Enantioselective addition of ArTi(OiPr)3 to aldehydes catalyzed by a titanium complex of an N-sulfonylated amino alcohol

Article abstract of DOI:10.1039/c4ra14173c

Asymmetric additions of ArTi(OⁱPr)₃ to aldehydes catalyzed by a titanium catalyst of N-sulfonylated amino alcohols were reported, and results showed that the chiral N-sulfonylated amino alcohol with two stereogenic centers could catalyze the asymmetric addition of ArTi(OⁱPr)₃ to aldehydes to afford desired secondary alcohols in good yields with good to excellent enantioselectivities of up to 95% ee.

Full text of DOI:10.1039/c4ra14173c

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Enantioselective addition of ArTi(OiPr)3 to
aldehydes catalyzed by a titanium complex of an
Cite this: RSC Adv., 2015, 5, 9368
N-sulfonylated amino alcohol†
a
b
a
*
*
Shih-Ju Chang, Shuangliu Zhou and Han-Mou Gau
Received 9th November 2014
Accepted 5th January 2015
Asymmetric additions of ArTi(OiPr)3 to aldehydes catalyzed by a titanium catalyst of N-sulfonylated amino
alcohols were reported, and results showed that the chiral N-sulfonylated amino alcohol with two
stereogenic centers could catalyze the asymmetric addition of ArTi(OiPr)3 to aldehydes to afford desired
secondary alcohols in good yields with good to excellent enantioselectivities of up to 95% ee.
DOI: 10.1039/c4ra14173c
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catalysts at a low temperature of ꢀ78 ꢁC.12 Recently, we have also
reported aryltitanium,13 3-furyltitanium,14 and alkyltitanium
compounds15 as efficient nucleophiles for catalytic asymmetric
addition reactions at a mild temperature of 0 ꢁC to room
temperature. To further explore aryltitanium compounds as
efficient nucleophiles for catalytic reactions, we report herein the
asymmetric addition of aryltitanium to aldehydes employing a
series of chiral N-sulfonylated amino alcohols as catalysts.
Introduction
The enantioselective addition of aryl organometallic reagents to
aldehydes provides a straightforward synthetic method for opti-
cally active diarylmethanols,1 which are key intermediates
leading to bioactive compounds.2 The use of an arylzinc nucelo-
phile for the catalytic asymmetric arylation of aldehydes has
received much attention in the past two decades. A variety of
arylzinc organometallic reagents, such as ZnPh2,3 mixtures of
ZnPh2/ZnR2 (R ¼ Me or Et),4 arylzinc reagents from trans-
metallation of arylboronic acid or arylboron with ZnEt2,5 and
arylzinc from in situ reactions of aryl nucleophile with dialkylzinc
or zinc halides,6 have been extensively employed in the titanium-
catalyzed asymmetric addition for the synthesis of diary-
lmethanols. Recent studies have demonstrated that AlArxEt3ꢀx
(THF) (x ¼ 3 or 1),7,8 ArMgX9 and ArLi10 compounds are efficient
aryl sources for titanium-catalyzed asymmetric aryl addition
reactions of organic carbonyls, and excess amounts of Ti(OiPr)4
are required to ensure the high stereocontrol of the addition
products. Mechanistic study suggested that the roles of excess
Ti(OiPr)4 are not only the formation of the dititanium active
species bearing a chiral ligand, but also the transmetalation of an
organic nucelophile from the organozinc or organoaluminum
compounds to form the organotitanium reagents as the actual
addition reagents.11 Therefore, direct asymmetric additions of
organotitanium reagents to organic carbonyls were the most
effective method without doubt. The rst catalytic asymmetric
addition of RTi(OiPr)3 (R ¼ alkyl or aryl) to aldehydes was
reported by Seebach and coworkers using Ti-TADDOLate
Results and discussion
Chiral b-amino alcohols have widely used as chiral ligands for a
variety of asymmetric syntheses.16 Here, the asymmetric addi-
tion of PhTi(OiPr)3 to 2-methoxybenzaldehyde (2a) were rst
screened using 10 mol% of the chiral N-sulfonylated amino
alcohols 1a–f with one or two stereogenic centers from
L-phenylalanine (Fig. 1), and the results are summarized in
Table 1. It was found that the ligands have a strong inuence on
the enantioselectivities in asymmetric phenylation reactions
(entries 1–6), and only the chiral N-sulfonylated amino alcohols
1e with two stereogenic centers showed high enantioselectivity
(entry 5). In our previous mechanistic study, we have demon-
strated that the dititanium complex that simultaneously beared
the chiral directing ligand and the phenyl nucleophile was an
active species in the crucial and nal step of the catalytic
aDepartment of Chemistry, National Chung Hsing University, Taichung 402, Taiwan.
E-mail: hmgau@dragon.nchu.edu.tw
bAnhui Key Laboratory of Functional Molecular Solids, College of Chemistry and
Materials Science, Anhui Normal University, Wuhu, Anhui 241000, China. E-mail:
slzhou@mail.ahnu.edu.cn
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c4ra14173c
Fig. 1 Different chiral N-sulfonylated amino alcohols.
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Table 1 Optimizations of asymmetric PhTi(OiPr)3 additions to 2-methoxybenzaldehydea
Entry
Ligand
PhTi(OiPr)3 (equiv.)
Solvent
Temp (ꢁC)
Convb. (%)
eec (%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1e
1e
1e
1e
1e
1e
1e
1e
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.6
1.2
1.4
1.4
THF
THF
THF
THF
THF
THF
Toluene
Hexane
CH2Cl2
Et2O
THF
THF
THF
THF
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
0
97
97
92
97
100
92
100
100
100
100
100
93
3 (R)
rac
4 (R)
22 (R)
88 (R)
4 (R)
75 (R)
66 (R)
82 (R)
75 (R)
85 (R)
88 (R)
89 (R)
95 (R)
9
10
11
12
13d
14e
100
100
0
a
b
2-MeOC6H4CHO (0.50 mmol), ligand (0.05 mmol), THF (4 mL), equiv. of PhTi(OiPr)3 is relative to 2-MeOC6H4CHO. Conversions based on 1H
c
NMR spectra. The ee values were determined by HPLC, and the absolute conguration of 4a was determined by comparison with optical
rotation of known compounds. Reaction time: 10 min. 2-MeOC6H4CHO (0.50 mmol) in 1 mL THF was added to the catalytic solution
dropwise over 20 min; then reacted another 10 min.
d
e
addition reaction of organic carbonyl compounds.13b The chiral substrates on the enantioselectivities of products was observed.
N-sulfonylated amino alcohols 1e with two stereogenic centers The addition reactions of aromatic aldehydes with an ortho-
showed high enantioselectivity probably due to the above substituent gave the corresponding products in the enantiose-
reason. The investigations for the choice of the solvent showed lectivities of $90% ee except for 2-nitrobenzaldehyde (85% ee,
that THF is the best one (entries 5, 7–10). The enantioselectiv- entry 15) and 1-naphthylaldehyde (86% ee, entry 18). The
ities of product 4a is nearly invariable with reduction of the addition reactions of aromatic aldehydes with a para-substit-
temperature of reaction (entry 13). In order to suppress the uent showed a slight lower enantioselectivities than those with
racemic background reactions that would lower the enantiose- an ortho-substituents. However, the addition reaction of heter-
lectivities, further study showed that substrate in 1 mL THF was oaromatic 2-furaldehyde furnished product 4t in good yield
added dropwise to the catalytic solution to afford 4a in excellent with a enantioselectivity of 78% ee (entry 20), and the addition
enantioselectivity of 95% ee (entry 14).
reaction of a,b-unsaturated (E)-cinnamaldehyde afforded 4u in
Next, we explored the scope of the asymmetric addition of a good enantioselectivity of 84% ee (entry 21). Different to our
PhTi(OiPr)3 to aldehydes using the best performing ligand 1e, previous catalytic system,7a the addition reaction of PhTi(OiPr)3
and the results are listed in Table 2. Regardless of the electronic to aliphatic aldehydes afforded the corresponding products in
nature or the steric effect of the substituent on the aryl groups, moderate enantioselectivities of 56 to 76% ee (entries 22–24).
asymmetric phenyl additions to aromatic aldehydes afforded The additions of aryl nucleophiles of ArTi(OiPr)3 (Ar ¼ p-tolyl,
diarylmethanols in high yields. However, a steric effect of the 4-MeOC6H4, 4-ClC6H4, 4-F3CC6H4, and 2-naphathyl) to aldehyde
were also studied, affording aryl addition products in excellent
enantioselectivities for electron-donating aryltitanium reagents
(entries 25, 26 and 35) but in moderate enantioselectivities for
electron-withdrawing aryltitanium reagents (entries 27, 28, and
34). For ortho-substituted aryltitanium reagents ArTi(OiPr)3 (Ar
¼ 1-naphathyl, o-tolyl, o-anisyl and o-chlorophenyl), the low
enantioselectivities were obtained (entries 30–33). Especially,
the racemic diarylmethanols 4d0 and 4a0 were obtained for the
bulky aryltitanium reagent (entries 31 and 32). For ortho-
substituted aryltitanium reagents, the low enantioselectivities
were obtained, probably because the steric hindrance made
aldehydes' coordination to titanium metal in Re-face and Si-face
equality of opportunities.
Fig. 2 (a) The Re-face addition of the phenyl nucleophile to ary-
laldehyde; (b) the Si-face addition of Ph to arylaldehyde.
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Table 2 Asymmetric ArTi(OiPr)3 addition to aldehydes catalyzed by the titanium catalyst of N-sulfonylated amino alcohola
Entry
Substrate
ArTi(OiPr)3
Product
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
2-MeOC6H4CHO
3-MeOC6H4CHO
4-MeOC6H4CHO
2-MeC6H4CHO
3-MeC6H4CHO
4-MeC6H4CHO
2-ClC6H4CHO
3-ClC6H4CHO
4-ClC6H4CHO
2-BrC6H4CHO
3-BrC6H4CHO
4-BrC6H4CHO
2-FC6H4CHO
4-F3CC6H4CHO
2-O2NC6H4CHO
3-O2NC6H4CHO
4-O2NC6H4CHO
1-Naphthaldehyde
2-Naphthaldehyde
Furan-2-carbaldehyde
Cinnamaldehyde
Isobutyraldehyde
Pivalaldehyde
Cyclohexane-carbaldehyde
C6H5CHO
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
93
92
95
97
93
83
91
94
96
98
90
92
90
95
91
93
89
93
96
90
91
85
88
96
86
89
91
59
93
51
57
64
55
89
91
95 (R)
86 (R)
92 (R)
91 (R)
90 (R)
84 (R)
90 (R)
90 (R)
80 (R)
90 (R)
86 (R)
82 (R)
90 (R)
77 (R)
90 (R)
76 (R)
72 (R)
86 (R)
82 (R)
78 (R)
84 (S)
76 (S)
56 (S)
73 (S)
90 (S)
87 (S)
62 (S)
53 (S)
77 (S)
12 (S)
rac
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
4s
4t
4u
4v
4w
4x
4c0
4f0
4i0
4n0
4s0
4r0
4d0
4a0
4g0
4y
4-OMeC6H4
4-MeC6H4
4-ClC6H4
4-CF3C6H4
2-Naphthyl
1-Naphthyl
2-MeC6H4
2-MeOC6H4
2-ClC6H4
4-ClC6H4
4-MeC6H4
C6H5CHO
C6H5CHO
C6H5CHO
C6H5CHO
C6H5CHO
C6H5CHO
C6H5CHO
C6H5CHO
3 (S)
52 (S)
72 (S)
93 (S)
2-OMeC6H4CHO
2-OMeC6H4CHO
4z
a
Substrate/1e/ArTi(OiPr)3 ¼ 0.50/0.05/0.70 mmol, substrates in 1 mL THF was added dropwise over 20 min; reaction time (30 min) including the
addition time of the substrate to the catalytic solution. Isolated yield. c The ee values were determined by HPLC.
b
Based on our previous mechanistic study, the phenyl group
of arylaldehyde pointing toward the same side of the bridging
oxygen donor of the chiral ligand, predominantly giving the
Experimental section
General methods
intermediate A for a Re-face addition of the nucleophile to
All syntheses and manipulations were carried out under a dry
nitrogen atmosphere using standard Schlenk techniques or in a
glovebox. Solvents were dried by reuxing for at least 24 h over
P2O5 (dichloromethane) or sodium/benzophenone (THF,
n-hexane or toluene) and were freshly distilled prior to use.
ArTi(OiPr)3 was prepared according to the literature proce-
dure.17 The chiral N-sulfonylated amino alcohols 1a, 1e and 1f
were prepared according to the literature procedure.18 1H NMR
spectra were obtained with a Varian Mercury-400 (400 MHz)
spectrometer, and 13C NMR spectra were recorded with the
aldehydes (Fig. 2).11e
Conclusion
In summary, the asymmetric aryl additions of ArTi(OiPr)3 to
aldehydes employing a series of N-sulfonylated amino alcohols
were examined. Results showed that the chiral N-sulfonylated
amino alcohol with two stereogenic centers could catalyzed
asymmetric addition of ArTi(OiPr)3 to aldehydes to afford the
desired optically active diarylmethanols in good yields with
good to excellent enantioselectivities of up to 95% ee.
1
Varian Mercury-400 (100.70 MHz). H and 13C chemical shis
were measured relative to TMS as the internal reference.
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CHO), 3.71 (s, 3H, OCH3), 2.77 (br, 1H, OH) ppm. 13C NMR
(100 MHz, CDCl3): d 159.6, 145.4, 143.6, 129.4, 128.3, 127.4,
126.4, 118.8, 112.8, 112.0, 75.9, 55.0 ppm.
Synthesis of chiral N-sulfonylated amino alcohol 1b–1d
A solution of p-tolylsulphonyl chloride (0.95 g, 5.00 mmol) in
ꢁ
CH2Cl2 (20 mL) was added to a cold (0 C) solution of the cor-
(4-Methoxyphenyl)phenylmethanol (4c).5a [a]D25
¼
+0.93
responding chiral amino alcohol (5.00 mmol) and Et3N (2.1 mL,
15 mmol) in CH2Cl2 (20 mL). The reaction mixture was allowed
to warm to room temperature and stirred overnight. The reac-
tion mixture was diluted with CH2Cl2 (10 mL) and washed with
1 N HCl (2–5 mL), saturated aqueous NaHCO3 (3–10 mL), and
brine (3–10 mL). The organic layer was dried over anhydrous
MgSO4, concentrated under reduced pressure, and recrystal-
lized from EA–hexane to afford the chiral N-sulfonylated amino
alcohols 1b–d.
(S)-3-(p-Toluenesulfonylamino)-2-methyl-4-phenyl-2-butanol
(1b). 1H NMR (400 MHz, CDCl3): d 7.34–6.89 (m, 9H, Ph and
Ph(SO2NH)), 5.30 (s, 1H, NH), 3.46 (m, 1H, CHN), 2.95 (m, 2H,
PhCHAHB, OH), 2.43 (m, 1H, PhCHAHB), 2.35 (s, 3H, CH3), 1.29
(s, 3H, (CH3)2CH) ppm. 13C NMR (100 MHz, CDCl3): d 142.6,
137.7, 137.1, 129.4, 129.0, 128.3, 126.6, 126.1, 72.8, 64.7, 37.4,
27.7, 25.5, 21.4 ppm.
(c 1.08, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.39–7.25 (m, 7H,
Ar), 6.87–6.81 (m, 2H, Ar), 5.81 (d, J ¼ 2.0 Hz, 1H, CHO), 3.79 (s,
3H, OCH3), 2.19 (d, J ¼ 3.2 Hz, 1H, OH) ppm. 13C NMR
(100 MHz, CDCl3): d 158.9, 144.0, 136.1, 128.4, 127.8, 127.3,
126.3, 113.8, 75.7, 55.2 ppm.
(2-Tolyl)phenylmethanol (4d).5h [a]D25
¼ ꢀ2.70 (c 1.11,
CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.47–7.45 (m, 1H, Ar),
7.32–7.10 (m, 8H, Ar), 5.88 (s, 1H, CHO), 2.55 (br, 1H, OH), 2.18 (s,
3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d 142.8, 141.4, 135.2,
130.4, 128.3, 127.4, 127.3, 127.0, 126.2, 126.0, 73.2, 19.3 ppm.
(3-Tolyl)phenylmethanol (4e).19 [a]D25
¼
+2.63 (c 1.14,
1
CH2Cl2). H NMR (400 MHz, CDCl3): d 7.33–7.05 (m, 9H, Ar),
5.69 (s, 1H, CHO), 2.60 (br, 1H, OH), 2.29 (s, 3H, CH3), ppm. 13
C
NMR (100 MHz, CDCl3): d 144.2, 144.1, 138.4, 128.73, 128.68,
128.6, 127.8, 127.5, 126.8, 124.0, 76.5, 21.8 ppm.
(4-Tolyl)phenylmethanol (4f).5a [a]D25
¼
+16.35 (c 1.04,
(S)-3-Phenyl-2-(p-toluenesulfonylamino)-1-propanol (1c). 1H
NMR (400 MHz, CDCl3): d 7.61–6.95 (m, 9H, Ph and Ph(SO2NH)),
5.74 (d, J ¼ 7.2 Hz, 1H, NH), 3.61 (m, 1H, CHAHBOH), 3.53–3.45
(m, 2H, CHAHBOH, CHN), 2.75 (m, 2H, PhCHAHB, OH), 2.63 (m,
1H, PhCHAHB), 2.35 (s, 3H, CH3) ppm. 13C NMR (400 MHz,
CDCl3): d 143.0, 137.0, 129.5, 129.0, 128.3, 126.8, 126.2, 63.7,
56.8, 37.4, 21.3 ppm.
(2R,3S)-3-(p-Toluenesulfonylamino)-4-phenyl-2-butanol (1d).
1H NMR (400 MHz, CDCl3): d 7.44–6.88 (m, 9H, Ph and
Ph(SO2NH)), 5.39 (d, J ¼ 7.6 Hz, 1H, NH), 3.97 (m, 1H,
PhCHOH), 3.42 (m, 1H, CHN), 2.72 (m, 1H, PhCHAHB), 2.56 (m,
1H, PhCHAHB), 2.36 (s, 3H, CH3), 1.23 (d, J ¼ 6.4 Hz, 3H, CH3-
CHOH) ppm. 13C NMR (100 MHz, CDCl3): d 142.9, 137.0, 136.5,
129.4, 128.9, 128.4, 126.8, 126.2, 68.9, 60.6, 35.4, 21.4, 18.2 ppm.
1
CH2Cl2). H NMR (400 MHz, CDCl3): d 7.32–7.09 (m, 9H, Ar),
5.69 (s, 1H, CHO), 2.51 (s, 1H, OH), 2.29 (s, 3H, CH3), ppm. 13
C
NMR (100 MHz, CDCl3): d 144.3, 141.3, 137.5, 129.5, 128.7,
127.7, 126.9, 126.8, 76.3, 21.4 ppm.
(2-Chlorophenyl)phenylmethanol (4g).5f [a]D25
¼
+15.26
(c 1.07, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.58–7.56 (m, 1H,
Ar), 7.36–7.17 (m, 8H, Ar), 6.17 (s, 1H, CHO), 2.60 (br, 1H, OH)
ppm. 13C NMR (100 MHz, CDCl3): d 142.2, 140.9, 132.4, 129.5,
128.7, 128.4, 128.0, 127.7, 127.0, 126.9, 72.6 ppm.
(3-Chlorophenyl)phenylmethanol (4h).18 [a]D25
¼ ꢀ29.36
(c 1.09, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.35–7.20 (m, 9H),
5.68 (s, 1H, CHO), 2.63 (br, 1H, OH) ppm. 13C NMR (100 MHz,
CDCl3): d 145.7, 143.1, 134.3, 129.6, 128.6, 127.8, 127.5, 126.5,
124.5, 75.5 ppm.
(4-Chlorophenyl)phenylmethanol (4i).5a [a]D25
¼ ꢀ12.50
(c 1.04, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.33–7.26 (m, 9H,
Ar), 5.76 (s, 1H, CHO), 2.48 (br, 1H, OH) ppm. 13C NMR
General procedure for the asymmetric aryl addition of
aldehydes
Under a dry nitrogen atmosphere, 1e (0.019 g, 0.05 mmol) and (100 MHz, CDCl3): d 143.4, 142.1, 133.2, 129.3, 128.6, 127.8,
i
ꢁ
ArTi(O Pr)3 (0.70 mmol) were mixed in dry THF (4 mL) at 0 C. 126.5, 116.6, 75.5 ppm.
Aer stirring for 30 min, and an aldehyde (0.50 mmol) in THF
(2-Bromophenyl)phenylmethanol (4j).5a [a]D25
¼
+24.64
(1 mL) was added dropwise to the resulting solution over 20 min (c 2.34, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.50–7.48 (m, 2H,
at 0 ꢁC. The mixture was allowed to react for 10 min at this Ar), 7.31–7.20 (m, 7H, Ar), 7.08–7.05 (m, 1H, Ar), 6.04 (s, 1H,
temperature, and then quenched with 2 M NaOH. The aqueous CHO), 3.02 (s, 1H, OH) ppm. 13C NMR (100 MHz, CDCl3): d
phase was extracted with ethyl acetate (3 ꢂ 10 mL), dried over 142.3, 142.0, 132.6, 128.9, 128.4, 128.3, 127.8, 127.6, 126.9,
MgSO4, ltered and concentrated. The residue was puried by 122.6, 74.5 ppm.
column chromatography to give the secondary alcohol. Enan-
tiomeric excesses of products were determined by HPLC using 1.01, CH2Cl2). H NMR (400 MHz, CDCl3): d 7.49–7.48 (m, 1H,
(3-Bromophenyl)phenylmethanol (4k).5g [a]D25 ¼ ꢀ29.70 (c
1
suitable chiral columns from Daicel.
Ar), 7.35–7.10 (m, 8H, Ar), 5.63 (s, 1H, CHO), 2.85 (d, J ¼ 5.6 Hz,
(2-Methoxyphenyl)phenylmethanol (4a).5a [a]D25 ¼ +47.84 1H, OH) ppm. 13C NMR (100 MHz, CDCl3): d 145.9, 143.0, 130.4,
(c 1.08, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.38–7.21 (m, 7H, 129.9, 129.4, 128.6, 127.8, 126.5, 125.0, 122.5, 75.4 ppm.
Ar), 6.94–6.85 (m, 2H, Ar), 6.03 (s, 1H, CHO), 3.77 (s, 3H, OCH3),
(4-Bromophenyl)phenylmethanol (4l).5a [a]D25
¼ ꢀ15.45
3.12 (br, 1H, OH) ppm. 13C NMR (100 MHz, CDCl3): d 156.6, (c 1.10, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.43–7.41 (m, 2H,
143.2, 131.9, 128.6, 128.1, 127.7, 127.1, 126.5, 120.7, 110.6, 72.1, Ar), 7.33–7.19 (m, 7H, Ar), 5.71 (s, 1H, CHO), 2.51 (br, 1H, OH)
55.3 ppm.
ppm. 13C NMR (100 MHz, CDCl3): d 143.2, 142.6, 131.5, 128.6,
(3-Methoxyphenyl)phenylmethanol (4b).4b [a]2D5 ¼ ꢀ15.23 128.2, 127.8, 126.5, 121.3, 75.5 ppm.
(c 1.16, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.33–7.18 (m, 6H,
(2-Fluorophenyl)phenylmethanol (4m).5h [a]D25
¼ ꢀ9.82
Ar), 6.88–6.91 (m, 2H, Ar), 6.77–6.69 (m, 1H, Ar), 5.69 (s, 1H, (c 0.95, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.47–6.94
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(m, 9H, Ar), 6.03 (s, 1H, CHO), 2.82 (s, 1H, OH) ppm. 13C NMR
(100 MHz, CDCl3): d 161.0, 158.5, 142.6, 130.9, 130.8, 129.4,
129.0, 128.9, 128.4, 127.6, 127.5, 126.3, 124.2, 115.3, 115.2,
115.1, 69.8 ppm.
2,2-Dimethyl-1-phenyl-propan-1-ol (4w).4b [a]D25 ¼ ꢀ17.13
(c 1.07, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.32–7.29 (m, 5H,
Ph), 4.40 (d, J ¼ 2.8 Hz, 1H, CHO), 1.87 (d, J ¼ 2.8 Hz, 1H, OH),
0.92 (s, 9H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d 142.1,
127.6, 127.5, 127.2, 82.3, 35.6, 25.9 ppm.
(4-Triuoromethylphenyl)phenylmethanol (4n).2c [a]D25
¼
ꢀ26.30 (c 1.09, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.55–7.54
(m, 2H, Ar), 7.44–7.42 (m, 2H, Ar), 7.33–7.21 (m, 9H, Ar), 5.75 (s,
1H, CHO), 2.74 (br, 1H, OH) ppm. 13C NMR (100 MHz, CDCl3): d
147.4, 143.0, 129.4, 128.7, 128.0, 126.61, 126.59, 125.45, 125.39,
125.35, 125.31, 125.28, 122.8, 75.6 ppm.
Cyclohexyl-phenyl-methanol (4x).3b [a]D25 ¼ ꢀ20.92 (c 1.02,
1
CH2Cl2). H NMR (400 MHz, CDCl3): d 7.34–7.24 (m, 5H, Ph),
4.33 (d, J ¼ 7.2 Hz, 1H, CHO), 1.96–0.89 (m, 11H, OH and Cy)
ppm. 13C NMR (100 MHz, CDCl3): d 143.6, 128.1, 127.3, 126.6,
79.3, 44.9, 29.2, 28.8, 26.4, 26.0, 25.9 ppm.
(2-Nitrophenyl)phenylmethanol (4o).20 [a]D25 ¼ +82.24 (c 1.07,
CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.90 (dd, J ¼ 8.0 Hz and 1.2
Hz, 1H, Ar), 7.72 (dd, J ¼ 8.0 Hz and 0.8 Hz, 1H, Ar), 7.63–7.59 (m,
1H, Ar), 7.45–7.40 (m, 1H, Ar), 7.36–7.11 (m, 5H, Ar), 6.39 (s, 1H,
CHO), 2.85 (br, 1H, OH) ppm. 13C NMR (100 MHz, CDCl3): d 148.2,
141.4, 138.4, 133.4, 129.3, 128.5, 128.4, 128.0, 126.9, 124.6,
71.4 ppm.
(4-Chlorophenyl)(2-methoxyphenyl)methanol (4y). [a]D25
¼
+44.34 (c 1.06, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.29–7.18
(m, 6H, Ar), 6.93–6.83 (m, 2H, Ar), 5.96 (s, 1H, CHO), 3.75 (s, 3H,
OCH3) ppm. 13C NMR (100 MHz, CDCl3): d 156.4, 141.8, 132.6,
131.4, 128.8, 128.1, 127.8, 127.5, 120.8, 110.7, 71.4, 55.3 ppm.
(4-Methylphenyl)(2-methoxyphenyl)methanol (4z).22 [a]D25
¼
+40.56 (c 1.20, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.25–7.19
(m, 4H, Ar), 7.10–7.08 (m, 2H, Ar), 6.93–6.82 (m, 2H, Ar), 5.99 (s,
1H, CHO), 3.75 (s, 3H, OCH3), 3.08 (s, 1H, OH), 2.30 (s, 1H, CH3)
ppm. 13C NMR (100 MHz, CDCl3): d 156.6, 140.3, 136.6, 132.0,
128.7, 128.5, 127.6, 126.4, 120.6, 110.6, 71.8, 55.3, 21.0 ppm.
(3-Nitrophenyl)phenylmethanol (4p).21 [a]D25 ¼ ꢀ42.31 (c 1.04,
CH2Cl2). 1H NMR (400 MHz, CDCl3): d 8.25–8.24 (m, 1H, Ar), 8.08–
8.05 (m, 1H, Ar), 7.68–7.66 (m, 1H, Ar), 7.48–7.43 (m, 1H, Ar), 7.36–
7.24 (m, 5H, Ar), 5.86 (s, 1H, CHO), 2.85 (br, 1H, OH) ppm. 13C
NMR (100 MHz, CDCl3): d 148.2, 145.7, 142.7, 132.4, 129.3, 128.8,
128.2, 126.6, 122.3, 121.2, 75.2 ppm.
(4-Nitrophenyl)phenylmethanol (4q).16b [a]D25 ¼ ꢀ57.02 (c
Acknowledgements
1
1.14, CH2Cl2). H NMR (400 MHz, CDCl3): d 8.13–8.10 (m, 2H,
Financial support under the grant number of NSC 99-2113-M-
005-005-MY3 from the National Science Council of Taiwan,
Republic of China is appreciated.
Ar), 7.52–7.50 (m, 2H, Ar), 7.35–7.28 (m, 5H, Ar), 5.85 (d, J ¼ 2.0
Hz 1H, CHO), 2.88 (br, 1H, OH) ppm. 13C NMR (100 MHz,
CDCl3): d 150.8, 147.2, 142.8, 128.8, 128.2, 127.0, 126.6, 123.5,
75.3 ppm.
Naphthalen-1-yl-phenylmethanol (4r).5a [a]D25
¼
+38.36
Notes and references
(c 1.06, CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.98–7.95 (m, 1H,
Ar), 7.83–7.76 (m, 2H, Ar), d 7.57–7.55 (m, 1H, Ar), d 7.45–7.19
(m, 8H, Ar), 6.43 (s, 1H, CHO), 2.55 (s, 1H, OH) ppm. 13C NMR
(100 MHz, CDCl3): d 143.1, 138.7, 133.9, 130.6, 128.7, 128.43,
128.39, 127.6, 127.0, 126.1, 125.5, 125.3, 124.5, 123.9, 73.5 ppm.
Naphthalen-2-yl-phenylmethanol (4s).4b [a]D25 ¼ ꢀ9.90 (c 1.01,
˜
1 For reviews, see: (a) C. Bolm, J. P. Hildebrand, K. Muniz and
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1
CH2Cl2). H NMR (400 MHz, CDCl3): d 7.81–7.71 (m, 4H, Ar),
´
7.46–7.17 (m, 8H, Ar), 5.87 (s, 1H, CHO), 2.64 (br, 1H, OH) ppm.
13C NMR (100 MHz, CDCl3): d 143.5, 141.0, 133.1, 132.8, 128.4,
128.2, 128.0, 127.6, 127.5, 126.6, 126.1, 125.9, 124.9, 124.7, 76.2
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CH2Cl2). H NMR (400 MHz, CDCl3): d 7.41–7.29 (m, 6H), 6.28
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(dd, J ¼ 2.0, 1.6 Hz, 1H), 6.07 (d, J ¼ 1.6, 0.8 Hz), 5.75 (s, 1H),
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CH2Cl2). 1H NMR (400 MHz, CDCl3): d 7.48–7.16 (m, 10H), 6.60–
6.56 (m, 1H), 6.33–6.27 (m, 1H), 5.26–5.24 (m, 1H), 2.91 (br, 1H)
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˜
1
CH2Cl2). H NMR (400 MHz, CDCl3): d 7.34–7.26 (m, 5H, Ph),
4.37–4.35 (m, 5H, CHPh), 1.97–1.95 (m, 1H, CH(CH3)2), 1.83 (s,
1H, OH), 1.01–0.99 (m, 3H, CH3), 0.80–0.78 (m, 3H, CH3) ppm.
13C NMR (100 MHz, CDCl3): d 143.6, 128.2, 127.4, 126.5, 80.0,
77.3, 77.0, 76.7, 35.2, 19.0, 18.2 ppm.
˜
C. Bolm, N. Hermanns, J. O. Hildebrand and K. Muniz,
Angew. Chem., Int. Ed., 2000, 39, 3465.
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