Novozym 435-catalyzed kinetic resolution of β-allenols. A facile route for the preparation of optically active β-allenols or allenyl acetates

Article abstract of DOI:10.1016/j.tet.2004.09.103

A variety of optically active β-allenols and β-allenyl acetates were synthesized via the Novozym 435-mediated kinetic resolution of racemic β-allenols. A dramatic solvent effect was observed for the stereoselectivity. The scope of the substrates and the e

Full text of DOI:10.1016/j.tet.2004.09.103

Tetrahedron 60 (2004) 11879–11887
Novozym 435-catalyzed kinetic resolution of b-allenols.
A facile route for the preparation of optically active b-allenols
or allenyl acetates
Daiwang Xu,a Zhan Lu,b Zuyi Lic and Shengming Maa,b,
*
aState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, People’s Republic of China
bLaboratory of Molecular Recognition and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310027,
People’s Republic of China
cState Key Laboratory of Bio-Organic & Natural Product Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, People’s Republic of China
Received 1 July 2004; revised 20 September 2004; accepted 23 September 2004
Available online 28 October 2004
Abstract—A variety of optically active b-allenols and b-allenyl acetates were synthesized via the Novozym 435-mediated kinetic resolution
of racemic b-allenols. A dramatic solvent effect was observed for the stereoselectivity. The scope of the substrates and the effect of the
concentration and temperature on the reaction were also investigated.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
routes to enantiomerically pure or enriched alcohols with
the advantages of easy availability of starting materials and
the biocatalyst. The kinetic resolution of 2-methylpenta-3,4-
dien-1-ol using Lipase AK and Novozym-435 (a form of
candida antarctica lipase B) as the biocatalyst has been
reported.14 The kinetic resolution of those b-allenols with
chiral centers connected with the hydroxyl group using an
enzyme or a microorganism as the catalyst has not been
reported. Previously, we have reported that Novozym-435
(a form of candida antarctica lipase B) is an efficient
biocatalyst for the kinetic resolution of a series of racemic
2,3-allenols15 and terminal aryl-substituted propargylic
alcohols that can be converted to the corresponding 2,3-
allenols.16 Here we wish to report our recent results on
Novozym-435-catalyzed kinetic resolution of b-allenols.
Allenes are a class of compounds with two cumulative
carbon–carbon double bonds, which demonstrate interesting
properties such as unique reactivity and chirality.1 In the
past decades, much attention has been paid to the synthesis
and reaction of functionalized allenes.2 Since the chirality of
allenes can be transformed to the products with one or more
chiral center, people are interested in the synthesis of
optically active allenes.3 Allenols are a very important
class of functionalized allenes, which can be converted to
many organic intermediates. For example, 2,3-allenols
can be stereoselectively converted into oxiranes,4 2,5-
dihydrofurans,5 a-methylenelactones,6 a or g-amino
alcohols7 etc. Starting from b-allenols, 3-oxacyclohexanone,8
3,6-dihydro-2H-pyran,9 2,3-dihydrofuran10 and furans11 can
also easily be obtained. Thus, the synthesis of optically
active allenols is of current interest. For optically active
2,3-allenols, some synthetic methods were developed in
recent years.12 However, the methodologies for the
synthesis of optically active b-allenols were very limited:
the methodologies for the optically active b-allenols
reported in the literature are mainly using optically active
3-en-5-yn-2-ols as the starting material, which are not easily
available.13 Biocatalytic methods are now well-established
2. Results and discussion
2.1. Synthesis of starting racemic 2,3-allenols
The required racemic b-allenols can be synthesized
according to the known procedure as shown in Scheme 1.17
2.2. Kinetic resolution
We started our research with the kinetic resolution of 1a
using the same reaction conditions reported in Ref. 15.
Optically active 2a was obtained in 35% yield with 96% ee
* Corresponding author. Tel.: C86 21 6416 3300; fax: C86 21 6416 7510;
e-mail: masm@mail.sioc.ac.cn
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.09.103

11880
D. Xu et al. / Tetrahedron 60 (2004) 11879–11887
Scheme 1.
while the ee value of unreacted 1a was not good (Eq. 1).
It was reported that the solvent may be critical to the
enzyme-catalyzed reaction.18 Some typical results using
Novozym 435 as the biocatalyst in different solvent are
listed in Table 1. As shown in Table 1, the solvent did affect
the reaction dramatically: using 1,4-dioxane as the solvent,
the reaction cannot occur (Table 1, entry 1); when the
reaction was carried out in vinyl acetate, E value of the
reaction is 62 (Table 1, entry 2); when using hexane,
benzene, acetone, or acetonitrile, the results are better with
the E values being 144, 148, 156, and 178, respectively
(Table 1, entries 3, 4, 5, and 6); while using the cyclohexane
as the solvent, optically active (S)-1a can be obtained in
44% yield and 74% ee and (R)-2a in 42% yield and 97% ee
(Table 1, entry 7). Changing the concentration (Table 2) and
reaction temperature (Eq. 2) did not greatly alter the
selectivity of the reaction (Eq. 2).
(1)
In order to identify the best enzyme for the present class of
compounds, extensive screening experiments were carried
out. Using PPL, CRL, Lipase AK, and Lipase Ps 30 as the
catalyst, the reaction is extremely slow or does not even occur
(Scheme 2).
(2)
Scheme 2.

D. Xu et al. / Tetrahedron 60 (2004) 11879–11887
Table 1. Novozym 435-catalyzed kinetic resolution of 1a in different solventsa
11881
Entry
Time (d)
Solvent
Alcohol (1a)
Yieldc (%)
Ester (2a)
Eb
ee (%)d
Yieldc (%)
eee (%)
1
2
3
4
5
6
7
4
4
3
4
3
4
4
1,4-Dioxane
Vinyl acetate
Hexane
Benzene
Acetone
NR
29
38
34
43
35
42
56
58
64
56
64
44
43
77
67
74
48
74
95
97
97
97
98
98
62
144
148
156
178
192
Acetonitrile
Cyclohexane
a The reaction was carried out at 30 8C using 1a (50 mg), vinyl acetate (55 mL), solvent (1.5 mL) and enzyme (35 mg).
b EZln[eeP(1KeeS)]/(eePCeeS)/ln[eeP(1CeeS)]/(eePCeeS).
c Isolated yield based on 1a.
d Determined after its conversion into the corresponding acetate.
e Enantiomeric excess determined via GC.
Table 2. Novozym 435-catalyzed kinetic resolution of 1a at different concentrationsa
Entry
Solvent (mL)
(S)-1a
(R)-2a
Eb
Yield (%)c
ee (%)d
Yield (%)c
ee (%)d
1
2
3
4
3.0
2.5
2
68
50
48
46
39
58
52
45
32
30
37
29
98
98
98
98
172
199
176
155
1
a The reaction was carried out at 30 8C using 1a (50 mg), vinyl acetate (55 mL), solvent (1.5 mL) and enzyme (35 mg).
b EZln[eeP(1KeeS)]/(eePCeeS)/ln[eeP(1CeeS)]/(eePCeeS).
c Isolated yield based on 1a.
d Enantiomeric excess determined by GC.
Subsequently, a series of b-allenols were resolved. Some
typical results were listed in Table 3. From the results shown
in Table 3, it can be clearly seen that this methodology can
accommodate a wide range of substrates. In most cases, the
reaction went well affording optically active b-allenols or
allenyl acetates in good yields and good ees. The
substituents have some effect on the stereoselectivity of
the reaction. The result with R2 being ethyl is better than
those with R2 being methyl, ethenyl, and ethynyl (Table 3,
entries 1, 10, 12, and 14). When R2 is beyond two carbon
atoms, the reaction is extremely slow or even does not occur
at all. Although R3 and R4 are far away from the chiral
center, they also affect the stereoselectivity of the reaction.
The results are different when R3 and R4 are H, methyl, and
cyclohexylidene (Table 3, entries 1, 8, and 9). When R1 is
t-butyl, perhaps due to the stereic hindrance, the reaction did
not occur. The absolute configuration of the obtained
(C)-4-methylhexa-4,5-dien-2-ol (1r) was determined to be
S by the comparison of the sign of the specific rotation
with the known (R)-(K)-4-methylhexa-4,5-dien-2-ol
(Scheme 3).13 The absolute configuration of the compounds
in Table 3 was tentatively assigned based on this result
(Scheme 3).
Scheme 3.
The resulting optically active allenol (1a) can easily be
converted to the corresponding 3,6-dihydropyran without
obvious racemization (Eq. 3).

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D. Xu et al. / Tetrahedron 60 (2004) 11879–11887
Table 3. Novozym-435-catalyzed kinetic resolution of b-allenolsa
Entry
1
1
2
Eb
R1
R2
R3
R4
Yield (%)c
ee (%)d
Yield (%)c
ee (%)d
1
2
3
4
n-C4H9
n-C3H7
n-C6H13
n-C7H15
Allyl
Et
Et
Et
Et
Et
Et
Et
Et
Et
Me
Me
Ethenyl
Ethenyl
Ethynyl
Ethynyl
H
H
H
H
H
H
Me
Me
H (1a)
H (1b)
H (1c)
H (1d)
H (1e)
H (1f)
46
39
51
40
48
38
27
46
42
37
38
43
44
38
40
83 (S-1a)
82 (S-1b)
58 (S-1c)
54 (S-1d)
50 (S-1e)
71 (S-1f)
93 (S-1g)
44 (S-1h)
96 (S-1i)
88 (S-1j)
91 (S-1k)
93 (R-1l)
93 (R-1m)
88 (R-1n)
90 (R-1o)
42
36
28
25
28
44
59
26
51
35
52
56
40
56
40
97 (R-2a)
96 (R-2b)
98 (R-2c)
98 (R-2d)
97 (R-2e)
72 (R-2f)
22 (R-2g)
95 (R-2h)
82 (R-2i)
89 (R-2j)
42 (R-2k)
75 (S-2l)
85 (S-2m)
44f (S-2n)
60 (S-2o)
199
143
178
191
111
12
4
66
41
52
5e
6e
7f
8
PhCH2
H
Me (1g)
Me (1h)
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C5H11
n-C4H9
n-C5H11
9
(CH2)5 (1i)
H (1j)
10e
11
12e
13
14
15
H
Me
H
H
H
Me (1k)
H (1l)
H (1m)
H (1n)
H (1o)
31
24
108
7
H
35
a The reaction was carried out at 30 8C using 1 (100 mg), vinyl acetate (2 equiv), Novozym 435 (100 mg), and cyclohexane (3.0 mL).
b EZln[eeP(1KeeS)]/(eePCeeS)/ln[eeP(1CeeS)]/(eePCeeS).
c Isolated yield based on 1.
d Enantiomeric excess determined via GC or HPLC.
e Novozym 435 (70 mg).
f
Reaction time: 1 day.
145 min. The mixture was stirred at 140–150 8C for 5 h as
the resulting EtOH was removed by a Dean–Stark trap.
After the starting material was completely consumed as
monitored by TLC, the mixture was cooled to room
temperature, evaporated, and purified by chromatography
on silica gel to afford 3-(n-butyl)penta-3,4-dienoic acid
ethyl ester, which was submitted to the next step without
further characterization.
(3)
To a suspension of LiAlH4 (2.13 g, 56.1 mmol) in dried
THF (72 mL) was added a solution of the obtained
3-(n-butyl)penta-3,4-dienoic acid ethyl ester in dried THF
(72 mL) dropwise at 0 8C. After stirring at rt for 1 h, the
reaction was quenched by the careful addition of water at
0 8C. Filtration, drying over anhydrous Na2SO4, and
concentration afforded the crude product, which was
purified by chromatography on silica gel (eluent: petroleum
ether/ethyl etherZ10/1) to afford pure 3-(n-butyl)penta-3,4-
dien-1-ol (4.65 g, 61% (two steps)).
In conclusion, we have developed an efficient and facile
method for the preparation of optically active b-allenols or
b-allenyl acetates under mild conditions. Due to the easy
availability of the catalyst and the synthetic potential of the
products, this methodology should be useful in organic
chemistry. Further studies on this reaction are being carried
out in our laboratory.
3. Experimental
A solution of 3-(n-butyl)penta-3,4-diene-1-ol (1.57 g,
11.2 mmol) in CH2Cl2 (5 mL) was added to a suspension
of Dess–Martin periodinane (DMP) (6.61 g, 17.6 mmol) in
CH2Cl2 (15 mL). After 0.5 h, the reaction was diluted with
ethyl ether (30 mL), and the resulting suspension was added
to a solution of saturated NaHCO3 (50 mL) with sodium
thiosulfate (30.00 g, 121 mmol). After the mixture was
stirred for 30 min, the ether layer was separated and the
aqueous layer was extracted with ethyl ether (3!30 mL).
The combined organic layer was dried over anhydrous
Na2SO4 and concentrated to afford the allenal, which was
used without further purification.
3.1. Synthesis of racemic b-allenols (1a–s)
The racemic b-allenols were synthesized according to the
procedure reported in the literature.17 A typical example
was presented as follows:
3.1.1. Synthesis of (G)-5-(n-butyl)hepta-5,6-dien-3-ol
(1a). To a dried three-neck flask were added hepta-2-yn-1-ol
(6.12 g, 54.7 mmol), triethyl orthoacetate (34.8 mL,
189 mmol), and propionic acid (0.68 mL) under nitrogen.
Additional 0.5 mL of propionic acid was added after

D. Xu et al. / Tetrahedron 60 (2004) 11879–11887
11883
To a solution of the obtained allenal in ethyl ether (20 mL)
was added EtMgBr (1 M in THF, 20 mL) dropwise at
K78 8C under nitrogen. Then, the resulting mixture was
stirred for 10 h at K78 8C as monitored by TLC. The
reaction was quenched with saturated NH4Cl at K78 8C.
After the temperature rose to rt, the organic layer was
separated. The aqueous layer was extracted with ethyl ether
(3!30 mL). The combined organic layer was dried over
anhydrous Na2SO4, concentrated, and purified by chroma-
tography on silica gel (eluent: petroleum ether/ethyl etherZ
15/1) to afford racemic 5-(n-butyl)hepta-5,6-dien-3-ol (1a)
(0.90 g, 48%); liquid; 1H NMR (300 MHz, CDCl3): d 4.80–
4.70 (m, 2H), 3.75–3.64 (m, 1H), 2.20–1.90 (m, 5H), 1.58–
1.28 (m, 6H), 0.96 (t, JZ7.5 Hz, 3H), 0.90 (t, JZ7.2 Hz,
3H); 13C NMR (75.4 MHz, CDCl3): d 205.7, 100.5, 75.9,
70.9, 39.9, 31.9, 29.5, 29.3, 22.2, 13.8, 9.8; IR (neat): 3388,
1956 cmK1; MS (m/z) 168 (MC, 2.47), 43 (100); HRMS
Calcd for C11H20O (MC): 168.1514. Found 168.1488.
3H), 0.91 (t, JZ7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3):
d 205.8, 100.4, 76.0, 71.0, 40.0, 34.4, 29.6, 20.6, 13.7, 9.9;
IR (neat): 3396, 1956 cmK1; MS (m/z) 154 (MC, 5.39), 43
(100); HRMS Calcd for C10H18O (MC): 154.1358. Found
154.1345. Compound (R)-2b: 96% ee (GC condition:
Column: RT-bDEXcst (30 m, 0.25 m ID, 0.25 mm DF);
carrier: N2, 10 psi; injector: 250 8C; Detector (FID, H2,
0.218 MPa): 250 8C; Oven temperature: 105 8C (40 min));
[a]2D0C19.5 (c 1.10, CHCl3); liquid; H NMR (300 MHz,
1
CDCl3): d 5.00–4.84 (m, 1H), 4.66–4.60 (m, 2H), 2.28–2.06
(m, 2H), 2.05 (s, 3H), 2.00–1.82 (m, 2H), 1.74–1.40
(m, 4H), 0.92 (t, JZ7.2 Hz, 3H), 0.88 (t, JZ7.2 Hz, 3H);
13C NMR (75.4 MHz, CDCl3): d 206.5, 170.7, 99.1, 75.2,
73.8, 36.7, 34.2, 26.8, 21.2, 20.6, 13.7, 9.5; IR (neat): 1958,
1740 cmK1; MS (m/z) 196 (MC, 1.64), 43 (100); HRMS
Calcd for C12H20O2 (MC): 196.1463. Found 196.1454.
3.2.3. Synthesis of (S)-5-(n-hexyl)hepta-5,6-dien-3-ol
((S)-1c) and (R)-5-(n-hexyl)hepta-5,6-dien-3-yl acetate
((R)-2c). The reaction of racemic 5-(n-hexyl)hepta-5,6-
diene-3-ol (100 mg) with Novozym-435 (100 mg) and vinyl
acetate (94 mL) afforded (S)-1c (51 mg, 51%) and (R)-2c
(34 mg, 28%). Compound (S)-1c: 58% ee (determined after
its conversion to the corresponding acetate); [a]2D0C1.4
3.2. Kinetic resolution of racemic b-allenols (1a–1o)
3.2.1. Synthesis of (S)-5-(n-butyl)hepta-5,6-dien-3-ol
((S)-1a) and (R)-5-(n-butyl)hepta-5,6-dien-3-yl acetate
((R)-2a). Typical procedure. Novozym 435 (100 mg) was
added into the mixture of racemic 5-(n-butyl)hepta-5,6-
dien-3-ol (100 mg), cyclohexane (3 mL) and vinyl acetate
(110 mL). After stirring at 30 8C for 96 h, the reaction was
stopped by filtration. Evaporation and purification by flash
chromatography on silica gel (petroleum ether/etherZ40/
1/10/1) afforded (S)-1a (46 mg, 46%) and (R)-2a (52 mg,
42%). Compound (S)-1a: 83% ee (determined after its
conversion to the corresponding acetate); [a]2D0C1.2
1
(c 1.05, CHCl3); liquid; H NMR (300 MHz, CDCl3): d
4.80–4.68 (m, 2H), 3.75–3.60 (m, 1H), 2.20–1.90 (m, 5H),
1.60–1.20 (m, 10H), 0.96 (t, JZ7.5 Hz, 3H), 0.88 (t, JZ
6.6 Hz, 3H); 13C NMR (75.4 MHz, CDCl3): d 205.7, 100.7,
76.1, 71.0, 40.1, 32.4, 31.7, 29.6, 28.9, 27.4, 22.6, 14.1,
10.0; IR (neat): 3398, 1956 cmK1; MS (m/z) 196 (MC,
1.96), 43 (100); HRMS Calcd for C13H24O (MC): 196.1827.
Found 196.1848. Compound (R)-2c: 98% ee (GC condition:
Column: RT-bDEXcst (30 m, 0.25 m ID, 0.25 mm DF);
carrier: N2, 8.0 psi; injector: 250 8C; Detector (FID, H2,
0.218 MPa): 250 8C; Oven temperature: 130 8C (80 min),
then 1 8C/min to 150 8C (2 min)); [a]2D0C16.8 (c 1.10,
1
(c 1.10, CHCl3); liquid; H NMR (300 MHz, CDCl3): d
4.80–4.70 (m, 2H), 3.75–3.64 (m, 1H), 2.20–1.90 (m, 5H),
1.58–1.28 (m, 6H), 0.96 (t, JZ7.5 Hz, 3H), 0.90 (t, JZ
7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3): d 205.7, 100.5,
75.9, 70.9, 39.9, 31.9, 29.5, 29.3, 22.2, 13.8, 9.8; IR (neat):
3388, 1956 cmK1; MS (m/z) 168 (MC, 2.47), 43 (100);
HRMS Calcd for C11H20O (MC): 168.1514. Found
168.1488. Compound (R)-2a: 97% ee (GC condition:
Column: RT-bDEXcst (30 m, 0.25 m ID, 0.25 mm DF);
carrier: N2, 10 psi; injector: 250 8C; Detector (FID, H2,
0.218 MPa): 250 8C; Oven temperature: 120 8C (10 min),
then 1.0 8C to 180 8C (20 min)); [a]2D0C5.8 (c 1.10, CHCl3);
1
CHCl3); liquid; H NMR (300 MHz, CDCl3): d 4.98–4.85
(m, 1H), 4.66–4.60 (m, 2H), 2.25–2.06 (m, 2H), 2.03
(s, 3H), 1.98–1.87 (m, 2H), 1.70–1.45 (m, 2H), 1.43–1.23
(m, 8H), 0.92–0.80 (m, 6H); 13C NMR (75.4 MHz, CDCl3):
d 206.4, 170.7, 99.3, 75.3, 73.8, 36.7, 32.1, 31.7, 28.9, 27.4,
26.8, 22.6, 21.2, 14.1, 9.5; IR (neat): 1958, 1740 cmK1; MS
(m/z) 238 (MC, 4.76), 43 (100); HRMS Calcd for C15H26O2
(MC): 238.1933. Found 238.1916.
1
liquid; H NMR (300 MHz, CDCl3): d 4.93–4.85 (m, 1H),
4.65–4.57 (m, 2H), 2.22–2.05 (m, 2H), 2.02 (s, 3H), 1.96–
1.87 (m, 2H), 1.64–1.50 (m, 2H), 1.50–1.23 (m, 4H), 0.87
(t, JZ7.5 Hz, 6H); 13C NMR (75.4 MHz, CDCl3): d 206.9,
170.5, 99.2, 75.2, 73.7, 36.6, 31.7, 29.5, 26.7, 22.2, 21.1,
13.8, 9.4; IR (neat): 1958, 1740 cmK1; MS (m/z) 210 (MC,
0.55), 43 (100); HRMS Calcd for C13H22O2 (MC):
210.1620. Found 210.1593.
3.2.4. Synthesis of (S)-5-(n-heptyl)hepta-5,6-dien-3-ol
((S)-1d) and (R)-5-(n-heptyl)hepta-5,6-dien-3-yl acetate
((R)-2d). The reaction of racemic 5-(n-heptyl)hepta-5,6-
dien-3-ol (100 mg) with Novozym-435 (100 mg) and vinyl
acetate (88 mL) afforded (S)-1d (40 mg, 40%) and (R)-2d
(30 mg, 25%). Compound (S)-1d: 54% ee (determined after
its conversion to the corresponding acetate); [a]2D0K1.5
1
(c 1.00, CHCl3); liquid; H NMR (300 MHz, CDCl3): d
3.2.2. Synthesis of (S)-5-(n-propyl)hepta-5,6-dien-3-ol
((S)-1b) and (R)-5-(n-propyl)hepta-5,6-dien-3-yl acetate
((R)-2b). The reaction of racemic 5-(n-propyl)hepta-5,6-
dien-3-ol (100 mg) with Novozym-435 (100 mg) and vinyl
acetate (117 mL) afforded (S)-1b (39 mg, 39%) and (R)-2b
(46 mg, 36%). Compound (S)-1b: 81% ee (determined after
its conversion to the corresponding acetate); [a]2D0C6.8
(c 0.75, CHCl3); liquid; H NMR (300 MHz, CDCl3): d
4.80–4.72 (m, 2H), 3.76–3.62 (m, 1H), 2.20–2.00 (m, 2H),
2.00–1.88 (m, 3H), 1.60–1.40 (m, 4H), 0.96 (t, JZ7.5 Hz,
4.80–4.70 (m, 2H), 3.74–3.62 (m, 1H), 2.20–1.92 (m, 5H),
1.70–1.38 (m, 4H), 1.38–1.20 (m, 8H), 0.96 (t, JZ7.5 Hz,
3H), 0.87 (t, JZ6.6 Hz, 3H); 13C NMR (75.4 MHz, CDCl3):
d 205.7, 100.7, 76.1, 71.0, 40.1, 32.4, 31.8, 29.6, 29.2, 29.1,
27.4, 22.6, 14.1, 10.0; IR (neat): 3383, 1956 cmK1; MS
(m/z) 210 (MC, 2.08), 43 (100); HRMS Calcd for C14H26O
(MC): 210.1984. Found 210.1965. Compound (R)-2d: 98%
ee (GC condition: Column: RT-bDEXcst (30 m, 0.25 m ID,
0.25 mm DF); carrier: N2, 8.0 psi; injector: 250 8C; Detector
(FID, H2, 0.218 MPa): 250 8C; Oven temperature: 130 8C
1

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D. Xu et al. / Tetrahedron 60 (2004) 11879–11887
(80 min), then 1 8C/min to 150 8C (2 min)); [a]2D0C15.9
(c 0.90, CHCl3); liquid; H NMR (300 MHz, CDCl3): d
43 (100); HRMS Calcd for C16H20O2 (MC): 244.1463.
Found 244.1424.
1
4.94–4.87 (m, 1H), 4.66–4.59 (m, 2H), 2.23–2.04 (m, 2H),
2.02 (s, 3H), 1.95–1.87 (m, 2H), 1.70–1.45 (m, 2H), 1.43–
1.19 (m, 10H), 0.91–0.83 (m, 6H); 13C NMR (75.4 MHz,
CDCl3): d 206.4, 170.7, 99.3, 75.3, 73.8, 36.7, 32.1, 31.8,
29.2, 29.1, 27.4, 26.8, 22.6, 21.2, 14.1, 9.5; IR (neat): 1958,
1740 cmK1; MS (m/z) 252 (MC, 5.28), 43 (100); HRMS
Calcd for C16H28O2 (MC): 252.2089. Found 252.2097.
3.2.7. Synthesis of (S)-7-methylocta-5,6-dien-3-ol ((S)-1g)
and (R)-7-methylocta-5,6-dien-3-yl acetate ((R)-2g). The
reaction of racemic 3-methylocta-5,6-dien-3-ol (100 mg)
with Novozym-435 (100 mg) and vinyl acetate (132 mL)
afforded (S)-1g (27 mg, 27%) and (R)-2g (77 mg, 59%).
Compound (S)-1g: 93% ee (determined after its conversion
to the corresponding acetate); [a]2D0K2.1 (c 0.50, CHCl3);
1
liquid; H NMR (300 MHz, CDCl3): d 5.02–4.90 (m, 1H),
3.2.5. Synthesis of (S)-5-allylhepta-5,6-dien-3-ol ((S)-1e)
and (R)-5-allylhepta-5,6-dien-3-yl acetate ((R)-2e). The
reaction of racemic 5-allylhepta-5,6-dien-3-ol (100 mg) with
Novozym-435 (70 mg) and vinyl acetate (122 mL) afforded
(S)-1e (48 mg, 48%) and (R)-2e (36 mg, 28%). Compound
(S)-1e: 50% ee (determined after its conversion to the
corresponding acetate); [a]2D0C0.8 (c 2.40, CHCl3); liquid;
1H NMR (300 MHz, CDCl3): d 5.86–5.76 (m, 1H), 5.12–5.04
(m, 2H), 4.80–4.70 (m, 2H), 3.73–3.67 (m, 1H), 2.76–2.74
(m, 2H), 2.20–2.03 (m, 2H), 1.92 (d, JZ3.0 Hz, 1H), 1.60–
1.47 (m, 2H), 0.97 (t, JZ7.5 Hz, 3H); 13C NMR (75.4 MHz,
CDCl3): d 206.1, 135.4, 116.3, 99.1, 76.2, 71.0, 39.5, 37.4,
29.6, 10.0; IR (neat): 3414, 1957, 1639 cmK1; MS (m/z) 152
(MC, 0.97), 79 (100); HRMS Calcd for C10H16O (MC):
152.1201. Found 152.1210. Compound (R)-2e: 97% ee (GC
condition: Column: RT-bDEXcst (30 m, 0.25 m ID, 0.25 mm
DF); carrier: N2, 10 psi; injector: 250 8C; Detector (FID, H2,
0.218 MPa): 250 8C; Oven temperature: 100 8C (60 min));
3.63–3.51 (m, 1H), 2.23–1.96 (m, 2H), 1.79 (d, JZ3.9 Hz,
1H), 1.70 (s, 3H), 1.69 (s, 3H), 1.59–1.44 (m, 2H), 0.96
(t, JZ7.5 Hz, 3H); 13C NMR (75.4 MHz, CDCl3): d 203.0,
95.3, 84.9, 72.4, 36.8, 29.3, 20.7, 20.6, 10.0; IR (neat): 3362,
1969 cmK1; MS (m/z) 140 (MC, 100), 125 (MCKCH3,
27.90); HRMS Calcd for C9H16O (MC): 140.1201. Found
140.1206. Compound (R)-2g: 22% ee (GC condition:
Column: RT-bDEXcst (30 m, 0.25 m ID, 0.25 mm DF);
carrier: N2, 10 psi; injector: 250 8C; Detector (FID, H2,
0.218 MPa): 250 8C; Oven temperature: 120 8C (20 min));
[a]2D0C12.2 (c 0.75, CHCl3); liquid; H NMR (300 MHz,
1
CDCl3): d 4.81–4.74 (m, 2H), 2.20–2.06 (m, 2H), 1.99 (s,
3H), 1.60 (s, 3H), 1.59 (s, 3H), 1.59–1.42 (m, 2H), 0.82 (t,
JZ7.5 Hz, 3H); 13C NMR (75.4 MHz, CDCl3): d 202.9,
170.8, 95.0, 84.0, 74.9, 33.5, 26.3, 21.2, 20.52, 20.46, 9.5;
IR (neat): 1970, 1740 cmK1; MS (m/z) 182 (MC, 8.40), 43
(100); HRMS Calcd for C11H18O2 (MC): 182.1307. Found
182.1292.
1
[a]2D0C23.9 (c 0.50, CHCl3); liquid; H NMR (300 MHz,
CDCl3): d 5.84–5.73 (m, 1H), 5.11–5.03 (m, 2H), 4.96–4.91
(m, 1H), 4.69–4.65 (m, 2H), 2.75–2.72 (m, 2H), 2.22–2.15
(m, 2H), 2.30 (s, 3H), 1.68–1.54 (m, 2H), 0.89 (t, JZ7.5 Hz,
3H); 13C NMR (75.4 MHz, CDCl3): d 206.8, 170.6, 135.4,
116.1, 97.7, 75.4, 73.6, 37.1, 36.0, 26.8, 21.2, 9.5; IR (neat):
1960, 1743, 1639 cmK1; MS (m/z) 194 (MC, 1.28), 43 (100);
HRMS Calcd for C12H18O2 (MC): 194.1307. Found
194.1271.
3.2.8. Synthesis of (S)-7-methyl-5-(n-butyl)octa-5,6-dien-
3-ol ((S)-1h) and (R)-7-methyl-5-(n-butyl)octa-5,6-dien-
3-yl acetate ((R)-2h). The reaction of racemic 7-methyl-5-
(n-butyl)octa-5,6-diene-3-ol (100 mg) with Novozym-435
(100 mg) and vinyl acetate (94 mL) afforded (S)-1h (46 mg,
46%) and (R)-2h (31 mg, 26%). Compound (S)-1h: 44% ee
(determined after its conversion to the corresponding
acetate); [a]2D0C0.7 (c 1.45, CHCl3); liquid; 1H NMR
(300 MHz, CDCl3): d 3.68–3.58 (m, 1H), 2.20–2.00 (m,
1H), 2.00–1.80 (m, 4H), 1.69 (s, 6H), 1.58–1.42 (m, 2H),
1.42–1.22 (m, 4H), 0.96 (t, JZ7.5 Hz, 3H), 0.89 (t, JZ
7.5 Hz, 3H); 13C NMR (75.4 MHz, CDCl3): d 198.6, 99.2,
96.5, 71.1, 40.7, 33.0, 29.7, 29.5, 22.3, 21.1, 20.8, 14.0,
10.1; IR (neat): 3373, 1960 cmK1; MS (m/z) 196 (MC,
5.64), 96 (100); HRMS Calcd for C13H24O (MC): 196.1827.
Found 196.1827. Compound (R)-2h: 95% ee (GC condition:
Column: RT-bDEXcst (30 m, 0.25 m ID, 0.25 mm DF);
carrier: N2, 10 psi; injector: 250 8C; Detector (FID, H2,
0.218 MPa): 250 8C; Oven temperature: 100 8C (60 min),
then 2 8C/min to 150 8C (60 min)); [a]2D0C10.7 (c 1.40,
3.2.6. Synthesis of (S)-5-benzylhepta-5,6-dien-3-ol ((S)-
1f) and (R)-5-benzylhepta-5,6-dien-3-yl acetate ((R)-2f).
The reaction of racemic 5-benzylhepta-5,6-dien-3-ol
(100 mg) with Novozym-435 (70 mg) and vinyl acetate
(92 mL) afforded (S)-1f (38 mg, 38%) and (R)-2f (53 mg,
44%). Compound (S)-1f: 71% ee (HPLC conditions:
Chiralcel OD Column (0.46 cmf!25 cm); l 254 nm;
rate: 0.7 mL/min; hexane: i-PrOHZ100: 1.25); [a]2D0K4.8
1
(c 1.10, CHCl3); liquid; H NMR (300 MHz, CDCl3): d
7.40–7.20 (m, 5H), 4.82–4.70 (m, 2H), 3.80–3.60 (m, 1H),
3.35 (t, JZ2.4 Hz, 2H), 2.20–1.98 (m, 3H), 1.60–1.40 (m,
2H), 0.94 (t, JZ7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3):
d 206.7, 139.1, 128.9, 128.3, 126.4, 100.1, 75.9, 71.1, 39.8,
39.1, 29.6, 10.0; IR (neat): 3398, 1957 cmK1; MS (m/z) 202
(MC, 27.45), 91 (100); HRMS Calcd for C14H18O (MC):
202.1358. Found 202.1371. Compound (R)-2f: 72% ee
(determined after its conversion to the corresponding
alcohol); [a]2D0C54.6 (c 1.10, CHCl3); liquid; 1H NMR
(300 MHz, CDCl3): d 7.33–7.12 (m, 5H), 5.00–4.80 (m,
1H), 4.67–4.63 (m, 2H), 3.32 (t, JZ2.4 Hz, 2H), 2.23–2.09
(m, 2H), 2.03 (s, 3H), 1.70–1.52 (m, 2H), 0.94 (t, JZ7.5 Hz,
3H); 13C NMR (75.4 MHz, CDCl3): d 207.4, 170.6, 139.1,
128.9, 128.2, 126.2, 98.8, 75.1, 73.6, 39.4, 35.6, 26.8, 21.2,
9.4; IR (neat): 1959, 1737 cmK1; MS (m/z) 244 (MC, 3.13),
1
CHCl3); liquid; H NMR (300 MHz, CDCl3): d 4.92–4.82
(m, 1H), 2.20–2.02 (m, 2H), 2.01 (s, 3H), 1.92–1.80 (m,
2H), 1.67 (s, 3H), 1.66 (s, 3H), 1.60–1.40 (m, 2H), 1.40–
1.20 (m, 4H), 0.87 (t, JZ7.2 Hz, 6H); 13C NMR (75.4 MHz,
CDCl3): d 199.3, 170.7, 97.8, 95.6, 74.2, 37.1, 32.7, 29.7,
26.8, 22.2, 21.3, 20.74, 20.71, 14.0, 9.5; IR (neat):
1740 cmK1; MS (m/z) 238 (MC, 1.01), 195 (MCKCOCH3,
3.11), 43 (100); HRMS Calcd for C13H23O (MCKCOCH3):
195.1749. Found 195.1765.
3.2.9. Synthesis of (S)-6-cyclohexylidene-5-(n-butyl)hexa-
5-en-3-ol ((S)-1i) and (R)-6-cyclohexylidene-5-(n-butyl)-
hex-5-en-3-yl acetate ((R)-2i). The reaction of racemic

D. Xu et al. / Tetrahedron 60 (2004) 11879–11887
11885
6-cyclohexylidene-5-(n-butyl)hexa-5-en-3-ol (100 mg)
with Novozym-435 (100 mg) and vinyl acetate (78 mL)
afforded (S)-1i (42 mg, 42%) and (R)-2i (60 mg, 51%).
Compound (S)-1i: 96% ee (determined after its conversion
to the corresponding benzoate (HPLC conditions: Chiralcel
OD Column (0.46 cmf!25 cm); l 254 nm; rate: 0.7 mL/
min; hexane: i-PrOHZ100: 0.1)); [a]2D0C0.5 (c 2.55,
1.88 (m, 5H), 1.70 (s, 3H), 1.69 (s, 3H), 1.40–1.25 (m, 4H),
1.20 (d, JZ6.6 Hz, 3H), 0.89 (t, JZ7.2 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3): d 198.6, 99.2, 96.4, 66.1, 42.8, 33.0,
29.7, 22.4, 22.2, 21.0, 20.8, 14.0; IR (neat): 3362, 1961 cmK1
;
MS (m/z) 182 (MC, 7.68), 45 (100); HRMS Calcd for
C12H22O (MC): 182.1671. Found 182.1693. Compound
(R)-2k: 42% ee (GC condition: Column: RT-bDEXcst
(30 m, 0.25 m ID, 0.25 mm DF); carrier: N2, 10 psi; injector:
250 8C; Detector (FID, H2, 0.218 MPa): 250 8C; Oven
temperature: 95 8C (120 min)); [a]2D0K1.6 (c 1.30, CHCl3);
1
CHCl3); liquid; H NMR (300 MHz, CDCl3): d 3.69–3.55
(m, 1H), 2.15–2.03 (m, 6H), 2.01–1.86 (m, 3H), 1.70–1.42
(m, 8H), 1.40–1.21 (m, 4H), 0.95 (t, JZ7.2 Hz, 3H), 0.88 (t,
JZ7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3): d 194.8,
104.3, 99.0, 71.2, 40.9, 33.0, 32.3, 32.0, 29.7, 29.4, 27.7,
1
liquid; H NMR (300 MHz, CDCl3): d 5.00–4.92 (m, 1H),
2.24–2.15 (m, 1H), 2.06–1.98 (m, 1H), 2.00 (s, 3H), 1.88
(t, JZ6.9 Hz, 2H), 1.64 (s, 3H), 1.63 (s, 3H), 1.38–1.27
(m, 4H), 1.21 (d, JZ6.6 Hz, 3H), 0.88 (t, JZ7.2 Hz, 3H);
13C NMR (75.4 MHz, CDCl3): d 199.2, 170.6, 97.8, 95.8,
69.9, 39.3, 32.8, 29.7, 22.2, 21.4, 20.8, 20.7, 19.9, 14.0; IR
(neat): 1961, 1740 cmK1; MS (m/z) 182 (MCC1KCOCH3,
15.04), 181 (MCKCOCH3, 33.90), 107 (100); HRMS
Calcd for C14H24O2 (MC): 224.1776. Found 224.1778.
26.2, 22.2, 15.3, 14.0, 10.1; IR (neat): 3375, 1959 cmK1
;
MS (m/z) 236 (MC, 8.77), 57 (100); HRMS Calcd for
C16H28O (MC): 236.2140. Found 236.2170. Compound
(R)-2i: 82% ee (determined after its conversion to the
corresponding benzoate); [a]2D0C5.3 (c 1.75, CHCl3);
1
liquid; H NMR (300 MHz, CDCl3): d 4.92–4.87 (m, 1H),
2.21–2.08 (m, 2H), 2.08–2.00 (m, 7H), 1.92–1.82 (m, 2H),
1.78–1.40 (m, 8H), 1.40–1.20 (m, 4H), 0.88 (t, JZ7.5 Hz,
6H); 13C NMR (75.4 MHz, CDCl3): d 195.7, 170.7, 103.3,
97.5, 74.2, 37.4, 32.7, 31.89, 31.86, 29.7, 27.7, 27.6, 26.6,
26.2, 22.2, 21.3, 14.0, 9.5; IR (neat): 1961, 1741 cmK1; MS
(m/z) 278 (MC, 0.77), 147 (100); HRMS Calcd for
C18H30O2 (MC): 278.2246. Found 278.2247.
3.2.12. Synthesis of (R)-5-(n-butyl)hepta-1,5,6-trien-3-ol
((R)-1l) and (S)-5-(n-butyl)hepta-1,5,6-trien-3-yl acetate
((S)-2l). The reaction of racemic 5-(n-butyl)hepta-1,5,6-
trien-3-ol (100 mg) with Novozym-435 (70 mg) and vinyl
acetate (111 mL) afforded (R)-1l (43 mg, 43%) and (S)-2l
(70 mg, 56%). Compound (R)-1l: 93% ee liquid; (deter-
mined after its conversion to the corresponding acetate);
3.2.10. Synthesis of (S)-4-(n-butyl)hexa-4,5-dien-2-ol
((S)-1j) and (R)-4-(n-butyl)hexa-4,5-dien-2-yl acetate
((R)-2j). The reaction of racemic 4-(n-butyl)hexa-4,5-
dien-2-ol (100 mg) with Novozym-435 (70 mg) and vinyl
acetate (120 mL) afforded (S)-1j (37 mg, 37%) and (R)-2j
(45 mg, 35%). Compound (S)-1j: 88% ee (determined after
its conversion to the corresponding acetate); [a]2D0C7.7
[a]2D0K2.4 (c 1.40, CHCl3); liquid; H NMR (300 MHz,
1
CDCl3): d 5.96–5.84 (m, 1H), 5.29 (dt, JZ22.4, 1.5 Hz,
1H), 5.12 (dt, JZ10.5, 1.5 Hz, 1H), 4.80–4.68 (m, 2H),
4.36–4.20 (m, 1H), 2.22–2.08 (m, 2H), 2.05–1.84 (m, 3H),
1.50–1.30 (m, 4H), 0.90 (t, JZ7.2 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3): d 206.0, 140.2, 114.6, 99.9, 76.2, 70.7,
40.3, 31.9, 29.5, 22.3, 13.9; IR (neat): 3377, 1957,
1645 cmK1; MS (m/z) 166 (MC, 3.65), 107 (100); HRMS
Calcd for C11H18O (MC): 166.1358. Found 166.1310.
Compound (S)-2l: 75% ee (GC condition: Column:
RT-bDEXcst (30 m, 0.25 m ID, 0.25 mm DF); carrier: N2,
10 psi; injector: 250 8C; Detector (FID, H2, 0.218 MPa):
250 8C; Oven temperature: 120 8C (40 min)); [a]2D0C1.8
1
(c 1.85, CHCl3); liquid; H NMR (300 MHz, CDCl3): d
4.69–4.74 (m, 2H), 4.00–3.80 (m, 1H), 2.10–2.00 (m, 3H),
2.00–1.88 (m, 2H), 1.43–1.26 (m, 4H), 1.20 (d, JZ6.0 Hz,
3H), 0.88 (t, JZ7.5 Hz, 3H); 13C NMR (75.4 MHz, CDCl3):
d 205.7, 100.6, 76.1, 65.9, 42.2, 32.0, 29.5, 22.7, 22.3, 13.9;
IR (neat): 3355, 1957 cmK1; MS (m/z) 154 (MC, 2.01), 43
(100); HRMS Calcd for C10H18O (MC): 154.1358. Found
154.1353. Compound (R)-2j: 89.3% ee (GC condition:
Column: RT-bDEXcst (30 m, 0.25 m ID, 0.25 mm DF);
carrier: N2, 10 psi; injector: 250 8C; Detector (FID, H2,
0.218 MPa): 250 8C; Oven temperature: 110 8C (5 min),
then 1 8C/min to 120 8C (20 min)); liquid; [a]2D0C2.3
(c 1.95, CHCl3); 1H NMR (300 MHz, CDCl3): d 5.08–
4.94 (m, 1H), 4.64 (m, 2H), 2.32–2.18 (m, 1H), 2.10–2.02
(m, 1H), 2.01 (s, 3H), 2.00–1.92 (m, 2H), 1.50–1.26 (m,
4H), 1.23 (d, JZ6.0 Hz, 3H), 0.89 (t, JZ7.2 Hz, 3H); 13C
NMR (75.4 MHz, CDCl3): d 206.3, 170.5, 99.3, 75.5, 69.5,
38.7, 31.9, 29.5, 22.3, 21.3, 19.9, 13.9; IR (neat): 1958,
1741 cmK1; MS (m/z) 196 (MC, 7.23), 43 (100); HRMS
Calcd for C12H20O2 (MC): 196.1463. Found 196.1455.
1
(c 1.80, CHCl3); liquid; H NMR (300 MHz, CDCl3): d
5.88–5.78 (m, 1H), 5.40–5.32 (m, 1H), 5.27 (dt, JZ17.1,
1.5 Hz, 1H), 5.16 (dt, JZ10.5, 1.5 Hz, 1H), 4.70–4.60
(m, 2H), 2.40–2.06 (m, 2H), 2.05 (s, 3H), 2.00–1.82
(m, 2H), 1.42–1.24 (m, 4H), 0.89 (t, JZ7.2 Hz, 3H); 13C
NMR (75.4 MHz, CDCl3): d 206.5, 170.2, 136.2, 116.6,
98.9, 75.8, 72.9, 37.2, 31.9, 29.5, 22.3, 21.2, 13.9; IR (neat):
1958, 1743, 1646 cmK1; MS (m/z) 208 (MC, 0.09), 166
(MCC1KCOCH3, 18.30), 165 (MCKCOCH3, 4.74), 43
(100); HRMS Calcd for C11H17O (MCKCOCH3):
165.1280. Found 165.1318.
3.2.13. Synthesis of (R)-5-(n-pentyl)hepta-1,5,6-trien-3-ol
((R)-1m) and (S)-5-(n-pentyl)hepta-1,5,6-trien-3-yl acet-
ate ((S)-2m). The reaction of racemic 5-(n-pentyl)hepta-1,
5,6-trien-3-ol (100 mg) with Novozym-435 (100 mg) and
vinyl acetate (103 mL) afforded (R)-1m (44 mg, 44%) and
(S)-2m (49 mg, 40%). Compound (R)-1m: 93% ee (deter-
mined after its conversion to the corresponding acetate);
[a]2D0K1.3 (c1.55, CHCl3); liquid; 1H NMR (300 MHz,
CDCl3): d 5.96–5.82 (m, 1H), 5.29 (dt, JZ17.1, 1.5 Hz,
1H), 5.12 (dt, JZ10.5, 1.5 Hz, 1H), 4.79–4.70 (m, 2H),
4.31–4.25 (m, 1H), 2.25–2.07 (m, 2H), 2.01–1.90 (m, 3H),
3.2.11. Synthesis of (S)-6-methyl-4-(n-butyl)hepta-4,5-
dien-2-ol ((S)-1k) and (R)-6-methyl-4-(n-butyl)hepta-4,5-
dien-2-yl acetate ((R)-2k). The reaction of racemic
6-methyl-4-(n-butyl)hepta-4,5-diene-2-ol (100 mg) with
Novozym-435 (100 mg) and vinyl acetate (102 mL) afforded
(S)-1k (38 mg, 38%) and (R)-2k (64 mg, 52%). Compound
(S)-1k: 91% ee (determined after its conversion to the
corresponding acetate); [a]2D0C6.0 (c 1.45, CHCl3); liquid;
1H NMR (300 MHz, CDCl3): d 3.93–3.85 (m, 1H), 2.11–

11886
D. Xu et al. / Tetrahedron 60 (2004) 11879–11887
1.49–1.20 (m, 6H), 0.88 (t, JZ7.2 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3): d 200.0, 140.2, 114.6, 100.0, 76.2,
70.7, 40.3, 32.2, 31.4, 27.0, 22.5, 14.0; IR (neat): 3384,
1957, 1644 cmK1; MS (m/z) 180 (MC, 0.40), 67 (100);
HRMS Calcd for C12H20O (MC): 180.1514. Found
180.1481. Compound (S)-2m: 85% ee (GC condition:
Column: RT-bDEXcst (30 m, 0.25 m ID, 0.25 mm DF);
carrier: N2, 10 psi; injector: 250 8C; Detector (FID, H2,
0.218 MPa): 250 8C; Oven temperature: 120 8C (60 min));
(MC, 0.31), 55 (100); HRMS Calcd for C12H18O (MC):
178.1358. Found: 178.1360. Compound (S)-2o: 60% ee (GC
condition: Column: RT-bDEXcst (30 m, 0.25 m ID,
0.25 mm DF); carrier: N2, 10 psi; injector: 250 8C; Detector
(FID, H2, 0.218 MPa): 250 8C; Oven temperature: 130 8C
1
(50 min)); [a]2D0K23.2 (c 1.30, CHCl3); liquid; H NMR
(300 MHz, CDCl3): d 5.48–5.37 (m, 1H), 4.74–4.66 (m,
2H), 2.52–2.30 (m, 3H), 2.07 (s, 3H), 2.00–1.90 (m, 2H),
1.49–1.36 (m, 2H), 1.34–1.20 (m, 4H), 0.88 (t, JZ6.6 Hz,
3H); 13C NMR (75.4 MHz, CDCl3): d 206.2, 169.8, 98.3,
81.2, 76.6, 73.4, 62.3, 37.4, 32.1, 31.4, 27.0, 22.5, 20.9,
14.0; IR (neat): 2257, 1959, 1746 cmK1; MS (m/z) 220
(MC, 0.31), 178 (MCC1KCOCH3, 4.43), 177
(MCKCOCH3, 2.83), 43 (100); HRMS Calcd for
C12H17O (MCKCOCH3): 177.1280. Found 177.1266.
1
[a]2D0C1.1 (c 1.10, CHCl3); liquid; H NMR (300 MHz,
CDCl3): d 5.87–5.74 (m, 1H), 5.39–5.10 (m, 3H), 4.69–4.60
(m, 2H), 2.35–2.10 (m, 2H), 2.03 (s, 3H), 1.96–1.86 (m,
2H), 1.44–1.20 (m, 6H), 0.86 (t, JZ6.9 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3): d 206.5, 170.1, 136.2, 116.5, 98.9,
75.8, 72.9, 37.2, 32.1, 31.4, 27.0, 22.5, 21.2, 14.0; IR (neat):
1958, 1744, 1648 cmK1; MS (m/z) 180 (MCC1KCOCH3,
1.07), 179 (MCKCOCH3, 1.21), 43 (100); HRMS Calcd for
C12H19O (MCKCOCH3): 179.1436. Found 179.1425.
3.2.16. PdII-catalyzed coupling cyclization of (R)-1a with
allylic bromide: synthesis of (R)-(K)-6-ethyl-3-allyl-4-
(n-butyl)-5,6-dihydro-2H-pyran ((R)-3a). A mixture of
(R)-1a (52 mg, 0.3 mmol, 97% ee obtained from hydrolysis
of (R)-2a), allylic bromide (0.13 mL, 1.5 mmol), and PdCl2
(0.003 g, 5 mol%) was stirred in N,N-dimethylacetamide
(1.8 mL) at room temperature. When the reaction was
complete as monitored by TLC, diethyl ether (50 mL) was
added. The resulting mixture was washed with brine (three
times) and dried over anhydrous sodium sulfate. The
product was purified by column chromatography on silica
gel (petroleum ether/ethyl etherZ80/1) to afford (R)-(K)-6-
ethyl-3-allyl-4-(n-butyl)-5,6-dihydro-2H-pyran ((R)-3a)
(41 mg, 64%) with 97% ee; (GC condition: Column: RT-
bDEXcst (30 m, 0.25 m ID, 0.25 mm DF); carrier: N2,
10 psi; injector: 250 8C; Detector (FID, H2, 0.218 MPa):
250 8C; Oven temperature: 135 8C (30 min)); [a]2D0K118.7
3.2.14. Synthesis of (R)-5-(n-butyl)hepta-5,6-dien-1-yn-
3-ol ((R)-1n) and (S)-5-(n-butyl)hepta-5,6-dien-1-yn-3-yl
acetate ((S)-2n). The reaction of racemic 5-(n-butyl)hepta-
5,6-dien-1-yn-3-ol (100 mg) with Novozym-435 (100 mg)
and vinyl acetate (113 mL) afforded (R)-1n (38 mg, 38%)
and (S)-2n (71 mg, 56%). Compound (R)-1n: 88% ee
(determined after its conversion to the corresponding
acetate); [a]2D0C5.6 (c 1.90, CHCl3); liquid; 1H NMR
(300 MHz, CDCl3): d 4.80–4.72 (m, 2H), 4.60–4.42
(m, 1H), 2.46 (d, JZ2.4 Hz, 1H), 2.42–2.38 (m, 2H), 2.16
(bs, 1H), 2.08–1.96 (m, 2H), 1.50–1.22 (m, 4H), 0.90 (t, JZ
7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3): d 205.9, 99.1,
84.5, 76.8, 72.7, 60.7, 40.4, 31.9, 29.4, 22.2, 13.9; IR (neat):
3310, 1957 cmK1; MS (m/z) 164 (MC, 0.50), 55 (100);
HRMS Calcd for C11H16O (MC): 164.1201. Found
164.1179. Compound (S)-2n: 44% ee (GC condition:
Column: RT-bDEXcst (30 m, 0.25 m ID, 0.25 mm DF);
carrier: N2, 8.0 psi; injector: 250 8C; Detector (FID, H2,
0.218 MPa): 250 8C; Oven temperature: 120 8C (10 min),
then 1 8C/min to 140 8C (30 min)); [a]2D0K15.9 (c 0.85,
1
(c 1.05, CHCl3); liquid; H NMR (300 MHz, CDCl3): d
5.86–5.59 (m, 1H), 5.10–4.85 (m, 2H), 4.02 (s, 2H), 3.39–
3.32 (m, 1H), 2.78 (dd, JZ6.3, 14.0 Hz, 1H), 2.60 (dd, JZ
6.9, 14.0 Hz, 1H), 2.10–1.89 (m, 4H), 1.65–1.40 (m, 2H),
1.39–1.21 (m, 4H), 0.95 (t, JZ7.8 Hz, 3H), 0.88 (t, JZ
7.5 Hz, 3H); 13C NMR (75.4 MHz, CDCl3): d 135.9, 129.7,
126.3, 115.2, 75.6, 68.3, 34.0, 33.0, 32.1, 30.2, 28.7, 22.8,
14.0, 9.9; IR (neat): 1637, 1465, 1150 cmK1; MS (m/z) 208
(MC, 5.85), 167 (100); HRMS Calcd for C14H24O (MC):
208.1827. Found 208.1859.
1
CHCl3); liquid; H NMR (300 MHz, CDCl3): d 5.50–5.40
(m, 1H), 4.75–4.66 (m, 2H), 2.57–2.38 (m, 3H), 2.08
(s, 3H), 2.02–1.92 (m, 2H), 1.44–1.28 (m, 4H), 0.90 (t, JZ
7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3): d 206.2, 169.8,
98.3, 81.2, 76.5, 73.4, 62.3, 37.4, 31.8, 29.5, 22.3, 20.9,
13.9; IR (neat): 2125, 1959, 1746 cmK1; MS (m/z) 164
(MCC1KCOCH3, 7.73), 163 (MCKCOCH3, 6.92), 43
(100); HRMS Calcd for C11H15O (MCKCOCH3):
163.1123. Found 163.1103.
Acknowledgements
Financial support from the Major State Basic Research
Development Program (Grant No. G2000077500), National
Natural Science Foundation of China, and Shanghai
Municipal Committee of Science and Technology are greatly
appreciated.
3.2.15. Synthesis of (R)-5-(n-pentyl)hepta-5,6-dien-1-yn-
3-ol ((R)-1o) and (S)-5-(n-pentyl)hepta-5,6-dien-1-yn-3-
yl acetate ((S)-2o). The reaction of racemic 5-(n-pentyl)-
hepta-5,6-dien-1-yn-3-ol (100 mg) with Novozym-435
(100 mg) and vinyl acetate (103 mL) afforded (R)-1o
(40 mg, 40%) and (S)-2o (50 mg, 40%). Compound (R)-
1o: 90% ee (determined after its conversion to the
corresponding acetate); [a]2D0C7.1 (c 1.10, CHCl3); liquid;
1H NMR (300 MHz, CDCl3): d 4.81–4.74 (m, 2H), 4.55–
4.48 (m, 1H), 2.46 (d, JZ1.5 Hz, 1H), 2.45–2.35 (m, 2H),
2.19–2.16 (m, 1H), 2.02–1.92 (m, 2H), 1.48–1.23 (m, 6H),
0.88 (t, JZ7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3): d
205.9, 99.2, 84.4, 76.8, 72.8, 60.7, 40.4, 32.2, 31.4, 27.0,
22.4, 14.0; IR (neat): 3385, 2249, 1957 cmK1; MS (m/z) 178
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