Baker's yeast reduction of α-methyleneketones

Article abstract of DOI:10.1016/S0957-4166(01)00134-3

The bioreduction of α-methyleneketones, R¹C(=O)C(=CH₂)R² (R¹ = Me, Et, Pr, iso-Bu, Ph, CH₂CH₂Ph; R² = Cl, Me, Et, n-Pr, iso-Pr, n-Bu, n-C₆H₁₃, Ph, CH₂Ph), was mediated by baker's yeast (Saccharomyces cerevisiae) to obtain the corresponding α-methylketones. The R¹ and R² groups had a significant influence on the rate and enantioselectivity of the reductions. The rate of C=C bond reduction was higher than that of C=O bond reduction. Only α-methyleneketones having R¹ = Me yielded α-methylketones in high enantioselectivity with e.e.s of 88-99%.

Full text of DOI:10.1016/S0957-4166(01)00134-3

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 847–852
Baker’s yeast reduction of a-methyleneketones
Ezequias P. Siqueira Filho, J. Augusto R. Rodrigues and Paulo J. S. Moran*
Universidade Estadual de Campinas, Instituto de Qu´ımica, 13081-970 Campinas-SP, Brazil
Received 29 January 2001; accepted 6 March 2001
Abstract—The bioreduction of a-methyleneketones, R1C(ꢀO)C(ꢀCH2)R2 (R1=Me, Et, Pr, iso-Bu, Ph, CH2CH2Ph; R2=Cl, Me,
Et, n-Pr, iso-Pr, n-Bu, n-C6H13, Ph, CH2Ph), was mediated by baker’s yeast (Saccharomyces cerevisiae) to obtain the
corresponding a-methylketones. The R1 and R2 groups had a significant influence on the rate and enantioselectivity of the
reductions. The rate of CꢀC bond reduction was higher than that of CꢀO bond reduction. Only a-methyleneketones having
R1=Me yielded a-methylketones in high enantioselectivity with e.e.s of 88–99%. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
formaldehyde, the corresponding ketone 1a–1n and a
catalytic amount of morpholine in anhydrous acetic
acid (Scheme 1).7
In the last decade, whole cells and enzymes have been
used extensively in organic synthesis to obtain
homochiral products in a variety of organic reactions.1
Baker’s yeast has been widely used, mainly in the
reduction of the carbonyl groups of prochiral ketones,2
producing alcohols with high enantiomeric purity. Sim-
ilarly, the carbonꢁcarbon double bonds of prochiral
alkenes may be reduced to obtain the corresponding
saturated compounds with high enantiomeric excesses.
The reduction of 2 by baker’s yeast was performed by
stirring the reaction mixture at 30°C. We observed that
ketone 3 and in some cases alcohol 4, were obtained as
reaction products from the CꢀC and CꢀO bond reduc-
tions, respectively (see Scheme 2).
As our interest lay in studying the effect of altering the
R1 and R2 alkyl groups in these reduction reactions,
samples were withdrawn from the reaction mixture
after appropriate intervals of time, and analyzed by
GCMS technique in order to determine the relative rate
of reduction (Fig. 1).
The a-methylketone structural moiety is present in a
variety of compounds including drugs and
pheromones.3 In most cases, the absolute configuration
of the a-carbon affects the bioactivity profile.4 Ketones
bearing a chiral a-carbon can be obtained by the enan-
tioselective reduction of prochiral a-methyleneketones.
In spite of a large number of studies involving the
enantioselective bioreduction of the CꢀC bond a- to a
ketone function,5 there are few involving the bioreduc-
tion of a-methyleneketones.6 Herein, we present a sys-
tematic study of the effect of R1 and R2 groups on the
enantioselectivity and rate of the baker’s yeast reduc-
tion of a-methyleneketones 2.
In general, there was a large difference between the
reduction rates of CꢀC and CꢀO bonds with baker’s
yeast. While CꢀC was reduced first and ketones 3a–3f
were obtained after 2 h, the appearance of alcohols
4a–4f (17–100% of reaction progress) only occurs after
reaction for 96–169 h (see Table 1). This chemoselectiv-
ity may be implemented as part of a synthetic strategy.
In contrast, the reduction rate of the CꢀC bond of
ketones 2h–2m was slower than that of 2a–2f and
formation of alcohols 4h–4m was not observed.
2. Results and discussion
It is interesting that when R1ꢀMe (compounds 2a–2d),
the ketone reduction rates were the fastest, irrespective
of the size of the R2 group. When R1=Ph, the reduc-
tion rates of the ketones were dependent on the R2
group size. When R1=Ph, the rates of reduction of the
ketones with R2=Cl, Me and Et, 2e–2g, were faster
The a-methyleneketones 2a–2n were prepared via the
Mannich reaction by refluxing a solution of aqueous
* Corresponding author. E-mail: moran@iqm.unicamp.br
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00134-3

848
E. P. Siqueira Filho et al. / Tetrahedron: Asymmetry 12 (2001) 847–852
Scheme 1.
than the reduction rates of ketones 2h–2j with R2=n–
Pr, n-Bu and Bn.
configuration of ketones 3b–3d may be assigned as (R)-
by comparing [h]2D0 signals to literature data. Since the
CD spectra of ketones 3a–3d exhibit a distinct negative
Cotton effect centered near 290 nm (Fig. 2) due to the
carbonyl group, we can assign the (R)-configuration to
ketone 3a.8
In general, the rate of reductions was very sensitive to
the size of the R1 alkyl group. There was a marked
difference in the reduction rate of ketone 2d (R1=Me;
R2=Ph), in comparison to ketone 2k (R1=Et; R2=
Ph). In the case of ketone 2n (R1=iso-Bu; R2=iso-Pr)
reduction did not occur.
When R1 was Ph 2e–2j, Et 2k, Pr 2l or PhCH2CH2 2m,
the reduction products 3e–3n were obtained with very
poor e.e. Only a-methyleneketones having R1=Me
yielded a-methylketones with high enantioselectivity.
As the products 3a–3d had (R)-configuration, it is
reasonable to conclude that hydride transfers pre-
The baker’s yeast reduction of 2a–2d (R1=Me) gave
3a–3d, respectively with good to excellent e.e. (88 to
>99%), irrespective of the size of the R2 group. The
Scheme 2.
Figure 1. Profile of baker’s yeast reduction of: (a) 3-propyl-3-buten-2-one 2a; (b) 1-phenyl-2-propyl-2-propen-1-one 2h.

E. P. Siqueira Filho et al. / Tetrahedron: Asymmetry 12 (2001) 847–852
849
Table 1. Baker’s yeast reduction of a-methyleneketones 2 yielding a-methylketones 3 and alcohol 4 at 30°C
2
3
4
Reaction progress e.e. (%) [h]2D0 (c, solv)
[q] (u, nm)
Conf.
Reaction time
d.e. (%)
(%) after 2 h
in MeOH
(reaction progress)
(a) R1=Me; R2=n-Pr
(b) R1=Me; R2=n-Hexyl
(c) R1=Me; R2=Bn
(d) R1=Me; R2=Ph
(e) R1=Ph; R2=Cl
97
70
66
100
80
100
100
6
92
\99
88
88
9
–
32
3
−8.8 (9.0, CHCl3)
−17.1 (3.2, CHCl3)
−28.0 (11.0, CHCl3)
−31 (280) R(−)a
168 h (20%)
53
40
91
88
26
–
–
–
–
–
−420 (283) R(−)6b 120 h (27%)
−1718 (285) R(−)6b 114 h (17%)
−214.8 (6.2, CHCl3) −15507 (288) R(−)9
169 h (35%)
96 h (100%)
144 h (20%)
–
–
–
–
(f) R1=Ph; R2=Me
(g) R1=Ph; R2=Et
−1.1 (oil)
R(−)10 n.r.
(h) R1=Ph; R2=n-Pr
(i) R1=Ph; R2=n-Bu
(j) R1=Ph; R2=Bn
–
–
–
–
–
–
–
–
–
–
–
–
n.r.
n.r.
n.r.
n.r.
n.r.
n.r.
n.r.
5
4
16
34
40
6
14
12
16
14
–
(k)R1=Et; R2=Ph
–
–
–
–
–
–
(l) R1=n-Pr; R2=Et
(m) R1=CH2CH2Ph; R2=Bn
(n) R1=iso-Bu; R2=iso-Pr
n.r.
a Inferred from CD spectrum.
–––
–––
Figure 2. CD spectra at 25°C of: (a) 3a R(−) (---) and 3b R(−) ( ); (b) 3c R(−) (---) and 3d R(−)( ), respectively.
ferentially to the Si-face of the CꢀC bond of 2a–2d
(Fig. 3).
3. Conclusions
The baker’s yeast reduction of the alkene function of
a-methyleneketones 2 were faster than those of the
carbonꢁoxygen double bonds, showing that this
chemoselectivity may be used as an important strategy
in synthetic organic chemistry. The stereoselectivity and
reduction rate of the carbonꢁcarbon double bond is
affected markedly by the R1 and R2 groups. Only
a-methyleneketones having R1=Me produced the cor-
responding a-methylketone in high enantioselectivity.
The results indicate that the active site of the principal
enzyme responsible for hydride transference to a-
methyleneketones is highly restricted with respect to the
R1 group: Chain homologation by one or two carbons
in R1 appears responsible for the poor e.e. values of
products 3k and 3l (12 and 16% e.e., respectively), in
comparison to 3d (88% e.e.). In addition, the fact that
the reduction rates of 2h–2n are lower than those of
2a–2d, indicates that assembly of the appropriate tran-
sition state on the active site of the enzyme with
ketones 2h–2n is not favored and as a result the reduc-
tion mediated by the yeast either loses stereospecificity,
or other pro-(S)- and pro-(R)- enzymes present in the
yeast may compete in the reaction.
The baker’s yeast reduction of intermediate ketones 3c
and 3d, which have aromatic groups at R2, gave the
alcohols 4c and 4d in good diastereoisomeric excess
(d.e.), whereas the baker’s yeast reduction of the
ketones 3a and 3b gave alcohols 4a and 4b with poor
d.e.
Figure 3. Re- and Si-faces of the alkenic bond of a-
methyleneketones 2a–d.

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E. P. Siqueira Filho et al. / Tetrahedron: Asymmetry 12 (2001) 847–852
4. Experimental
Hz), 2.23 (t, 2H, J=7.4 Hz), 2.33 (s, 3H), 5.75 (s, 1H),
6.01 (s, 1H); MS m/z 112 (M+, 3%), 97 (30%), 79 (1%),
The IR spectra were recorded on a BOMEM MB
SERIES Hartmann & Braun spectrometer. The 1H
NMR and 13C NMR were recorded on a VARIAN-
INOVA spectrometer. Mass spectra were recorded on a
Shimadzu GC–MS-QP 5000 gas chromatograph/mass
spectrometer and with helium as carrier gas. A 30
m×0.25 mm I.D. capillary column of fused silica
SUPELCO SIMPLICITY 1TM was used and the chiral
column employed in the determination of enantiomeric
excess (e.e.) was a 25 m×0.25 mm I.D. CHIRASIL-
DEX from CHROMPACK. An injector temperature of
230°C and a detector temperature of 280°C, with the
column at 50°C for 3 min; then using a rate of 20°C/
min up to 280°C, with a pressure of 100 kPa and gas
flow of 80 mL/min, was used. HRMS were obtained on
a Fison VG Autoespec. Optical rotations were mea-
sured using a Carl Weiss POLAMAT A polarimeter.
CD spectra were recorded on a Jasco-J720 spectropo-
larimeter at 25°C. Preparative column chromatography
was carried out using silica gel 60 (Merck).
69 (30%), 55 (10%), 43 (100%), 41 (80%).
4.4. 3-Methyl-2-hexanone 3a
IR (film) 2926, 2851, 1745, 1463, 1369, 1239 cm−1; H
1
NMR l MS m/z 114 (M+, 3%), 99 (3%), 72 (14%), 55
1
(5%), 43 (100%); H NMR l 0.91 (t, 3H, J=6.96 Hz),
1.07 (d, 3H, J=6.96 Hz), 1.20–1.70 (m, 4H), 2.13 (s,
3H), 2.50 (m, 1H).
4.5. 3-Hexyl-3-buten-2-one 2b
IR (film) 2957, 2926, 2858, 1684, 1465, 1365, 1148, 936
1
cm−1, H NMR l 0.88 (m, 3H), 1.30 (m, 8H), 2.20 (m,
2H), 2.33 (s, 3H), 5.74 (s, 1H), 5.99 (s, 1H); MS m/z
154 (M+, 2%), 139 (10%), 125 (2%), 111 (36%), 85
(21%), 69 (78%), 55 (57%), 41 (100%).
4.6. 3-Methyl-2-nonanone 3b
IR (film) 2959, 2929, 2857, 1713, 1361, 1171 cm−1; H
1
4.1. General procedure for the preparation of a-methyl-
NMR l 0.88 (t, 3H, J=6.96 Hz), 1.08 (d, 3H, J=7.00
Hz), 1.30 (m, 10H), 1.60 (m, 1H), 2.13 (s, 3H); MS m/z
156 (M+, 1%), 141 (1%), 113 (1%), 99 (1%), 72 (56%),
57 (21%), 43 (100%).
eneketones
Aqueous formaldehyde (24 mL, 37% solution, 0.3 mol)
and a catalytic quantity of morpholine (3 drops), were
added to a solution of ketone 1 (0.1 mol) in glacial
acetic acid (90 mL). The resulting solution was refluxed
overnight. Subsequently, the reaction mixture was
cooled and neutralized with aqueous NaOH (0.1 M).
The products were extracted three times with ethyl
acetate. The organic layer was washed with aqueous
NaHCO3 (10%) and brine and dried over magnesium
sulfate. The solvent was evaporated. The crude oil was
purified by silica gel column chromatography to obtain
the a-methyleneketone 2.
4.7. 3-Benzyl-3-buten-2-one 2c
IR (film) 3085, 3063, 3028, 2925, 1676, 1495, 1363, 733,
1
698, 505 cm −1; H NMR l 2.33 (s, 3H), 3.59 (s, 2H),
5.63 (s, 1H); 6.07 (s, 1H), 7.2 (m, 5H); MS m/z 160
(M+, 25%), 159 (25%), 145 (20%), 115 (40%), 91 (30%),
77 (5%), 43 (100%). HRMS found m/z: 160.0889; calcd
for C11H12O [M]+: 160.0888
4.8. 3-Methyl-4-phenyl-2-butanone 3c
4.2. General procedure for the biotransformations of 2
IR (film) 3028, 2971, 2933, 1713, 1449, 1351, 1165, 737,
700 cm −1; 1H NMR l 1.08 (d, 3H, J=7.10 Hz), 2.08 (s,
3H), 2.56 (dd, 1H, J=13.67 Hz, J=7.81 Hz), 2.82 (m,
1H, J=6.80 Hz, J=7.10 Hz, J=7.80 Hz), 2.98 (dd, 1H,
J=13.67 Hz, J=6.80 Hz), 7.13–7.35 (m, 5H); MS m/z
162 (M+, 20%), 147 (17%), 129 (2%), 119 (12%), 103
(2%), 91 (100%), 77 (2%), 65 (12%), 43 (100%).
The a-methyleneketone 2 (0.1 mol) was added to a
mixture of dry baker’s yeast (Emulzint® 5 g) in water
(100 mL) at 30°C. The resulting mixture was main-
tained at 30°C with constant stirring. Samples were
withdrawn from the reaction mixture at appropriate
intervals and analyzed by the GC/MS technique.
4.9. 3-Phenyl-3-buten-2-one 2d
Subsequently, at the end of the reactions, Celite®, ethyl
acetate (50 mL) and brine (50 mL) were added to the
reaction mixture, and stirring was continued for 30
min. The cells–Celite mixture was filtered off and the
filtrate extracted three times with ethyl acetate. The
organic layer was washed with aqueous NaHCO3 (10%)
and brine, dried over magnesium sulfate and the sol-
vent was evaporated. The crude oil was purified by
silica gel column chromatography to obtain the a-
methylketone 3 and in some cases, the alcohol 4.
IR (film) 3105, 3057, 2926, 2856, 1685, 1497, 1365,
1
1173, 950, 779, 704 cm−1; H NMR l 2.44 (s, 3H), 5.96
(s, 1H), 6.17 (s, 1H), 7.34 (m, 5H); MS m/z 146 (M+,
39%), 131 (19%), 103 (100%), 77 (39%), 63 (6%), 51
(40%), 43 (88%). HRMS found m/z: 146.0730; calcd for
C10H10O [M]+: 146.0731.
4.10. 3-Phenyl-2-butanone 3d
IR (film) 3029, 2978, 2932, 1718, 1495, 1453, 1356, 768,
1
4.3. 3-Propyl-3-buten-2-one 2a
702, 545 cm−1; H NMR l 1.39 (d, 3H, J=7.02 Hz),
2.04 (s, 3H), 3.74 (q, 1H, J=7.02 Hz), 7.22–7.33 (m,
5H); MS m/z 148 (M+, 6%), 133 (2%), 115 (1%), 105
(100%), 91 (2%), 77 (20%), 63 (2%), 51 (15%), 43 (63%).
1
IR (film) 2961, 2933, 1681, 1364, 1145, 938 cm−1; H
NMR l 0.92 (t, 3H, J=7.4 Hz), 1.43 (sx, 2H, J=7.4

E. P. Siqueira Filho et al. / Tetrahedron: Asymmetry 12 (2001) 847–852
851
4.11. 2-Chloro-1-phenyl-2-propen-1-one 2e
4.18. 2-Methyl-1-phenyl-1-pentanone 3h
IR (film) 3114, 3063, 3028, 1675, 1449, 964, 697 cm−1;
1H NMR l 6.06 (s, 1H), 6.27 (s, 1H), 6.60 (m, 5H); MS
m/z 166 (M+, 20%), 138 (2%), 131 (5%), 105 (100%), 77
(40%), 61 (10%), 51 (65%); HRMS found m/z:
166.0184; calcd for C9H7ClO [M]+: 166.0185
IR (film) 3065, 2959, 2935, 2873, 1679, 1596, 971, 703
1
cm−1; H NMR l 0.90 (t, 3H, J=7.32 Hz), 1.19 (d, 3H,
J=6.84 Hz), 1.34 (m, 2H), 1.42 (m, 1H), 1.78 (m, 1H),
3.50 (sx, 1H, J=6.84), 7.40–7.90 (m, 5H); MS m/z 176
(M+, 2%), 147 (2%), 134 (20%), 105 (100%), 91 (2%), 77
(36%), 51 (17%).
4.12. 2-Chloro-1-phenyl-1-propanone 3e
4.19. 1-Phenyl-2-buthyl-2-propen-1-one 2i
IR (film) 3063, 2985, 2932, 1691, 1595, 1447, 956, 720,
1
683 cm−1, H NMR l 1.74 (d, 3H, J=6.60 Hz), 5.25 (q,
IR (film) 3085, 2958, 2930, 2873, 1658, 981, 752, 695
1
cm−1; H NMR l 0.92 (t, 3H, J=7.32 Hz), 1.32–1.44
1H, J=6.60 Hz), 7.40–8.10 (m, 5H); MS m/z 168 (M+,
2%), 132 (2%), 105 (100%), 77 (47%), 63 (2%), 51
(36%).
(m, 4H), 2.46 (t, 2H, J=7.50 Hz), 5.56 (s, 1H), 5.80 (s,
1H), 7.40–7.80 (m, 5H). MS m/z 188 (M+, 10%), 187
(10%), 173 (2%), 159 (18%), 145 (18%), 131 (15%), 117
(5%), 105 (100%), 91 (5%), 77 (70%), 51 (30%), 41
(20%). HRMS found m/z: 188.1207; calcd for C13H16O
[M]+: 188.1201.
4.13. 2-Methyl-1-phenyl-2-propen-1-one 2f
IR (film) 3062, 2927, 1656, 1449, 1330, 1200, 754, 714
1
cm−1; H NMR l 2.05 (s, 3H), 5.60 (s, 1H), 5.88 (s,
4.20. 2-Methyl-1-phenyl-1-hexanone 3i
1H), 7.40–7.70 (m, 5H); MS m/z 146 (M+, 20%), 131
(2%), 118 (20%), 105 (100%), 91 (2%), 77 (80%), 51
(50%), 41 (20%). HRMS found m/z: 146.0749; calcd for
C10H10O [M]+: 146.0731.
IR (film) 3062, 2959, 2933, 2872, 1682, 1594, 970, 702
1
cm−1; H NMR l 0.86 (m, 3H), 1.23 (d, 3H, J=6.60
Hz), 1.30–1.50 (m, 5H), 1.80 (m, 1H), 3.45 (sx, 1H,
J=6.60 Hz), 7.40–7.97 (m, 5H); MS m/z 190 (M+, 2%),
171 (1%), 161 (1%), 147 (2%), 134 (41%), 115 (1%), 105
(100%), 91 (2%), 77 (50%), 69 (2%), 51 (20%).
4.14. 2-Methyl-1-phenyl-1-propanone 3f
IR (film) 3065, 2972, 1681, 1449, 1387, 1222, 979, 790,
1
702 cm−1; H NMR l 1.22 (d, 6H, J=6.96 Hz), 3.56
4.21. 2-Benzyl-1-phenyl-2-propen-1-one 2j
(hep, 1H, J=6.96 Hz), 7.40–7.96 (m, 5H); MS m/z 148
(M+, 6%), 134 (1%), 105 (100%), 91 (1%), 77 (42%), 51
(25%).
IR (film) 3085, 3062, 3029, 2925, 1648, 1495, 985, 756,
1
698; H NMR l 3.80 (s, 2H), 5.67 (s, 1H), 5.74 (s, 1H),
7.20–7.70 (m, 10H); MS m/z 222 (M+, 3%), 221 (3%),
210 (22%), 191 (1%), 178 (1%), 165 (1%), 152 (1%), 131
(3%), 116 (3%), 105 (100%), 91 (10%), 77 (41%), 65
(5%), 51 (17%). HRMS found m/z: 222.1044; calcd for
C16H14O [M]+: 222.1045.
4.15. 2-Ethyl-1-phenyl-2-propen-1-one 2g
IR (film) 3062, 2966, 1658, 1448, 979, 752, 703 cm−1; 1H
NMR l 1.12 (t, 3H, J=7.53 Hz), 2.49 (q, 2H, J=7.53
Hz), 5.56 (s, 1H), 5.80 (s, 1H), 7.40–7.70 (m, 5H); MS
m/z 160 (M+, 20), 159 (22%), 145 (25%), 131 (15%), 117
(10%), 105 (100%), 91 (3%), 77 (80%), 51 (40%), 39
(12%). HRMS found m/z: 160.0887; calcd for C11H12O
[M]+: 160.0888.
4.22. 2-Methyl-1,3-diphenyl-1-propanone 3j
IR (film) 3085, 3062, 3028, 2970, 2931, 2872, 1680,
1
1595, 1450, 1229, 972, 740, 697 cm−1; H NMR l 1.20
(d, 3H, J=6.84 Hz), 2.68 (dd, 1H, J=13.67 Hz, J=
7.81 Hz), 3.16 (dd, 1H, J=13.67 Hz, J=6.35 Hz), 3.76
(m, 1H); MS m/z 224 (M+, 13%), 209 (2%), 191 (1%),
181 (2%), 165 (1%), 145 (1%), 131 (2%), 117 (2%), 105
(100%), 91 (19%), 77 (31%), 65 (5%), 51 (13%).
4.16. 2-Methyl-1-phenyl-1-butanone 3g
IR (film) 3062, 2935, 2875, 1682, 1598, 1448, 1219, 970,
1
701 cm−1; H NMR l 0.91 (t, 3H, J=7.32 Hz), 1.18 (d,
3H, J=6.60 Hz), 1.48 (m, 1H), 1.90 (m, 1H), 3.40 (m,
1H), 7.40–7.97 (m, 5H); MS m/z 162 (M+, 7%), 144
(1%), 134 (7%), 105 (100%), 91 (2%), 77 (43%), 63 (1%),
51 (21%).
4.23. 2-Phenyl-1-penten-3-one 2k
IR (film) 3060, 2979, 2934, 1685, 1494, 1121, 939, 774,
1
703 cm−1; H NMR l 1.11 (t, 3H, J=7.31 Hz), 2.73 (q,
4.17. 1-Phenyl-2-propyl-2-propen-1-one 2h
2H, J=7.31 Hz), 5.84 (s, 1H), 6.07 (s, 1H), 7.26–7.34
(m, 5H); MS m/z 160 (M+, 30%), 145 (1%), 131 (17%),
115 (1%), 103 (100%), 91 (1%), 77 (37%), 63 (3%), 57
(42%). HRMS found m/z: 160.0887; calcd for C11H12O
[M]+: 160.0888.
IR (film) 3084, 3062, 2960, 2932, 2872, 1657, 1445, 982,
1
753, 706, 694 cm−1; H NMR l 0.96 (t, 3H, J=7.32
Hz), 1.53 (sx, 2H, J=7.32 Hz), 2.45 (t, 2H, J=7.32
Hz), 5.58 (s, 1H), 5.82 (s, 1H), 7.40–7.80 (m, 5H); MS
m/z 174 (M+, 10%), 173 (12%), 159 (20%), 145 (15%),
132 (12%), 131 (12%), 105 (100%), 77 (80%), 51 (40%),
41 (25%). HRMS found m/z: 174.1048; calcd for
C12H14O [M]+: 174.1045.
4.24. 2-Phenyl-3-pentanone 3k
IR (film) 3056, 3024, 2976, 2937, 1714, 1602, 1496,
1
1454, 759, 701 cm−1; H NMR l 0.96 (t, 3H, J=7.32

852
E. P. Siqueira Filho et al. / Tetrahedron: Asymmetry 12 (2001) 847–852
Hz), 1.40 (d, 3H, J=6.97), 2.36 (m, 2H), 3.76 (q, 1H,
J=6.97 Hz); MS m/z 162 (M+, 4%), 133 (4%), 115
(1%), 105 (82%), 91 (3%), 77 (19%), 57 (100%), 51
(13%).
Acknowledgements
We thank FAPESP for financial support, CNPq for a
scholarship for E.P.S.F.
4.25. 2-Ethyl-1-hexen-3-one 2l
References
IR (film) 2965, 2875, 1680, 1458, 934 cm−1, H NMR
1
1. Loughlin, W. A. Bioresour. Technol. 2000, 74, 49–62.
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Ferrabochi, P.; Grisenti, P.; Manzocchi, A. Chem. Rev.
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G.; Servi, S. Adv. Appl. Microbiol. 1997, 44, 81–123; (e)
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Enzym. 1998, 5, 238–245; (d) Kawai, Y.; Saitou, K.; Hida,
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2633–2638; (e) Koul, S.; Crout, D. H. G.; Errington, W.;
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971–972; (b) Sakai, T.; Matsumoto, S.; Hidaka, S.; Imajo,
N.; Tsuboi, S.; Utaka, M. Bull. Chem. Soc. Jpn. 1991, 64,
3473–3475; (c) Ferraboschi, P.; Reza-Elahi, S.; Verza, E.;
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2642; (d) Siqueira Filho, E. P.; Rodrigues, J. A. A.; Moran,
P. J. S.; J. Mol. Catal B: Enzym., in press.
l 0.94 (t, 3H, J=7.32 Hz), 1.03 (t, 3H, J=7.45 Hz),
1.64 (sx, 2H, J=7.32 Hz), 2.29 (q, 2H, J=7.45 Hz),
2.66 (t, 2H J=7.32 Hz), 5.71 (s, 1H), 5.98 (s, 1H); MS
m/z 126 (M+, 3%), 111 (7%), 97 (14%), 83 (86%), 71
(9%), 55 (100%), 43 (63), 41 (30%), 39 (40%).
4.26. 3-Methyl-4-heptanone 3l
IR (film) 2964, 2883, 1715, 1463 cm−1; 1H NMR l
0.87 (t, 3H, J=7.32 Hz), 0.91 (t, 3H, J=7.32 Hz),
1.06 (d, 3H, J=6.84 Hz), 1.38 (m, 1H), 1.59–1.69 (m,
3H), 2.40–2.46 (m, 3H); MS m/z 128 (M+, 6%), 113
(1%), 100 (4%), 85 (8%), 71 (60%), 57 (71%), 43
(100%).
4.27. 2-Benzyl-5-phenyl-1-penten-3-one 2m
IR (film) 3084, 3061, 3028, 2922, 1678, 1449, 1073,
943, 741, 699; 1H NMR l 2.91 (t, 2H, J=8.0 Hz),
3.01 (t, 2H, J=8.0 Hz), 3.60 (s, 2H), 5.60 (s, 1H), 6.05
(s, 1H), 7.15–7.30 (m, 10H); MS m/z 250 (M+, 22%),
235 (2%), 217 (2%), 202 (2%), 191 (2%), 172 (5%), 159
(25%), 145 (25%), 129 (20%), 117 (70%), 91 (100%), 77
(20%), 65 (30%), 51 (20%), 39 (40%). HRMS found
m/z: 250.1356; calcd for C18H18O [M]+: 250.1358.
4.28. 2-Methyl-1,5-diphenyl-3-pentanone 3m
IR (film) 3086, 3062, 3027, 2927, 1712, 1496, 1454,
1
743, 700 cm−1; H NMR l 1.05 (d, 3H, J=6.84 Hz),
2.56 (m, 2H), 2.70–2.80 (m, 4H), 2.94 (m, 1H), 7.10–
7.30 (m, 10H). MS m/z 252 (M+, 5%), 234 (1%), 219
(1%), 202 (1%), 191 (1%), 181 (1%), 161 (2%), 147
(12%), 133 (24%), 119 (12%), 105 (50%), 91 (100%), 77
(12%), 65 (13%), 51 (9%), 41 (17%).
7. (a) Kim, M. Y.; Lim, G. J.; Lim, J. I.; Kim, D. S.; Kim,
I. Y.; Yang, J. S. Heterocycles 1997, 45, 2041–2043; (b)
Ezquerra, J.; Pedregal, C.; Mico´, I.; Na´jera, C. Tetra-
hedron: Asymmetry 1994, 5, 921–926.
8. Kirk, D. N. Tetrahedron 1986, 42, 777–818.
9. Smadja, W.; Czernecki, S.; Ville, G.; Georgoulis, C.
Organometallics 1987, 6, 166–169.
10. Brown, H. C.; Srebnik, M.; Bakshi, R. K.; Cole, T. E. J.
Am. Chem. Soc. 1987, 109, 5420–5426.
4.29. 2-Isopropyl-5-methyl-1-hexen-3-one 2n
IR (fim) 2958, 2871, 1676, 1464, 1366, 924 cm−1; H
1
NMR l 0.928 (d, 6H, J=6.6 Hz), 1.02 (d, 6H, J=6.6
Hz), 2.10 (m, 3H), 2.93 (hept, 1H, J=6.6 Hz), 5.66 (s,
1H), 5.93 (s, 1H). MS m/z 154 (M+, 5%), 139 (60%),
125 (8%), 111 (10%), 97 (100%), 85 (20%), 69 (90%),
57 (80%), 41 (100%).
.