Asymmetric reduction of ketones under mild conditions using NaBH 4 and TarB-NO2: An efficient and unusual chiral acyloxyborohydride reducing system

Article abstract of DOI:10.1002/ejoc.200500397

High enantioselectivities are obtained for the reduction of a series of ketones using the inexpensive and mild reducing agent NaBH₄ with TarB-NO₂ (1). This easily prepared tartaric acid-based reagent combines a Lewis acid with carboxylic acids in a single bifunctional reagent. When combined with NaBH₄, the resulting chiral acyloxyborohydride mediates the reduction of aromatic ketones to provide the product alcohols in enantiomeric excesses of 93-98%. Several aliphatic ketones were also reduced with moderate to excellent enantioselectivity. A unique mechanism is provided with supporting calculations for the proposed active species and transition state. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

Full text of DOI:10.1002/ejoc.200500397

FULL PAPER
DOI: 10.1002/ejoc.200500397
Asymmetric Reduction of Ketones Under Mild Conditions Using NaBH and
4
TarB-NO : An Efficient and Unusual Chiral Acyloxyborohydride Reducing
2
System
[
a]
[a]
[a]
[a]
David B. Cordes, Thao M. Nguyen, Tracey J. Kwong, Jeff T. Suri,
[b]
[a]
Richard T. Luibrand, and Bakthan Singaram*
Dedicated to the memory of Richter von Grunenfeld
Keywords: Asymmetric synthesis / Boron / Lewis acids / Acyloxyborohydride / Sodium borohydride
High enantioselectivities are obtained for the reduction of a
series of ketones using the inexpensive and mild reducing
agent NaBH with TarB-NO (1). This easily prepared tartaric
4 2
acid-based reagent combines a Lewis acid with carboxylic
acids in a single bifunctional reagent. When combined with
in enantiomeric excesses of 93–98%. Several aliphatic
ketones were also reduced with moderate to excellent
enantioselectivity. A unique mechanism is provided with
supporting calculations for the proposed active species and
transition state.
NaBH
4
, the resulting chiral acyloxyborohydride mediates the
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
reduction of aromatic ketones to provide the product alcohols
Introduction
cently, Mukaiyama has developed a catalytic system utiliz-
ing alcohol-modified NaBH4 combined with a catalytic
amount of a chiral β-ketoiminato cobalt() complex to pro-
vide high ee values for the reduction of a number of prochi-
Asymmetric reduction of prochiral ketones often pro-
vides the most efficient route to optically active secondary
alcohols. A number of boron-based reagents have been de-
veloped for this transformation. These include both borane-
modified catalysts, such as CBS catalyst[ and numerous
chirally modified borohydride reducing agents.[ Among
borohydride reagents, those obtained through modification
[
13–15]
ral ketones and imines at reduced temperatures.
Inter-
estingly, while the use of NaBH with achiral carboxylic
1]
4
acids is well established as an efficient achiral reducing sys-
tem, the application of chiral carboxylic acids with NaBH4
for the asymetric reduction of ketones has not been thor-
oughly investigated.
2]
of mild and inexpensive sodium borohydride (NaBH ) are
4
of particular interest.[ Over the past few decades, chirally
modified NaBH4 has been used for the asymmetric re-
duction of ketones with varying degrees of success under a
wide range of experimental conditions. Early work involved
3]
Sodium borohydride has been used with carboxylic acids
to carry out a wide range of reductions of nitrogen- and
[
16,17]
oxygen-based functionalities.
Borohydrides and car-
boxylic acids combine to form acyloxyborohydrides, a ro-
bust reducing species that is described in the following sec-
chiral modification of NaBH with phase-transfer cata-
4
[
4]
[5,6,7]
lysts,
alcohols,
monosaccharide
derivatives,
amino
tion. The particular combination of NaBH and acetic acid,
[
8,9,10]
[11,12]
4
and amino acids.
Several researchers
well-known as Gribble conditions, is commonly used to ef-
fect non-enantioselective reductions of ketones and imines.
found that both reaction rate and chiral induction improved
when Lewis acids, such as salts of zinc or zirconium, were
[
18,19]
For the enantioselective reduction of ketones, Hirao
included in the reaction mixture.[
5,7,–10]
These systems often
[
20]
and Morrison utilized NaBH with achiral carboxylic ac-
4
provided low conversions with low to moderate enantio-
selectivities for the reduction of prochiral ketones. More re-
ids and chiral sugar derivatives to obtain ee values as high
as 64%. The use of NaBH modified with optically active
4
[
21]
carboxylic acids was investigated by Nasipuri and Bian-
chi using mandelic and lactic acids, while Adams and
Yamazaki utilized tartaric acid. Additional work by Yat-
[
[
a] Department of Chemistry and Biochemistry, University of Cali-
fornia,
[
22]
[23]
Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA
Fax: +1-831-459-2935
[24]
[
25,26]
[27]
E-mail: singaram@chemistry.ucsc.edu
agai
and Polyak with tartaric acid-modified NaBH
4
b] Department of Chemistry, California State University,
East Bay, Hayward, CA 94542, USA
gave moderate ee values for the reduction of some α- and
β-substituted ketones, though enantioselectivities were
lower for simple, unmodified ketones.
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2005, 5289–5295
© 2005 Wiley-VCH Verlag GmbH & Co. KgaA, Weinheim
5289

D. B. Cordes, T. M. Nguyen, T. J. Kwong, J. T. Suri, R. T. Luibrand, B. Singaram
FULL PAPER
Previously, we reported the use of TarB-NO (1), a tar- ing agent is dissolved. Initially, we experimented with
2
taric acid-derived boronate ester, with lithium borohydride homogeneous reducing systems in which the unmodified
(
LiBH ) to provide high enantioselectivities for aryl ketone NaBH is entirely dissolved. Because TarB-NO and its de-
4
4
2
[
28]
reduction. Reagent 1 and other variously substituted tar- rivatives are sensitive to ester hydrolysis by polar hydroxylic
taric acid-boronate esters are easily and quantitatively pre- solvents, our homogeneous reaction system was limited to
pared by combining tartaric acid with the appropriately less polar aprotic solvents. We investigated the use of the
substituted arylboronic acid in refluxing THF in the pres- solvents N-methylpyrrolidone (NMP), diglyme (DG), and
ence of CaH2 (Scheme 1). CaH2 acts to remove water tetraglyme (TG) to prepare homogeneous NaBH solutions
4
formed during esterification of the boronic acid and helps that were added dropwise to the ketone/TarB-NO mixture.
2
push the reaction to completion. A THF solution of the Of these solvents, highest ee values were obtained using a
TarB-NO reagent is obtained by filtering the reaction mix- NaBH /DG solution added dropwise to a premixed solu-
2
4
ture to remove the calcium salts. Ketone reductions can tion of the ketone substrate and reagent 1 in THF (Entry
then be caried out by using this TarB-NO solution with 3, Table 1).
2
lithium or sodium borohydride. Either enantiomer of the
product alcohol can be obtained by appropriate choice of
Table 1. Effects of solvents on enantioselectivities in the reduction
2 4
of acetophenone with ()-TarB-NO and NaBH under homogen-
(
)- or ()-tartaric acid for use in TarB-NO preparation.
[a]
2
eous conditions.
Routine workup allows rapid separation of the product
alcohol from TarB-NO with an easy procedure for recov-
2
ery of over 70% of the boronic acid. Other workers have
since made use of the TarB-NO reagent with LiBH to
2
4
complete difficult reduction steps.[
29,30]
[
a] Overall ratio of Solvent A to Solvent B was 1:1. Reactions car-
ried out by dropwise addition of NaBH /solvent B solution to
solution in solvent A at room temperature. A
/NaBH ratio of 1:2:2 was used except for the re-
4
ketone/TarB-NO
ketone/TarB-NO
2
2
4
action in tetraglyme where a 1:2:1 ratio was used. [b] Determined
by GC analysis with a Supelco BetaDex 120 column. All reactions
gave 100% conversion to according to the GC.
2
Scheme 1. Preparation of TarB-NO reagent.
Attempts to use diglyme as the solvent for both the
borohydride and ketone solutions resulted in lower ee (En-
While LiBH is quite effective when used with TarB-
4
try 4). While NMP was useful for solubilizing NaBH , we
4
NO , it is considerably more expensive and difficult to han-
2
[
31]
observed complete conversion of the ketone to the racemic
alcohol with some reduction of the pyrrolidone solvent to
a pyrrolidine (Entry 1). 11B NMR analysis of a mixture
of NaBH , TarB-NO and NMP showed formation of a
dle than NaBH4. Here we report the successful extension
of TarB-NO chemistry to inexpensive NaBH for the enan-
2
4
tioselective reduction of aromatic and aliphatic ketones at
room temperature through the intermediacy of a chiral so-
dium acyloxyborohydride active species. We describe sol-
vent effects on enantioselectivity and conversion, and pro-
pose a mechanism with supporting calculations.
4
2
BH :NMP adduct which we speculate to function as an
3
[
32]
achiral reducing species.
NMP was found to work
smoothly, however, when used with 3 parts THF to prepare
a homogeneous NaBH solution that could then be added
4
to the ketone substrate and TarB-NO in THF (Entry 2).
2
While affording good enantioselectivity, the use of both
NMP and DG required lengthy extractions to separate the
Results and Discussion
As part of our studies of TarB-NO -mediated reactions, product alcohols from these high-boiling solvents.
2
we decided to investigate the use of NaBH with reagent 1
Our survey of the literature found several indications that
4
for asymmetric reduction of ketones under both homo- and the use of NaBH under heterogeneous conditions in sol-
4
heterogeneous conditions. The reducing efficiency of modi- vents such as benzene, toluene, and THF could improve
[
7,12,22,33]
fied and unmodified NaBH is known to vary widely de- the enantioselectivities.
An explanation lies in the
4
pending on the solvent and the degree to which the reduc- solubility of the active reducing species. In a homogeneous
5290
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4 2
Asymmetric Reduction of Ketones with NaBH and TarB-NO
FULL PAPER
system, both chirally modified and unmodified achiral so- difficult to reduce with high induction. Using the same con-
dium borohydride may compete for the ketone substrate. In ditions reported for our reductions of aromatic ketones, we
solvents such as THF, however, only the chirally modified were able to obtain good results for the asymmetric re-
borohydride is soluble, thus limiting achiral reduction by duction of several aliphatic ketones. These results compare
unmodified borohydride. Based on this speculation, we favorably with similar results reported by other groups for
used a heterogeneous suspension of NaBH /THF. In our the asymmetric reduction of aliphatic ketones (Table 3).
4
optimized procedure, we added 2 equiv. of NaBH in a sin-
4
Table 3. Enantioselectivities for reductions of aliphatic ketones with
gle portion to a 1:2 ketone/TarB-NO solution in THF un-
2
(
2
)-TarB-NO . All ee values and conversions were determined by
GC analysis with a Chiral BetaDex 120 column.
der nitrogen at 25 °C. Addition of the NaBH causes a ra-
4
pid evolution of hydrogen gas which subsides after approxi-
mately fifteen minutes. The reaction is complete in less than
30 minutes and the product alcohol is obtained in very high
enantiomeric excess and with 100% conversion. We found
that this procedure is more convenient than using NMP or
DG and compares very favorably with a homogeneous
LiBH /THF system (Table 2).
4
Table 2. Enantioselectivities for reductions of aromatic ketones
with ()-TarB-NO . All products were of the (R) configuration as
2
determined by optical rotation. All ee values were determined by
GC analysis with a Chiral BetaDex 120 column. All reactions gave
100% conversion to the alcohol according to GC.
The relatively hindered dimethylcyclopentanone and pin-
acolone substrates were both reduced with excellent
enantioselectivity, while lower, though moderate optical in-
duction was obtained for the reduction of unhindered 2-
octanone. As with the aromatic substrates, we observed that
the heterogeneous NaBH system provided superior results
4
to those obtained using a homogeneous LiBH system.
4
Interestingly, the difference in solubility in THF between
NaBH and LiBH may explain the superior results ob-
4
4
tained with NaBH . Unmodified and achiral LiBH4 is
4
highly soluble in THF and may reduce the ketone achirally
before it reacts with TarB-NO to form the chiral acyloxy-
2
borohydride. On the other hand, unmodified and achiral
NaBH is essentially insoluble and, so, will not appreciably
4
reduce the ketone until it is brought into solution through
reaction with the TarB-NO reagent to produce the soluble,
2
chiral, and highly reactive acyloxyborohydride.
Based on 11B NMR and hydrogen evolution experiments,
the active reducing species responsible for the asymmetric
reduction in our system appears to be a chiral acyloxy-
borohydride. We have also observed indications of acyloxy-
borohydride formation when using TarB-X reagents with
[
34]
LiBH4.
Combination of borohydride reagents with car-
boxylic acids is known to provide variously substituted acy-
loxyborohydride species with concomitant production of
[
16,17,34,35,36]
hydrogen gas (Scheme 2).
The identity of the
dominant acyloxyborohydride reducing species depends
largely on the molar ratio between carboxylic acid and the
borohydride, though exact determination of the dominant
[
a] Isolated yields.
We also experimented with the TarB-NO system and ali- species is difficult.[16,17,37–39] Generally, triacyloxyborohy-
2
phatic substrates. Aliphatic ketones, especially unhindered, drides are the most easily prepared and characterized,
[
37,38]
straight-chain ketones such as 2-octanone, are notoriously though other stable mono-
and diacyloxyborohy-
Eur. J. Org. Chem. 2005, 5289–5295
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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D. B. Cordes, T. M. Nguyen, T. J. Kwong, J. T. Suri, R. T. Luibrand, B. Singaram
FULL PAPER
2
Scheme 2. Generation of a generic acyloxyborohydride and ()-TarB-NO monoacyloxyborohydride.
dride[39] species have been reported. In our procedure,
TarB-NO2 and NaBH4 are used in equimolar amounts,
which would tend to favor the formation of a single
monoacyloxyborohydride moiety per TarB-NO molecule
2
(
Scheme 2). The dominance of the monoacyloxyborohy-
1
1
dride is consistent with both B NMR spectroscopic data
from LiBH and NaBH titration experiments, and with
4
4
our observation that approximately 1 equiv. of H gas is
2
liberated in the first ten minutes after addition of equimolar
[34]
amounts of TarB-NO and NaBH .
2
4
Most often prepared and used in situ, acyloxyborohyd-
rides are known to facilitate numerous transformations of
oxygen- and nitrogen-containing functionalities in high
yield, though their deliberate employment in conjunction
with Lewis acids for asymmetric synthesis has been limited.
Scheme 3. Proposed mechanism for reduction of acetophenone by
TarB-NO
2
.
When used with borohydrides, TarB-NO (1) and related
2
reagents can combine the reducing efficiency of acyloxy-
borohydride species with the coordinating ability of chiral tion, the proximal complex shown in Figure 1 in which the
boron-Lewis acids to provide for the highly enantioselective carbonyl carbon of formaldehyde is closer to the carboxyl
reduction of ketones to secondary alcohols. We speculate group was calculated to be more stable than the distal com-
that the carbonyl oxygen of the prochiral ketone substrate plex (carbonyl carbon oriented away from carboxyl) by
coordinates to the boron of the TarB-X reagent, thus pref- 0.95 kcal/mol (B3LYP/6-31G*//B3LYP/6-31G*). Formation
erentially presenting one face of the ketone for attack by of the more stable proximal formaldehyde complex with the
an acyloxyborohydride moiety. Our proposed mechanism is TarB-NO analog was calculated to be exothermic by 6.6
2
given in Scheme 3. (HF/6-31G*//MP2/6-31G*) and 4.7 (HF/6-31G*//B3LYP/6-
The reduction of ketone substrates with borohydride rea- 31G*) kcal/mol.
gents occurs much more rapidly in the presence of carbox-
Addition of sodium borohydride results in loss of hydro-
ylic acids such as TarB-NO than without. In fact, while gen and the formation of a sodium complex (see Figure 2).
2
TarB-NO mediated reduction of acetophenone is complete Here, the proximal acyloxyborohydride/formaldehyde is cal-
2
in less than thirty minutes, the same reduction using only culated to be more stable than distal by 2.1 kcal/mol (HF/
NaBH in THF is only 10% complete after a half-hour and 6-31G*//MP2/6-31G*) and 1.4 kcal/mol (HF/6-31G*//
4
even after a full day the conversion only reaches 45%. B3LYP/6-31G*).
These differences indicate that there is a considerably lower
Three transition states (two proximal, one distal) corre-
activation energy for the TarB-NO2 acyloxyborohydride- sponding to the delivery of hydrogen from boron to the
mediated reduction. To better understand the implications carbonyl carbon were characterized. We found one transi-
of the proposed mechanism and to investigate the differ- tion state (proximal) to be lower in energy than the other
ences in activation energy, a series of computational studies two by more than 18 kcal/mol; its structure is shown in Fig-
were carried out. As a computational model for the reaction ure 2. In this favored transition state, the sodium has mi-
of TarB-NO with acetophenone, we examined the reaction grated away from the BH boron (4.07 Å), toward the di-
2
3
of 1,3,2-dioxoborolane-4-carboxylic acid with formalde- oxoborolane boron (3.12 Å), and is coordinated with the
[
40]
hyde (Figure 1).
With regard to initial complex forma- carbonyl oxygen (2.13 Å), a dioxoborolane oxygen (2.51 Å),
5292
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4 2
Asymmetric Reduction of Ketones with NaBH and TarB-NO
FULL PAPER
Figure 1. 1,3,2-Dioxoborolane-4-carboxylic acid and proximal formaldehyde complex (HF/6-31G*). Unlabelled atoms represent carbon.
Figure 2. Sodium complex and the proximal transition state (HF/6-31G*). Unlabelled atoms represent carbon.
and a carboxylate oxygen (2.25 Å). By contrast, in the each of the transition states shows a vibration correspond-
higher energy transition states the sodium is associated with ing to the shortening of the C–H bond, and corresponding
the two carboxylate oxygen atoms and the BH3 boron. lengthening of the B–H bond, as would be expected for
Proximity of the sodium ion with three oxygen atoms ap- transfer of H from B to C.
pears to be the key feature in stabilization of the favored
It is interesting to compare the activation energies for the
transition state. At the transition state, the forming C–H above reaction to the direct combination of formaldehyde
bond length is 1.46 Å, and the breaking B–H bond length and sodium borohydride in the absence of the TarB-NO2
is 1.33 Å, compared to a B–H length of 1.24 Å in the initial analog. For the direct combination of formaldehyde with
complex. The electron density surface shows that the B– NaBH the transition state occurs much later on the reac-
4
H bond has greater electron density than the C–H bond, tion coordinate with C–H and B–H bond lengths of 1.1 Å
indicating that this is an early transition state.[ The acti- and 2.2 Å respectively. The activation energy calculated at
vation energy for this process is calculated at 5.7 kcal/mol different levels of theory for this is 26.4 kcal/mol (HF/6-
41]
(HF/6-31G*//MP2/6-31G*) and 1.7 kcal/mol (HF/6-31G*// 31G*//MP2/6-31G*), 24.8 kcal/mol (HF/6-31G*//B3LYP/6-
B3LYP/6-31G*). For comparison, the corresponding value 31G*), and 25.0 kcal/mol (B3LYP/6-31G*//B3LYP/6-
calculated for the reaction of formaldehyde with lithium 31G*). These values do not take into account the effect of
aluminum hydride is 2.1 kcal/mol (B3LYP/6-31G**// solvent, which Eisenstein and co-workers have shown can
[
42]
[43]
B3LYP/6-31G**).
Normal mode vibration analysis for dramatically lower the calculated activation energy.
For
Eur. J. Org. Chem. 2005, 5289–5295
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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D. B. Cordes, T. M. Nguyen, T. J. Kwong, J. T. Suri, R. T. Luibrand, B. Singaram
FULL PAPER
1
comparison, the experimental activation energy for the re- Identities of alcohol products were confirmed using H NMR spec-
troscopy.
duction of acetone by sodium borohydride in water is
[
44]
7.6± 0.5 kcal/mol.
We conclude from these calculations Preparation of (
L)-TarB-NO : A 500-mL round-bottomed flask
2
that TarB-NO dramatically lowers the activation energy with sidearm and stir bar was oven-dried, cooled under nitrogen
2
and charged with 3-nitrophenylboronic acid (20.04 g, 120 mmol),
for reduction of ketones with borohydride reagents and pro-
vides a pathway for the hydride to be delivered in a stereose-
lective manner.
This reduction process appears to be analogous to reac-
tions involving enzymes, in the sense that the TarB-NO2
analog provides a complex with the substrate in which there
is a lower energy reduction pathway than in the absence
(
)-tartaric acid (18.00 g, 120 mmol) and CaH
2
(10.30 g,
24.5 mmol), sealed with a septum and fitted with a reflux con-
denser. Dry THF (240 mL) was added through the sidearm and
the system was refluxed for 1 hour followed by cooling. The sus-
pension was cannulated from the sealed reaction vessel to a sealed
medium frit filter under inert atmosphere to remove calcium salts.
The clear, yellow-brown solution was directly collected in an at-
of the TarB-NO analog. While our model formaldehyde tached, dry flask then transferred via cannula to a dry ampoule as
2
1
substrate is not prochiral, it follows from the calculations a 0.5  solution in THF. H NMR indicates that the yield is Ͼ98%.
2
and from observed data that the TarB-NO molecule is cap- TarB-NO solutions were stored in sealed ampoules at room tem-
2
perature and kept away from light. These stock solutions are stable
for as long as one year. (Note: TarB-X reagents are moisture-sensi-
tive. Air-sensitive techniques and dry glassware should be used in
their preparation and application.)
able of forming an analogous structure with prochiral sub-
strates thus providing a pathway to deliver hydride enantio-
selectively. From the calculated data, it appears that both
proximal and distal complexes can form rapidly and revers-
ibly, but that only the proximal complex leads to the favored
transition state. The special stabilization of this transition
state comes from the ability of the sodium ion to coordinate
with three oxygen atoms.
Representative Isolation Scale Procedure: A 200-mL round-bot-
tomed flask was flame-dried, cooled under N
acetophenone (1.16 mL, 10 mmol) and TarB-NO
0
2
, then charged with
(40 mL of a
.5  solution in THF, 20 mmol) and stirred for ten minutes.
2
NaBH
the ketone/TarB-NO
4
(0.755 g, 20 mmol), was then added in a single portion to
solution causing rapid gas evolution. The re-
2
action was left to stir for 30 min and then slowly quenched with
3  HCl until gas evolution was no longer observed. The mixture
was brought to pH 12 with 3  NaOH and extracted with diethyl
ether (3×50 mL). The combined ether extracts were washed with
DI H O (2×50 mL) and dried with MgSO . GC analysis with a
Conclusions
Aromatic ketones can be reduced quantitatively and with
a high degree of enantioselectivity using TarB-NO2 and
2
4
borohydride reducing agents. Significantly, inexpensive Supelco Beta-Dex 120 column revealed 100% conversion and 98%
NaBH can be used to provide results that are often supe- ee of (R)-1-phenylethanol. After solvent removal, the crude alcohol
4
rior to those obtained using LiBH . The reduction appears product was distilled under reduced pressure (60 °C, ca. 5 Torr) to
4
afford the pure product alcohol in 90% yield. The boronic acid
was recovered by acidification of the aqueous layer with 12  HCl
followed by chilling the solution at 4 °C. The boronic acid precipi-
tate was filtered and washed with pentane (2.40 g, 71% recovery).
to operate through an acyloxyborohydride intermediate and
we were able to obtain computational support for both the
intermediate and an analogous transition state structure.
Studies are in progress to expand the scope of reactions
promoted by this inexpensive, convenient, and easily pre-
pared TarB-X reagent. The concept of preparing chiral acy-
Computational Methods: Geometries of reactants, complexes, and
transition-state structures were optimized using ab initio molecular
orbital theory employing the Hartree–Fock 6-31G* basis set. All
loxyborohydrides from borohydrides and chiral bifunc-
transition states were characterized by having only one imaginary
tional reagents possessing both Lewis and carboxylic acids
may well provide a new approach to asymmetric synthetic
methodology.
frequency. Calculations were carried out using the SpartanЈ02 elec-
tronic structure program. Electron correlation is accounted for by
evaluating second-order Møller–Plesset and Becke 3LYP density
functional energies[ for the HF/6-31G* geometries.
45]
Supporting Information Available (for details see footnote on the
1
13
Experimental Section
first page of this article): Synthetic preparation and H, C, and
1
1
B NMR spectra for ()-TarB-NO
2
. Analytical scale procedures.
with
B NMR spectra from reaction in NMP solvent. Pro-
General: All reactions and transfers conducted in oven- or flame-
dried glassware under inert atmosphere using air-sensitive tech-
niques. All ketones purchased from Aldrich and used without puri-
Procedure and 11B NMR spectra from titrations of NaBH
TarB-NO .
2
4
1
1
cedure for hydrogen evolution experiments. Details of computa-
tional experiments and Figure of transition state electron density
surface.
2
fication. 3-nitrophenylboronic acid, CaH , and tartaric acid pur-
chased from Acros and used without purification. THF was dis-
tilled from Na benzophenone ketyl under nitrogen and stored in a
1
13
sealed ampoule before use. H NMR and C NMR spectra were
acquired with a Varian 500 spectrometer using [D ]THF (internal
[
1] For a review of CBS-catalyzed reductions see: E. J. Corey, C. J.
8
1
13
Helal, Angew. Chem. Int. Ed. Engl. 1998, 37, 1986–2012.
reference at δ = 1.73 ppm for H NMR and 25.4 for C NMR).
1
1
[2] For a review of both borohydride and aluminohydride re-
B NMR spectra were acquired using a Bruker 250 spectrometer
BF –Et O external reference at 0 ppm). Configurations deter-
ductions see: P. Daverio, M. Zanda, Tetrahedron: Asymmetry
(
3
2
2
001, 12, 2225–2259.
3] M. Periasamy, M. Thirumalaikumar, J. Organomet. Chem.
000, 609, 137–151.
mined using a Jasco DIP-370 polarimeter at 25 °C. Gas chromatog-
raphy analysis was performed with a Supelco Beta Dex 120 chiral
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4 2
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