Asymmetric aldol reactions from titanium enolates of α-seleno ketones and esters

Article abstract of DOI:10.1016/j.tetasy.2003.12.035

Asymmetric aldol condensations using titanium enolates of (R)-camphorselenoacetone and of methyl (R)-camphorselenoacetate are reported. The reactions with aromatic, α,β-unsaturated or aliphatic aldehydes proceed with good chemical yields giving a mixture of the syn and anti aldols. These diastereoisomers were easily separated by column chromatography. The two syn diastereoisomers were obtained in enantiomerically pure form.

Full text of DOI:10.1016/j.tetasy.2003.12.035

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 783–791
Asymmetric aldol reactions from titanium enolates of a-seleno
ketones and esters
Marcello Tiecco,* Lorenzo Testaferri, Francesca Marini, Silvia Sternativo, Claudio Santi,
Luana Bagnoli and Andrea Temperini
Dipartimento di Chimica e Tecnologia del Farmaco, Sez. di Chimica Organica, Universitꢀa di Perugia, I-06123 Perugia, Italy
Received 10 November 2003; revised 11 December 2003; accepted 12 December 2003
Abstract—Asymmetric aldol condensations using titanium enolates of (R)-camphorselenoacetone and of methyl (R)-camphor-
selenoacetate are reported. The reactions with aromatic, a,b-unsaturated or aliphatic aldehydes proceed with good chemical yields
giving a mixture of the syn and anti aldols. These diastereoisomers were easily separated by column chromatography. The two syn
diastereoisomers were obtained in enantiomerically pure form.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
reactions can be synthetically important because the
optically active selenoaldols so formed may be con-
verted into several other derivatives taking advantage of
the versatile chemistry of the organoselenium com-
pounds.1;3 The only previous example of stereoselective
aldol reactions using selenium reagents is the recently
reported reaction of titanium enolates of chiral N-acyl
selones with aldehydes.6
Organoselenium reagents have been widely employed in
organic synthesis to effect nonconventional conversions
of functional groups. In recent years, several research
groups have been involved in the preparation of opti-
cally active diselenides, which have found extensive
application in electrophilic addition reactions. Depend-
ing on the efficiency of the chiral diselenide asymmetric
inductions from good to excellent have been observed.
Thus, highly diastereoselective seleno-alkoxylation,
seleno-hydroxylation,1 selenoazidation reactions of
alkenes,2 as well as cyclofunctionalization reactions,1
have been recently reported.
2. Results and discussion
On the basis of the results of some preliminary experi-
ments we observed that, in the present case, the most
convenient chiral diselenide was the (R,R)-camphor
diselenide introduced by Back et al.7 Thus, starting from
this diselenide and using standard procedures we have
prepared two new camphor derivatives: (R)-camphor-
selenoacetone 1 and methyl (R)-camphorselenoacetate 2.
As shown in Scheme 1, (R)-camphorselenoacetone 1 was
prepared from acetone and camphorselenenyl chloride
On the other hand, asymmetric additions of selenium-
containing nucleophiles are still poorly explored.3 Ste-
reoselective aldol reactions between enolates of a-phe-
nylseleno substituted carbonyl compounds and various
aldehydes have recently appeared in the literature.4
These reactions allow syn aldols to be formed as race-
mates with high diastereoselectivity. The use of enolates
generated from enantiomerically pure selenium-con-
taining carbonyl compounds may be a useful elabora-
tion of this methodology and an interesting alternative
to the more classical chiral auxiliary mediated aldol
condensations, which are still the subject of intense
synthetic and mechanistic studies.5 Moreover, these
O
O
1
Me
Me
CfSeCl
CfSeCH2
Me
Se)2
O
O
O
2
OMe
BrH2C
OMe
CfSeNa
CfSeH2C
CfSe)2
* Corresponding author. Tel.: +39-075-5855100; fax: +39-075-58551-
16; e-mail: tiecco@unipg.it
Scheme 1. Synthesis of the (R)-camphorseleno acetone 1 and the
methyl (R)-camphorseleno acetate.
0957-4166/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.12.035

784
M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 783–791
generated in situ from camphor diselenide and SO2Cl2 in
dichloromethane at 0 °C (55% yield).8 Methyl
(R)-camphorselenoacetate 2 was synthesized by nucleo-
philic substitution starting from methyl bromoacetate
and sodium camphorselenolate, generated in situ by
treatment of the camphor diselenide with sodium boro-
hydride in methanol (97% yield).9 Compounds 1 and 2
were used as precursors of chiral titanium enolates
in aldol condensations, according to the following
protocol.
(4:5) and anti selectivities (6:7) were observed in the
various cases. The two enantiomerically pure syn aldols
4 and 5 could be easily separated by flash chromato-
graphy, whereas the anti isomers, with the exception of
6a and 7a, were obtained as mixtures, which could not
be separated.
The structural determination of the b-hydroxy carbonyl
compounds 4, 5, 6, and 7 was not straightforward. The
relative configuration of aldol-type products is generally
assigned on the basis of the values of the 1H NMR
coupling constants of the vicinal protons.5c;11 In fact, the
A solution of the a-seleno carbonyl compound 1 or 2 in
CH2Cl2 was treated with 1.1 equiv of TiCl4 at )78 °C
under nitrogen. After 5 min 2 equiv of Et3N were added
and the resulting yellow mixture turned immediately
dark.10 After 1 h 1.1 equiv of an aromatic, a,b-unsatu-
rated or aliphatic aldehyde 3 were added dropwise and
the reaction mixture was stirred at the same temperature
for about 6 h. In the cases of the aldehydes 3c, 3g, and 3h
at the end of the addition the reaction temperature was
slowly allowed to raise to )30 °C. The reaction was then
quenched with a saturated solution of NH4Cl and
extracted with CH2Cl2. The crude mixtures were puri-
fied by flash chromatography using mixtures of diethyl
ether and light petroleum (40–60 °C) as the eluant.
3
anti aldols show larger JAB values (7–10 Hz) than the
a consequence of
syn aldols (3JAB ¼ 2–5 Hz) as
the preferentially assumed chair-like conformations in
which hydrogen bonds exist between the hydroxy and
the carbonyl groups. This seems not to be valid in the
3
present case since all the JAB coupling constants of the
b-hydroxyketones and of the b-hydroxyesters 4, 5, 6,
and 7 are large. As an example, the values of the cou-
pling constants observed for 4a, 5a, 6a, and 7a are
JAB ¼ 8:5, 7.9, 7.7, and 9.5, respectively. These large
3JAB values are consistent with an antiperiplanar orien-
tation of HA and HB protons, in both the syn and the
anti adducts, as indicated in the proposed preferentially
adopted conformation reported in Figure 1. These
conformations also explain the shielding effects observed
in the chemical shifts of the methyl group in the syn
products 4a and 5a and in the chemical shifts of the
proton HX in the anti adducts 6a and 7a. These effects
are due to the presence of the methyl or of the HX in the
shielding cone of the phenyl group.12
The condensation reactions generated the four possible
enantiomerically pure diasteroisomers. The reaction
products, the yields and the diastereomeric ratios,
1
measured by H NMR on the crude mixtures and con-
firmed after column chromatography purification, are
collected in Table 1. Good yields and good or moderate
selectivities in favor of the syn products (syn:anti ratio
up to 81:19) were observed in every case. Starting from
the a-selenoketone 1 the syn:anti ratios were higher than
those obtained from the a-selenoester 2. Different syn
The proposed absolute configurations of 4a, 5a, 6a, and
7a were confirmed by the results of the simple reactions
indicated in Scheme 2 and in Scheme 3. Scheme 2 refers
Table 1. TiCl4-mediated aldol condensation between 1 and 2 and various aldehydes
OH
R1
O
OH
O
+
+
R
R
R1
R1
R
R
SeCf
SeCf
5
O
O
TiCl4, Et3N
4
+
CfSe
R
R1
H
OH
O
OH
O
1 or 2
3
R1
SeCf
SeCf
6
7
R
R1
syn:antia
syn 4b
syn 5b
4:5a
anti 6+7b
16
6:7c
a
b
c
Me
Me
Ph
PhCH2CH2
76:24
81:19
73:27
61:39
65:35
60:40
65:35
63:37
41
33
27
35
28
12
24
18
9
28
20
17
15
24
11
6
82:18
54:46
57:43
68:32
65:35
33:67
69:31
75:25
58:42
70:30
56:44
80:20
80:20
67:33
70:30
19:81
14c
17c
33c
23c
24c
19c
14c
Me
PhCH2OCH2
Ph
d
e
OMe
OMe
OMe
OMe
OMe
p-OMe-C6H4
PhCH@CH
PhCH2CH2
PhCH2OCH2
f
g
h
a The diastereomeric ratios were determined by 1H NMR on the crude mixtures and confirmed after chromatographic separation.
b Percentage yields of the isolated products.
c
1
With the exception of 6a and 7a, all the other couples of diastereoisomers could not be separated. The ratios were determined by H NMR of the
mixtures.

M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 783–791
785
syn 5a
syn 4a
anti 6a
anti 7a
HA
HA
HA
HA
HCO
Ph
Ph
CfSe
OHC
Ph
O
OHC
SeCf
HCO
CfSe
Ph
Me
Cf*=
HX
Me
O
SeCf
MeHB
HB
O
HB
HBO
2.18 δ
O
Me
2.47 δ
3.61 δ
3.87 δ
2.71 δ
3.54 δ
2.42 δ
2.16 δ
Figure 1. Proposed preferred conformations for 4a, 5a, 6a, and 7a.
OH
O
4-phenylbutan-2-one 8 and ent-8 with those reported in
the literature.
OH
O
OH
O
O
90%
55%
70%
60%
Ph
Ph
Me
Me
Ph
Ph
Me
Me
Ph
Ph
Me
Me
SeCf
6a
SeCf
4a
As indicated in Scheme 2, 4a and 6a gave the (4R)-iso-
mer 8, while 5a and 7a gave the (4S)-isomer ent-8.13
8
OH
OH
O
OH
O
Scheme 3 describes the conversions of 4a, 5a, and 7a
into the corresponding acetonides 10, 11, and 12. For
this purpose the a-selenoaldols were reduced with
NaBH4 in MeOH and the resulting 1,3-diols were treat-
ed with 2,2-dimethoxypropane in acetone in the pres-
ence of catalytic amounts of p-toluensulphonic acid.4a
Only the reduction of 4a was completely stereoselective,
giving the indicated diol 9 as a single isomer. On the
contrary, the reductions of 5a and 7a gave mixtures of
the two possible diastereomeric diols. For the sake of
simplicity, Scheme 3 reports only the acetonides 11 and
12, deriving from the major isomers of the diols. The
observed 1H NMR vicinal coupling constants of the
acetonides and the results of some NOESY experiments
fully confirm the indicated configurations. In particular
SeCf
5a
SeCf
7a
ent-8
Scheme 2. Reductive deselenenylations of 4a, 5a, 6a, and 7a with
Ph3SnH and catalytic AIBN in refluxing C6H6.
HB
Me
OH OH
Me
H
a
b
Ph
HA
Me
O
4a
5a
Ph
O
Me
SeCf
SeCf
9
JAB = 1.7 Hz
10
SeCf
Ph
a,b
HA
a,b
3
7a
the JAB values, clearly indicate the relative stereo-
chemistry of the -Ph and the -SeCf substituents: syn in
O
Ph
HA
Me
O
Me
Me
CfSe
Me
O
Me
Me
O
HB
10 and 11 and anti in 12.14
HB
H
H
11 major isomer
AB = 1.8 Hz
12 major isomer
The absolute configuration of the carbon bearing the
hydroxy group in compounds 4b–d,f,h, 5b–d,f,h,
6b,d,f,h, and 7b–d,f,h was determined by reductive de-
selenenylation.15 The stereochemistry of all the aldols
J
JAB = 10.9 Hz
MeO OMe
b
, pTSA
a NaBH4, MeOH
Me
Me
1
was assigned by comparison of the H, 13C and 77Se
Scheme 3. Formation of the acetonides of compounds 4a, 5a, and 7a.
spectra with those of 4a, 5a, 6a, and 7a.16
In order to test their potential use as chiral building
blocks some simple manipulations of the aldols, pro-
duced as described above, were effected. Scheme 4 shows
the radical allylation of the syn b-hydroxy-a-camphor-
seleno esters, 4d and 5d, effected with allyltriphenyltin in
to the reductive deselenenylations of 4a, 5a, 6a, and 7a.
These reactions allow the absolute configuration at the
benzylic carbon to be assigned by comparison of the
specific rotations of the two enantiomers of 4-hydroxy-
OH
O
OH O
+
OH
O
Ph3SnCH2CH=CH2
Ph
OMe Ph
OMe
AIBN, refluxing benzene
Ph
OMe
SeCf
36%
[α]= +26.7
13 54%
[α]= +8.0
14
4d
OH
O
OH
O
OH
O
+
Ph
OMe
Ph
OMe
Ph3SnCH2CH=CH2
Ph
OMe
AIBN, refluxing benzene
SeCf
ent 13 33%
[α]= -8.9
27%
[α]= -27.4
ent 14
5d
Scheme 4. Radical allylation of the b-hydroxy-a-camphorseleno esters 4d and 5d.

786
M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 783–791
the presence of AIBN in refluxing benzene. In both cases
the substitution products 13 and 14 or their enantiomers
ent-13 and ent-14 were isolated by column chromatog-
raphy in good yields. Thus, all the four possible
enantiomerically pure isomers of the methyl 2-
[hydroxy(phenyl)methyl]pent-4-enoate were obtained.
These unsaturated hydroxyesters may be used as start-
ing materials for further stereospecific transformations.
For example, they may be easily converted into enan-
tiomerically pure trisubstituted tetrahydrofurans by ring
closure reactions promoted by electrophilic reagents.1
m=z (rel. int.) 288 (100), 231 (44), 202 (42), 177 (13), 152
(15), 121 (54), 109 (21), 93 (16), 83 (44), 79 (15), 67 (13),
55 (24). Anal. Calcd for C13H20O2Se: C, 54.36; H, 7.02.
Found: C, 54.01; H, 6.98.
4.3. Methyl (R)-camphorselenoacetate 2
25
1
Oil; ½aꢀ ¼ )23.9 (c 3.2, CHCl3). H NMR: d 3.99 (dd,
1H, JD¼ 2:0, 4.7 Hz), 3.75 (s, 3H), 3.55 (d, 1H,
J ¼ 12:7 Hz), 3.27 (d, 1H, J ¼ 12:7 Hz), 2.24 (t, 1H,
J ¼ 4:3 Hz), 1.80–1.60 (m, 3H), 1.58–1.30 (m, 1H), 1.03
(s, 3H), 0.95 (s, 6H). 13C NMR: d 217.4, 171.7, 58.1,
52.4, 47.8, 47.2, 46.8, 30.5, 23.3, 22.3, 19.6, 19.4, 9.5. MS
m=z (rel. int.) 304 (100), 276 (18), 244 (9), 231 (91), 203
(15), 193 (26), 151 (45), 137 (10), 123 (81), 109 (30), 107
(32), 95 (28), 93 (28), 91 (29), 83 (69), 81 (46), 79 (29), 67
(20), 55 (50). Anal. Calcd for C13H20O3Se: C, 51.49; H,
6.65. Found: C, 51.92; H, 6.21.
3. Conclusion
In conclusion, we have reported that the titanium eno-
lates deriving from (R)-camphorselenoacetone 1 and
methyl (R)-camphorselenoacetate 2 can be successfully
employed as chiral nucleophiles in asymmetric crossed
aldol reactions in the presence of aromatic, conjugated
or aliphatic aldehydes. Enantiomerically pure syn and
anti aldols have been separated in good yields and with
moderate selectivities. Several simple manipulations of
the b-hydroxy-a-camphorseleno ketones or esters were
carried out in order to determine their structures and to
study their potential application as intermediates in
asymmetric synthesis.
4.4. Aldol reactions: general procedure
A solution of the a-seleno carbonyl compound 1 or 2 in
CH2Cl2 was treated with 1.1 equiv of TiCl4 at )78 °C
under nitrogen. After 5 min 2 equiv of Et3N were added
and immediately the yellow mixture turned dark. After
1 h 1.1 equiv of an aromatic, a,b-unsaturated or ali-
phatic aldehyde 3 were added dropwise and the reaction
mixture was stirred at the same temperature for about
6 h. In the cases of the aldehydes 3c, 3g, and 3h, at the
end of the addition, the reaction temperature was slowly
allowed to rise to )30 °C. The reaction was then
quenched with a saturated solution of NH4Cl and
extracted with CH2Cl2. The crude mixture was purified
by flash chromatography using mixtures of diethyl ether
and light petroleum (40–60 °C) as the eluant. The com-
pounds 4a–g, 5a–g, 6a, 7a, and the mixtures of 4h/5h and
6b–h/7b–h were separated and characterized. Physical
and spectral data of these products are reported below.
4. Experimental
1
New compounds were characterized by MS, H, 77Se
and 13C NMR spectroscopy. GLC analyses and MS
spectra were carried out with an HP 6890 gas chro-
matograph (25 m dimethyl silicone capillary column)
equipped with an HP 5973 Mass Selective Detector; for
the ions containing selenium only the peaks arising from
the selenium-80 isotope is given. 1H, 77Se and 13C NMR
spectra were recorded at 400, 76.27 and 100.62 MHz,
respectively, on a Bruker DRX 400 instrument; unless
otherwise specified, CDCl3 was used as solvent and
TMS as standard. Optical rotations were measured with
a Jasco DIP-1000 digital polarimeter. Elemental analy-
ses were carried out on a Carlo Erba 1106 Elemental
Analyzer.
4.5. (3R,4S)-3-(camphorseleno)-4-hydroxy-4-phenyl
butan-2-one 4a
20
D
1
Oil; ½aꢀ ¼ +70.0 (c 2.4, CHCl3). H NMR: d 7.40–7.15
(m, 5H), 4.97 (d, 1H, J ¼ 8:5 Hz), 4.60 (br s, 1H), 3.96
(d, 1H, J ¼ 8:5 Hz), 3.61 (dd, 1H, J ¼ 1:8, 4.8 Hz), 2.18
(s, 3H), 2.11 (t, 1H, J ¼ 4:2 Hz), 1.92–1.30 (m, 4H), 0.98
(s, 3H), 0.95 (s, 3H), 0.89 (s, 3H). 13C NMR: d 220.9,
204.5, 146.0, 128.3 (two carbons), 127.8, 126.7 (two
carbons), 71.0, 58.6, 55.7, 48.6, 46.0, 41.7, 30.8, 29.1,
23.7, 19.7, 19.0, 9.5. 77Se NMR: d 480.3. Anal. Calcd for
C20H26O3Se: C, 61.06; H, 6.66. Found: C, 61.60; H, 6.75.
4.1. Syntheses of the (R)-camphorselenoacetone 1 and of
the methyl (R)-camphorselenoacetate 2
The a-selenoketone 1 and the a-selenoester 2 have been
prepared starting from the (R,R)-camphor diselenide
using standard procedures.8;9
4.2. (R)-Camphorselenoacetone 1
20
D
1
4.6. (3R,4S)-3-(camphorseleno)-4-hydroxy-6-phenyl
hexan-2-one 4b
Oil; ½aꢀ ¼ +18.3 (c 1.2, CHCl3). H NMR: d 3.76 (dd,
1H, J ¼ 2:0, 4.6 Hz), 3.55 (d, 1H, J ¼ 12:0 Hz), 3.37 (d,
1H, J ¼ 12:0 Hz), 2.34 (s, 3H), 2.20 (t, 1H, J ¼ 4:2 Hz),
1.85–1.50 (m, 3H), 1.45–1.20 (m, 1H), 0.99 (s, 3H), 0.90
(s, 3H), 0.89 (s, 3H). 13C NMR: d 217.3, 203.8, 58.1,
47.7, 47.4, 46.7, 32.2, 30.5, 27.8, 23.2, 19.5, 19.4, 9.5. MS
21
Oil; ½aꢀ ¼ +47.3 (c 2.7, CHCl3). H NMR: d 7.35–7.15
1
D
(m, 5H), 4.37 (d, 1H, J ¼ 3:7 Hz), 3.88–3.80 (m, 1H),
3.71 (dd, 1H, J ¼ 2:3–4.5 Hz), 3.51 (d, 1H, J ¼ 9:5 Hz),

M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 783–791
787
3.04–2.95 (ddd, 1H, J ¼ 5:5, 8.2, 13.8 Hz), 2.69 (dt, 1H,
J ¼ 8:2, 13.8 Hz), 2.31 (s, 3H), 2.15 (t, 1H, J ¼ 4:4 Hz),
1.92–1.65 (m, 4H), 1.52–1.38 (m, 2H), 1.0 (s, 3H), 0.98
(s, 3H), 0.95 (s, 3H). 13C NMR: d 221.2, 203.8, 142.1,
128.4 (two carbons), 128.2 (two carbons), 125.6, 68.2,
58.6, 54.6, 48.7, 47.2, 45.8, 36.9, 32.7, 30.7, 29.0, 23.9,
19.7, 19.0, 9.5. 77Se NMR: d 481.4. Anal. Calcd for
C22H30O3Se: C, 62.70; H, 7.18. Found: C, 62.39; H, 7.40.
J ¼ 6:5, 15.9 Hz), 4.73 (d, 1H, J ¼ 4:0 Hz), 4.52 (ddd,
1H, J ¼ 4:0, 6.5, 9.3 Hz), 4.27 (dd, 1H, J ¼ 2:3, 4.6 Hz),
3.71 (s, 3H), 3.52 (d, 1H, J ¼ 9:3 Hz), 2.29 (t, 1H,
J ¼ 4:4 Hz), 1.95–1.83 (m, 1H), 1.81–1.75 (m, 1H), 1.58–
1.40 (m, 2H), 1.04 (s, 3H), 0.99 (s, 3H), 0.98 (s, 3H). 13C
NMR: d 221.1, 172.4, 136.5, 132.4, 128.5 (two carbons),
127.8, 127.2, 126.6 (two carbons), 70.8, 58.7, 52.3, 48.8,
47.3, 46.1, 45.7, 30.8, 23.7, 19.7, 19.1, 9.6. 77Se NMR: d
503.0. Anal. Calcd for C22H28O4Se: C, 60.69; H, 6.48.
Found: C, 60.99; H, 6.60.
4.7. (3R,4S)-5-(benzyloxy)-3-(camphorseleno)-4-hydroxy
pentan-2-one 4c
4.11. Methyl (2R,3S)-2-(camphorseleno)-3-hydroxy-5-
phenylpentanoate 4g
22
D
1
Oil; ½aꢀ ¼ +49.3 (c 1.4, CHCl3). H NMR: d 7.47–7.28
(m, 5H), 4.57 (d, 1H, J ¼ 11:9 Hz), 4.50 (d, 1H,
J ¼ 11:9 Hz), 4.49 (br s, 1H), 4.18–4.03 (m, 1H), 3.84
(dd, 1H, J ¼ 2:5, 4.7 Hz), 3.81 (d, 1H, J ¼ 9:3 Hz), 3.68
(dd, 1H, J ¼ 4:6, 10.0 Hz), 3.64 (dd, 1H, J ¼ 5:2,
10.0 Hz), 2.31 (s, 3H), 2.19 (t, 1H, J ¼ 4:4 Hz), 1.98–1.65
(m, 2H), 1.52–1.30 (m, 2H), 1.0 (s, 3H), 0.97 (s, 3H),
0.95 (s, 3H). 13C NMR: d 221.2, 204.0, 135.0, 128.3 (two
carbons), 127.7 (two carbons), 127.6, 73.4, 71.7, 68.0,
58.5, 51.5, 48.8, 46.8, 45.9, 30.7, 28.6, 23.9, 19.7, 19.0,
9.5. 77Se NMR: d 468.4. Anal. Calcd for C22H30O4Se: C,
60.41; H, 6.91. Found: C, 60.19; H, 6.99.
17
D
1
Oil; ½aꢀ ¼ )41.6 (c 3.5, CHCl3). H NMR: d 7.30–7.08
(m, 5H), 4.50 (br s, 1H), 4.14 (dd, 1H, J ¼ 2:3, 4.6 Hz),
3.80 (dt, 1H, J ¼ 2:9, 9.0 Hz), 3.70 (s, 3H), 3.35 (d, 1H,
J ¼ 9:0 Hz), 2.99 (ddd, 1H, J ¼ 5:0, 10.5, 13.8 Hz), 2.70
(ddd, 1H, J ¼ 6:4, 11.0, 13.8 Hz), 2.22 (t, 1H,
J ¼ 4:4 Hz), 1.98–1.70 (m, 4H), 1.65–1.35 (m, 2H), 1.0
(s, 3H), 0.92 (s, 3H), 0.90 (s, 3H). 13C NMR: d 221.1,
173.0, 142.0, 128.5 (two carbons), 128.3 (two carbons),
125.7, 69.1, 58.7, 52.3, 48.8, 47.2, 46.4, 45.6, 36.7, 32.5,
30.7, 24.3, 19.7, 19.1, 9.6. 77Se NMR: d 505.3. Anal.
Calcd for C22H30O4Se: C, 60.41; H, 6.91. Found: C,
60.73; H, 6.98.
4.8. Methyl (2R,3S)-2-(camphorseleno)-3-hydroxy-3-
phenylpropanoate 4d
4.12. Methyl (2R,3S) and (2S,3R)-4-(benzyloxy)-2-
(camphorseleno)-3-hydroxybutanoate 4h and 5h
25
D
1
Oil; ½aꢀ ¼ )41.2 (c 1.5, CHCl3). H NMR: d 7.49–7.35
(m, 2H), 7.35–7.20 (m, 3H), 4.88 (dd, 1H, J ¼ 3:9,
9.0 Hz), 4.75 (d, 1H, J ¼ 3:9 Hz), 4.19 (dd, 1H, J ¼ 2:3,
4.6 Hz), 3.69 (d, 1H, J ¼ 9:0 Hz), 3.55 (s, 3H), 2.20 (t,
1H, J ¼ 4:3 Hz), 1.90–1.68 (m, 3H), 1.50–1.40 (m, 1H),
1.0 (s, 3H), 0.96 (s, 6H). 13C NMR: d 220.8, 172.3, 140.1,
128.2 (two carbons), 127.9, 126.4 (two carbons), 72.0,
58.5, 52.0, 48.6, 47.7, 47.1, 45.6, 30.6, 23.4, 19.6, 19.0,
9.4. 77Se NMR: d 505.2. Anal. Calcd for C20H26O4Se: C,
58.68; H, 6.40. Found: C, 58.80; H, 6.46.
1
Major diastereoisomer (2R,3S): H NMR d 7.38–7.30
(m, 5H), 4.61 (d, 1H, J ¼ 11:8 Hz), 4.54 (d, 1H,
J ¼ 11:8 Hz), 4.28–4.22 (m, 1H), 3.98 (d, 1H,
J ¼ 6:2 Hz), 3.97 (dd, 1H, J ¼ 2:6, 5.0 Hz), 3.77 (d, 1H,
J ¼ 2:9 Hz), 3.72 (s, 3H), 3.70–3.67 (m, 2H), 2.30 (t, 1H,
J ¼ 4:3 Hz), 1.95–1.80 (m, 1H), 1.78–1.60 (m, 2H), 1.58–
1.40 (m, 1H), 1.03 (s, 3H), 0.96 (s, 3H), 0.93 (s, 3H). 13C
NMR: d 218.7, 173.2, 138.3, 128.8 (two carbons), 128.3
(two carbons), 128.1, 73.9, 72.0, 70.8, 58.6, 52.9, 49.2,
48.3, 47.3, 45.2, 31.0, 23.9, 20.0, 19.7, 10.1. 77Se NMR: d
501.3. Anal. Calcd for C22H30O5Se: C, 58.28; H, 6.67.
Found: C, 58.43; H, 6.70. Minor diastereoisomer
(2S,3R) (distinct signals): 1H NMR: d 4.64 (d, 1H,
J ¼ 4:7 Hz), 4.58 (d, 1H, J ¼ 11:8 Hz), 4.53 (d, 1H,
J ¼ 11:8 Hz), 4.25–4.21 (m, 1H), 4.14–4.07 (m, 1H), 3.63
(s, 3H), 2.25 (t, 1H, J ¼ 4:3 Hz), 1.02 (s, 3H), 0.98 (s,
3H), 0.97 (s, 3H). 13C NMR: d 221.6, 128.7, 128.2, 128.0,
72.2, 69.2, 59.1, 52.6, 49.3, 47.7, 46.2, 44.3, 31.2, 24.1,
20.1. 77Se NMR: d 496.7.
4.9. Methyl (2R,3S)-2-(camphorseleno)-3-hydroxy-3-(4-
methoxyphenyl)propanoate 4e
26
D
Oil; ½aꢀ ¼ )40.4 (c 2.0, CHCl3). 1H NMR: d 7.30 (A2B2
system, 2H), 6.83 (A2B2 system, 2H), 4.83 (dd,
1H, J ¼ 3:9, 9.3 Hz), 4.67 (d, 1H, J ¼ 3:9 Hz), 4.17 (dd,
1H, J ¼ 2:3, 4.6 Hz), 3.80 (s, 3H), 3.67 (d, 1H,
J ¼ 9:3 Hz), 3.54 (s, 3H), 2.21 (t, 1H, J ¼ 4:3 Hz), 1.80–
1.30 (m, 4H), 1.0 (s, 3H), 0.93 (s, 6H). 13C NMR: d
221.3, 172.8, 159.7, 132.8, 128.3 (two carbons), 114.2
(two carbons), 72.3, 59.1, 55.6, 52.6, 49.2, 48.3, 47.7,
46.2, 31.3, 24.1, 20.2, 19.6, 10.0. 77Se NMR: d 505.6.
Anal. Calcd for C21H28O5Se: C, 57.40; H, 6.42. Found:
C, 57.73; H, 6.19.
4.13. (3S,4R)-3-(camphorseleno)-4-hydroxy-4-phenyl
butan-2-one 5a
22
D
Oil; ½aꢀ ¼ )125.0 (c 0.4, CHCl3). 1H NMR: d 7.35–7.01
(m, 5H), 5.08 (dd, 1H, J ¼ 2:2, 7.9 Hz), 4.13 (d, 1H,
J ¼ 2:2 Hz), 3.99 (d, 1H, J ¼ 7:9 Hz), 3.87 (dd, 1H,
J ¼ 2:2, 4.6 Hz), 2.32 (t, 1H, J ¼ 4:4 Hz), 2.16 (s, 3H),
1.92–1.50 (m, 4H), 1.04 (s, 3H), 0.95 (s, 6H). 13C NMR:
d 217.9, 204.7, 140.5, 128.3 (two carbons), 128.0, 127.4
(two carbons), 73.1, 58.2, 57.7, 49.0, 48.8, 47.0, 30.4,
4.10. Methyl (2R,3S,4E)-2-(camphorseleno)-3-hydroxy-
5-phenylpent-4-enoate 4f
23
Oil; ½aꢀ ¼ )58.1 (c 1.6, CHCl3). H NMR: d 7.50–7.25
1
D
(m, 5H), 6.73 (d, 1H, J ¼ 15:9 Hz), 6.20 (dd, 1H,

788
M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 783–791
29.3, 23.5, 19.7, 19.4, 9.5. 77Se NMR: d 478.0. Anal.
Calcd for C20H26O3Se: C, 61.06; H, 6.66. Found: C,
61.22; H, 6.79.
(s, 3H), 0.97 (s, 3H). 13C NMR: d 219.4, 172.0, 159.8,
132.7, 128.8 (two carbons), 114.1 (two carbons), 74.4,
58.7, 55.6, 52.7, 51.2, 49.4, 49.3, 47.4, 31.0, 23.8, 20.1,
19.7, 10.0. 77Se NMR: d 510.0. Anal. Calcd for
C21H28O5Se: C, 57.40; H, 6.42. Found: C, 57.85; H, 6.20.
4.14. (3S,4R)-3-(camphorseleno)-4-hydroxy-6-phenyl
hexan-2-one 5b
4.18. Methyl (2S,3R,4E)-2-(camphorseleno)-3-hydroxy-
5-phenylpent-4-enoate 5f
24
D
Oil; ½aꢀ ¼ )105.7 (c 0.4, CHCl3). 1H NMR: d 7.30–7.18
(m, 5H), 4.04-3.97 (m, 1H), 3.83 (dd, 1H, J ¼ 2:4,
4.5 Hz), 3.76 (d, 1H, J ¼ 6:4 Hz), 3.63 (br s, 1H), 2.90
(ddd, 1H, J ¼ 5:3, 9.6, 13.6 Hz), 2.75 (ddd, 1H, J ¼ 7:1,
9.2, 13.6), 2.39 (s, 3H), 2.29 (t, 1H, J ¼ 4:4 Hz), 1.99–
1.40 (m, 6H), 1.05 (s, 3H), 0.96 (s, 3H) 0.90 (s, 3H). 13C
NMR: d 217.6, 206.1, 142.2, 129.0 (two carbons), 128.8
(two carbons), 126.3, 70.1, 58.6, 56.1, 49.4, 49.3, 48.5,
36.9, 32.3, 30.9, 29.3, 24.0, 20.1, 19.8, 10.0. 77Se NMR: d
473.6. Anal. Calcd for C22H30O3Se: C, 62.70; H, 7.18.
Found: C, 62.99; H, 7.30.
24
D
1
Oil; ½aꢀ ¼ )50.4 (c 2.5, CHCl3). H NMR: d 7.42–7.23
(m, 5H), 6.74 (d, 1H, J ¼ 15:9 Hz), 6.26 (d, 1H, J ¼ 6:4,
15.9 Hz), 4.72 (ddd, 1H, J ¼ 2:7, 6.4, 7.2 Hz), 4.15 (d,
1H, J ¼ 2:7 Hz) 3.97 (dd, 1H, J ¼ 2:3, 4.6 Hz), 3.91 (d,
1H, J ¼ 7:2 Hz), 3.75 (s, 3H), 2.27 (t, 1H, J ¼ 4:4 Hz),
1.90–1.80 (m, 1H), 1.75–1.53 (m, 2H), 1.50–1.35 (m,
1H), 1.02 (s, 3H), 0.96 (s, 3H), 0.93 (s, 3H). 13C NMR: d
218.8, 172.2, 136.5, 132.6, 128.5 (two carbons), 127.8,
127.4, 126.7 (two carbons), 72.7, 58.2, 52.5, 48.8, 48.1,
48.0, 47.0, 30.5, 23.4, 19.7, 19.2, 9.6. 77Se NMR: d 507.8.
Anal. Calcd for C22H28O4Se: C, 60.69; H, 6.48. Found:
C, 60.99; H, 6.50.
4.15. (3S,4R)-5-(benzyloxy)-3-(camphorseleno)-4-
hydroxypentan-2-one 5c
24
D
1
Oil; ½aꢀ ¼ )64.9 (c 0.5, CHCl3). H NMR: d 7.48–7.28
4.19. Methyl (2S,3R)-2-(camphorseleno)-3-hydroxy-5-
phenylpentanoate 5g
(m, 5H), 4.56 (d, 1H J ¼ 11:9 Hz), 4.49 (d, 1H,
J ¼ 11:9 Hz), 4.20 (dt, 1H, J ¼ 5:0, 6.5 Hz), 3.91 (d, 1H,
J ¼ 6:5 Hz), 3.79 (dd, 1H, J ¼ 2:7, 4.7 Hz), 3.66 (dd, 1H,
J ¼ 5:0, 9.7 Hz), 3.62 (dd, 1H, J ¼ 5:0, 9.7 Hz), 3.50 (br
s, 1H), 2.40 (s, 3H), 2.26 (t, 1H, J ¼ 4:4 Hz), 1.98–1.50
(m, 4H), 1.0 (s, 3H), 0.98 (s, 3H) 0.95 (s, 3H). 13C NMR:
d 217.7, 205.2, 137.6, 128.4 (two carbons), 127.9 (two
carbons), 127.8, 73.5, 71.5, 69.6, 58.2, 52.6, 49.0, 48.4,
46.9, 30.5, 28.6, 23.6, 19.7, 19.3, 9.6. 77Se NMR: d 467.5.
Anal. Calcd for C22H30O4Se: C, 60.41; H, 6.91. Found:
C, 60.93; H, 6.72.
19
D
1
Oil; ½aꢀ ¼ )79.5 (c 1.7, CHCl3). H NMR: d 7.27–7.08
(m, 5H), 4.50 (br s, 1H), 3.99 (ddd, 1H, J ¼ 3:8, 5.3,
9.0 Hz), 3.91 (dd, 1H, J ¼ 2:2, 4.6 Hz), 3.88 (d, 1H,
J ¼ 5:3 Hz), 3.74 (s, 3H), 2.87 (ddd, 1H, J ¼ 5:4, 9.7,
13.8 Hz), 2.74 (ddd, 1H, J ¼ 7:1, 9.2, 13.8 Hz), 2.27 (t,
1H, J ¼ 4:4 Hz), 2.02–1.91 (m, 1H), 1.91–1.79 (m, 2H),
1.78–1.68 (m, 1H), 1.64–1.55 (m, 1H), 1.51–1.41 (m,
1H), 1.01 (s, 3H), 0.97 (s, 3H), 0.96 (s, 3H). 13C NMR: d
218.8, 173.6, 141.8, 128.6 (two carbons), 128.3 (two
carbons), 125.8, 70.4, 58.2, 52.4, 48.7, 47.3, 47.0, 46.9,
36.1, 31.7, 30.5, 23.5, 19.6, 19.2, 9.6. 77Se NMR: d 505.5.
Anal. Calcd for C22H30O4Se: C, 60.41; H, 6.91. Found:
C, 60.58; H, 6.99.
4.16. Methyl (2S,3R)-2-(camphorseleno)-3-hydroxy-3-
phenylpropanoate 5d
26
D
1
Oil; ½aꢀ ¼ )86.4 (c 2.5, CHCl3). H NMR: d 7.40–7.35
(m, 2H), 7.35–7.20 (m, 3H), 5.05 (dd, 1H, J ¼ 1:8,
8.3 Hz), 4.48 (d, 1H, J ¼ 1:8 Hz), 3.93 (dd, 1H, J ¼ 2:2,
4.6 Hz), 3.91 (d, 1H, J ¼ 8:3 Hz), 3.55 (s, 3H), 2.29 (t,
1H, J ¼ 4:4 Hz), 1.92–1.81 (m, 1H), 1.75–1.66 (m, 1H),
1.61 (ddd, 1H, J ¼ 3:7, 9.2, 13.1 Hz), 1.50–1.36 (m, 1H),
1.01 (s, 3H), 0.93 (s, 3H), 0.91 (s, 3H). 13C NMR: d
218.8, 171.6, 140.2, 128.3 (two carbons), 128.2, 126.6
(two carbons), 74.3, 58.3, 52.3, 50.6, 49.0, 48.8, 47.0,
30.6, 23.4, 19.7, 19.3, 9.6. 77Se NMR: d 509.4. Anal.
Calcd for C20H26O4Se: C, 58.68; H, 6.40. Found: C,
58.89; H, 6.49.
4.20. (3S,4S)-3-(camphorseleno)-4-hydroxy-4-phenyl
butan-2-one 6a
1
Oil (purity about 90%, [a] not determined); H NMR: d
7.50–7.20 (m, 5H), 5.50 (dd, 1H, J ¼ 3:4, 7.7 Hz), 4.08
(d, 1H, J ¼ 7:7 Hz), 3.54 (dd, 1H, J ¼ 2:1, 4.6 Hz), 3.44
(d, 1H, J ¼ 3:4 Hz), 2.42 (s, 3H), 2.19 (t, 1H,
J ¼ 4:0 Hz), 1.98–1.30 (m, 4H), 1.02 (s, 3H), 0.91 (s,
3H), 0.85 (s, 3H). 13C NMR: d 216.8, 206.5, 140.9, 128.4
(two carbons), 128.1, 126.7 (two carbons), 75.2, 58.1,
52.6, 48.5, 47.9, 46.8, 30.4, 29.2, 23.5, 19.6, 19.5, 9.6.
4.17. Methyl (2S,3R)-2-(camphorseleno)-3-hydroxy-3-
(4-methoxyphenyl)propanoate 5e
4.21. (3S,4S)- and (3S,4R)-3-(camphorseleno)-4-hydroxy-
6-phenylhexan-2-one 6b and 7b
26
D
Oil; ½aꢀ ¼ )51.3 (c 1.3, CHCl3). 1H NMR: d 7.31 (A2B2
1
system, 2H), 6.85 (A2B2 system, 2H), 5.0 (dd, 1H,
J ¼ 2:4, 8.3 Hz), 4.39 (d, 1H, J ¼ 2:4 Hz), 3.94 (dd, 1H,
J ¼ 2:3, 4.3 Hz), 3.87 (d, 1H, J ¼ 8:3 Hz), 3.80 (s, 3H),
3.54 (s, 3H), 2.30 (t, 1H, J ¼ 4:5 Hz), 1.98–1.80 (m, 1H),
1.77–1.52 (m, 2H), 1.48–1.30 (m, 1H), 1.13 (s, 3H), 0.98
Oil; Major diastereoisomer (3S,4S): H NMR: d 7.30–
7.20 (m, 5H), 3.92–3.84 (m, 1H), 3.72 (d, 1H,
J ¼ 8:0 Hz), 3.56 (dd, 1H, J ¼ 2:9, 3.9 Hz), 3.11 (d, 1H,
J ¼ 5:5 Hz), 2.97–2.85 (m, 1H), 2.85–2.70 (m, 1H), 2.45
(s, 3H), 2.16 (t, 1H, J ¼ 4:3 Hz), 1.98–1.52 (m, 6H), 0.97

M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 783–791
789
(s, 3H), 0.91 (s, 3H) 0.84 (s, 3H). 13C NMR: d 217.5,
206.6, 142.1, 129.2 (two carbons), 128.8 (two carbons),
126.3, 70.7, 58.4, 53.6, 49.4, 48.3, 47.2, 36.2, 32.1, 30.8,
29.3, 24.1, 20.0, 19.8, 10.0. 77Se NMR: d 492.8. Anal.
Calcd for C22H30O3Se: C, 62.70; H, 7.18. Found: C,
62.85; H, 7.28. Minor diastereoisomer (3R,4R) (distinct
1H, J ¼ 5:7 Hz), 2.14 (t, 1H, J ¼ 4:3 Hz), 1.95–1.55 (m,
3H), 1.50–1.28 (m, 1H), 1.0 (s, 3H), 0.90 (s, 3H) 0.80 (s,
3H). 13C NMR: d 218.0, 173.7, 159.7, 133.3, 128.0 (two
carbons), 114.2 (two carbons), 75.2, 58.6, 55.6, 52.8,
48.6, 47.6, 47.2, 45.2, 30.9, 23.8, 20.0, 19.9, 10.0. 77Se
NMR: d 535.6. Anal. Calcd for C21H28O5Se: C, 57.40;
H, 6.42. Found: C, 57.71; H, 6.55. Minor diastereoiso-
1
signals): H NMR: d 4.12–4.06 (m, 1H), 3.71 (dd, 1H,
1
J ¼ 2:1, 4.9 Hz), 3.66 (d, 1H, J ¼ 8:2 Hz), 2.99 (d, 1H,
J ¼ 7:2 Hz), 2.43 (s, 3H), 1.01 (s, 3H), 0.96 (s, 3H). 13C
NMR: d 217.7, 206.4, 142.4, 129.0 (two carbons), 126.2,
72.1, 58.6, 51.9, 48.8, 47.5, 47.3, 32.5, 30.1, 29.4, 23.9,
10.1. 77Se NMR: d 500.6.
mer (2R,3R) (distinct signals): H NMR: d 7.36 (A2B2
system, 2H), 5.04 (d, 1H, J ¼ 8:5 Hz), 3.98 (d, 1H,
J ¼ 8:5 Hz), 3.74 (s, 3H), 3.45 (dd, 1H, J ¼ 1:9, 4.6 Hz),
3.30 (br s, 1H), 1.98 (t, 1H, J ¼ 4:3 Hz), 0.95 (s, 3H),
0.87 (s, 3H), 0.75 (s, 3H). 13C NMR: d 173.2, 128.5, 75.5,
53.0, 45.8, 30.8, 23.6, 19.7. 77Se NMR: d 526.7.
4.22. (3S,4S) and (3S,4R)-5-(benzyloxy)-3-(camphor-
seleno)-4-hydroxypentan-2-one 6c and 7c
4.25. Methyl (2S,3S,4E)- and (2R,3R,4E)-2-(camphor-
seleno)-3-hydroxy-5-phenylpent-4-enoate 6f and 7f
Oil; 1H NMR: d 7.46–7.25 (m, 10H), 4.64–4.55 (m, 4H),
4.29–4.20 (m, 1H), 4.19–4.10 (m, 1H), 4.02 (dd, 1H,
J ¼ 4:0, 10.1 Hz), 3.94 (d, 1H, J ¼ 9:3 Hz), 3.91 (d, 1H,
J ¼ 8:6 Hz), 3.84 (dd, 1H, J ¼ 3:3, 10.1 Hz), 3.83–3.79
(m, 2H), 3.78–3.74 (m, 2H), 3.20 (br s, 1H), 2.99 (br s,
1H), 2.45 (s, 6H), 2.20–2.10 (m, 2H), 1.98–1.50 (m, 8H),
1.0 (s, 3H), 0.98 (s, 3H), 0.92 (s, 3H), 0.91 (s, 3H), 0.88
(s, 3H), 0.87 (s, 3H). 13C NMR: d 217.6 (two carbons),
205.2, 204.9, 137.9 (two carbons), 128.4 (four carbons),
127.8 (six carbons), 73.5 (two carbons), 71.6, 71.3, 71.2,
71.0, 58.2, 58.0, 49.0, 48.8, 48.5 (two carbons), 47.3,
47.0, 46.9, 46.8, 30.4 (two carbons), 28.7, 28.2, 23.6,
23.5, 19.6, 19.5, 19.4, 19.3, 9.6 (two carbons). 77Se
NMR: d 492.8 and 490.3. Anal. Calcd for C22H30O4Se:
C, 60.41; H, 6.91. Found: C, 60.75; H, 6.70.
1
Oil; Major diastereoisomer (2S,3S): H NMR: d 7.45–
7.20 (m, 5H), 6.77 (dd, 1H, J ¼ 1:1, 15.9 Hz), 6.37 (dd,
1H, J ¼ 6:0, 15.9 Hz), 4.80–4.70 (m, 1H), 4.15 (d, 1H,
J ¼ 5:3 Hz) 3.96 (dd, 1H, J ¼ 2:2, 4.7 Hz), 3.79 (s, 3H),
3.69 (d, 1H, J ¼ 8:9 Hz), 2.28 (t, 1H, J ¼ 4:6 Hz), 1.95–
1.55 (m, 3H), 1.52–1.40 (m, 1H), 1.03 (s, 3H), 0.96 (s,
3H), 0.93 (s, 3H). 13C NMR: d 218.4, 173.0, 136.4, 132.2,
128.5 (three carbons), 127.8, 126.7 (two carbons), 73.0,
58.2, 52.5, 48.5, 47.2, 46.9, 45.1, 30.5, 23.4, 19.6, 19.3,
9.6. 77Se NMR: d 521.7. Anal. Calcd for C22H28O4Se: C,
60.69; H, 6.48. Found: C, 60.79; H, 6.23. Minor dia-
stereoisomer (2R,3R) (distinct signals): 1H NMR: d 6.73
(dd, 1H, J ¼ 1:1, 15.9 Hz), 6.36 (dd, 1H, J ¼ 6:2,
15.9 Hz), 4.17 (dd, 1H, J ¼ 2:2, 4.6 Hz), 3.76 (d, 1H,
J ¼ 6:9 Hz), 3.43 (d, 1H, J ¼ 6:6 Hz), 2.47 (t, 1H,
J ¼ 4:4 Hz), 1.2 (s, 3H), 0.95 (s, 3H), 0.91 (s, 3H). 13C
NMR: d 217.4, 172.5, 136.3, 132.3, 128.2, 127.9, 73.2,
58.2, 48.4, 47.7, 43.9, 23.3, 19.4.
4.23. Methyl (2S,3S)- and (2R,3R)-2-(camphorseleno)-3-
hydroxy-3-phenylpropanoate 6d and 7d
1
4.26. Methyl (2S,3S)- and (2R,3R)-2-(camphorseleno)-3-
hydroxy-5-phenylpentanoate 6g and 7g
Oil; Major diastereoisomer (2S,3S): H NMR: d 7.48–
7.25 (m, 5H), 5.12 (dd, 1H, J ¼ 6:2, 7.9 Hz), 4.22 (d, 1H,
J ¼ 6:2 Hz), 3.80 (d, 1H, J ¼ 7:9 Hz), 3.70 (dd, 1H,
J ¼ 2:2, 4.7 Hz), 3.68 (s, 3H), 2.16 (t, 1H, J ¼ 4:3 Hz),
1.88–1.76 (m, 1H), 1.72–1.60 (m, 2H), 1.45–1.35 (m,
1H), 0.99 (s, 3H), 0.89 (s, 3H) 0.83 (s, 3H). 13 C NMR: d
217.6, 173.1, 140.7, 128.2 (two carbons), 127.8, 126.1
(two carbons), 75.0, 58.0, 52.3, 48.0, 46.9, 46.7, 44.3,
30.3, 23.2, 19.4, 19.3, 9.4. 77Se NMR: d 539.8. Anal.
Calcd for C20H26O4Se: C, 58.68; H, 6.40. Found: C,
58.77; H, 6.31. Minor diastereoisomer (2R,3R) (distinct
1
Oil; Major diastereoisomer (2S,3S): H NMR: d 7.35–
7.15 (m, 5H), 4.50 (br s, 1H), 3.93 (d, 1H, J ¼ 5:7 Hz),
3.91 (dt, 1H, J ¼ 3:5, 5.7 Hz), 3.85 (dd, 1H, J ¼ 2:1,
4.6 Hz), 3.76 (s, 3H), 2.95–2.88 (m, 1H), 2.80–2.69 (m,
1H), 2.11 (t, 1H, J ¼ 4:4 Hz), 2.15–2.01 (m, 1H), 1.94–
1.77 (m, 2H), 1.74–1.64 (m, 1H), 1.61–1.53 (m, 1H),
1.48–1.38 (m, 1H), 0.99 (s, 3H), 0.92 (s, 3H), 0.89 (s,
3H). 13C NMR: d 218.2, 173.4, 141.6, 128.5 (two car-
bons), 128.3 (two carbons), 125.8, 71.5, 58.1, 52.4, 48.6,
47.0, 46.8, 44.9, 36.6, 31.9, 30.4, 23.5, 19.6, 19.3, 9.5. 77Se
NMR: d 526.2. Anal. Calcd for C22H30O4Se: C, 60.41;
H, 6.91. Found: C, 60.60; H, 6.99. Minor diastereoiso-
mer (2R,3R) (distinct signals): 1H NMR: d 4.14 (dd, 1H,
J ¼ 2:3, 4.5 Hz), 4.0 (ddd, 1H, J ¼ 3:2, 6.3, 9.4 Hz), 3.52
(d, 1H, J ¼ 6:3 Hz), 2.20 (t, 1H, J ¼ 4:4 Hz), 1.1 (s, 3H),
0.93 (s, 3H), 0.81 (s, 3H). 13C NMR: d 217.0, 173.2, 71.9,
48.5, 47.3, 43.7, 32.0, 23.3, 19.4, 9.6.
1
signals): H NMR: d 5.07 (dd, 1H, J ¼ 1:2, 8.3 Hz), 4.0
(d, 1H, J ¼ 8:3 Hz), 3.72 (s, 3H), 3.50 (d, 1H,
J ¼ 1:2 Hz), 3.44 (dd, 1H, J ¼ 1:9, 4.6 Hz), 1.90 (t, 1H,
J ¼ 4:3 Hz), 0.92 (s, 3H), 0.86 (s, 3H) 0.73 (s, 3H). 13C
NMR: d 172.7, 128.1, 126.7, 75.3, 52.4, 46.8, 44.9, 30.1,
23.0, 19.1. 77Se NMR: d 527.9.
4.24. Methyl (2S,3S)- and (2R,3R)-2-(camphorseleno)-3-
hydroxy-3-(4-methoxyphenyl) propanoate 6e and 7e
4.27. Methyl (2S,3S)- and (2R,3R)-4-(benzyloxy)-2-
(camphorseleno)-3-hydroxybutanoate 6h and 7h
1
Oil; Major diastereoisomer (2S,3S): H NMR: d 7.30
(A2B2 system, 2H), 6.60 (A2B2 system, 2H), 5.06 (dd,
1H, J ¼ 5:7, 6.5 Hz), 4.16 (d, 1H, J ¼ 6:5 Hz), 3.79 (s,
3H), 3.73 (dd, 1H, J ¼ 2:2, 4.7 Hz), 3.71 (s, 3H), 3.63 (d,
1
Major diastereoisomer (2R,3R): H NMR d 7.40–7.25
(m, 5H), 4.59 (d, 1H, J ¼ 11:8 Hz), 4.56 (d, 1H, J ¼ 11:8

790
M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 783–791
Hz), 4.20 (ddt, 1H, J ¼ 5:1, 7.1, 8.3 Hz), 3.99 (dd, 1H,
J ¼ 2:2, 4.6 Hz), 3.98 (d, 1H, J ¼ 7:1 Hz), 3.84 (dd, 1H,
J ¼ 5:0, 9.8 Hz), 3.76 (dd, 1H, J ¼ 5:0, 9.8 Hz), 3.74 (s,
3H), 3.37 (d, 1H, J ¼ 8:3 Hz), 2.25 (t, 1H, J ¼ 4:4 Hz),
1.95–1.80 (m, 1H), 1.75–1.50 (m, 2H), 1.50–1.35 (m,
1H), 1.03 (s, 3H), 0.95 (s, 3H), 0.91 (s, 3H). 13C NMR: d
217.9, 173.3, 138.2, 128.8 (two carbons), 128.2 (three
carbons), 73.9, 72.1, 72.0, 58.5, 52.9, 49.1, 48.5, 47.3,
42.1, 30.9, 23.8, 20.0, 19.9, 10.0. 77Se NMR: d 520.0.
Anal. Calcd for C22H30O5Se: C, 58.28; H, 6.67. Found:
C, 58.51; H, 6.49. Minor diastereoisomer (2S,3S) (dis-
added. The reactions were stirred at room temperature
for 2 h, then a 10% aqueous solution of NaOH and
diethyl ether were added and the mixtures were left
under stirring for 10 min. The organic layers were dried
with Na2SO4 and evaporated under reduced pressure.
The pure acetonides were separated by column chro-
matography on florisil.
4.31. (4R,5S,6S)-5-(camphorseleno)-2,2,4-trimethyl-6-
phenyl-1,3-dioxane 10
1
tinct signals): H NMR: d 4.61 (d, 1H, J ¼ 11:6 Hz),
26
D
1
4.54 (d, 1H, J ¼ 11:6 Hz), 3.81 (dd, 1H, J ¼ 5:7, 9.7 Hz),
3.72 (s, 3H), 3.19 (d, 1H, J ¼ 7:7 Hz), 2.30 (t, 1H,
J ¼ 4:3 Hz), 1.03 (s, 3H), 0.94 (s, 3H), 0.93 (s, 3H). 13C
NMR: d 218.7, 173.1, 138.3, 128.7, 128.3, 128.1, 71.4,
58.6, 49.0, 47.6, 40.3, 20.1, 19.8. 77Se NMR: d 519.6.
M.p. 90–91 °C; ½aꢀ ¼ )113.5 (c 1.4, CHCl3). H NMR:
d 7.50–7.40 (m, 2H), 7.35–7.15 (m, 3H), 5.23 (d, 1H,
J ¼ 1:7 Hz), 4.38 (dq, 1H, J ¼ 1:7, 6.2 Hz), 3.77 (t, 1H,
J ¼ 1:7 Hz), 2.02 (dd, 1H, J ¼ 1:3, 4.5 Hz), 1.80–1.40
(m, 5H), 1.55 (s, 3H), 1.53 (s, 3H), 1.44 (d, 3H,
J ¼ 6:2 Hz), 0.82 (s, 3H), 0.78 (s, 3H), 0.41 (s, 3H). Anal.
Calcd for C23H32O3Se: C, 63.44; H, 7.41. Found: C,
63.39; H, 7.30.
4.28. (3R,4R)-3-(camphorseleno)-4-hydroxy-4-phenyl
butan-2-one 7a
24
D
1
Oil; ½aꢀ ¼ +56.1 (c 0.9, CHCl3). H NMR: d 7.52–7.15
4.32. (4S,5R,6R)-5-(camphorseleno)-2,2,4-trimethyl-6-
phenyl-1,3-dioxane 11
(m, 5H), 5.14 (dd, 1H, J ¼ 3:6, 9.5 Hz), 4.31 (d, 1H,
J ¼ 9:5 Hz), 3.13 (d, 1H, J ¼ 3:6 Hz), 2.71 (dd, 1H,
J ¼ 1:9, 4.6 Hz), 2.47 (s, 3H), 1.79 (t, 1H, J ¼ 4:0 Hz),
1.95–1.30 (m, 4H), 0.92 (s, 3H), 0.89 (s, 3H), 0.63 (s,
3H). 13C NMR: d 218.3, 206.9, 140.7, 128.2 (three car-
bons), 127.4 (two carbons), 75.2, 58.1, 53.4, 48.1, 46.7,
46.4, 30.4, 29.3, 23.4, 19.5, 19.1, 9.5. 77Se NMR: d 513.7.
Anal. Calcd for C20H26O3Se: C, 61.06; H, 6.66. Found:
C, 61.00; H, 6.42.
1H NMR d 7.55–7.15 (m, 5H), 5.24 (d, 1H, J ¼ 1:8 Hz),
4.35 (dq, 1H, J ¼ 1:8, 5.9 Hz), 3.21 (t, 1H, J ¼ 1:8 Hz),
2.80 (dd, 1H, J ¼ 1:7, 4.5 Hz), 1.78 (t, 1H, J ¼ 4:3 Hz),
1.70–1.30 (m, 4H), 1.55 (s, 3H), 1.54 (s, 3H), 1.43 (d, 3H,
J ¼ 5:9 Hz), 1.26 (s, 3H), 0.92 (s, 3H), 0.77 (s, 3H). Anal.
Calcd for C23H32O3Se: C, 63.44; H, 7.41. Found: C,
63.60; H, 7.52. The acetonide is impure of the
1
(4R,5R,6R)-isomer (distinct signals): H NMR: d 4.38
(dq, 1H, J ¼ 1:7, 6.2 Hz), 3.78 (t, 1H, J ¼ 1:7 Hz), 2.03
(dd, 1H, J ¼ 1:5, 4.5 Hz), 1.56 (s, 3H), 1.53 (s, 3H), 1.41
(d, 3H, J ¼ 6:1 Hz), 0.82 (s, 3H), 0.79 (s, 3H).
4.29. Radical deselenenylations of the a-camphorseleno-b-
hydroxyketones and of the a-camphorseleno-b-hydroxy-
esters. General procedure
4.33. (4S,5S,6R)-5-(camphorseleno)-2,2,4-trimethyl-6-
phenyl-1,3-dioxane 12
To a solution of the a-camphorseleno-b-hydroxyketone
or ester (0.2 mmol) in benzene under nitrogen triphe-
nyltin hydride (0.6 mmol) and a catalytic amount of
AIBN were added and the reaction was refluxed for 2 h.
The residue obtained after removal of the solvent under
reduced pressure was purified by column chromatogra-
phy on silica gel. Physical and spectral data of the
obtained b-hydroxy ketones and esters are in good
agreement with those already described in the litera-
ture.13;15
1
Oil; H NMR: d 7.52–7.40 (m, 2H), 7.35–7.18 (m, 3H),
4.80 (d, 1H, J ¼ 10:9 Hz), 3.92 (dq, 1H, J ¼ 6:0,
11.2 Hz), 3.12 (dd, 1H, J ¼ 10:9, 11.2 Hz), 2.27 (dd, 1H,
J ¼ 1:5, 4.4 Hz), 1.75–1.25 (m, 5H), 1.54 (s, 3H), 1.50 (d,
3H, J ¼ 6:0 Hz), 1.44 (s, 3H), 1.21 (s, 3H), 0.78 (s, 3H),
0.76 (s, 3H). Anal. Calcd for C23H32O3Se: C, 63.44; H,
7.41. Found: C, 63.12; H, 7.49. The (4R,5S,6R)-isomer
1
was also present. Oil; H NMR: d 7.70–7.52 (m, 2H),
7.48–7.25 (m, 3H), 5.26 (d, 1H, J ¼ 9:2 Hz), 4.54 (dq,
1H, J ¼ 5:5, 6.4 Hz), 3.81 (dd, 1H, J ¼ 1:7, 4.5 Hz), 3.40
(dd, 1H, J ¼ 5:5, 9.2 Hz), 2.10 (t, 1H, J ¼ 4:3 Hz), 1.85–
1.40 (m, 4H), 1.44 (s, 3H), 1.43 (s, 3H), 1.38 (d, 3H,
J ¼ 6:6 Hz), 0.97 (s, 3H), 0.92 (s, 3H), 0.74 (s, 3H).
4.30. Synthesis of the acetonides 10, 11 and 12. General
procedure
To a 0 °C cooled solution of 4a, 5a or 7a (0.15 mmol) in
methanol (5 mL) NaBH4 (0.17 mmol) was added and the
resulting mixture was stirred for 1 h. The reaction mix-
ture was poured into water and extracted with diethyl
ether. The organic layers were dried with Na2SO4 and
evaporated. The resulting crude diols were obtained in
virtually quantitative yields and were used for the next
step without any purification. The diols were dissolved
in 2,2-dimethoxypropane (3 mL) and acetone (1 mL)
and a catalytic amount of p-toluensulphonic acid was
4.34. General procedure for the radical allylation of the
camphorselenoesters 4d and 5d
To a solution of 4d or 5d (0.15 mmol) in dry benzene
(3 mL) allyltributylstannane (1.5 mmol) and a catalytic
amount of AIBN were added in three portions over a
period of 3 h and the reaction was stirred for 4 h. The
crude mixture obtained after evaporation of the solvent

M. Tiecco et al. / Tetrahedron: Asymmetry 15 (2004) 783–791
791
2. Tiecco, M.; Testaferri, L.; Santi, C.; Tomassini, C.;
Marini, F.; Bagnoli, L.; Temperini, A. Angew. Chem.,
Int. Ed. 2003, 42, 3131.
3. Ponthieux, S.; Paulmier, C. In Topics in Current Chemis-
try. Organoselenium Chemistry: Modern Developments in
Organic Synthesis; Wirth, T., Ed.; Springer: Heidelberg,
2000; pp 113–142. Chapter 5.
under reduced pressure was filtered through florisil and
then purified by chromatography on a silica gel column.
Physical and spectral data of the resulting products 13,
ent-13, 14, and ent-14 were reported below. The ee was
>98% in every case.
4.35. Methyl (2R)-2-[(R)-hydroxy(phenyl)methyl] pent-4-
enoate 13
4. (a) Ponthieux, S.; Outurquin, F.; Paulmier, C. Tetrahedron
Lett. 1998, 39, 4017; (b) Nakamura, S.; Hayakawa, T.;
Nishi, T.; Watanabe, Y.; Toru, T. Tetrahedron 2001, 57,
6703.
24
D
1
Oil; ½aꢀ ¼ +8.0 (c 0.8, CHCl3). H NMR: d 7.48–7.30
5. For recent examples of titanium mediated asymmetric
aldol condensations see: (a) Crimmins, M. T.; King, B. W.;
Tabet, E. A. J. Am. Chem. Soc. 1997, 119, 7883; (b)
Crimmins, M. T.; Chaudary, K. Org. Lett. 2000, 2, 775;
(c) Ghosh, A. K.; Kim, J. H. Tetrahedron Lett. 2001, 42,
1227; (d) Casper, D. M.; Burgeson, J. R.; Esken, J. M.;
Ferrence, G. M.; Hitchcock, S. R. Org. Lett. 2002, 4, 3739;
(e) Casper, D. M.; Hitchcock, S. R. Tetrahedron: Asym-
metry 2003, 14, 517; (f) Wang, Y. C.; Su, D. W.; Lin, C.
M.; Tseng, H. L.; Li, C. L.; Yan, T. H. Tetrahedron Lett.
1999, 40, 3577; (g) Yan, T. H.; Hung, A. W.; Lee, H. C.;
Chang, C. S.; Liu, W. H. J. Org. Chem. 1995, 60, 3301; (h)
(m, 5H), 5.75 (dddd, 1H, J ¼ 6:5, 7.6, 10.3, 17.1 Hz),
5.15–5.0 (m, 3H), 3.61 (s, 3H), 2.86 (ddd, 1H, J ¼ 4:5,
5.5, 10.0 Hz), 2.84 (d, 1H, J ¼ 3:0 Hz), 2.51 (dddt, 1H,
J ¼ 1:0, 7.6, 10.0, 14.0 Hz), 2.41 (dddt, 1H, J ¼ 1:4, 4.5,
6.5, 14.0 Hz). 13C NMR: d 174.6, 141.3, 135.3, 128.4
(two carbons), 127.8, 126.1 (two carbons), 116.8, 73.8,
52.7, 51.6, 31.4. Anal. Calcd for C13H16O3: C, 70.89; H,
7.32. Found: C, 70.73; H, 7.42.
4.36. Methyl (2S)-2-[(S)-hydroxy(phenyl)methyl] pent-4-
enoate ent-13
ꢀ
Solsona, J. G.; Romea, P.; Urpı, F.; Villarasa, J. Org. Lett.
2003, 4, 519.
25
½aꢀ ¼ )8.9 (c 0.8, CHCl3).
6. Li, Z.; Wu, R.; Michalczyk, R.; Dunlap, R. B.; Odom,
J. D.; Silks, L. A. J. Am. Chem. Soc. 2000, 122, 386.
7. Back, T. G.; Dyck, B. P.; Parvez, M. J. Org. Chem. 1995,
60, 703.
8. Sharpless, K. B.; Lauer, R. F.; Teranishi, A. Y. J. Am.
Chem. Soc. 1973, 95, 6137.
D
4.37. Methyl (2S)-2-[(R)-hydroxy(phenyl)methyl] pent-4-
enoate 14
25
D
9. Lebarillier, L.; Outurquin, F.; Paulmier, C. Tetrahedron
2000, 56, 7483.
10. The H NMR spectrum of a CD2Cl2 solution of 2 after
1
Oil; ½aꢀ ¼ +26.7 (c 0.5, CHCl3). H NMR: d 7.50–7.15
(m, 5H), 5.70 (dddd, 1H, J ¼ 6:5, 7.7, 10.4, 17.0 Hz),
5.15–5.0 (m, 2H), 4.84 (dd, 1H, J ¼ 5:3, 7.8 Hz), 3.70 (s,
3H), 2.94 (d, 1H, J ¼ 5:3 Hz), 2.88 (ddd, 1H, J ¼ 5:1,
7.8, 9.2 Hz), 2.35–2.25 (m, 1H), 2.20–2.10 (m, 1H). 13C
NMR: d 175.0, 141.7, 134.3, 128.6 (two carbons), 128.1,
126.4 (two carbons), 117.3, 74.9, 52.8, 51.7, 33.8. Anal.
Calcd for C13H16O3: C, 70.89; H, 7.32. Found: C, 70.92;
H, 7.18.
1
treatment with 1.1 equiv of TiCl4 and 2 equiv of Et3N at
)40 °C was recorded in order to collect information about
the enolization step. Under these conditions a single
enolate is formed as demonstrated by the presence of a
single vinyl signal at 4.60 ppm. The geometry of the
enolate could not be determined by NOESY because the
MeO signal was partially overlapped by the methylene
signal of the triethylamine.
11. Evans, D. A.; Nelson, J. V.; Taber, T. R. In Topics in
Stereochemistry; Allinger, N. L., Eliel, E. L., Wilen, S. H.,
Eds.; Wiley: New York, 1983; Vol. 13, pp 1–115.
12. Oare, D. A.; Heathcock, C. H. J. Org. Chem. 1990, 55,
157.
4.38. Methyl (2R)-2-[(S)-hydroxy(phenyl)methyl] pent-4-
enoate ent-14
25
½aꢀ ¼ )27.4 (c 0.5, CHCl3).
D
13. Rho, H. S. Synth. Commun. 1997, 27, 3887.
3
14. The JAB values of the two acetonides formed from the
minor diols deriving from 5a and 7a, not represented in
the scheme, confirm this stereochemical attribution. In
Acknowledgements
fact, the acetonide deriving from 5a presents
3JAB ¼ 1:7 Hz and the one deriving from 7a
3JAB ¼ 9:2 Hz.
a
a
Financial support from MIUR, National Project ÔSte-
reoselezione in Sintesi Organica. Metodologie ed
ApplicazioniÕ, FIRB Project ÔProgettazione, Preparazi-
one e Valutazione Biologica e Farmacologica di Nuove
Molecole Organiche Quali Potenziali Farmaci Innov-
ativiÕ and the University of Perugia, Progetti di Ateneo,
is gratefully acknowledged.
15. (a) Schneider, F.; Simon, R. Synthesis 1986, 582; (b)
Evans, D. A.; Kozlowski, M. C.; Murry, J. A.; Burgey, C.
S.; Campos, K. R.; Connell, B. T.; Staples, R. J. J. Am.
ꢀ
Chem. Soc. 1999, 121, 669; (c) Guette, M.; Capillon, J.;
Guette, J. P. Tetrahedron 1973, 29, 3659; (d) Meyer, H. H.
ꢀ
Liebigs Ann. 1979, 484; (e) Abood, N. A. Synth. Commun.
1993, 23, 811.
16. For the assignment of the configurations the following
trends in 13C and 77Se NMR spectra were particularly useful:
References and notes
1. Tiecco, M. In Topics in Current Chemistry. Organosele-
nium Chemistry: Modern Developments in Organic Synthe-
sis; Wirth, T., Ed.; Springer: Heidelberg, 2000; pp 7–54.
Chapter 2.
13C C3
C2
77Se
syn < anti Dd 0.3–3.9 ppm
syn > anti Dd 1.0–4.2 ppm
syn ꢁ anti Dd 10–35 ppm.
O
OH
C2
C3
R
R
1
SeCf