Kinetic resolution of allylic alcohols promoted by electrophilic selenium reagents

Article abstract of DOI:10.1080/10426500590906355

The first example of a kinetic resolution process promoted by an electrophilic selenium reagent is reported. Racemic allylic alcohols react with half equivalents of a selenenylating agent in methanol leading to the regiospecific formation of the corresponding addition products with a very high level of facial selectivity (98% de). The unreacted alcohol can be recovered in a optically enriched form (92% ee). Copyright Taylor & Francis Inc.

Full text of DOI:10.1080/10426500590906355

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Kinetic Resolution of Allylic
Alcohols Promoted by
Electrophilic Selenium
Reagents
C. Santi a , M. Tiecco a , L. Testaferri a , C. Tomassini
a , F. Marini a , L. Bagnoli a & A. Temperini a
a Dipartimento di Chimica e Tecnologia del Farmaco,
Sezione di Chimica Organica, University of Perugia ,
via del Liceo, Perugia, 06100, Canada
Published online: 01 Feb 2007.
To cite this article: C. Santi , M. Tiecco , L. Testaferri , C. Tomassini , F. Marini ,
L. Bagnoli & A. Temperini (2005) Kinetic Resolution of Allylic Alcohols Promoted by
Electrophilic Selenium Reagents, Phosphorus, Sulfur, and Silicon and the Related
Elements, 180:3-4, 1071-1075, DOI: 10.1080/10426500590906355
To link to this article: http://dx.doi.org/10.1080/10426500590906355
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Phosphorus, Sulfur, and Silicon, 180:1071–1075, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500590906355
Kinetic Resolution of Allylic Alcohols Promoted
by Electrophilic Selenium Reagents
C. Santi
M. Tiecco
L. Testaferri
C. Tomassini
F. Marini
L. Bagnoli
A. Temperini
Dipartimento di Chimica e Tecnologia del Farmaco, Sezione di Chimica
Organica, University of Perugia, via del Liceo, 06100 Perugia, Italy
The first example of a kinetic resolution process promoted by an electrophilic sele-
nium reagent is reported. Racemic allylic alcohols react with half equivalents of a
selenenylating agent in methanol leading to the regiospecific formation of the cor-
responding addition products with a very high level of facial selectivity (98% de).
The unreacted alcohol can be recovered in a optically enriched form (92% ee).
Keywords Chiral diselenide; kinetic resolution; selenoadditions
INTRODUCTION
During the last 10 years, several research groups have described the
synthesis of a number of chiral nonracemic diselenides which can be
transformed in situ into electrophilic selenenylating agents to effect
efficient asymmetric synthesis.1−3 A common characteristic of all these
optically active diselenides is the close proximity of an oxygen or a
nitrogen atom to the selenium atom. We recently reported a new class
of chiral diselenides containing a sulphur atom in the chiral moiety.
On the basis of several experimental evidences it was deduced that the
Received February 23, 2004; accepted October 4, 2004.
Financial support from MIUR, National Project “Stereoselezione in Sintesi Organica.
Metodologie ed Applicazioni,” FIRB Project RBNE01MTYS-007, and from the University
of Perugia, Progetti di Ateneo is greatfully aknowledged.
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
1071

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C. Santi et al.
interaction of selenium with the sulphur atom probably could be more
important than those with oxygen or nitrogen.4−7
The di-2-[methoxy-6-[(1S)-1-methylthio]ethyl]phenyl] diselenide 1 is
a suitable precursor for very efficient electrophilic reagents.5−6 Treat-
ment of 1 with bromine in diethyl ether leads to the precipitation of the
corresponding bromide 2 as a red-yellow solid that can be fully charac-
terized by 1H-NMR 13C-NMR and 77Se-NMR experiments.
SCHEME 1
We now report that the electrophilic species aryl selenenyl triflate 3,
prepared from 2 by reaction with AgOTf in CH2Cl2 at 0◦C, can be used to
effect the kinetic resolution of racemic allylic alcohols (R,S)-4 (Scheme
2) through a methoxyselenenylation reaction. To the best of our knowl-
edge this is the first example of a kinetic resolution promoted by an
organoselenium reagent from which a very common class of organic
substrates can be obtained in an enantiomerically enriched form.
Two equivalents of the racemic allylic alcohol (R,S)-4 react with 1 eq
of the selenenylating reagent 3 in a mixture of CH2Cl2/MeOH (10:1) at
−30◦C, affording the addition product 5 with complete regioselectivity
and a very high facial selectivity (45% de). From the reaction mixture
the unreacted alcohol (S)-4 can be recovered in 88% yield and in an
enantiomerically enriched form (92% ee). The enantiomeric excess has
1
been determined by recording the H-NMR spectra in the presence of
(S)-(+)-2,2,2-trifluoro-1-(9-antryl)-ethanol.
SCHEME 2

Selenium-Promoted Resolution of Allylic Alcohols
1073
The geometry and the absolute configuration of the adduct 5 were
assigned by radical deselenenylation promoted by triphenyltin hydride
and AIBN in refluxing benzene (Scheme 3) affording the derivative 6.8
Furthermore, the resolution process can be completed by transform-
ing the organoselenium compound 5 into the corresponding starting
allylic alcohol (R)-4 (98% ee) by treatment with CF3SO3H and styrene
at room temperature.
SCHEME 3
In order to investigate the regioselectivity of the process we re-
peated the reaction starting from the mono substituted alkenes 7a–b
(Scheme 4). Even if in these substrates the facial selectivity was very
low, in both cases the addition to the double bound resulted completely
regiospecific and only the anti-Markovnicov regioisomers were obtained
in a diasteroisomeric ratios of 60:40.
SCHEME 4
These results seem to indicate an active participation of the hydroxy
group in governing the attack of the electrophilic reagents to the double
bond by giving rise to a Se O stabilizing interaction. Carrying out the
reaction of 7a in the presence of silica gel the intramolecular Se O in-
teraction becomes less important and the regioselectivity decreases, the
Markovnicov and the anti Markovnicov regioisomers are in fact formed
in a ratios of 30:70. In conclusion we report a simple procedure to effect
efficient kinetic resolution of allylic alcohols using an organoselenium

1074
C. Santi et al.
reagent under very mild conditions. The application of the present pro-
cedure to other kind of substrates is under investigation.
EXPERIMENTAL
Starting allylic alcohols (R,S)-7a and (R,S)-7b were commercial prod-
ucts and were used without further purification. Compound (R,S)-4
was prepared starting from the corresponding ketone by reduction with
LiAlH4 in Et2O at 0◦C.
The kinetic resolution experiments were carried out as follows: 0.5
mmol of AgOTf were added to a solution of the bromide 2 in CH2Cl2
(3mL) at 0◦C and the mixture was cooled at −30◦C. The allylic alco-
hol (1 mmol), dissolved in 0.3 mL of methanol was added. The reaction
was stirred for 12 h at the same temperature and then poured into a
10% solution of NaHCO3. The crude product was purified by flash chro-
matography on a silica gel column using a mixture of dichloromethane
methanol (99:1) as eluant. All the compounds were fully characterized
1
by H-NMR, 13C-NMR experiments, and by GC-MS analysis. Selected
physical and spectral data are reported below. 1H- and 13C-NMR were
recorded in a Bruker Advance DRX-400 spectrometer. Optical rotations
were measured with a JASCO DIP-1000 digital polarimeter.
(2R,3S,4R)-4-Methoxy-3-(2-methoxy-6-[(1R)-1-(methylsulfa-
nyl)ethyl]phenylselanyl)-4-phenylbutan-2-ol (5): Oil, 1H NMR
(CDCl3)δ 7.34–7.25 (m, 4H), 7.18–7.13 (m, 3H), 6.80 (dd, 1H, J = 1.1
and 8.2 Hz), 4.75 (q, 1H, J = 7.0 Hz), 4.52 (d, 1H, J = 5.1 Hz), 4.20 (dq,
1H, J = 1.5 and 6.2 Hz), 3.91 (s, 3H), 3.73 (s, 1H), 3.60 (dd, 1H, J = 1.5
and 5.1 Hz), 3.31 (s, 3H), 1.93 (s, 3H), 1.52 (d, 3H, J = 7.0 Hz),1.35 (d,
3H, J = 6.2 Hz); 13C NMR (CDCl3)δ 160.2, 149.1, 139.9, 129.8, 128.7,
128.5, 128.2, 127.1, 119.8, 109.7, 87.3, 67.4, 58.3, 57.3, 56.4, 44.5, 22.2,
21.6, 14.3
(2S,3E )-4-Phenyl-3-buten-2-ol (S)-4: Oil [α]2D0.8 = −7.8 (c = 0.52,
CHCl3)9
(3R )-1-hepten-3-ol (R)-7: Oil, [α]2D3.3 = −7.2 (c = 0.25, CH3CH2-
OH). Enantiomeric excess was determined by gaschromatography us-
ing an HP 5890 gas chromatograph with a 25 m Chirasilidex capillary
column. The absolute configuration is reported in the literature.
REFERENCES
[1] M.Tiecco, In Topics in Current Chemistry: Organoselenium Chemistry: Modern De-
velopments in Organic Synthesis; T. Wirth, Ed. Electrophilic Selenium, Selenocy-
clizations (Springer-Verlag: Heidelberg, 2000), pp. 7–54.

Selenium-Promoted Resolution of Allylic Alcohols
1075
[2] Back, T. G. Ed. Organoselenium Chemistry-A Pratical Approach (Oxford: New York,
2000).
[3] T. Wirth, Angew. Chem. Int. Ed. 39, 3742 (2000).
[4] M. Tiecco, L. Testaferri, C. Santi, C. Tomassini, F. Marini, L. Bagnoli, and A.
Temperini, Tetrahedron Asymmetry, 11, 4654 (2000).
[5] M. Tiecco, L. Testaferri, C. Santi, C. Tomassini, F. Marini, L. Bagnoli, and A.
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