'N-stereogenic quaternary ammonium salts' from L-amino acids: Synthesis, separation, and absolute configuration

Article abstract of DOI:10.1002/hlca.200800326

Diastereoisomeric linear and cyclic 'N-chiral quaternary ammonium salts' (QASs) were efficiently synthesized from corresponding L-amino acids in high yields. The diastereoisomers of each pair of 'N-chiral QASs' were successfully separated. The absolute configurations of these QASs were determined predominately by X-ray single-crystal analysis. The ¹H-NMR data of 'N-chiral QASs' provided characteristic information on the configuration of the N-chiral center. 'N-Chiral QASs' exemplified by [N(R)]-2a and [N(S)]-2a are stable in protic and aprotic solvents within a broad pH and temperature range.

Full text of DOI:10.1002/hlca.200800326

Helvetica Chimica Acta – Vol. 92 (2009)
677
ꢀN-Stereogenic Quaternary Ammonium Saltsꢁ from l-Amino Acids:
Synthesis, Separation, and Absolute Configuration
by Hua-Fang Wua), Wen-Bin Linb), Li-Zi Xiab), Ying-Gang Luob), Xiao-Zhen Chenb), Guo-You Lib),
Guo-Lin Zhang*b), and Xin-Fu Pan*a)
a) Department of Chemistry, State Key Laboratory of Applied Organic Chemistry, Lanzhou University,
Lanzhou 730000, P. R. China
b) Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, P. R. China
(phone/fax: þ 86-28-85225401; e-mail: zhanggl@cib.ac.cn)
Diastereoisomeric linear and cyclic ꢀN-chiral quaternary ammonium saltsꢁ (QASs) were efficiently
synthesized from corresponding l-amino acids in high yields. The diastereoisomers of each pair of ꢀN-
chiral QASsꢁ were successfully separated. The absolute configurations of these QASs were determined
predominately by X-ray single-crystal analysis. The 1H-NMR data of ꢀN-chiral QASsꢁ provided
characteristic information on the configuration of the N-chiral center. ꢀN-Chiral QASsꢁ exemplified by
[N(R)]-2a and [N(S)]-2a are stable in protic and aprotic solvents within a broad pH and temperature
range.
Introduction. – Chiral quaternary ammonium salts (QASs) are of great potential in
asymmetric phase-transfer-catalyzed reactions [1]. Among them cinchona-alkaloid-
derived QASs give more impressive enantioselectivity for various reactions than other
phase-transfer catalysts (PTCs) do, with only few notable exceptions [2]. However, the
major drawback of those QASs is the difficulty in modifying the structure for a better
selectivity or reactivity. Furthermore, the role of the N-atom in those chiral QASs was
neglected by organic chemists, whereas chiral C- [3], P- [4], and S-centered [5]
molecules have been studied intensively. In addition, there are few reports dealing with
an intentional construction of ꢀN-chiral QASꢁ [6]. Investigations on their properties
and applications were hampered by their separations which are much more difficult
than the separations of other chiral compounds. Only two methods, repeated fractional
crystallization and resolution by chiral materials, were reported as convenient and
successful separations of ꢀN-chiral QASsꢁ. However, the two methods bear insur-
mountable disadvantages: i) Repeated fractional crystallization gave only one single
diastereoisomer1); ii) separation of ꢀN-chiral QASsꢁ by chiral materials is difficult to
operate, not applicable universally, and the method gave unsatisfactory optical purities
[7][8]. Recently, Tayama and Tanaka resolved a N-centered tetraalkylammonium salts
with (R)-binol as chiral complexing agent and obtained two pure enantiomers from
each enantiomer mixture [9] (binol ¼ [1,1’-binaphthalene]-2,2’-diol).
1
)
When the introduction order of the two substituents at the N-atom was reversed, the ratio of the
two diastereoisomers was also reversed. So the other diastereoisomer was obtained by repeated
fractional crystallization. See [6b – d].
ꢂ 2009 Verlag Helvetica Chimica Acta AG, Zꢃrich

678
Helvetica Chimica Acta – Vol. 92 (2009)
Chiral amino acids and their derivatives have been widely used in asymmetric
synthesis. Recently, proline derivatives were employed as starting materials to prepare
ꢀN-chiral QASsꢁ [6a – d]. Other amino acids with various functional groups provide the
possibility to diversify the structures of ꢀN-chiral QASsꢁ. Furthermore, the ꢀN-chiralityꢁ
in ꢀN-chiral QASsꢁ may be induced by the ꢀC-chiralityꢁ of tertiary amines formed from
l-amino acids. Therefore, synthesis of ꢀN-chiral QASsꢁ from well-available compounds
with convenient separation procedures is of great practical value. Herein, we describe
the successful synthesis, separation, absolute-configuration determination, and stability
of ꢀN-chiral QASsꢁ from l-amino acids.
Results and Discussion. – l-Amino acids with different side chains were used as
starting materials to prepare tertiary amines by a modified ꢀone-potꢁ method in high
yields2). Allylation of the obtained tertiary amines afforded linear ꢀN-chiral QASsꢁ
2a – 2f (Scheme and Table 1). Alkylations of the cyclic tertiary amine (3S)-1,2,3,4-
tetrahydro-2-methylisoquinoline-3-methanol prepared from l-phenylalanine [11] gave
the cyclic ꢀN-chiral QASsꢁ 2g – 2i (Scheme and Table 1).
1
The H-NMR data of the prepared ꢀN-chiral QASsꢁ 2 suggested that they are
mixtures of diastereoisomers with a ratio of 1.1:1 to 1.5 :1, indicating that the induction
of the ꢀN-chiralityꢁ by ꢀC-chiralityꢁ was only modest.
Scheme
a) 1. NaHCO3 (1.2 equiv.), MeOH, 08, 15 min; 2. PhCHO (1.05 equiv.), r.t., 2.0 – 3.5 h; 3. KBH4 (0.4
equiv.), 08 to r.t., 0.5 – 1 h; 4. 37% HCHO soln. (1.8 equiv.), r.t., 2.5 – 4.5 h; 5. KBH4 (2.0 equiv.), 08 to r.t.,
5 – 11 h; total yield 78 – 91%. b) LiAlH4 (1.0 equiv.), 0.5 – 1 h, Et2O, 08; 87 – 97%. c) RX (2.0 equiv.),
MeCN, reflux 5 – 48 h; 84 – 95%. d) Separation.
2
)
The tertiary amines were prepared by reduction of the corresponding l-amino acid esters by
LiAlH4, and the esters were prepared according to [10]. The neutralization of l-amino acid ester
hydrochlorides and imine (iminium) formation/reduction was carried out in the same flask without
isolation.

Helvetica Chimica Acta – Vol. 92 (2009)
679
Table 1. Synthesis of N-Chiral QASs 2 from l-Amino Acid Derivativesa)
R1
R2
RX
Yield [%]
2a
2b
2c
2d
2e
2f
2g
2h
2i
Me
i-Bu
Ph
Bn
Bn
Bn
Bn
Bn
Bn
Bn
H2C¼CHCH2Br
H2C¼CHCH2Br
H2C¼CHCH2Br
H2C¼CHCH2Br
H2C¼CHCH2Br
H2C¼CHCH2Br
H2C¼CHCH2Br
Me2C¼CHCH2Br
9-(chloromethyl)anthracene
95
90
91
92
89
90
95
92
84
PhCH2CH2
4-OHꢀBn
H2CꢀC6H4ꢀCH2
H2CꢀC6H4ꢀCH2
H2CꢀC6H4ꢀCH2
b
b
b
)
)
)
a) The d.e. of these N-chiral QASs is 1.1 : 1 to 1.5 : 1. b) Resulting in an isoquinolinium structure.
Separation of enantiomeric or diastereoisomeric ꢀN-chiral QASsꢁ is a difficult
problem in the research of ꢀN-chiral QASꢁ-catalyzed reactions. Based on the methods
previously used for the separation of ꢀN-chiral QASsꢁ, we attempted to separate the
diastereoisomers 2. However, only three pairs of ꢀN-chiral QASsꢁ were separated
successfully, i.e., the diastereoisomers of ꢀN-chiral QASsꢁ 2f and 2i by recrystallization,
and the diastereoisomers of 2a by the method of Tayama and Tanaka with (R)-binol
and (S)-binol.
Precipitation and column chromatography were introduced to separate the ꢀN-
chiral QASsꢁ. In view of the different solubility of the diastereoisomeric ꢀN-chiral
QASsꢁ, we attempted to separate the ꢀN-chiral QASsꢁ by precipitation, and to our
surprise, the diastereoisomers of 2b, 2d, and 2e were separated efficiently. The
diastereoisomers of 2c were separated by classical column chromatography, and those
of 2g and 2h by the combination of column chromatography and the method of Tayama
and Tanaka. Thus, nine pairs of diastereoisomeric ꢀN-chiral QASsꢁ were successfully
separated, and eighteen pure ꢀN-chiral QASsꢁ were obtained.
The absolute configuration of these QASs was determined predominately by X-ray
single-crystal analysis. The two diastereoisomers of 2d were crystallized from EtOH
and acetone, respectively, to give suitable single crystals for X-ray analysis of [N(S)]-2d
and [N(R)]-2d, respectively (Fig.)3).
Only one of the diastereoisomer 2b, 2e, 2f, and 2i could be crystallized for X-ray
crystallographic analysis, and they were successively determined as [N(S)]-2b, [N(R)]-
2e, [N(S)]-2f, and [N(R)]-2i3). One of the diastereoisomers of 2a, 2g, and 2h was
crystallized as a 1:1 complex with (S)-binol; X-ray crystallographic analysis of these
complexes revealed that they were [N(R)]-2a, [N(R)]-2g, and [N(R)]-2h3). The
absolute configurations of their corresponding diastereoisomers could be thus assigned
as [N(S)]-2a, [N(R)]-2b, [N(S)]-2e, [N(R)]-2f, [N(S)]-2g, [N(S)]-2h, and [N(S)]-2i.
3
)
CCDC-689671 (complex of [N(R)]-2h and (S)-binol), CCDC-689672 (complex of [N(R)]-2a and
(S)-binol), CCDC-689673 ([N(R)]-2d), CCDC-689674 ([N(S)]-2b), CCDC-689675 ([N(R)]-2i),
CCDC-689788 (complex of [N(R)]-2g and (S)-binol), CCDC-689789 ([N(R)]-2e), CCDC-689790
([N(S)]-2d), and CCDC-689791 ([N(S)]-2f) contain the supplementary crystallographic data for this
work. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif.

680
Helvetica Chimica Acta – Vol. 92 (2009)
Figure. ORTEP Diagrams of the two diastereoisomers of N-chiral QASs 2d: a) [N(R)]-2d and b)
[N(S)]-2d. H-Atoms and solvent molecules are omitted for clarity.
The absolute configurations of the two diastereoisomers of 2c had to be determined
by other methods since none of them afforded crystals suitable for X-ray crystal
1
analysis. We investigated the H-NMR spectra of the ꢀN-chiral QASsꢁ with known
absolute configuration determined by X-ray crystallography in detail. The differences
of the chemical shifts of the two H-atoms of PhCH2N in ꢀ[N(R)]-QASsꢁ and those of
ꢀ[N(S)]-QASsꢁ were determined (Table 2). It was found that the differences of the
chemical shifts Dd (0.34 to 0.80 ppm) of the two H-atoms in ꢀ[N(R)]-QASsꢁ were much
larger than those (0.00 to 0.50 ppm) in the ꢀ[N(S)]-QASsꢁ (Table 2). The correspond-
ing Dd of the two diastereoisomers of 2c were 0.74 and 0.91, respectively. Therefore, the
former diastereoisomer was deduced as [N(S)]-2c and the latter as [N(R)]-2c.
Table 2. Differences Dd of the Chemical Shifts of the Two H-Atoms in PhCH2N of Linear [N(R)]- and
a
[N(S)]-QASs 2 and the Differences DDd between DdR and DdS
)
Configuration at N-atom
Dd [ppm]
DDd ¼ DdR ꢀ DdS [ppm]
2a
2b
2c
2d
2e
2f
R
S
R
S
R
S
R
S
R
S
R
S
0.60
0.05
0.80
0.50
0.91
0.74
0.65
0.22
0.34
0.06
0.35
0.00
0.55
0.30
0.17
0.43
0.28
0.35
a) 1H-NMR in CDCl3, except for 2e and 2f whose 1H-NMR were recorded in (D6)DMSO.
As potential PTCs, the stability of ꢀN-chiral QASsꢁ is the first concern for their
application. We investigated the stability of the ꢀN-chiral QASsꢁ as exemplified by the
ꢀN-chiral QASsꢁ [N(R)]-2a and [N(S)]-2a at various pH values (1.0, 4.0, 7.0, 11.0, and

Helvetica Chimica Acta – Vol. 92 (2009)
681
14.0), temperatures (0, 25, and 508), and intervals (10, 24, and 48 h) by means of
1H-NMR (D2O) spectra to monitor possible changes. No detectable changes were
observed, indicating that the QASs are stable under these conditions. Additionally, no
racemization of [N(R)]-2a and [N(S)]-2a was found in DMSO, MeOH, or CHCl3 even
after two weeks. These results suggest that these ꢀN-chiral QASsꢁ have potential in an
asymmetric phase-transfer-catalyzed reaction, and they are being investigated in our
lab.
Conclusions. – We have successfully synthesized and separated a series of linear and
cyclic ꢀN-chiral QASsꢁ from the corresponding l-amino acid derivatives. The absolute
configurations of these QASs were determined by X-ray single-crystal analysis. In the
linear ꢀN-chiral QASsꢁ, the differences of the chemical shifts of the two H-atoms of the
PhCH2N moiety in ꢀ[N(R)]-QASsꢁ are much larger than those in the diastereoisomeric
ꢀ[N(S)]-QASsꢁ. No racemization of ꢀN-chiral QASsꢁ was found in protic and aprotic
solvents, and they were stable in broad pH and temperature ranges, suggesting that
these ꢀN-chiral QASsꢁ have potential in phase-transfer-catalyzed reactions.
This work was financially supported by the National Natural Science Foundation of China (No.
20672108). Prof. Kai-bei Yu and Zhi-hua Mao carried out the X-ray single-crystal analysis.
Experimental Part
1. General. Commercial reagents were used without purification. All solvents including petroleum
ether (60 – 908) were distilled prior to use. Anh. MeCN was freshly distilled from CaH2. The
hydrochloride salts of amino esters were synthesized via reported procedures. Column chromatography
(CC): Silica gel (SiO2; 200 – 300 mesh). TLC: SiO2 GF254 plates. M.p.: X-6 melting-point apparatus;
uncorrected. Optical rotations: Perkin-Elmer 341 automatic polarimeter. IR Spectra: Perkin-Elmer FT-
IR spectrometer. NMR Spectra: Bruker Advance-600 spectrometer, with SiMe4 as internal standard.
Electrospray-ionization mass spectra (ESI-MS) and HR-ESI-MS: Bruker Daltonics-Bio-TOF-Q mass
spectrometer. X-Ray measurement: Enraf-Nonius-CAD4 or Rigaku-Raxis-Rapid diffractometer;
programs used: Siemens SHELXTL plus/SHELXL-97.
2. N-Benzyl-N-methyl-Substituted Amino Acid Esters: General Procedure. NaHCO3 (101 mg,
1.2 mmol) was added to a soln. of l-amino acid ester hydrochloride (1.0 mmol) in MeOH (5 ml) with
stirring. After 15 min, benzaldehyde (0.11 ml, 1.05 mmol) was added. The resulting soln. was stirred for
2.0 – 3.5 h at r.t. The mixture was cooled to 08, then KBH4 (22 mg, 0.4 mmol) was added, and the mixture
stirred for 0.5 – 1 h at r.t. to give the corresponding benzylamino derivative. The latter was treated with
37% HCHO soln. (0.14 ml, 1.8 mmol) and stirred for 2.5 – 4.5 h. The resulting soln. was again treated with
KBH4 (108 mg, 2 mmol) below 08 and then stirred for 5 – 11 h at r.t. The org. solvents were evaporated to
afford a slurry syrup, which was diluted with H2O (5 ml) and extracted with AcOEt (3 ꢁ 8 ml). The org.
layer was washed with brine, dried, and concentrated, and the residue separated by CC (SiO2) to give one
of the title compounds with yields between 78% and 91%.
3. N-Benzyl-N-methyl-Substituted Amino Alcohols 1a – 1f: General Procedure. To the N-benzyl-N-
methyl-substituted amino acid ester (1 mmol) in anh. Et2O (5 ml), LiAlH4 (38 mg, 1 mmol) was added at
08. After 0.5 – 1 h, the soln. was quenched by the sequential addition of H2O (0.04 ml), 10% NaOH soln.
(0.04 ml), and H2O (0.12 ml). The resulting slurry was filtered through Celite, and the filtrate was dried.
Then the solvent was evaporated to give one of the title compounds with yields between 87% and 97%.
These materials can be used directly for the next step.
4. ꢀN-Chiral QASsꢁ 2: General Procedure. A mixture of the tertiary amine 1 (1 mmol) and allyl
bromide (0.17 ml, 2 mmol) in anh. MeCN (5 ml) was refluxed for 5 – 48 h. After being cooled to r.t., the
excess allyl bromide and MeCN were evaporated. The residue was purified by flash CC (SiO2, AcOEt/

682
Helvetica Chimica Acta – Vol. 92 (2009)
MeOH 10 :1) to afford the diastereoisomer mixtures 2 of the ꢀN-chiral QASsꢁ with yields between 84%
and 95%.
5. Separation of Diastereoisomers of ꢀN-Chiral QASsꢁ. 5.1. Precipitation. The two diastereoisomers of
the QASs 2b, 2d, and 2e were separated by precipitation. Taken the separation of the diastereoisomers of
2e as an example, a white solid appeared immediately when acetone was added to the slurry of 2e
obtained above. Acetone was added till no more white solid appeared. The mixture was stirred at r.t. for
0.5 – 1 h. The solid collected by filtration was [N(R)]-2e. The filtrate was concentrated to give [N(S)]-2e.
Also the two diastereoisomers of 2b and 2d were separated by this procedure.
5.2. Column Chromatography. The two diastereoisomers of 2c (1 mmol) were separated by CC
(SiO2, AcOEt/MeOH 60 :1 (800 ml), 40 :1 (500 ml), 20 :1 (400 ml), and 10 :1 (200 ml)): [N(R)]-2c
(65 mg, 0.18 mmol) and [N(S)]-2c (101 mg, 0.28 mmol).
After the separation of [N(R)]-2g (1 mmol) and [N(R)]-2h (1 mmol) by Tayama and Tanakaꢁs
method (chiral binol complexes with ꢀN-chiral QASsꢁ), the rest of the mixtures of 2g and 2h were
subjected to CC (SiO2, AcOEt/MeOH 60 :1 (500 ml), 30 :1 (300 ml), and 10 :1 (200 ml)): [N(S)]-2g
(104 mg, 0.35 mmol) and [N(S)]-2h (107 mg, 0.33 mmol).
5.3. Recrystallization. [N(S)]-2f and [N(S)]-2i were recrystallized from the EtOH soln. of 2f and the
MeOH soln. of 2i, resp. After removal of [N(S)]-2f and [N(S)]-2i from their mother liquor, [N(R)]-2f
and [N(R)]-2i were crystallized from the mother liquor.
5.4. Tayama and Tanakaꢁs Method: Chiral binol Complexes with ꢀN-Chiral QASsꢁ. To a soln. of 2a
(299 mg, 1.00 mmol) in CH2Cl2 (3.0 ml) was added (S)-binol (126 mg, 0.44 mmol) at r.t., and the mixture
was stirred for 24 h. The precipitate was isolated by filtration and crystallized in EtOH to give the
corresponding 1:1 complex as colorless crystals. The complex was extracted with H2O and Et2O to
dissociate the complex. From the H2O layer, we obtained the single diastereoisomer of [N(R)]-2a
(110 mg, 0.37 mmol). The same procedure, but with (R)-binol (160 mg, 0.37 mmol), afforded [N(S)]-2a
(143 mg, 0.48 mmol).
With 0.55 equiv. of (S)-binol, [N(R)]-2g and [N(R)]-2h were separated according to the above
procedure.
6. Data of Synthesized Compounds. N-Benzyl-N-methyl-l-alanine Methyl Ester. CC (SiO2,
petroleum ether/AcOEt 25 :1). Yield 85%. Colorless oil. [a]2D5 ¼ ꢀ71 (c ¼ 0.10, MeOH). IR (film):
3027, 2983, 2950, 2845, 1737, 1453, 1193, 736. 1H-NMR (600 MHz, CDCl3): 7.29 – 7.34 (m, 4 H); 7.23 – 7.26
(m, 1 H); 3.73 (s, 3 H); 3.71 (d, J ¼ 13.4, 1 H); 3.61 (d, J ¼ 13.4, 1 H); 3.48 (q, J ¼ 7.1, 1 H); 2.28 (s, 3 H);
1.34 (d, J ¼ 7.1, 3 H ) . 13C-NMR (150 MHz, CDCl3): 173.9; 139.4; 128.8; 128.2; 127.0; 60.7; 58.4; 51.2; 37.9;
14.8. ESI-MS: 208.0 ([M þ H]þ).
N-Benzyl-N-methyl-l-alaninol (1a). CC (SiO2, petroleum ether/AcOEt 10 :1). Yield 97%. Colorless
oil. [a]2D5 ¼ þ44 (c ¼ 0.10, MeOH). IR (film): 3433, 3027, 2965, 1493, 1452, 1042, 734. 1H-NMR (600 MHz,
CDCl3): 7.29 – 7.33 (m, 4 H); 7.24 – 7.26 (m, 1 H); 3.67 (d, J ¼ 13.1, 1 H); 3.45 (d, J ¼ 13.1, 1 H); 3.36 – 3.43
(m, 2 H); 2.94 – 3.00 (m, 1 H); 2.14 (s, 3 H); 0.92 (d, J ¼ 6.7, 3 H). 13C-NMR (150 MHz, CDCl3): 139.2;
128.8; 128.4; 127.1; 62.9; 58.7; 57.8; 35.4; 8.5. ESI-MS: 180.1 ([M þ H]þ), 202.1 ([M þ Na]þ).
N-Benzyl-N-methyl-l-leucine Methyl Ester. CC (SiO2, petroleum ether/AcOEt 30 :1). Yield 87%.
Off-yellow liquid. [a]2D5 ¼ ꢀ70 (c ¼ 0.10, MeOH). IR (film): 3029, 2954, 2870, 1732, 1454, 1156, 736.
1H-NMR (600 MHz, CDCl3): 7.29 – 7.32 (m, 4 H); 7.21 – 7.24 (m, 1 H); 3.78 (d, J ¼ 13.6, 1 H); 3.72 (s,
3 H); 3.58 (d, J ¼ 13.6, 1 H); 3.40 (dd, J ¼ 8.2, 7.1, 1 H); 2.25 (s, 3 H); 1.73 – 1.78 (m, 1 H); 1.63 – 1.68 (m,
1 H); 1.53 – 1.58 (m, 1 H); 0.92 (d, J ¼ 6.7, 3 H); 0.87 (d, J ¼ 6.5, 3 H). 13C-NMR (150 MHz, CDCl3):
173.5; 139.7; 128.7; 128.2; 126.9; 63.7; 58.5; 50.9; 38.7; 37.7; 24.7; 23.0; 22.0. ESI-MS: 250.1 ([M þ H]þ),
272.1 ([M þ Na]þ).
N-Benzyl-N-methyl-l-leucinol (1b). CC (SiO2, petroleum ether/AcOEt 15 :1). Yield 95%. Pale
yellow liquid. [a]2D5 ¼ þ22 (c ¼ 0.10, MeOH). IR (film): 3431, 3029, 2955, 2868, 1454, 1366, 1020, 735.
1H-NMR (600 MHz, CDCl3): 7.28 – 7.32 (m, 4 H); 7.23 – 7.26 (m, 1 H); 3.69 (d, J ¼ 13.2, 1 H); 3.53 (dd,
J ¼ 10.4, 4.9, 1 H); 3.47 (d, J ¼ 13.2, 1 H); 3.33 (t, J ¼ 10.4, 1 H); 2.83 – 2.87 (m, 1 H); 2.15 (s, 3 H); 1.51 –
1.57 (m, 1 H); 1.40 – 1.44 (m, 1 H); 1.05 – 1.09 (m, 1 H); 0.94 (d, J ¼ 7.1, 3 H); 0.89 (d, J ¼ 7.1, 3 H ) .
13C-NMR (150 MHz, CDCl3): 139.3; 128.8; 128.4; 127.1; 61.6; 61.3; 57.9; 35.7; 33.8; 25.4; 23.8; 22.2. ESI-
MS: 222.0 ([M þ H]þ).

Helvetica Chimica Acta – Vol. 92 (2009)
683
(2S)-N-Benzyl-N-methyl-2-phenylglycine Methyl Ester. CC (SiO2, petroleum/AcOEt 35 :1). Yield
89%. Colorless liquid. [a]2D5 ¼ þ79 (c ¼ 0.10, MeOH). IR (film): 3028, 2949, 2842, 1735, 1601, 1493, 1452,
1340, 1204, 1165, 737. 1H-NMR (600 MHz, CDCl3): 7.46 (d, J ¼ 6.9, 2 H); 7.28 – 7.37 (m, 7 H); 7.22 – 7.25
(m, 1 H); 4.34 (s, 1 H); 3.73 (s, 3 H); 3.65 (d, J ¼ 13.4, 1 H); 3.51 (d, J ¼ 13.4, 1 H); 2.21 (s, 3 H). 13C-NMR
(150 MHz, CDCl3): 172.4; 138.9; 136.6; 128.9; 128.8; 128.5; 128.2; 128.1; 127.0; 72.1; 58.6; 51.7; 39.1. ESI-
MS: 270.1 ([M þ H]þ), 292.1 ([M þ Na]þ).
(2S)-N-Benzyl-N-methyl-2-phenylglycinol (1c). CC (SiO2, petroleum ether/AcOEt 10 :1). Yield
92%. Colorless liquid. [a]2D5 ¼ þ39 (c ¼ 0.10, MeOH). IR (film): 3425, 3028, 2932, 2880, 1601, 1493, 1452,
1
1031, 737. H-NMR (600 MHz, CDCl3): 7.38 (t, J ¼ 6.8, 2 H); 7.29 – 7.35 (m, 5 H); 7.24 (d, J ¼ 6.8, 3 H);
4.05 (t, J ¼ 10.6, 1 H); 3.86 (dd, J ¼ 9.8, 5.1, 1 H); 3.68 (dd, J ¼ 10.6, 5.1, 1 H); 3.62 (d, J ¼ 13.1, 1 H); 3.36
(d, J ¼ 13.1, 1 H); 2.14 (s, 3 H). 13C-NMR (150 MHz, CDCl3): 138.9; 135.5; 129.1; 128.9; 128.4; 128.3;
127.9; 127.2; 68.2; 60.8; 58.5; 36.9. ESI-MS: 242.2 ([M þ H]þ).
N-Benzyl-N-methyl-l-phenylalanine Methyl Ester. CC (SiO2, petroleum ether/AcOEt 35 :1). Yield
87%. Colorless liquid. [a]2D5 ¼ ꢀ80 (c ¼ 0.10, MeOH) ([12]: [a]D23 ¼ ꢀ81.6 (c ¼ 0.5, CDCl3)). IR (film):
3028, 2930, 2848, 2801, 1732, 1604, 1495, 1454, 1165, 1025, 737. 1H- and 13C-NMR and MS: identical with
those reported [12].
N-Benzyl-N-methyl-l-phenylalaninol (1d). CC (SiO2, petroleum ether/AcOEt 10 :1). Yield 96%.
Colorless liquid. [a]2D5 ¼ ꢀ35 (c ¼ 0.10, MeOH). IR (film): 3437, 3027, 2938, 2857, 1602, 1494, 1454, 1032,
730. 1H-NMR (600 MHz, CDCl3): 7.24 – 7.36 (m, 7 H); 7.19 (t, J ¼ 7.0, 1 H); 7.13 (d, J ¼ 7.0, 2 H); 3.76 (d,
J ¼ 13.0, 1 H); 3.56 (d, J ¼ 13.0, 1 H); 3.38 – 3.45 (m, 2 H); 3.04 – 3.09 (m, 1 H); 3.00 (dd, J ¼ 13.4, 4.4,
1 H); 2.39 (dd, J ¼ 13.4, 9.8, 1 H); 2.28 (s, 3 H). 13C-NMR (150 MHz, CDCl3): 139.2; 139.0; 129.0; 128.9;
128.6; 128.5; 127.3; 126.2; 65.6; 60.6; 58.2; 35.9; 31.4. ESI-MS: 256.1 ([M þ H]þ).
N-Benzyl-N-methyl-l-homophenylalanine Ethyl Ester. CC (SiO2, petroleum ether/AcOEt 40 :1).
Yield 91%. Colorless liquid. [a]2D5 ¼ ꢀ75 (c ¼ 0.10, MeOH). IR (film): 3026, 2940, 1728, 1603, 1495, 1454,
1369, 1155, 1028, 699. 1H-NMR (600 MHz, CDCl3): 7.30 – 7.35 (m, 4 H); 7.23 – 7.28 (m, 3 H); 7.18 (d, J ¼
7.3, 3 H); 4.15 – 4.21 (m, 2 H); 3.82 (d, J ¼ 13.6, 1 H); 3.61 (d, J ¼ 13.6, 1 H); 3.31 (t, J ¼ 7.1, 1 H); 2.76 –
2.81 (m, 1 H); 2.64 – 2.69 (m, 1 H); 2.30 (s, 3 H); 2.02 – 2.09 (m, 2 H); 1.31 (t, J ¼ 7.1, 3 H ) . 13C-NMR
(150 MHz, CDCl3): 172.5; 141.8; 139.6; 128.7; 128.5; 128.4; 128.2; 126.9; 125.9; 65.0; 60.0; 58.4; 37.7; 32.4;
31.5; 14.6. ESI-MS: 312.2 ([M þ H]þ).
N-Benzyl-N-methyl-l-homophenylalaninol (1e). CC (SiO2, petroleum ether/AcOEt 10 :1). Yield
94%. Colorless liquid. [a]2D5 ¼ þ20 (c ¼ 0.10, MeOH). IR (film): 3424, 3025, 2932, 2857, 1602, 1494, 1453,
1362, 1126, 1037, 699. 1H-NMR (600 MHz, CDCl3): 7.29 – 7.31 (m, 4 H); 7.18 – 7.25 (m, 6 H); 3.70 (d, J ¼
13.1, 1 H); 3.62 (dd, J ¼ 10.4, 5.0, 1 H); 3.47 (d, J ¼ 13.1, 1 H); 3.41 (t, J ¼ 10.4, 1 H); 2.81 – 2.85 (m, 1 H);
2.64 – 2.68 (m, 1 H); 2.53 – 2.58 (m, 1 H); 2.18 (s, 3 H); 1.93 – 1.99 (m, 1 H); 1.47 – 1.53 (m, 1 H).
13C-NMR (150 MHz, CDCl3): 141.8; 139.1; 128.8; 128.5; 128.4; 128.2; 127.2; 126.1; 63.1; 60.9; 58.2; 35.7;
33.3; 26.9. ESI-MS: 270.2 ([M þ H]þ).
N-Benzyl-N-methyl-l-tyrosine Methyl Ester. CC (SiO2, petroleum ether/AcOEt 15 :1). Yield 81%.
Colorless liquid. [a]2D5 ¼ ꢀ43 (c ¼ 0.10, MeOH) ([12]: [a]2D3 ¼ ꢀ39.2 (c ¼ 0.011, MeOH)). 1H- and
13C-NMR and MS: identical with those reported in [12].
N-Benzyl-N-methyl-l-tyrosinol (1f). CC (SiO2, petroleum ether/AcOEt 5 :1). Yield 87%. Colorless
liquid. [a]2D5 ¼ ꢀ20 (c ¼ 0.10, MeOH). IR (film): 3452, 3028, 2941, 1614, 1495, 1360, 1231, 1036, 734.
1H-NMR (600 MHz, CDCl3): 7.24 – 7.34 (m, 5 H); 6.90 (d, J ¼ 8.2, 2 H); 6.66 (d, J ¼ 8.2, 2 H); 3.76 (d, J ¼
12.9, 1 H); 3.56 (d, J ¼ 12.9, 1 H); 3.39 (br. d, J ¼ 8.0, 2 H); 2.99 – 3.03 (m, 1 H); 2.91 (dd, J ¼ 13.5, 4.2,
1 H); 2.30 (dd, J ¼ 13.5, 3.4, 1 H); 2.27 (s, 3 H). 13C-NMR (150 MHz, CDCl3): 154.8; 138.8; 130.1; 129.9;
128.9; 128.6; 127.4; 115.6; 65.2; 60.3; 58.2; 35.9; 30.3. ESI-MS: 272.0 ([M þ H]þ), 294.0 ([M þ Na]þ).
(3S)-1,2,3,4-Tetrahydro-2-methylisoquinoline-3-methanol (1g). Yield 75%. Colorless crystals
(CH2Cl2/hexane). M.p. 103 – 1058 ([12]: m.p. 104 – 1068). [a]2D5 ¼ ꢀ69 (c ¼ 1.0, CHCl3) ([12]: [a]2D3
¼
ꢀ64 (c ¼ 1.0, CHCl3)). 1H- and 13C-NMR and MS: identical with those reported in [12].
[N(R)]-N-Allyl-N-benzyl-N-[(1S)-2-hydroxy-1-methylethyl]-N-methylammonium
Bromide
(¼ [N(R)]-N-[(1S)-2-Hydroxy-1-methylethyl]-N-methyl-N-prop-2-en-1-ylbenzenemethanaminium Bro-
mide; [N(R)]-2a). Yield 37%. Pale yellow liquid. [a]2D5 ¼ þ6.4 (c ¼ 0.60, MeOH). IR (KBr): 3400, 3017,
2986, 1457, 1072, 759. 1H-NMR (600 MHz, CDCl3): 7.69 (d, J ¼ 6.7, 2 H); 7.43 – 7.48 (m, 3 H); 5.96 – 6.03
(m, 1 H); 5.73 (d, J ¼ 16.8, 1 H); 5.68 (d, J ¼ 10.1, 1 H); 5.43 (t, J ¼ 5.7, 1 H); 5.17 (d, J ¼ 12.9, 1 H); 4.57

684
Helvetica Chimica Acta – Vol. 92 (2009)
(d, J ¼ 12.9, 1 H); 4.35 – 4.38 (m, 1 H); 4.26 (dd, J ¼ 13.5, 7.3, 1 H); 4.05 – 4.07 (m, 1 H); 3.91 (dd, J ¼ 13.5,
7.2, 1 H); 3.78 – 3.81 (m, 1 H); 3.14 (s, 3 H); 1.60 (d, J ¼ 6.9, 3 H). 13C-NMR (150 MHz, CDCl3): 133.6;
130.7; 129.3; 128.9; 127.1; 124.7; 68.0; 63.8; 62.8; 60.6; 47.1; 12.7. HR-ESI-MS: 220.1689 ([M ꢀ Br]þ,
C14H22NOþ; calc. 220.1696).
X-Ray Analysis of the 1:1 Complex of [N(R)]-2a and (S)-binol [12]. Slow evaporation of a soln. of
the complex in EtOH gave a single crystal suitable for X-ray analysis (0.42 ꢁ 0.40 ꢁ 0.38 mm; colorless).
C34H36BrNO3 (586.55): Orthorhombic P212121; a ¼ 10.660(4), b ¼ 13.834(4), c ¼ 20.015(2) ꢄ, b ¼ 908,
V¼ 2951.8 (13) ꢄ3; Z ¼ 4, Dcalc ¼ 1.427 Mg/m3. Intensities were measured on a CAD4 diffractometer,
with MoKa radiation (l 0.71073, q ¼ 1.79 – 25.45, m ¼ 1.427 mmꢀ1) at 292 K. Of the total 4778 reflections,
4394 were independent, and 2717 were observed. R ¼ 0.0391, Rw ¼ 0.0926.
[N(S)]-N-Allyl-N-benzyl-N-[(1S)-2-hydroxy-1-methylethyl]-N-methylammonium
Bromide
(¼ [N(S)]-N-[(1S)-2-Hydroxy-1-methylethyl]-N-methyl-N-prop-2-en-1-ylbenzenemethanaminium Bro-
mide; [N(S)]-2a). Yield 48%. Pale yellow liquid. [a]2D5 ¼ ꢀ23.5 (c ¼ 0.70, MeOH). 1H-NMR
(600 MHz, CDCl3): 7.61 (d, J ¼ 6.9, 2 H); 7.38 – 7.41 (m, 3 H); 6.04 – 6.11 (m, 1 H); 5.64 (d, J ¼ 17.9,
1 H); 5.61 (d, J ¼ 9.6, 1 H); 5.51 (br. s, 1 H); 4.79 – 4.85 (m, 2 H); 4.47 – 4.51 (m, 1 H); 4.25 (br. d, J ¼ 12.4,
1 H); 3.92 (br. d, J ¼ 12.8, 1 H); 3.69 – 3.74 (overlap, 2 H); 3.00 (s, 3 H); 1.58 (d, J ¼ 5.2, 3 H). 13C-NMR
(150 MHz, CDCl3): 133.4; 130.7; 129.3; 128.6; 127.2; 125.0; 68.0; 63.2; 62.9; 60.5; 46.5; 12.6. HR-ESI-MS:
220.1693 ([M ꢀ Br]þ, C14H22NOþ; calc. 220.1696).
[N(S)]-N-Allyl-N-benzyl-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-N-methylammonium Bro-
mide (¼ [N(S)]-N-[(1S)-1-(Hydroxymethyl)-3-methylbutyl]-N-methyl-N-prop-2-en-1-ylbenzenemethan-
aminium Bromide; [N(S)]-2b). Yield 42%. Colorless crystals (acetone). M.p. 143 – 1448. [a]2D5 ¼ ꢀ23
(c ¼ 1.50, MeOH). IR (KBr): 3423, 3021, 2949, 1632, 1458, 1053, 760. 1H-NMR (600 MHz, CDCl3): 7.70
(d, J ¼ 6.8, 2 H); 7.44 – 7.49 (m, 3 H); 5.99 – 6.04 (m, 1 H); 5.67 (d, J ¼ 9.8, 1 H); 5.66 (d, J ¼ 17.6, 1 H);
5.46 (t, J ¼ 6.8, 1 H); 5.17 (d, J ¼ 12.9, 1 H); 4.91 (dd, J ¼ 13.6, 6.5, 1 H); 4.67 (d, J ¼ 12.9, 1 H); 4.53 (dd,
J ¼ 14.5, 5.7, 1 H); 4.04 (d, J ¼ 14.5, 1 H); 3.62 (dd, J ¼ 13.6, 7.6, 1 H); 3.47 (dd, J ¼ 8.9, 2.1, 1 H); 2.97 (s,
3 H); 2.16 (td, J ¼ 12.0, 3.7, 1 H); 1.82 – 1.86 (m, 1 H); 1.53 (t, J ¼ 12.0, 1 H); 1.07 (d, J ¼ 6.7, 3 H); 0.97 (d,
J ¼ 6.5, 3 H). 13C-NMR (150 MHz, CDCl3): 133.5; 130.8; 129.3; 128.8; 127.1; 124.8; 71.7; 63.4; 63.2; 57.2;
46.7; 33.5; 26.0; 24.0; 21.4. HR-ESI-MS: 262.2159 ([M ꢀ Br]þ, C14H22NOþ; calc. 262.2165).
X-Ray Analysis of [N(S)]-2b [12]. Slow evaporation of a soln. of [N(S)]-2b in acetone gave a single
crystal suitable for X-ray analysis (0.48 ꢁ 0.42 ꢁ 0.40 mm; colorless). C17H28BrNO (342.31): Ortho-
rhombic P212121; a ¼ 8.083(4), b ¼ 11.977(5), c ¼ 18.029(12) ꢄ, b ¼ 908, V¼ 1745.5(17) ꢄ3; Z ¼ 4, Dcalc
¼
1.303 Mg/m3. Intensities were measured on a CAD4 diffractometer, with MoKa radiation (l 0.71073, q ¼
2.04 – 25.52, m ¼ 2.352 mmꢀ1) at 292 K. Of the total 2002 reflections, 1842 were independent, and 1187
were observed. R ¼ 0.0637, Rw ¼ 0.1835.
[N(R)]-N-Allyl-N-benzyl-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-N-methylammonium Bro-
mide (¼ [N(R)]-N-[(1S)-1-(Hydroxymethyl)-3-methylbutyl]-N-methyl-N-prop-2-en-1-ylbenzenemethan-
aminium Bromide; [N(R)]-2b). Yield 30%. Pale yellow liquid. [a]2D5 ¼ þ26.7 (c ¼ 2.40, MeOH).
1H-NMR (600 MHz, CDCl3): 7.70 (d, J ¼ 6.7, 2 H); 7.44 – 7.48 (m, 3 H); 5.94 – 5.97 (m, 1 H); 5.69 (d, J ¼
17.3, 1 H); 5.67 (d, J ¼ 10.3, 1 H); 5.31 (d, J ¼ 12.6, 1 H); 4.51 (d, J ¼ 12.6, 1 H); 4.49 (d, J ¼ 11.8, 1 H);
4.24 – 4.26 (m, 1 H); 4.06 (d, J ¼ 13.4, 1 H); 3.92 – 3.96 (m, 1 H); 3.51 (d, J ¼ 10.0, 1 H); 3.16 (s, 3 H); 2.17
(m, 1 H); 1.85 (br. s, 2 H); 1.59 (t, J ¼ 11.0, 1 H); 1.05 (d, J ¼ 6.4, 3 H); 0.91 (d, J ¼ 6.3, 3 H). 13C-NMR
(150 MHz, CDCl3): 133.7; 130.7; 129.3; 128.9; 127.2; 124.7; 71.1; 64.4; 62.9; 57.3; 47.4; 33.6; 26.0; 24.0; 21.3.
HR-ESI-MS: 262.2175 ([M ꢀ Br]þ, C14H22NOþ; calc. 262.2165).
[N(R)]-N-Allyl-N-benzyl-N-[(1S)-2-hydroxy-1-phenylethyl]-N-methylammonium
Bromide
(¼ [N(R),aS]-a-(Hydroxymethyl)-N-methyl-N-(phenylmethyl)-N-prop-2-en-1-ylbenzenemethanamini-
um Bromide; [N(R)]-2c). [N(R)]-2c was eluted after [N(S)]-2c. Yield 18%. Colorless oil. [a]2D5 ¼ þ65
(c ¼ 0.11, MeOH). IR (KBr): 3421, 2920, 1627, 1458, 1054, 752. 1H-NMR (600 MHz, CDCl3): 7.55 – 7.62
(m, 3 H); 7.44 – 7.49 (m, 7 H); 6.12 – 6.19 (m, 1 H), 5.93 (br. s, 1 H); 5.76 (d, J ¼ 16.9, 1 H); 5.73 (d, J ¼
10.4, 1 H); 5.25 (d, J ¼ 13.0, 1 H); 5.02 – 5.04 (m, 1 H); 4.80 – 4.85 (m, 1 H); 4.59 (dd, J ¼ 13.4, 7.5, 1 H);
4.51 (d, J ¼ 13.0, 1 H); 4.39 (br. d, J ¼ 13.6, 1 H); 3.92 (dd, J ¼ 13.4, 6.3, 1 H); 3.00 (s, 1 H). 13C-NMR
(150 MHz, CDCl3): 133.7; 130.9; 130.8; 130.7; 129.6; 129.4; 129.2; 127.1; 125.0; 75.3; 64.9; 62.1; 60.8; 47.3.
HR-ESI-MS: 282.1856 ([M ꢀ Br]þ, C14H22NOþ; calc. 282.1852).

Helvetica Chimica Acta – Vol. 92 (2009)
685
[N(S)]-N-Allyl-N-benzyl-N-[(1S)-2-hydroxy-1-phenylethyl]-N-methylammonium
Bromide
(¼ [N(S),aS]-a-(Hydroxymethyl)-N-methyl-N-(phenylmethyl)-N-prop-2-en-1-ylbenzenemethanamini-
um Bromide; [N(S)]-2c). [N(S)]-2c was eluted before [N(R)]-2c. Yield 28%. Colorless oil. [a]2D5 ¼ þ32
(c ¼ 0.18, MeOH). 1H-NMR (600 MHz, CDCl3): 7.61 (br. d, J ¼ 6.9, 4 H); 7.41 – 7.52 (m, 6 H); 6.07 – 6.14
(m, 1 H); 5.95 (br. s, 1 H); 5.65 (d, J ¼ 10.2, 1 H); 5.61 (d, J ¼ 12.5, 1 H); 5.56 (d, J ¼ 16.9, 1 H); 5.02 (dd,
J ¼ 7.9, 2.3, 1 H), 4.95 (dd, J ¼ 13.4, 6.9, 1 H); 4.88 (dd, J ¼ 14.0, 8.1, 1 H); 4.70 (d, J ¼ 12.5, 1 H); 4.37 (d,
J ¼ 14.0, 1 H); 3.59 (dd, J ¼ 13.4, 7.1, 1 H); 2.77 (s, 3 H). 13C-NMR (150 MHz, CDCl3): 133.8; 131.0; 130.7;
129.6; 129.3; 129.0; 127.0; 125.6; 75.8; 63.7; 63.4; 60.7; 47.0. HR-ESI-MS: 282.1853 ([M ꢀ Br]þ,
C14H22NOþ; calc. 282.1852).
[N(S)]-N-Allyl-N-benzyl-N-[(1S)-1-(hydroxymethyl)-2-phenylethyl]-N-methylammonium Bromide
(¼ [N(S),aS]-a-(Hydroxymethyl)-N-methyl-N-(phenylmethyl)-N-prop-2-en-1-ylbenzeneethanaminium
Bromide; [N(S)]-2d). Yield 41%. Colorless crystals (EtOH). M.p. 185 – 1868. [a]2D5 ¼ ꢀ48 (c ¼ 2.00,
MeOH). IR (KBr): 3430, 2970, 1634, 1456, 1115, 741. 1H-NMR (600 MHz, CDCl3): 7.75 (d, J ¼ 6.8, 2 H);
7.43 – 7.48 (m, 3 H); 7.29 – 7.32 (m, 4 H); 7.24 – 7.27 (m, 1 H); 5.99 – 6.06 (m, 1 H); 5.72 (d, J ¼ 16.9, 1 H);
5.68 (d, J ¼ 10.4, 1 H); 5.43 (t, J ¼ 6.1, 1 H); 5.16 (d, J ¼ 12.9, 1 H); 4.94 (d, J ¼ 12.9, 1 H); 4.85 (dd, J ¼
14.3, 5.8, 1 H); 4.41 (dd, J ¼ 14.3, 6.1, 1 H); 3.75 (dd, J ¼ 13.7, 8.0, 2 H); 3.52 (d, J ¼ 11.0, 1 H); 3.45 (t, J ¼
11.0, 1 H); 3.37 (d, J ¼ 12.1, 1 H); 3.18 (s, 3 H). 13C-NMR (150 MHz, CDCl3): 137.1; 133.7; 130.9; 129.8;
129.5; 129.2; 128.4; 127.6; 127.5; 126.6; 73.5; 63.7; 63.0; 56.6; 47.0; 30.4. HR-ESI-MS: 296.2002 ([M ꢀ
Br]þ, C20H26NOþ; calc. 296.2009).
X-Ray Analysis of [N(S)]-2d [12]. Slow evaporation of a soln. of [N(S)]-2d in EtOH gave a single
crystal suitable for X-ray analysis (0.42 ꢁ 0.40 ꢁ 0.20 mm; colorless). C20H26BrNO (376.33): Ortho-
rhombic P212121; a ¼ 8.270(5), b ¼ 11.477 (6), c ¼ 20.560(9) ꢄ, b ¼ 908, V¼ 1951.3(17) ꢄ3; Z ¼ 4, Dcalc
¼
1.281 Mg/m3. Intensities were measured on a CAD4 diffractometer, with MoKa radiation (l 0.71073, q ¼
1.98 – 25.49, m ¼ 2.111 mmꢀ1) at 292 K. Of the total 3474 reflections, 2985 were independent, and 1534
were observed. R ¼ 0.0491, Rw ¼ 0.1293.
[N(R)]-N-Allyl-N-benzyl-N-[(1S)-1-(hydroxymethyl)-2-phenylethyl]-N-methylammonium Bro-
mide (¼ [N(R),aS]-a-(Hydroxymethyl)-N-methyl-N-(phenylmethyl)-N-prop-2-en-1-ylbenzeneethan-
aminium Bromide; [N(R)]-2d). Yield 31%. Colorless crystals (acetone). M.p. 171 – 1728. [a]2D5 ¼ þ12
(c ¼ 0.08, MeOH). 1H-NMR (600 MHz, CDCl3): 7.78 (d, J ¼ 7.0, 2 H); 7.43 (t, J ¼ 7.3, 1 H); 7.38 (t, J ¼ 7.3,
2 H); 7.19 – 7.29 (m, 5 H); 5.93 – 6.02 (m, 1 H); 5.82 (d, J ¼ 16.8, 1 H); 5.69 (d, J ¼ 10.0, 1 H); 5.40 (t, J ¼
5.4 Hz, 1 H); 5.35 (d, J ¼ 12.7, 1 H); 4.71 (overlap, 1 H); 4.70 (d, J ¼ 12.7, 1 H); 4.29 (dd, J ¼ 14.4, 5.3,
1 H); 3.91 (dd, J ¼ 13.7, 6.6, 1 H); 3.75 (br. d, J ¼ 13.7, 1 H); 3.53 – 3.57 (m, 2 H); 3.37 – 3.41 (m, 1 H); 3.16
(s, 3 H). 13C-NMR (150 MHz, CDCl3): 135.9; 133.8; 130.6; 129.5; 129.2; 129.1; 129.0; 127.4; 127.2; 124.7;
73.3; 64.4; 63.3; 56.1; 47.4; 31.0. HR-ESI-MS: 296.2008 ([M ꢀ Br]þ, C20H26NOþ; calc. 296.2009).
X-Ray Analysis of [N(R)]-2d [12]. Slow evaporation of a soln. of [N(R)]-2d in acetone gave a single
crystal suitable for X-ray analysis (0.46 ꢁ 0.36 ꢁ 0.23 mm; colorless). C20H26BrNO (376.33): Ortho-
rhombic P212121; a ¼ 9.6683(18), b ¼ 13.6013(13), c ¼ 14.616(3) ꢄ, b ¼ 908, V¼ 1922.1(6) ꢄ3; Z ¼ 4,
Dcalc ¼ 1.300 Mg/m3. Intensities were measured on a CAD4 diffractometer, with MoKa radiation (l
0.71073, q ¼ 2.53 – 25.46, m ¼ 2.143 mmꢀ1) at 292 K. Of the total 2383 reflections, 2291 were independent,
and 1046 were observed. R ¼ 0.0555, Rw ¼ 0.1451.
[N(R)]-N-Allyl-N-benzyl-N-[(1S)-1-(hydroxymethyl)-3-phenylpropyl]-N-methylammonium Bro-
mide (¼ [N(R),aS]-a-(Hydroxymethyl)-N-methyl-N-(phenylmethyl)-N-prop-2-en-1-ylbenzenepropan-
aminium Bromide; [N(R)]-2e). Yield 45%. Colorless crystals (EtOH). M.p. 179 – 1808. [a]2D5 ¼ þ51
(c ¼ 5.00, MeOH). IR (KBr): 3429, 3016, 2993, 2786, 1457, 1091, 785. 1H-NMR (600 MHz, (D6)DMSO):
7.60 (d, J ¼ 6.7, 2 H); 7.46 – 7.52 (m, 3 H); 7.28 – 7.33 (m, 4 H); 7.20 – 7.23 (m, 1 H); 5.87 – 5.91 (m, 1 H);
5.61 (t, J ¼ 5.2, 1 H); 5.53 (d, J ¼ 18.4, 1 H); 5.52 (d, J ¼ 9.7, 1 H); 4.76 (d, J ¼ 13.0, 1 H); 4.42 (d, J ¼ 13.0,
1 H); 4.24 (dd, J ¼ 13.6, 7.7, 1 H), 4.13 – 4.16 (m, 1 H); 4.01 – 4.03 (m, 1 H); 3.64 (dd, J ¼ 13.6, 6.5, 1 H);
3.33 (overlap with the signal of the H2O in DMSO, 1 H); 2.94 (s, 3 H); 2.77 – 2.82 (m, 1 H); 2.48 – 2.55 (m,
1 H); 2.23 – 2.31 (m, 1 H); 2.18 – 2.22 (m, 1 H). 13C-NMR (150 MHz, (D6)DMSO): 141.0; 133.8; 130.6;
129.3; 129.1; 128.9; 128.4; 127.5; 126.7; 126.5; 71.9; 63.1; 62.7; 57.2; 46.8; 32.5; 26.5. HR-ESI-MS: 310.2150
([M ꢀ Br]þ, C21H28NOþ; calc. 310.2165).
X-Ray Analysis of [N(R)]-2e [12]. Slow evaporation of a soln. of [N(R)]-2e in EtOH gave a single
crystal suitable for X-ray analysis (0.40 ꢁ 0.30 ꢁ 0.18 mm; colorless). C21H28BrNO (390.35): monoclinic

686
Helvetica Chimica Acta – Vol. 92 (2009)
P21; a ¼ 9.128(4), b ¼ 12.148(3), c ¼ 9.773(2) ꢄ, b ¼ 114.80(2)8, V¼ 983.8(5) ꢄ3; Z ¼ 2, Dcalc ¼ 1.318 Mg/
m3. Intensities were measured on a CAD4 diffractometer, with MoKa radiation (l 0.71073, q ¼ 2.30 –
25.53, m ¼ 2.096 mmꢀ1) at 292 K. Of the total 2157 reflections, 2109 are independent, and 1524 were
observed. R ¼ 0.0542, Rw ¼ 0.1539.
[N(S)]-N-Allyl-N-benzyl-N-[(1S)-1-(hydroxymethyl)-3-phenylpropyl]-N-methylammonium Bro-
mide (¼ [N(S),aS]-a-(Hydroxymethyl)-N-methyl-N-(phenylmethyl)-N-prop-2-en-1-ylbenzenepropan-
aminium Bromide; [N(S)]-2e). Yield 35%. Pale yellow viscous liquid. [a]2D5 ¼ þ34 (c ¼ 1.00, MeOH).
1H-NMR (600 MHz, (D6)DMSO): 7.46 – 7.53 (m, 5 H); 7.29 – 7.35 (m, 4 H); 7.22 – 7.25 (m, 1 H); 6.02 –
6.09 (m, 1 H); 5.61 (d, J ¼ 17.0, 1 H); 5.56 (d, J ¼ 10.2, 1 H); 5.56 (overlap, 1 H); 4.61 (d, J ¼ 13.2,
1 H); 4.55 (d, J ¼ 13.2, 1 H); 4.27 (dd, J ¼ 13.6, 6.6, 1 H); 4.03 – 4.08 (m, 1 H); 3.93 – 4.01 (m, 1 H); 3.77
(dd, J ¼ 13.6, 7.5, 1 H); 3.25 (br. d, J ¼ 11.0, 1 H); 2.94 (s, 3 H); 2.76 – 2.81 (m, 1 H); 2.54 – 2.59 (m, 1 H);
2.28 – 2.38 (m, 1 H); 2.13 – 2.19 (m, 1 H). 13C-NMR (150 MHz, (D6)DMSO): 141.0; 133.6; 130.7; 129.4;
129.1; 128.9; 128.5; 127.6; 126.8; 126.6; 72.1; 63.3; 62.6; 57.2; 46.7; 32.5; 26.6. HR-ESI-MS: 310.2154
([M ꢀ Br]þ, C21H28NOþ; calc. 310.2165).
[N(S)]-N-Allyl-N-benzyl-N-[(1S)-1-(hydroxymethyl)-2-(4-hydroxyphenyl)ethyl]-N-methylammo-
nium Bromide (¼ [N(S),aS]-4-Hydroxy-a-(hydroxymethyl)-N-methyl-N-(phenylmethyl)-N-prop-2-en-
1-ylbenzeneethanaminium Bromide; [N(S)]-2f). Yield 41%. Pale yellow crystal (EtOH). M.p. 176 –
1778. [a]2D5 ¼ ꢀ41.6 (c ¼ 0.80, MeOH). IR (KBr): 3297, 3034, 1612, 1515, 1464, 1264, 1058, 850.
1H-NMR (600 MHz, (D6)DMSO): 9.35 (s, 1 H); 7.65 (d, J ¼ 7.5, 2 H); 7.49 – 7.53 (m, 3 H); 7.09 (d, J ¼ 8.3,
2 H); 6.72 (d, J ¼ 8.3, 2 H); 6.11 – 6.15 (m, 1 H); 5.64 (d, J ¼ 16.9, 1 H); 5.58 (d, J ¼ 10.2, 1 H); 5.49 (t, J ¼
4.6, 1 H); 4.73 (s, 2 H); 4.27 (dd, J ¼ 13.8, 6.1, 1 H); 3.85 – 3.91 (overlap, 2 H); 3.61 (d, J ¼ 13.8, 1 H); 3.42
(d, J ¼ 11.5, 1 H); 3.31 (overlap with the signal of the H2O in DMSO, 1 H); 3.04 (s, 3 H); 3.03 (overlap,
1 H). 13C-NMR (600 MHz, (D6)DMSO): 156.8; 133.7; 130.8; 129.4; 128.5; 127.4; 126.9; 126.8; 116.0; 73.9;
63.7; 62.9; 56.6; 47.0; 29.6. HR-ESI-MS: 312.1944 ([M ꢀ Br]þ, C20H26NO2þ ; calc. 312.1958).
X-Ray Analysis of [N(S)]-2f [12]. Slow evaporation of a soln. of [N(S)]-2f in EtOH gave a single
crystal suitable for X-ray analysis (0.45 ꢁ 0.43 ꢁ 0.40 mm; pale yellow). C20H26BrNO2 (392.33):
Orthorhombic P212121; a ¼ 10.3716(10), b ¼ 12.1566(10), c ¼ 15.6790(16) ꢄ, b ¼ 908, V¼ 1976.9(3) ꢄ3;
Z ¼ 4, Dcalc ¼ 1.318 Mg/m3. Intensities were measured on a Rigaku-Raxis-Rapid diffractometer, with
MoKa radiation (l 0.71073, q ¼ 3.09 – 27.47, m ¼ 2.090 mmꢀ1) at 293 K. Of the total 18872 reflections, 4524
were independent, and 2606 were observed. R ¼ 0.0540, Rw ¼ 0.2107.
[N(R)]-N-Allyl-N-benzyl-N-[(1S)-1-(hydroxymethyl)-2-(4-hydroxyphenyl)ethyl]-N-methylammo-
nium Bromide (¼ [N(R),aS]-4-Hydroxy-a-(hydroxymethyl)-N-methyl-N-(phenylmethyl)-N-prop-2-en-
1-ylbenzeneethanaminium Bromide; [N(R)]-2f). Yield 32%. Pale yellow solid. M.p. 171 – 1728. [a]D25
¼
1
þ17 (c ¼ 0.08, MeOH). H-NMR (600 MHz, (D6)DMSO): 9.35 (s, 1 H); 7.65 (d, J ¼ 6.7, 2 H ) , 7.49 –
7.54 (m, 3 H); 7.07 (d, J ¼ 8.2, 2 H); 6.73 (d, J ¼ 8.2, 2 H); 6.05 – 6.12 (m, 1 H); 5.72 (d, J ¼ 16.9, 1 H);
5.64 (d, J ¼ 10.3, 1 H); 5.54 (br. s, 1 H); 4.91 (d, J ¼ 12.8, 1 H); 4.56 (d, J ¼ 12.8, 1 H); 4.42 (dd, J ¼ 13.7,
8.2, 1 H); 3.95 (br. d, J ¼ 13.7, 1 H); 3.77 (dd, J ¼ 14.1, 5.4, 1 H); 3.62 (br. d, J ¼ 13.7, 1 H); 3.51 (br. d, J ¼
10.9, 1 H); 3.35 (overlap with the signal of the H2O in DMSO, 1 H); 3.07 (t, J ¼ 12.4, 1 H); 3.03 (s, 3 H).
13C-NMR (150 MHz, (D6)DMSO): 156.8; 133.8; 130.8; 130.7; 129.4; 128.3; 127.3; 127.0; 126.8; 116.0; 73.4;
63.7; 63.0; 56.5; 47.1; 29.4. HR-ESI-MS: 312.1948 ([M ꢀ Br]þ, C20H26NO2þ ; calc. 312.1958).
[N(R),3S]-2-Allyl-1,2,3,4-tetrahydro-3-(hydroxymethyl)-2-methylisoquinolinium
Bromide
(¼ [N(R),3S]-1,2,3,4-Tetrahydro-3-(hydroxymethyl)-2-methyl-2-prop-2-en-1-ylisoquinolinium Bromide;
[N(R)]-2g). Yield 43%. Pale yellow liquid. [a]2D5 ¼ ꢀ5.0 (c ¼ 0.50, MeOH). IR (KBr): 3429, 2976, 1629,
1
1457, 1054, 756. H-NMR (600 MHz, CDCl3): 7.37 (t, J ¼ 7.5, 1 H); 7.23 – 7.28 (m, 2 H); 7.15 (d, J ¼ 7.5,
1 H); 6.15 – 6.19 (m, 1 H); 5.98 (d, J ¼ 16.8, 1 H); 5.77 (d, J ¼ 10.2, 1 H); 5.27 (br. s, 1 H); 4.88 (d, J ¼ 15.2,
1 H); 4.81 (dd, J ¼ 12.9, 6.4, 1 H); 4.71 (dd, J ¼ 12.9, 8.3, 1 H); 4.52 (d, J ¼ 15.2, 1 H); 4.39 (br. d, J ¼ 13.5,
1 H); 4.08 – 4.13 (m, 1 H); 4.03 (br. d, J ¼ 13.5, 1 H); 3.40 (dd, J ¼ 18.3, 11.0, 1 H); 3.25 (s, 3 H); 3.19 (dd,
J ¼ 18.3, 4.6, 1 H). 13C-NMR (150 MHz, CDCl3): 130.5; 129.9; 129.0; 128.7; 127.6; 127.3; 125.9; 124.6; 67.7;
65.9; 62.8; 59.3; 44.0; 27.6. HR-ESI-MS: 218.1531 ([M ꢀ Br]þ, C14H20NOþ; calc. 218.1539).
X-Ray Analysis of the 1:1 Complex of [N(R)]-2g and (S)-binol [12]. Slow evaporation of a soln. of
the complex in EtOH gave a single crystal suitable for X-ray analysis (0.44 ꢁ 0.40 ꢁ 0.25 mm; colorless).
C34H34BrNO3 (584.53): monoclinic P21; a ¼ 11.148(4), b ¼ 9.995(4), c ¼ 13.628(3) ꢄ, b ¼ 107.93(3)8, V¼
1444.7(9) ꢄ3 ; Z ¼ 2, Dcalc ¼ 1.344 Mg/m3. Intensities were measured on a Enraf-Nonius-CAD4

Helvetica Chimica Acta – Vol. 92 (2009)
687
diffractometer, with MoKa radiation (l 0.71073, q ¼ 1.57 – 25.50, m ¼ 1.46 mmꢀ1) at 289 K. Of the total
3339 reflections, 3257 were independent, and 2525 were observed. R ¼ 0.0403, Rw ¼ 0.1082.
[N(S),3S]-2-Allyl-1,2,3,4-tetrahydro-3-(hydroxymethyl)-2-methylisoquinolinium
Bromide
(¼ [N(S),3S]-1,2,3,4-Tetrahydro-3-(hydroxymethyl)-2-methyl-2-prop-2-en-1-ylisoquinolinium Bromide;
[N(S)]-2g). Yield 35%. Primrose yellow liquid. [a]2D5 ¼ þ3.0 (c ¼ 0.45, MeOH). 1H-NMR (600 MHz,
CDCl3): 7.35 – 7.38 (m, 1 H); 7.26 – 7.31 (m, 2 H); 7.06 (d, J ¼ 7.6, 1 H); 5.93 – 5.99 (m, 1 H); 5.68 (d, J ¼
9.9, 1 H); 5.53 (d, J ¼ 16.7, 1 H); 4.68 (dd, J ¼ 13.3, 6.8, 1 H); 4.57 (d, J ¼ 15.3, 1 H); 4.41 (d, J ¼ 15.3, 1 H);
4.36 – 4.39 (m, 1 H); 4.28 – 4.32 (m, 1 H); 4.14 – 4.19 (m, 1 H); 3.75 (dd, J ¼ 13.3, 7.4, 1 H); 3.56 (s, 3 H);
3.32 – 3.37 (m, 1 H); 3.24 – 3.26 (m, 1 H). 13C-NMR (150 MHz, CDCl3): 130.4; 130.0; 129.3; 129.1; 127.8;
126.8; 125.7; 124.1; 71.0; 62.3; 59.7; 58.1; 49.8; 27.5. HR-ESI-MS: 218.1551 ([M ꢀ Br]þ, C14H20NOþ; calc.
218.1539).
[N(R),3S]-1,2,3,4-Tetrahydro-3-(hydroxymethyl)-2-methyl-2-(3-methylbut-2-en-1-yl)isoquinolini-
um Bromide ([N(R)]-2h). Yield 40%. Colorless solid. M.p. 149 – 1508. [a]2D5 ¼ ꢀ30 (c ¼ 0.45, MeOH). IR
(KBr): 3421, 2976, 2928, 1638, 1454, 1082, 766. 1H-NMR (600 MHz, CDCl3): 7.31 (t, J ¼ 7.3, 1 H); 7.22 –
7.26 (m, 2 H); 7.14 (d, J ¼ 7.6, 1 H); 5.51 (t, J ¼ 7.7, 1 H); 5.25 – 5.29 (m, 1 H); 4.70 (d, J ¼ 15.5, 1 H); 4.59 –
4.67 (m, 2 H); 4.51 (d, J ¼ 15.5, 1 H); 4.40 (br. d, J ¼ 12.3, 1 H); 4.08 – 4.13 (m, 1 H); 4.04 – 4.07 (m, 1 H);
3.42 (dd, J ¼ 18.5, 10.5, 1 H); 3.28 (s, 3 H); 3.19 (dd, J ¼ 18.5, 4.8, 1 H); 1.93 (s, 3 H); 1.89 (s, 3 H).
13C-NMR (150 MHz, CDCl3): 149.2; 130.0; 128.9; 128.7; 127.5; 127.3; 126.1; 110.8; 66.8; 61.8; 59.4; 44.1;
27.6; 26.6; 19.6. HR-ESI-MS: 246.1850 ([M ꢀ Br]þ, C16H24NOþ; calc. 246.1852).
X-Ray Analysis of the 1:1 Complex of [N(R)]-2h and (S)-binol [12]. Slow evaporation of a soln. of
the complex in EtOH gave a single crystal suitable for X-ray analysis (0.42 ꢁ 0.31 ꢁ 0.18 mm; colorless).
C36H35BrNO3 (609.56): monoclinic P21; a ¼ 11.3972(5), b ¼ 10.1329(4), c ¼ 13.8151(5) ꢄ, b ¼ 107.93(3)8,
V¼ 1517.58(11) ꢄ3; Z ¼ 2, Dcalc ¼ 1.334 Mg/m3. Intensities were measured on a Rigaku-Raxis-Rapid
diffractometer, with MoKa radiation (l 0.71073, q ¼ 3.09 – 27.48, m ¼ 1.391 mmꢀ1) at 153 K. Of the total
15042 reflections, 6319 were independent, and 4162 were observed. R ¼ 0.0465, Rw ¼ 0.1810.
[N(S),3S]-1,2,3,4-Tetrahydro-3-(hydroxymethyl)-2-methyl-2-(3-methylbut-2-en-1-yl)isoquinolinium
Bromide ([N(S)]-2h). Yield 33%. Pale yellow liquid. [a]2D5 ¼ þ60 (c ¼ 0.22, MeOH). 1H-NMR
(600 MHz, CDCl3): 7.35 (t, J ¼ 7.3, 1 H); 7.26 – 7.28 (m, 2 H); 7.06 (d, J ¼ 7.7, 1 H); 5.26 – 5.37 (m, 2 H);
4.63 (d, J ¼ 15.2, 1 H); 4.51 (dd, J ¼ 13.2, 7.4, 1 H); 4.45 (br. d, J ¼ 13.2, 1 H); 4.38 – 4.41 (m, 1 H); 4.36 (d,
J ¼ 15.2, 1 H); 4.14 (br. d, J ¼ 12.0, 1 H); 3.83 (dd, J ¼ 13.2, 9.7, 1 H); 3.55 (s, 3 H); 3.44 (dd, J ¼ 18.3, 11.2,
1 H); 3.26 (br. d, J ¼ 17.6, 1 H). 13C-NMR (150 MHz, CDCl3): 148.7; 130.4; 129.3; 129.0; 127.7; 126.9;
126.1; 110.0; 70.6; 62.3; 59.7; 53.7; 49.9; 27.6; 26.5; 18.7. HR-ESI-MS: 246.1844 ([M ꢀ Br]þ, C16H24NOþ;
calc. 246.1852).
[N(S),3S]-2-(Anthracen-9-ylmethyl)-1,2,3,4-tetrahydro-3-(hydroxymethyl)-2-methylisoquinolinium
Chloride ([N(S)]-2i). Yield 40%. Yellow solid. M.p. 127 – 1288. [a]2D5 ¼ ꢀ113 (c ¼ 0.26, MeOH). IR
(KBr): 3413, 3038, 2927, 1626, 1454, 1083, 761. 1H-NMR (600 MHz, CD3OD): 8.75 (s, 1 H); 8.61 (d, J ¼
8.7, 1 H); 8.15 (t, J ¼ 8.7, 2 H); 7.72 (t, J ¼ 7.5, 1 H); 7.50 – 7.59 (m, 5 H); 7.34 – 7.38 (m, 2 H); 7.15 (d, J ¼
7.5, 1 H); 6.34 (d, J ¼ 14.6, 1 H); 5.30 (d, J ¼ 14.6, 1 H); 4.67 (d, J ¼ 12.7, 1 H); 4.40 (d, J ¼ 16.0, 1 H); 4.34
(d, J ¼ 16.0, 1 H); 4.25 (br. d, J ¼ 13.5, 1 H); 4.03 – 4.11 (m, 2 H); 3.39 (br. d, J ¼ 15.8, 1 H); 2.78 (s, 3 H).
13C-NMR (150 MHz, CD3OD): 133.9; 132.8; 131.9; 131.7; 131.6; 131.4; 129.7; 129.5; 129.1; 128.9; 128.0;
127.5; 127.4; 127.3; 126.8; 125.2; 125.1; 123.8; 123.2; 118.5; 72.1; 64.1; 59.3; 50.0; 26.9. HR-ESI-MS:
368.2017 ([M ꢀ Cl]þ, C14H22NOþ; calc. 368.2009).
[N(R),3S]-2-(Anthracen-9-ylmethyl)-1,2,3,4-tetrahydro-3-(hydroxymethyl)-2-methylisoquinolinium
Chloride ([N(R)]-2i). Yield 33%. Yellow crystals (MeOH). M.p. 122 – 1238. [a]2D5 ¼ ꢀ91 (c ¼ 0.14,
MeOH). 1H-NMR (600 MHz, CD3OD): 8.57 (s, 1 H); 8.35 (d, J ¼ 8.9, 1 H); 8.02 – 8.05 (m, 2 H); 7.60 –
7.63 (m, 1 H); 7.55 – 7.58 (m, 2 H); 7.46 – 7.52 (m, 3 H); 7.18 – 7.21 (m, 1 H); 7.00 – 7.04 (m, 2 H); 5.91 (d,
J ¼ 14.7, 1 H); 4.70 (d, J ¼ 14.7, 1 H); 4.59 (d, J ¼ 14.3, 1 H); 4.29 (br. d, J ¼ 15.7, 1 H); 4.09 – 4.17 (m,
2 H); 3.95 (d, J ¼ 12.7, 1 H); 3.87 – 3.92 (m, 1 H); 3.32 (d, J ¼ 15.7, 1 H); 2.62 (s, 3 H). 13C-NMR
(150 MHz, CD3OD): 133.6; 132.4; 131.9; 131.5; 131.4; 131.1; 129.6; 129.5; 129.1; 128.8; 128.0; 127.4; 127.3;
127.1; 126.7; 125.2; 125.1; 123.7; 123.0; 118.2; 71.9; 64.1; 59.1; 49.6; 26.8. HR-ESI-MS: 368.2022 ([M ꢀ
Cl]þ, C14H22NOþ; calc. 368.2009).
X-Ray Analysis of [N(R)]-2i [12]. Slow evaporation of a soln. of [N(R)]-2i in MeOH gave a single
crystal suitable for X-ray analysis (0.52 ꢁ 0.41 ꢁ 0.36 mm; yellow). C26H28ClNO2 (421.94): Orthorhombic

688
Helvetica Chimica Acta – Vol. 92 (2009)
P212121; a ¼ 10.6986(3), b ¼ 15.9588(5), c ¼ 25.0076(6) ꢄ, b ¼ 908, V ¼ 4269.7(2) ꢄ3; Z ¼ 8, Dcalc
¼
1.313 Mg/m3. Intensities were measured on a Rigaku-Raxis-Rapid diffractometer, with MoKa radiation
(l 0.71073, q ¼ 3.03 – 27.48, m ¼ 1.46 mmꢀ1) at 153 K. Of the total 39571 reflections, 9780 were
independent, and 6119 were observed. R ¼ 0.0387, Rw ¼ 0.1240.
REFERENCES
[1] B. Lygo, B. I. Andrews, Acc. Chem. Res. 2004, 37, 518; T. Ooi, K. Maruoka, Acc. Chem. Res. 2004, 37,
526.
[2] K. Maruoka, T. Ooi, Chem. Rev. 2003, 103, 3013; T. Ooi, K. Maruoka, Angew. Chem., Int. Ed. 2007,
46, 4222; T. Hashimoto, K. Maruoka, Chem. Rev. 2007, 107, 5656; M. Kitamura, Y. Arimura, S.
Shirakawa, K. Maruoka, Tetrahedron Lett. 2008, 49, 2026; P. Elsner, L. Bernardi, G. Dela Salla, J.
Overgaard, K. A. Jørgensen, J. Am. Chem. Soc. 2008, 130, 4897.
[3] I. Denissova, L. Barriault, Tetrahedron 2003, 59, 10105; O. Rlant, J. Hannedouche, Org. Biomol.
Chem. 2007, 5, 873; K. Fuji, Chem. Rev. 1993, 93, 2037.
`
[4] O. Molt, T. Schrader, Synthesis 2002, 2633; G. Chelucci, G. Orru, G. A. Pinna, Tetrahedron 2003, 59,
9471; W. Tang, X. Zhang, Chem. Rev. 2003, 103, 3029.
[5] M. Mellah, A. Voituriez, E. Schulz, Chem. Rev. 2007, 107, 5133; S. Allenmark, Chirality 2008, 20, 544.
[6] a) E. V. Dehmlow, S. Schrader, Pol. J. Chem. 1994, 68, 2199; b) E. V. Dehmlow, R. Klauck, S.
Dꢃttmann, B. Neumann, H.-G. Stammler, Tetrahedron: Asymmetry 1998, 9, 2235; c) K. W. Glaeske,
F. G. West, Org. Lett. 1999, 1, 31; d) E. Tayama, S. Nanbara, T. Nakai, Chem. Lett. 2006, 35, 478;
e) A. Shimomoto, H. Yonezawa, S. Takizawa, H. Sasai, Jap. Pat. 2006076911, 2006; f) R. von
Matusch, M. Kreh, U. Mꢃller, Helv. Chim. Acta. 1994, 77, 1611; g) M. Hirnschall, M. Treu, K.
Mereiter, C. Hametner, J. Frçhlich, U. Jordis, Tetrahedron: Asymmetry 2003, 14, 675; h) E. Tayama,
H. Tanaka, T. Nakai, Heterocycles 2005, 66, 95.
[7] W. J. Pope, S. J. Peachey, J. Chem. Soc. 1899, 75, 1127; V. Y. Torbeev, K. A. Lyssenko, O. N. Kharybin,
M. Y. Antipin, R. G. Kostyanovsky, J. Phys. Chem. B 2003, 107, 13523.
[8] H. O. Jones, J. Chem. Soc. 1904, 85, 223; b) M. B. Thomas, H. O. Jones, J. Chem. Soc. 1906, 89, 280;
H. O. Jones, J. R. Hill, J. Chem. Soc. 1908, 93, 295.
[9] E. Tayama, H. Tanaka, Tetrahedron Lett. 2007, 48, 4183.
[10] K. N. White, J. P. Konopelski, Org. Lett. 2005, 7, 4111.
[11] A. G. Schultz, T. J. Guzi, E. Larsson, R. Rahm, K. Thakkar, J. M. Bidlack, J. Org. Chem. 1998, 63,
7795.
[12] J. D. Park, K. J. Lee, D. H. Kim, Bioorg. Med. Chem. 2001, 9, 237.
Received August 21, 2008