Cyclization Reactions with Vinyl Selenones
FULL PAPER
corresponding tosylamides 16a and 16c and employing the
vinyl selenone 3a (Table 4, entries 1–3). In the case of cyclo-
hexanediamine 16b, the piperazine 17b was isolated after
benzoylation.[6a]
inal chemistry.[2] Owing to the ready availability of the start-
ing material and to the extremely simple operational proce-
dure, the present method compares favorably with other
methods reported in the literature. Moreover, the present
investigation represents the first
example of the use of vinyl se-
Table 4. Synthesis of enantiopure piperazines, thiomorpholine, benzodiazepine, and benzoxazepine.
lenones in the synthesis of six-
or seven-membered heterocy-
clic rings through a MIRC reac-
tion.
Entry Selenone
Substrate
Conditions
Product
Yield [%]
99
1
NaH, CH2Cl2, 08C to RT, 15 h
Experiments in which more
substituted vinyl selenones are
used as starting products are
under investigation in our labo-
ratory
2
NaH,CH2Cl2, 08C to RT, 15 h[a]
45
3
4
DBU, toluene, 08C to RT, 15 h[b]
Et3N, CH2Cl2, 08C to RT, 15 h[c]
57
92
Experimental Section
General: All new compounds were
characterized by GC-MS and 1H and
13C NMR spectroscopic analyses. 1H
and 13C NMR spectra were recorded
at 400 and 100.62 MHz, respectively,
with a Bruker DRX 400 instrument.
Unless otherwise specified, CDCl3 was
used as the solvent; J values are given
in Hertz. GC analyses and MS spectra
were recorded with an HP 6890 gas
chromatograph (25 m dimethyl sili-
cone capillary column) equipped with
an HP 5973 Mass-Selective Detector
at an ionizing voltage of 70 eV. For the
ions containing selenium, only the
peaks arising from the selenium-80
isotope are given. Optical rotations
5
NaH, CH2Cl2, 08C to RT, 24 h[d]
NaH, CH2Cl2, 08C to RT, 2 d[e]
80
6
80
[a] Isolated after benzoylation.[6a] [b] A second equivalent of selenone was added and 3 equiv of DBU were
used. [c] 2.8 equiv of Et3N were used. [d] 3.5 equiv of NaH were used. [e] 5.5 equiv of NaH were used.
By using a similar procedure, reactions were also carried
out starting from b-aminothiol 16d and vinyl selenone 3a.
The expected thiomorpholine 17d was obtained in excellent
yield using triethylamine as base (Table 4, entry 4).
were measured in a 50 mm cell with a Jasco DIP-1000 digital polarimeter.
Enantiomeric purity was determined by HPLC performed with a HP
1100 instrument equipped with
a chiral column (Chiralpack AD-H
Finally, we applied this procedure to the synthesis of
seven-membered 1,4-heterocycles fused to an aromatic
group, such as 1,4-benzodiazepine. These compounds pres-
ent interesting therapeutic activities,[22] including dampening
of the central nervous system, and can act as a muscle relax-
ant. Employing the N-tosyl-1,3-diamine 16e and the N-
tosyl-1,3-amino alcohol 16 f, the 1,4-benzodiazepine 17e and
1,4-benzoxazepine 17 f, respectively, were obtained in excel-
lent yields (Table 4, entries 5 and 6).
column) and a UV detector. Elemental analyses were carried out with a
Carlo Erba 1106 Elemental Analyzer. Flash column chromatography was
performed using Merk silica gel 60 (230–400 mesh).
Starting materials: Vinylselenones 3a–c were prepared according to the
procedure reported by us previously (Scheme 1).[13–17] Enantiopure mono-
substituted 1,2-diol 4a and disubstituted 1,2-diols 4b–d are commercially
available. The N-tosyl derivatives of b-amino alcohols 11a and 11c were
prepared by treatment of (R)-phenylglycinol and methyl l-serinate hy-
drochloride, which are both commercially available, with tosyl chloride,
DMAP, and triethylamine in dichloromethane, according to the proce-
dure described in the literature.[18] The N-benzyl derivative of b-amino al-
cohol 11b was prepared by condensation of (R)-phenylglycinol with ben-
zaldeyde followed by reduction of the obtained oxazolidine in situ.[19]
Conclusion
General procedure for the synthesis of dioxanes 7a–h and 8c–h: A
stirred solution of enantiopure diol 4a–d (1 mmol) in CH2Cl2 (6 mL) was
treated with NaH (1.2 mmol) at 08C under argon (see differences in
A novel and concise synthetic route to enantiomerically
pure substituted 1,4-dioxanes, morpholines, and piperazines
starting from vinyl selenones and commercially available
enantiopure 1,2-diols, amino alcohols, and diamines is de-
scribed. This simple one-step procedure can also be extend-
ed to the preparation of enantiomerically pure thiomorpho-
lines, 1,4-benzoxazepine, and 1,4-benzodiazepine. All of
these compounds have very important applications in medic-
Table 2, entry 5). After 10 min,
a solution of vinyl selenone 3a–c
(1.2 mmol) in CH2Cl2 (3 mL) was added and the reaction was allowed to
warm to RT and stirred for the times indicated in the Table 2. The reac-
tion mixture was poured into aqueous ammonium chloride and extracted
with CH2Cl2, washed with water and brine, dried over Na2SO4, filtered,
and evaporated under vacuum. Reaction products were obtained in pure
form after flash column chromatography of the residue on silica gel. The
reaction products 7a–h and 8c–h and the reaction yields are reported in
Table 2. Starting from selenone 3b, the acetals 10c–e were also obtained
Chem. Eur. J. 2011, 17, 993 – 999
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
997