Indium hydride catalyzed chemo- and diastereoselective reductive aldol reactions

Article abstract of DOI:10.1016/j.jorganchem.2013.07.083

The reductive aldol reaction of enones has been established catalyzed by Br₂InOMe (cat.)-MePhSiH₂ system where Br₂InH acted as an active catalytic species. Addition of 1.0 equivalent of MeOH was essential for catalytic turnover. The system, Br₂InOMe(cat.)- MePhSiH₂-MeOH, provided highly chemoand diastereoselective reductive aldol reaction of enones with functionalized substrates such as α-bromo carbonyls, α-keto esters and α-alkoxy ketones.

Full text of DOI:10.1016/j.jorganchem.2013.07.083

Journal of Organometallic Chemistry 751 (2014) 471e474
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Indium hydride catalyzed chemo- and diastereoselective reductive
aldol reactions
Ryosuke Ieki, Shinji Miyamoto, Shinji Tsunoi, Ikuya Shibata*
Research Center for Environmental Preservation, Osaka University, 2-4 Yamadaoka, Suita, Osaka 565-0871, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 May 2013
Received in revised form
The reductive aldol reaction of enones has been established catalyzed by Br InOMe (cat.)eMePhSiH
2
2
system where Br
essential for catalytic turnover. The system, Br
and diastereoselective reductive aldol reaction of enones with functionalized substrates such as
carbonyls, -keto esters and -alkoxy ketones.
2
InH acted as an active catalytic species. Addition of 1.0 equivalent of MeOH was
InOMe(cat.)eMePhSiH eMeOH, provided highly chemo-
-bromo
2
2
30 July 2013
a
Accepted 31 July 2013
a
a
Ó 2013 Elsevier B.V. All rights reserved.
Keywords:
Reductive aldol reaction
Enones
Ketones
Silanes
Indium hydride
1. Introduction
phenyl-2-buten-1-one (1) with cyclohexanone (2a) in the presence
of a catalytic amount of Br InOMe and stoichiometric MePhSiH
2
2
The reductive aldol reaction of enones with aldehydes promoted
by metal hydrides is a valuable method for obtaining -hydrox-
yketones in one-pot synthesis [1]. To date, metal-catalyzed reduc-
tive aldol reaction of enones has been investigated [2]. We have
(Table 1). Without additives, no aldol product 3a was obtained at rt
for 3 h (entry 1). When MeOH was used as an additive, product 3a
was obtained (entry 2). However, undesirable side product, 1-
phenyl-butan-1-one, was formed by conjugate reduction of 1 in
84% yield. The reaction at lower temperature provided a maximum
b
2
previously reported that dibromoindium hydride (Br InH) as stoi-
chiometric metal hydride promoted reductive aldol reaction of
enones with aldehydes [3]. Moreover, catalytic generation of in-
yield of 3a (52%) (entry 3). Yields were not satisfactory when H
2
O or
PrOH was used in place of MeOH (entries 4 and 5). The use of
Ph SiH as a hydride source slightly decreased the yield of 3a (entry
6). PhSiH and Et SiH were not effective as stoichiometric re-
i
dium hydride species was successful by InBr
3
(cat.)eEt
3
SiH [4a] and
SiH
2
2
In(OAc) (cat.)ePhSiH systems [4b]. Although InBr
3
3
3
(cat.)eEt
3
3
3
underwent highly diastereoselective reactions [4a], functionalized
substrates were not applicable because of accompanying an acidic
ductants (entries 7 and 8).
2
A plausible catalytic cycle is shown in Scheme 2. Initially, Br InH
by-product Et
mild method for generating Br
InBr and applied to radical cyclization of functionalized substrates
5]. We report here the catalytic reductive aldol reaction of enones
by Br InOMe(cat.)ehydrosilane system, and accomplished high
chemo- and diastereoselectivities (Scheme 1).
3
SiBr in the transmetallation. We have developed a
is formed by the transmetallation of Br
2 2
InOMe with MePhSiH .
2
InH by using Br InOMe instead of
2
Br InH undergoes conjugate reduction to enone 1 to give indium
2
3
enolate A [6]. In this step, Br
2
InH could reduce ketone 2a. The
ꢀ
[
conditions at 0 C allows the predominant reduction of enone 1.
Next, generated indium enolate A reacts with ketone 2a to form
indium aldolate B. In the final step, aldolate B is protonated by
2
2
MeOH, and aldol product 3a is obtained with regeneration of Br I-
nOMe. We assume that this is the rate determining step. The choice
of additive is important. Thus MeO group has effects on both steps of
2
. Results and discussion
trapping of indium aldolate B and of generation of Br
2
InH. Using
PrOH instead of MeOH does not promote protonation of indium
aldolate and generation of Br InH due to less acidity and generation
To optimization of conditions for the indium-catalyzed reduc-
tive aldol reaction, initially, we performed the simple example of 1-
i
2
of sterically hindered indium alkoxide compared with MeOH.
We next tried to use functionalized substrates. In the reaction
with a-bromo alkylaldehyde 2b, desired product 3b was obtained
*
Corresponding author. Tel.: þ81 6 6879 8975; fax: þ81 6 6879 8978.
E-mail address: shibata@epc.osaka-u.ac.jp (I. Shibata).
0
022-328X/$ e see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jorganchem.2013.07.083

472
R. Ieki et al. / Journal of Organometallic Chemistry 751 (2014) 471e474
Scheme 1. Reductive aldol reaction of enones.
in 40% yield (Scheme 3). Noteworthy is high diastereoselectivity of
the reaction via ZimmermaneTraxler six-membered transition
state C [7]. Previously reported system, InBr
in low yield. Thus in the generation of Br
system [4a] accompanied acidic Et SiBr which would decompose
functionalized compounds, 2b and 3b. In contrast, starting from
Br InOMeeMePhSiH accompanied silyl methoxide as a mild and
neutral by-product.
3
(cat.)eEt
3
SiH, resulted
2
InH, InBr
3
(cat.)eEt SiH
3
Scheme 2. Plausible catalytic cycle.
3
2
2
required. Highly chemo- and diastereoselective aldol products
were obtained in the case using
a-halo ketones,
a-keto esters and
The reactions using other functionalized ketones are summa-
rized in Table 2. The highly chemoselective reaction was also
a-alkoxy ketones. We are now enlarging the scope of substrates.
applicable to a-bromo acetophenone (2c) (entry 2). The presented
4
. Experimental
reductive aldol reaction has limited application for simple ketone
such as acetophenone. However, dehalogenation of product 3c
afforded adduct 4 which corresponds to the product using aceto-
phenone (Scheme 4).
4.1. General experimental methods
To a dry nitrogen-filled 10-mL round-bottomed flask containing
3
(0.1 mmol) in MeCN (1 mL) was added NaOMe (0.12 mmol) at
Functionalized ketones such as
also reactive to give products, 3d and 3e, respectively (entries 2 and
). No by-products derived from the reduction of 2d and 2e were
a-keto esters, 2d and 2e, were
InBr
rt. The mixture was stirred at room temperature for 30 min. To the
solution were added MePhSiH (1.1 mmol), enones 1 (1 mmol),
carbonyl 2 (1 mmol) and MeOH (1 mmol) and the resulting mixture
was stirred at 0 C for 24 h. After quenching with saturated NaCl
3
2
obtained. Noteworthy is high diastereoselectivities of these re-
actions which could be rationalized by bicyclic transition state D as
shown in Scheme 5.
The use of a-methoxy acetophenone 2f also underwent highly
diastereoselective reaction where OMe group acts as coordinating
group to indium (entry 4). The reaction with benzoin methyl ether
ꢀ
(
(
aq) (2 mL), the reaction mixture was extracted with ether
10 mL ꢁ 2). The combined organic layer was dried over MgSO and
4
concentrated. The residue was subjected to column chromatog-
raphy eluting with hexane/EtOAc. Indium and silane residue were
removed by this treatment. The crude product was then purified by
flash column chromatography eluted by hexane/EtOAC with
gradation mode changing from 9/1 to 3/7. The desired product was
obtained at hexane/EtOAC ¼ 7:3.
(2g) gave diastereoselective product 3g with three contiguous
stereogenic centers (entry 5). In this reaction, among possible
chelated cyclic transition states, an excellent stereocontrol was
achieved through E as sterically least hindered cyclic transition
state (Scheme 6).
0
4
.1.1. 2-(1 -Hydroxy-cyclohexyl)-1-phenyl-butan-1-one (3a)
3
. Conclusions
The NMR data well agree with the reported data in Ref. [2i].
Colorless liquid. IR (neat) 3493 cm (OH), 1659 cm (C]O).
MS (EI, 70 eV) m/z 246 (M , 5), 105 (PhCO, 100), 77 (Ph, 28). HRMS
calcd for
ꢂ1
ꢂ1
We have established that MePhSiH
2
and MeOH promoted
þ
reductive aldol reaction of enones in the presence of a catalytic
amount of dibromoindium methoxide (Br InOMe). Br InH acted as
an active catalytic species. The reactions were performed only using
main group metals and any expensive transition metals were not
C
H
16 22
1
O
2
:
246.1620, found: m/z 246.1614 (EI,
, 400 MHz) 8.00e7.98 (m, 2H,
2
2
þ
M , ꢂ0.6 mmu). H NMR (CDCl
3
d
Ph(o)), 7.62e7.57 (m, 1H, Ph(p)), 7.51e7.47 (m, 2H, Ph(m)), 3.51 (dd,
J ¼ 4.3 and 9.9 Hz, 1H, C]OCH), 3.47 (s, 1H, OH), 1.93e1.18 (m, 12H,
1
3
CH
(CDCl
3
2
Me, cyclohexyl CH
, 100 MHz)
5.2, 25.7, 21.8, 21.7, 20.9, 12.7.
2
), 0.83 (t, J ¼ 7.48 Hz, 3H, CH
3
). C NMR
Table 1
d 208.6, 138.9, 133.4, 128.7, 128.2, 73.0, 54.7, 37.7,
3
a
Optimization of reductive aldol reaction of enone 1 with 2a.
4.1.2. 4-Bromo-2-ethyl-3-hydroxy-1, 5-diphenyl-pentan-1-one
(
3b)
ꢂ1
ꢂ1
Pale yellow liquid. IR (neat) 3444 cm (OH), 1651 cm (C]O).
þ
MS (CI, 200 eV) m/z 362 (M þ 1, 20.38). HRMS calcd for
Entry
Silane
Conditions
rt, 3 h
Additive
3a Yield%b
1
2
3
4
5
6
7
8
MePhSiH
MePhSiH
MePhSiH
MePhSiH
MePhSiH
2
2
2
2
2
None
MeOH
MeOH
Trace (5)
12 (84)
52 (37)
Trace (15)
Trace (14)
37 (26)
rt, 3 h
ꢀ
0
0
0
0
0
0
C, 24 h
C, 24 h
C, 24 h
C, 24 h
C, 24 h
C, 24 h
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
H
2
O
i
PrOH
MeOH
MeOH
MeOH
Ph
PhSiH
Et SiH
2
SiH
2
3
10 (72)
Trace (trace)
3
a
2
Conditions: Br InOMe (0.1 mmol), silane (1.1 mmol), additive (1.0 mmol), 1
(
1 mmol), 2a (1 mmol), MeCN (1 mL).
Yields of 1-phenyl-butan-1-one in parentheses.
b
Scheme 3. The reaction of 1 with a-bromo alkylaldehyde (2b).

R. Ieki et al. / Journal of Organometallic Chemistry 751 (2014) 471e474
473
Table 2
Reductive aldol reaction of enone 1 with functionalized ketones 2.
a
Scheme 5. Plausible mechanism through chelated cyclic transition state.
Entry
1
Ketone 2
Product 3
Yield% (dr)
64 (99:1)
2
3
0), 149 (100), 105 (PhCO, 18). HRMS calcd for C18
H
19BrO
2
:
þ
46.0568, found: m/z 347.0650 (CI, M þ 1, þ0.3 mmu). Major
1
isomer (2R*,3R*) H NMR (CDCl
Ph(o)), 7.64e7.60 (m,1H,1-Ph(p)), 7.57e7.54 (m, 2H, 3-Ph(o)), 7.50e
.48 (m, 2H, 1-Ph(m)), 7.39e7.35 (m, 2H, 3-Ph(m)), 7.30e7.28 (m,
H, 3-Ph(p)), 4.81 (s, 1H, OH), 4.13 (dd, J ¼ 3.6 and 10.1 Hz, 1H,
CHEt), 3.76 (d, J ¼ 10.6 Hz, 1H, CH Br), 3.56 (d, J ¼ 10.6 Hz, 1H,
CH Me), 1.54
Br), 1.82 (qdd, J ¼ 7.4 and 10.1 and 13.7 Hz, 1H, CH
qdd, J ¼ 3.6 and 7.7 and 13.7 Hz, 1H, CH Me), 0.68 (t, J ¼ 7.4 and
, 100 MHz) 207.2, 142.0, 137.9,
34.0, 128.8, 128.5, 128.1, 127.4, 125.5, 77.5, 52.7, 42.3, 23.2, 12.4.
3
, 400 MHz) d 8.03e8.00 (m, 2H, 1-
7
1
2
2
71 (>99:1)
2
2
(
2
13
7.7 Hz, 3H, Me). C NMR (CDCl
3
d
1
3
4
60 (85:15)
1
3
Minor isomer (2S*,3R*) H NMR (CDCl , 400 MHz) d 7.85 (d,
J ¼ 7.4 Hz, 2H, 1-Ph(o)), 7.55e7.52 (m, 1H, 1-Ph(p)), 7.46e7.39 (m,
4
1
H,1-Ph(m) and 3-Ph(o)), 7.26e7.22 (m, 2H, 3-Ph(m)), 7.18e7.14 (m,
H, 3-Ph(p)), 4.39 (s, 1H, OH), 4.17 (dd, J ¼ 3.8 and 10.6 Hz, 1H,
61 (>99:1)
CHEt), 3.97 (d, J ¼ 10.6 Hz, 1H, CH Br), 3.91 (d, J ¼ 10.6 Hz, 1H,
2
CH
2
Br), 2.00 (qdd, J ¼ 7.2 and 10.6 and 13.7 Hz, 1H, CH
Me), 0.84 (dd, J ¼ 7.2 and
, 100 MHz) 205.7, 143.5, 138.4,
33.4, 128.5, 128.3, 128.0, 127.4, 125.8, 77.3, 53.5, 40.4, 21.5, 12.6.
2
Me), 1.85
(
7
qdd, J ¼ 3.8 and 7.7 and 13.7 Hz, 1H, CH
2
13
.7 Hz, 3H, Me). C NMR (CDCl
3
d
5
72 (96:4)
1
a
4.1.4. (2R*,3R*)-3-Benzoyl-2-hydroxy-2-phenyl-pentanoic acid
methyl ester (3d)
Conditions: Br
2
InOMe (0.1 mmol), MePhSiH
2
(1.1 mmol), MeOH (1.0 mmol), 1
(
1 mmol), 2 (1 mmol), MeCN (1 mL).
The NMR data well agree with the reported data in Ref. [2i].
ꢀ
ꢂ1
ꢂ1
þ
White solid. Mp 73 C. IR (KBr) 3409 cm (OH), 1720 cm (C]
C
19
H
21BrO
2
: 361.2728, found: m/z 361.0799 (CI, M þ 1, ꢂ0.4 mmu).
ꢂ1
þ
1
O), 1650 cm (C]O). MS (CI, 200 eV) m/z 313 (M þ 1, 100), 165
58), 149 (84). HRMS calcd for C19 : 312.1362, found: m/z
, 400 MHz) 8.07e
.05 (m, 2H, COPh(o)), 7.71e7.69 (m, 2H, 2-Ph(o)), 7.64e7.59 (m, 1H,
Major isomer (2S*,3S*,4R*) H NMR (CDCl
3
, 400 MHz) d 7.99 (d,
(
3
8
20 4
H O
J ¼ 7.2 Hz, 2H, 1-Ph(o)), 7.60 (d, J ¼ 7.2 Hz, 1H, 1-Ph(p)), 7.48 (t,
þ
1
13.1444 (CI, M þ 1, þ0.4 mmu). H NMR (CDCl
3
d
J ¼ 7.2 Hz, 2H, 1-Ph(m)), 7.36e7.21 (m, 5H, 5-Ph), 4.46 (d, J ¼ 9.4 Hz,
1
H, OH), 4.17 (ddd, J ¼ 2.9, 7.0 and 10.4 Hz, 1H, CHEt), 4.03 (ddd,
COPh(p)), 7.53e7.39 (m, 4H, 2-Ph(m) and COPh(m)), 7.35e7.31 (m,
J ¼ 2.9, 8.9 and 12.3 Hz, 1H, CHBr), 3.96 (ddd, J ¼ 2.9, 9.4 and
Ph), 3.08
Me), 1.00
201.1, 138.1,
36.8, 134.0, 129.6, 128.8, 128.7, 128.2, 126.6, 75.8, 59.1, 47.4, 40.9,
1
3
H, 2-Ph(p)), 5.36 (s, 1H, OH), 4.31 (dd, J ¼ 4.8 and 8.2 Hz, 1H, CHEt),
.55 (s, 3H, OMe), 1.66e1.50 (m, 2H, CH
Me), 0.61 (t, J ¼ 7.7 Hz, 3H,
208.3, 174.8, 139.0, 137.2, 133.7,
1
(
(
1
2
2.3 Hz, 1H, CHOH), 3.73 (dd, J ¼ 2.9 and 14.7 Hz, 1H, CH
dd, J ¼ 8.9 and 14.7 Hz, 1H, CH Ph), 1.90e1.83 (m, 2H, CH
t, J ¼ 7.5 Hz, 3H, Me). C NMR (CDCl , 100 MHz)
2
2
2
2
13
13
Me). C NMR (CDCl
3
, 100 MHz)
d
3
d
1
28.6, 128.5, 128.3, 127.9, 125.0, 81.0, 53.5, 52.7, 21.0, 12.5.
1
4.4, 12.2. Minor isomer (2S*,3R*,4R*) H NMR (CDCl
3
, 400 MHz)
0
.1.5. (2R*,3R*)-3-Benzoyl-2-(4 -bromo-phenyl)-2-hydroxy-
4
d
7.98 (d, J ¼ 7.2 Hz, 2H, 1-Ph(o)), 7.65e7.21 (m, 8H, 1-Ph(p), 1-
pentanoic acid methyl ester (3e)
Ph(m), 5-Ph(o), 5-Ph(m) and 5-Ph(p)), 4.43 (ddd, J ¼ 1.7, 7.5 and
.7 Hz, 1H, CHBr), 4.00 (brs, 1H, OH), 3.93 (dd, J ¼ 1.7 and 8.0 Hz, 1H,
CHOH), 3.84 (ddd, J ¼ 4.8, 8.0 and 8.0 Hz, 1H, CHEt), 3.38 (dd, J ¼ 7.5
and 14.2 Hz, 1H, CH Ph),
Ph), 3.26 (dd, J ¼ 7.7 and 14.3 Hz, 1H, CH
.77e1.51 (m, 2H, CH
Me), 0.75 (t, J ¼ 7.7 Hz, 3H, Me). C NMR
CDCl , 100 MHz) 203.3, 137.9, 133.5, 129.1, 128.7, 128.5, 128.4,
The NMR data well agree with the reported data in Ref. [2i].
White solid. Mp 112 C, recrystallization from hexane/Et
KBr) 3444 cm (OH),1723 cm (C]O),1659 cm (C]O). MS (CI,
7
ꢀ
2
O. IR
ꢂ1
ꢂ1
ꢂ1
(
2
2
þ
13
200 eV) m/z 391 (M þ 1, 20), 243 (30), 149 (84). HRMS calcd for
1
(
2
þ
C
19
H
19BrO
H NMR (CDCl
.47 (m, 7H, COPh(m) and COPh(p) and 2-Ph(o) and 2-Ph(m)), 5.37
s, 1H, OH), 4.25 (dd, J ¼ 4.8 and 8.2 Hz, 1H, CHEt), 3.57 (s, 3H, OMe),
.67e1.58 (m, 1H, CH Me), 1.54e1.44 (m, 1H, CH Me), 0.63 (t,
, 100 MHz) 208.0, 174.5, 138.2,
4
: 390.0467, found: m/z 391.0543 (CI, M þ 1, ꢂ0.2 mmu).
3
d
1
3
, 400 MHz)
d
8.04 (d, J ¼ 8.6 Hz, 2H, COPh(o)), 7.66e
126.9, 125.2, 72.5, 63.4, 52.7, 42.8, 23.3, 11.0.
7
(
1
4
1
.1.3. (2R*,3R*)-4-Bromo-2-ethyl-3-hydroxy-1, 3-diphenyl-butan-
-one (3c)
The NMR data well agree with the reported data in Ref. [2i].
2
2
13
J ¼ 7.4 Hz, 3H, Me). C NMR (CDCl
3
d
ꢂ1
ꢂ1
137.2, 133.9, 131.6, 128.7, 128.6, 127.0, 122.2, 80.8, 53.4, 53.0, 21.0,
12.6.
Colorless liquid. IR (neat) 3433 cm (OH), 1655 cm (C]O).
MS (CI, 200 eV) m/z 347 (M þ 1, 4), 199 (Mþ ꢂ PhCOCH
þ
2
2 3
CH CH ,
Scheme 4. Dehalogenation of 3c.
Scheme 6. Control of diastereoselectivity of three contiguous stereogenic centers.

474
R. Ieki et al. / Journal of Organometallic Chemistry 751 (2014) 471e474
4
1
.1.6. (2R*,3R*)-2-Ethyl-3-hydroxy-4-methoxy-1,3-diphenyl-butan-
-one (3f)
d
208.7, 146.1, 138.6, 133.8, 128.8, 128.4, 128.1, 126.5, 124.8, 75.6,
55.8, 30.4, 22.4, 12.5.
The NMR data well agree with the reported data in Ref. [2i].
ꢀ
ꢂ1
ꢂ1
White solid. Mp 72 C. IR (KBr) 3444 cm (OH), 1658 cm (C]
Acknowledgments
þ
O). MS (CI, 200 eV) m/z 299 (M þ 1, 1.7), 151 (100), 149 (44). HRMS
calcd for
C
19
22
H O
3
:
298.1569, found: m/z 299.1648 (CI,
: C, 76.48; H, 7.43,
, 400 MHz) 8.04 (d,
J ¼ 8.2 Hz, 2H, 1-Ph(o)), 7.63e7.59 (m, 3H, 1-Ph(p) and 3-Ph(o)), 7.52
t, J ¼ 8.2 Hz, 2H, 1-Ph(m)), 7.38 (t, J ¼ 7.2 Hz, 2H, 3-Ph(m)), 7.30 (d,
J ¼ 7.2 Hz, 1H, 3-Ph(p)), 4.79 (s, 1H, OH), 3.99 (dd, J ¼ 3.6 and
0.8 Hz, 1H, CHEt), 3.48 (d, J ¼ 9.4 Hz, 1H, CH OMe), 3.37 (d,
J ¼ 9.4 Hz, 1H, CH OMe), 2.97 (s, 3H, OMe), 1.83e1.77 (m, 1H,
CH Me), 1.35e1.29 (m, 1H, CH
NMR (CDCl , 100 MHz) 207.6, 143.1, 138.9, 133.2, 128.6, 128.2,
This research was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Sports, and Cul-
ture and the Naito Foundation.
þ
M
þ 1, þ0.1 mmu). Anal. calcd for C19
22 3
H O
1
found: C, 76.49; H, 7.41. H NMR (CDCl
3
d
(
Appendix A. Supplementary data
1
2
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.jorganchem.2013.07.083.
2
13
2
2
Me), 0.65 (t, J ¼ 7.4 Hz, 3H, Me).
C
3
d
References
1
28.1, 127.0, 125.3, 80.4, 78.2, 58.6, 51.8, 22.3, 12.3.
[1] For reviews on reductive aldol reaction, see: (a) H.C. Guo, J.A. Ma, Angew. Chem.
4
.1.7. (2R*,3R*,4S*)-2-Ethyl-3-hydroxy-4-methoxy-1,3,4-triphenyl-
Int. Ed. 45 (2006) 354e366;
(b) H. Nishiyama, T. Shiomi, Top. Curr. Chem. 279 (2007) 105e137.
butan-1-one (3g)
[
2] For rhodium catalyzed reductive aldol reaction of enones with aldehydes
mediated by silane: (a) I. Matsuda, K. Takahashi, S. Sato, Tetrahedron Lett. 31
(1990) 5331e5334. For rhodium catalyzed reaction of enones with aldehydes
mediated by hydrogen, see:;
The NMR data well agree with the reported data in Ref. [2i].
ꢀ
White solid. Mp 141 C, recrystallization from hexane/Et
2
O. IR
ꢂ1
ꢂ1
(
(
KBr) 3346 cm (OH), 1647 cm (C]O). MS (CI, 200 eV) m/z 375
M
þ
(b) H.Y. Jang, R.R. Huddleston, M.J. Krische, J. Am. Chem. Soc. 124 (2002) 15156e
þ 1, 6), 227 (100), 195 (81), 149 (97). HRMS calcd for C25
26 3
H O :
15157;
þ
1
3
(
3
7
74.4721, found: m/z 375.1953 (CI, M þ 1, ꢂ0.8 mmu). H NMR
CDCl , 400 MHz)
8.15 (d, J ¼ 6.7 Hz, 2H, 1-Ph(o)), 7.63e7.54 (m,
H, arom), 7.35e7.30 (m, 2H, arom), 7.24e7.21 (m, 2H, arom), 7.17e
.13 (m, 1H, arom), 7.07e6.98 (m, 3H, arom), 6.85e6.86 (m, 2H,
arom), 5.18 (s, 1H, OH), 4.28 (s, 1H, CHOMe), 4.08 (dd, J ¼ 3.3 and
1.1 Hz, 1H, CHEt), 2.54 (s, 3H, OMe), 1.83 (qdd, J ¼ 7.4 and 11.1 and
3.5 Hz, 1H, CH
Me), 1.26 (qdd, J ¼ 3.3 and 7.4 and 13.5 Hz, 1H,
CH
(c) C.K. Jung, S.A. Garner, M.J. Krische, Org. Lett. 8 (2006) 519e522;
(d) C. Bee, S.B. Han, A. Hassan, H. Iida, M.J. Krische, J. Am. Chem. Soc. 130 (2008)
3
d
2746e2747. For copper catalyzed reaction of enones with aldehydes mediated
by silane:;
(e) T. Ooi, K. Doda, D. Sakai, K. Maruoka, Tetrahedron Lett. 40 (1999) 2133e2136.
For platinum catalyzed reaction of enones with aldehydes mediated by silane
or hydrogen:;
1
1
(
f) H. Lee, M.S. Jang, Y.J. Song, H.Y. Jang, Bull. Korean Chem. Soc. 30 (2009) 327e
33. For Lewis base catalyzed reaction of enones with aldehydes mediated by
silane:;
2
3
13
2
Me), 0.67 (t, J ¼ 7.4 Hz, 3H, Me). C NMR (CDCl
3
, 100 MHz)
(g) M. Sugiura, N. Sato, S. Kotani, M. Nakajima, Chem. Commun. (2008)4309e4311;
d
205.6, 142.1, 139.1, 136.3, 132.7, 128.7, 128.6, 127.8, 127.7, 127.1,
26.8, 126.6, 125.5, 90.7, 83.0, 56.0, 51.6, 23.3, 12.0.
(h) K. Osakama, M. Sugiura, M. Nakajima, S. Kotani, Tetrahedron Lett. 53 (2012)
1
4
199e4201. For tin hydride catalyzed reaction of enones with aldehydes mediated
by silane:;
i) I. Shibata, S. Tsunoi, K. Sakabe, S. Miyamoto, H. Kato, H. Nakajima, M. Yasuda,
(
4
.1.8. Dehalogenation of 3c and determination of stereochemistry
A. Baba, Chem. Eur. J. 16 (2010) 13335e13338.
major isomer 4
[
3] K. Inoue, T. Ishida, I. Shibata, A. Baba, Adv. Synth. Catal. 344 (2002) 283e287.
The column chromatography purification of the reaction
mixture of 1 with 2c afforded major isomer 3c. The radical deha-
[4] For indium catalyzed reaction mediated by silane: (a) I. Shibata, H. Kato,
T. Ishida, M. Yasuda, A. Baba, Angew. Chem. Int. Ed. 43 (2004) 711e714;
(b) K. Miura, Y. Yamada, M. Tomita, A. Hosomi, Synlett (2004) 1985e1989.
2 2
logenation of 3c (major isomer) with Bu SnH in the presence of V-
[5] (a) A. Baba, I. Shibata, in: Leo A. Paquette (Ed.), Encyclopedia of Reagents for
Organic Synthesis, John Wiley & Sons, 2008;
7
0 [8] as initiator at rt for 5 h afforded the aldol product 4 which did
not agree with reported values of threo isomer [9]. Hence major
isomer is determined as erythro isomer.
(b) A. Baba, I. Shibata, Chem. Rec. 5 (2005) 323e335;
(
c) N. Hayashi, I. Shibata, A. Baba, Org. Lett. 7 (2005) 3093e3096.
6] Z)-Indium enolate can be considered to be generated initially because of the
preferred conjugate addition of Br InH to the s-cis form of enone: (a)
[
2
4
.1.9. (2S*,3S*)-2-Ethyl-3-hydroxy-1,3-diphenyl-1-butan-1-one (4)
G.P. Boldrini, F. Mancini, E. Tagliavini, C. Trombini, A.U. Ronchi, J. Chem. Soc.
Chem. Commun. (1990) 1680e1681;
ꢂ1
ꢂ1
1
Colorless liquid. IR (neat) 3474 cm (OH), 1655 cm (C]O). H
NMR (CDCl , 400 MHz) 8.07e8.04 (m, 2H, 1-Ph(o)), 7.67e7.63 (m,
H, arom), 7.57e7.52 (m, 4H, arom), 7.39e7.36 (m, 2H, arom), 7.28e
.24 (m,1H, arom), 4.50 (s, 1H, OH), 3.83 (dd, J ¼ 3.6 and 10.3 Hz,1H,
CHEt), 1.92e1.76 (m, 1H, CH Me), 1.45 (s, 1H, Me), 1.40e1.30 (m, 1H,
CH
Me), 0.64 (t, J ¼ 7.4 Hz, 3H, Me). C NMR (CDCl
(
b) G.P. Boldrini, M. Bortolotti, F. Mancini, E. Tagliavini, C. Trombini, A.U. Ronchi,
J. Org. Chem. 56 (1991) 5820e5826.
[7] H.E. Zimmerman, M.D. Traxler, J. Am. Chem. Soc. 79 (1957) 1920e1923.
3
d
1
7
[
8] M. Matsugi, K. Gotanda, C. Ohira, M. Suemura, A. Sano, Y. Kita, J. Org. Chem. 64
1999) 6928e6930.
(
2
[
9] T. Mukaiyama, N. Iwasawa, R.W. Stevens, T. Haga, Tetrahedron 40 (1984)
13
2
3
, 100 MHz)
1381e1390.