Contrast performance in catalytic ability - New cinchona phase transfer catalysts for asymmetric synthesis of α-amino acids

Article abstract of DOI:10.1016/j.tet.2004.12.005

Two new cinchona phase transfer catalysts are prepared from dihydrocinchonidine using 13-picenylmethyl bromide and 1-pyrenylmethyl bromide, respectively. A total contrast in catalytic efficiency is observed during the asymmetric alkylation of glycinate es

Full text of DOI:10.1016/j.tet.2004.12.005

Tetrahedron 61 (2005) 1443–1447
Contrast performance in catalytic ability—new cinchona phase
transfer catalysts for asymmetric synthesis of a-amino acids
*
Shanmugam Elango, Murugapillai Venugopal, P. S. Suresh and Eni
Institute of Chemical and Engineering Sciences, 1 Pesek road, Jurong Island 627833, Singapore
Received 3 September 2004; revised 9 November 2004; accepted 2 December 2004
Available online 16 December 2004
Abstract—Two new cinchona phase transfer catalysts are prepared from dihydrocinchonidine using 13-picenylmethyl bromide and
1-pyrenylmethyl bromide, respectively. A total contrast in catalytic efficiency is observed during the asymmetric alkylation of glycinate
esters; with one catalyst, the reaction is either incomplete or the enantioselectivity is very poor (15% ee) while the other catalyst afforded high
selectivity up to 94% ee.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
ammonium salts, which allow many options for rational
design and fine-tuning for improving greater reactivity and
selectivity. The unusual aromatic-F effect in cinchona based
PTCs on the selectivity was also demonstrated by Park et
al.8 Furthermore, non-cinchona chiral catalysts, such as
phosphonium salts,9 TADDOL,10 and salen–metal com-
plexes11 have also been introduced for asymmetric PTC
reactions. However, there has been little understanding over
the arylmethyl groups employed for the quaternization of
cinchonidine and their influence on asymmetric induction.
Here we wish to report the total contrast in the performance
of two cinchona PTCs and the reasons for the difference in
catalytic ability are analyzed.
The growing importance of enantiomerically pure com-
pounds for life-science applications has fueled a wealth of
research in asymmetric synthesis. In particular, since the
pioneering work by O’Donnell1 et al. in 1989 on
asymmetric alkylation of glycinate esters using the
benzylammonium salt of cinchona alkaloid 1, there has
been tremendous achievements over the development of
novel chiral phase transfer catalysts. Lygo2 and Corey3
independently reported an improved version by introducing
a 9-anthracenylmethyl group onto the nitrogen of the
quinuclidine ring in cinchonidine (CD) 2.
2. Results and discussions
Prompted by the successful results from anthracenylmethyl
and naphthylmethyl groups employed for the formation of
PTCs, we envisioned that 13-picenylmethyl and 1-pyrenyle-
methyl groups having additional benzene ring(s) but fused
in a different manner could be beneficial for the exploration
of efficient chiral PTCs due to extended planarity of the
aromatics and the steric bulkiness. Thus, dihydrocincho-
nidine (CDH2) was reacted with 13-picenylmethyl bromide
or 1-pyrenylmethyl bromide at 100 8C in toluene for 6 h to
provide 5 or 6, respectively (91 or 92% yield). 13-
Picenylmethyl bromide 3 was prepared from LAH reduction
of the picene-13-carboxylic acid methyl ester12 group and
then bromination of the resulting alcohol. 1-Pyrenylmethyl
bromide13 4 was prepared from 1-pyrenecarboxaldehyde
through a sequence of reduction and bromination by
conventional methods. Both the catalysts 5 and 6 were
Further modifications of the above system include dimeric4,5
and trimeric6 phase transfer catalysts (PTCs) Maruoka7
reported chiral binol-based versatile C2-symmetric spiral
Keywords: Chiral phase transfer catalyst; Cinchona alkaloids.
* Corresponding author. Tel.: C65 67963912; fax: C65 63166184;
e-mail: s_elango@ices.a-star.edu.sg
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.12.005

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S. Elango et al. / Tetrahedron 61 (2005) 1443–1447
thoroughly characterized by 1H and 13C NMR spectroscopic
studies. The impact of the bulky unit on the hydroxyl group
in 6 was also studied by alkylating with allyl bromide and
9-anthracenylmethyl bromide in aq NaOH to obtain 7 and
10, respectively, following the literature method
(Scheme 1).4b
exhibiting enhanced enantioselectivity of about 13%
compared to cinchonidine derived PTC 8 (entries 4 and 9)
CD. As endorsed previously, low temperature reactions
favored mild improvement in asymmetric induction com-
pared to the room temperature reactions (entries 4 and 5).
Despite the fact that by switching over the solvent system
from toluene to a mixture of toluene: CHCl3 (7:3) there was
substantial increase in selectivity (w8%), it led to
simultaneous retardation of the reaction rate remarkably
(entries 4 and 8); the reaction time increased from 8 to 14 h.
With our catalyst, the enantioselectivity obtainable in
toluene (83%) is nearer to that in a mixture of toluene and
CHCl3 (91%). There was little preference between the bases
NaOH and KOH (entries 7 and 8). We introduced a more
bulky anthracenylmethyl group on the hydroxyl (10) but
there was a drop in ee about 10% (entries 8 and 13). The
N-pyrenyl-1-methyl hydrocinchonidinium bromide 6
proved to be most efficient of all other catalysts (7–9)
providing up to w94% ee under reasonably moderate
conditions (entry 7) with reproducibility of G5% ee.
For the purpose of evaluation of the catalysts, the
conventional alkylation reaction of t-butylglycine ester
was studied. Initially, when the N-picenylmethyl hydro-
cinchonidinium bromide 5 was employed, it surprisingly
resulted in disappointing results. Not only that did it provide
low optical purity but the catalytic efficiency was also
sluggish. Thus, reactions did not go to completion even with
reactive alkylating agents. With allyl bromide, it took 19 h
to consume the starting material and the reaction proceeded
with poor selectivity of only 10% ee (entry 1). The possible
reason could be, due to rigid transition state formed through
hydrogen bonding and p-stacking between the glycine
enolate and PTC 5, the glycine moiety is sandwiched
between linearly fused picene aromatics and the cincho-
nidine moiety and consequently the electrophile is
hampered from approaching the enolate. This is further
substantiated by the increase in reaction time observed as
the size of the alkylating agent increases from allyl bromide
to benzyl bromide. There was no product formation with
piperonyl bromide at 0 8C for 24 h. This observation
indicates that although the cinchona alkaloid is the best
template for making chiral PTCs, it may not be a better
performer when sterically overcrowded with the quaterniz-
ing group.
3. Conclusion
We have developed a new cinchona based chiral PTC and
established its efficacy. This new catalyst provides high
enantioselectivity (86–94% ee) at either 0 8C or room
temperature. At the same time, we have also shown the
contrasting behavior towards asymmetric induction in two
PTCs (5 and 6) due to the influence of the arylmethyl group.
Then, we decided to introduce an optimal group using
1-pyrenylmethyl bromide and thus prepared 6–9. With this
system, CDH2 derived PTC 6 was a better template,
4. General
All the chemicals were used as received. The NMR spectra
Scheme 1.

S. Elango et al. / Tetrahedron 61 (2005) 1443–1447
1445
were recorded on a Bruker Avance 400 instrument,
(30 mL) and the turbid solution filtered over celite pad,
partly concentrated and crystallized along with ether to
afford 5 as a pale yellow solid in 91% yield. [a]D23Z
K383.23 (cZ2.0, DMSO); mp 180.3–182.1 8C (decomp);
IR (KBr) 3327, 3192, 3050, 2951, 1591, 1509, 1458,
808 cmK1. dH 1H NMR (400 MHz, MeOH-d4) 9.36 (s, 1H),
8.97 (d, JZ8.0 Hz, 1H), 8.89 (d, JZ8.1 Hz), 8.82 (d, JZ
4.4 Hz, 1H), 8.75–8.66 (m, 2H), 8.44 (d, JZ8.5 Hz, 1H), 8.1
(d, JZ8.5 Hz, 1H), 8.0–7.93 (m, 3H), 7.90–7.80 (m, 2H),
7.78 (d, JZ4.2 Hz, 1H), 7.7 (q, JZ8.6 Hz, 2H), 7.62 (t, JZ
8.4 Hz, 2H), 6.82 (s, 1H), 6.72 (d, JZ12.1 Hz, 1H), 5.87 (d,
JZ12.2 Hz, 1H), 4.0–3.89 (m, 1H), 3.83 (t, JZ9.3 Hz, 1H),
2.78 (d, JZ12.8 Hz, 1H), 2.40 (t, JZ12.6 Hz, 1H), 2.35–
2.67 (m, 1H), 1.97 (t, JZ12.4 Hz, 1H), 1.75–1.56 (m, 2H),
1.32–1.05 (m, 3H); 13C NMR (JZ100 Hz, MeOH-d4):
151.0, 148.8, 147.6, 134.6, 133.6, 133.6, 132.1, 131.6,
131.2, 131.2, 131.1, 131.0, 130.4, 130.3, 129.9, 129.7,
129.4, 129.3, 129.1, 128.8, 128.7, 128.5, 128.4, 127.7,
126.2, 124.8, 124.5, 122.9, 122.8, 122.2, 121.2. MS (EI)
587; HRMS (EI) calcd for [C42H39N2O]C 587.3053, found
587.3055.
1
operating at 400 and 100.1 MHz for H and 13C nuclei,
respectively. IR spectra were recorded for KBr pellets on
Biorad FTS3000MX spectrometer. Low and high-resolution
EI mass spectra (MS and HRMS) were taken on a Finnigan
MAT 95 XP spectrometer. Melting points were determined
(uncorrected) on a Buchi (B-540) apparatus. Column
chromatography was carried out using silica gel (Merck
400–230 mm).
5. Experimental
5.1. General
5.1.1. Preparation of 13-bromomethyl-picene (3). Picene-
13-carboxylic acid methyl ester12 (1.18 g, 3.5 mmol) was
dissolved in dry THF (25 mL) under argon atmosphere and
LAH (250 mg) was added in portion over the period of
15 min at room temperature. After the addition, the reaction
mixture was stirred for another 15 min and then quenched
with water (2 mL) by slow addition. The reaction mixture
was then acidified with 1 N HCl and extracted with ethyl
acetate (3!50 mL). The combined organic layer washed
with water, dried over magnesium sulfate and removal of
the solvent in vacuo gave picen-13-ol (1.04 g, 97%) as off-
5.1.3. N-1-Pyrenylmethylhydrocinchonidinium bromide
6. The same procedure as above was followed to obtain 6 as
a off-white solid (92%, 1.84 g). [a]2D3ZK243 (cZ2,
MeOH); mp 186.5–188 8C (decomp); IR (KBr) 3420,
3195, 1590, 1459, 855 cmK1. dH 1H NMR (400 MHz,
MeOH-d4) 8.61 (d, JZ4.6 Hz, 1H), 8.56 (d, JZ9.4 Hz,
1H), 8.39–8.36 (m, 1H), 8.34–8.32 (m, 3H), 8.31–8.28 (m,
2H), 8.20 (d, JZ9.20 Hz, 1H), 8.12 (d, JZ9.20 Hz, 1H),
8.10–8.04 (m, 2H), 7.99 (d, JZ7.8 Hz, 1H), 7.84–7.76 (m,
2H), 6.87 (bs, 1H), 6.04 (d, JZ13.2 Hz, 1H), 5.49 (d, JZ
13.2 Hz, 1H), 4.76–4.73 (m, 1H), 4.21 (t, JZ8.4 Hz, 1H),
3.61–3.55 (m, 1H), 3.46–3.40 (m, 1H), 3.14–3.07 (m, 1H),
2.29–2.22 (m, 1H), 2.18–2.10 (m, 1H), 1.93–1.86 (m, 1H),
1.70–1.61 (m, 1H), 1.59–1.50 (m, 1H), 1.42–1.33 (m, 1H),
1.30–1.13 (m, 2H), 0.67 (t, JZ7.4 Hz, 3H); 13C NMR
(100 MHz, MeOH-d4): d 151.2, 148.9, 147.9, 134.7, 134.0,
133.6, 132.7, 131.8, 131.3, 130.8, 130.5, 130.5, 129.4,
128.4, 128.0, 127.9, 127.4, 126.3, 126.3, 126.0, 125.5,
124.5, 124.0, 121.7, 121.6, 69.67, 67.0, 64.6, 61.8, 53.3,
37.7, 27.6, 26.7, 25.5, 22.6, 11.8. MS (EI) 511; HRMS (EI)
calcd for [C36H35N2O]C 511.2741, found 511.2709.
1
white solid; mp 189.4 8C; IR (KBr) 3485, 1460 cmK1. H
NMR (400 MHz, CDCl3) d 9.03 (1H, s), 8.93 (d, JZ8.0 Hz,
1H), 8.84 (d, JZ8.0 Hz, 1H), 8.75 (d, JZ9.20 Hz, 1H), 8.69
(d, JZ9.20 Hz, 1H), 8.0–7.90 (m, 4H), 7.72–7.63 (m, 4H),
5.52 (s, 2H); 13C NMR (100 MHz, CDCl3) d 135.73, 132.99,
131.97, 130.21, 130.13 (2C), 128.87, 128.50, 128.42,
127.91, 127.82, 126.91, 126.75 (2C), 126.37, 126.30,
123.36, 124.35, 123.13, 121.96, 121.90, 121.55, 67.17.
MS m/e (%) 308 (MC, 45), 291 (40), 289 (20), 136 (65), 107
(20), 89 (20), 77 (20); HRMS (EI) calcd for C23H16O
308.1204, found 308.1233.
Picen-13-ol obtained above (678 mg, 2.2 mmol) was
dissolved in chloroform (5 mL) and HBr (48% aq solution,
4 mL) was added to it and stirred for 4 h at room
temperature. The reaction mixture was diluted with chloro-
form (20 mL) and organic layer separated, washed with
water (2!30 mL), dried over magnesium sulfate and
concentrated. The crude product was crystallized in
CH2Cl2–hexane mixture as yellow solid 3. (710 mg,
87%); mp 169–172 8C (decomp); IR (KBr) 1210, 797,
5.1.4. N-1-Pyrenylmethyl-O(9)-allylhydrocinchoni-
dinium bromide 7. Pale yellow solid. [a]2D3ZK185.34
(cZ2.0, DMSO); mp 166.9–169.0 8C (decomp); IR (KBr)
3375, 2947, 1458, 852 cmK1. dH 1H NMR (400 MHz,
MeOH-d4) 8.94 (d, JZ4.6 Hz, 1H), 8.49–8.41 (m, 1H),
8.38–8.32 (m, 2H), 8.31–8.26 (m, 1H), 8.25–8.18 (m, 1H),
8.17–8.05 (m, 3H), 8.0 (t, JZ7.3 Hz, 1H), 7.97–7.87 (m,
3H), 6.63 (bs, 1H), 6.36–6.23 (m, 1H), 5.78 (d, JZ12.9 Hz,
1H), 5.58–5.49 (m, 2H), 5.44 (d, JZ11.9 Hz, 1H), 4.47–
4.19 (m, 4H), 3.69–3.59 (m, 1H), 3.37 (t, JZ11.9 Hz, 1H),
3.17–3.02 (m, 1H), 2.39–2.27 (m, 1H), 2.17–2.05 (m, 1H),
1.93–1.83 (bs, 1H), 1.66–1.37 (m, 3H), 1.30–1.02 (m, 2H),
0.66 (t, JZ7.3 Hz, 3H); 13C NMR (100 MHz, MeOH-d4): d
151.1, 149.3, 143.2, 134.8, 134.7, 133.9, 133.5, 132.6,
131.7, 131.5, 130.8, 130.6, 130.5, 129.5, 128.3, 127.9,
127.8, 127.4, 127.0, 126.3, 126.0, 125.5, 124.2, 123.7,
121.6, 121.1, 119.4, 71.5. MS (EI) 551; HRMS (EI) calcd
for [C39H39N2O]C 551.3053, found 551.3035.
1
732 cmK1. H NMR: (400 MHz, CDCl3) d 9.05 (d, JZ
8.4 Hz, 1H), 9.00 (s, 1H), 8.82 (d, JZ8.4 Hz, 1H), 8.71 (d,
JZ8.8 Hz, 1H), 8.65 (d, JZ9.2 Hz, 1H), 7.99 (m, 2H), 7.75
(m, 2H), 7.66 (m, 2H), 5.4 (s, 2H); 13C NMR (100 MHz,
CDCl3) d 133.1, 132.8, 131.9, 130.4, 129.9, 128.8, 128.6,
128.5, 128.4, 128.3, 128.1, 128.0 (2C), 127.9, 127.8, 127.1,
126.9, 126.5, 126.4, 123.1, 121.9, 121.5, 38.8. MS (EI) 370;
HRMS (EI) calcd for [C23H15Br]C 370.0357, found
370.0375.
5.1.2. Preparation of N-13-picenylmethylhydrocinchoni-
dinium bromide 5. A mixture of (K)-hydrocinchonidine
(1 g, 3.39 mmol) with 13-picenylmethy l bromide (1.26 g,
3.39 mmol) in toluene (40 mL) was stirred at 100 8C for 8 h.
After cooling the reaction mixture to room temperature, the
suspension was filtered off and the solid dissolved in MeOH

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S. Elango et al. / Tetrahedron 61 (2005) 1443–1447
5.1.5. N-1-Pyrenylmethylcinchonidinium bromide 8. Off-
white white solid. [a]2D3ZK290.01 (cZ2.2, CH2Cl2); mp
184.7–185.9 8C (decomp); IR (KBr) 3632, 3180, 1585,
1459, 848 cmK1. dH 1H NMR (400 MHz, MeOH-d4) 8.87
(d, JZ4.6 Hz, 1H), 8.47 (d, JZ10.1 Hz, 1H), 8.42–8.37 (m,
2H), 8.35 (t, JZ8.30 Hz, 3H), 8.23–8.16 (m, 2H), 8.10–7.92
(m, 3H), 7.88 (d, JZ9.20 Hz, 1H), 7.70–7.62 (m, 2H), 6.84
(s, 1H), 6.06 (d, JZ12.8 Hz, 1H), 5.66 (d, JZ12.8 Hz, 1H),
5.63–5.51 (m, 1H), 5.39 (s, 1H), 5.06 (d, JZ17.5 Hz, 1H),
4.86 (d, JZ11.0 Hz, 1H), 4.67–4.56 (m, 1H), 4.24 (t, JZ
8.3 Hz, 1H), 3.97–3.88 (m, 1H), 3.36 (t, JZ11.9 Hz, 1H),
3.06–2.94 (m, 1H), 2.48–2.37 (m, 1H), 2.19–2.09 (m, 1H),
2.05–1.96 (m, 1H), 1.56–1.43 (m, 1H), 1.32–1.16 (m, 1H),
0.67 (t, JZ7.4 Hz, 3H); 13C NMR (100 MHz, MeOH-d4): d
150.9, 148.8, 147.8, 138.9, 134.5, 134.0, 133.5, 132.7,
131.8, 131.2, 130.8, 130.5, 130.4, 130.23, 129.3, 128.3,
128.0, 127.9, 127.4, 126.2, 126.0, 125.5, 124.5, 124.0,
121.6, 121.4, 117.7, 68.6, 67.1, 62.54, 61.6, 53.1, 39.4, 27.8,
26.2, 23.1. MS (EI) 509; HRMS (EI) calcd for
[C36H33N2O]C 509.2585, found 509.2560.
5.1.6. N-1-Pyrenylmethyl-O(9)-allylcinchonidinium
bromide 9. Yellow solid. [a]2D3ZK199.61 (cZ2,
DMSO); mp 164.5–165.1 8C (decomp). IR (KBr) 3383,
Table 1. Enantioselective alkylation of glycinate ester
Entry
1
RX
Catalyst
T (8C)
Time (h)
19
Yielda %
89
ee %b (config.)c
5
25
10% (S)
2
3
5
5
25
0
22
24
78
10% (S)
No reaction
4
6
6
6
6
6
8
9
7
7
10
6
25
0
8
91
83% (S)
89% (S)
93% (S)
94% (S)
91% (S)
69% (S)
74% (S)
93% (S)
84% (S)
80% (S)
84% (S)
5
10
15
15
14
13
13
21
12
15
8
94
6
0
93d
91e
91d
91
7
0
8
25
25
25
0
9
10
11
12
13
14
93
89d
91
25
25
25
91
90
15
16
CH3I
CH3CH2I
6
6
25
25
48
48
94
88
52% (S)
79% (S)
17
18
19
6
6
6
25
7
89
89
86
88% (S)
87% (S)
90% (S)
0
10
12
25
20
6
25
9
91
88% (S)
The reaction was carried out with RX (5 equiv for entries 1–2 and 4–13 and more than 10 equiv for entries 15 and 16; 1.1 equiv for entries 3 and 17–20) and aq
NaOH (50%, 13 equiv) in the presence of catalyst (5 mol%) in toluene unless otherwise mentioned.
a Yields of isolated product.
b Determined by HPLC analysis using a chiral column (DAICEL, Chiralcel OD-H) with hexane/2-propanol (500:0.5 to 500:1) as solvent.
c The absolute configuration was determined by comparison of its optical rotation with that of an authentic sample, which was independently synthesized by the
reported procedure.2a
d KOH is the base.
e Solvent is toluene/chloroform (7:3).

S. Elango et al. / Tetrahedron 61 (2005) 1443–1447
1447
3042, 2950, 1589, 852 cmK1. dH 1H NMR (400 MHz,
MeOH-d4) 8.94 (d, JZ4.6 Hz, 1H), 8.45–8.35 (m, 3H),
8.34–8.29 (m, 1H), 8.28–8.21 (m, 3H), 8.20–8.15 (m, 1H),
8.14–8.08 (m, 2H), 8.04 (t, JZ7.4 Hz, 1H), 7.86–7.80 (m,
3H), 6.66 (bs, 1H), 6.38–6.25 (m, 1H), 5.86 (d, JZ13.8 Hz,
1H), 5.63–5.52 (m, 3H), 5.47 (d, JZ10.1 Hz, 1H), 5.03 (d,
JZ18.4 Hz, 1H), 4.90 (d, JZ11.0 Hz, 1H), 4.48–4.18 (m,
4H), 3.93–3.84 (m, 1H), 3.46 (t, JZ12.8 Hz, 1H), 3.20–3.10
(m, 1H), 2.52–2.42 (m, 1H), 2.40–2.30 (m, 1H), 2.17–2.05
(m, 1H), 1.98–1.90 (m, 1H), 1.68–1.55 (m, 1H), 1.51–1.40
(m, 1H); 13C NMR (100 MHz, MeOH-d4): d 151.1, 149.3,
143.1, 138.5, 134.8, 134.7, 133.9, 133.5, 132.6, 131.7,
131.5, 130.8, 130.6, 130.5, 129.5, 128.3, 127.9, 127.8,
127.4, 126.9, 126.3, 126.1, 125.5, 124.3, 123.6, 121.5,
121.1, 119.4, 117.7, 71.5 (2C), 69.6, 62.5, 62.2, 53.2, 39.16,
27.72, 26.1, 23.1. MS (EI) 549; HRMS (EI) calcd for
[C39H37N2O]C 549.2887, found 549.2863.
on silica gel (hexane–EtOAcZ30:1) to afford the desired
product (Table 1).
Acknowledgements
The authors thank ICES and A*Star for the financial support
of this project.
References and notes
1. O’Donell, M. J.; Bennett, W. D.; Wu, S. J. Am. Chem. Soc.
1989, 111, 2353–2355.
2. (a) Lygo, B.; Wainwright, P. G. Tetrahedron Lett. 1997, 38,
8595–8598. (b) Lygo, B.; Crosby, J.; Peterson, A. J.
Tetrahedron Lett. 1999, 40, 8671–8867. (c) Lygo, B.;
Humphreys, D. L. Tetrahedron Lett. 2002, 43, 6677–6679.
3. Corey, E. J.; Xu, F.; Noe, M. C. J. Am. Chem. Soc. 1997, 119,
12414–12415.
5.1.7. N-1-Pyrenylmethyl-O(9)-9-anthracenylhydro-
cinchonidinium bromide 10. Yellow solid. [a]2D3Z
K160.36 (cZ2, CH2Cl2); mp 178.9–180.3 8C (decomp);
IR (KBr) 3379, 2957, 1457, 853 cmK1. dH 1H NMR
(400 MHz, MeOH-d4) 9.19 (d, JZ4.6 Hz, 1H), 8.70 (bs,
1H), 8.44–8.33 (m, 2H), 8.32–8.24 (m, 5H), 8.22–8.16 (m,
3H), 8.16–8.11 (m, 2H), 8.11–8.03 (m, 4H), 7.99 (t, JZ
7.4 Hz, 1H), 7.85 (t, JZ8.7 Hz, 1H), 7.60 (t, JZ8.7 Hz,
1H), 7.52 (t, JZ7.4 Hz, 2H), 6.66–6.55 (m, 2H), 6.01 (d,
JZ12.9 Hz, 1H), 5.76 (d, JZ12.9 Hz, 1H), 5.08 (d, JZ
12.0 Hz, 1H), 4.26, 4.20–4.01 (m, 1H), 3.84–3.72 (m, 1H),
3.30–3.23 (m, 1H) 2.99 (t, JZ11 Hz, 1H), 2.81–2.69 (m,
1H), 2.61–2.50 (m, 1H), 2.21–2.08 (m, 1H), 1.97–1.89 (bs,
1H), 1.64 (t, JZ14 Hz, 1H), 1.55–1.41 (m, 1H), 1.12–1.10
(m, 2H), 0.59 (t, JZ7.4 Hz, 3H); 13C NMR (100 MHz,
MeOH-d4): d 151.1, 149.3, 143.2, 134.8, 134.7, 133.9,
133.5, 132.6, 131.7, 131.5, 130.8, 130.6, 130.5, 129.5,
128.3, 127.9, 127.8, 127.4, 127.0, 126.3, 126.0, 125.5,
124.2, 123.7, 121.6, 121.1, 119.4, 71.5 (2C), 69.7, 64.5,
62.4, 53.3, 37.3, 27.3, 26.7, 25.4, 22.7, 11.6. MS (EI) 701;
HRMS (EI) calcd for [C51H45N2O]C 701.3521, found
701.3495.
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5.2. Representative procedure for enantioselective
alkylation using chiral PTC
To a mixture of N-(diphenylmethylene) glycine t-butyl ester
(30 mg, 0.1 mmol) and chiral PTC (5 mol%) in toluene/
chloroform (1 mL, vol. ratio 7:3) or in toluene (1 mL) was
added the alkyl halide. Then 50% aqueous base was added
to the reaction mixture at the required temperature and
stirred until the starting material had been consumed by
TLC. The suspension was diluted with ethyl acetate
(15 mL), washed with water (2!5 mL), dried over
MgSO4, filtered and concentrated in vacuo. The crude
material was purified through flash column chromatography
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6105–6108. (b) Belokon’, Y. N.; Davies, R. G.; North, M.
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