Kinetic resolution of propargylic and allylic alcohols by Candida antarctica lipase (Novozyme 435)

Article abstract of DOI:10.1016/j.tetasy.2004.08.022

A number of chiral propargylic and allylic alcohols were resolved by lipase-catalyzed kinetic resolution (Novozyme 435). In some cases the enantiomeric excess was high (up to >99%).

Full text of DOI:10.1016/j.tetasy.2004.08.022

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 3117–3122
Kinetic resolution of propargylic and allylic alcohols by
Candida antarctica lipase (Novozyme 435)
*
´
Cristiano Raminelli, Joa˜o V. Comasseto, Leandro H. Andrade and Andre L. M. Porto
´ ´
Laboratorio de Quımica Fina e Biocatalise, Instituto de Quımica, Universidade de Sa˜o Paulo, Av. Prof. Lineu Prestes,
´
748, CEP 05508-900, Sa˜o Paulo, SP, Brazil
´
Received 25 June 2004; accepted 19 August 2004
Abstract—A number of chiral propargylic and allylic alcohols were resolved by lipase-catalyzed kinetic resolution (Novozyme 435).
In some cases the enantiomeric excess was high (up to >99%).
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Chiral allylic and propargylic alcohols are versatile
building blocks for the synthesis of natural products
and biologically active compounds.1 Among the various
methods available for the synthesis of such systems, we
can mention the addition of organometallics to alde-
hydes in the presence of a chiral ligand,2 asymmetric
organozinc additions to aldehydes3 and the elimination
of chiral vinyl sulfoxides.4 As well as these methods to
access chiral unsaturated alcohols, biocatalytic proce-
dures have emerged as advantageous alternatives to
meet this goal. In this way, chiral propargylic alcohols
have been obtained by enzymatic esterifications5 and
hydrolysis6 using lipases, asymmetric reduction of acet-
ylenic ketones by alcohol dehydrogenases7 and micro-
bial hydrolysis.8 Recently, it has been reported that
Novozyme 435 (Candida antarctica lipase B) efficiently
resolves allenols9 and aryl propargylic alcohols10 with
high enantiomeric excess. Over the course of a study
on the hydrotelluration of propargylic alcohols we
needed these compounds enantiomerically pure. For this
end we decided to use CAL-B (Novozyme 435) as the
lipase for the kinetic resolution of a number of propar-
gylic alcohols 1a–e with different steric demand around
the chiral carbinolic carbon (Tables 1 and 2). The same
enzyme was used to resolve allylic enynes 2a and b
(Table 3).
2.1. Kinetic resolution of propargylic and allylic alcohols
by Novozyme 435
In Tables 1–3 are shown the allylic and propargylic alco-
hols used in this study as well as the reactions per-
formed. Initially, we investigated the influence of the
solvent in the kinetic resolution. Racemic alcohol 1a
was used in this exploratory study in view of the results
reported in the literature on the kinetic resolution of this
substrate using other enzymes and reaction conditions.10
In this way, the efficiency of the reported studies and the
present work could be compared. In Table 1 are shown
the results obtained by us.
As can be observed from the data in Table 1, tetrahy-
drofuran and diethyl ether were not efficient solvents
for the kinetic resolution of 1a. The conversion was very
low and did not increase over time. Using hexane and
benzene as solvents, the kinetic resolution was very effi-
cient, with both the (S)-(+)-1a alcohol and the (R)-(+)-
3a acetate were obtained in up to 99% ee. In order to
check if the reaction in hexane was also efficient on a
preparative scale, it was repeated using 560 mg of
(RS)-1a (see Section 4.3). After 40min at 32ꢁC, (S)-
(+)-1a was obtained in 39% isolated yield with 99% ee
while (R)-(+)-3a was obtained in 46% isolated yield with
98% ee. The enantiomeric rate (E) for the kinetic resolu-
tion of compound (RS)-1a was E >200.11 A recent study
reported the resolution of 1-phenyl-2-propynol 1a using
the enzyme Novozyme 435 and vinyl acetate both as the
acetate donor and the reaction solvent.10 Under these
*
Corresponding author. Tel.: +11 3091 2287; fax: +11 3815 5579;
e-mail: almporto@iq.usp.br
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.08.022

3118
C. Raminelli et al. / Tetrahedron: Asymmetry 15 (2004) 3117–3122
Table 1. Kinetic resolution of (RS)-phenyl propargylic alcohol 1a catalyzed by Novozyme 435a
OH
OAc
OH
Novozyme 435
+
+
H
solvents
H
H
OAc
1a (racemic)
(R)-3a
(S)-1a
t
THF or Et2O
Benzene
Ee 3a
Hexane
Ee 3a
c
Ee 1a
Ee 3a
E
c
Ee 1a
E
c
Ee 1a
96 (S)
E
20
40
2
2
2
2
2
2
2
2
2
2
2
2 (S)
2 (S)
2 (S)
2 (S)
2 (S)
2 (S)
2 (S)
2 (S)
2 (S)
2 (S)
2 (S)
99 (R)
99 (R)
99 (R)
99 (R)
99 (R)
99 (R)
99 (R)
99 (R)
99 (R)
99 (R)
99 (R)
Nc
Nc
Nc
Nc
Nc
Nc
Nc
Nc
Nc
Nc
Nc
45
49
50
50
50
50
50
50
50
50
50
80 (S)
94 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
>99 (R)
>99 (R)
>99 (R)
>99 (R)
>99 (R)
>99 (R)
>99 (R)
>99 (R)
>99 (R)
>99 (R)
>99 (R)
491
712
49
50
50
50
50
50
50
50
50
50
50
>99 (R)
>99 (R)
>99 (R)
>99 (R)
99 (R)
99 (R)
98 (R)
98 (R)
98 (R)
98 (R)
97 (R)
789
>99 (S)
>99 (S)
>99 (S)
>99 (S)
>99 (S)
>99 (S)
>99 (S)
>99 (S)
>99 (S)
>99 (S)
1057
1057
1057
1057
1057
525
70
1057
1057
1057
1057
1057
1057
1057
1057
1057
100
160
220
280
340
400
460
520
525
525
525
347
a The reaction was carried out at 32ꢁC using alcohol 1a (50lL), vinyl acetate (100lL), solvents (10mL) and Novozyme 435 (100mg); t: time
(minutes); c (%): calculated from the eeÕs of the substrate (ees) and the product (eep): c: ees/(eep + ees); ee (%) enantiomeric excess; E: enantiomeric
ratio; Nc: Not calculated.
Table 2. Kinetic resolution of (RS)-propargylic alcohols 1b–d catalyzed by Novozyme 435a
OH
OH
H
H
Novozyme 435
hexane
vinyl acetate
AcO
+
R
R
R
3b-3e
H
1b-1e
H
1
H
R = n-C6H13 (1b, 3b); i-C3H7 (1c, 3c); Et (1d, 3d); Me (1e, 3e)
t
c
Ee 1b
Ee 3b
E
c
Ee 1c
Ee 3c
E
c
Ee 1d
Ee 3d
E
20
40
21
33
41
46
51
52
52
51
51
50
50
27 (R)
49 (R)
67 (R)
81 (R)
98 (R)
99 (R)
98 (R)
94 (R)
91 (R)
85 (R)
84 (R)
99 (S)
99 (S)
98 (S)
97 (S)
95 (S)
93 (S)
92 (S)
90 (S)
89 (S)
86 (S)
85 (S)
259
324
199
164
179
144
110
67
8
8 (R)
93 (S)
93 (S)
93 (S)
92 (S)
90 (S)
88 (S)
87 (S)
86 (S)
84 (S)
82 (S)
79 (S)
29
31
21
33
34
32
32
33
38
33
35
50
26 (R)
51 (R)
75 (R)
99 (R)
99 (R)
—
26 (S)
19 (S)
11 (S)
5 (S)
2 (S)
0
2.2
2.3
2.3
2.3
2.6
2.6
–
14
21
26
39
44
46
49
53
53
55
15 (R)
24 (R)
33 (R)
58 (R)
70 (R)
75 (R)
82 (R)
93 (R)
93 (R)
97 (R)
73
87
95
98
70
100
160
220
280
340
400
460
520
>99
—
—
—
—
—
—
—
–
54
35
—
—
—
—
–
—
—
–
32
—
—
–
a The reaction was carried out at 32ꢁC using alcohols 1b,c and 1d (50lL), vinyl acetate (100lL), hexane (10mL) and Novozyme 435 (100mg); t:
time (min); c (%): calculated from the eeÕs of the substrate (ees) and the product (eep): c: ees/(eep + ees); ee (%) enantiomeric excess; E: enantiomeric
ratio.
conditions, (S)-1a and (R)-3a were obtained in 36% yield
(95% ee) and 35% yield (96% ee), respectively, after 24h
at 60ꢁC.10 Resolution of 1b under these conditions gave
(R)-1b in 40% yield and 97% ee and (S)-3b in 45% yield
and 67% ee after 14h at 60ꢁC.10
After determining the ideal reaction conditions, we
decided to apply them to different alcohols. The results
summarized in Table 2 indicate that compounds 1c
and d show moderate kinetic resolution under the stan-
dard conditions employed by us. This is expected in view
of the size of the substituents, which are not large
enough to ensure a good resolution.5a,12 Methyl alcohol
1e was not acetylated by the lipase CAL-B (results not
shown). Allylic alcohols 2a and 2b were obtained by
deprotection of the corresponding dimethyl tert-butyl-
silyl ether prepared by a method recently developed in
our laboratory, which consists of the coupling of vinylic
By using our reaction conditions (Table 2), the same
compounds (R)-1b and (S)-3b were obtained in 41%
and 45% yield, respectively, both with 96% ee. Compar-
ison of our results with the above mentioned study
showed that the use of hexane as the solvent gave a bet-
ter resolution in a shorter reaction time.

C. Raminelli et al. / Tetrahedron: Asymmetry 15 (2004) 3117–3122
3119
Table 3. Kinetic resolution of (RS)-allylic alcohols 2a and b catalyzed by Novozyme 435a
OH
H
OH
H
AcO
Novozyme 435
+
hexane
vinyl acetate
R
R
R
2
4a,4b
2a,2b
R = n-C5H11 (2a, 4a); Ph (2b, 4b)
t
c
Ee 2a
Ee 4a
E
c
Ee 2b
Ee 4b
E
20
40
37
37
42
42
50
51
51
52
52
52
53
57 (S)
57 (S)
73 (S)
73 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (R)
99 (R)
95 (R)
95 (R)
95 (R)
94 (R)
92 (R)
91 (R)
92 (R)
91 (R)
87 (R)
354
354
85
32
43
45
52
46
56
—
—
—
—
—
46 (S)
85 (S)
83 (S)
86 (S)
94 (S)
95 (S)
—
96 (R)
63 (R)
68 (R)
79 (R)
79 (R)
77 (R)
—
77
11
13
23
29
27
70
100
160
220
280
340
400
460
520
85
205
170
125
111
125
111
74
—
—
—
—
—
—
—
—
a The reaction was carried out at 32ꢁC using alcohols 2a and 2b (50lL), vinyl acetate (100lL), hexane (10mL) and Novozyme 435 (100mg); t:
time (min); c (%): calculated from the eeÕs of the substrate (ees) and the product (eep): c: ees/(eep + ees); ee (%) enantiomeric excess; E: enantiomeric
ratio.
TBAF, THF
N2, 1h, r.t.
PdCl2 (10 mol%)
CuCl2 (2eq.),
TeBu
R
H (2eq.)
Si
O
Si
O
OH
R
R
3
Et3N (4eq.), MeOH, 48h, r.t.
5a; R = n-C5H11; 68%
5b; R = Ph; 40%
2a; R = n-C5H11; 77%
2b; R = Ph; 85%
Scheme 1. Synthesis of allylic alcohols.
3. Conclusion
In conclusion, propargylic alcohols and allylic enynes
are efficiently resolved by Novozyme 435 in hexane fol-
lowing the Kazlauskas predictions concerning stereo-
chemical demands in the enzymatic resolution of
secondary alcohols.
4. Experimental
4.1. General
Chemical syntheses were monitored by TLC analyses on
precoated silica gel foils (Aluminum foil, 60 F254
Merck). Spots were visualized by p-anisaldehyde/sulfu-
ric acid or vanillin followed by heating at about
120ꢁC. The purification of the compounds was carried
out by column chromatography using silica gel (230–
400 or 230–80mesh). Conversions and enantiomeric
excesses of the enzyme-catalyzed reactions were deter-
mined using a Shimadzu GC-17A gas chromatograph
equipped with a chiral capillary column Chirasil-Dex
CB b-cyclodextrin (25m · 0.25mm). The carrier gas
was hydrogen with a pressure of 100kPa. GCMS analy-
ses were performed in equipment Shimadzu (QP 5050A)
equipped with capillary column DB-5 (JW Scientific
30m · 0.25mm · 0.25lm) and the carrier gas was
Figure 1. (a) Chromatograms of ( )-2a and ( )-4a. (b) Chromatogram
of the kinetic resolution of alcohol ( )-2a by Novozyme 435 (220min).
tellurides with alkynes under PdCl2 catalysis (Scheme
1).13 These compounds were submitted to a kinetic res-
olution with Novozyme 435 in hexane at 32ꢁC. The re-
sults are shown in Table 3. Compound 2a was efficiently
resolved by Novozyme 435 as illustrated in Figure 1.

3120
C. Raminelli et al. / Tetrahedron: Asymmetry 15 (2004) 3117–3122
1
helium. H and 13C NMR spectra were recorded on a
Bruker DPX300 (1H: 300MHz; 13C: 75MHz) or AC-
200 (1H: 200MHz; 13C: 50MHz) spectrometers using
CDCl3 as solvent. Near IR spectra were obtained on a
Bomen MB-100 spectrometer. Optical rotation values
were measured in a Jasco DIP-378 polarimeter and the
reported data refer to the Na-line value using a 1dm
cuvette. Novozyme 435: Immobilized lipase from
Candida antartica was obtained as a gift from Novo
95 (13.6%), 77 (33.0%), 64 (23.8%), 51 (30.8%), 43
(86.7%).
4.2.3. Racemic propargylic and allylic acetates. (RS)-1-
Phenyl-prop-2-yn-1-acetyloxy 3a, (RS)-non-1-yn-3-acet-
yloxy 3b, (RS)-4-methyl-pent-1-yn-3-acetyloxy 3c, (RS)-
4-pentyn-3-acetyloxy 3d, (RS)-3-butyn-2-acetyloxy 3e,
(RS)-undec-3-en-5-yn-2-acetyloxy 4a and (RS)-6-phen-
yl-hex-3-en-5-yn-2-acetyloxy 4b were prepared by litera-
ture procedure,15 by treating the appropriate alcohol
with excess acetic anhydride in pyridine.
´
Nordisk (Parana-Brazil). Vinyl acetate, 4-pentyn-3-ol
1d and 3-butyn-2-ol 1e were purchased from Aldrich
Company.
4.2.3.1. (RS)-Undec-3-en-5-yn-2-acetyloxy 4a. Yield
90mg (72%); 300MHz H NMR (CDCl3) (ppm) 5.84–
4.2. Synthesis of the substrates
1
5.70 (m, 2H), 5.53 (dt, J = 10.1Hz, 2.2Hz, 1H), 2.33
(td, J = 7.0Hz, 2.2Hz, 2H), 2.04 (s, 3H), 1.55 (quint,
J = 7.0Hz, 2H), 1.45–1.28 (m, 4H), 1.34 (d, J = 6.1Hz,
3H), 0.91 (t, J = 7.0Hz, 3H); 75MHz 13C NMR
(CDCl3) (ppm) 140.42, 111.27, 97.44, 75.98, 69.47,
31.10, 29.72, 28.36, 22.19, 21.28, 20.03, 19.56, 13.97;
near IR (film) (cmꢀ1) 2960, 2930, 2863, 2215, 1743,
1460, 1372, 1240; LRMS m/z (relative intensity)
208 (M+, 2.3%), 193 (1.4%), 179 (0.4%), 165
(13.9%), 151 (8.7%), 137 (4.3%), 123 (6.4%), 109
(14.6%), 95 (30.0%), 91 (21.5%), 81 (10.9%), 67 (9.0%),
43 (100.0%).
4.2.1. Propargylic alcohols. 1-Phenyl-prop-2-yn-1-ol
1a, non-1-yn-3-ol 1b and 4-methyl-pent-1-yn-3-ol 1c
were synthesized by literature procedures14 and purified
by horizontal distillation under reduced pressure.
4.2.2. Allylic alcohols 2a and b. To a 25mL two-necked
round-bottomed flask under nitrogen atmosphere was
added the appropriate allylic dimethyl tert-butylsilyl
ether (5a or 5b, 3mmol)13 and tetrabutylammonium
fluoride (1.0molLꢀ1 solution in THF) (6mL,
6mmol). The reaction mixture was stirred for 1h at
room temperature. After that, the reaction was
quenched by the addition of brine (50mL) and extracted
with ethyl acetate (3 · 50mL). The combined organic
phases were dried over magnesium sulfate and then fil-
tered. The organic solvent was evaporated under re-
duced pressure and the residue purified by silica gel
column chromatography using hexane/ethyl acetate
(8:2) as eluent.
4.2.3.2.
(R,S)-6-Phenyl-hex-3-en-5-yn-2-acetyloxy
4b. Yield 92mg (74%); 300MHz 1H NMR (CDCl3)
(ppm) 7.79–7.42 (m, 2H), 7.38–7.30 (m, 3H), 5.99–5.82
(m, 2H) 5.78 (d, J = 10.1Hz, 1H), 2.05 (s, 3H), 1.40
(d, J = 6.6Hz, 3H); 75MHz 13C NMR (CDCl3) (ppm)
170.11, 141.70, 131.55, 128.42, 128.29, 123.03, 110.77,
95.82, 84.72, 69.21, 21.18, 20,00; near IR (film) (cmꢀ1
)
3059, 3030, 2959, 2929, 2855, 2199, 1739, 1446, 1371,
1240, 757, 692; LRMS m/z (relative intensity) 214
(M+, 5.6%), 199 (5.8%), 185 (0.3%), 171 (34.0%), 157
(90.4%), 153 (18.1%), 128 (13.3%), 115 (6.8%),
102 (4.1%), 89 (1.8%), 77 (14.0%), 63 (5.4%), 43
(100.0%).
4.2.2.1. (Z)-Undec-3-en-5-yn-2-ol 2a. Yield 0.384g
(77%) after horizontal distillation under reduced pres-
sure; 200MHz 1H NMR (CDCl3) (ppm) 5.85 (dd,
J = 11.0Hz, 7.9Hz, 1H), 5.48 (dtd, J = 10.8Hz, 2.2Hz,
0.9Hz, 1H), 4.82 (dqd, J = 7.9Hz, 6.6Hz, 0.9Hz, 1H),
2.33 (td, J = 7.0Hz, 2.2Hz, 2H), 2.11 (sbroad, 1H), 1.55
(quint, J = 7.0Hz, 2H); 1.38–1.33 (m, 4H), 1.29 (d,
J = 6.6Hz, 3H), 0.91 (t, J = 7.0Hz, 3H); 50MHz
13C NMR (CDCl3) (ppm) 144.93, 109.66, 96.50, 76.25,
66.25, 31.02, 28.32, 22.45, 22.11, 19.42, 13.88. Near IR
(film) (cmꢀ1) 3348, 3025, 2960, 2932, 2861, 2217, 1619,
1461, 1367, 1288, 1110, 1056, 755; LRMS m/z (relative
intensity) 166 (M+, 0.3%), 165 (1.0%), 151 (2.2%), 137
(2.2%), 123 (7.2%), 109 (67.3%), 95 (27.7%), 81
(44.4%), 67 (26.1%), 55 (17.8%), 43 (100.0%).
4.3. Preparative-scale enzymatic reaction
To a 50mL Erlenmeyer flask containing 10mL of hex-
ane (HPLC grade), 1 mL of vinyl acetate and 300mg
Novozyme was added the appropriate alcohol [1a–c
(500lL), 2a, b (100lL)]. The reaction mixture was stir-
red on a rotary shaker (32ꢁC, 170rpm) until appropriate
consumption of the starting material. After that, the
mixture was filtered and the solvent evaporated. The res-
idue was purified by silica gel column chromatography
using hexane/ethyl acetate (9:1) as eluent.
4.2.2.2. (Z)-6-Phenyl-hex-3-en-5-yn-2-ol 2b. Yield
0.440g (85%); 200MHz 1H NMR (CDCl3) (ppm)
7.46–7.39 (m, 2H), 7.35–7.30 (m, 3H), 5.99 (dd,
J = 10.7Hz, 8.1Hz, 1H), 5.72 (dd, J = 11.0Hz, 0.9Hz,
1H), 4.94 (dqd, J = 8.1Hz, 6.1Hz, 0.9Hz, 1H), 1.86
(sbroad, 1H), 1.35 (d, J = 6.1Hz, 3H); 50MHz 13C
NMR (CDCl3) (ppm) 146.28, 131.43, 128.41, 128.35,
123.04, 109.17, 95.03, 85.00, 66.46, 22.57. Near IR (film)
(cmꢀ1) 3357, 3059, 3026, 2972, 2927, 2198, 1680,
1599, 1490, 1061, 756, 691; LRMS m/z (relative
intensity) 172 (M+, 22.3%), 171 (36.6%), 157 (100.0%),
152 (12.4%), 128 (97.8%), 115 (33.4%), 102 (24.7%),
4.4. Small scale enzymatic reactions16
To a 50mL Erlenmeyer flask containing 10mL of hex-
ane (HPLC grade), 50–100lL of vinyl acetate and
100mg of Novozyme were added 50lL of the appropri-
ate alcohol (1a–e and 2a,b). The reaction mixture was
stirred on a rotary shaker (32ꢁC, 170rpm) until appro-
priate consumption of the starting material. Alterna-
tively, the reactions were performed using 50lL of

C. Raminelli et al. / Tetrahedron: Asymmetry 15 (2004) 3117–3122
3121
25
propargylic alcohol 1, 20mL of hexane, 50lL of vinyl
acetate and 32mg (1000 PLU) of Novozyme.
4.6.6. (S)-(ꢀ)-4-Methyl-pent-1-yn-3-acetyloxy 3c. ½aꢁ
¼
D
ꢀ80:8 (c 6.88, CHCl3).
4.5. Control of the enzymatic resolution of propargylic
and allylic alcohols by Novozyme 435
The absolute configuration of (S)-2a was attributed after
its hydrogenation using Pd/C to give (S)-(+)-undecan-
2-ol.7e The last compound was prepared by kinetic reso-
lution of ( )-undecan-2-ol using Novozyme 435.
The reaction progress was monitored (Tables 1–3) by
collecting 0.1mL samples from time to time. These sam-
ples were analyzed by GC/FID (1lL) in a chiral capil-
lary column. The products of the biocatalyzed
reactions were compared with the racemic mixtures pre-
viously analyzed. General GC conditions: injector
200ꢁC; detector 220ꢁC.
25
4.6.7. (S)-(ꢀ)-Undec-3-en-5-yn-2-ol 2a. ½aꢁ ¼ ꢀ35:2 (c
D
0.54, CHCl3), ee 99%.
25
D
4.6.8. (R)-(+)-Undec-3-en-5-yn-2-acetyloxy 4a. ½aꢁ
ꢀ55:7 (c 1.31, CHCl3), ee 94%.
25
¼
4.5.1. (RS)-1-Phenyl-prop-2-yn-1-ol 1a and (RS)-1-phen-
yl-prop-2-yn-1-acetyloxy 3a. Oven 100ꢁC; rate 0ꢁC
(30min); retention time for 1a (R = 23.5min;
S = 24.1min); 3a (S = 12.1min; R = 15.8min).
4.6.9. (S)-(+)-Undecan-2-ol. ½aꢁ ¼ þ5:5 (c 2.01,
D
25
D
EtOH); {Lit. ½aꢁ ¼ þ7:44 (c 1.27, EtOH)}.12
25
D
4.6.10. (S)-(+)-6-Phenyl-hex-3-en-5-yn-2-ol 2b. ½aꢁ
þ46:9 (c 3.37, CHCl3), ee 80%.
¼
4.5.2. (RS)-Non-1-yn-3-ol (1b) and (RS)-non-1-yn-3-acet-
yloxy 3b. Oven 100ꢁC; rate 0ꢁC (15min); retention time
for 1b (S = 11.1min; R = 11.9min); 3b (R = 8.1min;
S = 9.7min).
4.6.11.
25
4b. ½aꢁ ¼ ꢀ116:6 (c 3.32, CHCl3), ee 70%.
(R)-(ꢀ)-6-Phenyl-hex-3-en-5-yn-2-acetyloxy
D
4.5.3. (RS)-4-Methyl-pent-1-yn-3-ol 1c and (RS)-4-
methyl-pent-1-yn-3-acetyloxy 3c. Oven 70ꢁC; rate
0ꢁC (10min); retention time for 1c (S = 7.4min;
R = 8.0min); 3c (R = 5.2min; S = 6.9min).
Acknowledgements
The authors express their gratitude to Novo Nordisk
´
(Curitiba-Parana-Brazil) for a gift of CAL-B (Novo-
zyme 435). C. Raminelli, A. L. M. Porto, L. H. And-
rade, thank FAPESP for fellowships. J. V. Comasseto
thanks FAPESP and CNPq for support.
4.5.4. (RS)-Undec-3-en-5-yn-2-ol 2a and (RS)-undec-3-
en-5-yn-2-acetyloxy 4a. Oven 90ꢁC; rate 0ꢁC (70min);
retention time for 2a (R = 51.4min; S = 59.9min); 4a
(S = 44.6min; R = 46.1min).
References
4.5.5. (RS)-6-Phenyl-hex-3-en-5-yn-2-ol 2b and (RS)-6-
phenyl-hex-3-en-5-yn-2-acetyloxy 4b. Oven 100ꢁC; rate
1ꢁC/70min; retention time for 2b (R = 33.8min;
S = 36.4min); 4b (S = 29.5min; R = 30.1min).
1. (a) Modern Acetylene Chemistry; Stang, P. J., Diederich,
F., Eds.; VCH: Weinhein, 1995; (b) Kolasa, T.; Stewart,
A. O.; Brooks, C. D. W. Tetrahedron: Asymmetry 1996, 7,
729; (c) Roush, W. R.; Sciotti, R. J. J. Am. Chem. Soc.
´
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1994, 116, 6457; (d) Fontana, A.; dIppolito, G.; DSouza,
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4.6. Assignment of the absolute configuration
The absolute configurations were determinated by com-
parison of the sign of the measured optical rotation with
those of the literature.
2. Bouz-Bouz, S.; Pradaux, F.; Cossy, J.; Ferroud, C.;
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25
4.6.1. (S)-(+)-1-Phenyl-prop-2-yn-1-ol 1a. ½aꢁ ¼ þ16:3
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25
D
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25
D
4.6.2. (R)-(+)-1-Phenyl-prop-2-yn-1-acetyloxy 3a. ½aꢁ
1.07, CHCl3), ee 85%}.6b
¼
25
þ4:4 (c 4.33, CHCl3), ee 98%; {Lit. ½aꢁ ¼ þ3:4 (c
D
25
4.6.3. (R)-(+)-Non-1-yn-3-ol 1b. ½aꢁ ¼ þ9:15 (c 4.59,
D
CHCl3), ee 96%.
25
4.6.4. (S)-(ꢀ)-Non-1-yn-3-acetyloxy 3b. ½aꢁ ¼ ꢀ48:6
D
(c 4.01, CHCl3), ee 96%.
25
4.6.5. (R)-(+)-4-Methyl-pent-1-yn-3-ol 1c. ½aꢁ ¼ þ17:2
D
25
D
(c 46.4, CHCl3); {Lit. ½aꢁ ¼ þ13:8 (c 2.00, dioxane), ee
86%}.7c

3122
C. Raminelli et al. / Tetrahedron: Asymmetry 15 (2004) 3117–3122
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