Structurally simple chiral thioureas as chiral solvating agents in the enantiodiscrimination of α-hydroxy and α-amino carboxylic acids

Article abstract of DOI:10.1016/j.tet.2007.05.021

C₂-Symmetrical chiral thioureas (S,S)-1 and (S,S)-2 were prepared in good yield by the reaction of 2 equiv of inexpensive (S)-1-phenylethylamine, or the corresponding naphthyl analog, with 1 equiv of thiophosgene in the presence of excess triet

Full text of DOI:10.1016/j.tet.2007.05.021

Tetrahedron 63 (2007) 7673–7678
Structurally simple chiral thioureas as chiral solvating agents
in the enantiodiscrimination of a-hydroxy and a-amino
carboxylic acids
*
Marcos Hern ꢀa ndez-Rodr ꢀı guez and Eusebio Juaristi
Departamento de Qu ꢀı mica, Centro de Investigaci oꢀ n y de Estudios Avanzados del Instituto Polite´cnico Nacional,
Apartado Postal 14-740, 07000 Me´xico, D.F., Mexico
Received 22 January 2007; revised 19 April 2007; accepted 7 May 2007
Available online 22 May 2007
2
Abstract—C -Symmetrical chiral thioureas (S,S)-1 and (S,S)-2 were prepared in good yield by the reaction of 2 equiv of inexpensive (S)-1-
phenylethylamine, or the corresponding naphthyl analog, with 1 equiv of thiophosgene in the presence of excess triethylamine. The presence
of asymmetric elements in (S,S)-1 and (S,S)-2, and their capacity to act as receptors for anionic species via hydrogen bonding were exploited in
1
the development of H NMR spectroscopic enantiodiscrimination of chiral carboxylic acids. In particular, the diastereomeric complexes
derived from thioureas (S,S)-1 and (S,S)-2 with ammonium salts of the chiral acids gave rise to well separated signals of the a-hydrogens
and simple integration provides the corresponding enantiomeric ratios. Furthermore, it was observed that C –H in the (R) enantiomers of
a
the chiral a-hydroxy and a-amino carboxylic acids studied in this work consistently appears downfield relative to the same signals in the
(
S) enantiomers.
Ó 2007 Elsevier Ltd. All rights reserved.
1
. Introduction
enzymes, as well as other natural products contain carboxyl-
ate functions that are essential for their corresponding
1
2
Molecular recognition by synthetic receptors is an important
undertaking in the field of supramolecular and bioorganic
chemistries. In this regard, whereas the sensing of cations
is a well established field of research, it is only recently
that anion recognition, complexation, and transport have
been recognized as a most relevant pursuit.
biochemical behavior. Molecular recognition of carboxyl-
ates is therefore a relevant endeavor. Furthermore, the pres-
ence of asymmetric elements in the receptor offers the
possibility of enantiodiscrimination of chiral carboxylic
1
2
1
3
13b
guests. Indeed, Echavarren and co-workers reported in
1989 that chiral guanidinium salts such as A (Chart 1) can
differentiate enantiomeric carboxylates by means of NMR
spectroscopy. More closely related to the present work,
Rebek and co-workers developed neutral, asymmetric urea
receptors such as B (Chart 1) that bind to chiral carboxylates
3
4
5
Several synthetic neutral receptors possessing amide, urea,
6
and thiourea moieties as a binding site for anion recognition
have been reported, in which the binding takes place via hy-
drogen bonding interaction. Here it is worth mentioning that
several chiral (thio)ureas have recently proved to be useful
1
4
by the N–H urea hydrogens. More recently, chiral (thio)-
ureas C–E (Chart 1) have been explored as NMR spectro-
7
15
16
17
organocatalysts in enantioselective 1,4-additions, Mannich
reactions, Strecker reactions, Baylis–Hillman reactions,
and others. These applications demonstrate the usefulness
of hydrogen bonding in the activation of prochiral substrates
for the preparation of enantioenriched derivatives.
scopic, electrochemical, or fluorescent probes in the
enantiodifferentiation of chiral carboxylic acids.
8
9
10
1
1
Most pertinent in connection with the present report is the
1
8
recent communication by Yang and co-workers that C2-
symmetric receptor F (Chart 1) functions as a chiral shift
reagent for the determination of enantiomeric composition
The carboxylate group is an anionic entity of prime impor-
tance in biological systems. For example, amino acids,
1
19
of chiral carboxylic acids by H NMR spectroscopy.
Given the increasing demand for convenient methods of
Keywords: Chiral solvating agents; Chiral thioureas; Enantiomeric purity;
1-Phenylethylamine derivatives; Density functional theory; Chiral ligands;
Enantiodiscrimination.
19,20
measuring enantiomeric purity, and taking into consid-
eration the relevant role played by enantiomerically pure
carboxylic acids in nature, we examined the potential of
2
1
*
Corresponding author. E-mail: juaristi@relaq.mx
0
040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.05.021

7674
M. Hern aꢀ ndez-Rodr ꢀı guez, E. Juaristi / Tetrahedron 63 (2007) 7673–7678
Cl−
N
S
N
H
+ N
H
N
H
N
H
O
O
O
O
N
N
N
N
O
O
N
H
N
H
O
H
H
H
H
O
O
O
O
N
N
Bn
Bn
Ph
Ph
NH2
NH2
A, ref. 13
B, ref. 14
C, ref. 15
H3C
Ph
H
H
N
H
N
O
O
S
N
H
Ph
N
Ph
Fe
O
O
N
N
O
NO2
N
O
H
H
O
HN
NH
D, ref. 16
F, ref. 18
E, ref. 17a
Chart 1.
several simple thioureas containing the 1-phenylethyl
group as chiral solvating agents (CSA). This report sum-
marizes the results.
in phenylglycine appears at two nonequivalent chemical
shifts (d ¼4.28 ppm, d ¼4.33 ppm; Dd¼0.05 ppm) as a
2
2
1
2
consequence of the formation of diastereomeric complexes
(
Fig. 1).
2
. Results and discussion
As expected, when each enantiomer of phenylglycine
was separately treated with (S,S)-1, only one C–H signal is
recorded (Fig. 2). It can be noticed that (1) the (R) enantio-
mer of phenylglycine exhibits the C–H chemical shift at
higher frequency (lower field), and (2) no racemization of
the a-amino acid is induced by the thiourea.
2
.1. Synthesis of chiral thioureas
C -Symmetrical thiourea (S,S)-1 was prepared by the
2
reaction of 2 equiv of inexpensive (S)-1-phenylethylamine
with 1 equiv of thiophosgene in the presence of excess
(
2.2 equiv) of triethylamine (Scheme 1a). Naphthyl thio-
The observed difference in the chemical shifts of the C–H
a-protons of the two enantiomeric phenylglycinates in the
presence of receptor (S,S)-1 prompted us to examine the
enantiomeric discriminating ability of this chiral thiourea
with other chiral carboxylic acids. A broad variety of
racemates was selected for this study, including additional
a-amino acids, a-hydroxy acids, a-halo acids, and pharma-
cologically relevant naproxen. As shown in Table 1, receptor
urea analog (S,S)-2 was similarly prepared in one step
from commercially available 1-(a-naphthyl)ethylamine
(
Scheme 1b).
S
S
S
Et3N
Et3N
(
a)
2
2
NH2 +
N
H
N
H
Cl
Cl
Cl
Cl
(S,S)-1 induces sufficiently large chemical shift nonequiv-
alences to give base-line resolution of the appropriate a-
(
S,S)-1
protons in all the chosen carboxylic acids registered on a
ꢀ
S
4
00 MHz NMR instrument at 25 C.
NH2
+
N
H
N
H
(
b)
Table 2 summarizes the results of the examination of the
enantiomeric discriminating ability of naphthyl thiourea
(
S,S)-2. The most salient observation is the significantly in-
(
S,S)-2
creased chemical shift nonequivalences that are obtained
with this receptor, probably as a consequence of the larger
size of the aromatic ring and its corresponding stronger
anisotropic effect.
Scheme 1.
2
(
.2. Binding properties of chiral thioureas (S,S)-1 and
S,S)-2 toward carboxylates
The other salient observation from Table 2 is the consistent
higher-frequency chemical shift recorded for the a-proton
in the (R) enantiomers, both in a-amino acids (six
examples) and a-hydroxy acids (three examples). This
result offers the possibility that chiral thiourea receptor
(S,S)-2 could be used for the assignment of the absolute
configuration in chiral a-amino and a-hydroxy carboxylic
acids.
We studied the carboxylate binding properties of (S,S)-1
by NMR analysis in solution (chloroform-d ) with tetra-
1
butylammonium salts of racemic amino acids. A typical
spectrum that illustrates the use of this methodology is
shown in Figure 1. It is noticed that the signals of the urea
hydrogens shift downfield, indicating binding by the carb-
oxylate. Most important, however, the methine C–H signal

M. Hern aꢀ ndez-Rodr ꢀı guez, E. Juaristi / Tetrahedron 63 (2007) 7673–7678
7675
S
S
Ph
N
H
N
H
Ph
Ph
N
H
N
H
- O
Ph
NH2
O
1
) NBu4OH
OH
+
Ph
-
O
2
) 1.2 eq.
O
O
S
Ph
N
H
N
H
Ph
(± )
Ph
NH2
2
H N
Ph
(
S,S)-1
H
H
(
S,S,S)
(S,S,R)
1
Figure 1. H NMR spectra (400 MHz) of (ꢁ)-phenylglycine (a) before the addition of (S,S)-1 and (b) followed by the addition of 1.2 equiv of (S,S)-1.
1
In conclusion, we have demonstrated that simple chiral thio-
ureas (S,S)-1 and (S,S)-2 are efficient receptors to chiral
carboxylates. The diastereomeric complexes obtained from
such complexation give rise to distinguishable signals in
H NMR spectra, which can be used for the determination
of the enantiomeric purity as well as for the assignment of
the absolute configuration of the corresponding carboxylic
acids.
1
Figure 2. Partial H NMR spectra (400 MHz) highlighting the C–H signal in (a) racemic phenylglycine, (b) (R)-phenylglycine, and (c) (S)-phenylglycine. All
three experiments were carried out in the presence of 1.2 equiv of (S,S)-1.

7676
M. Hern aꢀ ndez-Rodr ꢀı guez, E. Juaristi / Tetrahedron 63 (2007) 7673–7678
1
Table 1. Determination of H NMR chemical shift nonequivalences (DDd)
1
Table 2. Determination of H NMR chemical shift nonequivalences (DDd)
1
of racemic carboxylic acids in the presence of receptor (S,S)-1 by H NMR
1
of racemic carboxylic acids in the presence of receptor (S,S)-2 by H NMR
ꢀ
ꢀ
(
400 MHz) in CDCl
3
at 25 C
(400 MHz) in CDCl
3
at 25 C
b
b
Entry
Racemic carboxylic
acid
DDd
(ppm)
Entry
1
Carboxylic
acid
DDd
(ppm)
Enantiomer
at lower field
a
a
NH2
NH2
OH
OH
1
2
3
4
5
0.05
0.10
(R)
Ph
Ph
O
OH
O
NH2
OH
0.01
0.02
0.01
OH
c
Ph
2
3
4
5
6
7
8
9
0.18
(R)
(R)
(R)
(R)
(R)
(R)
(R)
O
NH2
O
NH2
OH
Ph
OH
0.05
0.05
0.03
0.04
0.05
0.04
0.02
0.004
0.02
0.02
0.16
O
O
Cl
NH2
OH
OH
Br
O
O
Br
NH2
OH
c
0.02
HO
OH
Ph
O
O
NH2
O
OH
OH
6
0.02
H2N
O
MeO
O
OH
a
All samples were prepared by mixing 1 equiv of tetrabutylammonium
carboxylate (0.1 M in CDCl ) and 1.2 equiv of thiourea (S,S)-1 in NMR
3
OH
Ph
tubes.
O
b
c
1
OH
H NMR chemical shift nonequivalences of the methine protons on the
centers of chirality of the acids.
Significant autocondensation of bromo phenylacetic acid was observed.
OH
O
O
O
OH
OH
OH
(R)
HO
HO
3
. Experimental part
O
OH
3
.1. General
e
1
1
1
0
1
2
3
OH
Cl
O
Anhyd CH Cl was obtained by distillation from P O . TLC:
2 5
2
2
DC-F254 plates, detection by UV light. Flash column chro-
matography: silica gel (230–400 mesh). Melting points are
not corrected. H NMR spectra: 400 MHz and 270 MHz
spectrometers. C NMR spectra: 100 MHz and 67.5 MHz
spectrometers. Chemical shifts (d) are given in parts per
million downfield from internal TMS reference; the coupling
constants (J) are given in hertz. Elemental analysis was
obtained from the analytical department at the Chemistry
Department of Cinvestav-IPN.
OH
OH
d
d
Br
1
O
Br
1
3
Ph
O
OH
1
(R)
O
MeO
a
All samples were prepared by mixing 1 equiv of tetrabutylammonium
carboxylate (0.1 M in CDCl ) and 1.2 equiv of thiourea (S,S)-2 in NMR
3
0
3
.2. N,N -Bis[(S)-1-phenylethyl]thiourea, (S,S)-1
tubes.
b
1
H NMR chemical shift nonequivalences of the methine protons at the
stereogenic carbons of the acids.
Tetramethylammonium carboxylate was used in this case.
Not determined.
DDd Difference too small to permit secure assignment of configuration.
In a 100-mL round-bottom flask provided with magnetic
stirrer were placed 2.0 g (16.5 mmol) of (S)-1-phenylethyl-
amine and 2.5 mL (18 mmol) of triethylamine dissolved in
c
d
e
2
0 mL of anhyd dichloromethane. The resulting mixture
ꢀ
was cooled to 0 C before the dropwise addition of a solution
containing 0.63 mL (8.25 mmol) of thiophosgene dissolved
in 15 mL of dichloromethane. The ice-bath was removed
and the reaction mixture was stirred at ambient temperature
for 24 h. Addition of 30 mL of 1.0 M HCl led to the forma-
tion of a biphasic system. The organic layer was separated,
the aqueous phase was extracted with 50 mL of dichloro-
methane, the organic layers were combined, dried, and
concentrated to give the crude product that was purified by
flash chromatography (hexane–EtOAc, 80:20) to afford a
ꢀ
+114.3 (c 1.0, CHCl ). H NMR (CDCl , 270 MHz) d 1.46
25
23
25
198–200 C). [a]D +114.2 (c¼1.05, CHCl ); lit. [a]D
3
1
3
3
(d, J¼6.9 Hz, 6H), 5.05 (br, 2H), 6.13 (br, 2H), 7.01–7.40
1
3
(m, 10H). C NMR (CDCl , 67.5 MHz) d 23.1, 54.1,
3
125.7, 127.6, 128.9, 142.2, 180.1.
0
3.3. N,N -Bis[(S)-1-(a-naphthyl)ethyl]thiourea, (S,S)-2
The same procedure used for the preparation of (S,S)-1 was
followed with 1 g (5.8 mmol) of (S)-1-(a-naphthyl)ethylamine
ꢀ
23
white solid, 1.80 g (77% yield), mp 199–200 C (lit. mp

M. Hern aꢀ ndez-Rodr ꢀı guez, E. Juaristi / Tetrahedron 63 (2007) 7673–7678
7677
and 0.88 mL (6.4 mmol) of thiophosgene. Thiourea (S,S)-2
4. (a) Jagessar, R. C.; Burns, D. H. Chem. Commun. 1997,
1685; (b) Redman, J. E.; Beer, P. D.; Dent, S. W.; Drew,
M. G. B. Chem. Commun. 1998, 231; (c) Watanabe, S.;
Onogawa, O.; Komatsu, Y.; Yoshida, K. J. Am. Chem. Soc.
1998, 120, 229.
(
814 mg, 73% yield) was obtained as a white solid, mp
ꢀ
63–164 C. [a] +171.3 (c 0.75, CHCl ); lit. mp 163–
D 3
25
23
1
1
2
2
1
1
1
ꢀ
25
D
1
65 C, [a] +172.5 (c 1.0, CHCl ). H NMR (CDCl ,
3
3
70 MHz) d 1.48–1.57 (m, 6H), 5.81 (br, 2H), 6.02 (br,
H), 7.02 (dd, J ¼11.1 Hz, J ¼7.5 Hz, 2H), 7.35–7.95 (m,
1
2
5. (a) Curran, D. P.; Kuo, L. H. J. Org. Chem. 1994, 59, 3259; (b)
Kelly, T. R.; Kim, M. H. J. Am. Chem. Soc. 1994, 116, 7072; (c)
Scheerder, J.; Van Duynhouen, J. P. M.; Engbersen, J. F. J.;
Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1996, 35,
1090; (d) Jagessar, R. C.; Shang, M.; Scheidt, W. R.; Burns,
D. H. J. Am. Chem. Soc. 1998, 120, 11684; (e) Amemiya, S.;
B €u hlmann, P.; Umezawa, Y.; Jagessar, R. C.; Burns, D. H.
Anal. Chem. 1999, 71, 1049; (f) Boiocchi, M.; Del Boca, L.;
G ꢀo mez, D. E.; Fabbrizzi, L.; Licchelli, M.; Monzani, E.
J. Am. Chem. Soc. 2004, 126, 16507; (g) Bondy, C. R.; Gale,
P. A.; Loeb, S. J. J. Am. Chem. Soc. 2004, 126, 5030; (h)
Zlatuskov ꢀa , P.; Stibor, I.; Tkadlecov ꢀa , M.; Lhot ꢀa k, P.
Tetrahedron 2004, 60, 11383.
1
3
2H). C NMR (CDCl , 67.5 MHz) d 21.7, 50.4, 122.6,
3
25.2, 125.8, 126.7, 128.4, 129.0, 130.1, 133.7, 136.9,
79.7. MS: m/z 384 (M ), 229, 171, 170, 155, 129, 44.
+
Anal. Calcd for C H N S: C, 78.09; H, 6.29; N, 7.28; S,
5 24 2
2
8
.34. Found: C, 77.89; H, 6.38; N, 7.63; S, 8.43.
3
.4. General procedure for the determination of ee
In a 5-mL round-bottom flask were placed 0.06 mmol of the
chiral carboxylic acid and 0.67 mL of a 0.09 M solution of
tetrabutylammonium hydroxide in isopropanol. Methanol
(
1–3 mL) was added and the flask was submerged in an
ultrasound bath until complete dissolution of the carboxylic
acid. The solvent was removed under reduced pressure and
the residue (tetrabutylammonium carboxylate salt) was
mixed with 27 mg (0.072 mmol) of (S,S)-2 before the addi-
tion of 0.7 mL of CDCl . The resulting solution was stirred
3
at ambient temperature for 10 min and transferred to an
NMR tube for measurement.
6. (a) Wilcox, C. S.; Kim, E.-I.; Romano, D.; Kuo, L. H.; Burt,
A. L.; Curran, D. P. Tetrahedron 1995, 51, 621; (b)
Nishizawa, S.; B €u hlmann, P.; Iwao, M.; Nishizawa, S.;
Amemiya, S.; Umezawa, Y. Tetrahedron Lett. 1995, 36,
6483; (c) Xiao, K. P.; B €u hlmann, P.; Umezawa, Y. Anal.
Chem. 1997, 69, 1038; (d) Nishizawa, S.; Teramae, N. Anal.
Sci. 1997, 13, 485; (e) Nishizawa, S.; Kaneda, H.; Uchida, T.;
Teramae, N. J. Chem. Soc., Perkin Trans. 2 1998, 2325; (f)
Tobe, Y.; Sasaki, S.; Mizuno, M.; Naemura, K. Chem. Lett.
1998, 835; (g) Lee, D. H.; Lee, H. Y.; Lee, K. H.; Hong, J.-I.
Tetrahedron Lett. 2001, 42, 5447; (h) Nie, L.; Li, Z.; Han, J.;
Zhang, X.; Yang, R.; Liu, W.-X.; Wu, F.-Y.; Xie, J. W.; Zhao,
Y. F.; Jiang, Y.-B. J. Org. Chem. 2004, 69, 6449; (i) Zeng,
Z.-Y.; He, Y.-B.; Wu, J.-L.; Wei, L.-H.; Liu, X.; Meng, L.-Z.;
Yang, X. Eur. J. Org. Chem. 2004, 2888; (j) Gunnlaugsson,
T.; Kruger, P. E.; Jensen, P.; Tierney, J.; Ali, H. D. P.; Hussey,
G. M. J. Org. Chem. 2005, 70, 10875; (k) Amendola, V.;
Esteban-G ꢀo mez, D.; Fabbrizzi, L.; Liccherlli, M. Acc. Chem.
Res. 2006, 39, 343; (l) Bryantsev, V. S.; Hay, B. P. J. Am.
Chem. Soc. 2006, 128, 2035; (m) Jun, E. J.; Swamy,
K. M. K.; Bang, H.; Kim, S.-J.; Yoon, J. Tetrahedron Lett.
Reuse of the chiral thiourea (S,S)-2 is feasible following
extraction of the NMR solution with 20 mL of dichloro-
methane, previous addition of 20 mL of water. Concentration
of the organic phase afforded (S,S)-2, which was purified
by flash column chromatography (hexane–EtOAc, 1:1).
Acknowledgements
We are grateful to Conacyt, Mexico, for financial support via
Grant No. 45157-Q.
References and notes
2
006, 47, 3103; (n) Kondo, S.; Sato, M. Tetrahedron 2006,
1
. (a) Lehn, J.-M. Supramolecular Chemistry, Concepts
and Perspectives; VCH: Weinheim, Germany, 1995; (b)
Supramolecular Chemistry of Anions; Bianchi, A., Bowman-
James, K., Garc ꢀı a-Espa n˜ a, E., Eds.; Wiley-VCH: New York,
NY, 1997; (c) Steed, J. W.; Atwood, J. L. Supramolecular
Chemistry; Wiley-VCH: Chichester, UK, 2000.
62, 4844; (o) Yen, Y.-P.; Ho, K.-W. Tetrahedron Lett. 2006,
47, 1193; (p) Wu, F.-Y.; Li, Z.; Guo, L.; Wang, X.; Lin,
M.-H.; Zhao, Y.-F.; Jiang, Y.-B. Org. Biomol. Chem. 2006, 4,
624; (q) Bonizzoni, M.; Fabbrizzi, L.; Taglietti, A.; Tiengo,
F. Eur. J. Org. Chem. 2006, 3567; (r) Fremantle, M. Chem.
Eng. News 2006, February 13, 83.
2
. (a) de Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, T.;
Huxley, A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice,
T. E. Chem. Rev. 1997, 97, 1515; (b) Rurack, K.; Resch-
Genger, U. Chem. Soc. Rev. 2002, 31, 116.
7. (a) Huang, H.; Jacobsen, E. N. J. Am. Chem. Soc. 2006, 127,
7170; (b) Tsogoeva, S. B.; Wei, S. Chem. Commun. 2006,
1451; (c) Li, H.; Wang, J.; Zu, L.; Wang, W. Tetrahedron
Lett. 2006, 47, 2585; (d) Li, H.; Zu, L.; Wang, J.; Wang, W.
Tetrahedron Lett. 2006, 47, 3145; (e) Xu, X.; Yabuta, T.;
Yuan, P.; Takemoto, Y. Synlett 2006, 137; (f) Okino, T.;
Hoashi, Y.; Furukawa, T.; Xu, X.; Takemoto, Y. J. Am. Chem.
Soc. 2005, 127, 119.
8. (a) Tillman, A. L.; Ye, J.; Dixon, D. J. Chem. Commun. 2006,
1191; (b) Song, J.; Wang, Y.; Deng, L. J. Am. Chem. Soc.
2006, 128, 6048; (c) Yoon, T. P.; Jacobsen, E. N. Angew.
Chem., Int. Ed. 2005, 44, 466; (d) Wenzel, A. G.; Lalonde,
M. P.; Jacobsen, E. N. Synlett 2003, 1919; (e) Wenzel, A. G.;
Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 12964.
3
. (a) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40,
4
9
86; (b) Sessler, J. L.; Davis, J. M. Acc. Chem. Res. 2001, 34,
89; (c) Wiskur, S. L.; Ait-Haddou, H.; Anslyn, E. V.;
Lavigne, J. J. Acc. Chem. Res. 2001, 34, 963; (d)
Fitzmaurice, R. J.; Kyne, G. M.; Douheret, D.; Kilburn, J. D.
J. Chem. Soc., Perkin Trans. 1 2002, 841; (e) Suksai, C.;
Tuntulani, T. Chem. Soc. Rev. 2003, 32, 192; (f) Vilar, R.
Angew. Chem., Int. Ed. 2003, 42, 1460; (g) Mart ꢀı nez-M ꢀa n˜ ez,
R.; Sancen ꢀo n, F. Chem. Rev. 2003, 103, 4419; (h) Coord.
Chem. Rev. 2003, 240, numbers 1 and 2; (i) Schug, K. A.;
Linder, W. Chem. Rev. 2005, 105, 67; (j) Blondeau, P.;
Segura, M.; P ꢀe rez-Fern ꢀa ndez, R.; de Mendoza, J. Chem. Soc.
Rev. 2007, 36, 198–210.
9. (a) Vachal, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124,
10012; (b) Vachal, P.; Jacobsen, E. N. Org. Lett. 2000, 2,
867; (c) Sigman, M. S.; Vachal, P.; Jacobsen, E. N. Angew.

7678
M. Hern aꢀ ndez-Rodr ꢀı guez, E. Juaristi / Tetrahedron 63 (2007) 7673–7678
Chem., Int. Ed. 2000, 39, 1279; (d) Sigman, M. S.; Jacobsen,
17. (a) Gunnlaugsson, T.; Davis, A. P.; Hussey, G. M.; Tierney, J.;
Glynn, M. Org. Biomol. Chem. 2004, 2, 1856; See also:
(b) Mei, X.; Wolf, C. J. Am. Chem. Soc. 2004, 126, 14736; (c)
Xu, K.-X.; Wu, X.-J.; He, Y.-B.; Liu, S.-Y.; Qing, G.-Y.;
Meng, L.-Z. Tetrahedron: Asymmetry 2005, 16, 833; (d) Kim,
S. K.; Singh, N. J.; Kim, S. J.; Swamy, K. M. K.; Kim, S. H.;
Lee, K.-H.; Kim, K. S.; Yoon, J. Tetrahedron 2005, 61, 4545.
18. Yang, D.; Li, X.; Fan, Y.-F.; Zhang, D.-W. J. Am. Chem. Soc.
2005, 127, 7996.
E. N. J. Am. Chem. Soc. 1998, 120, 4901; For cyanosilylation
of carbonyl compounds, see: (e) Fuerst, D. E.; Jacobsen,
E. N. J. Am. Chem. Soc. 2006, 127, 8964; (f) Steele, R. M.;
Monti, C.; Gennari, C.; Piarulli, U.; Andreoli, F.; Vanthuyne,
N.; Roussel, C. Tetrahedron: Asymmetry 2006, 17, 999.
1
1
0. (a) Wang, J.; Li, H.; Yu, X.; Zu, L.; Wang, W. Org. Lett. 2005, 7,
4293; (b) Sohtome, Y.; Tanatani, A.; Hashimoto, Y.; Nagasawa,
K. Tetrahedron Lett. 2004, 45, 5589.
1. (a) Berkessel, A.; Cleemann, F.; Mukherjee, S.; M €u ller, T. N.;
Lex, J. Angew. Chem., Int. Ed. 2005, 44, 807; (b) Taylor, M. S.;
Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 10558; (c) Joly,
G. D.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 4102; (d)
Okino, T.; Nakamura, S.; Furukawa, T.; Takemoto, Y. Org.
Lett. 2004, 6, 625.
19. For reviews on the use of chiral reagents for the determination
of enantiomeric excess and absolute configuration using NMR
spectroscopy, see: (a) Parker, D. Chem. Rev. 1991, 91, 1441; (b)
Wenzel, T. J.; Wilcox, J. D. Chirality 2003, 15, 256; (c) Seco,
J. M.; Qui n˜ o ꢀa , E.; Riguera, R. Chem. Rev. 2004, 104, 17.
20. See also: (a) Sweeting, L. M.; Crans, D. C.; Whitesides, G. M.
J. Org. Chem. 1987, 52, 2273; (b) Costa, V. E. U.; Art, M.
Magn. Reson. Chem. 1996, 34, 929; (c) Anaya de Parrodi,
C.; Moreno, G. E.; Quintero, L.; Juaristi, E. Tetrahedron:
Asymmetry 1998, 9, 2093; (d) Uccello-Barreta, G.;
Bernardini, R.; Lazzaroni, R.; Salvadori, P. Org. Lett. 2000,
2, 1795; (e) Menezes, P. H.; Goncalves, S. M. C.; Hallwass,
F.; Silva, R. O.; Bieber, L. W.; Simas, A. M. Org. Lett. 2003,
5, 1601.
1
2. Cf.: Voet, D.; Voet, J. G. Biochemistry; Wiley: New York, NY,
1
990.
3. (a) Jadhav, V. D.; Schmidtchen, F. P. Org. Lett. 2006, 8, 2329;
b) Echavarren, A.; Gal ꢀa n, A.; Lehn, J.-M.; de Mendoza, J.
1
(
J. Am. Chem. Soc. 1989, 111, 4994; (c) For a pioneering study
via diastereomeric salts, see: Fulwood, R.; Parker, D. J. Chem.
Soc., Perkin Trans. 2 1994, 57; (d) Ma, F.; Ai, L.; Shen, X.;
Zhang, C. Org. Lett. 2007, 9, 125.
1
4. (a) Hamann, B. C.; Branda, N. R.; Rebek, J. Tetrahedron Lett.
1993, 34, 6837; For early studies with achiral (thio)urea recep-
21. (a) Nicolaou, K. C.; Snyder, S. A. Classics in Total Synthesis II;
Wiley-VCH: Weinheim, 2003; (b) Second Edition of
Enantioselective Synthesis of b-Amino Acids; Juaristi, E.,
Soloshonok, V. A., Eds.; Wiley-VCH: New York, NY, 2005.
22. For recent reviews on applications of 1-phenylethylamine in
the preparation of enantiomerically pure compounds, see: (a)
Juaristi, E.; Escalante, J.; Le ꢀo n-Romo, J. L.; Reyes, A.
Tetrahedron: Asymmetry 1998, 9, 715; (b) Juaristi, E.; Le ꢀo n-
Romo, J. L.; Reyes, A.; Escalante, J. Tetrahedron:
Asymmetry 1999, 10, 2441.
tors, see: (b) Smith, P. J.; Reddington, M. V.; Wilcox, C. S.
Tetrahedron Lett. 1992, 41, 6085; (c) Fan, E.; Van Arman,
S. A.; Kincaid, S.; Hamilton, A. D. J. Am. Chem. Soc. 1993,
115, 369; (d) Hayashita, T.; Onodera, T.; Kato, R.;
Nishizawa, S.; Teramae, N. Chem. Commun. 2000, 755.
5. Kyne, G. M.; Light, M. E.; Hursthouse, M. B.; de Mendoza, J.;
Kilburn, J. D. J. Chem. Soc., Perkin Trans. 1 2001, 1258.
6. Laurent, P.; Miyaji, H.; Collinson, S. R.; Prokes, E.; Moody,
C. J.; Tucker, J. H. R.; Slawin, A. M. Z. Org. Lett. 2002, 4,
1
1
23. V ꢀa zquez, J.; Bern ꢁe s, S.; Reyes, Y.; Moya, M.; Sharma, P.;
Alvarez, C.; Guti ꢀe rrez, R. Synthesis 2004, 1955.
4037.