Catalytic asymmetric alkynylation and arylation of aldehydes by an H 8-binaphthyl-based amino alcohol ligand

Article abstract of DOI:10.1002/adsc.200700215

A novel chiral H₈-1,1'-binaphthyl-based amino alcohol ligand (1R_a,2S,3R)-2 has been synthesized and applied in the direct nucleophilic addition of organozincs (alkynylzinc and arylzinc prepared in situ) to aldehydes, yielding the corresponding optically active propargylic alcohols and diarylmethanols in high yields and good to excellent enantioselectivities. For the asymmetric arylation reaction, one catalyst (1R_a,2S,3R)-2 can afford both enantiomers of many pharmaceutically interesting diarylmethanols by a proper combination of various arylzinc reagents and aldehydes.

Full text of DOI:10.1002/adsc.200700215

FULL PAPERS
DOI: 10.1002/adsc.200700215
Catalytic Asymmetric Alkynylation and Arylation of Aldehydes
by an H8-Binaphthyl-Based Amino Alcohol Ligand
Jiwu Ruan,a,b Gui Lu,a,b,* Lijing Xu,b Yue-Ming Li,b and Albert S. C. Chanb,*
a
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Peopleꢀs Republic of China
Open Laboratory of Chirotechnology of the Institute of Molecular Technology for Drug Discovery and Synthesis and
b
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon,
Hong Kong SAR, Peopleꢀs Republic of China
Fax : (+852)-2362-2578; e-mail: bcachan@polyu.edu.hk
Received: April 29, 2007; Revised: September 5, 2007; Published online: December 20, 2007
Abstract: A novel chiral H8-1,1’-binaphthyl-based lyst (1Ra,2S,3R)-2 can afford both enantiomers of
amino alcohol ligand (1Ra,2S,3R)-2 has been synthe- many pharmaceutically interesting diarylmethanols
sized and applied in the direct nucleophilic addition by a proper combination of various arylzinc reagents
of organozincs (alkynylzinc and arylzinc prepared in and aldehydes.
situ) to aldehydes, yielding the corresponding opti-
cally active propargylic alcohols and diarylmethanols Keywords: alkynylation; amino alcohols; arylation;
in high yields and good to excellent enantioselectivi- asymmetric catalysis; H8-binaphthyl; nucleophilic ad-
ties. For the asymmetric arylation reaction, one cata- dition
Introduction
quently, several efficient ligands have been developed
in this type of aryl transfer reaction and good results
Chiral ligands bearing a binaphthyl framework, such were obtained.[14]
as BINOL and BINAP, have earned a prominent
We have recently reported the preparation and ap-
status through their successful applications in a varie- plication of the new binaphthyl-derived amino alcohol
ty of catalytic asymmetric reactions over the last ligand (1Ra,2S,3R)-1 (Figure 1) in the asymmetric al-
three decades,[1] and the partially hydrogenated bi- kynylzinc and arylzinc additions.[12b,14h] Its H8-analogue
naphthyl scaffold (H8-binaphthyl) has received more (1Ra,2S,3R)-2 is expected to be more rigid, displaying
attention in recent years.[2] Positive effects have been larger biaryl torsional angles and thus may bestow
observed in some asymmetric catalytic reactions such better performance on the asymmetric alkylation re-
as asymmetric hydrogenation, alkylation, epoxidation action of carbonyl compounds. Herein, we report the
and hetero-Diels–Alder reactions, possibly due to the synthesis of the partially hydrogenated chiral ligand
more preferable electronic and steric effects caused (1Ra,2S,3R)-2 and its applications in the asymmetric
by the electron-rich tetralin unit with more steric bulk addition of alkynylzinc and arylzinc reagents (all pre-
and a larger dihedral angle. However, in some cases, pared in situ) to various aldehydes. The reactions pro-
some disadvantageous effects were also observed.[2]
ceeded readily, giving the corresponding addition
Enantiomerically pure propargylic alcohols and di- products with high stereoselectivity and broad sub-
arylmethanols are useful building blocks and impor- strate tolerance.
tant precursors for pharmaceutically and biologically
interesting molecules.[3–11] The preparation of these
compounds via the nucleophilic addition of organo- Results and Discussion
zincs (alkynylzinc and arylzinc prepared in situ) to al-
À
dehydes is of great interest because both the C C Ligand Synthesis
bond and the stereogenic center can be formed in one
step.[12]
There are two possible approaches for the synthesis
Bolm and co-workers reported a general protocol of (1Ra,2S,3R)-2, one is via the bromination of (R)-
for the enantioselective, catalytic synthesis of diaryl- H8-BINOL, the other is based on the partial hydroge-
methanol compounds from aldehydes by using a nu- nation of (R)-BINOL-CH2Br (Scheme 1). Compound
cleophilic arylzinc species generated in situ from mix- (R)-H8-BINOL-CH2Br was a key intermediate for
tures of arylboronic acids and diethylzinc.[13] Subse-
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Catalytic Asymmetric Alkynylation and Arylation of Aldehydes
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Figure 1. Molecular structures of (1Ra,2S,3R)-1 and (1Ra,2S,3R)-2. The hydrogen atoms are omitted for the purpose of clarity.
The dihedral angles of the axial biaryl groups were estimated by ChemDraw 3D calculations (MM2). (The minus sign is ar-
bitrarily given by the program.)
Scheme 1. Synthetic analysis of (1Ra,2S,3R)-2.
Scheme 2. Synthetic approach from (R)-H8-BINOL.
both routes, therefore our first effort was focused on
Attempts on the direct partial hydrogenation of
the synthesis of (R)-H8-BINOL-CH2Br.
(R)-BINOL-CH2Br with PtO2 also failed to give the
When we tried to access (1Ra,2S,3R)-2 from (R)- desired product. Taking an alternative strategy, we
H8-BINOL, we failed to get (R)-H8-BINOL-CH2Br in chose diol (R)-3 as a key intermediate. This com-
reasonable yield, only mixtures of various substitued pound could be obtained from (R)-BINOL-CH2Br
bromides were obtained during the bromination of either by reaction with AgNO3 or by tandem reaction
(R)-H8-BINOL-CH3
with
N-bromosuccinimide with KOAc and KOH. The latter approach was supe-
(Scheme 2).
rior in chemical yield (Scheme 3). Probably owing to
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Scheme 3. Synthetic approach from (R)-BINOL-CH2Br.
the harsh reaction conditions, the bromination of the Asymmetric Arylation Reaction
H8-diol (R)-4 thus obtained with HBr caused some
racemization in the product. Another approach using The direct addition of arylzinc (prepared in situ) to al-
PPh3 in CBr4 was more successful, giving (R)-5 in dehydes afforded optically active diarylmethanols in
80% yield, which can be further converted to high yields and excellent enantioselectivities (up to
(1Ra,2S,3R)-2 through the reaction with (1R,2S)-(+)- 96% ee) using H8-ligand (1Ra,2S,3R)-2 (Table 2).
2-amino-1,2-diphenylethanol (Scheme 3).
High ees were obtained even in the case of the steri-
cally hindered 1-naphthaldehyde (entry 9). Reactions
also worked well when different arylboronic acids
were used as aryl sources, except for the case of 2-
bromophenylboronic acid which gave the racemic ary-
Asymmetric Alkynylation Reaction
The newly prepared ligand (1Ra,2S,3R)-2 induced a lation product (entry 12). Using the same ligand
comparable enantioselectivity with (1Ra,2S,3R)-1 in (1Ra,2S,3R)-2, both enantiomers of the corresponding
the asymmetric alkynylation reactions. Table 1 sum- diarylmethanols could be obtained in good yields and
marizes the results of asymmetric additions of alkyn- high enantiomeric excesses by proper combination of
ylzinc (prepared in situ) to various aldehydes using arylboronic acids and aromatic aldehydes (entries 1
ligand (1Ra,2S,3R)-2, yielding the corresponding opti- and 10).[14h] Most results induced by chiral ligand
cally active propargylic alcohols in high yields and (1Ra,2S,3R)-2 were comparable with those of its
good to excellent enantioselectivities. The results parent ligand (1Ra,2S,3R)-1. Particularly noteworthy
from entries 4 and 5 demonstrate that this catalyst is are o-methylbenzhydrol (entry 6), p-methylbenzhy-
applicable to both aromatic and aliphatic acetylenes. drol (entry 11) and p-chlorobenzhydrol (entries 1 and
Substituted benzaldehydes gave better enantioselec- 10), which are useful precursor for some pharmaceuti-
tivities than benzaldehyde, while aliphatic aldehydes cals.
such as cyclohexanecarboxaldehyde gave low enantio-
It is quite interesting to note that using 2-bromo-
selectivities (34% ee, entry 8), possibly due to the un- phenylboronic acid gave the racemic arylation prod-
favorable electronic effect of the aldehyde. For ben- uct (entry 12), while combining phenylboronic acid
zaldehydes with electron-donating substituents such and 2-bromobenzaldehyde afforded 91% ee for the
as 2-methylbenzaldehyde and 2-methoxybenzalde- arylation product (entry 7). Although the mechanism
hyde, (1Ra,2S,3R)-2 offered better ees (84% and of the reaction is still not clear, it may be helpful to
76%, respectively) than its parent compound explain the influence of chiral ligands by speculating
(1Ra,2S,3R)-1 (entries 6 and 7).
on possible transition states of the aryl transfer step.
Generally the major enantiomer is produced from the
anti-trans path, in which the aldehyde coordinates to
the catalytic Zn center through the trans lone pair,
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Catalytic Asymmetric Alkynylation and Arylation of Aldehydes
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Table 1. Asymmetric alkynylation of aldehydes catalyzed by (1Ra,2S,3R)-2.[a]
[a]
Aldehyde:alkyne:ligand:ZnMe2 =1:2.4:0.1:2.2 (molar ratio).
[b]
The ees were determined by HPLC. Absolute configurations were determined by comparison of the order of the peaks
observed from HPLC with literature values.
[c]
The ees were obtained by using (1Ra,2S,3R)-1 under identical reaction conditions.[12b]
and the R group anti to the ligand is transferring.[14i] Conclusions
In the presence of (1Ra,2S,3R)-2, the syn-trans TS is
higher in energy than the anti-trans TS, and hence In summary, we have prepared an H8-1,1’-binaphthyl-
good selectivities result for substituted benzaldehydes derived amino alcohol ligand (1Ra,2S,3R)-2, and suc-
(Figure 2, a). An exception is the arylation of in situ cessfully applied it in the asymmetric addition of alky-
prepared 2-bromophenylzinc, which experiences a nylzinc and arylzinc (prepared in situ) to various alde-
severe steric clash that only slightly disfavors the syn- hydes. The ligand showed good enantioselectivities
trans pathway, and it leads to racemic product (up to 85% ee) in the asymmetric alkynylation and
(Figure 2, b).
excellent enantioselectivities (up to 96% ee) in the
asymmetric arylation of aromatic aldehydes. A di-
verse array of optically active diarylmethanols, which
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Table 2. Asymmetric aryl transfer to aromatic aldehydes catalyzed by (1Ra,2S,3R)-2.[a]
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Catalytic Asymmetric Alkynylation and Arylation of Aldehydes
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Table 2. (Continued)
[a]
Ar’CHO:ligand:ArB(OH)2:ZnEt2 =0.5:0.05:1.2:3.6 (molar ratio).
[b]
The ees were determined by HPLC. Absolute configurations were determined by comparison of the order of the peaks
observed from HPLC with literature values.
[c]
[d]
The ees were obtained by using (1Ra,2S,3R)-1 under identical reaction conditions.[14h]
Data were obtained at À208C.[14h]
Figure 2. Proposed transition states for the asymmetric arylation of aldehydes.
are of high interest in biological and pharmaceutical
sciences, can be obtained in one step by alternating
the nucleophiles and the aldehydes. Mechanistic stud-
ies, synthetic applications of these transformations as
well as the extension of our catalyst to other organic
transformations are currently being investigated in
our laboratory.
sidual proton resonance in CDCl3 (d=7.26 ppm), or with
tetramethylsilane (TMS, d=0.00 ppm) as the internal stan-
dard. Chemical shifts (d) were reported as parts per million
(ppm) in the d scale downfield from TMS. 13C NMR spectra
were recorded on a Varian 500 spectrometer and referenced
to CDCl3 (d=77.0 ppm). Mass spectra were obtained on a
Finnigan Model Mat 95 ST mass spectrometer. HPLC analy-
ses were carried out with a Waters 600 model instrument
using a Daicel Chiralcel OD column. The products were
eluted with 10% i-PrOH in hexane at a flow rate of
1.0 mLminÀ1 unless otherwise indicated, and were detected
at 254 nm with a Waters 486 detector. Optical rotations
were measured with a Perkin–Elmer Model 341 polarimeter
at 208C. The absolute configurations of products were de-
duced based on the comparison of HPLC patterns and/or
the direction of optical rotation with known compounds.
Experimental Section
All experiments were carried out under a nitrogen atmos-
phere. Unless otherwise stated, commercial reagents were
used as received without further purification. The reactions
were carried out in solvents distilled from standard drying
agents. Toluene and tetrahydrofuran (THF) were freshly dis-
tilled from sodium and benzophenone under nitrogen. Alde-
hydes were freshly distilled under reduced pressure before
Synthesis of Compound (R)-4[15]
The diol (R)-3 (944 mg, 3 mmol), which was prepared ac-
cording to a literature method,[12b,16] was dissolved in 20 mL
of glacial acetic acid. Platinum oxide (68 mg, 0.3 mmol) was
1
use. H NMR spectra were recorded on a Varian (500 MHz)
spectrometer. Spectra were referenced internally to the re-
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added and the mixture was stirred under 500 psi of H2 for
10 h at 408C. The solution was filtered, and the filtrate was
evaporated under reduced pressure. The residue was dis-
solved in CH2Cl2, and the solution was washed with aqueous
NaHCO3. After drying with Na2SO4 and evaporation of sol-
vents, the crude product was purified via column chromatog-
raphy (silica gel, hexane:ethyl acetate=5:1) to give octahy-
drodiol (R)-4 as a white solid; yield: 842 mg (87%).
1H NMR (500 MHz, CDCl3): d=7.23 (d, J=8.0 Hz, 2H,
ArH), 7.09 (d, J=8.0 Hz, 2H, ArH), 4.15 (d, J=11.0 Hz,
2H, CH2), 4.09 (s, 2H, OH), 3.97 (d, J=11.0 Hz, 2H, CH2),
2.83–2.81 (m, 4H, CH2), 2.09–1.98 (m, 4H, CH2), 1.77–1.62
(m, 8H, CH2); 13C NMR (125 MHz, CDCl3): d=138.4,
137.7, 135.8, 134.9, 129.1, 127.5, 63.1, 30.2, 28.00, 23.6, 23.1;
HR-MS (ESI): m/z=323.1991, calcd. for C22H27O2 [M+H]+:
323.2011; [a]2D0: +91.6 (c 1.0, CH2Cl2).
General Procedure for the Nucleophilic Addition of
Alkynes to Aldehydes[17]
To a solution of phenylacetylene (52.7 mL, 0.48 mmol) in tol-
uene (1 mL) was added a solution of dimethylzinc (2M,
0.22 mL, 0.44 mmol) in toluene. The mixture was stirred at
08C for 30 min.
A solution of (1Ra,2S,3R)-2 (10 mg,
0.02 mmol) in toluene (1 mL) was added. After stirring the
mixture for 30 min, the aldehyde (0.2 mmol) was added in
one portion with a syringe. The mixture was stirred at 08C
for 24 h, and the reaction was quenched with aqueous HCl
solution (5%, 2 mL). The mixture was extracted with dieth-
yl ether (3ꢂ2 mL). The organic layer was separated and
concentrated at reduced pressure, and was purified using
flash chromatography to afford the product. The enantio-
meric excess of the product was determined by HPLC anal-
ysis.
(S)-1,3-Diphenylprop-2-yn-1-ol:[18] Yield: 87%; 72% ee
determined by HPLC analysis; Daicel Chiralcel OD-H, l=
254 nm, hexane:i-PrOH=90:10, 1.0 mLminÀ1, retention
time: tr(R)=11.4 min, tr(S)=22.0 min.
Synthesis of Compound (R)-5
The octahydrodiol (R)-4 (807 mg, 2.5 mmol) was dissolved
in 100 mL of dried CH2Cl2. P P 3h(2.62 g, 10 mmol) and CBr4
(4.98 g, 15 mmol) were added, and the mixture was stirred
at 258C for 36 h. 40 mL of saturated aqueous NaHCO3 were
added and the mixture was stirred for another 15 min. The
organic layer was separated and the water layer was extract-
ed with CH2Cl2 (3ꢂ20 mL). The organic layers were com-
bined and dried with Na2SO4. After evaporation of the sol-
vent, the residue was purified via column chromatography
(silica gel, hexane:ethyl acetate=10:1) to give octahydrodi-
bromide (R)-5 as a white solid; yield: 897 mg (80%).
1H NMR (500 MHz, CDCl3): d=7.36 (d, J=8.0 Hz, 2H,
ArH), 7.15 (d, J=8.0 Hz, 2H, ArH), 4.15 (q, J=10.0 Hz,
4H, CH2), 2.86–2.84 (m, 4H, CH2), 2.40–2.34 (m, 2H, CH2),
2.14–2.08 (m, 2H, CH2), 1.84–1.67 (m, 8H, CH2); 13C NMR
(125 MHz, CDCl3): d=138.6, 137.9, 135.6, 132.4, 129.6,
128.1, 33.1, 30.1, 27.7, 23.2, 22.8; HR-MS (ESI): m/z=
447.0305, calcd. for C22H25Br2 [M+H]+: 447.0323; [a]D20:
+36.5 (c 1.0, CH2Cl2).
(S)-1-(2-Chlorophenyl)-3-phenylprop-2-yn-1-ol:[18] Yield:
86%; 82% ee determined by HPLC analysis; Daicel Chiral-
cel OD, l=254 nm, hexane:i-PrOH=90:10, 1.0 mLminÀ1,
retention time: tr(R)=7.8 min, tr(S)=9.2 min.
(+)-1-(2-Fluorophenyl)-3-phenylprop-2-yn-1-ol:[17] Yield:
83%; 77% ee determined by HPLC analysis; Daicel Chiral-
cel OD, l=254 nm, hexane:i-PrOH=90:10, 1.0 mLminÀ1,
retention time: t
rACHRTUNEG(minor)=7.3 min, trACHTREUNG
(major)=12.0 min.
(+)-1-(2-Nitrophenyl)-3-phenylprop-2-yn-1-ol:[17]
Yield:
90%; 85% ee determined by HPLC analysis; Daicel Chiral-
cel OD, l=254 nm, hexane:i-PrOH=90:10, 1.0 mLminÀ1,
retention time: trACTHERNGU(major)=16.7 min, trACHTREU(GN minor)=20.6 min.
(+)-1-(2-Nitrophenyl)hex-2-yn-1-ol:[17] Yield: 88%; 83%
ee determined by HPLC analysis; Daicel Chiralcel OJ, l=
254 nm, hexane:i-PrOH=90:10, 1.0 mLminÀ1, retention
time: trACTHER(UGN minor)=10.1 min, trACHTRE(UNG major)=12.0 min.
(S)-1-(2-Methoxyphenyl)-3-phenylprop-2-yn-1-ol:[19]
Yield: 87%; 76% ee determined by HPLC analysis, Daicel
Synthesis of Ligand (1Ra,2S,3R)-2[12b]
Chiralcel
OD,
l=254 nm,
hexane:i-PrOH=90:10,
1.0 mLminÀ1, retention time: tr(R)=16.5 min, tr(S)=
20.9 min.
The octahydrodibromide (R)-5 (897 mg, 2 mmol) was dis-
solved in 100 mL of CH3CN. Et3N (510 mg, 5 mmol)
and (1R, 2S)-(+)-2-amino-1,2-diphenylethanol (534 mg,
2.5 mmol) were added and the mixture was refluxed for
24 h. The solvent was removed, and the residue was purified
via column chromatography (silica gel, hexane:ethyl ace-
tate=5: 1) to give (1Ra,2S,3R)-2 as a white solid; yield:
800 mg (80%). 1H NMR (500 MHz, CDCl3): d=7.17–7.13
(m, 3H, ArH), 7.10 (d, J=7.5 Hz, 2H, ArH), 7.06–7.04 (m,
3H, ArH), 6.99–6.96 (m, 2H, ArH), 6.93 (d, J=7.5 Hz, 2H,
ArH), 6.83–6.81 (m, 2H, ArH), 5.30 (s, 1H, CH), 3.80 (d,
J=12.0 Hz, 2H, CH2), 3.40 (s, 1H, CH), 3.05 (d, J=12.0 Hz,
2H, CH2), 2.90–2.85 (m, 4H, CH2), 2.75–2.70 (m, 2H, CH2),
2.30–2.25 (m, 2H, CH2), 1.85–1.80 (m, 6H, CH2), 1.60–1.55
(m, 2H, CH2); 13C NMR (125 MHz, CDCl3): d=141.1,
138.4, 137.4, 137.2, 135.8, 131.8, 129.8, 128.1, 127.5, 127.4,
127.2, 126.6, 126.2, 126.1, 73.5, 71.9, 52.7, 29.6, 27.8, 22.9,
22.8; HR-MS (ESI): m/z=500.2889, calcd. for C36H38NO
[M+H]+: 500.2953; [a]D20: +5.6 (c 1.0, CH2Cl2).
(S)-1-(2-Methylphenyl)-3-phenylprop-2-yn-1-ol:[19] Yield:
85%; 84% ee determined by HPLC analysis; Daicel Chiral-
cel
OD-H,
l=254 nm,
hexane:i-PrOH=90:10,
1.0 mLminÀ1, retention time: tr(R)=8.7 min, tr(S)=
21.5 min.
(S)-1-Cyclohexyl-3-phenylprop-2-yn-1-ol:[18] Yield: 81%;
34% ee determined by HPLC analysis; Daicel Chiralcel
OD-H, l=270 nm, hexane:i-PrOH=90:10, 1.0 mLminÀ1, re-
tention time: tr(R)=5.8 min, tr(S)=12.0 min.
General Procedure for the Catalytic Addition of
Arylzinc to Benzaldehyde[14h]
A
toluene solution (1.5 mL) of phenylboronic acid
(1.2 mmol, 146.3 mg) was mixed with a diethylzinc solution
(1.1M in toluene, 3.6 mmol, 3.27 mL) in a sealed vessel
under nitrogen atmosphere. After stirring the reaction mix-
ture at 608C for 12 h, the vessel was cooled to 08C and a
toluene solution of (1Ra,2S,3R)-2 (0.05 mmol) was added
with continued stirring for 15 min. 4-Chlorobenzaldehyde
(0.50 mmol, 70.3 mg) was subsequently added and the mix-
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Catalytic Asymmetric Alkynylation and Arylation of Aldehydes
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ture was allowed to stir at 08C overnight. The reaction was References
then quenched with aqueous HCl solution (5%, ~6 mL).
The reaction mixture was extracted with ethyl acetate (3ꢂ
5 mL) and was dried with Na2SO4. The crude product diaryl-
methanol was purified by column chromatography (silica
gel, 10% EtOAc-hexane), giving the product with 95%
yield and 96% ee. The enantiomeric excess was determined
by HPLC analysis with a 25 cmꢂ4.6 mm Chiralcel OB-H
column (Daicel Chemical Industries Ltd.).
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(R)-(4-Chlorophenyl)phenylmethanol:[20] Yield: 95%;
96% ee determined by HPLC analysis; Daicel Chiralcel
OB-H, l=270 nm, hexane:i-PrOH=90:10, 1.0 mLminÀ1, re-
tention time: tr(R)=13.5 min, tr(S)=21.2 min.
(R)-(2-Chlorophenyl)phenylmethanol:[20] Yield: 92%;
95% ee determined by HPLC analysis; Daicel Chiralcel
OD-H, l=254 nm, hexane:i-PrOH=95:5, 1.0 mLminÀ1, re-
tention time: tr(R)=11.2 min, tr(S)=14.8 min.
(R)-(3-Chlorophenyl)phenylmethanol:[21] Yield: 93%;
95% ee determined by HPLC analysis; Daicel Chiralcel
OB-H, l=254 nm, hexane:i-PrOH=95:5, 1.0 mLminÀ1, re-
tention time: tr(R)=24.8 min, tr(S)=42.4 min.
(R)-(4-Biphenyl)phenylmethanol:[20] Yield: 93%; 92% ee
determined by HPLC analysis; Daicel Chiralcel OB-H, l=
254 nm, hexane:i-PrOH=95:5, 1.0 mLminÀ1, retention time:
tr(R)=40.2 min, tr(S)=61.0 min.
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91% ee determined by HPLC analysis; Daicel Chiralcel
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(S)-(4-Tolyl)phenylmethanol:[20] Yield: 92%; 95% ee de-
termined by HPLC analysis; Daicel Chiralcel OD-H, l=
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tention time: tr(R)=8.0 min, tr(S)=10.3 min.
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We thank the Hong Kong Research Grants Council (Project
number PolyU 5002/05P), the University Grants Committee
Area of Excellence Scheme in Hong Kong (Project AoE P/
10–01) and the Hong Kong Polytechnic University ASD
Fund for financial support of this study.
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