A convenient synthesis of unsymmetrical pinacols by coupling of structurally similar aromatic aldehydes mediated by low-valent titanium

Article abstract of DOI:10.1055/s-0028-1083264

The one-pot, selective cross pinacol-type couplings between two structurally similar aromatic aldehydes promoted by low-valent titanium generated unsymmetrical pinacols in moderate to good isolated yields in an erythrolthreo ratio of up to 91:9. This synt

Full text of DOI:10.1055/s-0028-1083264

PAPER
277
A Convenient Synthesis of Unsymmetrical Pinacols by Coupling of
Structurally Similar Aromatic Aldehydes Mediated by Low-Valent Titanium
Synthesis of
U
nsym
i
metric
n
al Pinacols -Fang Duan,* Jian-Xia Feng, Guo-Fu Zi, Zhan-Bin Zhang
Department of Chemistry, Beijing Normal University, Beijing, 100875, P. R. of China
Fax +86(10)58802075; E-mail: xinfangduan@vip.163.com
Received 11 September 2008; revised 17 September 2008
tions are simple, this one-pot synthesis proves to be more
convenient and effective than those previously reported.
Abstract: The one-pot, selective cross pinacol-type couplings be-
tween two structurally similar aromatic aldehydes promoted by
low-valent titanium generated unsymmetrical pinacols in moderate
to good isolated yields in an erythro/threo ratio of up to 91:9. This
synthetic methodology significantly extends the scope of the cross
pinacol-type couplings.
Our initial experiments in the cross pinacol-type coupling
involved the use of benzaldehyde (1a) and p-anisaldehyde
(1g) in the presence of various low-valent titanium (LVT)
species and the results are summarized in Table 1. The re-
sults indicate that the Ti(0) species generated by reducing
TiCl4 with two equivalents of different metals (assuming
that the reductions proceeded to completion, Table 1, en-
tries 1–5) showed significant effect on the outcome of the
cross coupling, while the Ti(III) species (Table 1, entries
6 and 7) did not. It was observed that the reactions initiat-
ed by TiCl4–Mn (1:2) species afforded the cross pinacol
products in 68% isolated yield (Table 1, entry 5), which
indicated that the low-valent titanium was a promising
mediator for this selective cross-coupling transformation.
An attempt to achieve a pinacol-type coupling using a cat-
alytic amount of Cp2TiCl2 in the presence of zinc powder
was disappointing (Table 1, entry 9).
Key words: pinacol, pinacol-type coupling, cross coupling,
McMurry coupling, low-valent titanium
Pinacols are a very important class of compounds and
ubiquitous in the structure of natural products as well as
drugs. They can also serve as a key structural motif in total
synthesis and chiral auxiliaries. Besides, they can be con-
verted into amino alcohols, epoxides, ketones, etc. As a
result, a variety of methods leading to their synthesis have
been developed involving pinacol coupling,1 dihydroxy-
lation of olefins,2 ring-opening of epoxides,3 and reduc-
tion of a-hydroxy carbonyls.4 The symmetric and cyclic
pinacols can be conveniently prepared through a homo or
intramolecular pinacol-type coupling. For example, this
intramolecular transformation has been highlighted as a
key step in synthesis of natural products such as taxol,5
( )-crassin,6 (+)-4,5-deoxyneodolabelline,7 and periplan-
one C.8 However, the synthesis of unsymmetrical pinacols
using an intermolecular cross pinacol-type coupling re-
mains a challenge, because the reported cross-couplings
between two different carbonyl compounds are rather few
and significantly dependent upon the structural or elec-
tronic differences between the two reactants and the low-
valent metals.9 Thus, the development of easily accessi-
ble, environmentally friendly, operationally simple, and
effective synthetic methods for unsymmetrical pinacols is
still a desirable goal.
The results (Table 2) showed that the reaction was rather
sluggish with low selectivity of the cross-coupling when
two equivalents of titanium species were used (Table 2,
entry 1). Increasing the ratio of the titanium species to
substrate, increased the selectivity of the cross-coupling
product 3ag (Table 2, entries 1–6), and the best selectivity
(68%) was obtained when five equivalents of titanium
species were used (Table 2, entry 4). The additives
(Table 2, entries 7 and 8) and temperature (Table 2, en-
tries 9 and 10) had no significant effect on the transforma-
tion, however, the solvent did. The reaction gave alkenes
in MeCN while no reaction was observed in CH2Cl2
(Table 2, entries 11 and 12).
Under the optimized reaction conditions, a variety of un-
symmetrical pinacols were conveniently and efficiently
prepared in 55–76% isolated yields through the cross pi-
nacol-type coupling reactions between two structurally-
similar aromatic aldehydes (Table 3). The results clearly
showed that the cross couplings proceeded with consider-
able selectivity when the substrates containing nitrogen or
oxygen-atom functional groups such as OH, OMe, NMe2,
NHC(O)Ph, C(O)NHPh, and C(O)OPh groups were used
(Table 3, entries 3–21). On the contrary the coupling reac-
tion between 1a and 1b or 1c, namely in the presence of
Me and F groups, gave a nearly statistical mixture of the
possible pinacols, which were inseparable by column
chromatography in our hands (Table 3, entries 1 and 2).
Both electron-deficient and electron-rich aromatic alde-
Recently, we have reported that the general and selective
McMurry cross-couplings between two carbonyl com-
pounds can be initiated by TiCl4–Zn species.10 To further
explore this transformation, we have recently extended
our research work to TiCl4–Mn system. We report herein
a facile synthesis of unsymmetrical pinacols through the
selective cross couplings between structurally similar ar-
omatic aldehydes in the presence of TiCl4–Mn species.
Because the reagents are readily available and the opera-
SYNTHESIS 2009, No. 2, pp 0277–0282
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Advanced online publication: 12.12.2008
DOI: 10.1055/s-0028-1083264; Art ID: Z21008SS
© Georg Thieme Verlag Stuttgart · New York

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X.-F. Duan et al.
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Table 1 Results of the Cross-Couplings of 1a with 1g Mediated by Various Low-Valent Titanium Species
OMe
H
O
OMe
+
OH
O
OH
OH
H
LVT
+
+
OH
OH
OH
3ag
MeO
MeO
1a
1g
2aa
4gg
Entry
[Ti]
Ti (equiv) Solvent
Temp (°C) Time
Yield (%)a
2aa
3ag
4gg
1
TiCl4–Zn (1:2)b
TiCl4–Mg (1:2)
TiCl4–Sm (1:2)
TiCl4–Sn (1:2)
TiCl4–Mn(1:2)
5
THF
–10
–10
–10
–10
–10
25
60 min
50 min
60 min
7 h
18
10
18
20
14
32
24
23
10
49
32
54
28
68
36
31
46
9
25
25
18
21
10
10
13
12
7
2c
3
5
THF
5
THF
4d
5
5
THF
5
THF
40 min
25 min
37 min
1 h
6
TiCl4–Zn–TMEDA–THF (2:1:3:6.4)
TiCl4–Mn–TMEDA–THF (2:1:3:6.4)
Cp2TiCl2–Zn–TMSCl (1:1: 1.5)
Cp2TiCl2–Zn–TMSCl (1:33.3:50)
5
CH2Cl2
CH2Cl2
THF
7
5
25
8
2
25
9d
0.06
THF
25
5.5 h
a Isolated yields after column chromatography.
b Mole ratio.
c Alkenes were also formed.
d The reaction could not proceed to completion.
Table 2 Influence of the Amount of Low-Valent Titanium, Temperature, Additive and Solvent on the Cross-Couplings of 1a with 1g
OMe
H
O
OMe
OH
O
OH
OH
H
LVT
+
+
+
OH
OH
OH
3ag
MeO
MeO
1a
1g
2aa
4gg
Entry
Ti (equiv)a
Solvent
Temp (°C)
Time
Yield (%)b
2aa
3ag
4gg
1
2
2
3
4
5
7
9
5
5
5
5
5
5
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
MeCN
CH2Cl2
–10
–10
–10
–10
–10
–10
–10
–10
–20
–40
–10
–10
6.5 h
22
44
54
51
68
59
56
64
56
59
64
32
25
25
16
21
21
18
18
14
18
1 h
16
3
1 h
20
4
40 min
30 min
20 min
30 min
18 min
40 min
50 min
35 min
3 h
14
5
12
6
20
7c
8d
9
12
20
19
10
11
12
12
alkenes
no reaction
a Low-valent Ti generated from TiCl4–Mn (1:2).
b Isolated yields after column chromatography.
c Pyridne (2.5 equiv) was used as an additive.
d TMSCl (2.5 equiv) was used as an additive.
Synthesis 2009, No. 2, 277–282 © Thieme Stuttgart · New York

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Synthesis of Unsymmetrical Pinacols
279
hydes gave moderate to good yields (Table 3, entries 3– It seems that these substituents affect the outcome of the
19), and the selective cross coupling also successfully oc- reactions through their strong affinity to the surface of the
curred with heteroaromatic aldehydes such as thiophene- titanium rather than through altering the reduction poten-
2-carbaldehyde and 6-methoxynicotinaldehyde (Table 3, tial or electronic density of the carbonyl moiety, because
entries 20 and 21). Besides, it should be mentioned that all both electron-donating groups (Table 3, entries 3–14) and
the cross couplings gave the erythro-rich pinacol prod- electron-withdrawing groups (Table 3, entries 15–18) dis-
ucts, and the best stereoselectivity was up to 91% play such effects. This postulation is further strengthened
(Table 3, entry 6).
by comparing entries 2 with 19.
Table 3 Preparations of Unsymmetrical Pinacols via the Cross Pinacol-Type Couplings between Structurally Similar Aromatic Aldehydes
Promoted by TiCl4–Mn–THFa
O
OH
O
TiCl4–Mn (1:2)
–10 °C, THF
H
H
+
OH
3ab–av
Y
Y
1b–v
1a
Entry
Aldehyde
Time (min) Product
Yield (%)b
erythro/threoc
1a or 1u
1b–1v
1
2
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1uf
1a
1b: Y = 4-F
22
3ab
3ac
3ad
3ae
3af
40d,e
41d,e
70
76
73
68
61
65e
64
58
64
65
57
70
63
66
58
55
65
58
55
–
1c: Y = 4-Me
24
40
40
45
30
40
30
30
40
30
30
30
40
45
45
45
45
30
40
40
–
3
1d: Y = 4-morpholinyl
1e: Y = 4-Me2N
1f: Y = 4-piperidinyl
1g: Y = 4-MeO
1h: Y = 3-MeO
1i: Y = 2-MeO
82:18
88:12
90:10
91:9
4
5
6
3ag
3ah
3ai
7
80:20
–
8
9
1j: Y = 4-HO
3aj
85:15
80:20
76:24
79:21
75:25
80:20
68:32
74:26
67:33
71:29
83:17
73:27
79:21
10
11
12
13
14
15
16
17
18
19
20
21
1k: Y = 3-HO
3ak
3al
1l: Y = 3-MeO-4-HO
1m: Y = 3,4-(MeO)2
3am
3an
3ao
3ap
3aq
3ah
3as
3at
1n: Y = 3,4-methylenedioxy
1o: Y = 4-NHCOPh
1p: Y = 4-CONHPh
1q: Y = 4-CONEt2
1r: Y = 4-COOPh
1s: Y = 4-COOMe
1t: Y = 4-CH2NHPh
1d: Y = 4-morpholinyl
1v: 6-methoxynicotinaldehyde
3ud
3av
a Low-valent Ti was generated from TiCl4–Mn (1:2) in THF and charged in 5 equiv. The reaction was carried out at –10 °C.
b Isolated yields after column chromatography.
c The ratio of erythro/threo was determined by lH NMR analysis.
d These two cross-couplings generated a roughly statistical mixture of the three coupling products. Other cross-couplings in Table 3 occurred
obviously selectively over the two homo-couplings and the mole ratios of their three products (2aa:3ad–3av:4dd–4vv) ranged from 1:7:1 to
1:3:0.9.
e The three coupling products in these cases could not be separated by column chromatography in our hands, the yield was determined by HPLC.
f Thiophene-2-carbaldehyde.
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IR (KBr): 3505.3, 3400.4, 2893.1, 1620.2, 1527.6, 1355.9, 1192.5,
1048.2, 808.0, 776.9, 703.4 cm–1.
In conclusion, a facile synthetic approach to the unsym-
metrical pinacols through a selective cross pinacol-type
coupling between structurally similar aromatic aldehydes 1H NMR (400 MHz, CDCl3): d = 2.91 (s, 6 H), 4.59–4.72 (m, 2 H),
6.61 (d, J = 8.28 Hz, 2 H), 7.01 (d, J = 8.72 Hz, 2 H), 7.13–7.23 (m,
5 H).
promoted by TiCl4–Mn–THF has been developed. Its ad-
vantages are: (a) the reagents are readily available; (b) the
two aldehydes are charged in equalmolar amounts; and (c)
the operations are simple and performed in one flask. Fur-
thermore, this synthetic methodology significantly ex-
tends the scope of the cross pinacol-type couplings.
erythro/threo-1-Phenyl-2-[4-(piperidin-1-yl)phenyl]ethane-1,2-
diol (3af)
White solid; mp 131.2–132.7 °C.
IR (KBr): 3502.8, 3398.0, 2942.7, 1614.6, 1516.0, 1239.0, 1193.5,
1044.1, 811.6, 775.0, 703.9 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.55 (m, 2 H), 1.68 (m, 4 H), 2.80
(s, OH), 3.01 (s, OH), 3.10 (m, 4 H), 4.58–4.69 (m, 2 H), 6.79 (d,
J = 8.6 Hz, 2 H), 6.98 (d, J = 8.64 Hz, 2 H), 7.11–7.22 (m, 5 H).
Melting points were obtained on a microscopical instrument and un-
corrected. NMR spectra were recorded at 400 or 500 MHz spec-
trometer and TMS as internal standard. IR spectra were recorded on
a FT-IR spectrometer. All reagents and solvents used for pinacol-
type couplings were freshly dried before use. All corresponding
glassware was oven dried (120 °C) and cooled under a stream of ar-
gon.
MS (EI): m/z (%) = 279 (M – 18, 35), 263 (29), 250 (50), 190 (100),
174 (82), 105 (47), 77 (57).
Anal. Calcd for C19H28NO2: C, 76.73; H, 7.80; N, 4.71. Found: C,
76.55; H, 8.26; N, 4.51.
Pinacols 3ad–3av; erythro/threo-1-(4-Methoxyphenyl)-2-phe-
nylethane-1,2-diol (3ag); Typical Procedure
erythro/threo-1-(3-Methoxyphenyl)-2-phenylethane-1,2-diol
(3ah)
Colorless liquid.
Under argon, a four-necked flask equipped with a magnetic stirrer
was charged with Mn powder (1.75 g, 32 mmol) and THF (50 mL).
The mixture was cooled to –10 °C and TiCl4 (1.75 mL, 16 mmol)
was slowly added using a syringe. The mixture was warmed to r.t.,
stirred for 0.5 h, and then refluxed for 2.5 h. The mixture was again
cooled to –10 °C, and a solution of benzaldehyde (1a; 3.39 g, 3.2
mmol) and p-anisaldehyde (1g; 4.35 g, 3.2 mmol) in THF (20 mL)
was added. The mixture was kept at –10 °C until the carbonyl com-
pounds were consumed (monitored by TLC). The reaction was
quenched with aq 10% NaHCO3 (30 mL) and extracted with CH2Cl2
(3 × 20 mL). The organic layers were combined and dried
(Na2SO4). The solvent was removed and the resulting residue was
purified by flash chromatography to give the title compound 3ag as
a white solid; mp 118.2 °C (Lit.12 mp 129.2–131.0 °C).
IR (KBr): 3407.0, 3030.7, 2901.9, 1603.3, 1488.5, 1454.2, 1262.6,
1043.5, 761.4, 700.1 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.86 (br s, OH), 3.57 and 3.59
(two sets of singlets, 3 H), 4.51–4.61 (m, 2 H), 6.53–6.72 (m, 3 H),
7.00–7.01 (m, 2 H), 7.12–7.17 (m, 4 H).
MS (EI): m/z (%) = 227 (M – 18, 43), 138 (100), 107 (70), 94 (43),
77 (56), 51 (28).
Anal. Calcd for C15H16O3: C, 73.75; H, 6.60. Found: C, 73.31; H,
6.86.
erythro/threo-1-(4-Hydroxyphenyl)-2-phenylethane-1,2-diol
(3aj)
IR (KBr): 3576.6, 3300.3, 2885.7, 1614.0, 1515.5, 1250.9, 1036.2,
827.7, 699.1 cm–1.
White solid; mp 188.3–190.2 °C (Lit.13 mp 165–167 °C).
1H NMR (400 MHz, CDCl3): d = 3.76 and 3.80 (two sets of singlets,
3 H), 4.64–4.70 (m, 2 H), 6.75 (d, J = 8.8 Hz, 2 H), 7.04 (d, J = 8.8
Hz, 2 H), 7.10–7.23 (m, 5 H).
IR (KBr): 346.9, 3027.6, 2896.3, 1600.5, 1519.2, 1454.0, 1254.7,
1225.9, 1069.0, 1045.9, 1006.8, 833.6, 696.9 cm–1.
1H NMR (400 MHz, acetone-d6): d = 4.44–4.61 (m, 2 H), 6.65 (d,
J = 6.6 Hz, 2 H), 6.95 (d, J = 6.56 Hz, 2 H), 7.11–7.18 (m, 5 H),
8.15 (s, OH).
Note: The cross-coupled pinacols were isolated as a mixture of
erythro- and threo-isomers, and the ratio of erythro/threo was deter-
mined by lH NMR analysis after column chromatography. Analyti-
cal samples were obtained by recrystallization from the above-
mentioned samples. The crystallization would result in a little
change in the ratio of erythro/threo.
erythro/threo-1-(3-Hydroxyphenyl)-2-phenylethane-1,2-diol
(3ak)
White solid; mp 109.5–110.6 °C.
IR (KBr): 3255.7, 1590.6, 1492.1, 455.2, 1312.4, 1266.8, 1148.9,
1042.9, 999.0, 788.3, 766.6, 698.5 cm–1.
1H NMR (400 MHz, acetone-d6): d = 4.72–4.78 (m, 2 H), 6.65 (m,
2 H), 6.79 (m, 1 H), 6.97 (m, 1 H), 7.14 (m, 5 H).
erythro/threo-1-(4-Morpholinophenyl)-2-phenylethane-1,2-diol
(3ad)
White solid; mp 133.0–133.9 °C.
IR (KBr): 3505.5, 3353.6, 2859.4, 1615.4, 1519.2, 1450.6, 1241.0,
1114.9, 1046.2, 928.0, 811.9, 701.3 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.77 (s, OH), 2.91 (s, OH), 3.13
(br s, 4 H), 3.84 (br s, 4 H), 4.63–4.71 (m, 2 H), 6.79 (d, J = 6.6 Hz,
2 H), 7.04 (d, J = 8.64 Hz, 2 H), 7.13–7.31 (m, 5 H).
MS (EI): m/z (%) = 212 (M – 18, 10), 165 (9), 124 (98), 107 (88),
95 (100), 79 (83), 77 (88), 51 (29).
Anal. Calcd for C14H14O3: C, 73.03; H, 6.13. Found: C, 72.79; H,
6.13.
MS (EI): m/z (%) = 300 (M + 1, 26), 281 (28), 265 (44), 191 (100),
176 (52), 132 (82), 120 (53), 105 (97), 77 (51).
erythro/threo-1-(4-Hydroxy-3-methoxyphenyl)-2-phenyl-
ethane-1,2-diol (3al)
White solid; mp 83–84.6 °C.
Anal. Calcd for C18H21NO3: C, 72.22; H, 7.07; N, 4.68. Found: C,
72.07; H, 7.22; N, 4.48.
IR (KBr): 3414.6, 3030.2, 1605.0, 1518.2, 1453.1, 1272.3, 1033.5,
765.8, 700.7 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.73 and 3.77 (two sets of singlets,
3 H), 4.62–4.79 (m, 2 H), 5.54 and 5.60 (two sets of singlets, OH),
6.57–6.88 (m, 3 H), 7.11–7.33 (m, 5 H).
erythro/threo-1-[4-(Dimethylamino)phenyl]-2-phenylethane-
1,2-diol (3ae)
White solid; mp 135–136.9 °C (Lit.11 mp 112 °C).
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Synthesis of Unsymmetrical Pinacols
281
MS (EI): m/z (%) = 242 (M – 18, 70), 226 (47), 213 (40), 152 (100),
125 (76), 110 (62), 105 (97), 93 (85), 77 (94), 65 (57).
erythro/threo-1-[4-(Phenoxycarbonyl)phenyl]-2-phenylethane-
1,2-diol (3ar)
White solid; mp 102.7–103.8 °C.
Anal. Calcd for C15H16O4: C, 69.22; H, 6.20. Found: C, 68.98; H,
6.34.
IR (KBr): 3405.8, 1728.9, 1486.4, 1267.6, 1200.7, 1078.3, 1061.4,
747.3, 701.7 cm–1.
erythro/threo-1-(3,4-Dimethoxyphenyl)-2-phenylethane-1,2-
diol (3am)14
White solid; mp 84.5–86.3 °C.
1H NMR (400 MHz, CDCl3): d = 2.65 (br s, 2 H), 4.66–4.97 (m, 2
H), 7.11–7.13 (m, 1 H), 7.18–7.33 (m, 9 H), 740–7.44 (m, 2 H), 8.04
(d, J = 8.4 Hz, 1 H), 8.09 (d, J = 8.4 Hz, 1 H).
IR (KBr): 3440.5, 2934.1, 1517.8, 1263.0, 1235.7, 1139.3, 1026.8,
764.3, 701.9 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.73 and 3.77 (two sets of singlets,
3 H), 3.86 and 3.89 (two sets of singlets, 3 H), 4.65–4.80 (m, 2 H),
6.58–6.75 (m, 3 H), 7.13–7.35 (m, 5 H).
MS (EI): m/z (%) = 335 (M + 1, 10), 317 (M – 18, 6) 241 (42), 228
(100), 207 (37), 165 (39), 133 (94), 105 (95), 94 (64), 77 (98), 51
(74).
Anal. Calcd for C21H18O4: C, 75.43; H, 5.43. Found: C, 75.41; H,
5.62.
erythro/threo-1-(3,4-Methylenedioxyphenyl)-2-phenylethane-
1,2-diol (3an)
erythro/threo-1-[4-(Methoxycarbonyl)phenyl]-2-phenylethane-
1,2-diol (3as)16
White solid; mp 115.1–115.9 °C.
White solid; mp 98.3–99.7 °C (Lit.15 mp 92–93 °C).
IR (KBr): 3378.2, 2900.2, 1503.7, 1489.5, 1445.0, 1249.2, 1037.6,
758.4, 700.6 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.54 (br s, 2 H), 4.64–4.79 (m, 2
H), 5.96 (m, 1 H), 6.53–6.84 (m, 3 H), 7.16–7.35 (m, 5 H).
IR (KBr): 3456.7, 1691.1, 1608.2, 1434.2, 1285.1, 1114.5, 728.1,
700.4 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.87 and 3.89 (two sets of singlets,
3 H), 4.73–4.92 (m, 2 H), 7.06–7.28 (m, 6 H), 7.86 (d, J = 8.4 Hz,
1 H), 7.91 (d, J = 8.4 Hz, 1 H).
erythro/threo-1-(4-Benzamidophenyl)-2-phenylethane-1,2-diol
(3ao)
erythro/threo-1-{4-[(Phenylamino)methyl]phenyl}-2-phenyl-
ethane-1,2-diol (3at)
White solid; mp 204.0–205.7 °C.
IR (KBr): 3334.4, 2904.2, 1650.9, 1602.6, 1533.2, 1411.8, 1325.6,
1028.0, 697.6 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.23 (s, OH), 4.54 (s, OH), 4.66–
4.84 (m, 2 H), 7.12 (d, J = 8.56 Hz, 1 H), 7.18–7.29 (m, 6 H), 7.48–
7.67 (m, 3 H), 7.68–7.73 (m, 2 H), 7.97–8.00 (m, 2 H), 9.42 (s, NH).
White solid; mp 122.3–123.7 °C.
IR (KBr): 3407.2, 3371.6, 2893.1, 1604.3, 1503.8, 1318.7, 1062.8,
1032.4, 823.1, 748.1, 700.0 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.28 and 4.32 (two sets of singlets,
2 H), 4.70 and 4.81 (two sets of singlets, 2 H), 6.61 (d, J = 7.6 Hz,
2 H), 6.73 (t, J = 7.6 Hz, 1 H), 7.09–7.18 (m, 6 H), 7.22–7.25 (m, 5
H).
MS (EI): m/z (%) = 334 (M + 1, 10), 316 (M – 18, 23), 226 (100),
123 (32), 105 (56), 77 (25), 51 (17).
Anal. Calcd for C21H19NO3: C, 75.66; H, 5.74; N, 4.20. Found: C,
75.37; H, 5.94; N, 4.08.
MS (EI): m/z (%) = 319 (M+, 16), 212 (40), 120 (41), 106 (100), 104
(30), 51 (26).
Anal. Calcd for C21H21NO2: C, 78.97; H, 6.63; N, 4.39. Found: C,
78.61; H, 6.60; N, 4.16.
erythro/threo-1-[4-(Phenylcarbamoyl)phenyl]-2-phenylethane-
1,2-diol (3ap)
White solid; mp 219.1–219.7 °C.
erythro/threo-1-(4-Morpholinophenyl)-2-(thiophen-2-
yl)ethane-1,2-diol (3ud)
White solid; mp 144.3–145 °C.
IR (KBr): 3334.2, 1651.2, 1598.9, 1530.3, 1441.7, 1324.9, 1057.2,
753.0, 692.8 cm–1.
1H NMR (500 MHz, acetone-d6): d = 4.49 and 4.55 (two sets of sin-
glets, OH), 4.71 and 4.77 (two sets of singlets, OH), 4.74–4.95 (m,
2 H), 7.11 (m, 1 H), 7.21–7.39 (m, 6 H), 7.34–7.39 (m, 3 H), 7.84–
7.88 (m, 4 H), 9.49 (s, NH).
IR (KBr): 3466.4, 2959.7, 1614.6, 1517.7, 1448.5, 1242.9, 1114.7,
1036.8, 924.4, 818.3, 718.7 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.82 (s, OH), 3.07 (s, OH), 3.13
(t, J = 4.96 Hz, 4 H), 3.84 (t, J = 4.64 Hz, 4 H), 4.70–4.99 (m, 2 H),
6.68 (d, J = 3.2 Hz, 1 H), 6.81–6.86 (m, 3 H), 7.13 (d, J = 8.4 Hz,
2 H), 7.20–7.22 (m, 1 H).
MS (EI): m/z (%) = 334 (M + 1, 9), 315 (M – 18, 5), 227 (100), 207
(33), 133 (82), 105 (55), 77 (50).
Anal. Calcd for C21H19NO3: C, 75.66; H, 5.74; N, 4.20. Found: C,
75.44; H, 6.026; N, 4.13.
MS (EI): m/z (%) = 306 (M + 1, 18), 287 (M–18, 29), 191 (100),
132 (98), 112 (72), 84 (58), 77 (50), 49 (54).
Anal. Calcd for C16H19NO3S: C, 62.93; H, 6.27; N, 4.59. Found: C,
62.63; H, 6.37; N, 4.37.
erythro/threo-1-[4-(Diethylcarbamoyl)phenyl]-2-phenylethane-
1,2-diol (3aq)
Colorless liquid.
erythro/threo-1-(6-Methoxypyridin-3-yl)-2-phenylethane-1,2-
IR (KBr): 3388.5, 2974.1, 1607.7, 1475.5, 1434.6, 1289.1, 1098.4,
1051.6, 832.7, 701.7 cm–1.
diol (3av)
White solid; mp 91–92.2 °C.
1H NMR (400 MHz, CDCl3): d = 0.91 (br s, 3 H), 1.07 (br s, 3 H),
3.02 (br s, 2 H), 3.34 (br s, 2 H), 4.34–4.43 (m, 2 H), 6.86–7.03 (m,
9 H).
IR (KBr): 3440.9, 3259.8, 2898.8, 1607.5, 1573.9, 1497.1, 1394.5,
1295.6, 1261.5, 1040.2, 836.0, 756.7, 701.0 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.14 (br s, 2 H), 3.89 and 3.92
(two sets of singlets, 3 H), 4.64–4.86 (m, 2 H), 6.63 and 6.66 (two
sets of d, J = 6.84 Hz, 1 H), 7.13–7.31 (m, 5 H), 7.37 and 7.48 (two
sets of d, J = 6.84 Hz, 1 H), 7.81 and 7.95 (two sets of singlets, 1 H).
MS (EI): m/z (%) = 314 (M + 1, 42), 296 (M – 18, 22), 206 (78), 133
(78), 105 (95), 77 (100).
Anal. Calcd for C19H23NO3: C, 72.82; H, 7.40; N, 4.47. Found: C,
72.52; H, 7.82; N, 3.99.
Synthesis 2009, No. 2, 277–282 © Thieme Stuttgart · New York

282
X.-F. Duan et al.
PAPER
Guy, R. K.; Shibayama, K. J. Am. Chem. Soc. 1995, 117,
MS (EI): m/z (%) = 246 (M + 1, 11), 227 (M – 18, 15), 210 (90), 198
(39), 180 (41), 137 (82), 105 (77), 95 (49), 77 (77), 51 (100).
645.
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Acknowledgment
We gratefully acknowledge the funding from National Nature Sci-
ence Foundation of China (Grant 20672014) and the support of
Beijing Key Subject Program as well as Beijing Municipal Com-
mission of Education.
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Synthesis 2009, No. 2, 277–282 © Thieme Stuttgart · New York