Alkoxide-catalyzed reduction of ketones with pinacolborane

Article abstract of DOI:10.1021/jo201142g

The reduction of ketones with pinacolborane (4,4,5,5-tetramethyl-1,3,2- dioxaborolane) is catalyzed by 5 mol % NaOt-Bu at ambient temperature. The reaction is high yielding and general, providing complete conversion of aryl and dialkyl ketones. Although spectroscopic studies of the active hydride source in benzene-d₆ were complicated due to poor solubility, the data are consistent with the active hydride source being the trialkoxyborohydride, which is believed to be present in low concentration under the reaction conditions. Performing analogous studies in tetrahydrofuran resulted in a complex equilibrium between several different boron-containing species in which the trialkoxyborohydride compound was the major species.

Full text of DOI:10.1021/jo201142g

NOTE
pubs.acs.org/joc
Alkoxide-Catalyzed Reduction of Ketones with Pinacolborane
,
†
Ian P. Query, Phillip A. Squier, Emily M. Larson, Nicholas A. Isley, and Timothy B. Clark*
Department of Chemistry, Western Washington University, 516 High Street, Bellingham, Washington 98225, United States
S Supporting Information
b
ABSTRACT: The reduction of ketones with pinacolborane
(
4,4,5,5-tetramethyl-1,3,2-dioxaborolane) is catalyzed by 5 mol %
NaOt-Bu at ambient temperature. The reaction is high yielding
and general, providing complete conversion of aryl and dialkyl
ketones. Although spectroscopic studies of the active hydride
source in benzene-d were complicated due to poor solubility,
6
the data are consistent with the active hydride source being the trialkoxyborohydride, which is believed to be present in low
concentration under the reaction conditions. Performing analogous studies in tetrahydrofuran resulted in a complex equilibrium
between several different boron-containing species in which the trialkoxyborohydride compound was the major species.
he versatility of the carbonꢀboron bond in target-directed
these conditions, the reduction of acetophenone with pinacol-
borane reached full conversion at 22 °C in 3 h. Trialkoxyborane
product 1 was hydrolyzed on silica gel to provide 2-phenyl-
ethanol and analyzed by gas chromatography (chiral support
column), which showed that the alcohols were racemic in
both cases.
1
ꢀ3
T
synthesis
has led to numerous valuable methods to
4
ꢀ14
incorporate boron substituents into organic substrates.
The hydroboration of double and triple bonds, for example,
has served as a long-standing method to synthesize alkyl- and
4
ꢀ6
vinylboronate esters.
Over the past several decades, metal
catalysts have been used in hydroboration reactions to increase
the substrate scope, enhance reaction rates, and alter the regio-
and chemoselectivity.
Scheme 1. Metal-Catalyzed Reduction of Acetophenone
The advent of metalꢀligand bifunctional catalysts in the
hydrogenation of polarized double bonds has led to highly
1
5ꢀ19
efficient and stereoselective catalysts.
Our interest in devel-
2
0,21
oping metalꢀligand bifunctional borylation catalysts
led us
to explore the effectiveness of boranes as surrogates for hydrogen
gas (or a hydrogen source) in Noyori’s asymmetric hydrogena-
tion and transfer hydrogenation reactions. In the process of
studying these transformations, we found that the reduction of
ketones with pinacolborane was mediated by a catalytic amount
of sodium tert-butoxide. This transformation represents an
important metal-free reaction that should be considered when
designing and studying base-mediated catalytic hydroboration
reactions. The prevalence of base additives in metal-catalyzed
8,22ꢀ24
borylation reactions
prompted a detailed investigation
The complete lack of stereoselectivity in these transforma-
tions was puzzling on the basis of the high stereoselectivity
into the nature of the active hydride source. We herein report
a brief survey of the reaction scope and a spectroscopic study of
the alkoxide-mediated reduction of ketones with pinacolborane.
The hydrogenation of ketones using Noyori’s hydrogenation
and transfer hydrogenation catalysts provides secondary alcohols
1
5ꢀ18
induced by the parent hydrogenation reactions.
A control
experiment was conducted to determine the active species of
the catalytic addition of pinacolborane. The reduction was
repeated in the absence of precatalyst 2 or 3, which also
provided reduction of acetophenone in 3 h at 22 °C (eq 1),
demonstrating that the alkoxide could catalytically activate
pinacolborane toward addition to acetophenone. We initiated
a study of this transformation to provide insight into the role
15ꢀ18
in high enantioselectivity.
There are, however, some classes
of substrates that result in moderate to low selectivity. Replacing
the acidic hydrogen of these catalysts with the sterically more
demanding Lewis acid Bpin (4,4,5,5-tetramethyl-1,3,2-dioxo-
borolane) was expected to enhance the stereoselectivity. Initial
experiments were conducted with 5 mol % Noyori precatalysts 2
and 3 and 20 mol % NaOt-Bu, a required additive to generate the
Received: June 4, 2011
Published: June 24, 2011
25
catalytically active 16-electron complexes (Scheme 1). Under
r 2011 American Chemical Society
6452
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|J. Org. Chem. 2011, 76, 6452–6456

The Journal of Organic Chemistry
NOTE
Scheme 2. Explanation of Observed Spectroscopic Data
Figure 1. Proposed active reducing agent.
of base additives in transition metal-catalyzed borylation
8
,22ꢀ24
reactions.
In the early 1980s, Brown described the reactivity of alkali
metal hydrides (LiH, NaH, KH) toward trialkoxyboranes, de-
monstrating that an equivalent of the metal hydride could be
added to trialkoxyboranes to provide trialkoxyborohydrides
resonances were observed (δ 23.1, 10.2, 6.2, ꢀ13.1, ꢀ41.2 ppm).
The resonance at 6.2 ppm is significantly larger than the
remaining four peaks and was tentatively assigned as complex
4 on the basis of the chemical shifts reported by Brown for
2
6,27
cleanly (eq 2).
Potassium hydride was shown to provide
27
trialkoxyborohydrides (vide supra).
complete conversion to products in the shortest reaction times.
The resulting trialkoxyborohydrides were also shown to reduce
1
11
A H-coupled B NMR spectrum was then obtained, reveal-
2
7
ing singlets for the three upfield resonances, a broad doublet at δ
ketones rapidly. On the basis of this precedent, we postulated
that the active hydride source was trialkoxyborohydride 4,
derived from addition of NaOt-Bu to pinacolborane (Figure 1).
2
9
ꢀ
13.1 ppm (J = 77.1 Hz), and a quintet at δ ꢀ41.2 ppm (J =
8
1.0 Hz). The quintet was identified as NaBH by comparison to
4
30
an authentic sample. Although the major peak (δ 6.2 ppm) is
not a doublet, several of the trialkoxyborohydrides reported by
Brown were reported as broad singlets (for example, potassium
27
tricyclopentoxyborohydride). For comparison, trialkoxyboro-
hydride 5 was synthesized by the addition of KH to pinBOi-Pr
To examine the nature of the catalytically active borohydride, a
(
2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane) by heat-
ing to 80 °C for 24 h in THF-d (eq 4). The resulting product was
stoichiometric equivalent of NaOt-Bu was added to pinacolborane in
1
8
benzene-d and examined by NMR spectroscopy. In the H NMR
1
11
6
analyzed by H-coupled B NMR spectroscopy, revealing one
major singlet at δ 7.6 ppm. On the basis of these results, we have
assigned the resonance at δ 6.2 ppm as complex 4.
spectrum, the tert-butyl hydrogens of NaOt-Bu (1.30 ppm) and the
tetramethyl hydrogens of the pinacol group (0.99 ppm) were
completely replaced by new resonances at 1.38 and 1.06 ppm,
11
1
respectively. In the B{ H} NMR spectrum, the resonance for
28
pinacolborane (28.5 ppm) shifted to 22.2 ppm. Although it was
apparent that a reaction between NaOt-Bu and pinacolborane had
11
occurred, the B NMR chemical shift was not consistent with the
1
1
27
trialkoxyborohydrides reported by Brown ( B NMR: δ0ꢀ7ppm).
The probable insolubility of 4 in benzene-d led to a re-
6
examination of this reaction in THF, which also allowed closer
On the basis of the spectroscopic data reported above, the catalytic
comparison to the borohydrides reported by Brown in his
reaction conditions (in benzene-d ) are believed to involve low
1
6
studies. In THF-d , a complex H NMR spectrum resulted.
8
concentrations of trialkoxyborohydride 4, which is in equilibrium
with the associated disproportionation products 6 and 7 (Scheme 2).
Sodium trialkoxyborohydride and sodium borohydride may also be
Characteristic peaks for the pinacol and tert-butyl hydrogens
were not readily identified, but a resonance representing a boron-
bound hydride was present at ꢀ0.09 ppm (split into four equally
31
present in low concentrations by analogy to the spectroscopic
sized singlets, J = 81.5 Hz). The complex nature of the
BH
studies in THF-d . In benzene-d , all of the tetra-substituted borate
8
6
spectrum and the presence of boron-bound hydrides are con-
sistent with a dynamic equilibrium between several complexes,
including the disproportionation reaction reported by Brown for
salts have poor solubility, which leaves trialkoxyborane as the only
observable product by NMR spectroscopy. On the basis of the rapid
exchange between all the borohydride derivatives, it is possible that
any of these complexes serve as the active hydride source.
27
trialkoxyborohydrides (eq 3).
A proposed catalytic cycle is shown (Scheme 3), which assumes
that 4 is the active hydride source in order to simplify the
mechanistic picture. An initial activation of pinacolborane by
NaOt-Bu is followed by hydride addition to acetophenone to
generate sodium R-phenylethylalkoxide, the catalytically relevant
alkoxide base. The R-phenylethylalkoxide could then activate a
1
1
1
A B { H} NMR spectrum of the reaction between NaOt-Bu
0
0
and pinacolborane in THF-d was obtained to clarify the identity
of the mixture and the boron-bound hydride complexes. Five
second equivalent of pinacolborane to generate 4 . Hydride 4 can
then form reduced product 1 upon addition to acetophenone.
8
6
453
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The Journal of Organic Chemistry
NOTE
Scheme 3. Proposed Catalytic Cycle for Alkoxide-Mediated
Reduction of Ketones
A brief study of the reaction scope was carried out to gain
more insight into this transition metal-free reduction. Several
acetophenone derivatives were subjected to the reaction conditions
(
2
1.1 equivalents of HꢀBpin, 5 mol % NaOt-Bu, toluene, 22 °C,
.5 h). The resulting reduction products were purified by silica gel
chromatography, resulting in hydrolysis of the OꢀB bond. The
corresponding secondary alcohols were isolated in >90% yield
(
Table 1, eq 5).
The reduction of dialkyl ketones was achieved under condi-
tions identical to the acetophenone derivatives, providing high
yields of the corresponding secondary alcohol (Table 2, eq 6).
The reduction of 2-methylcyclohexanone was explored to de-
termine the inherent selectivity imparted during the reduction;
2
-methylcyclohexanol was formed in a 1.3:1 ratio of transꢀcis
diastereomers. This selectivity is comparable to the selectivities
reported by Brown for the reduction of 2-methylcyclohexanone
with sterically hindered potassium trialkoxyborohydrides and
2
7
32
for addition of NaBH4.
Table 2. Alkoxide-Catalyzed Reduction of Dialkyl Ketones
eq 6)
(
In summary, alkoxide-mediated reduction of ketones with pina-
colborane is a potential competing reaction in metal-catalyzed
borylation reactions. A catalytic amount of sodium tert-butoxide
mediates the reduction of ketones by hydride addition to the
carbonyl. The active hydride source could not be isolated, but
spectroscopic data and literature precedent support an equilibrium
between sodium trialkoxyborohydride and sodium borohydride, as
well as the di- and trihydride complexes. A range of ketones were
subjected to the reaction conditions, providing the corresponding
alcohols in high yields demonstrating the potential of this transfor-
mation as an operationally simple reduction of carbonyls.
Table 1. Alkoxide-Catalyzed Reduction of Acetophenone
Derivatives (eq 5)
’
EXPERIMENTAL SECTION
General Experimental Information. All materials were manipu-
lated under a positive pressure of dry nitrogen. Stoichiometric reactions
for spectroscopic studies of the active hydride source were handled
under dry nitrogen in an inert atmosphere glovebox. NMR spectra were
1
13
collected at 500 MHz for H NMR, 125 MHz for C NMR, and
1
1
1
1
60 MHz for B NMR. H NMR spectra are referenced to chloroform-d
at 7.24 ppm or benzene-d at 7.16 ppm. The H NMR data are reported
6
1
as follows: chemical shift in ppm, multiplicity (s, singlet; d, doublet; t,
triplet; q, quartet; qn, quintet; sep, septet; m, multiplet), coupling
6
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The Journal of Organic Chemistry
NOTE
1
3
constants (Hz), and integration. C NMR spectra are referenced to
Purification by flash column chromatography (50:50 ethyl acetateꢀ
1
1
chloroform-d at 77.23 ppm or benzene-d at 128.39 ppm. B NMR
spectra were referenced to an external BF
was purchased from a chemical supplier and was
dried and distilled from CaH ; degassed using three freeze, pump, thaw
hexanes) provided 1-(4-trifluoromethylphenyl)ethanol as a colorless oil
6
1
3
3
Et
2
O sample in benzene-d
6
(0.451 g, 93%): H NMR (CDCl
3
, 500 MHz) δ 7.58 (d, J = 8.3 Hz,
(
0.0 ppm). Benzene-d
6
2 H), 7.48 (d, J = 7.8 Hz, 2 H), 4.96 (q, J = 6.3 Hz, 1 H), 1.92 (br s, 1 H),
1
3
1.48 (d, J = 6.3 Hz, 3 H); C NMR (CDCl , 125 MHz) δ 149.9, 125.7,
2
3
cycles; and stored in an inert atmosphere glovebox. Toluene was dried in a
solvent purification system by passing through an activated alumina column
and an oxygen scavenging column under nitrogen. Sodium tert-butoxide,
125.6, 125.4 (q, J = 3.8 Hz), 110.2, 70.0, 25.6; IR (neat) 3336 (br), 2977,
ꢀ1
1621, 1414, 1322, 1205, 1162, 1114, 1088, 1066, 1015, 898, 839, 737 cm
.
3
5
1-(4-Bromophenyl)ethanol. The general procedure was followed
with 4-bromoacetophenone (0.511 g, 2.57 mmol). Purification by flash
column chromatography (20:80 ethyl acetateꢀhexanes) provided 1-(4-
pinacolborane, tetrahydrofuran-d , and chloroform-d were purchased and
8
used as received. Ketones were typically distilled from CaH
2
and stored
1
under nitrogen prior to use. Potassium hydride was washed with hexanes
bromophenyl)ethanol as a colorless oil (0.503 g, 97%): H NMR
(
ꢁ 3), dried in vacuo, and stored in an inert atmosphere glovebox.
(CDCl
3
, 500 MHz) δ 7.47 (d, J = 8.3 Hz, 2 H), 7.26 (d, J = 7.8 Hz, 2
Addition of NaOt-Bu to Pinacolborane. In Benzene-d . To a
H), 4.88 (q, J = 6.4 Hz, 1 H), 1.82 (br s, 1 H), 1.48 (d, J = 6.8 Hz, 3 H);
6
1
3
resealable NMR tube was added sodium tert-butoxide (0.024 g, 0.250
mmol), benzene-d (0.50 mL), and pinacolborane (0.036 mL, 0.250
mmol). After 0.5 h, the resulting reaction mixture was examined by
NMR spectroscopy. H NMR (500 MHz, benzene-d
1
2
C NMR (CDCl
3
, 125 MHz) δ 144.8, 131.7, 127.3, 121.3, 70.0, 25.5;
IR (neat) 3319 (br), 2972, 1592, 1488, 1447, 1401, 1111, 1069, 1008,
896, 820, 770, 715 cm
Cyclohexanol. The general procedure was followed with cyclo-
hexanone (0.270 mL, 2.57 mmol). Purification by flash column chro-
6
ꢀ
1
.
1
36
6
): δ 1.38 (s, 9H),
): δ 81.4, 73.1, 29.9,
): δ 22.2.
In Tetrahydrofuran-d . To a resealable NMR tube was added sodium
13
.06 (s, 12H); C NMR (125 MHz, benzene-d
4.2; B { H} NMR (160 MHz, benzene-d
6
11
1
matography (15:85 ethyl acetateꢀhexanes) provided cyclohexanol as a
6
1
colorless oil (0.165 g, 64%): H NMR (CDCl
, 500 MHz) δ 3.59 (qn,
8
3
tert-butoxide (0.024 g, 0.250 mmol), tetrahydrofuran-d
pinacolborane (0.036 mL, 0.250 mmol). After 0.5 h, the resulting
8
(0.50 mL), and
J = 3.9 Hz, 1 H), 1.88 (m, 2 H), 1.71 (m, 2 H), 1.65ꢀ1.46 (m, 2 H), 1.38
13
(br, 1 H), 1.32ꢀ1.08 (m, 4 H); C NMR (CDCl
3
, 125 MHz) δ 70.6,
1
reaction mixture was examined by NMR spectroscopy. H NMR (500
35.8, 25.7, 24.3; IR (neat) 3324 (br), 2928, 2853, 1449, 1362, 1298,
11
ꢀ1
7,38
MHz, THF-d ) complex mixture; B NMR (160 MHz, THF-d ): δ
1065, 1024, 967, 889, 862 cm
2-Methylcyclohexanol.
.
8
8
3
2
3.1, 10.2, 6.2, ꢀ13.1 (d, J = 77.1 Hz), ꢀ41.2 (qn, J = 81.0 Hz).
The general procedure was followed
Addition of KH to 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-
with 2-methylcyclohexanone (0.320 mL, 2.57 mmol). A 1.3:1 mixture
1
dioxaborolane. To a resealable NMR tube was added potassium
hydride (0.008 g, 0.199 mmol), tetrahydrofuran-d (0.50 mL), and
-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.020 mL, 0.098
mmol). After 24 h at 80 °C, the reaction mixture was analyzed by NMR
of transꢀcis 2-methylcyclohexanol was observed by H NMR spec-
troscopy. Purification by flash column chromatography (15:85 ethyl
8
2
acetateꢀhexanes) provided 2-methylcyclohexanol as a colorless oil
1
(0.252 g, 86%): trans isomer: H NMR (CDCl
3
, 500 MHz) δ 3.75
1
11
spectroscopy. H NMR (500 MHz, THF-d
NMR (160 MHz, THF-d
): δ 7.6, ∼6.8, ∼22 (br).
General Procedure for the Reduction of Ketones. 1-Phenyl-
8
) complex mixture;
B
(br s, 1 H), 1.92 (br, 1 H), 1.73ꢀ1.15 (m, 9 H), 0.99 (d, J = 6.3 Hz, 3 H);
13
C NMR (CDCl
3
, 125 MHz) δ 76.7, 40.5, 35.7, 33.9, 25.9, 25.4, 18.7;
8
1
cis isomer: H NMR (CDCl , 500 MHz) δ 3.09 (br, 1 H), 1.92 (br, 1
3
1
3
33
H), 1.73ꢀ1.15 (m, 9 H), 0.92 (d, J = 7.3 Hz, 3H); C NMR (CDCl
3
,
ethanol. To a 50 mL round-bottom flask equipped with a stir bar
was added NaOt-Bu (0.0115 g, 0.120 mmol), toluene (23 mL), aceto-
phenone (0.300 mL, 2.57 mmol), and pinacolborane (0.410 mL,
1
2
25 MHz) δ 71.3, 36.0, 32.7, 29.0, 24.7, 20.8, 12.5; IR (neat) 3345 (br),
924, 2845, 1448, 1066, 1052, 1036, 1015, 977, 928, 843 cm
ꢀ
1
.
3
9
4-Phenyl-2-butanol. The general procedure was followed with
2.85 mmol). After 2.5 h of stirring under nitrogen gas, the volatiles were
benzylacetone (0.390 mL, 2.57 mmol). Purification by flash column
removed in vacuo. The crude reaction mixture was purified by flash column
chromatography (30:70 ethyl acetateꢀhexanes) provided 4-phenyl-2-
chromatography (20:80 ethyl acetateꢀhexanes) to provide 1-phenyletha-
1
1
butanol as a colorless oil (0.379 g, 98%): H NMR (CDCl
3
, 500 MHz) δ
nol as a colorless oil (0.291 g, 93%): H NMR (CDCl , 500 MHz) δ 7.34
3
7.27 (t, J =7.8 Hz, 2 H), 7.20 (m, 3 H), 3.82(q, J =5.9Hz, 1 H), 2.78 (ddd,
(
(
d, J = 7.3 Hz, 2 H), 7.25 (t, J = 5.8 Hz, 2 H), 4.87 (q, J = 6.4 Hz, 1 H), 1.95
d, J= 6.6 Hz, 1 H), 1.48 (d, J= 6.4 Hz, 3H); C NMR(CDCl , 125 MHz)
3
13
J = 16.1, 9.3, 6.8 Hz, 1 H), 2.69 (ddd, J = 16.1, 9.2, 7.3 Hz, 1H) 1.77 (m, 2
1
3
H), 1.36 (br s, 1 H), 1.22 (d, J = 5.8 Hz, 3 H); C NMR (CDCl
3
, 125
δ 146.0, 128.7, 127.7, 125.6, 70.6, 25.4; IR (neat) 3343 (br), 2972, 1492,
ꢀ
1
MHz) δ 142.3, 128.6, 126.0, 67.7, 41.1, 32.3, 23.8; IR (neat) 3339 (br),
1
449, 1203, 1097, 1075, 1028, 1009, 897, 758, 697 cm .
1
ꢀ
1
33
2
926, 1495, 1453, 1373, 1127, 1083, 1053, 953, 934, 904, 746, 696 cm .
5
-(4-Fluorophenyl)ethanol. The general procedure was followed
4
0
-Hexene-2-ol. The general procedure was followed with 5-
with 4-fluoroacetophenone (0.310 mL, 2.57 mmol). Purification by flash
hexene-2-one (0.300 mL, 2.57 mmol). Purification by flash chromatog-
column chromatography (20:80 ethyl acetateꢀhexanes) provided 1-(4-
1
raphy (20:80 ethyl acetateꢀhexanes) provided 5-hexene-2-ol as a color-
fluorophenyl)ethanol as a colorless oil (0.337 g, 94%): H NMR
1
less oil (0.170 g, 66%): H NMR (CDCl , 500 MHz) δ 5.81 (qn, J =
(
CDCl
Hz, 1 H), 1.79 (d, J = 3.4 Hz, 1H), 1.46 (d, J = 6.3 Hz, 3 H); C NMR
CDCl , 125 MHz) δ 163.3, 141.7 (d, J = 2.8 Hz), 127.2 (d, J = 7.7 Hz),
15.4 (d, J = 21.1 Hz), 70.0, 25.5; IR (neat) 3331 (br), 2973, 1603, 1508,
3
, 500 MHz) δ 7.32 (m, 2 H), 7.01 (m, 2 H), 4.89 (q, J = 3.4
3
1
3
6
.9 Hz, 1 H), 4.98 (m, 2 H), 3.81 (q, J = 5.3 Hz, 1 H), 2.12 (m, 2 H), 1.52
1
3
(m, 2 H), 1.47 (s, 1 H), 1.18 (d, J = 6.8 Hz, 3 H); C NMR (CDCl
3
, 125
(
1
1
3
MHz) δ 138.7, 115.0, 67.9, 38.4, 30.4, 23.7; IR (neat) 3340, 3078, 2968,
ꢀ
1
ꢀ
1
2928, 1641, 1450, 1374, 1120, 1083, 994, 950, 934, 908, 846 cm .
220, 1106, 1082, 1008, 897, 832 cm
.
33
1-(4-Methoxyphenyl)ethanol. The general procedure was fol-
lowed with 4-methoxyacetophenone (0.386 g, 2.57 mmol). Purification
’
ASSOCIATED CONTENT
Supporting Information. Selected spectra of products
by flash column chromatography (35:65 ethyl acetateꢀhexanes) pro-
1
vided 1-(4-methoxyphenyl)ethanol as a colorless oil (0.370 g, 95%): H
S
b
NMR (CDCl
3
, 500 MHz) δ 7.27 (d, J = 8.8 Hz, 2 H), 6.87 (d, J = 8.3 Hz,
and spectroscopic studies. This material is available free of charge
via the Internet at http://pubs.acs.org.
2
H), 4.81 (q, J = 6.3 Hz, 1 H), 3.78 (s, 3 H), 1.78 (br s, 1 H), 1.47
13
(d, J = 6.3 Hz, 3 H); C NMR (CDCl , 125 MHz) δ 159.0, 138.2, 126.9,
3
1
1
14.0, 70.2, 55.5, 25.2; IR (neat) 3350 (br), 2969, 1611, 1510, 1241,
’
AUTHOR INFORMATION
ꢀ
1
204, 1174, 1115, 1086, 1033, 1004, 829, 807 cm
.
34
1-(4-Trifluoromethylphenyl)ethanol. The general procedure was
Corresponding Author
*Email: clarkt@sandiego.edu.
followed with 4-trifluoromethylacetophenone (0.483 g, 2.57 mmol).
6
455
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The Journal of Organic Chemistry
NOTE
1
1
Present Addresses
Department of Chemistry and Biochemistry, University of
San Diego, 5998 Alcala Park, San Diego, CA 92110.
(28) For examples of trialkoxyborohydrides with B NMR chemical
†
shifts, see: Brown, H. C.; Cha, J. S.; Nazer, B. Inorg. Chem. 1984, 23,
2
929–2931.
(
29) This broad doublet has poorly defined shoulders that are
consistent with a quartet. The peak is therefore assigned as a monoalk-
oxyborohydride. See Supporting Information for spectrum.
’
ACKNOWLEDGMENT
(
30) The disproportionation of sodium trimethoxy- and triethoxy-
Acknowledgement is made to the donors of the American
borohydrides into sodium borohydride and sodium tetraalkoxyboranes
has been reported. More hindered trialkoxyborohydrides (such as
sodium triisopropoxyborohydride) were not prone to this dispropor-
tionation. See Brown, H. C.; Mead, E. J.; Shoaf, C. J. J. Am. Chem. Soc.
1956, 78, 3616–3620.
Chemical Society Petroleum Research Fund for partial support
of this research (47598-GB3), Cambridge Isotope Laboratories,
Inc. Research Grant, which generously provided tetrahydrofur-
an-d , the M.J. Murdock Charitable Trust and Research Cor-
8
1
11
poration for Science Advancement in the form of a department
(31) No resonances were observed by H or B NMR spectroscopy
development grant, and Western Washington University.
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