Regio- and stereoselective synthesis of Z-vinylic tellurides from propargylic alcohols: A route to chiral Z-enynes

Article abstract of DOI:10.1016/j.tet.2004.10.087

tert-Butyldimethylsilyl ethers of propargylic alcohols are hydrotellurated regioselectively to give 1,2-Z-vinylic tellurides. Enantiomerically pure propargylic alcohols give enantiomerically pure vinylic tellurides, which are coupled with alkynes under Pd

Full text of DOI:10.1016/j.tet.2004.10.087

Tetrahedron 61 (2005) 409–415
Regio- and stereoselective synthesis of Z-vinylic tellurides from
propargylic alcohols: a route to chiral Z-enynes
´
Cristiano Raminelli, Nathalia C. da Silva, Alcindo A. Dos Santos, Andre L. M. Porto,
*
Leandro H. Andrade and Joa˜o V. Comasseto
´
Instituto de Quımica, Universidade de Sa˜o Paulo, Av. Prof. Lineu Prestes, 748, CEP 05508-900 Sa˜o Paulo, SP, Brazil
Received 23 September 2004; revised 25 October 2004; accepted 28 October 2004
Available online 13 November 2004
Abstract—tert-Butyldimethylsilyl ethers of propargylic alcohols are hydrotellurated regioselectively to give 1,2-Z-vinylic tellurides.
Enantiomerically pure propargylic alcohols give enantiomerically pure vinylic tellurides, which are coupled with alkynes under Pd catalysis
to give enantiomerically pure allylic enynols.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Hydrotelluration of alkynes gives Z-vinylic tellurides
exclusively,1 whereas other hydrometallation reactions
give the E-vinyl organometallics preferentially.2 The
transformation of Z-vinylic tellurides into Z-organometallics
is well established1 and recently it was used in the first step
of the synthesis of Macrolactin A, an antiviral macro-
lactone.3 Although the hydrotelluration of conjugated
alkynes gives only the 1,2-regioisomer, the hydrotelluration
of propargylic alcohols 1 leads to the formation of 1,2- and
2,2-substituted allylic alcohols 2 and 3, respectively4
(Scheme 1). Another limitation of the hydrotelluration
reaction consists in the traditional use of dibutylditelluride
as starting material, which is a bad smelling compound and
is not commercially available. Recently, we solved this
problem by substituting the classically used methodology1
by a different one, consisting in the reaction of commer-
cially available elemental tellurium and n-butyllithium,
which generates lithium butyltellurolate.1 In the presence of
water or ethanol, this intermediate reacts with alkynes5
leading to Z-vinylic tellurides in yields similar to the ones
obtained by the dibutylditelluride/sodium borohydride
method (Scheme 1).1,5 In view of the occurrence of allylic
alcohols in the structure of many natural products6 or
synthetic intermediates,7 we decided to investigate the
hydrotelluration of propargylic alcohols in order to control
its regiochemistry. In this work the lithium n-butyltellur-
olate/EtOH methodology was employed throughout.
Initially, the propargylic alcohols 1a–d were hydrotellur-
ated by reacting them with the system n-BuTeLi/EtOH in
order to verify the influence of their structures in the
isomeric ratios of the formed vinylic tellurides. The results
are presented in Table 1.
As can be observed, isomeric mixtures of 2 and 3 were
obtained. The isomeric ratios suggest that the nature of the R
group has a deep influence in the regioselectivity of the
hydrotelluration reaction. As the steric demand of the R group
increases,theamountofthedesired1,2-regioisomerincreases.
In view of these results, we decided to increase the steric
demand at C3 by protecting the OH function with bulky
protecting groups. Three commonly used protecting groups
were chosen for this purpose (Scheme 2, Table 2). Initially
alcohol 1b was protected with the three bulky protecting
groups, leading to the propargylic ethers 4a–c, which were
submitted to hydrotelluration (Scheme 2, Table 2).
As can be observed the hydrotelluration of 4a,b occurred in
good yields and with high regioselectivity. The tert-
butyldimethylsilyl (TBDMS) protected product presented
Keywords: Z-Vinylic tellurides; Propargylic alcohols; Chiral Z-enynes.
* Corresponding author. Tel.: C55 11 3091 2176; fax: C55 11 3815 5579;
e-mail: jvcomass@iq.usp.br
Scheme 1.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.10.087

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C. Raminelli et al. / Tetrahedron 61 (2005) 409–415
Table 1. Hydrotelluration of propargylic alcohols 1a–d produced according to Scheme 1
Entry
R
Time (h)
Yield (%)a
Isomeric ratio (2:3)b
1
2
3
4
H (a)
CH3 (b)
(CH3)2CH (c)
Ph (d)
4
6
6
6
80
74
60
60
1:3
2:3
2:1
2:1
a Isolated yields after column chromatography on silica gel.
b The isomeric ratio was determined by 1H NMR data and confirmed by GC analysis.
Table 3. Coupling of chiral Z-vinylic tellurides with zincates using
palladium and copper as catalysts produced according to Scheme 6
Entry
R
Compound
Yield (%)a
1
2
3
4
n-C5H11
n-C5H11
Ph
(S)-(C)-13a
(R)-(K)-13a
(S)-(C)-13b
(R)-(K)-13b
77
71
87
87
Ph
a Isolated yields after column chromatography on silica gel.
Scheme 2.
a 10:1 regioisomeric ratio in favor of the 1,2-isomer 5a,
confirming the steric control of the reaction. The tetra-
hydropyranyl group conferred a moderate selectivity
leading to a 6:1 ratio (entry 2, Table 2). The propargylic
alcohol protected by the trityl group did not react with
the hydrotellurating agent (entry 3, Table 3). In view of the
good results obtained by using the TBDMS group, the
propargylic ethers 7a,b were prepared and submitted to
the hydrotelluration conditions. In this case, it was observed
the exclusive formation of the 1,2-substituted vinylic
tellurides 8a,b in 72% isolated yield (Scheme 3).
Scheme 3. Regioselective synthesis of Z-vinylic tellurides 8a,b from
propargylic ethers 7a,b.
In order to use catalytic amounts of Pd, we then performed
the coupling reaction of (S)-(C)-8b and (R)-(K)-8b with
the zinc alkynoate as described recently.9b In this case
10 mol% of Pd(PPh3)4 was used as catalyst, leading to the
coupled products 13a,b in good yields (Scheme 6, Table 3).
Recently, we obtained chiral propargylic alcohols by a
kinetic resolution of the racemic mixture using Novozyme
435.8 In order to prepare enantiomerically enriched vinylic
tellurides, we prepared (S)-(C)-11a and (R)-(K)-11a
(Scheme 4) using our kinetic resolution conditions and
submitted them to the hydrotelluration conditions, obtaining
the chiral vinylic tellurides (S)-(C)-8b and (R)-(K)-8b
(Scheme 4). Vinylic tellurides are precursors of enynes and
enediynes by Te-Sonogashira reactions with alkynes9,10 or
alkynoates9 promoted by Pd. In order to obtain chiral allylic
enynols, we submitted compound 8b to the coupling
reaction with 1-heptyne promoted by PdCl2/CuI9,10 and
then deprotected the TBDMS-ether 13 with tetrabutyl-
ammonium fluoride (TBAF). Initially racemic 14 was pre-
pared and then the whole sequence was repeated to obtain
(S)-(C)-14 and (R)-(K)-14 (Scheme 5).
To demonstrate that the enantiomeric excesses of the
starting materials (S)-(C)-11a and (R)-(C)-12 are kept
unchanged throughout the transformations described in
Schemes 4–6, compound (R)-(K)-13a was deprotected with
TBAF to give alcohol (R)-(K)-14 with an enantiomeric
excess similar to the one of (R)-(C)-12 (Fig. 1).
3. Conclusions
In conclusion, the hydrotelluration of propargylic alcohols
Table 2. Hydrotelluration of propargylic ethers 4a–c produced according to Scheme 2
Entry
1
P
Time (h)
8
Yield (%)a
74
Isomeric ratio (5:6)b
10:1
(a)
2
3
8
73
6:1
—
(b)
24
N.R.c
(c)
a Isolated yields after column chromatography on silica gel.
b The isomeric ratio was determined by 1H NMR data and confirmed by GC analysis.
c The product was not formed.

C. Raminelli et al. / Tetrahedron 61 (2005) 409–415
411
Figure 1. Chiral chromatography of (C/K)-12, (C/K)-14, (R)-(C)-12
and (R)-(K)-14.
can be controlled to give the 1,2-regioisomer by transform-
ing them into the bulky tert-butyldimethylsilyl ether. By
using an enantiomerically enriched starting propargylic
alcohol, enantiomerically enriched vinylic tellurides are
obtained, which are chiral building blocks to the synthesis of
chiral allylic enynols.
4. Experimental
4.1. Materials
All reagents and solvents used were previously purified and
dried in agreement with the literature.11 THF was distilled
from sodium/benzophenone under N2 immediately before
use.11 n-BuLi was titrated using 1,10-phenanthroline as
indicator prior to use.12 N2 gas used in the reactions was
deoxygenated and dried as described in the literature.11,13
All operations were carried out in flame-dried glassware.
Column chromatography separations were carried out with
Vetec silicagel 60 (0.063–0.200 mm, 70–230 mesh) or
Acros Organics silicagel (0.035–0.075 mm, pore diameter
ca 6 nm). Tellurium metal (K200 mesh) was obtained from
Aldrich Chemical Co. and dried overnight in an oven at
100 8C. Palladium dichloride and copper (I) iodide were
purchased from Aldrich Chemical Co. and dried in a
desiccator containing CaCl2 and P2O5 under vacuum.
Tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4) was
prepared as described in the literature14 and maintained in
amber flask under nitrogen atmosphere. The following
reagents were prepared according to literature procedures:
4-methyl-pent-1-yn-3-ol (1c);15 1-phenyl-2-propyn-1-ol
(1d);15 tert-butyl (but-3-yn-2-yloxy) dimethylsilane (4a);16
2-(but-3-yn-2-yloxy)-tetrahydro-2H-pyran (4b);17 (but-3-
yn-2-yloxy) triphenylmethane (4c);18 (4-methyl-pent-1-yn-
3-yloxy) (tert-butyl) dimethylsilane (7a)16 and (1-phenyl-
prop-2-ynyloxy) (tert-butyl) dimethylsilane (7b).16 These
last compounds presented analytical data which agree with
the proposed structures. Novozyme 435 (immobilized lipase
from Candida antartica) was obtained as a gift from
Scheme 4. Regioselective synthesis of chiral Z-vinylic tellurides (S)-(C)-
8b and (R)-(K)-8b.
Scheme 5. Synthesis of racemic and chiral Z-enynes 13a and 14.
´
Novozymes Brasil (Parana-Brazil). The remaining chemi-
cals were obtained from commercial sources.
4.2. Instrumentation
1H and 13C NMR spectra were obtained on a Bruker AC-200
1
1
(200 MHz, H; 50 MHz, 13C) or DRX-500 (500 MHz, H;
Scheme 6.

412
C. Raminelli et al. / Tetrahedron 61 (2005) 409–415
125 MHz, 13C) or on a Varian INOVA 300 (300 MHz, H;
75 MHz, 13C) spectrometers. All spectra were taken in
CDCl3 and the chemical shifts are given in ppm with respect
to tetramethylsilane (TMS) used as internal standard. 125Te
NMR spectra were obtained on a Bruker DRX-500
(157 MHz, 125Te) spectrometer using CDCl3 as solvent.
The chemical shifts refer to diphenyl ditelluride (PhTe)2 in
CDCl3 (1 mol LK1) (dZ420 ppm at 25 8C) as external
standard. Enantiomeric excesses of the enzyme-catalyzed
reactions were determined using a Shimadzu GC-17A gas
chromatograph equipped with a chiral capillary column
Chirasil-Dex CB b-cyclodextrin (25 m!0.25 mm) or with a
chiral capillary column Gamma Dex 120 Supelco (30 m!
0.25 mm!0.25 mm film thickness). Optical rotation values
were measured in a Jasco DIP-378 polarimeter and the
reported data refer to the Na-line value using a 0.1 dm
cuvette. Low resolution mass spectra were obtained on a
Shimadzu CG-17A/CGMS-QP5050A instrument. Near IR
spectra were obtained on a Bomem MB-100 spectrometer.
Elemental analyses were performed at the Microanalytical
Laboratory of the Institute of Chemistry, Universidade de
Sa˜o Paulo. The IUPAC names were obtained using the
software ChemDraw Ultra, version 8.0.
1.27 (d, JZ6.6 Hz, 3H), 0.92 (t, JZ7.2 Hz, 7.5H); 13C
NMR (75 MHz, CDCl3) d (ppm) 142.0, 135.6, 120.7, 103.2,
74.1, 70.5, 34.0, 33.4, 25.1, 24.9, 23.8, 22.4, 13.3, 7.1, 6.4;
Near IR (film) n (cmK1) 3387, 2959, 2926, 2866, 1597,
1455, 1370, 1177; LRMS m/z (relative intensity) 258 (13%,
MC), 184 (21%), 71 (30%), 57 (100%)/258 (13%, MC), 184
(7%), 71 (100%), 57 (60%). Anal. Calcd for C8H16OTe C
37.56, H 6.30. Found C 37.75, H 6.12.
1
4.3.4. (C/K)-(Z)-1-(Butyltellanyl)-4-methyl-pent-1-en-
3-ol (2c)/(C/K)-2-(butyltellanyl)-4-methyl-pent-1-en-3-
ol (3c). Eluent: hexane/ethyl acetate (9:1); yield: 0.341 g
1
(60%); H NMR (500 MHz, CDCl3) d (ppm) 6.82 (dd, JZ
9.8, 0.8 Hz, 1H), 6.28 (dd, JZ9.8, 7.1 Hz, 1H), 6.11 (d, JZ
0.9 Hz, 1H), 5.48 (s, 1H), 3.90 (dd, JZ6.5, 6.48 Hz, 1H),
3.53 (d, JZ7.1 Hz, 1H), 2.75 (dt, JZ7.5, 3.0 Hz, 2H), 2.65
(dt, JZ7.5, 1.9 Hz, 2H), 1.78 (m, 6H), 1.40 (m, 4H), 1.00 (d,
JZ6.6 Hz; 3H), 0.96 (d, JZ6.7 Hz, 6H), 0.92 (m, 9H), 0.86
(d, JZ6.7 Hz, 4H); 13C NMR (125 MHz, CDCl3) d (ppm)
139.3, 133.9, 122.2, 105.7, 84.1, 79.2, 34.1, 33.8, 33.5, 33.4,
25.2, 24.5, 19.5, 18.1, 17.8, 17.7, 13.3, 7.1, 6.4; Near IR
(film) n (cmK1) 3429, 3060, 2958, 2927, 2870, 1598, 1463,
1380, 1030, 1009; LRMS m/z (relative intensity) 284 (11%,
MC), 282 (7%), 185 (13%), 183 (9%), 99 (10%), 81 (87%),
57 (100%), 284 (7%, MC), 282 (4%), 185 (11%), 183 (7%),
99 (6%), 81 (16%), 57 (100%). Anal. Calcd for C10H20OTe
C 42.31, H 7.10. Found C 42.59, H 6.61.
4.3. Typical procedures
4.3.1. Preparation of Z-vinylic tellurides.5b To a 50 mL
two-necked round-bottomed flask equipped with magnetic
stirring, heating and reflux condenser under nitrogen
atmosphere were added elemental tellurium (0.254 g,
2 mmol) and THF (10 mL). To the suspension obtained,
n-BuLi (1.3 mL, 2 mmol of a 1.5 mol LK1 solution in
hexane) was added dropwise at room temperature. A clear
solution was formed after 5 min of stirring. After that, the
appropriate alkyne (2.4 mmol) in deoxygenated ethanol
(20 mL) was added and the resulting mixture was refluxed
by the time indicated in the Tables 1 and 2 and Scheme 3.
The reaction was quenched with brine (50 mL) followed by
extraction with ethyl acetate (3!50 mL). The extracts were
dried over MgSO4 and then filtered. The solvent was
evaporated under reduced pressure and the residue was
purified by column chromatography on silica gel using
appropriate eluent.
4.3.5. (C/K)-(Z)-3-(Butyltellanyl)-1-phenyl-prop-2-en-
1-ol (2d)/(C/K)-2-(butyltellanyl)-1-phenyl-prop-2-en-1-
ol (3d). Eluent: hexane/ethyl acetate (9:1); yield: 0.382 g
(60%); 1H NMR (300 MHz, CDCl3) d (ppm) 7.34 (m, 7.5H),
6.86 (dd, JZ9.9, 1.5 Hz, 1H), 6.48 (dd, JZ9.9, 6.6 Hz, 1H),
6.29 (d, JZ1.2 Hz, 0.5H), 5.62 (d, JZ1.2 Hz, 0.5H), 5.26
(d, JZ6.3 Hz, 1H), 5.20 (d, JZ3.6 Hz, 0.5H), 2.67 (t, JZ
7.2 Hz; 3H), 2.57 (t, JZ7.5 Hz, 1.5H), 2.46 (d, JZ5.1 Hz,
0.5H), 2.16 (d, JZ2.7 Hz, 1H), 1.79 (m, 4H), 1.66 (m, 2H),
1.40 (m, 5H), 0.93 (t, JZ7.5 Hz, 4H), 0.87 (t, JZ7.2 Hz,
2H); 13C NMR (75 MHz, CDCl3) d (ppm) 142.5, 140.1,
132.7, 128.6, 128.3, 127.8, 127.7, 126.4, 126.2, 123.6,
105.0, 79.8, 76.4, 34.3, 33.6, 25.3, 25.2, 13.5, 7.7, 7.3; Near
IR (film) n (cmK1) 3397, 3084, 3061, 3025, 2957, 2925,
2870, 2857, 1596, 1491, 1454, 1377, 1035, 761, 699; LRMS
m/z (relative intensity) 320 (18%, MC), 318 (17%), 204
(28%), 115 (100%), 89 (8%), 77 (47%), 57 (62%), 320
(13%, MC), 318 (13%), 261 (25%), 149 (20%), 131 (88%),
115 (100%), 91 (7%), 77 (88%), 57 (72%). Anal. Calcd for
C13H18OTe C 49.12, H 5.71. Found C 49.36, H 5.46.
4.3.2. (Z)-3-(Butyltellanyl)prop-2-en-1-ol (2a)/2-(butyl-
tellanyl) prop-2-en-1-ol (3a).4a Eluent: hexane/ethyl acet-
ate (9:1); yield: 0.386 g (80%); 1H NMR (300 MHz, CDCl3)
d (ppm) 6.77 (ddd, JZ9.6, 1.2, 1.5 Hz, 0.4H), 6.40 (ddd, JZ
9.6, 5.2, 5.4 Hz, 0.4H), 6.16 (dd, JZ1.6, 1.5 Hz, 1H), 5.52
(dd, JZ1.3, 1.2 Hz, 1H), 4.19 (s, 1H), 4.11 (dd, JZ3.6,
3.3 Hz, 0.4H), 2.72 (t, JZ7.5 Hz, 2H), 2.60 (t, JZ4.8 Hz,
0.8H), 1.74 (m, 2.8H), 1.36 (m, 2.8H); 13C NMR (75 MHz,
CDCl3) d (ppm) 137.4, 127.1, 122.7, 104.6, 70.1, 64.9, 34.0,
33.7, 25.0, 24.8, 13.3, 7.1, 6.1.
4.3.6. (C/K)-((Z)-4-(Butyltellanyl) but-3-en-2-yloxy)
(tert-butyl) dimethylsilane (5a)/(C/K)-(3-(butyltellanyl)
but-3-en-2-yloxy) (tert-butyl)dimethylsilane (6a). Eluent:
hexane; yield: 0.548 g (74%); 1H NMR (300 MHz, CDCl3)
d (ppm) 6.54 (dd, JZ9.9, 0.6 Hz, 1H), 6.23 (dd, JZ9.9,
7.2 Hz, 1H), 4.28 (dt, JZ6.7, 0.9 Hz, 1H), 2.63 (dt, JZ7.8,
3.6 Hz, 2H), 1.75 (quint, JZ7.2 Hz, 2H), 1.38 (sext, JZ
7.5 Hz, 2H), 1.18 (d, JZ6.6 Hz, 3H), 0.89 (s, 9H), 0.08 (s,
3H), 0.07 (s, 3H); 13C NMR (75 MHz, CDCl3) d (ppm)
143.9, 100.2, 72.0, 34.1, 26.0, 24.9, 23.4, 18.2, 13.3, 6.8,
K4.3, K4.6; 125Te NMR (157 MHz, CDCl3) d (ppm) 265;
Near IR (film) n (cmK1) 2958, 2929, 2886, 2857, 1640,
1463, 1200, 1117, 1092; LRMS m/z (relative intensity) 372
(6%, MC), 370 (5%), 315 (13%), 241 (12%), 185 (22%),
4.3.3. (C/K)-(Z)-4-(Butyltellanyl)but-3-en-2-ol (2b)/
(C/K)-3-(butyltellanyl) but-3-en-2-ol (3b). Eluent: hexane/
ethyl acetate (9:1); yield: 0.379 g (74%); 1H NMR
(300 MHz, CDCl3) d (ppm) 6.69 (dd, JZ9.6, 0.9 Hz, 1H),
6.28 (dd, JZ9.6, 6.9 Hz, 1H), 6.12 (d, JZ0.9 Hz, 1.5H),
5.40 (s, 1.5H), 4.33 (quint, JZ6.3 Hz, 1H), 4.22 (q, JZ
5.7 Hz, 1.5H), 2.73 (t, JZ7.9 Hz, 3H), 2.65 (t, JZ7.5 Hz,
2H), 1.77 (m, 5H), 1.39 (m, 5H), 1.33 (d, JZ6.3 Hz, 4.5H),

C. Raminelli et al. / Tetrahedron 61 (2005) 409–415
413
183 (15%), 181 (11%), 127 (100%), 75 (47%), 73 (59%), 57
(18%), 55 (20%). Anal. Calcd for C14H30OSiTe C 45.44, H
8.17. Found C 45.38, H 8.05.
(1d) (0.560 g, 4 mmol). The reaction mixture was stirred
on a rotary shaker (32 8C, 170 rpm) for 40 min. After that,
the mixture was filtered and the solvent evaporated. The
residue was purified by silica gel column chromatography
using hexane/ethyl acetate (9:1) as eluent. The enatiomeric
rate (E) for the kinetic resolution of 1-phenyl-prop-2-yn-1-
ol (1d) was > 200 and the convertion (c) was 50%.
4.3.7. (C/K)-2-((Z)-4-(Butyltellanyl) but-3-en-2-yloxy)-
tetrahydro-2H-pyran (5b)/(C/K)-2-(3-(butyltellanyl)
but-3-en-2-yloxy)-tetrahydro-2H-pyran (6b). Eluent:
hexane; yield: 0.496 g (73%); 1H NMR (500 MHz,
CDCl3) d (ppm) 6.79 (dd, JZ9.7, 0.6 Hz, 1H), 6.67 (dd,
JZ9.8, 0.9 Hz, 0.2H), 6.31 (dd, JZ9.8, 7.1 Hz, 0.2H), 6.13
(dd, JZ9.7, 7.9 Hz, 1H), 6.09 (d, JZ1.0 Hz, 0.2H), 6.08 (d,
JZ1.0 Hz, 0.2H), 4.71 (dd, JZ4.4, 3.1 Hz, 0.2H), 4.61 (dd,
JZ4.5, 3.0 Hz, 0.2H), 4.59 (dd, JZ6.5, 0.6 Hz, 1H), 4.34
(ddt, JZ7.8, 6.5, 0.6 Hz, 1H), 4.30–4.26 (m, 0.4H); 13C
NMR (125 MHz, CDCl3) d (ppm) 145.0, 140.1, 134.3,
120.2, 105.5, 102.4, 96.7, 96.5, 96.1, 74.5, 73.7, 63.1, 62.6,
62.6, 34.1, 33.4, 30.9, 30.9, 30.6, 26.0, 25.5, 25.4, 25.3,
22.9, 20.5, 20.0, 19.7, 19.6, 19.4, 13.4, 6.9, 6.8, 5.2; Near IR
(film) n (cmK1) 2954, 2929, 2870, 1598, 1462, 1454, 1368,
1201, 1121, 1077, 1034, 1021, 986; LRMS m/z (relative
intensity) 340 (6%, MC), 256 (3%), 242 (10%), 184 (17%),
85 (70%), 67 (25%), 57 (100%), 340 (5%), 256 (8%), 201
(10%), 182 (6%), 85 (87%). Anal. Calcd for C13H24O2Te C
45.93, H 7.12. Found C 45.91, H 6.83.
4.3.11. (S)-(C)-1-Phenyl-prop-2-yn-1-ol (11a). Yield:
0.218 g (39%); enantiomeric excess (ee): >99%;
[a]D25ZC16.3 (c 4.34, CHCl3), 99% ee {Lit. [a]2D5Z
C20.0 (c 1.13, CHCl3), 72% ee}19 1H NMR (200 MHz,
CDCl3) d (ppm) 7.56–7.51 (m, 2H), 7.50–7.28 (m, 3H), 5.43
(d, JZ2.2 Hz, 1H), 2.65 (d, JZ2.0 Hz, 1H), 2.49 (sbroad
1H); 13C NMR (125 MHz, CDCl3) d (ppm) 140.0, 128.6,
128.4, 126.5, 83.5, 74.7, 64.3; Near IR (film) n (cmK1
,
)
3371, 3293, 3088, 3065, 3033, 2880, 2118, 1454, 1276,
1022, 739, 699, 651; LRMS m/z (relative intensity) 132
(86%, MC), 131 (100%), 115 (26%), 103 (42%), 89 (12%),
77 (75%), 63 (20%), 53 (84%).
4.3.12. (R)-(C)-1-Phenyl-prop-2-ynyl acetate (12). Yield:
0.339 g (46%); enantiomeric excesses (ee): 96–99%;
[a]D25ZC4.4 (c 4.33, CHCl3), 98% ee; {Lit. [a]2D5ZC3.4
(c 1.07, CHCl3), 85% ee}19 1H NMR (200 MHz, CDCl3) d
(ppm) 7.59–7.52 (m, 2H), 7.47–7.39 (m, 3H), 6.48 (d, JZ
2.2 Hz, 1H), 2.68 (d, JZ2.0 Hz, 1H), 2.13 (s, 1H); 13C NMR
(50 MHz, CDCl3) d (ppm) 169.6, 136.5, 129.0, 128.6, 127.6,
80.2, 75.3, 65.2, 20.9; Near IR (film) n (cmK1) 3289, 3066,
3036, 2940, 2126, 1742, 1456, 1371, 1228, 760, 698, 653;
LRMS m/z (relative intensity) 174 (MC, 9.6%), 132
(37.2%), 114 (100.0%), 103 (8.0%), 89 (11.8%), 77
(11.2%), 63 (13.5%), 43 (44.6%).
4.3.8. (C/K)-((Z)-1-(Butyltellanyl)-4-methyl-pent-1-en-
3-yloxy) (tert-butyl)dimethylsilane (8a). Eluent: hexane;
yield: 0.573 g (72%); 1H NMR (300 MHz, CDCl3) d (ppm)
6.67 (dd, JZ9.6, 0.6 Hz, 1H), 6.17 (dd, JZ9.6, 8.1 Hz, 1H),
3.78 (dd, JZ7.9, 5.7 Hz, 1H), 2.65 (m, 2H), 1.76 (quint, JZ
7.5 Hz, 2H), 1.70 (m, 1H), 1.39 (dq, JZ7.2, 7.5 Hz, 2H),
0.92 (t, JZ7.2 Hz, 3H), 0.86 (d, JZ6.9 Hz, 6H), 0.89 (s,
9H), 0.07 (s, 3H), 0.04 (s, 3H); 13C NMR (125 MHz,
CDCl3) d (ppm) 142.0, 103.0, 80.6, 34.9, 34.1, 25.9, 24.9,
18.4, 18.1, 17.9, 13.3, 6.9, K4.0, K4.8; 125Te NMR
4.3.13. Preparation of compound (R)-(K)-11a.20 To a
25 mL two-necked round-bottomed flask equipped with
magnetic stirring were added (R)-(C)-12 (0.330 g,
1.9 mmol), methanol (3 mL), water (3 mL) and K2CO3
(0.262 g, 1.9 mmol). The mixture was stirred at room
temperature for 12 h. After that, the reaction was quenched
with brine (15 mL) followed by extraction with ethyl acetate
(4 x 15 mL). The extracts were dried over MgSO4 and then
filtered. The solvent was evaporated under reduced pressure.
(157 MHz, CDCl3) d (ppm) 267; Near IR (film) n (cmK1
)
2957, 2929, 2886, 2857, 1598, 1465, 1125, 1069; LRMS m/z
(relative intensity) 398 (2%, MC), 357 (28%), 355 (24%),
155 (23%), 115 (5%), 81 (15%), 75 (36%), 73 (100%), 57
(19%), 55 (11%). Anal. Calcd for C16H34OSiTe C 48.27, H
8.61. Found C 48.45, H 8.21.
4.3.9. (C/K)-((Z)-3-(Butyltellanyl)-1-phenyl-allyloxy)
(tert-butyl)dimethylsilane (8b). Eluent: hexane; yield:
0.622 g (72%); 1H NMR (500 MHz, CDCl3) d (ppm)
7.38–7.37 (m, 2H), 7.33–7.29 (m, 2H), 7.21–7.24 (m, 1H),
6.68 (dd, JZ9.6, 0.6 Hz, 1H), 6.33 (dd, JZ9.6, 7.6 Hz, 1H),
5.21 (d, JZ7.6 Hz, 1H), 2.64–2.74 (m, 2H), 1.79 (dt, JZ
7.5, 7.4 Hz, 2H), 1.40 (dq, JZ7.5, 7.4 Hz, 2H), 0.92 (t, JZ
4.1 Hz, 3H), 0.92 (s, 9H), 0.11 (s, 3H), 0.08 (s, 3H); 13C
NMR (125 MHz, CDCl3) d (ppm) 143.5, 142.5, 128.3,
127.1, 125.8, 102.2, 34.1, 26.0, 24.9, 18.3, 13.4, 7.4, K4.2,
K4.6; 125Te NMR (157 MHz, CDCl3) d (ppm) 278; Near IR
(film) n (cmK1) 3062, 3025, 2956, 2929, 2888, 2857, 1597,
1463, 1254, 1089, 1066, 868, 838; LRMS m/z (relative
intensity) 432 (3%, MC), 377 (7%), 303 (3%), 247 (20%),
189 (23%), 115 (100%), 73 (82%), 57 (17%). Anal. Calcd
for C19H32OSiTe C 52.81, H 7.46. Found C 53.15, H 7.27.
(R)-(K)-1-Phenyl-prop-2-yn-1-ol (11a). Yield: 0.238 g
(95%); [a]2D5ZK24.7 (c 2.20, CHCl3). (The spectral data
agreed with those obtained for compound (S)-(C)-11a.)
4.3.14. Preparation of (S)-(C)-7b and (R)-(K)-7b.16 To a
25 mL two-necked round-bottomed flask equipped with
magnetic stirring under nitrogen atmosphere were added
(S)-(C)-11a or (R)-(K)-11a (0.210 g, 1.6 mmol), CHCl3
(2.5 mL), tert-butyldimethylsilyl chloride (0.271 g,
1.8 mmol) and imidazole (0.238 g, 3.5 mmol). The mixture
was stirred at room temperature for 12 h. After that, the
reaction was diluted with CH2Cl2 (20 mL) and washed with
water (3!100 mL). The organic phase was dried over
MgSO4 and then filtered. The solvent was evaporated under
reduced pressure.
4.3.10. Kinetic resolution of compound 1d using Novo-
zyme 435.8 To a 125 mL Erlenmeyer flask were added
hexane (HPLC grade) (20 mL), vinyl acetate (1 mL),
Novozyme 435 (0.300 g) and 1-phenyl-prop-2-yn-1-ol
(R)-(K)-1-Phenyl-prop-2-ynyloxy) (tert-butyl) dimethyl
silane (7b).16b Yield: 0.331 g (84%); [a]2D5ZK16.62 (c
2.10, CHCl3). H NMR (200 MHz, CDCl3) d (ppm) 7.51–
1

414
C. Raminelli et al. / Tetrahedron 61 (2005) 409–415
7.47 (m, 2H), 7.38–7.28 (m, 3H), 5.48 (d, JZ2.2 Hz, 1H),
2.53 (d, JZ2.2 Hz, 1H), 0.94 (s, 9H), 0.18 (s, 3H), 0.14 (s,
3H); LRMS m/z (relative intensity) 231 (1%), 189 (100%),
179 (46%), 159 (1%), 145 (2%), 135 (18%), 115 (78%), 105
(28%), 89 (9%), 83 (45%), 75 (21%), 57 (8%).
Calcd for C22H34OSi C 77.13, H 10.00. Found C 77.39, H
10.05.
((S,Z)-(C)-1-Phenyl-dec-2-en-4-ynyloxy) (tert-butyl) dimethyl-
silane (13a). Yield: 0.187 g (78%); [a]2D5ZC192.50 (c
2.30, CHCl3). (The spectral data agreed with those obtained
for compound (C/K)-13).
(S)-(C)-1-Phenyl-prop-2-ynyloxy) (tert-butyl) dimethyl
silane (7b). Yield: 0.315 g (80%); [a]2D5ZC9.35 (c 2.00,
CHCl3). (The spectral data agreed with those obtained for
compound (R)-(K)-7b).
((R,Z)-(K)-1-Phenyl-dec-2-en-4-ynyloxy) (tert-butyl)
dimethylsilane (13a). Yield: 0.204 g (85%); [a]2D5ZK254.35
(c 2.30, CHCl3). (The spectral data agreed with those
obtained for compound (C/K)-13).
4.3.15. Preparation of compounds (S)-(C)-8b and (R)-
(K)-8b. The reactions were performed as described in
Section 4.3.1. in a 1.2 mmol scale.
4.3.18. Preparation of compounds (C/K)-14, (S)-(C)-14
and (R)-(K)-14.21 To a 15 mL two-necked round-bottomed
flask equipped with magnetic stirring under nitrogen
atmosphere were added the appropriate Z enyne (C/K)-
13 (0.150 g, 0.4 mmol) and tetrabutylammonium fluoride
(1.0 mol LK1 solution in THF) (0.8 mL, 0.8 mmol). The
reaction mixture was stirred under nitrogen atmosphere at
room temperature for 1 h. The reaction was quenched with
brine (50 mL) followed by extraction with ethyl acetate
(3!50 mL). The extracts were dried over MgSO4 and then
filtered. The solvent was evaporated under reduced pressure
and the residue was purified by column chromatography on
silica gel using hexane/ethyl acetate (9:1) as eluent. The
analytical data of the products were obtained after
purification by preparative thin layer chromatography
using hexane/ethyl acetate (9:1) as eluent.
((S,Z)-(C)-3-(Butyltellanyl)-1-phenylallyloxy) (tert-butyl)-
dimethylsilane (8b). Yield: 0.373 g (72%); [a]2D5ZC137.39
(c 2.30, CHCl3). (The spectral data agreed with those
obtained for compound (C/K)-8b).
((R,Z)-(K)-3-(Butyltellanyl)-1-phenylallyloxy) (tert-butyl)-
dimethylsilane (8b). Yield: 0.373 g (72%); [a]2D5ZK144.50
(c 2.00, CHCl3). (The spectral data agreed with those
obtained for compound (C/K)-8b).
4.3.16. Preparation of compounds (C/K)-13, (S)-(C)-
13a and (R)-(K)-13a: cross-coupling reaction using
PdCl2/CuI.9a,10 To a 25 mL two-necked round-bottomed
flask equipped with magnetic stirring under nitrogen
atmosphere were added PdCl2 (0.124 g, 0.7 mmol), CuI
(0.133 g, 0.7 mmol), methanol (7 mL) and the telluride 8b
(0.300 g, 0.7 mmol). The mixture was stirred at room
temperature for 15 min under nitrogen atmosphere. After
that, 1-heptyne (0.135 g, 1.4 mmol) and triethylamine
(0.4 mL, 0.283 g, 2.8 mmol) were added to the reaction
mixture which was stirred under nitrogen atmosphere at
room temperature for 24 h. Then, the solids were filtered off
over celitew, washing several times with methanol. The
solvent was evaporated under reduced pressure. To the
residue was added brine (30 mL), and the mixture was
extracted with ethyl acetate (3!30 mL). The combined
organic phases were dried over MgSO4 and then filtered.
The organic solvent was evaporated under reduced pressure,
and the residue was purified by column chromatography on
silica gel using hexane as eluent. The analytical data of
products were obtained after purification by preparative thin
layer chromatography using hexane as eluent.
4.3.19. (C/K)-(Z)-1-Phenyl-dec-2-en-4-yn-1-ol 14. Yield:
0.077 g (85%). 1H NMR (200 MHz, CDCl3) d (ppm) 7.47–
7.23 (m, 5H), 5.99 (dd, JZ10.5, 8.3 Hz, 1H), 5.79 (d, JZ
8.3 Hz, 1H), 5.60 (dt, JZ10.5, 2.0 Hz, 1H), 2.37 (td, JZ7.0,
2.2 Hz, 2H), 2.22 (sbroad, 1H), 1.58 (quint, JZ6.9 Hz, 2H),
1.48–1.25 (m, 4H), 0.91 (t, JZ6.8 Hz, 3H); 13C NMR
(50 MHz, CDCl3) d (ppm) 142.8, 142.8, 128.5, 127.6, 125.8,
110.7, 96.8, 76.6, 72.0, 31.1, 28.41, 22.2, 19.6, 14.0; Near
IR (film) n (cmK1) 3386, 3085, 3062, 3029, 2957, 2931,
2860, 2214, 1602, 1493, 1453, 1378, 1046, 746, 699; LRMS
m/z (relative intensity) 228 (3%, MC), 213 (0.5%), 199
(2%), 185 (6%), 171 (34%), 157 (44%), 143 (14%), 128
(29%), 115 (20%), 105 (100%), 91 (36%), 77 (65%), 65
(16%), 55 (31%); Anal. Calcd for C16H20O C 84.16, H 8.83.
Found C 83.98, H 8.66.
(S,Z)-(C)-1-Phenyl-dec-2-en-4-yn-1-ol (14). Yield: 0.079 g
(87%); [a]2D5ZC350.50 (c 2.00, CHCl3). (The spectral data
agreed with those obtained for compound (C/K)-14).
4.3.17. (C/K)-(Z)-tert-Butyl-dimethyl-(1-phenyl-dec-2-
en-4-ynyloxy)-silane (13). Yield: 0.170 g (71%). H NMR
1
(R,Z)-(K)-1-Phenyl-dec-2-en-4-yn-1-ol (14). Yield: 0.079 g
(87%); [a]2D5ZK308.33 (c 1.20, CHCl3). (The spectral data
agreed with those obtained for compound (C/K)-14).
(200 MHz, CDCl3) d (ppm) 7.46–7.41 (m, 2H), 7.35–7.18
(m, 3H), 5.90–5.78 (m, 2H), 5.55–5.42 (m, 1H), 2.39 (td,
JZ6.8, 2.2 Hz, 2H), 1.59 (quint, JZ7.0 Hz, 2H), 1.47–1.24
(m, 4H), 0.93 (s, 9H), 0.90 (t, JZ7.0 Hz, 3H), 0.11 (s, 3H),
0.10 (s, 3H); 13C NMR (50 MHz, CDCl3) d (ppm) 144.6,
143.9, 128.2, 127.0, 125.4, 108.7, 95.6, 77.1, 72.2, 31.2,
28.5, 25.9, 22.2, 19.5, 18.3, 13.4, K4.4, K4.9; Near IR
(film) n (cmK1) 3063, 3029, 2956, 2931, 2859, 2216, 1603,
1492, 1464, 1390, 1254, 1091, 1068, 874, 837, 744, 698;
LRMS m/z (relative intensity) 342 (1%, MC), 327 (1%), 285
(91%), 267 (1%), 229 (4%), 211 (26%), 203 (7%), 189
(8%), 169 (4%), 153 (18%), 141 (18%), 129 (9%), 115
(17%), 105 (5%), 91 (25%), 75 (100%), 55 (2%). Anal.
4.3.20. Cross-coupling reaction using Pd(PPh3)4 and CuI
as catalysts.9b Preparation of the zinc reagent. To a 15 mL
two-necked round-bottomed flask equipped with magnetic
stirring under nitrogen atmosphere were added the appro-
priate alkyne (1 mmol) and THF (4 mL). Then, n-BuLi
(0.77 mL, 1 mmol of a 1.3 mol LK1 solution in hexane) was
added dropwise at K70 8C, and the mixture was stirred for
10 min. After that, Et2Zn (1 mL, 1 mmol of a 1.0 mol LK1
solution in THF) was added to the reaction mixture which was

C. Raminelli et al. / Tetrahedron 61 (2005) 409–415
415
Chemie, 4th ed.; Mu¨ller, E., Ed.; Georg Thieme Verlag:
Stuttgart, 1990; Vol. E12b. (b) Petragnani, N. Tellurium in
Organic Synthesis; Academic: New York, 1994. For recent
reviews see: (c) Comasseto, J. V.; Ling, L. W.; Petragnani, N.;
Stefani, H. A. Synthesis 1997, 373. (d) Comasseto, J. V.;
Barrientos-Astigarraga, R. E. Aldrichim. Acta 2000, 33, 66.
(e) Vieira, M. L.; Zinn, F. K.; Comasseto, J. V. J. Braz. Chem.
Soc. 2001, 12, 586.
then warmed to room temperature. The zinc reagent became
ready for use.
Cross-coupling reaction. To a 25 mL two-necked round-
bottomed flaskequippedwith magneticstirringundernitrogen
atmosphere were added the telluride 8b (0.216 g, 0.5 mmol),
THF (4 mL), Pd(PPh3)4 (0.027 g, 0.05 mmol), CuI (0.095 g,
0.05 mmol), DMF (4 mL) and the appropriate zinc reagent
(1 mmol of the solution prepared above) via syringe. The
reaction mixture was stirred under inert atmosphere at room
temperature for 2 h. The reaction was quenched with brine
(50 mL) followed by extraction with ethyl acetate (3!
50 mL). TheextractsweredriedoverMgSO4 and thenfiltered.
The solvent was evaporated under reduced pressure and the
residue was purified by column chromatography on silica gel
using hexane as eluent. The analytical data of the products
were obtained after purification by preparative thin layer
chromatography using hexane as eluente.
2. Casson, S.; Kocienski, P. In Organometallic Reagents in
Organic Synthesis; Batesson, J. H., Mitchel, M. B., Eds.;
Academic: London, 1994; Chapter 7, pp 129–159.
3. Marino, J. P.; McClure, M. S.; Holub, D. P.; Comasseto, J. V.;
Tucci, F. C. J. Am. Chem. Soc. 2002, 124, 1664.
4. (a) Takahashi, H.; Ohe, K.; Uemura, S.; Sugita, N. Nippon
Kagaku Kaishi 1987, 1508. (b) Ohe, K.; Takahashi, H.;
Uemura, S.; Sugita, N. J. Organomet. Chem. 1987, 326, 35.
(c) Barros, S. M.; Dabdoub, M. J.; Dabdoub, V. M. B.;
Comasseto, J. V. Organometallics 1989, 8, 1661.
5. (a) Sashida, H. Rev. Heteroatom Chem. 2000, 22, 59 and
references cited therein. (b) Zeni, G.; Formiga, H. B.;
Comasseto, J. V. Tetrahedron Lett. 2000, 41, 1311.
6. See Commemorative issue of Natural Product Reports in
honor of Professor John Falkner, D. Nat. Prod. Rep. 2004, 21,
1–210.
((S,Z)-(C)-1-Phenyl-dec-2-en-4-ynyloxy) (tert-butyl)
dimethylsilane (13a). Yield: 0.133 g (78%). (For spectral
data see Section 4.3.16.)
((R,Z)-(K)-1-Phenyl-dec-2-en-4-ynyloxy) (tert-butyl)
dimethylsilane (13a). Yield: 0.145 g (85%). (For spectral
data see Section 4.3.16.)
7. Corey, E. J.; Cheng, X.-M. In The Logic of Chemical
Synthesis; Wiley: New York, 1989.
8. Raminelli, C.; Comasseto, J. V.; Andrade, L. H.; Porto,
A. L. M. Tetrahedron: Asymmetry 2004, 15, 3117.
9. (a) Zeni, G.; Comasseto, J. V. Tetrahedron Lett. 1999, 40,
4619. (b) Dabdoub, M. J.; Dabdoub, V. B.; Marino, J. P.
Tetrahedron Lett. 2000, 41, 437. For a review see: Zeni, G.;
Braga, A. L.; Stefani, H. A. Acc. Chem. Res. 2003, 36, 731.
10. Raminelli, C.; Prechtl, M. H. G.; Santos, L. S.; Eberlin, M. N.;
Comasseto, J. V. Organometallics 2004, 23, 3990.
11. Perrin, D. D.; Armarego, W. L. F. In Purification of
Laboratory Chemicals; Pergamon: Oxford, 1980.
12. Watson, S. C.; Eastham, J. F. J. Organomet. Chem. 1967, 9,
165.
((S,Z)-(C)-1,5-Diphenyl-pent-2-en-4-ynyloxy) (tert-butyl)
dimethylsilane (13b). Yield: 0.151 g (87%); [a]2D5ZC266.67
(c 0.37, CHCl3). 1H NMR (200 MHz, CDCl3) d (ppm) 7.50–
7.23 (m, 10H), 6.01 (d, JZ10.5 Hz, 1H), 5.97 (dd, JZ9.9,
9.0 Hz, 1H), 5.72 (d, JZ9.9 Hz, 1H), 0.94 (s, 9H), 0.14 (s,
3H), 0.13 (s, 3H); 50 MHz RMN 13C (CDCl3) (ppm) 145.9,
143.5, 131.5, 128.4, 128.3, 128.3, 127.1, 125.5, 108.1, 94.2,
85.9, 72.3, 25.8, 25.8, 18.3, K4.4, K4.9; Near IR (film) n
(cmK1) 2955, 2930, 2857, 1948, 1877, 1805, 1740, 1597,
1490, 1467, 1254, 1092, 1064, 1027, 1005, 954, 939; LRMS
m/z (relative intensity) 348 (3%, MC), 293 (7%), 292
(28%), 291 (100%), 218 (16%), 217 (78%), 216 (17%), 215
(51%), 213 (31%), 202 (39%), 115 (40%), 91 (18%), 75
(47%), 73 (34%), 57 (14%); Anal. Calcd for C23H28OSi C
79.26, H 8.10. Found C 79.38, H 8.10.
13. Tucci, F. C.; Chieffi, A.; Comasseto, J. V. J. Org. Chem. 1996,
61, 4975.
14. Komiya, S. In Komiya, S., Ed.; Synthesis of Organometallic
Compounds—A Practical Guide; Wiley: Chichester, 1997;
Vol. 1, p 286.
((R,Z)-(K)-1,5-Diphenyl-pent-2-en-4-ynyloxy) (tert-butyl)
dimethylsilane (13b). Yield: 0.151 g (87%); [a]2D5ZK308.33
(c 0.37, CHCl3). (The spectral data agreed with those
obtained for compound (S)-(C)-13b).
15. Mortier, J.; Vaultier, M.; Carreaux, F.; Douin, J.-M. J. Org.
Chem. 1998, 63, 3515.
16. (a) Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972,
94(17), 6190. (b) Horsham, M. A.; Class, T. J.; Johnston, J. J.;
Casida, J. E. J. Agric. Food Chem. 1989, 37, 777.
17. Bongini, A.; Cardilho, G.; Orena, M.; Sandri, S. Synthesis
1979, 618.
Acknowledgements
´
The authors acknowledge Novozymes Brasil (Parana-
18. Chaudhary, S. K.; Hernandez, O. Tetrahedron Lett. 1979, 2,
95.
Brazil) for a gift of Novozyme 435 and CNPq and FAPESP
for financial support.
19. Waldinger, C.; Schneider, M.; Botta, M.; Corelli, F.; Summa,
V. Tetrahedron: Asymmetry 1996, 7, 1485.
20. Danda, H.; Nagatomi, T.; Maehara, A.; Umemura, T.
Tetrahedron 1991, 47, 8701.
References and notes
21. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley: New York, 1999; pp 127–141.
1. (a) Irgolic, K. J. In Houben Weyl: Methoden der Organischen