31P NMR assays for rapid determination of enantiomeric excess in catalytic hydrosilylations and transfer hydrogenations

Article abstract of DOI:10.1016/j.tetasy.2009.01.022

Chiral chlorophosphine (S)-(1,1′-binaphthalen-2,2′-dioxy)chlorophosphine (S)-2 was tested for its performance as a chiral-derivatizing agent (CDA) using solutions of various alcohols, amines, and N-BOC amino acids. Based on ³¹P NMR spectroscopy, the enantiomeric excess was determined within less than 5 min per sample, reaching an accuracy of ±1%. One-pot procedures for a combination of the method with typical homogenous catalytic transformations of prochiral ketones were established. Hydrosilylation products may be analyzed after conversion into alcohols using HF bound to PS-vinyl pyridine co-polymer beads. Transfer hydrogenations simply require solvent evaporation prior to the use of the CDA.

Full text of DOI:10.1016/j.tetasy.2009.01.022

Tetrahedron: Asymmetry 20 (2009) 362–367
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Tetrahedron: Asymmetry
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31P NMR assays for rapid determination of enantiomeric excess in catalytic
hydrosilylations and transfer hydrogenations
*
Thomas Reiner, Frederik N. Naraschewski, Jörg Eppinger
Technische Universität München, Department Chemie, Lichtenbergstr. 4, D-85747 Garching, Germany
a r t i c l e i n f o
a b s t r a c t
Chiral chlorophosphine (S)-(1,10-binaphthalen-2,20-dioxy)chlorophosphine (S)-2 was tested for its perfor-
mance as a chiral-derivatizing agent (CDA) using solutions of various alcohols, amines, and N-BOC amino
acids. Based on 31P NMR spectroscopy, the enantiomeric excess was determined within less than 5 min
per sample, reaching an accuracy of 1%. One-pot procedures for a combination of the method with typ-
ical homogenous catalytic transformations of prochiral ketones were established. Hydrosilylation prod-
ucts may be analyzed after conversion into alcohols using HF bound to PS-vinyl pyridine co-polymer
beads. Transfer hydrogenations simply require solvent evaporation prior to the use of the CDA.
Ó 2009 Elsevier Ltd. All rights reserved.
Article history:
Received 10 December 2008
Accepted 20 January 2009
Available online 13 March 2009
1. Introduction
solvents with good sensitivity, narrow line width, large chemical
shift dispersion, responsiveness to structural changes in diastereo-
Rapid progress in asymmetric synthesis and increasing demand
for enantiopure compounds require development of accurate and
reliable techniques for the determination of enantiomeric excess
(ee).1–3 Currently, accurate analyses of mixtures of enantiomers
are dominated by chromatographic methods.2 Progress has been
made in the rapid analysis of enantiomers by chiral GC, which
has become a powerful tool for high throughput ee determination.3
However, problems arise from decomposition or racemization at
elevated temperatures.4 Hence, the advent of combinatorial meth-
ods for asymmetric catalysis triggered the progress of several alter-
native approaches.3,5,1a Recent reports of rapid assays cover a
broad range of technologies including reaction microarrays,6 mass
spectrometry,7 imprinted polymers,8 supramolecular systems9 as
well as chromogenic,10 enzymatic,11 or immuno assays.12 Specifi-
cally NMR-based determinations of ee have gained interest, due
to the speed and simplicity of the related protocols.13 These rely
on the use of chiral shift reagents,14 chiral transition metal com-
plexes,15 or chiral-derivatizing agents (CDAs/CSAs).13,16 In particu-
lar, CDAs have become of great importance for the analysis of
configuration and enantiomeric excess.17 Discrete diastereomers
generated by this method show chemical inequivalent shifts that
are typically five times higher than the use of other chiral re-
meric adducts, and the simplicity of broad band decoupled 31P
NMR spectra.20
In spite of their favorable properties, to the best of our knowl-
edge there are very few reports about the applications of phospho-
rus-based CDAs in catalyst screening. We attribute this fact to the
high sensitivity of these reagents towards protic and nucleophilic
components, which are typical for protocols of many asymmetric
catalytic reactions, for example, transfer hydrogenations or hydro-
silylations. However, a reactive functionality is intrinsic for an
effective conversion of alcohol, amine, or carboxylic acid-directed
CDAs. Hence, the key to a rapid CDA-based evaluation of asymmet-
ric catalysts is post-catalytic procedures, which efficiently remove
unwanted reactive components without necessitating demanding
or expensive sample preparation.
We here report an efficient protocol for 31P NMR-based determi-
nation of enantiomeric excess in catalytic reactions. This protocol
utilizes the BINOL-derived CDA (S)-2 or (R)-2 introduced by Tang
and co-workers for discrimination of chiral alcohols or amines,
which is comfortably available from economic precursors (Fig. 1).21
agents.13 Since Mosher introduced MPTA (
a-methoxy-a-(trifluoro-
O
O
PCl3
OH
OH
P
Cl
methyl)-phenylacetic acid) for the resolution of chiral amines in
1969,18 a broad range of reagents have been used to monitor the
respective diastereomeric shifts by 1H and heteronuclear NMR
spectroscopy.13,19 Of all nuclei applied, 31P seems to be most
attractive since it combines the economic use of non-deuterated
1
2
(S)-
(R)-1
(S)-
(R)-2
* Corresponding author. Tel.: +49 89 289 13097; fax: +49 89 289 13473.
E-mail address: joerg.eppinger@ch.tum.de (J. Eppinger).
Figure 1. Synthesis of chiral-derivatizing agents (R)- and (S)-(1,10-binaphthalen-
2,20dioxy)chlorophosphine (S)-2 and (R)-2.21
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.01.022

T. Reiner et al. / Tetrahedron: Asymmetry 20 (2009) 362–367
363
Table 1
2. Results and discussion
31P NMR chemical shift d and shift differences
D
d in ppm of products formed from (S)-
(1,10-binaphthalen-2,2’dioxy)chlorophosphine (S)-2 and alcohols, amines, or amino
(1,10-Binaphthalen-2,20-dioxy)chlorophosphines (S)-2 and (R)-2
are availible in a one-step one-day synthesis from trichlorophos-
phine and (R)- or (S)-BINOL, respectively (Fig. 1).21 The chiral-
derivatizing agents are obtained in quantitative yield and can be
stored under argon for months without any sign of decomposition.
In the presence of a tertiary amine such as NEt3, CDAs (S)-2, or (R)-
2 react cleanly with alcohols, amines, or carboxylic acids to the
respective phosphite derivatives. Since the phosphorus atom is lo-
cated on the C2-axis of the chelating BINOL-frame, it is not stereo-
chemically active and only two diastereomers can be formed
(Fig. 2). Correspondingly, for non-enantiopure samples, two reso-
nances were observed by 31P NMR, which exhibit identical chemi-
cal shifts for either enantiomer of the CDA. Hence, in contrast to
chiral GC or HPLC, the signal originating from each enantiomer of
a compound can be assigned by conversion of an enantiomerically
pure sample with both enantiomers of the CDA.
acids
Entrya
Substrate
(R,S)//(S,R)
(S,S)//(R,R)
Dd
OH
1
141.03
147.65
6.62
6.72
*
Cl
OH
Ph
2
144.01
137.29
*
2-Naph
OH
3
4
143.90
137.41
138.03
137.43
5.87
0.02
*
Ph
*
OH
Ph
OH
*
5
6
135.61
142.93
140.80
143.85
5.19
0.92
(R)
(S)
(R)
(S)
O
P
O
P
O
P
O
P
E
O
E
O
E
O
E
O
(R)
(S)
(S)
(R)
OH
*
R
R'
R
R'
R
R'
R
R'
6
enantiomers
enantiomers
NH2
7
8
151.11
150.04
149.10
146.37
2.01
4.46
*
Ph
diastereomers
NH2
*
Figure 2. Illustration of the correlation between structure and observed 31P NMR
resonances. E = O, NH, COO.
1-Naph
The two diastereomeric 31P NMR signals for both enantiomers
of the compounds tested are listed in Table 1. Except for entry 4,
base line separation of the signals was achieved on a 400 MHz
NH2
*
9
145.67
150.13
4.46
spectrometer in all cases. In general,
strates possessing an aryl group on the
D
d values are highest for sub-
-carbon, and decrease
a
NH2
*
depending on the nature of the functionality in the order: alco-
hols > amines > carboxylic acids. For benzylic alcohols, diastereo-
meric shifts ranging from 6.72 to 5.19 ppm were observed
(entries 1–4). Smaller signal separation results for benzyl amines
(4.46–2.01 ppm, entries 7 and 8). For aliphatic compounds diaste-
reomeric signals are split by less then 1 ppm. The observed trend is
in agreement with values reported for other compounds.21 Broad-
ening the scope of the method, we found that CDAs (S)-2/(R)-2 are
also well suited to determine the configuration and enantiomeric
excess of carboxylic acids. We therefore tested a range of N-pro-
10
11
152.49
151.28
152.17
151.56
0.32
0.28
Cy
NH2
*
12
13
14
15
Boc-Ala-OH
Boc-Ile-OH
Boc-Leu-OH
Boc-Val-OH
140.56
139.14
139.48
139.00
141.80
141.11
141.06
140.57
1.24
1.97
1.51
1.58
tected amino acids, which show
spite the broad applicability, the method tested encounters some
Dd values larger than 1 ppm. De-
a
Conditions: CDA/substrate/Et3N = 2:1:4. Solvent: THF.
limitations. For an alcohol with a stereogenic center at the b-posi-
tion (entry 4), the observed
Dd value of 0.02 ppm does not give
base line separation of the signals. Compounds with more than
one CDA-reactive functional group such as diols, amino alcohols,
diamines, or unprotected amino acids lead to complex signal pat-
terns, which cannot be used for quantification of enantiomeric
excess.
We examined the accuracy of the method over the full range of
enantiomeric ratios probing samples of known ee, which were re-
ceived by mixing enantiomerically pure (R)- and (S)-1-phenyl eth-
anol (Fig. 3). Differences between determined and theoretical
values are less than 1%, and do not show any systematic trend.
While conversion of CDAs (S)-2 or (R)-2 with all nucleophiles
tested is completed within less than 5 min, kinetic resolution im-
pairs quantifications of enantiomeric ratios, if the CDA is the limit-
ing component. Thus, for racemic 1-phenylethanol 63% ee (S) is
derived from 31P NMR analysis, if a (S)-2/alcohol ratio of 1:20 is ap-
plied. Using excess of (S)-2 leads to correct values. To account for
this effect, samples, which might still contain substances consum-
ing the chlorophosphite reagent, a CDA/product ratio of at least
1.5:1 was applied.
Generally, the use of deuterated solvent is not necessary for cat-
alytic runs, as 31P NMR shifts can be referenced to the signal of ex-
cess CDA. Due to the good NMR sensitivity of the 31P nuclei, only
500 lL of a 36 mM substrate solution are necessary to obtain sat-
isfactory signal to noise ratio after 150 pulses, which translates
to a measurement time of less than 5 min. Such product concentra-
tions are typical for catalytic screenings.
Having established the scope and accuracy of the method, we
examined its applicability for on-line ee determination in combi-
nation with standard catalytic protocols. Asymmetric hydrosilyla-
tion has become a versatile tool for the synthesis of chiral

364
T. Reiner et al. / Tetrahedron: Asymmetry 20 (2009) 362–367
excesses detected, ees values of up to 81% for the CuH/BINAP sys-
tem were seen. The CuH catalysts, which have been developed
based on the original ‘Styker’s reagent’ by Lipshutz et al. and Yun
et al. were generated in situ from Cu(OAc)2, diphenyl silane and
chiral diphosphines.24,25 Controls revealed a divergence of less
than 2% for the enantiomeric excess determined using CDA 1 in
the one-pot procedure versus values obtained by chiral GC. The ob-
served ees correspond well with available literature values; for
example, Yun et al. reported 79% ee (S) for conversion of acetophe-
none using CuH/BINAP at 0 °C in toluene.25 Our slightly reduced ee
(entry 1 in Table 2) may be attributed to the higher reaction tem-
perature and a change of solvent. Interestingly, determination of
yields based on the consumption of the defined amount of CDA
added differed by less then 7% from GC-derived values. Thus, in
catalytic hydrosilylations, CDA (S)-2 can be applied for 31P NMR-
based parallel quantification of enantiomeric excess and reaction
yields.
Figure 3. Correlation between theoretical and calculated enantiomeric excess for
defined mixtures of (R)- and (S)-1-phenyl ethanol. The latter were calculated from
the integral ratios of the respective diastereomeric 31P NMR resonances after
conversion with (S)-2.
alcohols.22 Here, the originally produced silanols need to be con-
verted to alcohols prior to application of the CDA.23 Generally,
small quantities of water present in reagents or solvent consume
the CDA under formation of the oxo-bridged dimer 3rac, giving rise
to an intense signal at 134.23 ppm. (3meso is formed additionally
from racemic mixtures of CDA; d(31P) = 133.11 ppm). To minimize
the excess of CDA required, anhydrous proton and fluoride-based
cleavage protocols were investigated, including addition of pTsOH,
trifluoroacetic acid, or tetrabutyl ammonium fluoride in alcoholic
or THF solution. The cleanest and most effective method turned
out to be fluoride-induced desilylation with HF bound to PS-vinyl
pyridine co-polymer beads (SP-py/HF). Conversion is completed
within 10 min after which the solid-phase reagent can conve-
niently be removed by filtration. Figure 4 depicts the reaction se-
quence applied for the CDA-based evaluation of the asymmetric
hydrosilylation catalysts. With the exception of 6 all catalysts
tested achieve high to near quantitative conversion within 24 h
(Table 2). Unsurprisingly, no asymmetric induction was found
using achiral NHC–Rh(I) systems 5 and 6. For all enantiomeric
P
O
O
O
O
O
P
(S,S)-3rac
In addition to asymmetric hydrosilylation, Rh and Ru catalyzed
transfer hydrogenations have developed into a versatile tool for the
generation of chiral alcohols from prochiral ketones.26 Thus, we
investigated options to apply CDA (S)-2/31P NMR-based determina-
tion of enantiomeric excess in combination with typical transfer
hydrogenation protocols. Initial investigations revealed that for
procedures employing aqueous formate as a reducing agent, te-
dious work-up procedures or residual water limited the usability
of our technique. A common method for transfer hydrogenations
uses catalysts generated in situ from precursors such as [(g
6-are-
ne)RuCl2]2 or [(Cp*)RhCl2]2 and amino alcohols in iPrOH as solvent
and hydrogen sources.26,27 The high reactivity of the P–Cl moiety in
(S)-2 toward alcohols requires complete removal of the solvent
O
SiHPh2
R'
1. SP-py/HF
(S)
+ H2SiPh2, r.t.
2
P
2. 1.5 eq. (S)- ,
O
O
(THF)
O
O
3.0 eq. NEt3
*
[Cu(OAc)2/L] or [Rh]
*
R
R'
R
R
R'
P
P
PPh2
P(o-tol)2
PPh2
PPh2
PPh2
L=
Fe
PPh2
(S)-BINAP
(-)-NorPhos
(R,R)-Me-DuPHOS
(R,S)-PPF-P(o-tol)
L1
L2
L3
L4
tBu
Ph
Rh
Mes
N
N
N
N
Rh
Cl
Rh
[Rh]=
N
N
Cl
Cl
tBu
4
Mes
5
6
Ph
Figure 4. Hydrosilylation of ketones employing chiral copper24,25 or rhodium29,30 catalysts. For results see Table 2.

T. Reiner et al. / Tetrahedron: Asymmetry 20 (2009) 362–367
365
Table 2
example, Wills et al. reported ees of 91% (S) and 86% (S) for conver-
sion of acetophenone and acetonaphthone, respectively, using the
other enantiomers of L6 in combination with [(p-cymene)RuCl2]2
under similar conditions.27
Results for the hydrosilylation of prochiral ketones (see Fig. 4)
a
Entry
Catalystb
Ketonec
Yieldd (%)
eee (%)
1
2
3
4
5
6
7
8
9
10
11
12
14
15
16
17
18
19
20
Cu(OAc)2/L1
Cu(OAc)2/L1
Cu(OAc)2/L1
Cu(OAc)2/L2
Cu(OAc)2/L2
Cu(OAc)2/L2
Cu(OAc)2/L3
Cu(OAc)2/L3
Cu(OAc)2/L3
Cu(OAc)2/L4
Cu(OAc)2/L4
Cu(OAc)2/L4
4
K1
K2
K3
K1
K2
K3
K1
K2
K3
K1
K2
K3
K1
K2
K3
K1
K2
K1
K2
>99
>99
>99
86
79
79
92
90
85
>99
>99
>99
70
98
72
>99
>99
78
75 (S)
81 (S)
81 (S)
20 (S)
24 (S)
39 (S)
33 (R)
47 (R)
42 (R)
46 (S)
51 (S)
48 (S)
1 (S)
15 (S)
9 (S)
0
3. Conclusion
BINOL-derived chiral-derivatizing reagents (S)-2 and (R)-2 are
well suited for the 31P NMR-based determination of enantiomeric
excess in solutions containing chiral alcohols, amines, or amino
acids. The accuracy of the method has been verified. Maximum
deviations from theoretical values were less than 1% in all cases
tested with a total acquisition time for the 31P NMR of less than
5 min. The technique can be used in combination with standard
protocols for catalytic asymmetric hydrosilylations and transfer
hydrogenations of prochiral ketones, without introduction of te-
dious work-up procedures. Conversion of the hydrosilylation prod-
ucts into alcohols is easily achieved using hydrogen fluoride
coordinated to pyridine on solid support, while the chiral alcohols
from transfer hydrogenations can directly be analyzed after re-
moval of all volatiles. The one-pot protocols established here are
straight forward to parallelize. Due to a unique combination of par-
allel workup, inexpensive reagents, and non-deuterated solvents as
well as short 31P NMR acquisition time, the method seems to be
advantageous for enantiomeric excess determination in catalyst
screenings and may easily be extended to other phosphorus-based
CDAs.20
4
4
5
5
0
0
0
6f
6f
98
a
Reaction time 24 h.
L1–L4 see Figure 4.
K1: acetophenone, K2: 2-acetonaphthone, K3: 1-indanone.
b
c
d
Conversions determined by GC against diethyleneglycol dibutyl ether (internal
standard).
e
Ees determined by 31P NMR spectroscopy using CDA (S)-2.
Reaction time 7 days.
f
Table 3
Results for the transfer hydrogenations of prochiral ketones (see Fig. 5)
4. Experimental
Entrya
Catalystb
Ketonec
Yieldd (%)
eee (%)
1
2
3
4
5
6
7
8
9
[Ru]/L5
[Ru]/L5
[Ru]/L5
[Rh]/L5
[Rh]/L5
[Rh]/L5
[Rh]/L6
[Rh]/L6
[Rh]/L6
K1
K2
K3
K1
K2
K3
K1
K2
K3
64
91
88
57
68
74
69
82
69
89 (R)
85 (R)
93 (R)
73 (R)
78 (R)
81 (R)
28 (S)
21 (S)
33 (S)
4.1. General remarks
All reactions were performed under an argon atmosphere using
standard Schlenk glassware or a glove-box. NMR measurements
were recorded on JEOL JNM-GX 400. 31P NMR chemical shifts are
reported relative to external phosphoric acid (d = 0.0 ppm).
Cu(OAc)2ꢀH2O, amino alcohols, phosphine ligands, (S)-BINOL (R)-
BINOL, and all chiral alcohols, amines as well as amino acids were
obtained from commercial sources and used without further puri-
fication. Complexes 4–6 were synthesized according to literature
procedures.28–30 Derivatizing agents (S)- and (R)-(1,10-binaphtha-
len-2,20-dioxy) chlorophosphine (S)-2 and (R)-2 were synthesized
as described previously.21
a
Reaction time 2 h.
[Ru] = [(p-cymene)RuCl2]2, [Rh] = [(Cp*)RhCl2]2; L5, L6 see Figure 4.
K1: acetophenone, K2: 2-acetonaphthone, K3: 1-indanone.
b
c
d
Conversions determined by GC against diethyleneglycol dibutyl ether (internal
standard).
Ees determined by 31P NMR spectroscopy using CDA (S)-2 .
e
4.2. Derivatization of (R)- or (S)-(1,10-binaphthalen-2,20-
dioxy)chlorophosphine 1 with amines, alcohols, amino acids,
and phosphorus acids
prior to the addition of the CDA, which can most easily be achieved
by evaporation. The resulting protocol is depicted in Figure 5.
Using amino alcohol L5, good to high enantiomeric excess was ob-
served in combination with both transition metal catalyst precur-
sors, with Ru being slightly superior to Rh. Chiral induction
resulting from less rigid L6 was poor. Again, obtained results corre-
spond well with GC control and available literature values. For
(S)-(1,10-Binaphthalen-2,2’-dioxy)chlorophosphine (CDA (S)-2,
63 mg, 0.18 mmol) and triethylamine (48
lL, 0.36 mmol) were dis-
solved in 600 L THF. After the addition of the chiral racemic or
l
enantiomerically pure nucleophilic reagent (0.12 mmol), triethyl-
1. [M] / L = 1 / 1
1. evaporate
2. 1.5 eq. (S)- (THF)
3.0 eq. Et3N
(iPrOH), 2h, 40 ºC
2
O
P*
O
OH
*
2. iPrOK, 2 h, r.t.
O
O
R'
R'
R
R
*
R
R'
[M] = [(p-cymene)RuCl2]2, [Cp*RhCl2]2
L =
OH
L5 NH2
Figure 5. Transfer hydrogenation of ketones employing in situ-generated chiral Ru(II) or Rh(III) catalysts. For results see Table 3.
OH
NH2
L6

366
T. Reiner et al. / Tetrahedron: Asymmetry 20 (2009) 362–367
ammonium chloride was allowed to settle, before the reaction
mixture was analyzed by 31P NMR spectroscopy.
Acknowledgments
The authors are grateful to Professor W. A. Herrmann for gener-
ous support. We thank the Stifterverband für die deutsche Wissen-
schaft (Projekt-Nr. 11047: ForschungsDozentur Molekulare
Katalyse), the Elitenetzwerk Bayern (graduate fellowship for T.R.)
and the IDK NanoCat for funding.
4.3. NMR parameters
To achieve high accuracy in the quantification of NMR signals, a
p
/2 pulse delay of five times the longest T1 has to be maintained.31
However, T1 values may exceed 10 s for phosphites.32 Additional
effects like different variations in NOE signal enhancement for
broad band decoupled heteronuclear experiments or non-linear
instrumental responses may hamper comparability of quantifica-
tions for different resonances. Using 1-phenyl ethanol as a test sys-
tem, we achieved variances <1% for the diastereomers resulting
from conversion with CDA (S)-2 after using the following parame-
ters: relaxation delay: 2 s, x-offset: 100 ppm, x-sweep: 200 ppm,
pulse angle: 45° acquisition time: 1 s.
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l
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and 500
ethylamine (48
l
L THF containing CDA (S)-2 (63 mg, 0.18 mmol) and tri-
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ketone (0.12 mmol) and bis(ethyleneglycol) dibutylether
(0.06 mmol) in 0.5 mL THF was added. After stirring the solution
for the time given in Table 2, the silyl ether was cleaved using
HF/pyridine on solid phase (3 equiv based on amount of silane).
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l
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and 500
ethylamine (48
l
L THF containing CDA (S)-2 (63 mg, 0.18 mmol) and tri-
L, 0.36 mmol) were added. Triethylammonium
l
chloride was allowed to settle, before the reaction mixture was
analyzed by 31P NMR spectroscopy.
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(see Ref. 20a). However, a mixture of CDA (S)-2 and the diphenylsilyl ether of
1-phenylethanol is virtually inert at room temperature, while heating to 70 °C
results in formation of several species as judged by 31P NMR.
A solution of the catalyst precursor {A: [(Cp*)RhCl2]2 (0.15 mg,
0.24
the respective amino alcohol (0.48
(0.3 mL) were placed in a glass vial equipped with a stirring bar
and warmed to 40 °C for 2 h. Then, solution of ketone
l
mol) or B: [(p-cymene)RuCl2]2 (0.14 mg, 0.24
lmol)} and
l
mol), dissolved in isopropanol
a
(0.12 mmol) and bis(ethyleneglycol) dibutylether (0.06 mmol) in
0.5 mL THF was added, before the reaction was started by addition
of potassium isopropanolate (5 lL of a 0.2 M solution in isopropa-
nol). After 2 h, the reaction was quenched with acetic acid (0.2 mL,
3 mmol), and volatiles were removed in vacuo. The residue was
redissolved using 600
0.18 mmol) and triethylamine (48
l
L
THF containing CDA (S)-2 (63 mg,
L, 0.36 mmol). Triethylammo-
l
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was analyzed by 31P NMR spectroscopy.

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