNO3 and AgOTf/K2CO3 provided comparable yields (Table 1, entries
7 and 8). For comparison, when Cuꢀsalts are used as catalysts in place of Ag marginal yields (20ꢀ
26 %) of products are obtained in addition to considerable amount of dimerized product of
alkyne (Table 1, entries 9 and 10), whereas when other transition metal salts (Ni(acac)2,
Ru(PPh3)3Cl2, Co(acac)2 and iron nanoparticles) were used no reaction was observed in similar
conditions (Table 1, entries, 11, 12, 13 and 14). The reaction did not occur at all in the absence of
Ag2CO3 (Table 1, entry 15). Thus, in a representative experimental procedure, a mixture of 4ꢀ
methoxy phenylacetylene (0.3 mmol), Nꢀ(phenylseleno)phthalimide (0.3 mmol) and Ag2CO3 (10
mol%) in dry THF (5 ml) was heated at reflux under argon atmosphere for 12 h. The progress of
the reaction was monitored by TLC. Standard workꢀup followed by purification through column
chromatography provided the pure product.
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To investigate the substrate scope several diversely substituted terminal alkynes were subjected
to selenylation by this procedure. The results are summarized in Table 2 (Chart 1). Both aromatic
and aliphatic alkynes were selenylated efficiently with NPSP under the silver catalyzed protocol.
Electron donating group, OMe (Table 2, entries 1, 2, 5) as well as electron withdrawing groups,
F, CF3 (Table 2, entries 3, 4) in the aromatic ring did not have much influence in the control of
yields. The heteroaryl alkyne, 3ꢀethynylthiophene was selenylated cleanly by this procedure
(Table 2, entry 6). Aliphatic alkynes such as cyclohexyl acetylene (Table 2, entry 7) and ethyl
acetylene carboxylate (Table 2, entry 8) participated in the selenylation reaction to give good
yields of desired alkynyl selenides.
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Table 2.
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Being encouraged by the successful selenylation of alkynes using NPSP by this protocol we next
employed organoboronic acids as selenylating counterpart. Interestingly, it was observed that use
of Ag2CO3 under the same experimental conditions (Table 1) was not effective for boronic acids
(Table 3, entry 1). However, use of 1 equiv. of K2CO3 along with 10 mol % of Ag2CO3 improved
the yield of the reaction considerably providing 56% yield of 5aa (Table 3, entry 2). The increase
of catalyst loading did not improve the yield of the reaction substantially (Table 3, entry 3).
Interestingly, the use of AgNO3 (10 mol%) in place of Ag2CO3 together with 1 equiv. of K2CO3
in refluxing THF for 12 h produced the diaryl selenide product 5aa in 82% yield (Table 3, entry
4). However, the best yield was obtained using 20 mol % of AgNO3 (Table 3, entry 5).
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Table 3.
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Thus several organoboronic acids with wide structural variations were subjected to
phenylselenylation with NPSP by the optimized protocol (Table 4, Chart 1). The aryl boronic
acids containing electron donating groups (OiPr, Me) participated in the selenylation reaction to
offer the corresponding diaryl selenides in high yields (Table 4, entries 1, 3). The electronꢀ
withdrawing groups (OCF3, NO2) in the aryl ring did not affect the yield ofproducts (Table 4,
entries 2, 8). Phenylselenylation was successfully accomplished with bridged substrate like
acenaphtheneꢀ5ꢀboronic acid (Table 4, entry 4). The reactions proceeded satisfactorily with
substituted styrenyl boronic acids (Table 4, entries 5, 6) and pentynyl boronic acid (Table 4,
entry 7) without any difficulty. Naphthyl boronic acid also underwent CꢀSe crossꢀcoupling by
this procedure effectively (Table 4, entry 9).
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Table 4.
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The reaction of alkyl boronic acid such as MeꢀB(OH)2 with NPSP under the reaction conditions
was also investigated; however the reaction failed to provide the corresponding addition
product. To compare the reactivity of NPSP with other PhSe+ sources such as PhSeCN and
PhSeBr under the identical reaction conditions we found that the reaction of alkyne with PhSeBr
produced the alkynyl selenide, 3aa only in 48% yield, whereas with PhSeCN only trace (2%)
amount of the product was obtained.
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Regarding the reaction pathway of this selenylation process we suggest that NPSP initially
coordinates with Ag+, which makes the SePh moiety of NPSP more electrophilic16,23 (Scheme 3).
It is proposed that silver(I) subsequently activates the terminal alkyne24 to generate silver
acetylide type intermediate which interacts with activated NPSP producing the alkynyl selenide
product and phthalimide. Ag+ ion is released in the process and it participates in the next
catalytic cycle. In case of organoboronic acid, a base (K2CO3) is required to complete the octet of
boron atom in boronic acid so that aryl moiety is able to migrate with its bond pair of electrons25
and it reacts with electrophilic SePh leading to the formation of the diaryl selenide product.
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Scheme 3.
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AgNO3, having higher effective Lewis acidic activity compared to Ag2CO3, works more
efficiently in case of CꢀSe crossꢀcoupling with organoboronic acids.19e However, in case of
alkyne, the formation of silverꢀacetylide type intermediate through the interaction of Ag+ ion and
terminal alkyne is realized with comparable efficacy with both the salts, AgNO3 and Ag2CO3.
2ꢀ
Marginally higher activity of Ag2CO3 may be attributed to the higher basicity of CO3 in
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comparison to NO3 .
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Conclusion
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In summary, we have developed a convenient and comprehensive method for Ag(I)ꢀcatalyzed Cꢀ
Se bond formation using Nꢀ(phenylseleno)phthalimide as the mild SePh donor. The
phenylselenylation is accomplished efficiently with a broad spectrum of structurally diverse
alkynes as well as organoboronic acids. High yields of the products, clean reactions, easy
operating procedures and tolerance to various functional groups with structural diversity of the
substrates render the protocol synthetically useful. To the best of our knowledge this is the first
report of silver catalyzed phenylselenylation using NPSP as the selenium source.
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Experimental
General
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NMR spectra were recorded at 300, 400 and 500 MHz for 1H and 75, 100 and 125 MHz for C
spectra in CDCl3 solutions. Elemental analyses were done at our Institute with an autoanalyzer.
Ag2CO3, AgNO3, Nꢀ(phenylseleno)phthalimide, K2CO3, all acetylenes, and boronic acids were
procured commercially.
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Representative experimental procedure for the crossꢀcoupling of 4ꢀethynylanisole and Nꢀ
(phenylseleno)phthalimide (Table 2, 3aa)
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A mixture of 4ꢀethynylanisole (40 mg, 0.3 mmol), Nꢀ(phenylseleno)phthalimide (60 mg, 0.3
mmol), Ag2CO3 (8.2 mg, 0.03 mmol) in THF (3 mL) was heated at reflux under argon for 12 h
(TLC). The reaction mixture was then allowed to cool and was extracted with diethyl ether (3 x
20 mL). The extract was washed with water (10 mL) and brine (10 mL). Then the organic phase
was dried over Na2SO4 and evaporated to leave the crude product, which was purified by column
chromatography over silica gel (hexane/diethyl ether 98:2) to provide the pure ((4ꢀ
methoxyphenyl)ethynyl)(phenyl)selane as yellow gummy liquid, (82 mg, 95%); IR
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(neat): ν = 3306, 3140, 3007, 2925, 2851, 2316, 2150, 1595, 1575, 1511, 1470, 1452, 1398, 129
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6, 1255, 1161 cmꢀ1; 1H NMR (500 MHz, CDCl3): δ 3.82 (s, 3H), 6.87 (dd, J1 = 2 Hz, J2 = 6.5 Hz,
2H), 7.27ꢀ7.34 (m, 3H), 7.46 (dd, J1 = 2 Hz, J2 = 7 Hz, 2H), 7.58 (dd, J1 = 1 Hz, J2 = 8.5 Hz, 2H)
ppm; 13C NMR (100 MHz, CDCl3): δ 55.4, 67.3, 114.1, 115.4, 127.1, 129.0, 129.4, 129.6, 133.7,
160.1 ppm; anal. calcd. for C15H12OSe; C 62.73, H 4.21; found: C 62.77, H 4.28 %.
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This procedure was followed for all the reactions listed in Table 2 and Table 4. Although the
representative procedure is based on mmol scale reaction scaling up to 10 mmol also produced
similar results. All of the known compounds are identified by their spectroscopic data (1H NMR
and 13C NMR) and the data are consistent with those reported earlier. Similarly all of the
unknown compounds are well characterized by their spectroscopic and spectrometric data (IR,
1H NMR, 13C NMR and elemental analysis). All these data are provided in below.
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((2ꢀMethoxyphenyl)ethynyl)(phenyl)selane (Table 2, 3ab): Yellow viscous liquid, 90%, 77.54
mg, IR (neat): = 3061, 3019, 2160, 1589, 1472, 1425, 1263, 1213 cmꢀ1;1H NMR (300 MHz,
CDCl3): δ 3.90 (s, 3H), 6.88ꢀ6.93 (m, 2H), 7.25ꢀ7.33 (m, 4H), 7.60 (d, J = 7.5 Hz, 1H), 7.64 (dd,
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J = 1.5 Hz, 8.7 Hz, 2H) ppm ; C NMR (100 MHz, CDCl3): δ 55.9, 72.9, 99.8, 110.8, 112.6,
120.5, 126.9, 128.8, 129.5, 130.0, 130.4, 133.5, 134.3, 160.4 ppm; anal. calcd. for C15H12OSe; C
62.73, H 4.21; found: C 62.75, H 4.26 %.
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((3ꢀFluorophenyl)ethynyl)(phenyl)selane7d (Table 2, 3ac): Viscous liquid, 92%, 75.94 mg, 1H
NMR (400 MHz, CDCl3): δ 6.93ꢀ6.97 (m, 1H), 7.09 (dd, J = 1.5 Hz, J = 9.5 Hz, 1H), 7.16ꢀ7.21
(m, 3H), 7.22ꢀ7.27 (m, 2H), 7.49ꢀ7.51 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ 71.1, 101.6
(d, JC-F = 3 Hz), 115.9 (d, JC-F = 21 Hz), 118.5 (d, JC-F = 23 Hz), 125.1 (d, JC-F = 9 Hz), 127.4,
127.6 (d, JC-F = 3 Hz), 128.6, 129.4, 129.7, 130.0, 130.1, 162.4 (d, JC-F = 245 Hz) ppm.
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Phenyl((2ꢀ(trifluoromethyl)phenyl)ethynyl)selane (Table 2, 3ad): Colourless gummy liquid,
90%, 87.79 mg; IR (neat): ν = 3129, 2925, 2161, 1615, 1585, 1480, 1429, 1388, 1316, 1265,
1171, 1130 cmꢀ1 ;1H NMR ( 500 MHz, CDCl3): δ 7.27ꢀ7.30 (m, 1H), 7.34 (t, J = 7.5 Hz, 2H),
7.40 (t, J = 7.5 Hz, 1H), 7.50 (t, J = 7.5 Hz, 1H), 7.61 (d, J = 7.5 Hz, 3H), 7.66 (d, J = 8 Hz, 1H)
ppm ; 13C NMR (400 MHz, CDCl3): δ 76.4, 98.9, 121.5 (d, J = 2 Hz), 122.3, 125, 126 (q, J = 5
Hz), 127.4, 128, 128.5, 129.5 (q, J = 7 Hz), 131, 131.4 (d, J = 17 Hz), 133.9 ppm; anal. calcd. for
C15H9F3Se; C 55.40, H 2.79; found: C 55.37, H 2.77 %.
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(6ꢀMethoxynaphthalenꢀ2ꢀyl)(phenyl)selane7d (Table 2, 3ae): Colourless gummy liquid, 95%,
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89.26 mg, H NMR (300 MHz, CDCl3): δ 3.92 (s, 3H), 7.10ꢀ7.18 (m, 2H), 7.27ꢀ7.34 (m, 3H),
7.51 (dd, J1 = 1.5Hz, J2 = 8.4Hz, 1H), 7.60ꢀ7.71 (m, 4H), 7.95(s, 1H) ppm; 13C NMR (100 MHz,
CDCl3): δ 55.5, 68.7, 103.6, 106.0, 118.2, 119.6, 126.9, 127.2, 128.5, 129.1, 129.2, 129.2, 129.5,
129.7, 131.8, 134.5, 158.6 ppm.
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3ꢀ((Phenylselanyl)ethynyl)thiophene (Table 2, 3af): Colourless gummy liquid, 75%, 59 mg;
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IR (neat): ν = 3306, 3119, 2925, 2851, 1636, 1575, 1480, 1399, 1316, 1120 cmꢀ1; H NMR (300
MHz, CDCl3): δ 7.18 (dd, J1 = 5.1, J2 = 0.9 Hz, 1H), 7.26ꢀ7.36 (m, 4H), 7.53ꢀ7.59 (m, 3H) ppm;
13C NMR (100 MHz, CDCl3): δ 68.9, 97.9, 116.3, 122.4, 125.4, 127.2, 129.0, 129.2, 129.7, 129.9,
130.2ppm; anal. calcd. for C12H8SSe; C 54.76, H 3.06; found: C 54.78, H 3.03 %.
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(Cyclohexylethynyl)(phenyl)selane (Table 2, 3ag): Yellow gummy liquid, 92%, 72.6 mg; IR
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(neat): ν = 3305, 3140, 2935, 2851, 1636, 1575, 1480, 1440, 1399, 1109, 1007cmꢀ1; H NMR
(500 MHz, CDCl3): δ 1.23ꢀ1.26 (m, 3H), 1.42ꢀ1.48 (m, 3H), 1.64ꢀ1.68 (m, 2H), 1.77ꢀ1.80 (m,
2H), 2.53ꢀ2.57 (m, 1H), 7.11ꢀ7.15 (m, 1H), 7.17ꢀ7.22 (m, 2H), 7.41ꢀ7.43 (m, 2H) ppm; 13C NMR
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(75 MHz, CDCl3): δ24.9, 25.9, 30.4, 31.0, 32.8, 57.5, 109.0, 126.7, 128.5, 128.6, 129.4, 129.7
ppm; anal. calcd. for C14H16Se; C 63.88, H 6.13; found: C 63.82, H 6.17 %.
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Ethyl 3ꢀ(phenylselanyl)propiolate (Table 2, 3ah): Yellow gummy liquid, 90%, 68.35 mg; IR
(neat):ν = 3398, 3305,3129, 2976, 2925, 2851, 2150, 1697, 1575, 1480, 1441, 1392, 1368, 1245,
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1099, 1017, cmꢀ1; H NMR (400 MHz, CDCl3): δ 1.32 (t, J = 5.6Hz, 3H), 4.25 (q, J = 5.6Hz,
2H), 7.30ꢀ7.37 (m, 3H), 7.59 (dd, J1 = 1.2Hz, J2 = 6.4Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3):
14.2, 62.1, 74.9, 96.4, 116.2, 126.2, 128.3, 130.0, 130.3, 152.80 ppm; anal. calcd. for C11H10OSe;
C 52.19, H 3.98; found: C 52.23, H 3.94 %.
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((4ꢀPhenoxyphenyl)ethynyl)(phenyl)selane (Table 2, 3ai): Yellow gummy liquid, 89%, 93.2
mg; IR (neat): ν = 3295, 3140, 2925, 2851, 2150, 1570, 1490, 1429, 1388, 1245, 1192, 1151,
1109, 1017, 872 cmꢀ1 ; 1H NMR (500 MHz, CDCl3): δ 6.95 (dd, J1 = 9, J2 = 2.5 Hz, 2H), 7.04 (d,
J = 8 Hz, 2H), 7.15 (t, J = 7.5 Hz, 1H), 7.25ꢀ7.28 (m, 1H), 7.32ꢀ7.39 (m, 4H), 7.46ꢀ7.49 (m, 2H),
7.57ꢀ7.60 (m, 2H) ppm; 13C NMR (125 MHz, CDCl3): δ 68.4, 102.6, 117.8, 118.4, 119.6, 124.1,
127.2, 129.1, 129.2, 129.6, 130.0, 133.7, 156.4, 158.1 ppm; anal. calcd. for C20H14OSe; C 68.77,
H 4.04; found: C 68.73, H 4.08 %.
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(3ꢀIsopropoxyphenyl)(phenyl)selane (Table 4, 5aa): Yellow gummy liquid, 96%, 83.8 mg; IR
(neat): ν = 3140, 2976, 2935, 2851, 1718, 1585, 1480, 1440, 1378, 1276, 1245, 1171, 1120, 1017,
1
946 cmꢀ1; H NMR (500 MHz, CDCl3): δ 1.34 (d, J = 6Hz, 6H), 4.54 (m, 1H), 6.83 (dd, J1 = 2
Hz, J2 = 6.5 Hz, 2H), 7.19ꢀ7.22 (m, 3H), 7.33ꢀ7.35 (m,2H), 7.48 (dd, J = 2Hz, J = 6.5 Hz,2H)
ppm; 13C NMR (100 MHz, CDCl3): δ 22.0, 22.1, 70.1, 76.85, 117.0, 119.7, 126.5, 129.27, 131.1,
133.39, 136.6, 138.3, 158.3 ppm; anal. calcd. for C15H16OSe; C 61.86, H 5.54; found: C 61.44, H
5.14 %.
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Phenyl(4ꢀ(trifluoromethoxy)phenyl)selane (Table 4, 5ab): Yellow gummy liquid, 85%, 80.9
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mg; IR (neat): ν = 3130, 2915, 1636, 1398, 1181, 1110, 987, 760 cmꢀ1; H NMR (300 MHz,
CDCl3): δ 7.11 (dd, J1 = 1.2 Hz, J2 = 9 Hz, 2H), 7.28ꢀ7.33 (m, 3H), 7.43ꢀ7.51(m, 4H) ppm; 13C
NMR (75 MHz, CDCl3): δ 121.9, 122.2, 128.0, 129.6, 130.0, 130.4, 133.6, 134.0, 148.6 ppm;
anal. calcd. for C13H9F3OSe; C 49.23, H 2.86; found: C 49.27, H 2.88 %.
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Phenyl(oꢀtolyl)selane26 (Table 4, 5ac): Yellow liquid, 89%, 66 mg; H NMR (500 MHz,
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CDCl3): δ 2.46 (s, 3H), 7.10ꢀ7.13 (m, 1H), 7.23ꢀ7.39 (m,5H), 7.40ꢀ7.46 (m, 1H) ppm; C NMR
(100 MHz, CDCl3): 22.4, 126.8, 127.2, 127.9, 129.4, 130.3, 130.9, 131.8, 132.8, 133.8, 140.0
ppm.
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(1,2ꢀDihydroacenaphthylenꢀ5ꢀyl)(phenyl)selane (Table 4, 5ad): Colourless gummy liquid,
97%, 90 mg; IR (neat): ν = 3110, 2815, 1436, 1371, 1281, 1141 cmꢀ1; 1H NMR (400 MHZ,
CDCl3): δ 3.25ꢀ3.33 (m, 4H), 7.05ꢀ7.08 (m, 3H), 7.13ꢀ7.16 (m, 1H), 7.18ꢀ7.22 (m, 3H), 7.35ꢀ
7.44 (m, 1H), 7.76 (dd, J1 = 5.6 Hz, J2 = 24 Hz, 2H) ppm; 13CNMR (100 MHz, CDCl3): δ 30.2,
30.6, 120.0, 122.7, 122.9, 126.3, 128.9, 129.2, 130.6, 132.9, 133.5, 136.9, 140.0, 146.5, 148.2
ppm; anal. calcd. for C18H14Se; C 69.91, H 4.56; found: C 69.27, H 4.48 %.
265
266
267
268
(E)ꢀ(4ꢀMethylstyryl)(phenyl)selane7b (Table 4, 5ae): Yellow gummy liquid, 92%, 75.4 mg; 1H
NMR (500 MHz, CDCl3): δ 2.33 (s, 3H), 6.89 (dd, J1 = 4 Hz, J2 = 15.5 Hz, 1H), 7.10ꢀ7.14 (m,
3H), 7.23ꢀ7.33 (m, 5H), 7.53ꢀ7.55 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ 21.3, 117.9,
126.1, 127.4, 129.4, 129.5, 130.6, 132.4, 134.4, 135.8, 137.7 ppm.
269
270
(E)ꢀ(4ꢀMethoxystyryl)(phenyl)selane7a (Table 4, 5af): Yellow gummy liquid, 90%, 78.1 mg;
1H NMR (300 MHz, CDCl3): δ3.81 (s, 3H), 6.85ꢀ6.91 (m, 3H), 7.02 (d, J = 15.6 Hz, 1H), 7.25ꢀ
13

Page 14 of 24
13
271
272
7.31 (m, 5H), 7.52ꢀ7.55 (m, 2H) ppm; C NMR (75 MHz, CDCl3): δ 55.4, 114.2, 116.0, 127.2,
127.5, 129.4, 130.0, 130.9, 132.1, 136.0, 159.5 ppm.
1
273
274
275
276
Pentꢀ1ꢀynꢀ1ꢀyl(phenyl)selane27 (Table 4, 5ag): Yellow gummy liquid, 93%, 63 mg; H NMR
(400 MHz, CDCl3): δ 1.06 (t, J = 7.6 Hz, 3H), 1.65 (sextet, J = 7.2 Hz, 2H), 2.46 (t, J = 7.2 Hz,
2H), 7.23ꢀ7.34 (m, 3H), 7.53ꢀ7.55 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ 13.6, 22.3, 22.7,
57.7, 76.8, 104.6, 126.8, 128.7, 129.5 ppm.
1
277
278
279
280
(3ꢀNitrophenyl)(phenyl)selane12b (Table 4, 5ah): Yellow gummy liquid, 80%, 66.7 mg; H
NMR (300 MHz, CDCl3): δ7.36ꢀ7.41(m, 4H), 7.56ꢀ7.59 (m, 2H), 7.63ꢀ7.66 (m, 1H), 8.03ꢀ8.06
(m,1H), 8.20 (t, J = 2.1 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 121.7, 125.9, 128.6, 128.9,
129.9, 130.0, 134.9, 137.1, 148.8 ppm.
1
281
282
283
284
Naphthalenꢀ2ꢀyl(phenyl)selane7b (Table 4, 5ai): Yellow gummy liquid, 74%, 62.9 mg, H
NMR (300 MHz, CDCl3): δ 7.27 (dd, J1 = 6.3 Hz, J2 = 3.3 Hz, 3H), 7.44ꢀ7.54 (m, 5H), 7.73 (d, J
= 7.8 Hz, 2H), 7.78ꢀ7.82 (m, 1H), 7.99 (s, 1H) ppm; 13C NMR (75 MHz, CDCl3): δ 126.3,
126.6, 127.5, 127.9, 128.6, 128.9, 129.5, 130.6, 131.3, 132.2, 132.6, 133.0, 134.1 ppm.
285
Supplementary Material
286
287
288
Supplementary
material
is
available
with
the
article
through
the
1
13
journal website at ……… Supplementary material includes the H NMR and C NMR spectra
of all synthesized compounds listed in Table 2 and Table 4.
289
Acknowledgements
14

Page 15 of 24
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291
292
We are pleased to acknowledge the financial support from DST, New Delhi, in the form of the
award of J. C. Bose National Fellowship to B. C. R. (Grant no. SR/S2/JCBꢀ11/2008) and INSA,
New Delhi for offering an INSA Senior Scientist position to B. C. R.
293
References
294
295
296
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309
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376
377
378
18

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379
380
Scheme 1. Silver catalyzed phenylselenylation of alkynes and organoboronic acids.
381
382
383
Scheme 2. CꢀSe cross coupling reactions using various metal catalysts.
384
385
386
Scheme 3. Mechanistic proposal for Ag(I)ꢀcatalyzed CꢀSe bond formation.
387
19

Page 20 of 24
388
Table 1.Standardization of reaction parameters for phenylselenylation of alkynes.a
SePh
O
Catalyst
N SePh
Solvent, Temp.
MeO
MeO
2a
O
3aa
Yield (%)b
1a
Entry Catalyst (mol%)
Base
Solv.
THF
THF
THF
THF
NMP
PhMe
THF
THF
THF
THF
THF
THF
NMP
THF
THF
Time (h)
12
T (oC)
25
1
Ag2CO3(10)
Ag2CO3 (10)
Ag2CO3 (5)
Ag2CO3 (10)
Ag2CO3 (10)
Ag2CO3 (10)
AgNO3 (20)
AgOTf (20)
CuI (10)
0
2
12
66
95
72
78
62
43
85
95
26
20
0
3
12
66
4
10
66
5
12
100
100
66
6
12
7
12
8
K2CO3
K2CO3
K2CO3
K2CO3
12
66
9
12
66
10
11
12
13
14
15
CuBr (10)
12
66
Ni(acac)2 (10)
12
66
Ru(PPh3)3Cl2 (5) K2CO3
Co(acac)2 (10) K2CO3
12
66
trace
0
12
100
66
Fe nps (1 equiv.) K2CO3
K2CO3
12
0
12
66
0
389
390
391
392
a An equimolecular mixture of 4ꢀmethoxy phenyl acetylene (0.3 mmol) and Nꢀ
(phenylseleno)phthalimide (0.3 mmol) was subjected to reaction under various reaction
conditions. b Yields refer to the those of isolated purified product.
393
394
395
396
397
20

Page 21 of 24
398
Table 2. Silver catalyzed phenylselenylation of alkynes.
O
Ag2CO3 (10 mol%)
N SePh
R
R
SePh
3aa-3ai
THF, reflux, 12 h
O
2a-2i
1a
Entrya
Alkyne
2a
Product
3aa
Yield (%)b
1
2
95
90
3ab
2b
3
4
3ac
3ad
2c
2d
92
90
95
75
5
6
3ae
3af
2e
2f
7
3ag
92
90
89
2g
3ah
3ai
8
9
2h
2i
399
400
401
402
aA mixture of alkyne (0.3 mmol), Nꢀ(phenylseleno)phthalimide (0.3 mmol) and Ag2CO3 (10
mol%) was refluxed in dry THF for 12 h. bIsolated yields of the products after column
purification.
403
404
405
406
21

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407
Table 3. Optimization of the reaction conditions for phenylselenylation of organoboronic acid.
408
409
410
411
aA mixture of organoboronic acid (4a, 0.3 mmol), Nꢀ(phenylseleno)phthalimide (0.3 mmol),
K2CO3 (0.3 mmol) was refluxed in dry THF in the presence of silver catalyst for 12 h. b
Isolated yields of the product after column purification.
412
413
414
415
416
417
418
419
420
421
422
22

Page 23 of 24
423
Table 4. CꢀSe cross coupling of organoboronic acids with NPSP.
O
AgNO3 (20 mol%)
N SePh
R B(OH)2
R-SePh
K2CO3 (1 equiv)
THF, reflux, 12 h
5aa-5ai
4a-4i
O
1a
Entrya
Boronic acid
Product
Yield (%)b
1
2
3
96
85
5aa
5ab
4a
4b
5ac
5ad
89
97
4c
4d
4
5
6
5ae
5af
92
90
93
80
4e
4f
7
4g
5ag
5ah
5ai
4h
4i
8
9
74
424
425
426
427
aA mixture of organoboronic acid (0.3 mmol), Nꢀ(phenylseleno)phthalimide (0.3 mmol),
K2CO3 (0.3 mmol ) and AgNO3 (20 mol% ) was refluxed in dry THF for 12 h. b Isolated
yields of the product after column purification.
428
429
430
431
23

Page 24 of 24
432
Chart 1. The structures of alkynes, alkynyl selenides, boronic acids and diaryl selenides.
B(OH)2
SePh
SePh
O
O
MeO
MeO
2a
5aa
5ab
3aa
4a
SePh
SePh
B(OH)2
SePh
F3CO
F3CO
OMe
OMe
3ab
4b
2b
B(OH)2
SePh
4c
5ac
2c
3ac
F
F
SePh
CF3
CF3
B(OH)2
5ad
4d
SePh
3ad
2d
SePh
B(OH)2
SePh
SePh
MeO
MeO
2e
5ae
3ae
SePh
4e
B(OH)2
O
S
2f
O
5af
S
4f
3af
SePh
SePh
5ag
B(OH)2
4g
2g
3ag
EtO2C
B(OH)2
SePh
SePh
EtO2C
3ah
2h
5ah
NO2
NO2
4h
H
SePh
SePh
B(OH)2
Ph
Ph
O
3ai
O
5ai
2i
4i
433
24