β-Cyclodextrin-promoted addition of benzeneselenol to conjugated alkenes in water

Article abstract of DOI:10.1002/hlca.200800378

For the first time, a mild and efficient procedure was developed for the conjugate addition of α,β-unsaturated compounds to benzeneselenol providing β-(phenylseleno)-substituted compounds (Scheme). The reaction was promoted by β-cyclodextrin, proceeded in

Full text of DOI:10.1002/hlca.200800378

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Helvetica Chimica Acta – Vol. 92 (2009)
b-Cyclodextrin-Promoted Addition of Benzeneselenol to Conjugated Alkenes
in Water
by Boga Srinivas, Vydyula Pavan Kumar, Regati Sridhar, Vutukuri Prakash Reddy,
Yadavalli Venkata Durga Nageswar, and Kakulapati Rama Rao*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500007, India
(
phone: þ 91-40-27193164; e-mail: drkrrao@yahoo.com)
For the first time, a mild and efficient procedure was developed for the conjugate addition of a,b-
unsaturated compounds to benzeneselenol providing b-(phenylseleno)-substituted compounds
(
Scheme). The reaction was promoted by b-cyclodextrin, proceeded in H O at room temperature, and
2
gave impressive yields (Table). The mechanism of the addition reaction, taking place within the
1
cyclodextrin cavity, was supported by the analysis of the guests and host signals in the H-NMR spectra
(
Fig. 1).
Introduction. – CꢀSe Bond containing compounds are of great importance in
organic synthesis as key intermediates in various reactions [1]. In particular, b-
phenylseleno)-substituted carbonyl compounds are well established as potential
(
enone b-anion equivalents [2]; however, the reported methodologies for the synthesis
of these compounds are very limited [3]. In general, b-(phenylseleno)-substituted
carbonyl compounds are synthesized by the conjugate addition of benzeneselenol
generated in situ from diphenyl diselenide to olefins [4]. Even in these reactions, the
yields are not satisfactory, being low to moderate in most of the cases, and anhydrous
solvents and toxic reagents are involved. These conjugate additions also proceed by the
in situ formation of benzeneselenol from diphenyl diselenide in the presence of
catalysts such as La/I [5a], Na/Me SiCl [5b], In/Me SiCl [5c], etc. Apart from this,
2
3
3
benzeneselenol itself is sensitive to air [5d]. Thus, in view of these shortcomings, there
is a need to develop a mild and environmentally friendly synthetic procedure for these
high-value compounds, starting directly from benzeneselenol, if possible, and replacing
organic solvents, most of which are flammable, toxic, or carcinogenic, by H O in the
2
presence of a recyclable activator as part of a green-chemical approach [6]. To achieve
these ideal conditions, the best choice appeared to be a supramolecular catalysis
involving cyclodextrins wherein benzeneselenol can be encapsulated in the hydro-
phobic cavity thus allowing to carry out the reaction in H O.
2
Cyclodextrins (CDs) are cyclic oligosaccharides possessing hydrophobic cavities
which bind substrates selectively and catalyze chemical reactions with high selectivity.
They catalyze reactions by supramolecular catalysis involving reversible formation of
host – guest complexes by noncovalent bonding as seen in enzymes. Complexation
depends on the size, shape, and hydrophobicity of the guest molecule. Thus, mimicking
biochemical selectivity, which is due to the orientation of the substrate by complex
formation thus making available only certain regions of the guest to a favorable attack,
ꢀ
2009 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 92 (2009)
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will be superior to chemical selectivity which involves random attack. Our earlier
expertise in the field of biomimetic modeling of organic chemical reactions involving
cyclodextrins [7] prompted us to attempt the conjugate addition of olefins to
benzeneselenol under biomimetic conditions in the presence of cyclodextrins and in
the solvent H O at room temperature (Scheme).
2
Scheme. Addition of Benzeneselenol to Conjugated Alkenes
Results and Discussions. – In general, the conjugate addition reaction was carried
out by dissolving b-cyclodextrin (b-CD) in H O and then adding successively the
2
benzeneselenol and the olefin while stirring at room temperature to give the
corresponding Michael adduct in impressive yields (Table). The reaction went on
smoothly at room temperature. The catalyst b-CD was easily recovered and could be
reused. Though a b-CD complex with benzeneselenol was formed in situ, it was
prepared separately, and the ratio b-CD/benzeneselenol was found to be 1:1 from the
amount of benzeneselenol extracted from the known amount of the complex. These
addition reactions did not proceed in the absence of b-CD. The products were
1
characterized by their H-NMR, MS, and IR data and compared with the known
compounds [4] (see the Table).
This is the first practically feasible conjugate addition of benzeneselenol with a
variety of conjugated alkenes in H O, proceeding efficiently at room temperature
2
without the need of any acid or base catalyst. The methodology can be applied to
various a,b-unsaturated ketones, esters, and nitriles under mild reaction conditions.
Moreover, these conjugate additions are clean with impressive yields compared to
conventional methods, have shorter reaction times and higher selectivities, and involve
a recyclable catalyst [7].
In this new biomimetic methodology, the catalyst b-CD plays a decisive role not
only by activating the benzeneselenol but also by promoting its conjugate addition due
to the formation of an inclusion complex. The mode of addition of benzeneselenol to
1
a,b-unsaturated alkenes via the b-CD complex was deduced from a H-NMR analysis,
one of the most important techniques used for the characterization of inclusion
complexes, by revealing chemical-shift changes in the resonances of the host (b-CD)
1
and the guest protons [7][8]. Thus, a comparison of the H-NMR spectra (D O; Fig. 1)
2
of b-CD and of the b-CD/benzeneselenol complex showed an upfield shift of HꢀC(3)
(
Dd 0.02) and HꢀC(5) (Dd 0.018) of b-CD in the b-CD/benzeneselenol complex as
compared to b-CD, indicating the formation of an inclusion complex of benzeneselenol
from the secondary (more open) side of b-CD. An upfield shift of CH (6) of b-CD (Dd
2
0.034) was further observed in the spectra of the freeze-dried reaction mixture of the b-
CD/benzeneselenol complex with methyl vinyl ketone (MVK) after 15 min, indicating
that the complexation of MVK takes place from the primary (more closed) side of b-

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Helvetica Chimica Acta – Vol. 92 (2009)
Table. Addition of Benzeneselenol to Conjugated Olefines in H O in the Presence of b-CD
2
Entry
1
Olefine
Product
Time [min]
20
Yield [%]
88
Ref.
[4g]
2
3
25
20
86
85
[4a]
[4a]
4
5
6
7
8
25
45
25
45
30
86
82
86
80
80
[4a]
[4a]
[4a]
[4a]
–
9
45
45
82
80
[4g]
[4g]
1
0
1
CD. These H-NMR data clearly demonstrate that the MVK is elegantly set for the
addition reaction with the benzeneselenol in the hydrophobic microenvironment of the
b-CD cavity (Fig. 2).
Conclusions. – The b-CD mediated addition reactions of benzeneselenol to
conjugated alkenes in H O are very useful both from an economical and an
2
environmental point of view. b-CD, apart from being nontoxic, is also considered as
metabolically safe [9]. In contrast to the existing addition reactions with diselenides,
which are activated by metal catalysts, our addition reaction is a straightforward
transformation starting directly from benzeneselenol and the alkene in the solvent H O
2
and in the presence of b-CD as the reusable catalyst.

Helvetica Chimica Acta – Vol. 92 (2009)
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Fig. 1. 1H-NMR Spectra (D O, 258) of a) b-CD, b) the b-CD/benzeneselenol complex, and c) the reaction
2
mixture of the b-CD/benzeneselenol complex and methyl vinyl ketone after 15 min
Fig. 2. Supramolecular addition of benzeneselenol to conjugated alkenes
within b-CD
B. S., V. P. K. , R. S., and V. P. R. thank CSIR, New Delhi, India, for the award of research fellowships.
Experimental Part
General. All reactions were carried out in an atmosphere of air without any special precautions.
1
Chemicals were purchased from Aldrich and S. D. Fine Chemicals and used as received. H-NMR
Spectra: Varian 200 or Brucker 300 spectrometer; d in ppm rel. to Me Si as internal standard, J in Hz. IR
4
ꢀ1
Spectra: Nicolet FT-IR spectrometer; in cm . MS: V.G.-Auto spectrometer; in m/z (rel. %).
General Procedure. Procedure exemplified by 3-(phenylseleno)propanamide (Table, Entry 8): To a
soln. of b-CD (113.4 mg, 0.1 mmol) in H O (15 ml), benzeneselenol (106 ml, 1 mmol) in acetone (1 ml)
2
was added dropwise at r.t. Prop-2-enamide (71 mg, 1 mmol) was then added and stirred until the reaction
was complete (Table). The org. material was extracted with AcOEt, the extract dried and concentrated,
and the resulting crude product further purified by recrystallization from AcOEt: 182 mg (80%) of pure
3
-(phenylseleno)propanamide. White solid. HPLC (C18 column, H O/MeCN 7:3 with 0.1% H PO , flow
2
3
4

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rate 0.7 ml/min, det. at 220 nm): purity > 98%. M.p. 103 – 1058. IR: 3375, 3182, 2929, 1652. H-NMR
(
3
300 MHz, CDCl ): 2.60 (t, J ¼ 7.5, 15.1, 2 H); 3.14 (t, J ¼ 7.6, 14.3, 2 H); 5.58 (br., NH ); 7.22 – 7.33 (m,
3
2
13
H); 7.45 – 7.57 (m, 2 H). C-NMR (75 MHz, CDCl ): 23; 36; 127; 128; 129; 133; 174. MS: 229 ([M þ
3
þ
H] ). Anal. calc. for C H NOSe (228.15): C 47.38, H 4.86; found: C 47.35, H 4.95.
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Received October 15, 2008