Regio- and stereoselective ring opening of epoxides with sodium phenylselenide under phase transfer conditions

Article abstract of DOI:10.3184/030823408X282659

The ring opening reaction of a wide range of mono-, di- and trisubstituted epoxides with the phenylselenide anion under PTC conditions provides a simple, mild and efficient method for preparation of β-hydroxy phenylselenides with high regio- and stereoselectivity in yields from 67 to 98%. The reactions are carried out in aqueous NaOH/ THF using aminoiminomethanesulfinic acid (thiourea dioxide, TDO) to generate sodium phenylselenide from diphenyldiselenide.

Full text of DOI:10.3184/030823408X282659

22 RESEARCH PAPER
JANUARY, 22–25
JOURNAL OF CHEMICAL RESEARCH 2008
Regio- and stereoselective ring opening of epoxides with sodium
phenylselenide under phase transfer conditions
Reginaldo Bezerra dos Santos*a, Valdemar Lacerda Juniora, Paulo Roberto Zanottob,
Timothy John Brocksomb and Ursula Brocksomb
aDepartamento de Química, Universidade Federal do Espírito Santo, Vitória - ES, 29075-910, Brazil
bDepartamento de Química, Universidade Federal de São Carlos, C.P. 676, São Carlos - SP, 13565-905, Brazil
The ring opening reaction of a wide range of mono-, di- and trisubstituted epoxides with the phenylselenide anion
under PTC conditions provides a simple, mild and efficient method for preparation of b-hydroxy phenylselenides
with high regio- and stereoselectivity in yields from 67 to 98%. The reactions are carried out in aqueous NaOH/
THF using aminoiminomethanesulfinic acid (thiourea dioxide, TDO) to generate sodium phenylselenide from
diphenyldiselenide.
Keywords: phenylselenide anion, opening of epoxides, thiourea dioxide
The use of arylselenide anions in various synthetic
transformations is based upon the extremely high
nucleophilicity of the selenium anion, coupled with facile
oxidation and elimination reactions.1-4 The phenylselenide
anion has been frequently used in these applications due to the
availability of diphenyldiselenide, phenylselenenyl halides
and benzeneselenol. Several methods for the preparation of
the phenylselenide anion have been reported.5,6
Results and discussion
Epoxides 1 to 7a–e were prepared by standard methodologies
of alkene epoxidation with MCPBA or enone epoxidation
with H2O2 in a basic medium and subsequent functional
group modifications. NaSePh was generated by phase transfer
catalysed (Bun NBr) cleavage of Ph–Se–Se–Ph in 13%
4
aqueous (NaOH/THF), using TDO as the reducing agent, as
depicted in Scheme 1.
The conditions used in generating the phenylselenide anion
involve reduction of diphenyldiselenide with NaBH4 in EtOH/
THF, according to the method of Sharpless.8,9 Liotta10 later
introduced the useful variation of reducing the Se–Se bond
with Nao in refluxing THF followed by solvation in HMPA.
Alternatively reduction of Ph–Se–Se–Ph can be accomplished
with Nao and ultrasound in THF,11 resin bound borohydride,12
LiAlH4,13 NaH in boiling THF,14 sodium formaldehyde
sulfoxylate,15 hypophosphorous acid,16,17 NaBH4/AlCl3
system,18 tributylphosphine and 10% NaOH,19 methyllithium20
In connection with a related study on the epoxidation and
subsequent nucleophilic ring opening reaction of monoterpene
epoxides, we have studied the generation of the phenylselenide
anion in phase transfer catalysis conditions and shown that the
reaction is quite effective in the ring opening of a wide range
of epoxides.
The corresponding b-hydroxy phenylselenides were
obtained in good to excellent yields (Tables 1 and 2), from
a variety of mono-, di- and trisubstituted epoxides of widely
differing steric accessibility. All the products were isolated
and characterised by spectroscopic methods (1H NMR, 13C
NMR and IR) and microanalyses. Compounds 2, 4, 9 and 11
are mixtures of epimers which were not separated.
Nucleophilic attack of phenylselenide anion at the less-
substituted carbon atom was consistently observed in all the
examples shown in Table 1. This afforded the corresponding b-
hydroxy phenylselenides with high regio- and stereoselectivity.
The behaviour of trans-epoxy-carveol 7a and the
derivatives 7b–7e (Scheme 2) when treated with PhSe- also
was studied to evaluate the effect of the protecting group a to
the epoxide (R = Piv, BOM, TBDMS and PMB) on the regio-
and stereoselectivity of the reaction. The results obtained in
these studies are summarised in Table 2.
As can be seen fromTable 2, the regioselectivity of the reaction
is influenced by the steric bulk of the protecting group a to the
epoxide. The nucleophilic attack on epoxides 7b–7d seems to be
controlled by steric effects, which determine the substitution at
the less-branched carbon, as observed for epoxides 1–6, shown in
Table 1. However, without any protection of the hydroxyl group
7a, an inversion of the regioselectivity is found. Nucleophilic
10
in ether or Zn/ZrCl4 system. The deprotonation of PhSeH
with NaH in dry refluxing THF has also been reported.22
The earliest method for generating phenylselenide anions
involves the reaction of diphenyldiselenide with refluxing
aqueous or ethanolic NaOH.23 This method, where three
quarters of the starting diphenyldiselenide are converted
into the phenylselenide anion, is, however, unattractive for
synthetic purposes owing to the drastic reaction conditions
required. It is also reported24,25 that the use of phase transfer
catalysis (PTC) conditions allows this reaction to proceed
under mild conditions. Some synthetic applications of aryl-
and alkylchalcogenides (RS-, RSe- and RTe-) obtained from
the corresponding diorganodichalcogenides by reduction with
aminoiminomethanesulfinic acid (thiourea dioxide, TDO)
have been demonstrated.26
We now describe an alternative method for regio- and
stereoselective nucleophilic ring opening of epoxides with the
phenylselenide anion generated under phase transfer catalysis
(PTC) conditions.
O
H N
2
O
R
1
H
S
H
HO
1
R
2
HN
OH
R
-
3
R
(PhSe)
3
2
PhSe
R
NaOH, H O / THF,
2
R
SePh
2
n
Bu NBr
4
Scheme 1 Nucleophilic ring opening reaction of epoxides with PhSe- in PTC conditions.
* Correspondent. E-mail: belo.ufes@gmail.com
PAPER: 07/5015

JOURNAL OF CHEMICAL RESEARCH 2008 23
OH
SePh
OH
Table 1 Synthesis of b-hydroxy phenylselenides under phase
O
RO
RO
SePh
RO
transfer conditions
-
PhSe
+
Entry
Substrate
Product
Reaction
time/h
Yield/%a
OH
O
7
15
14
PhSe
1
12
12
98
1
8
Scheme 2 Ring opening reaction of trans-epoxy-carveol
derivatives with PhSe-.
O
O
2
75
with a Bomem Michelson model 102 FTIR or with a Bomem Hartman
& Braun MB-Series. H and 13C NMR spectra were recorded either
1
PhSe
on a Bruker ARX-200 (200 MHz), a Bruker ARX-400 (400 MHz)
or a Varian FT-80A (80 MHz) spectrometer at a temperature of
300 K; deuteriochloroform was used as solvent and tetramethylsilane
as internal standard. GC analyses were obtained on a Shimadzu
GC-17A Chromatograph equipped with a DB-1 capillary column
(0.25 mm i.d.x30 m), using a 1.5 ml/min H2 carrier gas flow and a
temperature program from 70°C (for 1 min) to 250°C (for 10 min)
at 8°C/min. Column chromatography was performed on silica gel 60
(70-230 mesh ASTM Merck). Radial thin-layer chromatography
was carried out on a Chromatotron 8924 (silica gel 60PF254 Merck).
Analytical thin-layer chromatography (TLC) was performed on
(10 ¥ 5 cm) glass plates coated with silica gel 60 GF254 Merck:
methods of detection included the use of a UV handlamp, iodine
as well as vanillin acid solution. Optical rotations were taken on a
Perkin-Elmer polarimeter model 241. Microanalyses were performed
on a Fisons EA 1108 CHNS-0 Analyser, at the Department of
Chemistry, UFSCar. Solvents were distilled prior to use.
OH
O
9
2
HO
SePh
O
3
4
12
12
72
71
10
3
OH
OH
OAc
PhSe
O
4
11
OH
O
O
O
O
O
SePh
5
6
48
15
94
90
General procedure for the b-hydroxy phenylselenides
13% aqueous NaOH (7 ml) and TDO (453 mg; 4.2 mmol) were added
to a solution of PhSeSePh (650 mg; 2.1 mmol), Bun NBr (3.4 mg;
4
12
OH
5
0.011 mmol) in THF (4 ml) under nitrogen. The two-phase system was
vigorously stirred under reflux until the colour disappeared, and then
the epoxide 1–7a–e (4.2 mmol) in THF (4 ml) was added and the
mixture stirred under reflux for the time indicated in Tables 1 and 2.
The reaction mixture was quenched with Et2O (20 ml), the phases
were separated and the aqueous layer extracted with Et2O (3 × 15 ml).
The combined ethereal layer was washed with water (3 × 15 ml),
brine (3 × 15 ml), dried with MgSO4 and the solution concentrated
on a rotary evaporator. The crude product was first filtered through
a short column of silica-gel in hexane and then purified by silica-gel
column chromatography (hexane-ethyl acetate gradients), to afford the
corresponding products 8–15 in 67 to 98% yield as crystals or oil.
TDO is easily prepared27 by oxidation of thiourea with cold
aqueous 15% H2O2, with stirring for one hour, filtration and washing
with ice-water, followed by crystallisation from hot ethanol.
O
BOMO
BOMO
SePh
6
13
a Yield of the purified product.
attack occurs preferentially at the most substituted carbon atom.
This regioselectivity may be consistent with a directing effect of
the hydroxyl group, through an H-bond interaction between the
phenylselenide anion and the free OH.
1-phenylseleno-2-butanol (8): Treatment of epoxide 1 (0.303 g;
4.2 mmol) with sodium phenylselenide (4.2 mmol) gave 1-phenyl-
seleno-2-butanol 8 (0.944 g; 4.12 mmol; 98%) as a pale yellow oil;
Conclusion
A remarkable aspect of this work is the higher efficiency
and ease of generation of phenylselenide anion compared to
the known methods.8-21 The possibility of effecting the ring
opening reaction of epoxides with PhSe- under mild conditions
is the most important aspect of this work.
The methodology provides a convenient and efficient
method for preparation of b-hydroxy phenylselenides with
high regio- and stereoselectivity. These results make the
procedure an attractive reaction because of the simplicity and
mildness of this methodology.
IR nmax. (film): 3397; 3062; 2964; 1578; 1473; 1114; 1071; 1016; 737;
1
691 cm-1; H NMR (200 MHz, CDCl ) d: 0.91 (t, 3H, J 7.5 Hz,);
=
1.47–1.61 (m, 2H); 2.77–2.92 (m, 2H3); 3.10 (dd, 1H, J1 12.5 and
=
J2 3.9 Hz,); 3.59 (m, 1H); 7.18–7.25 (m, 3H); 7.45–7.53 (m, 2H);
=
13C NMR (50 MHz, CDCl3) d: 10.1; 29.4; 36.5; 71.2; 127.2; 129.1;
129.6; 132.8; Anal. Calcd for C10H14OSe: C, 52.40; H, 6.16. Found:
C, 52.79; H, 6.09.
(4R,8RS)-(+)-8-hydroxy-9-phenylseleno-p-menth-6-en-2-one
(9):
Treatment of epoxide 2 (0.698 g; 4.2 mmol) with sodium phenylselenide
(4.2 mmol) gave (4R,8RS)-(+)-8-hydroxy-9-phenylseleno-p-menth-6-
en-2-one 9 (1.018 g; 3.15 mmol; 75%) as a pale yellow oil; IR nmax.
(film): 3454; 2968; 1704; 1664; 1578; 1477; 1069; 1021; 738; 692 cm-1;
1H NMR (200 MHz, CDCl3) d: 1.22 (s, 3H); 1.75 (s, 3H); 1.90–2.60
(m, 5H); 3.14 (br. s, 2H); 6.80 (m, 1H); 7.15–7.30 (m, 3H); 7.45–7.59
(m, 2H); Anal. Calcd for C16H20O2Se: C, 59.44; H, 6.24. Found: C,
59.62; H, 6.48.
Experimental
General procedure
Melting points were determined on a Micro Química model APF-301
apparatus and are uncorrected. Infrared spectra were recorded either
Table 2 Regio- and stereoselectivity of the products of ring opening of trans-epoxy-carveol derivatives with PhSe-
Entry
Substrate
Products ratioa (14:15)
Reaction time/h
Yield/%b
1
2
3
4
5
7a, R = H
14a: 15a (17: 83)
14a (100) R = H
14c: 15c (88: 12)
14d: 15d (88.5: 11.5)
14e: 15e (87.5: 12.5)
2
70
75
82
74
67
7b, R = Piv
20
26
48
48
7c, R = BOM
7d, R = TBDMS
7e, R = PMB
aRatios determined by GC; byield of the purified product.
PAPER: 07/5015

24 JOURNAL OF CHEMICAL RESEARCH 2008
(1S,2S,5R)-(–)-6,6-dimethyl-10-phenylseleno-bicyclo [3.1.1] heptan-
2-ol (10): Treatment of epoxide 3 (0.639 g; 4.2 mmol) with sodium
phenylselenide (4.2 mmol) gave (1S,2S,5R)-(-)-6,6-dimethyl-10-
phenylseleno-bicyclo[3.1.1]heptan-2-ol 10 (0.935 g; 3.02 mmol;
p-menth-8-en-1-ol 14c and (1S,2R,4R,6R)-(–)-2-benzyloxymethyl
ether-1-phenylseleno-p-menth-8-en-6-ol 15c (0.534 g; 1.2 mmol;
82%) as a pale yellow oil;
(1S,2R,4S,6S)-(+)-2-benzyloxymethyl
ether-6-phenylseleno-p-
23
menth-8-en-1-ol (14c): [a]D23 + 59.8 (c 3.3, CHCl3); IR nmax. (film):
3450; 3068; 2939; 1644; 1578; 1476; 1378; 1026; 891; 741 cm-1;
1H NMR (400 MHz, CDCl3) d: 1.30 (s, 3H); 1.67 (s, 3H); 1.40–2.20
(m, 5H); 3.22 (dd, 1H, J1 = 13.0 and J2 = 4.0 Hz); 3.27 (br. s, 1H);
3.57 (dd, 1H, J1 = 12.0 and J2 = 4.0 Hz); 4.62–4.72 (m, 4H); 4.85
72%) as a pale yellow oil; [a]D –60.7 (c 1.52, CHCl3); IR nmax.
(film): 3465; 3061; 2920; 1578; 1475; 1024; 1003; 737; 692 cm-1;
1H NMR (200 MHz, CDCl3) d: 0.85 (s, 3H); 1.07 (s, 3H); 1.52 (d, 1H,
J
10.0 Hz); 1.87–2.20 (m, 8H); 3.25 (d, 1H, J 12.0 Hz); 3.32 (d,
=
=
=
1H, J 12.0 Hz,); 7.21–7.24 (m, 3H); 7.53–7.58 (m, 2H); 13C NMR
(d, 1H, J = 7.0 Hz); 4.95 (d, 1H, J = 7.0 Hz); 7.34–7.64 (m, 8H); 13
C
(50 MHz, CDCl3) d: 23.2; 24.8; 27.1; 27.2; 30.6; 37.9; 40.7; 45.0;
51.6; 75.6; 127.0; 129.0; 133.1; 133.5; Anal. Calcd for C16H22OSe:
C, 62.13; H, 7.17. Found: C, 62.35; H, 7.36.
NMR (100 MHz, CDCl3) d: 17.7; 20.5; 34.6; 37.3; 43.4; 55.8; 69.6;
75.2; 83.4; 94.9; 109.5; 127.3; 127.6; 127.7; 128.2; 128.8; 129.6;
134.3; 137.4; 147.0; Anal. Calcd for C24H30O3Se: C, 64.71; H, 6.79.
Found: C, 64.51; H, 6.80.
(–)-3,7-dimethyl-6-phenylseleno-octane-1,7-diol (11): Treatment
of epoxide 4 (0.900 g; 4.2 mmol) with sodium phenylselenide
(4.2 mmol) gave (–)-3,7-dimethyl-6-phenylseleno-octane-1,7-diol
11 (0.982 g; 2.98 mmol; 71%) as a pale yellow oil; IR nmax. (film):
3375; 3062; 2933; 1577; 1469; 1060; 737; 692 cm-1; 1H NMR
(1S,2R,4R,6R)-(–)-2-benzyloxymethyl ether-1-phenylseleno-p-menth-
23
8-en-6-ol (15c): [a]D -46,6 (c 1.78, CHCl3); IR nmax. (film): 3458;
3068; 2942; 2865; 1644; 1452; 1026; 890; 741 cm-1; 1H NMR
(400 MHz, CDCl3) d: 1.51 (s, 3H); 1.76 (s, 3H); 1.60–2.60 (m, 5H);
3.89–3.93 (m, 2H); 4.60–4.92 (m, 6H); 7.20–7.70 (m, 10H); 13C
NMR (100 MHz, CDCl3) d: 20.6; 24.3; 34.2; 37.4; 56.2; 69.7; 75.0;
79.3; 93.5; 109.4; 127.6; 127.8; 128.4; 128.6; 128.6; 129.0; 137.8;
138.8; 148.5. Anal. Calcd for C24H30O3Se: C, 64.71; H, 6.79. Found:
C, 64.60; H, 6.81.
(400 MHz, CDCl ) d: 0.88 (d, 3H, J 6.4 Hz); 1.25 (s, 3H); 1.35 (s,
=
3
3H); 1.48–1.60 (m, 4H); 1.82–2.12 (m, 2H); 2.80 (m, 1H); 3.06 (m,
1H, CH–SePh); 3.54–3.69 (m, 2H); 7.23–7.27 (m, 3H); 7.58–7.61 (m,
2H); Anal. Calcd for C16H26O2Se: C, 58.35; H, 7.96. Found: C, 58.03;
H, 8.07.
(1S,4S,6S)-(+)-2,2-ethylenedioxy-6-phenylseleno-p-menth-8-en-
1-ol (12): Treatment of epoxide 5 (0.883 g; 4.2 mmol) with sodium
phenylselenide (4.2 mmol) gave (1S,4S,6S)-(+)-2,2-ethylenedioxy-6-
phenyl seleno-p-menth-8-en-1-ol 12 (1.449 g; 3.94 mmol; 94%) as
(1S,2R,4S,6S)-(+)-2-tert-butyldimethylsilyl ether-6-phenylseleno-
p-menth-8-en-1-ol (14d):Treatment of epoxide 7d (0.283 g; 1.0 mmol)
with sodium phenylselenide (1.12 mmol) gave (1S,2R,4S,6S)-(+)-2-
tert-butyldimethylsilyl oxy-6-phenylseleno-p-menth-8-en-1-ol 14d
(0.325 g; 0.740 mmol; 74%) as a white crystalline solid;
23
1
a pale yellow oil; [a]D + 71.0 (c 5.0, CHCl3); H NMR (80 MHz,
CDCl3) d: 1.38 (s, 3H); 1.65 (s, 3H); 1.95–2.30 (m, 5H); 3.50 (dd,
1H, J1 13.0 and J 5.0 Hz,); 3.80–4.10 (m, 4H); 4.67 (br. s, 2H);
=
=
7.00–7.25 (m, 3H);27.40–7.67 (m, 2H); 13C NMR (20 MHz, CDCl3)
d: 19.3; 20.6; 37.1; 37.2; 42.0; 54.6; 65.6; 65.7; 76.8; 109.5; 110.7;
127.4; 128.9; 129.5; 134.6; 147.2; Anal. Calcd for C18H24O3Se: C,
58.85; H, 6.59. Found: C, 59.05; H, 6.70.
(1S,2R,4S,6S)-(+)-2-tert-butyldimethylsilyloxy-6-phenyl-seleno-
22
p-menth-8-en-1-ol (14d): M.p. 73-75°C; [a]D + 59.6 (c 10.7,
CHCl3); IR nmax. (KBr): 3471; 3077; 2972; 2853; 1644; 1578; 1474;
1247; 1123; 1008; 740; 693 cm-1; 1H NMR (400 MHz, CDCl3)
d: 0.08 (s, 3H); 0.11 (s, 3H); 0.90 (s, 9H); 1.24 (s, 3H); 1.67 (s, 3H);
1.30–2.10 (m, 5H); 2.48 (br. s, 1H); 3.21 (dd, 1H, J1 = 13.2 and
J2 = 3.8 Hz); 3.58 (dd, 1H, J1 = 11.6 and J2 = 4.5 Hz); 4.69 (br. s,
2H); 7.24–7.63 (m, 4H); 13C NMR (100 MHz, CDCl3) d: –4.5; –4.8;
17.3; 20.5; 25.7; 37.1; 37.6; 43.5; 55.2; 75.8; 77.2; 109.6; 127.3;
128.9; 129.7; 134.4; 147.3; Anal. Calcd for C22H36O2SiSe: C, 60.11;
H, 8.25. Found: C, 60.15; H, 8.33.
(1R,2R,4S,6R)-(–)-2-benzyloxymethoxy-6-phenyl-seleno-p-menth-
8-en-1-ol (13): Treatment of epoxide 6 (4.200 g; 14.57 mmol) with
sodium phenylselenide (16.4 mmol) gave (1R,2R,4S,6R)-(–)-2-
benzyloxy methoxy-6-phenylseleno-p-menth-8-en-1-ol 13 (5.839 g;
0.013 mol; 90%) as a white crystalline solid; m.p. 56.5–57.5°C;
[a]D24 –102.9 (c 2.0, CHCl3); IR nmax. (KBr): 3466, 3069, 3030, 1647,
1457, 1159 cm-1; 1H NMR (80 MHz, CDCl3) d: 1.52 (s, 3H); 1.70 (s,
3H); 1.80–2.40 (m, 5H); 3.58–3.70 (m, 1H); 3.94 (dd, 1H, J1 = 10.0
and J2 = 5.0 Hz); 4.60–4.90 (m, 6H); 7.15–7.36 (m, 8H); 7.40–7.65
(m, 2H); 13C NMR (20 MHz, CDCl3) d: 20.7; 26.9; 32.0; 32.1; 38.9;
52.9; 69.6; 73.9; 77.9; 93.1; 109.1; 127.3; 127.6; 127.7; 128.2; 128.9;
130.1; 134.3; 137.3; 148.2; Anal. Calcd for C24H30O3Se: C, 64.71; H,
6.79. Found: C, 64.80; H, 6.79.
(1S,2R,4S,6S)-(+)-6-phenylseleno-p-menth-8-en-1,2-diol(14a)and
(2R,,6R)-(+)-1-phenylseleno-p-menth-8-en-2,6-diol (15a): Treatment
of epoxide 7a (0.210 g; 1.25 mmol) with sodium phenylselenide
(1.4 mmol) gave (1S,2R,4S,6S)-(+)-6-phenylseleno-p-menth-8-en-
1,2-diol 14a and (2R,6R)-(+)-1-phenylseleno-p-menth-8-en-2,6-diol
15a (0.284 g; 0.873 mmol) as a white crystalline solid.
(1S,2R,4S,6S)-(+)-2-p-methoxybenzyloxy-6-phenylseleno-p-menth-
8-en-1-ol (14e) and (1S,2R,4R,6R)-(–)-2-p-methoxybenzyloxy-1-
phenylseleno-p-menth-8-en-6-ol (15e): Treatment of epoxide 7e
(0.288 g; 1.0 mmol) with sodium phenylselenide (1.12 mmol) gave
(1S,2R,4S,6S)-(+)-2-p-methoxybenzyl
ether-6-phenylseleno-p-
menth-8-en-1-ol 14e and (1S,2R,4R,6R)-(–)-2-p-methoxybenzyl
ether-1-phenylseleno-p-menth-8-en-6-ol 15e (0.298 g; 0.67 mmol;
82%) as a pale yellow oil;
(1S,2R,4S,6S)-(+)-2-p-methoxybenzyloxy-6-phenylseleno-p-menth-
23
8-en-1-ol (14e): [a]D
(c 2.0, CHCl ); IR n
(film): 3517;
+ 32.5
3
max.
3070; 2948; 2836; 1513; 1373; 1170; 1099; 890; 821; 741 cm-1; H
NMR (400 MHz, CDCl3) d: 1.30 (s, 3H); 1.67 (s, 3H); 1.30–2.20 (m,
5H); 2,76 (s, 1H); 3.21 (dd, 1H, J1 = 13.2 and J2 = 4.0 Hz); 3.38 (dd,
1H, J1 = 12.0 and J2 = 4.0 Hz); 3.78 (s, 3H); 4.62 (s, 2H); 4.69 (br.
s., 1H); 4.71 (br. s., 1H); 6.85–7.63 (m, 9H); 13C NMR (100 MHz,
CDCl3) d: 17.9; 20.6; 33.6; 37.5; 43.5; 55.1; 56.2; 72.0; 76.0; 83.2;
109.7; 113.7; 127.5; 129.0; 129.1; 129.7; 130.9; 134.5; 147.3; 159.0.
Anal. Calcd for C24H30O3Se: C, 64.71; H, 6.79. Found: C, 64.37;
H, 6.92.
1
(1S,2R,4S,6S)-(+)-6-phenylseleno-p-menth-8-en-1,2-diol (14a):
22
M.p. 61–63°C; [a]D + 109.96 (c 0.69, CHCl3); IR nmax. (KBr):
3319; 3068; 2942; 1640; 1580; 1476; 1160; 1080; 894; 728 cm-1;
1H NMR (400 MHz, CDCl3) d: 1.26 (s, 3H); 1.70 (s, 3H); 1.30–2.20
(m, 6H); 2.45 (br. s, 1H); 2.68 (br. s, 1H); 3.17 (dd, 1H, J1 = 13.0
and J2 = 4.0 Hz); 3.66 (dd, 1H, J1 = 12.0 and J2 = 4.3 Hz); 4.72 (br.
s, 2H); 7.26–7.30 (m, 3H); 7.60–7.62 (m, 2H); 13C NMR (100 MHz,
CDCl3) d: 16.7; 20.6; 34.7; 37.7; 43.2; 56.5; 75.5; 76.2; 109.5; 127.4;
129.0; 129.4; 134.2; 147.1. Anal. Calcd for C16H22O2Se: C, 59.07; H,
6.82. Found: C, 59.06; H, 6.81.
(1S,2R,4R,6R)-(–)-2-p-methoxybenzyloxy-1-phenylseleno-p-menth-
23
8-en-6-ol (15e): [a]D
(c 3.6, CHCl ); IR n
(film): 3466;
–10.0
3
max.
3070; 2933; 2862; 1612; 1513; 1451; 1248; 1024; 820; 734 cm-1; 1H
NMR (400 MHz, CDCl3) d: 1.44 (s, 3H); 1.77 (s, 3H); 1.58–2.41
(m, 5H); 2.60 (br. s., 1H); 3.29 (dd, 1H, J1 = 9.2 and J2 = 3.7 Hz);
3.59 (dd, 1H, J1 = 11.3 and J2 = 4.2 Hz); 3.80 (s, 3H); 4.40–4.80 (m,
4H); 6.85–7.65 (m, 9H); 13C NMR (100 MHz, CDCl3) d: 20.6; 24.2;
33.2; 34.3; 37.6; 55.2; 56.4; 71.0; 75.1; 80.1; 109.4; 127.4; 128.5;
128.9; 129.1; 129.4; 130.9; 134.5; 148.7; 159.0; Anal. Calcd for
C24H30O3Se: C, 64.71; H, 6.79. Found: C, 64.73; H, 6.79.
(2R,6R)-(+)-1-phenylseleno-p-menth-8-en-2,6-diol (15a): M.p. 65–
22
67°C; [a]D + 16.4 (c 1.5, CHCl3); IR nmax. (KBr): 3405; 2927;
1646; 1450; 1057; 946; 793; 739 cm-1; 1H NMR (400 MHz, CDCl3)
d: 1.31 (s, 3H); 1.76 (s, 3H); 1.46–2.52 (m, 7H); 3.73 (m, 1H); 4.21
(br. s, 1H); 4.77 (br. s, 2H); 7.30–7.38 (m, 3H); 7.61–7.63 (m, 2H);
13C NMR (100 MHz, CDCl3) d: 20.7; 23.3; 34.3; 37.1; 37.8; 60.2;
72.7; 75.5; 109.2; 126.2; 128.8; 128.9; 138.5; 148.2; Anal. Calcd for
C16H22O2Se: C, 59.07; H, 6.82. Found: C, 59.09; H, 6.76.
(1S,2R,4S,6S)-(+)-6-phenylseleno-p-menth-8-en-1,2-diol (14b):
Treatment of epoxide 7b (0.252 g; 1.0 mmol) with sodium
phenylselenide (1.12 mmol) gave (1S,2R,4S,6S)-(+)-6-phenylseleno-
p-menth-8-en-1,2-diol 14a (0.244 g; 0.750 mmol; 75%).
The authors wish to thank the following agencies for financial
support: FAPESP, CAPES and CNPq. The (R)-(-)-carvone
used as starting material was generously given by Symrise
Perfumes and Aromas Ltda.
(1S,2R,4S,6S)-(+)-2-benzyloxymethyl
ether-6-phenylseleno-p-
menth-8-en-1-ol (14c) and (1S,2R,4R,6R)-(–)-2-benzyloxymethyl
ether-1-phenylseleno-p-menth-8-en-6-ol (15c): Treatment of epoxide
7c (0.420 g; 1.46 mmol) with sodium phenylselenide (1.64 mmol)
gave (1S,2R,4S,6S)-(+)-2-benzyloxymethyl ether-6-phenyl-seleno-
Received 27 December 2007; accepted 14 January 2008
Paper 07/5015
doi: 10.3184/030823408X282659
PAPER: 07/5015

JOURNAL OF CHEMICAL RESEARCH 2008 25
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PAPER: 07/5015