Diastereoselective synthesis of substituted 2-phenyltetrahydropyrans as useful precursors of aryl C-glycosides via selenoetherification

Article abstract of DOI:10.3987/COM-03-9959

The cyclization of several substituted 5-phenyl-pent-4-en-1-ols with selenium electrophiles along some mechanistic considerations is discussed. In particular, an efficient diastereoselective synthesis of a 2,3,5,6-tetrasubstitued tetrahydropyran is report

Full text of DOI:10.3987/COM-03-9959

HETEROCYCLES, Vol. 63, No. 3, 2004, pp. 681 - 690
Received, 14th November, 2003, Accepted, 8th January, 2004, Published online, 19th January, 2004
DIASTEREOSELECTIVE
SYNTHESIS
OF
SUBSTITUTED
2-PHENYLTETRAHYDROPYRANS AS USEFUL PRECURSORS OF
ARYL C-GLYCOSIDES VIA SELENOETHERIFICATION
Michelangelo Gruttadauria,* Carmela Aprile, Paolo Lo Meo, Serena Riela,
and Renato Noto
Department of Organic Chemistry “E. Paternò”, University of Palermo, Viale
delle Scienze, Parco d’Orleans II, 90128 Palermo, Italy. E-mail: mgrutt@unipa.it.
Abstract – The cyclization of several substituted 5-phenyl-pent-4-en-1-ols with
selenium electrophiles along some mechanistic considerations is discussed. In
particular, an efficient diastereoselective synthesis of a 2,3,5,6-tetrasubstitued
tetrahydropyran is reported. These findings open an interesting approach: the use
of chiral selenium electrophiles for cyclization of chiral substrates. The cyclized
products are useful starting material for the synthesis of D- or L-aryl
C-glycosides.
Aryl C-glycosides are naturally-occurring, structurally diverse compounds that have attracted
considerable attention because they exhibit a vast array of important biological activities.1 In particular
they are able to form stable complexes with DNA.2 Molecular recognition involving van der Waals
and/or hydrogen bonding interactions between the sugar substituent and the DNA helix is implicated.
Recently, several C-glycoside derivatives have been found to possess binding constants and biological
properties very similar to those of their oxygen counterparts.3 The absence of an oxygen atom between
the carbohydrate and the aryl moiety results in greater stability of these compounds when compared to
O-glycosides. Indeed, they are very stable to acidic hydrolysis and less vulnerable to enzymatic
digestion.4
Since C-glycosides that do not occur in nature, but that are congeners of biologically important
O-glycosides may eventuate in the discovery of lead compounds having novel biological activities and
pharmaceutical value, there have been a wealth of synthetic approaches toward this class of

carbohydrate mimics.5,6 Usually, aryl C-glycosides are prepared by transformation of a functionalised
carbohydrate with an aryl group at the anomeric position7 or by a de novo synthesis.8 An interesting de
novo approach is the 6-endo selenoetherification of substituted (E)-5-arylpent-4-en-1-ols.8d-f Indeed, the
reductive elimination of the selenides affords deoxy-aryl C-glycosides whereas oxidative elimination
affords dihydropyrans that can be transformed into aryl C-glycosides by further dihydroxylation (Figure
1).
OH
R
R
R
PhSe
Ar
R
HO
Ar
ii
i
Ar
O
O
Ar
O
O
Figure 1. (i) reductive elimination; (ii) oxidative elimination.
Recently,9 we devoted our efforts to the diastereoselective synthesis of oxygenated heterocyclic rings
such as lactones, tetrahydropyrans and tetrahydrofurans using the selenium chemistry. Moreover, in the
last decade several authors have developed new chiral organoselenium compounds for the
enantioselective synthesis of the aforesaid heterocyclic rings.10 Such chiral compounds are able to
transfer their chirality into the substrate because of the intramolecular X--Se (X=O, N, S) interaction.
Here we report some results on the diastereoselective synthesis of 2-aryl-substituted tetrahydropyrans as
precursors for aryl C-glycosides along with some mechanistic considerations.
R
Ph
O
PhSe
SePh
R
2a:3a 4:1 ref. 11
2b:3b 9:1 this work
+
Ph
O
2a,b
3a,b
Ph
R
PhSe
PhSeCl, CH Cl , -78 °C
2c:3c 1:1 ref. 8f
2e:3e 16:1 ref. 12
2
2
Ph
+
R
R
O
O
R'
SePh
R'
Ph HO
R'
2c,e
3c,e
Ph
1a-f
SePh
Ph
2d:3d 1:1 this work
2f:3f 99:1 ref. 12
R
R
+
O
O
SePh
3d,f
R'
R'
2d,f
a: (E); R=OTBS; R’=H
c: (E); R=H; R’=Me
b: (E); R=OH; R’=H
d: (Z); R=H; R’=Me
e: 1,3-anti (E); R=OH; R’=Me f: 1,3-anti (Z); R=OH; R’=Me
Scheme 1
First we overviewed the behaviour of compounds (1) in order to complete the literature data. Hart11
reported that compound (1a) gave, as preferred product, the corresponding tetrahydropyran having the
4-OR group in axial position, invoking for such result the deactivating effect of the OR group when
equatorially disposed. However, we believe that this preference arise from the stabilizing Se--O

interaction during the course of the cyclization. For this reason we studied the cyclization of compound
(1b). We found higher diastereoselectivity (9:1) compared to 1a (4:1) in agreement with the higher
coordination effect of the unprotected OH group. We argued that intramolecular stabilizing Se--O
interaction is important in determining a high diastereoselectivity. As confirmation of this hypothesis
cyclization of 1c8f and 1d gave mixture of diastereoisomers without selectivity. Moreover, we carried
out the cyclization of 1b in the presence of silica gel. This reaction gave low diastereoselectivity (2:1)
according to the fact that the OH groups of silica give strong interactions with positively charged
selenium atom destroying the intramolecular Se--O interaction.12 These results, together with the high
diastereoselectivities observed in the cyclization of compounds (1e,f),12 are a clear evidence of the
important role played by the OH group in allylic position on the diastereoselectivity.
We, then, investigated the behaviour of compounds (7a,b) where the OR group was moved to the
homoallylic position. The absence of a substituent in allylic position should lead to a low
diastereoselectivity. Compounds (7a,b) were prepared as outlined in the Scheme 2.
Cl
LiAlH4, Et2O, reflux
3 h, 75%
Ti(OiPr)4,(+)-DET, CH2Cl2,
-20 °C, 20 h, 71%
ref 13
OH
Ph
Ph
Ph
Ph
OH
4
5
OR
OH
PhCOOH, Ti(OiPr)4, CH2Cl2, rt, 14 h, 60%
O
or
OH
Ph HO
7a,b
i-PrOH, Ti(OiPr)4, reflux, 18 h, 70%
a: R=COPh
b: R=i-Pr
6
Ph
ArSe
+
PhSeCl, CH2Cl2, -78 °C
Ph
OR
OH
OR
OH
O
O
or
Se
Et
12, CH2Cl2, -78 °C
Ar
8a,b
10a,b
9a,b
11a,b
O
Se
12
OTf
H
Et
8,9: Ar=Ph; 10,11: Ar=
OH
Scheme 2.
Reduction with LiAlH4 gave 5 that was submitted to Sharpless epoxidation conditions to give 6 in 71%
yield and 90% e.e. Epoxide ring opening was carried out with benzoic acid14 or 2-propanol15 in the
presence of Ti(OiPr)4 to give 7a and 7b respectively with good regioselectivity (90/10 for 7a; 93/7 for
7b). Cyclization of 7a with PhSeCl in CH2Cl2 at –78 °C gave 8a and 9a in 60:40 ratio (74% yield). The
reaction was highly regioselective but, as expected, without diastereoselectivity. Compound (7b) also
gave similar results, (8b:9b 67:33; 80% yield). The behaviour of compounds (7a,b) resembles that of 1c.
In these substrates the attack from the Re or Si face lead to seleniranium ions similar in energy,
moreover also their transition states (13) and (14) should be similar in energy. The presence of an

additional group in axial position in 14 (R1= OCOPh or OiPr; R2=OH in comparison with R1=R2=H) is
evidently not sufficient to cause severe steric interactions (see Scheme 3).
PhSe+
Re
R1
=
=
Se
3c
9a,b
R1
R2
2c
8a,b
HO
O
Se
Si
R1
R2
O
H
PhSe+
R2
H
13
14
Scheme 3. Transition states for cyclization of compounds (1c) and (7a,b) with PhSeCl.
Re
H
12
=
OR
=
Et
O
R1
R2
HO
Si
O
Se
O
10a,b
H
11a,b
Se
OH
H
Et
OR
OH
OH
12
H
H
15
16
Scheme 4. Transition states for cyclization of compounds (7a,b) with (12).
We reasoned that a chiral organoselenium reagent could increase the diastereoselectivity. Indeed, the
attack from the Re and Si faces should give seleniranium ions with different stability; moreover, the
chirality of the organoselenium reagent should increase the difference in energy of the corresponding
transition states.
We decided to use reagent (12) prepared by Wirth,16 one of the simplest chiral organoselenium
electrophiles. The mechanism of the stereoselective selenenylation reactions with 12 has been the subject
of three works.17
Compound (7a) gave a complex reaction crude from which we were able to isolate the major
diastereoisomer in modest yield (30%). However, the diastereoselectivity was certainly higher with
respect to the corresponding reaction with the achiral selenium reagent, since the minor diastereoisomer
was detected in mixture with other minor not identified product giving, at last, a roughly 80:20 ratio.
Compound (7b) gave a better result. Both yield and diastereoselectivity18 were high (79%; 93:7 10b:11b).
We also recovered some starting material (10%), having the same e.e. 19 These results are in agreement
with Wirth’s findings: the attack from the Si face on aryl-substituted double bonds is less favourable.
Moreover, we believe that transition state (16), compared to 15, experiences more severe steric
interactions than 14 (R1=OiPr; R2=OH) (see Scheme 4).
In conclusion we have showed how the substituents of several 5-phenylpent-4-en-1-ols affect the
diastereoselectivity in the cyclization reactions. Moreover, we have reported the first example of the use
of a chiral organoselenium electrophile for diastereoselective cyclization of a chiral substrate.20 This

approach allows the stereoselective synthesis of precursors of both D- and L-aryl C-glycosides depending
on the Sharpless epoxidation. In particular the de novo synthesis of L-aryl C-glycosides is of interest
since they are less available by transformation of a naturally occurring carbohydrate.
EXPERIMENTAL
General. Methylene chloride and diethyl ether were distilled prior to use. Reactions were routinely
carried out under argon with magnetic stirring. IR spectra were recorded on a Shimadzu FTIR 8300
1
13
spectrophotometer. H NMR and C NMR (COSY and HETCOR) spectra were recorded on a Bruker
AC-E series 250 MHz spectrometer in CDCl3 solution. Silica gel (Macherey-Nagel, 0.04-0.063 mm) was
used for column chromatography.
(1RS, 5Z)-6-Phenylhex-5-en-2-ol (1d)
To a solution of (1RS)-6-phenylhex-5-yn-2-ol8f (160 mg, 0.925 mmol) in ethanol (15 mL) containing
ethylenediamine (15 µL) was added Lindlar catalyst (16 mg). Hydrogen was allowed to flow through the
solution (1 atm, 50 NmL/min). After 4 h the reaction mixture was filtered and the solvent removed under
reduced pressure. The residue was chromatographed on silica gel, using light petrol ether (4:1) as eluent
to give 1d as oil (155 mg, yield 97%). 1H NMR: δ 1.19 (d, J=6.2 Hz, 3H), 1.54-1.67 (m, 2H), 2.03 (br s,
1H), 2.37-2.51 (m, 2H), 3.79-3.99 (m, 1H), 5.69 (dt, J=11.7 and 7.3 Hz, 1H), 6.48 (dt, J=11.7 and 1.6 Hz,
13
1H), 7.22-7.40 (m, 5H); C NMR: δ 23.3, 24.8, 39.0, 67.4, 126.5, 128.1, 128.6, 129.1, 132.2, 137.4. IR
(liquid film): 3356 cm-1. Anal. Calcd for C12H16O: C, 81.77; H, 9.15. Found: C, 81.80; H, 9.21.
(2E, 5E)-6-Phenylhexa-2,5-dien-1-ol (5)
To a solution of 4 (1.14 g, 6.61 mmol) in ether (59 mL) at 0 °C a solution of LiAlH4 in ether (4 mL, 4.00
mmol) was slowly added. The resulting solution was then stirred under reflux at 35 °C. After 3 h to the
reaction mixture water (148 µL), 15% aqueous NaOH (148 µL) and water (445 µL) were sequentially
added. The reaction mixture was warmed to rt, dried on anhydrous sodium sulfate, filtered on celite, and
the solvent was then removed under reduced pressure. The residue was chromatographed on silica gel,
1
using light petrol ether (4:1) as eluent to give 5 as oil (855 mg, yield 75%). H NMR: δ 2.98 (dd, J=6.0
and 6.0 Hz, 2H), 4.14 (d, J=4.2 Hz, 2H), 5.68-5.86 (m, 2H), 6.22 (dt, J=15.8 and 6.5 Hz, 1H), 6.42 (d,
J=15.8 Hz, 1H), 7.18-7.39 (m, 5H); 13C NMR: δ 35.3, 63.1, 125.8, 126.9, 127.9, 128.3, 130.1, 130.2,
130.7, 137.3. IR (liquid film): 3338 cm-1. Anal. Calcd for C12H14O: C, 82.72; H, 8.10. Found: C, 82.80; H,
8.13.
(2S, 3S, 5E)-2,3-Oxirane-6-phenylhex-5-en-1-ol (6)
At –20 °C Ti(OiPr)4 (820 µL, 2.76 mmol) and L-(+)-DET (557 µL, 2.76 mmol) were added to CH2Cl2
(23 mL) and allowed to stir for 5 min. Compound (5) (400 mg, 2.3 mmol) dissolved in CH2Cl2 mL was then

added via cannula. Last, TBPH (840 µL, 4.6 mmol) was added. The solution was allowed to stir at –20 °C
for about 20 h. The reaction was then quenched with an aqueous 10% solution of tartaric acid (6 mL). The
reaction mixture was warmed to rt and allowed to stir for 1 h. The organic phase was separated, washed
with aqueous saturated NaCl solution, dried on anhydrous sodium sulfate, and finally concentrated under
reduced pressure. The resulting yellow oil was purified by column chromatography on silica gel, using
light petrol-ethyl acetate (4:1) as eluent to give 6 as oil (308 mg, yield 71%). 1H NMR: δ 2.44 (br s, 1H),
2.50-2.55 (m, 2H), 3.00-3.05 (m, 1H), 3.10-3.16 (m, 1H), 3.64 (dd, J=12.6 and 4.5 Hz, 1H), 3.94 (dd,
J=12.6 and 2.4 Hz, 1H), 6.21 (dt, J=15.9 and 6.9 Hz, 1H), 6.51 (d, J=15.9 Hz, 1H), 7.19-7.39 (m, 5H); 13C
NMR: δ 34.6, 34.9, 38.0, 61.4, 124.1, 125.9, 127.2, 128.3, 132.6, 136.9. IR (liquid film): 3411 cm-1. Anal.
Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.80; H, 7.50.
(2S, 3R, 5E)-3-Benzoyloxy-6-phenylhex-5-ene-1,2-diol (7a)
To a solution of compound (6) (143 mg, 0.753 mmol) in CH2Cl2 (3.76 mL) at 0 °C, PhCOOH (138 mg,
1.13 mmol) and Ti(OiPr)4 (222 µL, 0.753 mmol) were added. The resulting solution was allowed to stir at
0 °C for 1 h and then at rt for 20 h. The reaction was quenched with saturated aqueous NaHCO3, and
subsequently extracted with CH2Cl2. The organic layer was washed with saturated aqueous NaCl, dried
on anhydrous sodium sulfate and concentrated under reduced pressure. The crude material was purified
by column chromatography on silica gel using light petrol-ethyl acetate (2:1) as eluent to give 7a as oil
(141 mg, yield 60 %). 1H NMR: δ 2.72-2.87 (m, 2H), 3.50 (br s, 2H), 3.68 (dd, J=11.9 and 5.1 Hz, 1H),
3.79 (dd, J=11.9 and 2.2 Hz, 1H), 3.85-3.93 (m, 1H), 5.21-5.29 (m, 1H), 6.25 (dt, J=15.8 and 7.3 Hz, 1H),
6.53 (d, J=15.8 Hz, 1H), 7.19-7.61 (m, 8H), 8.03-8.07 (m, 2H); 13C NMR: δ 34.3, 62.6, 72.3, 73.9, 124.6,
126.0, 127.1, 128.3, 129.5, 129.6, 133.3, 133.4, 137.1, 166.8. IR (liquid film): 3415, 1714 cm-1. Anal.
Calcd for C19H20O4: C, 73.06; H, 6.45. Found: C, 73.20; H, 6.50.
(2S, 3R, 5E)-3-i-Propoxy-6-phenylhex-5-ene-1,2-diol (7b)
To a solution of compound (6) (490 mg, 2.58 mmol) in i-PrOH (25.8 mL) Ti(OiPr)4 (1.15 mL, 3.87
mmol) were added. The resulting solution was refluxed at 80 °C for 18 h. The reaction was quenched
adding ether and aqueous 5% H2SO4, and allowed to stand until the two phases were distinctly separated
(about 2 h). The organic layer was separated, while the aqueous layer was extracted with diethyl ether.
The collected organic phases were washed with saturated aqueous NaCl, dried on anhydrous sodium
sulfate and concentrated under reduced pressure. The crude material was purified by column
chromatography on silica gel using light petrol-ethyl acetate (3:1) as eluent to give 7b as oil (450 mg,
yield 70 %). 1H NMR: δ 1.15 (d, J=6.1 Hz, 3H), 1.16 (d, J=6.0 Hz, 3H), 2.45-2.51 (m, 2H), 3.52-3.75 (m,
5H overlapped with 2H, OH), 6.26 (dt, J=15.9 and 7.2 Hz, 1H), 6.47 (d, J=15.9 Hz, 1H), 7.17-7.37 (m,
13
5H); C NMR: δ 22.1, 22.8, 34.8, 63.4, 71.1, 72.6, 78.4, 125.8, 126.1, 126.9, 128.3, 132.2, 137.3. IR
(liquid film): 3383 cm-1. Anal. Calcd for C15H22O3: C, 71.97; H, 8.86. Found: C, 72.10; H, 8.90.

General procedure for cyclization of compounds (1b,d) and (7a,b) with PhSeCl
To a solution of 7a (43 mg, 0.138 mmol) in CH2Cl2 (1.5 mL) at 0 °C K2CO3 (20 mg, 0.138 mmol) was
added. The resulting mixture was cooled to –78 °C, and PhSeCl (30 mg, 0.151 mmol) dissolved in
CH2Cl2 (1.5 mL) was added via cannula. After 1 h, the reaction was quenched adding water (3 mL). The
mixture was warmed to rt and extracted with CH2Cl2. The organic layer was washed with saturated
aqueous NaCl, dried on anhydrous sodium sulfate and concentrated under reduced pressure. Column
chromatography on silica gel, using light petrol-ethyl acetate (3:1) as eluent, gave compounds (8a) and
(9a) (48 mg, yield 74 %, oil).
1
Compounds (2b) and (3b). (Yield 70%; from light petrol-ethyl acetate 3:1, oil). H NMR: δ 1.92-2.14
(m, 2H, 2b+3b), 2.80 (br s, OH), 3.08 (dd, J=10.4 and 10.4 Hz, 3b), 3.56 (dd, J=11.0 and 2.4 Hz, 2b),
3.60-3.80 (m, 1H, 3b), 3.90 (ddd, J=11.3, 4.9 and 1.7 Hz, 1H, 2b), 4.06-4.16 (m, 2H, 2b+3b), 4.27 (d,
J=10.4 Hz, 3b), 4.75 (d, J=11.0 Hz, 2b), 7.14-7.38 (m, 10H); 13C NMR: δ 33.0 (2b), 34.3(3b), 55.9 (2b),
59.9 (3b), 62.7 (2b), 65.4 (2b), 66.2 (3b), 70.1 (3b), 78.2 (2b), 89.5 (3b), 127.3, 127.9, 128.0, 128.1,
128.2, 128.3, 128.8, 129.0 (2b+3b), 135.0 (2b), 135.7 (3b), 139.2 (3b), 140.0 (2b). IR (liquid film): 3421
cm-1. Anal. Calcd for C17H18O2Se: C, 61.26; H, 5.44. Found: C, 61.40; H, 5.55.
Compounds (2d) and (3d). These compounds were obtained as inseparable mixture together with the
1
THF ring coming from the 5-exo cyclization. (yield 52% 2d+3d, 13%THF as determined by H NMR;
from light petrol-ethyl acetate 3:1, oil). 1H NMR: δ 1.42 (d, J=6.8 Hz, 3H, 2d or 3d), 1.45 (d, J=6.5 Hz,
3H, 2d or 3d),), 1.46 (d, J=6.7 Hz, 3H, THF), 1.50-1.70 (m, 1H, 2d+3d+THF), 1.93-2.55 (m, 3H,
2d+3d+THF), 3.80-3.88 (m, 1H, THF), 4.19-4.71 (m, 3H, 2d+3d and 1H, THF), 5.27 (d, J=3.1 Hz, 1H,
13
THF), 7.29-7.58 (m, 10H, 2d+3d+THF); C NMR: δ 18.1(THF), 21.0(2d or 3d), 21.8(2d or 3d),
26.4(THF), 27.6(THF), 30.7(2d or 3d), 31.4(2d or 3d), 32.7(2d or 3d), 33.6(2d or 3d), 49.4(THF),
54.7(2d or 3d), 54.8(2d or 3d), 68.2(THF), 73.5(THF), 75.7(2d or 3d), 76.1(2d or 3d), 81.3(2d or 3d),
82.1(2d or 3d), 126.5, 127.0, 127.1, 127.2, 127.3, 127.5, 127.8, 127.9, 128.0, 128.3, 128.4, 128.6, 129.2,
129.5, 134.1(THF), 135.2(2d or 3d), 135.4(2d or 3d), 140.8(THF), 140.9(2d or 3d), 141.2(2d or 3d).
Anal. Calcd for C18H20OSe: C, 65.25; H, 6.08. Found: C, 65.40; H, 6.28.
Compound (8a). 1H NMR: δ 1.95 (ddd, J=12.8, 12.8 and 12.8 Hz, 1H), 2.22-2.28 (m, 1H), 2.81 (dt,
J=12.8 and 4.2 Hz, 1H), 3.38-3.49 (m, 1H), 3.57-3.80 (m, 3H), 4.42 (d, J=10.7 Hz, 1H), 5.07-5.17 (m,
1H), 7.10-7.67 (m, 13H), 8.00-8.08 (m, 2H); 13C NMR: δ 37.8, 43.4, 62.2, 68.5, 80.1, 84.9, 127.7, 128.0,
128.2, 128.4, 128.6, 128.7, 128.8, 129.6, 133.3, 135.7, 138.8, 167.0. IR (liquid film): 3421, 1718 cm-1.
Anal. Calcd for C25H24O4Se: C, 64.24; H, 5.18. Found: C, 64.40; H, 5.13.
Compound (9a). 1H NMR: δ 2.20-2.40 (m, 2H), 3.68-4.05 (m, 4H overlapped with 1H, OH), 4.97 (d,
J=7.0 Hz, 1H), 5.32-5.39 (m, 1H), 7.19-7.62 (m, 13H), 8.00-8.06 (m, 2H); IR (liquid film): 3386, 1716
cm-1. Anal. Calcd for C25H24O4Se: C, 64.24; H, 5.18. Found: C, 64.42; H, 5.29.

Compound (8b). (Yield 54%; from light petrol-ethyl acetate 3:1, white solid, mp 97-99 °C). 1H NMR:
δ 1.15 (d, J=6.1 Hz, 6H), 1.73 (dt, J=12.8 and 10.6 Hz, 1H), 2.16 (br s, 1H), 2.63 (dt, J=12.8 and 4.2 Hz,
1H), 3.22-3.39 (m, 2H), 3.44-3.54 (m, 1H), 3.63-3.84 (m, 3H), 4.32 d, J=10.6 Hz, 1H), 7.10-7.32 (m,
13
10H); C NMR: δ 22.1, 23.2, 39.1, 43.9, 62.4, 70.5, 72.2, 80.9, 84.6, 127.3, 127.7, 128.1, 128.3, 128.6,
135.6, 139.3. IR (liquid film): 3483 cm-1. Anal. Calcd for C21H26O3Se: C, 62.22; H, 6.46. Found: C,
62.38; H, 6.55. Compound (9b) was obtained in mixture with 8b. Some selected signals of 9b are: 1H
NMR: δ 2.05 (ddd, J=13.8, 8.7 and 4.0 Hz, 1H), 2.20 (dt, J=13.8 and 4.9 Hz, 1H), 4.14-4.16 (m, 1H), 5.07
(d, J=3.7 Hz, 1H); 13C NMR: δ 22.2, 23.0, 32.4, 42.6, 62.1, 69.7, 70.3, 74.8, 77.5, 134.6, 138.8.
General procedure for cyclization of compounds (7a,b) with 12
To a solution of the chiral diselenide (106 mg, 0.247 mmol) in CH2Cl2 (3.8 mL) cooled at –78 °C was
added a 1 M solution of bromine in CCl4 (247 µL). After 5 min, silver trifluoromethanesulfonate (2 M in
MeOH; 247 µL) was added. The resulting mixture was stirred for further 5 min then 7b (112.5 mg, 0.45
mmol) in CH2Cl2 (3.2 mL) was added. After 1 h at –78 °C a saturated aqueous solution of NaHCO3 was
added. The reaction mixture was diluted with CH2Cl2, the organic phase separate, dried (NaSO4) and
concentrated under reduced pressure. Purification by flash chromatography gave the cyclized products.
Compound (10a). (Yield 30%; from light petrol-ethyl acetate 2:1, oil) 1H NMR: δ 0.89 (t, J=7.3 Hz, 3H),
1.54-1.67 (m, 2H), 1.97-2.11 (m, 1H), 2.73 (dt, J=12.5 and 4.4 Hz, 1H), 3.46-3.79 (m, 3H), 4.46 (d,
13
J=10.6, 1H), 4.91 (dd, J=7.4 and 5.5 Hz, 1H), 5.04-5.14 (m, 1H), 7.00-7.59 (m, 12H); C NMR: δ 10.2,
31.3, 38.1, 43.9, 62.1, 68.4, 74.4, 80.3, 84.5, 126.2, 127.6, 127.7, 128.2, 128.4, 128.6, 128.8, 129.6, 129.7,
133.4, 136.1, 138.7, 147.2, 165.7. IR (liquid film): 3460, 1716 cm-1. Anal. Calcd for C28H30O5Se: C,
64.00; H, 5.75. Found: C, 64.18; H, 5.88.
Compound (10b). (Yield 73%; from light petrol-ethyl acetate 2:1, oil) 1H NMR: δ 0.88 (t, J=7.2 Hz, 3H),
1.08 (d, J=6.3 Hz, 3H), 1.11 (D, J=6.3 Hz, 3H, 1.51-1.81 (m, 3H), 2.43-2.50 (m, 3H); 3.29-3.45 (m, 3H),
3.58-3.78 (m, 3H), 4.31 (d, J=10.6 Hz, 1H), 4.87 (t, J=6.3 Hz, 1H), 6.98-7.04 (m, 1H), 7.13-7.47 (m, 8H);
13C NMR: δ 10.2, 22.0, 23.1, 31.2, 39.2, 43.9, 62.2, 70.5, 72.0, 74.1, 81.1, 84.2, 126.0, 126.6, 126.8,
127.3, 127.5, 128.1, 128.2, 128.4, 135.9, 139.0, 147.2. Anal. Calcd for C24H32O4Se: C, 62.20; H, 6.96.
Found: C, 62.30; H, 7.10.
ACKNOWLEDGEMENTS
Financial support from the University of Palermo (funds for selected research topics) and Italian MIUR
within the National Research Project “Non-aromatic heterocycles in stereocontrolled processes“ is
gratefully acknowledged. We thank Prof. T. Wirth for comments.

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