Stereocomplementary asymmetric bioreduction of boron-containing ketones mediated by alcohol dehydrogenases

Article abstract of DOI:10.1016/j.tetasy.2011.10.012

Optically active boron-containing alcohols were prepared via the stereoselective reduction of the corresponding carbonyl compounds by alcohol dehydrogenases. Depending on the substrate, both (R)-alcohols and (S)-alcohols were obtained with excellent enantioselectivity (up to >99% ee) employing either ADH-A or LB-ADH.

Full text of DOI:10.1016/j.tetasy.2011.10.012

Tetrahedron: Asymmetry 22 (2011) 1772–1777
Contents lists available at SciVerse ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereocomplementary asymmetric bioreduction of boron-containing
ketones mediated by alcohol dehydrogenases
Thiago Barcellos a, Katharina Tauber b, Wolfgang Kroutil b, , Leandro H. Andrade a,
⇑
⇑
a Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes 748, CEP 05508-900 São Paulo, SP, Brazil
b Department of Chemistry, Organic and Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, A-8010 Graz, Austria
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 September 2011
Accepted 26 October 2011
Optically active boron-containing alcohols were prepared via the stereoselective reduction of the corre-
sponding carbonyl compounds by alcohol dehydrogenases. Depending on the substrate, both (R)-alcohols
and (S)-alcohols were obtained with excellent enantioselectivity (up to >99% ee) employing either ADH-A
or LB-ADH.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
tolerance towards co-solvents, primarily acetone and 2-propanol,
and accepts a broad range of ketones.12 2-Propanol acts as a
Boron-containing organic compounds have received consider-
able attention due to their importance as synthetic intermediates
in organic synthesis.1 Boronic acids and their derivatives are em-
ployed in a broad range of organic reactions, mainly as nucleophilic
partners in cross-coupling reactions with organic electrophiles,
leading to the formation of new carbon–carbon bonds.2,3
In addition to their synthetic applications, organoboron com-
pounds have shown significant biological properties,4 primarily
due to the known inhibitory effect against the 20S proteasome.5
Furthermore, boronic acids and their esters have shown inhibitory
activity against other classes of enzyme, such as lipases6 and
glycosyltransferases.7
hydrogen donor that enables the in situ recycling of the requisite
nicotinamide cofactor NADH; in addition 2-propanol helps to
solubilise more hydrophobic ketone substrates. Recently, the
structure of this enzyme has been published.13 ADH-A preferen-
tially reduces small-bulky ketones to the (S)-alcohol, while the
alcohol dehydrogenase from Lactobacillus brevis (LB-ADH)14
produces the (R)-enantiomer; thus the two enzymes are
stereocomplementary.
2. Results and discussion
A
series of boron-containing ketones (1a–i, Fig. 1) were
Although new synthetic routes to obtain chiral and achiral
boron-containing compounds have been intensely investigated,8
very few reports regarding the use of enzymatic methodologies
in boron chemistry have been described.9,10 As part of our current
interest in biocatalytic reactions applied to boron chemistry, we
herein report the first study involving the bioreduction of
boron-containing carbonyl compounds mediated by enantiocom-
plementary alcohol dehydrogenases (ADHs).
employed as substrates for the bioreduction. We explored the
effect of different moieties attached at the ketone and the nature
of the boron species. Thus, aromatic, allylic, aliphatic ketones con-
taining pinacol boronate ester or boronic acid group were selected
as substrates.
Three different ADHs were chosen for this study; ADH-A, LB-
ADH, an ADH from a Ralstonia sp., whereby LB-ADH is enantiocom-
plementary to the two other ADHs (Scheme 1, Table 1).
The stereoselective reduction of carbonyl compounds by alco-
hol dehydrogenases and their cofactors has numerous advantages
compared to classical chemical reactions and has gained increased
relevance over the past few years, in particular for the synthesis of
important intermediates for pharmaceuticals and bioactive
compounds.11
When the ADH from Ralstonia sp. was employed, only ketone 1a
could be reduced, leading to the corresponding alcohols (S)-2a
with only 5% conversion, although alcohol (S)-2a was obtained
with excellent enantiomeric excess (ee >99%). Employing the ADHs
from R. ruber and L. brevis excellent conversions and enantioselec-
tivies were obtained; thus alcohols (S)-2a and (R)-2a were
obtained with excellent enantiomeric purity (ee >99%) (Table 1,
entries 1–3). ADH-A led to the (S)-enantiomer while LB-ADH gave
access to the (R)-enantiomer. The conversions were >99% for
ADH-A and 47% for LB-ADH, that is LB-ADH showed a lower activ-
ity. Furthermore, bioreductions in the presence of a co-solvent
(diethyl ether) did not lead to an improvement of conversion; in
For instance, the alcohol dehydrogenase ADH-A isolated from
the bacterium Rhodococcus ruber DSM 44541 possesses a high
⇑
Corresponding authors. Tel.: +55 1130912287; fax: +55 1138155579 (L.H.A.).
E-mail addresses: wolfgang.kroutil@uni-graz.at (W. Kroutil), leandroh@iq.usp.br
(L.H. Andrade).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.10.012

T. Barcellos et al. / Tetrahedron: Asymmetry 22 (2011) 1772–1777
1773
O
O
O
O
HO
O
B
B
B
B
1a
1b
1c
1d
OH
O
O
O
OH
HO
O
O
O
B
O
S
B
B
O
O
O
O
O
O
1f
1g
1e
O
O
O
B
B
O
O
1h
1i
Figure 1. Boron-containing ketones.
O
(R)-alcohol
(S)-alcohol
H OH
HO H
dehydrogenase
dehydrogenase
NADP+
NAD+
NADPH
B
B
NADH
B
RO OR
RO OR
RO OR
(R)-2a-e,h,i
1a-i
(S)-2a-e,h,i
(R)-ADH: L. brevis
(S)-ADH: Ralstonia sp, ADH-A
Scheme 1. Bioreduction of boron-containing ketones by ADH.
the case of LB-ADH diminished stereoselectivity was observed for
ketone 1a and LB-ADH (entry 4). In contrast, for ADH-A the co-sol-
vent did not diminish its excellent stereoselectivity.
accepted by ADH-A, leading to the allylic alcohol (S)-2h with excel-
lent conversion (>99%) and ee (>99%) (entries 29 and 30).
Additionally, the aliphatic ketone 1i (entries 33 and 34), con-
Both enzymes ADH-A and LB-ADH accepted nicely most of the
boron derivatives investigated affording the desired alcohols with
excellent enantioselectivity as shown in Table 1.
ADH-A catalysed the reduction of ketone 1b (entries 5 and 6),
bearing boronic ester group at the meta-position, with a decrease
in conversion compared to the reduction of 1a under the same
reaction conditions; thus alcohol (S)-2b was obtained with an
87% conversion. However, the reduction of 1b dropped signifi-
cantly when LB-ADH was used as the biocatalyst, giving alcohol
(R)-2b at only 3% conversion (entries 7 and 8).
taining a boronic ester group at the x-position was well accepted
by ADH-A, leading to alcohol (S)-2i with high conversion (92%)
and enantiomeric excess (>99%). LB-ADH gave alcohol (R)-2i with
a 14% conversion and excellent stereoselectivity (>99% ee).
Comparing these results with previous studies,12 it can be antic-
ipated that the presence of the boron moiety in the aromatic ke-
tones does not influence the reactivity of these substrates with
ADH.
3. Conclusion
ADH-A was able to efficiently reduce ketones 1c and 1d bearing
boronic acid groups at the para- as well as the meta-positions
(entries 9, 10, 13 and 14). In contrast, LB-ADH did only accept
the ketone 1c with a boronic acid at the para-position (entries 11
and 12), but the conversion dropped significantly in the case where
the boronic acid moiety was at the meta-position (1d, entries 15
and 16).
When ketone 1e was used as the substrate with ADH-A as the
biocatalyst (entries 17 and 18), alcohol 2e was obtained with a
50% conversion.
In conclusion, we have shown herein that optically active bor-
on-containing chiral alcohols can be successfully prepared by the
stereoselective reduction of carbonyl compounds by alcohol
dehydrogenases. Almost all of the ketones were reduced to the
corresponding alcohols with high conversions and excellent
enantiomeric excess (up to 99%) especially when ADH from R. ruber
(ADH-A) was employed.
ADH-A and LB-ADH transformed substrates bearing a boronic
ester or a boronic acid moiety at the para-position with compara-
ble conversions. ADH-A also accepted a boronic ester or a boronic
acid moiety at the meta-position.
However, a,b-unsaturated ketones 1f–g (entries 21–28) bearing
the terminal C@C bond were not suitable as substrates for the bio-
reduction with the ADHs evaluated. Neither the desired product
To the best of our knowledge, this is the first time that
boron-containing compounds have been employed as substrates
in alcohol dehydrogenase-catalysed reactions
nor any side-product was observed. However, the
a,b-unsaturated
ketone 1h, which contained an internal double bond, was well

1774
T. Barcellos et al. / Tetrahedron: Asymmetry 22 (2011) 1772–1777
Table 1
Bioreduction of boron-containing ketones catalysed by alcohol dehydrogenases from Rhodococcus ruber (ADH-A) and Lactobacillus brevis (LB-ADH)a
Entry
Substrate
ADH
Alcohol
Enantiomeric excessd (%)
Conversionc (%)
1
2
ADH-A
>99
>99
>99 (S)
>99 (S)
O
ADH-Ab
3
4
LB-ADH
47
30
>99 (R)
94 (R)
LB-ADHb
1a
O
B
O
5
6
ADH-A
87
86
>99 (S)
>99 (S)
O
ADH-Ab
7
8
LB-ADH
3
3
99 (R)
99 (R)
LB-ADHb
1b
B
O
O
9
10
ADH-A
91
91
>99 (S)
>99 (S)
O
ADH-Ab
11
12
LB-ADH
44
43
>99 (R)
>99 (R)
LB-ADHb
1c
HO
B
OH
13
14
ADH-A
84
83
>99 (S)
>99 (S)
O
ADH-Ab
15
16
LB-ADH
<2
<2
—
—
LB-ADHb
1d
1e
1f
B
HO
OH
17
18
19
20
ADH-A
50
50
4
96 (S)
95 (S)
67 (R)
79 (R)
ADH-Ab
O
B
LB-ADH
S
LB-ADHb
<2
O
O
21
22
23
24
O
ADH-A
n.c.
n.c.
n.c.
n.c.
—
—
—
—
ADH-Ab
LB-ADH
LB-ADHb
O
B
O
25
26
ADH-A
n.c.
n.c.
—
—
O
ADH-Ab
27
28
LB-ADH
n.c.
n.c.
—
—
LB-ADHb
1g
B
O
O
29
30
31
32
ADH-A
>99
>99
n.c.
n.c.
>99 (S)
>99 (S)
—
—
O
ADH-Ab
O
O
LB-ADH
B
1h
1i
LB-ADHb
O
33
34
O
ADH-A
LB-ADH
92e
14e
>99 (S)e
>99 (R)e
B
O
a
Reaction conditions: substrate (50 mM), 2-PrOH (100
(150 L, thermic precipitated), LB-ADH (300 L, crude extract), 24 h, 30 °C, 120 rpm.
Diethyl ether was employed as a co-solvent (20 L).
lM), phosphate buffer (50 mM, pH 7.5), NADH (1 mM in case of ADH-A), NADPH (1 mM in case of LB-ADH), ADH
l
l
b
l

T. Barcellos et al. / Tetrahedron: Asymmetry 22 (2011) 1772–1777
1775
c
d
e
Determined by GC analysis.
Determined by chiral HPLC analysis.
Conversion and ee were determined for the corresponding acetate derivative by CG analysis, (—) = not determined duo to low or none conversion. n.c. = no conversion.
4.2. Synthesis of 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)thiophen-2-yl)ethanone 1e
4. Experimental
4.1. General
The (5-acetylthiophen-2-yl)boronic acid (5 mmol, 850 mg) and
pinacol (5 mmol, 591 mg) were added to a 50 mL, two-necked,
round-bottomed flask containing anhydrous THF (30 mL). The
resulting solution was evaporated under reduced pressure at
40 °C. This procedure was repeated (3 times) until TLC analysis
indicated complete conversion. The crude product was purified
by column chromatography using hexanes/EtOAc (8:2) as the elu-
ent. Compound 1e was obtained as a white solid (mp = 67.9–
68.8 °C). Yield: 1.221 g (97%). 1H NMR (200 MHz, CDCl3) d = 1.35
(s, 12H), 2.58 (s, 3H), 7.58 (d, J = 3.8 Hz, 1H), 7.73 (d, J = 3.8 Hz,
1H). 13C NMR (50 MHz, CDCl3): d = 24.86, 27.56, 84.77, 132.81,
137.39, 149.62, 190.71. 11B NMR (96 MHz, CDCl3) d = 28.90. HRMS
[ESI (+)]: Calculated for C12H17BO3SNa [M+Na]+ = 275.0889; found:
275.0885.
Unless otherwise noted, commercially available materials were
used without further purification. The boron-containing ketones
1c, 1d are commercially available from Sigma-Aldrich. Ketones
1a, 1b and the alcohols 2a, 2b, 2h and 2i were synthesized as pre-
viously described.10a
All solvents were of HPLC or ACS grade. Solvents used for mois-
ture sensitive operations were distilled from drying reagents under
a nitrogen atmosphere: THF was distilled from Na/benzophenone.
CH2Cl2 was distilled from CaH2.
Nuclear magnetic resonance (NMR) spectra were recorded on a
Varian Gemini 200 spectrometer at operating frequencies of
200 MHz (1H NMR) or 50 (13C NMR). The 1H NMR chemical shifts
are reported in ppm relative to the TMS peak. Data are reported
as follows: chemical shift (d), multiplicity (s = singlet, d = doublet,
dd = double doublet, t = triplet) and coupling constant (J) in Hertz
and integrated intensity. The 13C NMR chemical shifts are reported
in ppm relative to CDCl3 or DMSO-d6 signal. The 11B NMR spectra
were obtained on a Varian Inova 300 spectrometer equipped with
the appropriate decoupling accessories. All 11B chemical shifts
were referenced to external BF3ÁOEt2 (0.00 ppm). A note about
the 13C NMR spectra: due to the boron quadrupole, carbons
directly attached to this element are often not detected in the
13C spectra.15
4.3. Synthesis of 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)thiophen-2-yl)ethanol 2e
Compound 1e (3 mmol, 756 mg) was added to a 50 mL, two-
necked, round-bottomed flask containing anhydrous methanol
(10 mL). The resulting solution was cooled to 0 °C with an ice bath.
Next, NaBH4 (3.6 mmol, 136 mg) was added, and the mixture was
stirred for 0.5 h at 0 °C and for an additional 3.5 h at room temper-
ature. The mixture was cooled to 0 °C and treated with 1 N HCl
aqueous solution until pH 7. The mixture was then extracted with
EtOAc (3 Â 5 mL), dried over anhydrous MgSO4 and the solvent
was evaporated under reduced pressure. The crude product was
purified by column chromatography using hexanes/EtOAc (8:2)
as eluent. Compound 2e was obtained as a colourless oil. Yield:
671 mg (88%). 1H NMR (200 MHz, CDCl3) d = 1.33 (s, 12H), 1.59
(d, J = 6.6 Hz, 3H), 5.15 (m, 1H), 7.05 (dd, J = 3.6, 0.8 Hz, 1H), 7.50
(d, J = 3.6 Hz, 1H). 13C NMR (50 MHz, CDCl3): d = 24.92, 25.59,
66.43, 84.27, 124.82, 137.36, 157.58. 11B NMR (96 MHz, CDCl3)
d = 29.00. HRMS (ESI): Calculated for C12H19BO3SNa [M+Na]+ =
277.1046; found: 277.1042.
Low-resolution mass spectra were obtained on
a GC/MS
Shimadzu spectrometer, operating at 70 eV. High-resolution
mass spectra (HRMS) were acquired using a Bruker Daltonics
MicroTOF instrument, operating in an electrospray ionization
(ESI) mode.
Gas chromatography (GC) analyses for the measurement of
enantiomeric excesses were obtained using a Shimadzu 17-A Gas
Chromatograph, equipped with autosampler, Flame Ionization
Detector (FID) and a chiral column Varian CP-Chirasil-DEX CB b-
cyclodextrin (25 m  0.25 mm  0.25
lm). The temperature of
the detector and injector was 220 °C; flow = 100 kPa, H2.
High performance liquid chromatograph (HPLC) analyses for
the measurement of enantiomeric excesses were performed on a
Shimadzu, LC-10AD liquid chromatograph equipped with auto-
sampler and a variable wavelength UV detector (deuterium lamp
4.4. Synthesis of 1-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)phenyl)prop-2-en-1-ol (RS)-2f,g
190–600 nm). Chiral columns: ChiralcelÒ OJ-H (0.46 cm
u
 25 cm)
The corresponding 1-(bromophenyl)prop-2-en-1-ol (115 mg,
5 mmol) was added to a 100 mL, two-necked, round-bottomed
flask containing anhydrous THF (20 mL). The resulting solution
was cooled to À70 °C and n-BuLi (10 mmol) was added dropwise
via syringe. After the reaction mixture was stirred for 30 min at
À70 °C, B(Oi-Pr)3 (1.880 g, 10 mmol) was added dropwise. The
reaction mixture was stirred for 1 h at À70 °C, and then the cooling
bath was removed. An aqueous HCl solution (1 mol LÀ1, 10 mL)
was added dropwise at 0 °C, and the reaction mixture was stirred
for 10 min. The organic phase was removed and the aqueous phase
was extracted with diethyl ether (3 Â 10 mL). The combined
organics were dried over anhydrous MgSO4, and the solvent was
evaporated under reduced pressure. The resulting solid was solubi-
lized with THF (20 mL) and pinacol was added (5 mmol). The resul-
tant solution was evaporated under reduced pressure at 40 °C. This
procedure was repeated (3 times) until TLC analysis indicated com-
plete conversion. The crude product was purified by column chro-
matography using hexanes/EtOAc (4:1) as the eluent.
or ChiralcelÒ OD (0.46 cm
u
 25 cm) from Daicel Chemical Ind. i-
PrOH and hexanes (60% n-hexane) HPLC grade purchased from J.
T. Baker were used as the eluting solvents.
The alcohol dehydrogenase ADH-A was used as a heat treated
crude recombinant enzyme preparation and prepared as previ-
ously described.13 The alcohol dehydrogenase from L. brevis was
used as a crude enzyme extract from the wild type strain L. brevis
DSM 20054. The strain was grown in an MRS-Medium (casein pep-
tone 10 g/L, peptone bact. 10 g/L, yeast extract 5 g/L, glucose 20 g/L,
Tween 80 1 g/L, potassium hydrogen phosphate 2 g/L, sodium ace-
tate tetrahydrate 8.3 g/L, ammonium citrate 2 g/L, magnesium sul-
phate heptahydrate 0.2 g/L, manganese chloride tetrahydrate
0.058 g/L) under ‘anaerobic conditions’, thus without shaking, at
30 °C for three days. Cells were harvested and disrupted using
ultrasonification (1 s pulse, 2 s pause, 20 min, 40° intensity), fol-
lowed by centrifugation (30 min 18,000 rpm, 4 °C). The superna-
tant containing the LB-ADH was then stored at À20 °C.

1776
T. Barcellos et al. / Tetrahedron: Asymmetry 22 (2011) 1772–1777
4.4.1. 1-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-
phenyl)prop-2-en-1-ol (RS)-2f
1.62 (m, 4H), 2.12 (s, 3H), 2.41 (t, J = 7.0 Hz, 2H). 13C NMR
(50 MHz, CDCl3): d = 23.90, 25.07, 26.75, 30.03, 43.95, 83.23,
209.57. 11B NMR (96 MHz, CDCl3) d = 34.15. HRMS (ESI): Calculated
for C12H23BO3Na [M+Na]+ = 249.1638; found: 249.1636.
Obtained as a colourless oil. Yield: 923 mg (71%). 1H NMR
(200 MHz, CDCl3): d = 1.34 (s, 12H), 1.99 (br, 1H), 5.15–5.35 (m,
3H), 6.03 (ddd, J = 17.1, 10.2, 6 Hz, 1H), 7.38 (d, J = 7.8 Hz, 2H),
7.80 (d, J = 7.8 Hz, 2H). 13C NMR (50 MHz, CDCl3): d = 25.05,
75.49, 84.01, 115.8, 125.78, 135.25, 140.31, 145.92. 11B NMR
(96 MHz, CDCl3) d = 30.12. HRMS (ESI): Calculated for C15H21BO3Na
[M+Na]+: 283.1262, found: 283.1265.
4.6. General procedure for the bioreduction of boron-
containing ketones 1a–i catalysed by ADH-A and ADH-LB
To a phosphate buffer solution (50 mM, pH 7.5, 1 mM NADPH in
the case of ADH-LB or 1 mM NADH in the case of ADH-A), sub-
4.4.2. 1-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-
phenyl)prop-2-en-1-ol (RS)-2g
strates (50 mM), 2-propanol (100
lL) and ADH-A (150 lL, thermic
precipitated) or ADH-LB (300 L, crude extract) were added lead-
l
Obtained as a colourless oil. Yield: 897 mg (69%). 1H NMR
(200 MHz, CDCl3): d = 1.34 (s, 12H), 2.14 (br, 1H), 5.15–5.40 (m,
3H), 6.06 (ddd, J = 17.0, 10.2, 6 Hz, 1H), 7.37 (t, J = 7.7 Hz, 1H),
7.49 (dt, J = 7.7, 1.7 Hz, 1H), 7.74 (dt, J = 7.7, 1.3 Hz, 1H), 7.79 (s,
1H). 13C NMR (50 MHz, CDCl3): d = 25.03, 75.48, 84.02, 115.17,
128.17, 129.46, 132.85, 134.38, 140.49, 142.21. 11B NMR
(96 MHz, CDCl3) d = 30.14. HRMS (ESI): Calculated for C15H21BO3Na
[M+Na]+: 283.1262, found: 283.1263.
ing to a final volume of 1 mL. Samples were incubated for 24 h at
30 °C and 120 rpm.
The reaction was stopped by the addition of diethyl ether
(500 lL). The mixture was mixed thoroughly and centrifuged for
5 min at 13,000 rpm. Then the organic layer was separated from
the aqueous phase and the procedure was repeated with diethyl
ether (400 lL). The combined organic layers were dried (Na2SO4)
and the supernatant was transferred into GC-glass-vials for
analysis.
4.5. General procedure for the preparation of ketones 1f–i
4.7. General procedure for the bioreduction of boron-
containing ketone 1a catalysed by ADH-A
The appropriate alcohol (2 mmol) was added to a 50 mL, two-
necked, round-bottomed flask containing anhydrous dichloro-
methane (10 mL). The mixture was cooled to 0 °C and pyridinium
dichromate (3 mmol, 1.128 g) was then added. The reaction was
monitored by TLC until consumption of the starting material.
Diethyl ether (10 mL) was added, and the precipitate formed
was decanted and washed with diethyl ether (3 Â 10 mL). The sol-
vent was filtered through a column of Celite. The solvent was evap-
orated under reduced pressure. The crude product was purified by
column chromatography using hexanes/EtOAc (8:2) as eluent.
Ketone 1a (100 mg) was used in a 10 mL reaction volume (6 mL
phosphate buffer, 50 mM, pH 7.5; 5.3 mg NADH; 1.2 mL ADH-A,
thermic precipitated; 800 lL 2-propanol).
The reaction was stopped by extraction with diethyl ether
(5 mL) and centrifuged for 5 min at 13,000 rpm. Then the organic
layer was separated from the aqueous phase and the procedure
was repeated with diethyl ether (5 mL). The combined organic
layer was dried (Na2SO4) prior to analysis (alcohol 2a, 80% yield).
4.5.1. 1-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-
phenyl)prop-2-en-1-one 1f
Acknowledgments
Obtained as a yellow oil. Yield 232 mg (45%). 1H NMR (200 MHz,
CDCl3): d = 1.36 (s, 12H), 5.94 (dd, J = 10.6, 1.7 Hz, 1H), 6.43 (dd,
J = 17.2, 1.7 Hz, 1H), 7.15 (dd, J = 17.2, 10.6 Hz, 1H), 7.91 (s, 4H).
13C NMR (50 MHz, CDCl3): d = 25.11, 84.44, 127.89, 130.48,
132.81, 135.15, 139.52, 192.79. 11B NMR (96 MHz, CDCl3)
We thank FAPESP (São Paulo Research Foundation) and CNPq
(National Council for Scientific and Technological Development)
for financial support.
d = 30.14. HRMS (ESI): Calculated for
C
15H19BO3Na [M+Na]+:
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281.1325, found: 281.1367.
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phenyl)prop-2-en-1-one 1g
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1
Obtained as a yellow oil. Yield 243 mg (47%). H NMR (200 MHz,
CDCl3): d = 1.36 (s, 12H), 5.92 (dd, J = 10.5, 1.8 Hz, 1H), 6.44 (dd,
J = 17.1, 1.8 Hz, 1H), 7.23 (dd, J = 17.1, 10.5 Hz, 1H), 7.48 (t, J = 7.8 Hz,
1H), 7.95–8.13 (m, 2H), 8.36 (s, 1H). 13C NMR (50 MHz, CDCl3):
d = 25.07, 84.33, 128.28, 130.15, 131.50, 132.72, 135.13, 136.92,
139.43, 191.23. 11B NMR (96 MHz, CDCl3) d = 30.17 HRMS (ESI): Calcu-
lated for C15H19BO3Na [M+Na]+: 281.1325, found: 281.1368.
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4.5.3. (E)-4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-
en-2-one 1h
Obtained as a colourless oil. Yield: 149 mg (38%). 1H NMR
(200 MHz, CDCl3): d = 1.30 (s, 12H), 2.30 (s, 3H), 6.54 (d, J =
18.6 Hz, 1H), 6.81 (d, J = 18.6 Hz, 1H). 13C NMR (50 MHz, CDCl3):
d = 28.87, 26.78, 84.25, 146.60, 199.04. 11B NMR (96 MHz, CDCl3)
d = 30.00. HRMS (ESI): Calculated for C10H17BO3Na [M+Na]+ =
219.1168; found: 219.1165.
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4.5.4. 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)hexan-2-
one 1i
Obtained as a colourless oil. Yield: 90 mg (20%). 1H NMR
(200 MHz, CDCl3): d = 0.78 (t, J = 7.0 Hz, 2H), 1.24 (s, 12H), 1.32–

T. Barcellos et al. / Tetrahedron: Asymmetry 22 (2011) 1772–1777
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