Adducts of rhodium(II) tetraacylates with methionine and its derivatives: 1H and 13C nuclear magnetic resonance spectroscopy and chiral recognition

Article abstract of DOI:10.1016/j.tetasy.2010.08.010

Complexation of rhodium(II) dimeric tetraacylates: tetraacetate Rh ₂AcO₄, tetratrifluoroacetate Rh₂TFA₄ , and (S)-Mosher's acid salt Rh₂MTPA₄ with both enantiomerically pure and racemic met

Full text of DOI:10.1016/j.tetasy.2010.08.010

Tetrahedron: Asymmetry 21 (2010) 2346–2355
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
1
Adducts of rhodium(II) tetraacylates with methionine and its derivatives: H
1
3
and C nuclear magnetic resonance spectroscopy and chiral recognition
Rafał Głaszczka , Jarosław Ja z´ wi n´ ski , Bohdan Kamie n´ ski a,b, Monika Kami n´ ska c
a
a,
⇑
a
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland
Institute of Physical Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland
The Faculty of Chemistry, University of Warsaw, ul. Pasteura 1, 02-093 Warsaw, Poland
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 July 2010
Accepted 12 August 2010
4
Complexation of rhodium(II) dimeric tetraacylates: tetraacetate Rh AcO , tetratrifluoroacetate Rh TFA ,
2
4
2
2 4
and (S)-Mosher’s acid salt Rh MTPA with both enantiomerically pure and racemic methionine and its
derivatives: hydrochloric salt of methionine, hydrochloric salt of methionine methyl ester, N-formyl
methionine, N-phthaloyl methionine, N-phthaloyl methyl ester of methionine, and methyl ester of N,N-
1
13
1
dimethylmethionine has been investigated by means of H and C nuclear magnetic resonance ( H
1
3
and C NMR) and absorption electronic spectroscopy in the visible range. Complexation processes were
investigated in D O or CDCl solutions, depending on the ligands’ and rhodium salts’ solubilities. Some
2
3
1
3
15
supporting measurements were performed in the solid phase, using C and N CPMAS NMR techniques.
All ligands investigated form 1:1 and 1:2 adducts in the solution, depending on the rhodium salt to
ligand molar ratios. The complexation site in the ligands (S atom) was deduced on the basis of the
NMR parameter adduct formation shift (
D
d = dadduct À dligand) and calculated chemical shifts (DFT, NMR
GIAO). In the cases of the Rh TFA and Rh
2
4
2
MTPA
4
adducts, decreasing the temperature within the range
2
20–254 K slowed down the ligand exchange and allowed us to observe the signals of all diastereoiso-
1
13
mers in the H and C NMR spectra.
Ó 2010 Elsevier Ltd. All rights reserved.
1
. Introduction
have been determined by a ‘dirhodium method’, using enantiome-
rically pure rhodium salts of Mosher’s acid (Rh MTPA ) as auxiliary
It has been mentioned that rhodium tetraacetate
formed a 1:2 axial adduct with methionine via the sulfur atom.
Cysteine, another amino acid bearing a sulfur function, irreversibly
2
4
1
9
Dimeric rhodium(II) salts are known to form adducts with a
reagents.
large number of organic ligands.1 These adducts as well as dirho-
dium salts have been widely used in organic chemistry as cata-
lysts;
species;
Furthermore, rhodium(II) dimeric salts have appeared to be active
as DNA replication inhibitors, and have been tested as anticancer
agents. The interaction of dirhodium salts with DNA bases, dinu-
cleotides, and oligonucleotides has been the subject of numerous
work; recent examples include published papers concerning
experimental studies and theoretical considerations.14–18 The
application of rhodium(II) salts in medicine justified the extension
of our research to adducts with biological importance, such as pep-
tides or amino acids.
2
–4
as auxiliary reagents in the spectroscopy of organic
replaced all the l-acetates in the dirhodium salt producing an
5
–11
and as building blocks in supramolecular chemistry.12
13,20
equatorial adduct.
Our previous works on dirhodium complexes include 1H, 13C,
and 1 N NMR studies of adducts with amines and heteroaromatic
5
1
3
21–27
ligands in CDCl
3
solution.
Chloroform was the solvent of
choice, due to the inability of adduct formation with a rhodium
salt. In contrast, solvents such as water, methanol, dimethylsulfox-
ide or acetonitrile were considered as less convenient because of
the formation of their own adducts with metal salts, and competi-
tion with the ligands. Nevertheless, these solvents have been
2
8,29
applied in special cases.
Herein we report the interaction of
A few papers have been devoted to rhodium(II) adducts with
amino acids. Rhodium(II) dimeric tetraacylate containing four pro-
dirhodium tetraacylates with methionine and some of their deriv-
atives. Since methionine was not soluble in chloroform, some
measurements were performed in a water solution. Water was in-
cluded in our investigations because of its importance in biological
applications. The present work is focused on the application of nu-
clear magnetic resonance spectroscopy (NMR) to the investigation
of the complexation process, and on the exploration of phenomena
related to chirality and chiral recognition.
line molecules in equatorial positions has been applied as a chiral
catalyst.3 The absolute configurations of a few
,4
a-amino acids
⇑
Corresponding author. Tel.: +48 22 3432014; fax: +48 22 6326681.
E-mail addresses: jarjazw@icho.edu.pl, jard@o2.pl (J. Ja z´ wi n´ ski).
0
957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.08.010

R. Głaszczka et al. / Tetrahedron: Asymmetry 21 (2010) 2346–2355
2347
2
. Results and discussion
and depends on the ligand to substrate molar ratio, concentrations,
temperature etc. This generally occurred for our measurements
The following dirhodium salts were used as substrates: tetra-
taken at room temperature, namely the complexation of Rh
in D O and CDCl . In contrast, experiments in a slow exchange
regime, when the signals of all the species are visible, provide
proper adduct chemical shifts and d. Such parameters character-
ize the adduct and remain invariable for a given solvent. This was
the case for the Rh MTPA and Rh TFA adducts, which were stud-
2 4
AcO
acetylate Rh
2
AcO
4
, trifluoroteraacetylate Rh
2
TFA4, and the enantio-
MTPA (Fig. 1).
2
3
merically pure salt of Mosher’s acid [(S)-isomer] Rh
2
4
Both enantiomers of methionine and its derivatives were applied
as ligands. The measurements were performed either in water or
in chloroform, depending on the ligand solubility. Experimental
and calculated NMR chemical shifts are shown in Table 1 and
Figure 3.
D
2
4
2
4
ied at decreased temperatures. In order to clarify the discussion
and in order to avoid mistakes, we denoted the first parameter as
Complexation conditions depended on the substrate and ligand
solubility. If both the substrate and ligand were soluble, the com-
position of the solutions depended only on the amount of reagents
Dd and the second as Ddadd. In the text, sample compositions were
given as a rhodium salt to ligand molar ratio (see Section 4 for
details). The NMR data for the ligands and adducts are shown in
Table 1.
added. These occurred for Rh
Rh TFA and Rh MTPA in CDCl
was poorly soluble in CDCl and practically all of the salt was de-
2
AcO
4
and Rh
2
TFA
4
in D
2
O and for
2
4
2
4
3
solutions. In contrast, Rh
2
AcO
4
2 4 2
2.1. Complexation of 1, 1-HCl and 2-HCl with Rh AcO in D O
3
posed on the bottom of NMR tube. The salt could only appear in
the solution as an adduct. Consequently the solution contained ad-
ducts and/or ligand excess and the composition of the solution de-
pended on the equilibrium between the soluble and insoluble
materials.
The appearance of NMR spectra depended on the ligand ex-
change rate. Fast ligand exchange (on an NMR timescale) resulted
in chemical shift averaging and, sometimes, in signal broadening.
These usually occur for NMR measurements performed at room
temperature. Consequently, the signals of the individual species
in the solution were not observed; quite often the spectra were dif-
ficult to interpret. In contrast, slow ligand exchange allowed us to
observe the signals of individual adducts in the solution. Slowing
down the exchange process was achieved by measurements at a
decreased temperature. The complexation process was quantified
Methionine 1, the hydrochloric salt of methionine 1-HCl and the
hydrochloric salt of methionine methyl ester 2-HCl were the first
ligands we investigated. All of these ligands are soluble in water
and insoluble in chloroform, which was the solvent of choice in
2
1–27
our previous investigations.
Water forms its own adducts
(dihydrates) with dirhodium salts and competes with the ligand.
Despite these inconveniences, the complexation occurred in water:
the addition of the ligand to a Rh AcO solution caused a color
2 4
change from blue to red. Titration experiments monitored by elec-
tronic absorption spectroscopy in the visible range (vis) (Fig. 2), re-
vealed the formation of at least two species in solution,
presumably the 1:1 and 1:2 adducts. At the beginning of the titra-
2 4
tion, the curves arising from the adduct crossed the Rh AcO
absorption line at 588 nm; then band intensities increased and
an isosbestic-like point appeared at 571–573 nm, due to the con-
version of the 1:1 adduct to the 1:2 adduct. All three ligands be-
haved similarly. It should be mentioned that in the case of HCl
by a parameter adduct formation shift
between chemical shifts of a signal in an adduct and the corre-
sponding signal in non-complexed (free) ligand (
ligand, in ppm). It should be noted that this parameter has in prac-
Dd, defined as a difference
D
d = dadduct
À
À
d
salts, the Cl anion should also be considered as a ligand.
tice two slightly different meanings, depending on the NMR data
used for the calculation. Under fast exchange conditions the signals
appear in averaged positions and the chemical shifts of the adduct
are not available; instead, signals derived from the equilibrium
mixture of the adduct and free ligand are observed. Consequently,
2 4
Titration experiments (from 1:0.5 to 1:2.5 Rh AcO to ligand
molar ratio) were repeated using NMR spectroscopy. Due to the
1
fast ligand exchange, H NMR spectra showed one set of signals
in averaged positions; that is, there were no signals of individual
species (1:1 and 1:2 adducts) in the spectra. The largest d was ob-
D
D
d is always equal to or smaller than the
D
d of the adduct alone,
served for the 1:0.5 sample; only a small decrease in Dd occurred
R
O
O
S
R'
S
R'
R
O
O
O
O
O
O
O
NR2
N
Rh
Rh
O
O
O O
1 R = H, R' = H
O
2
R = H, R' = CH
3
R
7 R = R' =CH
3
R
Rh AcO
(R = CH )
3
2
4
4
4
5
R' = H
R' = CH3
Rh TFA
(R = CF )
3
2
Rh MTPA (R = CPh(CF )(OCH ))
2
4
3
3
O
O
S
Me
O
OH
O
NH
O
NH
H
3
H
6
Figure 1. Dirhodium salts and ligands studied. The arrows mark the axial positions in the dirhodium salts, that are able to bond to organic ligands.

2
348
R. Głaszczka et al. / Tetrahedron: Asymmetry 21 (2010) 2346–2355
Figure 2. Absorption electronic spectra (visible range) of Rh
hydrochloride salt of methionine methyl ester 2-HCl (c). Green curves correspond to Rh
ligands in the molar ratio from 1:0.25 to 1:2.5 (step 0.25). Rh
titration.
2
AcO
4
adducts in D
2
O. Titration of Rh
AcO solutions; the next curves correspond to samples containing Rh
2 4
AcO concentrations (4.3, 8.9, and 6.1 mM solutions in 0.5 cm cell, respectively) were constant during each
2
AcO
4
by methionine 1 (a), hydrochloride salt of methionine 1-HCl (b), and
2
4
2
AcO and
4
Table 1
1
H
a
n
d
1
3
C
N
M
R
d
a
t
a
f
o
r
s
o
m
e
m
e
t
h
i
o
n
i
n
e
d
e
r
i
v
a
t
i
v
e
s
a
n
d
t
h
e
i
r
a
d
d
u
c
t
s
w
i
t
h
r
h
o
d
i
u
m
(
I
I
)
t
e
t
r
a
a
c
y
l
a
t
e
s
a
SCH
3
2
SCH CH
2
2
SCH CH
2
CH
C@O
R
Ligands, D
1
2
O solutions, 303 K
2.13(13.9)
2.63(28.9)
2.68(28.6)
2.70(28.4)
2.11/2.19(29.7) 3.85(53.9)
2.18/na(29.0) 4.15(52.2)
2.23/2.31(28.7) 4.31(51.7)
(174.3)
(172.2)
(170.6)
1
2
-HCl
-HCl
2.12(13.9)
2.13(13.9)
3.86(53.7) (OCH
3
)
Ligands, CDCl
3
solutions, 303 K
3
2.03(15.5)
2.46(29.8)
1.97/2.14(31.7) 4.75(50.2)
(172.0)
(172.5)
(169.5)
(172.3)
3.71(52.4) (OCH
3
); 8.18(160.6) (CHO);
6
.20 (NH)
7.73(134.5), 7.83(123.7), (131.1) (Ar);
167.6) (C@O)
3.67(52.8) (OCH
.81(123.6), (131.7)(Ar); (167.8) (C@O)
2.28(41.5) (N(CH ); 3.66(51.2) (OCH );
À356.8) (N)
b
b
4
5
7
2.03(15.0)
2.01(15.3)
2.03(15.4)
2.54 (26.6)
2.34/2.44 (30.1) 5.20(49.8)
(
b
b
2.45 (28.0)
2.40/2.50 (30.8) 5.03(50.8)
3
); 7.69(134.2),
7
2.47(30.7)
1.86/1.94(28.7) 3.27(66.0)
)
3 2
3
(
c
2 4 2
Adducts with Rh AcO , D O solution, 303 K
1
(1:1)
[0.37(1.6)]
[0.45(1.7)]
[0.25/
.29(À0.8)]
[0.25/na(À0.6)] [0.04(0.6)]
[na/na(À0.6)] [0.09(0.2)]
[0.11(À0.1)] [(À0.3)]
0
1
2
-HCl (1:1)
-HCl (1:1)
[0.39(1.7)]
[0.31(1.7)]
[0.44(2.0)]
[0.35(2.0)]
c
[(0.3)]
[(À0.3)]
[0.00(0.1)]
2 4 3
Adducts with Rh AcO , CDCl solution, 303 K
3
4
7
(1:1)
[0.44(2.2)]
[0.45(1.9)]
[0.38(0.6)]
[0.59(2.4)]
[0.47(4.9)]
[0.64(1.8)]
[0.37/0.39(0.6)] [0.06(0.4)]
3
[0.00(0.2)] (OCH ); [0.03(0.7)] (CHO)
[
0.22] (NH); [(À0.2)] (C@O)
(1:0.5)
(1:0.5)
[0.40/
.42(À4.0)]
[0.79/
.93(À0.2)]
[0.02(1.1)]
[1.06(3.5)]
[0.00(À0.1); À0.01(À0.1)] (Ar)
0
[(À0.1)]
[0.2(0.3)] (OCH
3
)
0
2
MTPA
4 3
, CDCl
solution, various temperaturesd
Adducts with (4S)-Rh
3
3
3
3
3
3
(rac) (1:1,
03 K)
2.43, 2.44
5.12
4.90
4.84
4.72
4.72
4.73
3.59, 3.61(OCH
3
); 8.24, 8.34 (CHO)
3
6.59 (NH); 3.06 (CH
3.58 (OCH ); 8.11 (CHO); 6.38 (NH);
.07 (CH , Rh salt)
3.63 (OCH
3
, Rh salt)
(S) (1:1, 254 K) 2.47
(R) (1:1, 254 K) 2.44
(S) (1:2, 254 K) 2.46
(R) (1:2, 254 K) 2.42
3
e
3
3
3
); 7.85 (CHO)
6.46 (NH); 3.08 (CH
3
, Rh salt)e
3.58 (OCH
3
); 7.97 (CHO); 6.18 d (NH)
3
.00 (CH
3.65 (OCH
.00 (CH , Rh salt)
3
3.58, 3.64, 3.65, 3.73 (OCH ); 7.39 , 7.49 ,
3
, Rh salt)
3
); 7.49 (CHO); 6.38 d (NH)
3
3
f
f
(rac) (1:2,
54 K)
2.37, 2.41, 2.46,
2.50
g
2
7.98, 7.99 (CHO); 6.19, 6.21, 6.38 (NH) ; 2.99 (CH
3
, Rh
h
salt)
4
4
4
4
(S) (1:1, 243 K) 2.48
(R) (1:1, 243 K) 2.46
(S) (1:2, 243 K) 2.43
(R) (1:2, 243 K) 2.46
5.20
5.14
4.99
5.09
7.52, 7.59 (Ar); 2.95 (CH
7.64; 7.74 (Ar); 2.96 (CH
7.58, 7.62 (Ar) 2.86 (CH
7.65, 7.74 (Ar); 2.91 (CH
, Rh salt)i
3
, Rh salt)i
, Rh salt)
3
3
3
Rh salt);
j
2.87, 2.89, 2.91 (CH
3
Rh salt)
4
5
5
(rac) (1:2,
43 K)
(R) (1:2, 243 K) 2.47(17.3)
2.40, 2.43, 2.46,
2.49
2.87, 2.89, 2.91 (CH
3
Rh salt) i
2
2.98(32.2)b
2.96m
2.81/2.70(26.9) 5.04(50.7)
3.63(53.5) (OCH
.74(123.5) (Ar); 2.92 (CH
3.62, 3.63, 3.64, 3.65 (OCH
7.60 (Ar); 2.87, 2.90, 2.91 (CH
); 7.68(134.1),
, Rh salt)i
); 7.74, 7.68,
, Rh salt)j
3
7
3
(rac) (1:2,
43 K)
2.42, 2.43, 2.46,
2.48
2.78m
5.04, 5.01,
4.93
3
2
3

R. Głaszczka et al. / Tetrahedron: Asymmetry 21 (2010) 2346–2355
2349
Table 1 (continued)
SCH
3
SCH
2
CH
2
2
SCH CH
2
CH
C@O
R
Adducts with Rh
2
TFA , CDCl
4
3
solution, 220 K
k
3
3
4
5
(S) (1:1)
(R) (1:2)l
(1:1)k
2.57(17.2)
2.59 (17.6)
2.54(16.5)
2.55(16.5)
3.08(31.8)
3.07(32.4)
3.02(31.7)m
2.98(32.1)m
2.26/2.52(29.5) 4.89(49.6)
2.26/2.50(29.6) 4.87(50.0)
(171.8)
(172.0)
(175.4)
(169.4)
3.73(52.8) (OCH
3
); 8.24(160.9) (CHO);
); 8.22(161.7) (CHO);
6
.45 (NH)
3.73(53.3) (OCH
.58 (NH)
7.73(133.9), 7.83(122.9), (131.2) (Ar);
167.8) (C@O)
3.71(52.6) (OCH
.84(123.0) (131.4) Ar; 167.7 (C@O)
3
6
2.76(25.4)m
2.81(26.5)m
5.11(49.4)
5.09(50.5)
(
(1:1)k
3
); 7.75(135.0),
7
13
2 4
C CPMAS NMR, 298 K, ligands and their adducts with Rh AcO
o
1
(lig).
(15.9, 17.7)
(31.5, 32.1, 32.8,
(53.0, 53.8)
(55.0)
(177.1,
177.5)
(174.9)
(À336.3) (N)
n
3
3.3)
(1:0.5)p
(17.8)
(31.6)
n
(24.2,24.2,192.5) (Rh
AcO
);
1
2
4
r
(
À338.5) (N)
7
7
(lig.)s
(1:1)
2.17(16.9)
(15.9)
2.61(32.6)
(31.3)
2.00(30.9)
(31.3)
3.44(67.4)
(69.6)
(173.7)
(172.7)
2.41(43.0) (N(CH
(40.2, 47.6) (NCH
23.4, 190.8); (Rh
3
)
2
); 3.77(52.6) (OCH
); (51.3) (OCH );
AcO
), (À358.2) (N)
3
)
t,u
3
3
(
2
4
a
All values were given in ppm. 1H chemical shifts (ppm) were given with respect to DSS or TMS signals (0 ppm), depending on the solvent (D
O or CDCl
3
); 13C chemical
2
shifts (in parentheses, ppm) were referred to the solvent signal (CDCl , 77.0 ppm) or DSS signal (0 ppm, D O solutions). Adduct formation sifts
3
2
D
d = dadduct À dligand (ppm) (or
D
d
add) were given in square brackets. All temperatures were read out from instrument panel and corrected; see Section 4.
b
1
1
13
1
H chemical shift read out from 2D C, H g-HSQC spectrum.
c
d
e
f
13
2 4
H and C (in parentheses) adduct formation shifts for the Rh AcO and ligand mixtures.
2 2
The signals of SCH CH moiety were not identified unambiguously and they were omitted in the table.
The 1H NMR spectrum of 1:0.5 sample showed up at 254 K an additional OCH
The signal not observed at 231 K due to broadening, see Figure 4.
At 231 K NH signals appeared at 6.53, 6.32 and 6.30 ppm, see Figure 4.
At 231 K the signal split into three components, see Figure 4.
3
2 4
signal of free Rh MTPA , this signal vanished in course of titration.
g
h
i
The 1H NMR spectrum of 1:0.5 sample (243 K) showed up two OCH
signals, of free dirhodium salt and R/4S adduct.
3
j
1
The H NMR spectrum of 1:0.5 sample (243 K) showed up three OCH
3
signals, one of free dirhodium salt and two of R/4S and S/4S adducts, respectively.
k
1
13
H( C) adduct formation shift (
), 0.62(2.0) (SCH
CH
D
d
add [ppm], calculated as differences between chemical shifts of an adduct at decreased temperature and ligand at 303 K: 3: 0.54(1.7)
(
SCH
3
2
), 0.29/0.38(À2.2) (SCH
2
CH
2
), 0.14(À0.6) (CH), (À0.2) (C@O), 0.02(0.4) (OCH
3 3 2
), 0.06(0.3) (CHO), 0.25 (NH); 4: 0.51(1.6) (SCH ), 0.48(5.1) (SCH ), 0.42/
0
.32(À4.7) (SCH
2
2
), À0.09(À0.4) (CH), (2.9) (C=O), this value reduced to 0.2 ppm if ligand spectrum taken at 220 K was used for the calculations, 0.00(À0.6), 0.00(À0.8),
(
0.1) (Ar), (0.2) (C@O); 5: 0.54(1.2) (SCH
3
), 0.53(4.1) (SCH
2
), 0.41/0.31(À4.3) (SCH
2
CH
2
), 0.06(À0.3) (CH), (À0.1) (C@O), 0.04(À0.2) (OCH ), 0.06(0.8), 0.03(À0.6), (À0.3) (Ar),
3
(À0.1) (C@O).
l
The 1H NMR spectrum of racemic 3 measured in the same conditions contains three signals in CHO and NH ranges (Fig. 6), CHO: 8.22, 8.19 and 8.18 ppm; NH 6.70, 6.67
and 6.55 ppm.
m
The assignments can be opposite.
n
o
p
r
2 2
The signal arising from SCH CH moiety, not assigned.
15
N signal, signal width at the half-height: 32 Hz.
A sample obtained by the evaporation of water solution containing Rh
2
AcO
4
4
and 1 in the molar ratio of 1:1.
and 7 in the molar ratio of 1:1.
15
N signal, signal width at the half-height: 370 Hz.
s
Chemical shifts of neat ligand.
A sample obtained by the evaporation of CDCl solution containing Rh
3
t
2
AcO
u
13
13
C adduct formation shift
D
d
add (ppm), calculated as differences between C chemical shifts of 1:1 adduct in the solid state and neat ligand (ppm): 1.0 (SCH
), 1.3 (OCH ).
3
), À1.3
(
SCH
2
2
2
), 0.4 (SCH CH ), 0.2 (CH), À1.0 (C@O), À2.8/4.6 (NCH
3
3
indicating that all of the added ligands were bonded by the dirho-
dium salt.
were expected to cancel out. The dependence of the calculated
chemical shifts on conformations and arrangements of the COOH
The bonding site in a ligand was another factor that was consid-
ered. Previous investigations on the adducts of dirhodium salts
2
and NH groups in methionine appeared to be the main difficulties.
Calculations performed for twelve arbitrarily selected conformers
3
0
1
with b-lactams suggested the following coordination selectivity:
C–S–C > C@O > C–O. As an aminoacid, methionine 1 is expected to
of 1 showed up theoretical H chemical shifts within the ranges
from 2.9 to 3.7 ppm for CH, 1.2–1.8 and 1.7–3.1 ppm for CHCH
pro-S and pro-R hydrogens, 2.7–3.6 ppm for SCH , and 2.1–
. Analogous ranges for the C chemical shifts
spanned 59–64 ppm (CH), 36–46 ppm (CHCH ), 44–47 ppm
(SCH ), and 26–27 ppm (SCH ). The chemical shift of the C@O sig-
nal varied from 180 to 188 ppm; N signals appeared within the
2
À
have a zwitterionic structure, containing –COO and protonated –
2
+
13
N H
3
groups. Conversely, carboxylic acids are generally weak and
2.2 ppm for SCH
3
the N-adduct of 1 could not be a priori excluded. Apart from the
nitrogen atom, the complexation could occur via either the sulfur
or oxygen atoms. Three complexation modes of the carboxylic
group should be considered: by @O, –OH or, assuming a zwitter-
2
2
3
1
5
1
range of À322 to À355 ppm. Experimental and theoretical
H
À
2
ionic structure, an ionized –O group. In the case of salts 1-HCl
chemical shifts correlated badly (r from 0.54 to 0.92, depending
2
13
and 2-HCl, nitrogen centers were protonated by a strong acid,
and were expected to be inactive in complexation.
on the structure); better results (r >0.95) were obtained for
C
chemical shifts. Additionally, the structures exhibiting the lowest
energy provided the worst correlations. Evidently, a model based
on the isolated molecule in vacuum was inadequate for our exper-
imental conditions. Since the population of the ligand and adduct
conformers in the solution were unknown, and the variations of
chemical shifts arising from the different conformers were larger
In order to explore the experimental NMR data, we attempted
1
13
to calculate
Calculations were performed by the application of density func-
tional theory (DFT), using a GAUSSIAN package.31 The
add values
Ddadd ( H and C) for some adducts of methionine.
D
d
were obtained as the difference between the calculated chemical
shifts for the adducts and the corresponding chemical shifts of
the free ligand. In this way the errors arising from the calculation
method and recalculation of shielding scale to chemical shift scale
than experimental
Dd values usually observed, these parameters
could not be calculated precisely. However, in order to obtain at
least rough data, we performed chemical shift calculations for a

2
350
R. Głaszczka et al. / Tetrahedron: Asymmetry 21 (2010) 2346–2355
H
N
H
N
H
H
0.53
(3.5)
0.58
(4.8)
0.04
H
H
2
.18
3.17
1.42
H
H
(
26.7)
(46.9)
(0.0)
(
59.4)
O
O
S
S
(
39.0)
(183.7)
(-2.2)
(-0.2)
H
3
.26
-0.07
Rh
H
O
O
H
2
.28
1.37
H
H
H
H
Rh
0.57
N
H
N
-
0.11
-0.10
-0.14
H
H
-
0.07
0.2)
-0.04
(0.2)
(
-0.6)
(0.8)
H
(-0.3)
(
O
H
(
1.9)
O
S
S
(-2.2)
1
(-0.1)
(
-0.9)
0
(-3.1)
H
1.72
Rh
0
.81
H
O
H
O
.15
.58
H
H
N
(
H
0
.03
0.09
0.21
H
(
0.0)
(0.01)
-0.09(-0.1)
3.2)
0.47(4.0)
0.52(3.6)
O
Rh
S
S
(
-0.9)
1
(18.6)
H
0.66(-2.1)
-0.01(0.2)
0
.29
Rh
H
O
.17
H
Figure 3. Calculated 1H(13C) chemical shifts for an arbitrarily selected conformer of methionine 1 and calculated adduct formation shifts (
D
d
add = dadduct À dligand) for its
hypothetical S-Rh, N-Rh, and O-Rh adducts. The last structure shows calculated
D
d
add for the adduct of 1-methylsulfanylbutane. All values are given in units of ppm.
23
few adducts with various complexation modes assuming the same
conformation for free ligand and ligand in an adduct (Fig. 3). For
the sake of comparison, calculations were also repeated for the
simple model, methylsulfanylbutane, which contains one
heteroatom.
amines,
D
d
add (15N) varied from ca. À5 to À30 ppm. Our attempts
1
5
2
to measure the N NMR spectra by an inverse technique in D O
solution were unsuccessful, probably due to the low adduct con-
centration and broad signals. In order to overcome these difficul-
ties, we performed NMR measurements in the solid state, using
C and N CPMAS NMR. Samples containing methionine and
Rh AcO /methionine mixtures in the molar ratios of 1:0.5 and
1:1 were obtained by evaporation of suitable solutions to dryness
(see Section 4). The C CPMAS NMR spectrum of methionine
showed two sets of narrow signals, indicating the presence of
two non-equivalent molecules in the solid state. However, the
N CPMAS NMR spectrum showed only one narrow N signal,
1
3
15
According to our theoretical findings, S-Rh adducts were ex-
pected to exhibit the largest positive
D
d
add for the hydrogen and
SCH group). Large positive
C) values should be observed
group. In the case of N-Rh and O-Rh adduct type,
add for the CH SCH group was expected to be relatively
small in comparison with the remaining atoms in the molecule.
2
4
carbon next to the sulfur atom (CH
3
2
1
13
13
D
d
add ( H) and negative
for the next CH
the
2
D
d
add
(
2
D
d
3
1
5
15
1
3
13
Large
D
d
add
(
C) of the carbonyl group was expected in the case
at À336.6 ppm. The C CPMAS NMR spectra of both adducts con-
of complexation via a C@O oxygen. The same relationships were
found for 1-methylsulfanylbutane, which contains a single hetero-
atom in the molecule.
tained broad irregular signals indicating the presence of amor-
1
5
phous or/and polymorphic material. The N CPMAS NMR spectra
contained one broad signal at ca. À338 ppm. The lack of a signifi-
1
5
Experimental results generally followed the findings for the S-
cant N chemical shift change excluded the nitrogen atom as a
1
Rh adduct type. The largest
found for the CH SCH CH
D
d ( H)s from 0.25 to 0.45 ppm were
binding site. Our attempt to measure Rh
onine in D O was unsuccessful, due to fast sample decomposition.
The third salt studied, Rh MTPA , was insoluble in D O.
2 4
TFA adducts with methi-
13
3
2
2
hydrogen atoms. Positive
D
d ( C)s, of
2
ca. 2 ppm were observed for the CH
bonded to the sulfur), whereas the SCH
3
SCH
2
carbon atoms (i.e., atoms
carbon atoms showed
2
4
2
2
CH
2
negative values, from À0.8 to À0.6 ppm (Table 1).
2.2. Complexation of 3, 4 and 5 with Rh
2
AcO
4
in CDCl
3
In order to validate our calculations using different adduct
types, we measured the Rh
2
TFA
4
adducts of N-formyl leucine
Rhodium tetraacetate, poorly soluble in CDCl
3
, was dissolved
1
13
methyl ester 6 in CDCl
3
( H and C NMR data are given in Sec-
over the course of a titration with 3–5. Typically, the mixture con-
tained Rh AcO and the ligand in molar ratios of ca. 1:1 at the
beginning of the titration (1:0.5 sample) and ca. 1:2 at the end
(1:2 sample). No significant change in d occurred during the titra-
tion; only the addition of ligand excess decreased d. The largest
S and SCH atoms (Ta-
tion 4). The lack of a sulfur atom in the molecule and the protected
NH group forced complexation via the oxygen atoms. The largest
2
4
1
3
D
d ( C) was expected for one or both carbonyl groups. In fact,
D
13
the COOCH
3
group shows the
D
d ( C) of À0.1 ppm, whereas
D
d
D
1
3
1
13
(
C) of the CHO reached a value of 5.8 ppm. The conclusion on
H and
C
D
d were observed for the CH
3
2
the complexation site is obvious in this case.
Previously, the adduct formation shifts of a nitrogen atom were
used as a convenient proof of complexation. In the case of the
ble 1), indicating the sulfur atom as a binding site. Since the ligand
exchange was fast on the NMR timescale, the titration experiment
did not answer whether the mixture contained 1:2 adduct or a

R. Głaszczka et al. / Tetrahedron: Asymmetry 21 (2010) 2346–2355
2351
mixture of adduct and free ligand. Due to the difficulty in control-
ling the solution composition in a two-phase sample, further mea-
surements using low temperature NMR were not continued for
these adducts.
combination of spectra of two diastereoisomers, (R,4S) and (S,4S)
A temperature decrease (254 K) resulted in signal broadening; nev-
3
ertheless the CHO, NH CH, and CH signals could be identified. The
OCH signal of the Mosher’s acid residue (1:0.5 sample, 254 K)
3
split, indicated the presence of a non-complexed and bonded
dirhodium salt in the solution. The signal of free salt vanished in
the spectrum of the 1:1 sample.
2
.3. Complexation of 3, 4 and 5 with (4S)-Rh
2 4 3
MTPA in CDCl
Typically, NMR measurements for these adducts were per-
Over the course of titration, the 1H chemical shifts changed
slightly, although signal splitting arising from the presence of 1:1
and 1:2 adducts was not observed, probably due to the minimal
chemical shift differences between these signals and the chemical
formed at reduced temperature. A temperature decrease caused
signal broadening, especially at the beginning of the titration
(
1:0.5 and 1:1 samples), but enabled us to observe the signals of
1
all the species in the 1:2 and 1:2.5 samples. The H NMR signals
of SCH and OCH groups appearing as singlets were the most diag-
nostic. Due to the large H multiplets of the SCH
its overlap with the SCH and OCH signals, the unambiguous iden-
tifications of these multiplets were difficult; their chemical shifts
2 4
shift averaging. The 1:2 mixture of (4S)-Rh MTPA and enantiome-
1
3
3
rically pure 3 showed one set of signals in the H NMR spectra, as-
signed to (R,R,4S) [or (S,S,4S)] isomers, depending on the
enantiomer used. At 254 K, the signals of the non-complexed 3 ap-
peared in the spectrum of the 1:2.5 mixture. In contrast, the spectra
of the 1:2 sample of racemic 3 contained additional signals arising
from (RS,4S) adduct (Fig. 4). At 254 K the CHO group showed up five
signals assigned to (S,S,4S), (R,R,4S), and (RS,4S) diastereoisomers
and to a non-complexed ligand. At 231 K two of these signals van-
ished due to broadening. The chemical shifts of the NH hydrogen
depended on the temperature; at 231 K four doublets were visible,
probably the result of two signals overlapping. The signal of the
1
2 2
CH moiety and
3
3
13
are omitted in Table 1. The C chemical shifts for the adducts were
1
3
1
taken from 2D C, H-HSQC spectra. Since the detection of quater-
nary carbon atom signals required additional experiments (2D
1
3
1
C, H-HMBC), these values were often omitted as unimportant
for further discussion. In order to explore the phenomena related
to the chirality, the adducts of both enantiomerically pure and
racemic ligands were investigated.
1
The H NMR spectra of enantiomerically pure ligands 3 (303 K,
OCH
nents, arising from three diastereoisomers. The SCH
groups in the ligand provide five and four signals respectively (thus,
3
group of the Mosher’s acid residue consists of three compo-
1
:0.5 and 1:1 samples) contained one set of signals each, as was
3
and OCH
3
expected. If racemic 3 was used, the spectrum was simply the
Figure 4. Partial 1H NMR spectra of (4S)-Rh
ranges were seen: the range of CHO signals (231 and 254 K) (a); the range of NH signals (231 and 254 K) (b), the range of OCH3, and SCH
the signals of three diastereoisomers (R,R,4S), (S,S,4S), and (RS,4S) and the free ligand. Signals were identified by comparison with the spectra of enantiomerically pure
adducts, (4S)-Rh MTPA -(S)-3, and (4S)-Rh MTPA -(R)-3.
solution, substrate to ligand in the molar ratio of 1:2.5, decreased temperature). The following
signals (231 K) (c). The spectra show
2 4 3
MTPA and rac-3 mixture (CDCl
3
2
4
2
4

2
352
R. Głaszczka et al. / Tetrahedron: Asymmetry 21 (2010) 2346–2355
Figure 5. Partial 1H NMR spectra of (4S)-Rh
ligands (b). The signals of SCH CH hydrogens form large broad multiplets and appeared in the spectra as baseline distortions.
2 4 3
MTPA and 4 mixture (CDCl solution, various substrate to ligand molar ratios, 243 K); enantiomerically pure (a) and racemic
2
2
two signals overlapped). The presence of additional signals in the
:2 sample and the lack of such signals in the 1:1 sample proved
the stepwise formation of the 1:1 and 1:2 adducts.
Additional signals in the spectrum, assigned to R/S adduct, ap-
peared for the NH and CHO groups (Fig. 6). Thus, the two ligands
mutually recognized each other in the 1:2 adduct. This effect sug-
gests an interesting extension of the ‘dirhodium NMR method’,
allowing us to determine the enantiomeric purity of the ligand
without the use of expensive enantiomerically pure dirhodium
derivatives.
In order to further explore this feature, we performed measure-
ments with phthaloyl derivatives of methionine, 4 and 5. Unfortu-
nately, we did not observe any such effects for these ligands,
despite NMR measurements at low temperature (220 K). The sig-
nals of the non-complexed ligand appeared at the beginning of
the titration (1:0.5 and 1:1 samples); thus the free ligand was pres-
ent in the equilibrium with an adduct in the mixture. The experi-
ment did not answer whether one adduct or a mixture of species
was in the samples. There were no differences between the spectra
of the pure isomer and racemic ligands. On the other hand, signals
in the spectra were quite broad, and the observation of subtle ef-
fects was rather difficult. This indicates that either mutual ligand
recognition did not occur, or that the differences between spectra
were too small to be observed.
1
Similar phenomena related to chirality were observed in the
case of the Rh
OCH groups illustrate these effects (Fig. 5). The 1:0.5 mixture of
Rh MTPA
spectrum (243 K) the signals of SCH
the (S,4S) [or (R,4S)] isomer, and additionally the signal of non-
complexed (free) Rh MTPA salt. Over the course of the titration,
the signal of the free rhodium salt vanished, and the signal of the
:2 adduct appeared. Finally, singlets assigned to the OCH and
SCH groups, arising from the (S,S,4S) [or (R,R,4S)] adduct were
visible. In the case of racemic 4, the spectrum of the 1:1 mixture
contains two doublets arising from the OCH and SCH groups
respectively, assigned to (S,4S)- and (R,4R)-isomers. The spectrum
of the 1:2 sample showed three signals for the Rh MTPA salt
and four signals for the SCH group, arising from the (R,R,4S)-,
S,S,4S)-, and (RS,4R)-isomers. The remaining signals (Ar and CH)
2 4 3
MTPA adduct with 4. The signals of the SCH and
3
1
2
4
and enantiomerically pure 4 illustrated in the H NMR
and OCH groups arising from
3
3
2
4
1
3
3
3
3
2
4
3
(
behaved similarly, although the effects were not so clearly visible
due to the multiplicity of these signals.
The spectra of Rh
2
MTPA
features. The H NMR spectrum (243 K) of the 1:0.5 sample con-
tained the OCH signal of non-complexed Rh MTPA , which van-
4
and 5 mixtures exhibited very similar
All the signals of the Rh
2
TFA
uously by 2D C– H correlation spectra (HSQC, HMBC) with the
exception of those in the SCH CH group. Hydrogen atoms
SCH CH are chemically non-equivalent due to the presence of a
stereogenic center, and produced two H signals (two multiplets).
In contrast, the SCH atoms appeared as one multiplet.
This feature allowed us to identify these signals in the Rh
3 adduct. However, the corresponding signals in the Rh TFA
Rh TFA -5 adducts appeared as single broad multiplets, and
4
adducts were identified unambig-
1
13
1
3
2
4
2
2
ished over course of the titration. The corresponding signal in the
adduct appears either as a singlet (enantiomerically pure 5) or as
a doublet (racemic ligand). The CO
in the 1:2 sample produced either one singlet each for enantiome-
2
2
1
2
CH
3
and SCH
3
methyl groups
2
2 4
TFA -
rically pure 5, or two sets of four signals each for racemic 5. The
2
4
-4 and
OCH
3
signal of the Rh
2
MTPA
4
core appeared in these cases as a sin-
2
4
1
3
glet or triplet, respectively.
assignments were carried out assuming the C signals order as
in the adduct of 3. The assigned chemical shifts were used for
1
13
2
.4. Complexation of 3, 4 and 5 with Rh
2
TFA
4
in CDCl
3
the calculation of a full set of H and
C Ddadd values (Table 1, in
the footnote). The add values were obtained using spectra of ad-
D
d
The NMR titration at 220 K was performed for Rh
2
TFA
4
and 3
ducts taken at reduced temperature and ligand spectra taken at
303 K. A decrease in temperature did not significantly change the
ligand chemical shifts, with the exception of the carbonyl signal
of 4 (172.4 ppm at 303 K, 175.2 ppm at 220 K). Generally, the
experimental findings followed the results of theoretical calcula-
using both the enantiomerically pure and racemic ligand. At the
start of the titration (1:0.5 sample), the signals were broad and
most of the adducts were deposited on the bottom of the NMR
tube. Over the course of the titration, the solid dissolved. Only min-
1
or H shift differences between the 1:1 and 1:2 samples were ob-
tions for the S-Rh adduct type. The largest positive
adopted by CH SCH CH hydrogen atoms; CH SCH carbon atoms
exhibited positive add, in contrast to SCH CH which showed
Ddadd values
served (Table 1). The spectra of the 1:1 and 1:2 samples differed,
depending on the ligand used; enantiomerically pure or racemic.
3
2
2
3
2
D
d
2
2

R. Głaszczka et al. / Tetrahedron: Asymmetry 21 (2010) 2346–2355
2353
points indicated that more than two species were present in the
solution. Thus, the stepwise formation of the two adducts, 1:1
and 1:2 was in agreement with these findings. The complexation
2 4
of Rh TFA with the formyl derivative of leucine methyl ester 6
was the third process studied. This ligand was expected to bond
to dirhodium salt via the oxygen atom only. Over the course of
the titration, a band attributed to the rhodium salt moved by ca.
2
0 nm only, and its intensity increased. The appearance of this
spectrum differs from those observed for Rh MTPA -3 and
Rh MTPA -4. Additionally, the measurement confirmed complexa-
2
4
2
4
tion via the oxygen atom under our experimental condition, which
was consistent with our previous NMR findings (see above).
This result suggested the possibility of a third kind of adduct in
3
the CDCl solution, appearing at the beginning of the titration, in
the presence of an excess of rhodium salt. Such adducts were ex-
pected to contain two dirhodium cores: one bonded via the S-site
and the second via the O-site (in case of 3 via CHO group). These
ternary compounds were expected to vanish over the course of
the titration, due to the replacement of O-Rh with S-Rh adducts.
2
.6. Two-phase samples
An interesting approach to the investigation of dirhodium ad-
ducts was the use of two-phase samples. In fact, the study of Rh
AcO adducts in CDCl was an example of such a method. Rhodium
tetraacetate was practically insoluble in CDCl , and dissolved over
the course of the titration. Complexation was a driving force, trans-
porting the rhodium salt to the solution as an adduct. We at-
2
4
3
3
Figure 6. Partial 1H NMR spectra of Rh
TFA and 3 mixtures (CDCl solution,
2 4 3
substrate to ligand in the molar ratio of 1:2.5, 220 K). The ranges of the CHO and NH
signals are shown. Bottom trace corresponds to the adduct of single enatiomer of 3;
upper trace corresponds to the adduct of the racemic ligand. Red asterisks indicate
the signals of the free ligand.
tempted to apply this method to the Rh
Rh AcO /5/D O mixtures. In the first case, the sample contained
a D O solution of 1 and Rh MTPA , insoluble in D O. The second
mixture consisted of Rh AcO in D O solution and 5, insoluble in
water. Both experiments were unsuccessful; the insoluble compo-
nent did not dissolve in D O despite the use of an ultrasonic bath.
However, application of a D
solutions of the Rh MTPA adduct with methionine 1 and Rh
2 4 2
MTPA /1/D O and
2
4
2
2
2
4
2
2
4
2
negative
values for both SCH
and 5 are noteworthy. This effect was also observed in the case of
Rh AcO
4. The values for the remaining atoms ranged from À1 to
ppm, with the exception of C@O signal of 4 (2.9 ppm). However,
D
dadd values. The large positive and negative
Dd
add (13C)
2
CH atoms in adducts of phthaloyl derivatives
2
2
4
2
O/CDCl
3
mixture yielded red CDCl
AcO
3
2
4
2
4
2
4
1
adduct with 5, respectively. Thus, the application of two solvents
enabled us to transport the insoluble component to the organic
phase.
this value was reduced to 0.2 ppm if both the ligand and adduct
spectra taken at 220 K were used as the base of calculations.
The 1H NMR spectra of the Rh
2 4 3
MTPA -1 adduct in CDCl were
2
5
.5. Absorption electronic spectroscopy in the visible range of 4,
and 6 adducts in CDCl solution
difficult to interpret, due to the broad signals of the ligand. Mea-
surements at a decreased temperature (231 K) allowed us to ob-
3
serve only a broad OCH
3
multiplet. The shape of this signal
For the sake of comparison, we performed some measurements
using electronic absorption spectroscopy in the visible range (vis)
Fig. 7). Titration of Rh MTPA in CDCl with 3 or 4 provided sim-
ilar spectra: free dirhidium salt absorbed at 641 nm; over the
course of the titration two bands showed up, assigned to the 1:1
differed depending on the ligand used; enantiomerically pure or
racemic. One component of the multiplet was identified as the sig-
nal of the non-complexed rhodium. Unfortunately, the results were
difficult for quantitative analysis. Nevertheless, this method of
sample preparation appears to be promising in future spectro-
scopic investigations and possibly in organic synthesis.
(
2
4
3
(
ca. 596 nm) and 1:2 adducts (537 nm). The lack of isosbestic
2 4 2 4 3 2 4 2 4 2 4
Figure 7. Absorption electronic spectra (visible range) of Rh MTPA and Rh TFA adducts in CDCl ; titration of Rh MTPA by 3 (a), Rh MTPA by 4 (b), Rh TFA by 6 (c). Green
curves correspond to dirhodiun salt solutions; the next curves correspond to samples containing dirhodium salts and ligands in the molar ratio from 1:0.5 to 1:2.5 (step 0.5).
The initial concentration of rhodium salt was ca. 1 mM; 0.5 cm cell was used.

2
354
R. Głaszczka et al. / Tetrahedron: Asymmetry 21 (2010) 2346–2355
2
.7. Complexation of N,N-dimethylmethionine methyl ester 7
The presence of N(CH and COOCH groups excludes the zwit-
(ii) Typically, fast ligand exchange (in the NMR timescale) oc-
curs at room temperature (303 K). As a consequence, signals in
averaged positions or broad signals were observed in the spectra.
3
)
2
3
terionic structure of this ligand. In theory, all complexation sites (S,
N and O) are able to bond to the dirhodium salts. Competition be-
tween S and N centers was expected. We examined the complexa-
The adduct of Rh
However, in the case of adducts with Rh
decreasing the temperature within the range 220 to 254 K slowed
down the exchange rate and enabled us to observe the signals of all
species in the solution.
2
AcO
4
and 1 (D
2
O solution) was a typical example.
TFA and Rh MTPA
4
2
4
2
tion of 7 with Rh
2
AcO
4
in the liquid and solid state.
solution suffered from
1
The H NMR spectra measured in CDCl
3
broad and overlapping signals, despite various temperatures (303
or 231 K). Not all signals could be identified; careful examination
of the 2D C, H-HSQC spectra allowed us to see some C chemical
shifts (Table 1). We were not able to unambiguously identify the
(iii) The signals of all the Rh
[(S,S,4S), (R,R,4S), and (RS,4R)] were observed in low-temperature
H NMR spectra. The combination of H NMR spectra of (S,S,4S)-
and (R,R,4S)-isomers differs from the spectrum of the adduct of race-
mic ligand, due to additional signals arising from the (RS,4R)-isomer.
Thus, the two ligands in both axial positions of the dirhodium unit
recognized each other, despite the distance between them.
2 4
MTPA diastereomeric adducts
1
3
1
13
1
1
2
signals of the N(Me) groups in the spectrum of the 1:0.5 sample
at 303 K; however decreasing the temperature (231 K) revealed
1
3
two signals of these groups, at 40.4 and 47.5 ppm. Similar
C
chemical shift dispersion was previously observed in the
2 4
(iv) Similar effects were observed in the case of the Rh TFA -3
adduct. The spectra of 1:2 adducts were different depending on
the ligand used; enantiomerically pure or racemic. Unfortunately,
*
*
27
adducts of amines R N(CH
3
)
2
(R denotes a chiral moiety).
The dispersion originated in the stereogenic center close to the
nitrogen atom, and slow inversion at the nitrogen atom caused
by complexation. In case of 7, the dispersion suggested the nitro-
gen as the binding site.
these phenomena were not observed for the Rh
Rh TFA -5 adducts. Nevertheless, mutual ligand recognition in
the two axial positions in Rh TFA suggests the interesting exten-
2 4
TFA -4 and
2
4
2
4
The HSQC spectrum of the 1:0.5 mixture taken at 231 K con-
tained some additional signals, for instance, the two signals of
Rh AcO methyl groups. This splitting disappeared over the course
2 4
sion of NMR dirhodium method, namely the determination of the
enantiomeric purity of the compound by NMR methods without
the need for an expensive enantiomerically pure dirhodium salt.
of the titration. Such features of the spectrum can be tentatively
explained by assuming the presence of a 2:1 adduct, containing
one ligand molecule and two non-equivalent dirhodium units;
one bonded via the nitrogen and the second by the sulfur atom.
Over the course of the titration, this compound transformed to
the 1:2 N-type adduct.
3 2
(v) Application of the two-phase CDCl /D O mixture resulted in
the extraction of an insoluble component to the organic phase as
the adduct.
4. Experimental
In order to eliminate dynamic processes in the solution, we per-
1
3
15
formed measurements in the solid state by the C and N CPMAS
(R)- and (S)-methionine 1 were commercially available and
were purchased. The following aminoacid derivatives were pre-
pared according to the published procedures: methionine methyl
esther 2 (as an HCl salt) by esterification of methionine with 2,2-
1
3
NMR techniques. The C spectrum contained broad signals, which
were assigned by comparison with the spectrum of neat (liquid) li-
gand (Table 1). The dispersion of N-methyl signals (40.2 and
3
2
4
7.6 ppm) also appeared in the solid phase. The adduct formation
dimethylpropane;
N-formyl derivative 3 by formylation of
13
33
shifts were calculated using C CPMAS NMR and neat ligand spec-
tra. Generally, the largest add values were observed for two N-
methyl groups (À2.8 and 4.6 ppm), and for CH atom (2.2 ppm).
Minor values adopted SCH and SCH carbon atoms, in contrast
to adducts of 1–5, measured in CDCl . This add pattern suggested
that rather N(CH than SCH group is the complexation site.
methionine methyl ester with ammonium formate; N-phthaloyl
methionine 4 from methionine and phthalic anhydride;34 N-
phthaloyl methionine methyl ester 5 from 2 and phthalic anhy-
dride, leucine formyl derivative 6 by formylation of leucine methyl
D
d
3
2
3
3
D
d
ester; and N,N-dimethylmethionine methyl ester 7 from methio-
3
35
)
3 2
3
nine methyl ester via reaction with formaldehyde and NaBH
The hydrochloride salts of the aminoacids were prepared by acid-
ification of the aminoacid with HClaq in H O solution and then
evaporation of the solvent in vacuo. Rhodium(II) tetraacetate and
tetratrifluoroacetate were purchased; the dirhodium tetra-(S)-
methoxy- -(trifluoromethyl)-phenylacetate dimer (Mosher’s acid
derivative, Rh MTPA ) was prepared from enantiomerically pure
3
CN.
Nitrogen-15 adduct formation shift is generally a good proof of
complexation. The complexation of amines occurring via the nitro-
2
1
5
gen atom produces negative
D
dadd values
N, from À4 to
2
3
À40 ppm. Unfortunately, in regard to our investigations this
a-
parameter was not diagnostic. Since 7 was a liquid, we had to
a
1
5
use N chemical shifts measured under various conditions (CDCl
solution for the ligand and the solid state for the adduct). The
3
2
4
D
d
add
(S)-Mosher’s acid (commercially available) and rhodium(II) tetra-
1
5
36
(
N) value of À1.4 ppm, was too small to conclude on the com-
acetate according to a published procedure.
1
13
plexation site.
3 2
H and C NMR spectra in the liquid phase (CDCl , D O and
neat liquid compounds) were measured on a Bruker Avance
DRX500 spectrometer, using 5 mm TBI probe equipped with z-
gradient coil. One-dimensional H NMR spectra was measured
1
3
. Conclusion
with the following parameters: an acquisition time of ca. 2.5 s,
relaxation delay of 1 ms, pulse width of 2.5 ls (ca. 30°) and spectral
width of 6500 Hz; 32 K points matrix was used for both data acqui-
Our results led to the following conclusions:
(
i) Dirhodium salts (Rh
2
4
AcO , Rh
2
TFA4, and Rh
2 4
MTPA ) form
with methionine and its derivatives, 1:1 and 1:2 axial adducts,
depending on the substrate to ligand molar ratios. The complexa-
tion of methionine occurred in D O solution despite the competi-
2
tion of the ligand with water molecules. Complexation process
can be monitored either by NMR spectroscopy (especially at re-
duced temperature) or by electronic absorption spectroscopy in
the visible range (vis). Analysis of adduct formation shifts, as well
as DFT calculations indicated that the sulfur atom is the complex-
ation site in ligands 1–5 and 7.
sition and Fourier transformation, giving spectral resolution of
1
3
0.2 Hz per point. C NMR chemical shifts of non-complexed li-
gands have been taken from one-dimensional spectra recorded
with the following parameter values: 2.2 s for the acquisition time,
500 ms for the relaxation delay and 4.3 ls (ca. 33°) for pulse width.
Spectral width of 15200 Hz and 64 K points matrix was used for
both data acquisition and Fourier transformation, giving a spectral
1
3
resolution of 0.23 Hz/point. C chemical shifts of adducts, due to
low sample concentration, were measured using 2D inverse

R. Głaszczka et al. / Tetrahedron: Asymmetry 21 (2010) 2346–2355
2355
gradient correlation techniques. Both experiments, 13C, H-gHSQC
1
shielding calculations (GIAO) were performed using B3LYP method
with LANL2DZ basis set for Rh and 6-311G(2d,p) basis set for C, H,
N, O, and S atoms. A shielding scale was converted to a chemical
shift scale using shielding values for TMS, provided by GAUSSIAN
package (B3LYP/6-311G+(2d,p) GIAO; 31.8821, and 182.4656 ppm
for H, and C, respectively). Adduct formation shifts were calcu-
lated as a difference between chemical shifts in adduct and chem-
ical shifts of corresponding signals in a free ligand.
(
‘invietgs’ Bruker’s pulse program: phase sensitive, E/A gradient
13
1
selection with decoupling during acquisition) and C, H-gHMBC
were applied with the following parameters: a 2048 Â 512 matrix
zero-filled to 2048 Â 1024 prior to FT, an acquisition time of 0.25 s,
relaxation delay of 1.2 s, and from 4 to 8 transients per experiment.
1
13
1
The final spectroscopic resolution of 2 Hz per point ( H domain)
and ca. 10 Hz per point ( C domain) was achieved. All H and
C chemical shifts were referred to the TMS or DSS signal
0 ppm), depending on the solvent used. The carbon signal of CDCl
13
1
1
3
(
3
Acknowledgements
was also used as a secondary reference (77.0 ppm with respect to
TMS signal). Sample temperatures (K) were read out directly from
the instrument panel and corrected using the calibration curve,
prepared on the basis of a methanol thermometer.
Complexation was investigated by the use of titration experi-
ments. To NMR tubes, containing ca. 10 mg of dirhodium salt and
This work was partially supported by the scientific network of
the Ministry of Science and Higher Education of Poland (decision
68/E-61/BWSN-0126/2008) ‘New applications of NMR spectros-
copy in chemistry, biology, pharmacy and medicine’.
0
2 3
.7 ml of D O or CDCl (depending on ligand and rhodium salt sol-
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3
C chemical shifts (in parentheses) and corresponding adduct for-
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.56/1.68(41.8) [0.23/0.24(0.3)] (CH ); 4.73(49.3) [0.73(1.6)]
); 5.94 [1.07] (NH); 8.21(160.5)
2
4
3
0
1
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2
(
[
CH); 3.75(52.4) [0.15(0.5)] (OCH
3
0.57(5.8)] (CHO); (173.0) [À0.1] (C@O).
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(