Diastereo and enantioselective synthesis of 1,2-diols promoted by electrophilic selenium reagents

Article abstract of DOI:10.1080/10426500801900881

Here we report the first example in which the phenylseleno group is directly substituted by a hydroxy function. The reaction is promoted by the PhSeOSO3H generated "in situ" by oxidation of (PhSe)2 with (NH4)2S2O8 at reflux in a 3:1 mixture of MeCN-H2O. I

Full text of DOI:10.1080/10426500801900881

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Diastereo and Enantioselective
Synthesis of 1,2-Diols
Promoted by Electrophilic
Selenium Reagents
C. Santi a , M. Tiecco a , L. Testaferri a , C. Tomassini
a , S. Santoro a & G. Bizzoca a
a Dipartimento di Chimica e Tecnologia del Farmaco.
Sezione di Chimica Organica , University of Perugia ,
Italy
Published online: 29 Oct 2008.
To cite this article: C. Santi , M. Tiecco , L. Testaferri , C. Tomassini , S. Santoro &
G. Bizzoca (2008) Diastereo and Enantioselective Synthesis of 1,2-Diols Promoted
by Electrophilic Selenium Reagents, Phosphorus, Sulfur, and Silicon and the Related
Elements, 183:4, 956-960, DOI: 10.1080/10426500801900881
To link to this article: http://dx.doi.org/10.1080/10426500801900881
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Phosphorus, Sulfur, and Silicon, 183:956–960, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500801900881
Diastereo and Enantioselective Synthesis of 1,2-Diols
Promoted by Electrophilic Selenium Reagents
C. Santi, M. Tiecco, L. Testaferri, C. Tomassini, S. Santoro,
and G. Bizzoca
Dipartimento di Chimica e Tecnologia del Farmaco. Sezione di Chimica
Organica. University of Perugia, Italy
Here we report the first example in which the phenylseleno group is directly substi-
tuted by a hydroxy function. The reaction is promoted by the PhSeOSO H gener-
3
ated “in situ” by oxidation of (PhSe) with (NH ) S O at reflux in a 3:1 mixture
2
4 2 2 8
of MeCN-H O. Interestingly the reaction can be performed in “one pot” using a cat-
2
alytic amount of diselenide affording the corresponding diols (5 and 6) with good
yield and good level of diastereo- and enantioselectivity.
Keywords Asymmetric synthesis; catalysis; selenium; 1,2-Diols
INTRODUCTION
In recent years, we,1 as well other research groups2 have studied
the application of electrophilic selenium species in diastereo and
enantioselective synthesis using chiral non racemic selenenylating
species extensively. One of the most attractive features of the selenium
chemistry is the possibility to manipulate the organoselenium moiety
affording, depending on the structure of the molecule, elimination,3,4
or substitution derivatives.5
A different approach for the synthesis of enantiomerically pure
β-hydroxyselenides is now proposed starting from unsatured natural
terpenes. According to the “chiral pool approach,” terpenes can be
considered convenient starting materials in asymmetric synthesis
because they are commercially available, not expensive and generally
easily accessible in both the enantiomeric forms.
Financial support from MIUR, National Projects PRIN2003, PRIN2005 and
FIRB2001, Consorzio CINMPIS, Bari and University of Perugia is gratefully acknowl-
edged.
Address correspondence to C. Santi, Dipartimento di Chimica e Tecnologia del Far-
maco. Sezione di Chimica Organica, University of Perugia, via del Liceo, 06100 Perugia,
Italy. E-mail: santi@unipg.it
956

Synthesis of 1,2-Diols Promoted by Electrophilic Selenium Reagents
957
TABLE I Reaction of Terpenes with PhSeOTf
and H2O at 20◦C
Entry Terpene
1
Products
Time (h)
24
Yield
50% 2a
2
3
24
40
70% 2b
40% 2c 56% 3c
RESULTS AND DISCUSSION
The hydroxyselenenylation of unsatured terpenes can be obtained by
treatment with PhSeOTf in a 3:1 mixture of MeCN-H2O at 20◦C. In a
typical experiment, silver triflate (1.1 mmol) was added to a solution of
PhSeBr (1.0 mmol) in MeCN (2.0 mL) at 0◦C. The reaction was stirred
for 30 min and then 1.0 mmol of the terpene 1a–c was added in a 1:1
mixture of MeCN-H2O (2.0 mL). The mixture was allowed to gradually
reach room temperature. The progress of the reaction was monitored by
TLC and GC-MS. Reaction times, chemical yields and diastereomeric
ratios are reported in Table I.
Starting from (+)-3-carene 1a (Table I, entry 1) and (+)-p-menth-1-
ene 1b (Table I, entry 2) the reaction leads to the stereospecific forma-
tion of compounds 2a and 2b, respectively, deriving from the attack of
the electrophilic selenium reagent from the less hindered face of the
double bond. When the addition occurs in an exocyclic olefin, as in the
case of (+)-aromadendrene 1c (Table I, entry 3), a lower diastereoselec-
tivity has been observed and the two isomers 2c and 3c were obtained
in a ratio of 42:58. The absolute configurations reported in Table I were
assigned by proton NMR on the basis of the coupling constants and
some n.O.e. correlations that are summarized in Scheme 1.

958
C. Santi et al.
SCHEME 1
We already observed that alkyl phenyl selenides, by reaction with
ammonium persulfate, suffer deselenenylation giving the substitution3
or elimination5 products depending on the reaction conditions and the
nature of the substrate. Treatment of 2a–c and 3c with ammonium
persulfate in a 3:1 mixture of MeCN-H2O at 85◦C affords the formation
of the corresponding 1,2-diols in good yields only in the case of the
menthene derivative 2b. In all the other cases, only small amounts of
the deselenenylation products were observed (Scheme 2).
SCHEME 2
Based on these preliminary results, we investigated the first example
of a multi-step one-pot selenium mediated synthesis of 1,2-diols. The
reaction is promoted by the ArSeOSO3H generated in situ by oxidation
of diselenide 7 or 8 with (NH4)2S2O8 at reflux in a 3:1 mixture of MeCN-
H2O and presumably proceeds according to the mechanism reported on
Scheme 3.
The results summarized in Table II clearly indicate that the reaction
leads to the formation of a couple of diols (5,6) in a ratio that depends
on the nature of the substrate. A stoichiometric amount of the catalyst
(7) affects the yields and the diastereoselectivity positively, and in all
the cases, at the end of the reaction, it can be completely recovered.
By replacing diphenyl diselenide with the chiral di-6-[(1S)-1-
methylthio]ethyl]phenyl] diselenide (8) the 1-phenylcyclohexene can
be stereospecifically converted into the corresponding cis-1,2-diol with
good yield and excellent facial selectivity (Table II, entry 8).

Synthesis of 1,2-Diols Promoted by Electrophilic Selenium Reagents
959
SCHEME 3
CONCLUSIONS
To the best of our knowledge, this is the first example in which the
phenylseleno group is directly substituted by a hydroxy function. The
reaction can be realized in “one pot” using the diselenide as catalyst
in the presence of an excess of ammonium persulfate affording the for-
mation of enantiomerically enriched diols. Further applications of this
reaction are actually under investigation.
EXPERIMENTAL6
All the starting materials were commercial products and were used
without further purification. In a typical procedure to a solution of dis-
elenide (0.05 mmol or 0.5 mmol) and ammonium persulfate (3 mmol) in
TABLE II One-Pot Selenium Mediated Synthesis of 1,2-Diols
Entry
R
R1
Diselenide (%)
5/6
Yield (%)
Ee (%)
1
2
3
4
5
6
7
8
Me
Me
Me
Me
Ph
Ph
Ph
Ph
i-Pr
i-Pr
H
H
H
H
H
H
7 (10)
7 (100)
7 (10)
7 (100)
7 (10)
7 (100)
8 (10)
35:65
30:70
72:28
80:20
65:35
95:5
60
90
35
90
37
85
40
80
100 (5) 100 (6)
100 (5) 100 (6)
—
—
—
—
20(5)
99 (5)
100:0
100:0
8 (100)

960
C. Santi et al.
MeCN (3 mL) and water (1 mL) 1 mmol of olefin 1 was added. The re-
action was stirred at reflux for 12–24 h. The crude product was purified
by flash chromatography on a silica gel column using a mixture of di-
ethyl ether-dichloromethane (99:1) as eluant. All the compounds were
fully characterized by 1H-NMR, 13C-NMR experiments and by GC-MS
analysis. Selected physical and spectral data are reported below.
(1S, 2S)-1-Phenyl-1,2-dihydroxycyclohexane7
C12H16O2, Oil [α]2D0.8 = −12.8 (c=0.52, CHCl3) IR (HATAR): ν(2OH) =
3504.99 cm−1; 1H NMR δ 7.55–7.50 ppm (m, 2H, 2CHAr), 7.40–7.35 (m,
3
3
2H, 2CHAr), 7.30–7.25 (m, 1H, CHAr), 3.99 (dd, 1H, J=4.5 Hz, J =
11.0 Hz, CHOH), 2.70–2.60 (br, s, OH), 1.90–1.80 (m, 3H), 1.80–1.60
(m, 4H), 1.60–1.50 (m, 1H), 1.45–1.40 (m, 1H); 13C NMR δ 146.3, 128.4,
126.9, 125.1, 75.7, 74.5, 38.5 29.2, 24.3, 21.0; GC-MS (70 eV): m/z (%):
192 (73) [M+.], 174 (31), 145 (16), 133 (100), 120 (50), 105 (66), 91 (22),
77 (39), 70 (13), 55 (24).
REFERENCES AND NOTES
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Temperini, Chem. Eur. J., 8, 1118 (2002); (b) M. Tiecco, L. Testaferri, C. Santi, C.
Tomassini, F. Marini, L. Bagnoli, and A. Temperini, Angew. Chem. Int. Ed., 42, 3131
(2003); (c) M. Tiecco, L. Testaferri, C. Santi, C. Tomassini, S. Santoro, F. Marini, L.
Bagnoli, A. Temperini, and F. Costantino Eur. J. Org. Chem. 4867 (2006); (d) M.
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A. Temperini Org. Lett., 6, 4751 (2004).
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3742 (2000).
[3] (a) M. Tiecco, L. Testaferri, M. Tingoli, and F. Marini Synlett, 373 (1994), and refer-
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(1998).
[5] M. Tiecco, L. Testaferri, M. Tingoli, and F. Marini, J. Org. Chem., 56, 5207 (1991),
and references cited therein.
[6] 1H and 13C NMR spectra were recorded at 400 and 100.62 MHz, respectively, on a
Bruker Avance-DRX 400 instrument. Unless otherwise specified, CDCl3 was used
as the solvent and TMS as internal standard. GC-MS analyses were carried out with
an HP-6890 gas chromatograph (dimethyl silicone column, 12.5 m) equipped with an
HP-5973 mass-selective detector. IR spectra were recorded on a JASCO FT/IR-410
spectrophotometer using a multiple reflection horizontal ATR (HATR) accessory.
Optical rotations were measured with a JASCO DIP-1000 digital polarimeter.
[7] S. Jonsson, H. Adolfsson, and J.-E. Backvall, Org. Lett., 3, 3463 (2001).