Remarkable Dependence of Diastereoselectivity on Anhydrous or Aqueous Solvent in the Indium Hydride Promoted Reductive Aldol Reaction of α,β-Unsaturated Ketones

Article abstract of DOI:10.1002/1615-4169(200206)344:3/4<283::AID-ADSC283>3.0.CO;2-S

Dichloroindium hydride generated by the transmetallation between tributyltin hydride and indium trichloride predominantly reduced α,β-unsaturated ketones (enones) with 1,4-selectively even in the presence of aldehydes. Under anhydrous conditions, the successive aldol reaction between the resulting enolates and the remaining aldehydes proceeded with high anti-selectivity. The stereo-chemistry was dramatically reversed to be syn-selective by the use of water and methanol as an additive and solvent, respectively.

Full text of DOI:10.1002/1615-4169(200206)344:3/4<283::AID-ADSC283>3.0.CO;2-S

COMMUNICATIONS
Remarkable Dependence of Diastereoselectivity on Anhydrous
or Aqueous Solvent in the Indium Hydride Promoted Reductive
Aldol Reaction of a,b-Unsaturated Ketones
Katsuyuki Inoue, Tatsuya Ishida, Ikuya Shibata, Akio Baba*
Department of Molecular Chemistry & Frontier Research Center, Graduate School of Engineering, Osaka University, 2-1
Yamada-Oka, Suita, Osaka 565-0871, Japan
Fax: (‡ 81)-6-6879-7387, e-mail: baba@ap.chem.eng.osaka-u.ac.jp
Received: November 13, 2001; Accepted: December 30, 2001
Table 1. Effect of solvents on the selective 1,4-reduction of
a,b-unsaturated ketones (enones) 1 with indium hydride.
Abstract: Dichloroindium hydride generated by the
transmetallation between tributyltin hydride and
indium trichloride predominantly reduced a,b-unsa-
turated ketones (enones) with 1,4-selectively even in
the presence of aldehydes. Under anhydrous con-
ditions, the successive aldol reaction between the
resulting enolates and the remaining aldehydes
proceeded with high anti-selectivity. The stereo-
chemistry was dramatically reversed to be syn-
selective by the use of water and methanol as an
additive and solvent, respectively.
[a]
InCl
3
3
O
Bu SnH
O
R1
R2
R1
R2
Solvent
–78 °C to rt, 1 h
1
2
Entry
1
R1
R2
Solvent
Yield of 2
(
%)[
b]
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
t-Bu
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Me (1b)
t-Bu (1c)
Ph (1d)
Ph (1e)
THF66 (33)
THF59 (34)
THF12
THF3
MeCN
[
[
[
c]
d]
e]
2
3
4
5
6
7
8
9
0
1
2
Keywords: aldol reaction; diastereoselectivity; hy-
drides; indium; water chemistry
32
34 (13)
CH Cl
2
2
MeOH
i-PrOH
97
85
77
15
97
THF/H O (9/1)
2
1
1
1
H O
2
The potential of indium compounds in the field of
MeOH
MeOH
MeOH
MeOH
organic syntheses has been intensively studied in this
99
decade.[ Although several indium hydrides such as 13
LiPh InH (n ˆ 0 ± 2), InH [CN(Mes)C H N(Mes)], 14
1]
[f]
28
66
[
2]
[g]
n
4±n
3
2
2
[
3]
and InH [P(C H ) ] have been reported, the synthetic
3
6
11 3
use of indium hydrides remains to be explored. We have
recently demonstrated that dichloroindium hydride
O
Ph
O
Ph
Ph
(
Cl InH) was generated by the transmetallation be-
2
tween tri-n-butyltin hydride (Bu SnH) and indium
3
Ph
[
4]
trichloride (InCl ), and that the hydride has accom-
3
plished the reduction of acid chlorides to aldehydes
3a
[
5]
and dehalogenation of alkyl bromides. During fur-
[
[
a]
b]
InCl 1 mmol, Bu SnH 1 mmol, 1 1 mmol, solvent 1 mL.
Values in parentheses are yields of dimerization product
a.
Galvinoxyl (0.1 mmol) was added.
AlCl was used instead of InCl .
3
3
ther study of the reduction of a,b-unsaturated ketones
(
enones), we discovered a three-component synthesis of
3
aldols (reductive aldol reaction) from Cl InH, enones,
[c]
2
[
[
[
[
d]
e]
f]
and aldehydes, in which a predominant 1,4-reduction
3
3
of enones by Cl InH is followed by the aldol reaction
BF ¥ OEt was used instead of InCl .
2
3
2
3
between the resulting enolates and the remaining
aldehydes. Noteworthy is that, in the reductive aldol
reaction, both anti- and syn-selective aldol reactions
were effected by the use of THFand an aqueous solvent,
respectively.
1,2-Reduction product was accompanied (4%).
,2-Reduction product was accompanied (8%).
g]
1
When anhydrous THFwas used as solvent, the 1,4-
Table 1 shows the results of the reduction of enones 1 reduction product 2a was obtained in 66% yield from
with indium hydride generated from Bu SnH and InCl . chalcone (1a), accompanied by the dimerization prod-
3
3
Adv. Synth. Catal. 2002, 344, No. 3+4
¹ VCH Verlagsgesellschaft mbH, 69451 Weinheim, Germany, 2002 1615-4150/02/3443+4-283 ± 287 $ 17.50+.50/0
283

COMMUNICATIONS
Akio Baba et al.
uct 3a in 33% yield (entry 1). The formation of 3a Table 2. Stereoselective reductive aldol reactions of 1b with 4
by using indium hydride.[
a]
indicates that the generation of the indium enolate is
followed by the Michael addition to residual 1a. The low
effect of galvinoxyl suggests that no radical process is
involved in this reaction (entry 2). Other group 13
element halides such as AlCl and BF ¥ OEt show less
O
InBr3
Bu3SnH
O
+
H
Ph
Me
Solvent
–78 °C to rt, 1 h
R3
3
3
2
1
b
4a - f
effects (entries 3 and 4). Employment of solvents such as
MeCN and CH Cl resulted in considerably lower yields
2
2
O
OH
Me
O
OH
(
entries 5 and 6). However, when MeOH and i-PrOH
OH
Ph
Ph
were used, the 1,4-reduced product 2a was obtained
+
+
R3
R3
R3
in good to excellent yields without accompanying 3a
Me
(
entries 7 and 8). These results indicate that indium
anti
syn
hydride has considerably stability for alcohols and that
the resulting indium enolate is smoothly protonated by
the alcohol solvents. The addition of small amounts of
5a - f
6a - f
Entry R3
4
Solvent
Yield [%]
water to THF(TH/FH
O ˆ 9/1) also induced the
5
syn:anti
6
2
selective formation of 2a (entry 9). Using water as a
solvent did not give a satisfying result (entry 10),
perhaps because of the insolubility of the substrates. In
MeOH, enones bearing a benzoyl moiety 1a, 1b, and 1c
were reduced to provide the corresponding ketones in
quantitative yields (entries 7, 11, and 12). In contrast,
the reduction of aliphatic ketones 1d and 1e resulted
in lower yields along with slight amounts of the 1,2-
reduction products (entries 13 and 14).
In the next stage, we could fortunately accomplish a
reductive aldol reaction of enones as shown in Table 2.
In general, the reductive aldol reaction using the three
components metal hydrides, enones, and aldehydes has
[b]
1
2
3
4
5
6
7
8
9
0
1
2
3
4
MeO 4a THF64 (
MeO 4a THF79 (
MeO 4a THF86 (
MeO 4a MeOH
5a)
5a)
5a)
9:91 14
14:86 12
4:96
[c]
6
69 (5a) > 99: > 1 19
94:6 13
4:96 11
MeO 4a THF/H O (9/1) 79 (5a)
2
Me
Me
Ph
Ph
H
H
Cl
Cl
Cl
4b THF89 (
5b)
4b THF/H O (9/1) 77 (5b)
95:5
5:95 14
93:7
10:90 11
18
2
4c THF85 (
5c)
4c THF/H O (9/1) 71 (5c)
29
2
1
1
1
1
1
4d THF87 (
5d)
4d THF/H O (9/1) 76 (5d)
91:9
19
2
4e THF83 (
5e)
7:97 16
85:15 32
90:10 22
14:86 16
63:37 56
4e THF/H O (9/1) 68 (5e)
2
4e MeOH
68 (5e)
5f)
[
6]
been a difficult issue because an aldehyde is more 15
susceptible than an enone to conventional metal hy- 16
drides. When the reduction of enone 1b was performed
NO2 4f THF70 (
NO2 4f THF/H O (9/1) 44 (5f)
2
[
a]
InBr 1.2 mmol, Bu SnH 1.2 mmol, 1b 1.5 mmol, 4 1 mmol,
3
3
in the presence of p-anisaldehyde (4a), the aldol product
a was obtained in 64% yield with high anti-selectivity
solvent 2 mL.
5
(
[
b]
InCl3 1 mmol, Bu SnH 1 mmol, 1b 1 mmol, 4 1 mmol,
solvent 2 mL.
InBr3 1 mmol, Bu SnH 1 mmol, 1b 1 mmol, 4 1 mmol,
solvent 2 mL.
3
syn:anti ˆ 9:91), in spite of the accompanying reduc-
tion of aldehyde 4a in 14% yield (Table 2 entry 1). The
predominant formation of the aldol adduct 5a indicates
that indium hydride reacts with enone 1b in preference
to aldehyde 4a, and that the generated indium enolate
[c]
3
reacts with 4a smoothly. When InBr was used instead of of aldol adducts 5 (entries 6 ± 16). In these cases, the
3
InCl , the yield of 5a was increased to 79% yield stereochemistry of syn- and anti-selectivities in 5 could
3
(
entry 2). Moreover, the use of a small excess amount of be controlled by the choice of solvents, THFand
enones and indium hydride achieved a high yield (86%) aqueous solvent. In the case of using p-nitrobenzalde-
and anti-diastereoselectivity (96%) of 5a (entry 3). To hyde (4f) under aqueous conditions, the yield and
our knowledge, this is the highest anti-selectivity selectivity of 5f are not favorable (entry 16). Moreover,
reported so far. To our surprise, even when MeOH an aliphatic aldehyde is not applicable. This is a
was used as a solvent, the aldol reaction effectively limitation of our method at this stage.
proceeded without decomposition of the intermediate
Although the mechanism for the presented diaster-
enolate (entry 4). The aldol reaction of the indium eoselective aldol reaction is not clear as yet, a tentative
enolate apparently took place much faster than proto- path is illustrated in Scheme 1. When Br InH is treated
2
nolysis (alcoholysis) by MeOH. Moreover, of particular with the mixture of enone and aldehyde, selective 1,4-
interest is that the obtained aldol product was solely the reduction of the enone occurs without the reduction of
syn-isomer, which was completely opposite to the anti- the aldehyde. The (Z)-enolate is generated initially
selective reaction in THFunder anhydrous conditions.
because of the preferred 1,4-addition of indium hydride
[
7]
When aqueous THF(THF/H O ˆ 9/1) was used, a high to the s-cis form of enone 1, and the enolate reacts
2
syn-selectivity was also obtained (entry 5). Various with aldehyde, giving the syn-indium aldolate syn-7 by
aromatic aldehydes 4 were applicable for the formation way of a Zimmerman±Traxler six-membered transition
284
Adv. Synth. Catal. 2002, 344, 283 ± 287

Dependence of Diastereoselectivity on Anhydrous or Aqueous Solvent in Aldol Reaction COMMUNICATIONS
O
Experimental Section
R1
R2
HInBr2
InBr2
General Remarks
1
IR spectra were recorded as thin film on a Horiba FT-720
spectrometer. All the H and C NMR spectra were recorded
with a JEOL JNM-GSX-270 (270 and 67.9 MHz, respectively)
InBr2
1
13
O
O
R1
in deuteriochloroform (CDCl ) containing 0.03% (w/v) of
3
R1
R2
tetramethylsilane as internal standard. Mass spectra were
recorded on a JEOL JMS-DS-303. Column chromatography
was performed using Fuji Davison silica gel FL-100DX.
Preparative TLC was carried out on Wakogel B-5Fsilica gel.
R2
(
Z)-enolate
(E)-enolate
3
3
Tri-n-butyltin hydride (n-Bu SnH) was prepared by the
R CHO
R CHO
3
4
4
reduction of tri-n-butyltin chloride (n-Bu SnCl) with LiAlH .
3
4
R1
H
R1
H
Commercially available InCl3 was used without further
purification. All aldehydes were purchased and purified by
usual methods. THFwas freshly distilled from sodium
benzophenone ketyl. All reactions were carried out under a
dry nitrogen atmosphere.
InBr2
O
O
InBr2
H
O
R2
O
R3
R2
R3
H
O
O
OInBr2
R3
OInBr2
R3
Representative Procedure for the 1,4-Reduction of
Enones
R1
R1
A mixture of InCl (0.221 g, 1 mmol) and Bu SnH (0.291 g,
1 mmol) in MeOH (1 mL) was stirred at ±78 8C for 5 min to
generate dichloroindium hydride. Chalcone 1a (0.208 g,
syn-7
anti-7
3
3
R2
H
R2
H
1
mmol) was added at this temperature and the reaction
mixture was warmed up to room temperature for 1 h. After
adding aqueous ammonium fluoride, the volume was extracted
with ether (50 mL Â 2). The combined extract was dried over
O
OH
O
OH
R1
R3
R1
R3
anhydrous MgSO , and concentrated. The residue was sub-
4
syn-5
anti-5
MeOH or THF/H2O
THF
R2
R2
jected to column chromatography eluting with hexane-EtOAc
(
9:1) to give product 2a; yield: 97%. Further purification was
Scheme 1. Plausible reacton path.
performed by silica gel TLC with hexane-Et O (9:1).
2
state.[8] In MeOH or aqueous THF(TH F/ H O ˆ 9/1),
2
syn-7 is immediately protonated to give the syn-aldol
product syn-5. On the other hand, in anhydrous THF,
the retro aldol reaction from syn-7 takes place to give
anti-aldolate anti-7 in which the transformation is
Representative Procedure for the Reductive Aldol
Reaction
A mixture of InBr (0.426 g, 1.2 mmol) and Bu SnH (0.349 g,
3
3
[
9]
1.2 mmol) in THF(2 mL) was stirred at ±78 8C for 5 min to
generate dichloroindium hydride. Enone 1b (0.219 g,
controlled thermodynamically. The resulting aldolate
anti-7 is hydrolyzed by water in after treatment to
produce the anti-aldol product anti-5.
1
.5 mmol), and aldehyde 4a (0.136 g, 1 mmol) were succes-
sively added and the reaction mixture was warmed up to room
temperature for 1 h. After then, similar treatments as above
were done. Column chromatography eluting with hexane-
In conclusion, dichloroindium hydride (Cl InH) fac-
2
ilely promoted the reductive aldol reaction of enones.
Noteworthy is that syn- and anti-selective aldol reac-
tions were accomplished in high levels by anhydrous and (6%). The product ratio was determined by H NMR spectro-
EtOAc (8:2) gave a mixture of 5a (86%, syn:anti ˆ 4:96) and 6a
1
aqueous solvents, respectively. The anti-selectivity scopy. Further purification was performed by silica gel TLC
(
96%) obtained is the highest one so far reported. In with hexane-Et
2
O (8:2).
threo-2-(Hydroxy-4'-methoxyphenylmethyl)-1-phenylbu-
addition, the first example of the reductive aldol
reaction in aqueous media is presented.
±1
1
tan-1-one (anti-5a): IR(neat): n ˆ 3494, 1666 cm ; H NMR
(
CDCl , 270 MHz): d ˆ 0.78 (t, J ˆ 7.81 Hz, 3H), 1.38 ± 1.78 (m,
3
2
4
7
6
1
H), 2.94 (d, J ˆ 4.88 Hz, 1H), 3.79 (s, 3H), 3.69 ± 3.83 (m, 1H),
.98 (dd, J ˆ 4.88 and 7.81 Hz, 1H), 6.82 ± 6.93 (m, 2H), 7.24 ±
1
3
.60 (m, 5H), 7.92 ± 7.98 (m, 2H); C NMR (CDCl ,
3
7.9 MHz): d ˆ 11.6, 23.6, 54.4, 55.3, 75.4, 113.8, 127.6, 128.3,
28.6, 133.2, 134.8, 138.3, 159.2, 205.7; MS: m/z ˆ 284 (0.2), 255
(
0.5), 148 (51), 135 (78), 120 (9), 105 (100), 92 (8), 77 (49);
HRMS: calcd. for C H O : 284.1413; found: 284.1409.
1
8
20
3
Adv. Synth. Catal. 2002, 344, 283 ± 287
285

COMMUNICATIONS
Akio Baba et al.
erythro-2-(Hydroxy-4'-methoxyphenylmethyl)-1-phenyl-
(CDCl , 270 MHz): d ˆ 0.78 (t, J ˆ 7.32 Hz, 3H), 1.63 ± 2.00 (m,
3
±1 1
butan-1-one (syn-5a): IR(neat): n ˆ 3494, 1666 cm ; H NMR
2H), 3.36 (d, J ˆ 1.95 Hz, 1H), 3.64 ± 3.72 (m, 1H), 5.07 (dd, J ˆ
(
2
4
(
5
2
1
CDCl , 270 MHz): d ˆ 0.79 (t, J ˆ 7.81 Hz, 3H), 1.70 ± 2.03 (m,
4.40 and 1.95 Hz, 1H), 7.23 ± 7.37 (m, 4H), 7.40 ± 7.63 (m, 3H),
3
1
3
H), 3.05 (br, 1H), 3.77 (s, 3H), 3.66 ± 3.83 (m, 1H), 5.03 (dd, J ˆ
7.86 ± 7.93 (m, 2H); C NMR(CDCl , 67.9 MHz): d ˆ 12.2,
3
.40 Hz, 1H), 6.77 ± 6.86 (m, 2H), 7.24 ± 7.60 (m, 5H), 7.84 ± 7.90
20.4, 53.8, 73.0, 127.6, 128.3, 128.4, 128.8, 133.1, 133.6, 137.2,
140.5, 205.2; MS: m/z ˆ 288 (15), 270 (9), 259 (52), 148 (100),
139 (51), 133 (66), 111 (23), 105 (89), 91 (5), 77 (55); HRMS:
calcd. for C H ClO : 288.0917; found: 288.0916.
m, 2H); 13C NMR (CDCl , 67.9 MHz): d ˆ 12.1, 20.7, 54.2,
3
5.2, 73.5, 113.6, 127.3, 128.3, 128.6, 133.3, 134.2, 137.5, 158.9,
05.2; MS: m/z ˆ 284 (10), 255 (11), 148 (94), 135 (100), 120 (9),
05 (99), 92 (9), 77 (54); HRMS: calcd. for C H O : 284.1413;
1
7
17
2
threo-2-(Hydroxy-4'-nitrophenylmethyl)-1-phenylbutan-1-
1
8
20
3
±
1 1
found: 284.1414.
one (anti-5f): IR(neat): n ˆ 3433, 1674 cm ; H NMR (CDCl ,
3
threo-2-(Hydroxy-4'-methylphenylmethyl)-1-phenylbutan-
270 MHz): d ˆ 0.92 (t, J ˆ 7.32 Hz, 3H), 1.64 ± 1.89 (m, 2H),
3.69 ± 3.85 (m, 1H), 3.82 (d, J ˆ 6.84 Hz, 1H), 5.14 (dd, J ˆ 6.35
and 6.84 Hz, 1H), 7.38 ± 7.65 (m, 5H), 7.80 ± 7.88 (m, 2H), 8.12 ±
±1
1
1
(
(
1
7
6
1
(
(
-one (anti-5b): IR(neat): n ˆ 3463, 1674 cm ; H NMR
CDCl , 270 MHz): d ˆ 0.79 (t, J ˆ 7.33 Hz, 3H), 1.41 ± 1.80
3
1
3
m, 2H), 2.32 (s, 3H), 2.93 (d, J ˆ 4.88 Hz, 1H), 3.69 ± 3.83 (m,
8.20 (m, 2H); C NMR (CDCl
3
, 67.9 MHz): d ˆ 11.8, 23.8, 53.5,
H), 4.98 (dd, J ˆ 4.88 and 7.33 Hz, 1H), 7.08 ± 7.33 (m, 4H),
74.3, 123.6, 127.0, 128.2, 128.8, 133.8, 137.3, 147.3, 150.3, 205.2;
1
3
.40 ± 7.60 (m, 3H), 7.90 ± 7.98 (m, 2H); C NMR (CDCl ,
MS: m/z ˆ 299 (5), 270 (13), 177 (13), 148 (100), 133 (42), 120
3
7.9 MHz): d ˆ 11.6, 21.1, 23.7, 54.3, 75.6, 126.4, 128.3, 128.6,
(6), 105 (85), 91 (3), 77 (34); HRMS: calcd. for C17
H17ClO :
2
29.1, 133.1, 137.5, 138.3, 139.7, 205.6; MS: m/z ˆ 268 (18), 250
299.1157; found: 299.1158.
5), 239 (25), 148 (100), 133 (47), 119 (35), 105 (70), 91 (33), 77
34); HRMS: calcd. for C H O : 268.1463; found: 268.1457.
erythro-2-(Hydroxy-4'-nitrophenylmethyl)-1-phenylbutan-
±1
1
1-one (syn-5f): IR(neat): n ˆ 3437, 1674 cm ; H NMR
1
8
20
2
(
CDCl , 270 MHz): d ˆ 0.77 (t, J ˆ 7.32 Hz, 3H), 1.61 ± 2.00
erythro-2-(Hydroxy-4'-methylphenylmethyl)-1-phenylbu-
3
-1
1
(m, 2H), 3.69 (d, J ˆ 1.46 Hz, 1H), 3.69 ± 3.84 (m, 1H), 5.21 (dd,
J ˆ 3.42 and 1.46 Hz, 1H), 7.38 ± 7.69 (m, 5H), 7.78 ± 7.99 (m,
tan-1-one (syn-5b): IR(neat): n ˆ 3463, 1674 cm ; H NMR
(
CDCl , 270 MHz): d ˆ 0.78 (t, J ˆ 7.32 Hz, 3H), 1.63 ± 2.03 (m,
3
1
3
2
1
H), 8.10 ± 8.26 (m, 2H); C NMR (CDCl , 67.9 MHz): d ˆ
2
5
7
6
1
H), 2.30 (s, 3H), 3.14 (d, J ˆ 1.46 Hz, 1H), 3.68 ± 3.81 (m, 1H),
.06 (dd, J ˆ 1.46 and 3.90 Hz, 1H), 7.08 ± 7.32 (m, 4H), 7.40 ±
3
2.2, 20.3, 53.3, 72.8, 123.5, 127.1, 128.4, 128.9, 133.9, 136.8,
1
3
147.2, 149.5, 204.9; MS: m/z ˆ 299 (6), 270 (23), 177 (6), 148
100), 133 (50), 120 (7), 105 (89), 91 (4), 77 (40); HRMS: calcd.
for C H ClO : 299.1158; found: 299.1155.
.60 (m, 3H), 7.86 ± 7.94 (m, 2H); C NMR (CDCl ,
3
(
7.9 MHz): d ˆ 12.1, 20.4, 21.1, 54.1, 73.6, 126.1, 128.3, 128.6,
28.9, 133.3, 137.0, 137.4, 139.0, 205.3; MS. m/z ˆ 268 (18), 250
17 17
2
CAS Registry Nos.: 1,3-diphenylpropan-1-one (2a), [1083-
0-3]; 1-phenylbutan-1-one (2b), [495-40-9]; 4,4-dimethyl-1-
(
(
7), 239 (38), 148 (100), 133 (52), 119 (48), 105 (81), 91 (41), 77
41); HRMS: calcd. for C H O : 268.1463; found: 268.1464.
3
1
8
20
2
phenylpentan-1-one (2c), [37608-93-8]; 4-phenylbutan-2-one
(2d), [2550-26-7]; 4,4-dimethyl-1-phenylpentan-3-one (2e),
threo-2-(Hydroxy-4'-phenylphenylmethyl)-1-phenylbutan-
±1
1
1
(
(
-one (anti-5c): IR(neat): n ˆ 3475, 1677 cm ; H NMR
[
[
5195-24-4]; 2-benzyl-1,3,5-triphenylpentane-1,5-dione (3a),
38335-02-3]; 2-(hydroxyphenylmethyl)-1-phenylbutan-1-one
CDCl , 270 MHz): d ˆ 0.84 (t, J ˆ 7.32 Hz, 3H), 1.50 ± 1.86
3
m, 2H), 3.12 (d, J ˆ 5.37 Hz, 1H), 3.76 ± 3.87 (m, 1H), 5.08 (dd,
(
5d), [60669-63-8].
J ˆ 7.32 and 5.37 Hz, 1H), 7.23 ± 7.61 (m, 12H), 7.91 ± 7.98 (m,
2
1
1
H); 13C NMR (CDCl , 67.9 MHz): d ˆ 11.6, 23.7, 54.2, 75.4,
3
26.8, 127.0, 127.2, 127.3, 128.3, 128.6, 128.8, 131.2, 138.2, 140.6,
40.7, 141.8, 205.6; MS: m/z ˆ 330 (4), 301 (7), 182 (100), 148 Acknowledgements
(
69), 133 (27), 120 (7), 105 (75), 90 (5), 77 (36); HRMS: calcd.
for C H O : 330.1620; found: 330.1613.
23
22
2
This work was financially supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Science and
Culture, and JSPS Research Fellowships for Young Scientists.
erythro-2-(Hydroxy-4'-phenylphenylmethyl)-1-phenylbu-
±
1
1
tan-1-one (syn-5c): IR(neat): n ˆ 3460, 1674 cm ; H NMR
(
2
CDCl , 270 MHz): d ˆ 0.81 (t, J ˆ 7.32 Hz, 3H), 1.70 ± 2.08 (m,
3
H), 3.26 (d, J ˆ 1.95 Hz, 1H), 3.74 ± 3.83 (m, 1H), 5.14 (dd, J ˆ
1
.95 and 4.39 Hz, 1H), 7.23 ± 7.61 (m, 12H), 7.88 ± 7.95 (m, 2H);
References and Notes
13
C NMR(CDCl , 67.9 MHz): d ˆ 12.1, 20.5, 54.0, 73.5, 126.6,
3
1
1
26.8, 127.0, 127.2, 128.3, 128.6, 128.7, 133.4, 137.4, 140.3, 140.8,
[
1] Barbier-type allylation: a) S. Araki, H. Ito, Y. Butsugan, J.
Org. Chem. 1988, 53, 1831 ± 1833; b) C. J. Li, T. H. Chan,
Tetrahedron Lett. 1991, 32, 7017 ± 7020; c) C. J. Li, T. H.
Chan, Tetrahedron 1999, 55, 11149 ± 11176; d) C. J. Li,
Tetrahedron Lett. 1995, 36, 517 ± 518; e) M. B. Isaac, T. H.
Chan, Tetrahedron Lett. 1995, 36, 8957 ± 8960; f) L. A.
Paquette, T. M. Mitzel, J. Org. Chem. 1996, 61, 8799-8804;
Pd-catalyzed allylation: g) S. Araki, T. Kamei, T. Hira-
shita, H. Yamamura, M. Kawai, Org. Lett. 2000, 2, 847-
849; pinacol coupling: h) H. J. Lim, G. Keum, S. B. Kang,
B. Y. Chung, Y. Kim, Tetrahedron Lett. 1998, 39, 4367-
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41.1, 205.3; MS: m/z ˆ 330 (3), 301 (5), 182 (100), 148 (51), 133
(
23), 120 (6), 105 (63), 90 (5), 77 (32); HRMS: calcd. for C H
23 22
O : 330.1620; found: 330.1634.
2
threo-2-(Hydroxy-4'-chlorophenylmethyl)-1-phenylbutan-
±1
1
1
(
(
-one (anti-5e): IR(neat): n ˆ 3433, 1674 cm ; H NMR
CDCl , 270 MHz): d ˆ 0.83 (t, J ˆ 7.32 Hz, 3H), 1.48 ± 1.79
3
m, 2H), 3.29 (d, J ˆ 5.86 Hz, 1H), 3.64 ± 3.79 (m, 1H), 5.00 (dd,
J ˆ 6.35 and 5.86 Hz, 1H), 7.23 ± 7.36 (m, 4H), 7.40 ± 7.63 (m,
1
3
3
1
1
1
H), 7.84 ± 7.94 (m, 2H); C NMR (CDCl , 67.9 MHz): d ˆ
3
1.7, 23.7, 54.1, 74.8, 127.7, 128.2, 128.5, 128.6, 133.4, 137.9,
41.3, 205.5; MS: m/z ˆ 288 (15), 270 (7), 259 (34), 148 (100),
39 (42), 133 (62), 111 (20), 105 (83), 91 (5), 77 (52); HRMS:
calcd. for C H ClO : 288.0917; found: 288.0918.
17
17
2
erythro-2-(Hydroxy-4'-chlorophenylmethyl)-1-phenylbu-
tan-1-one (syn-5e): IR(neat): n ˆ 3433, 1674 cm ; H NMR
±1
1
286
Adv. Synth. Catal. 2002, 344, 283 ± 287

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287