Indium(III) acetate-catalyzed 1,4-reduction and reductive aldol reactions of α-enones with phenylsilane

Article abstract of DOI:10.1055/s-2004-830862

A catalytic amount of In(OAc)₃ smoothly promoted 1,4-reduction of certain α-enones with PhSiH₃ in ethanol at ambient temperature. The intermediary enolates could be used for inter- and intramolecular aldol reactions and intramolecular Michael addition.

Full text of DOI:10.1055/s-2004-830862

LETTER
1985
Indium(III) Acetate-Catalyzed 1,4-Reduction and Reductive Aldol Reactions
of a-Enones with Phenylsilane
1, 4-Reduction
and
a
Reductive
t
Aldol
R
s
eactions
u
of
a
-
Enone
s
kiyo Miura,* Yusuke Yamada, Mitsuru Tomita, Akira Hosomi*
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, and CREST, Japan Science and
Technology Corporation (JST), Tsukuba, Ibaraki 305-8571, Japan
Fax +81(29)8536503; E-mail: hosomi@chem.tsukuba.ac.jp
Received 18 June 2004
Table 1 Optimization of Reaction Conditions for In(OAc)3-Cata-
Abstract: A catalytic amount of In(OAc)3 smoothly promoted 1,4-
reduction of certain a-enones with PhSiH3 in ethanol at ambient
temperature. The intermediary enolates could be used for inter- and
intramolecular aldol reactions and intramolecular Michael addition.
lyzed 1,4-Reductiona
In(OAc)3
O
(10 mol%)
OInX2
+
PhSiH3
Key words: indium, reductions, enones, silicon, aldol reactions
Ph
Ph
Ph
Ph
(1 equiv)
1a
4a
O
O
Catalytic 1,4-hydrometalation of a-enones provides a re-
liable and efficient method for regioselective formation of
metal enolates.1–4 Recently, much attention has been giv-
en to the development of catalytic systems effecting both
the enolate formation and the subsequent reaction with co-
existent carbon electrophiles.5–7 Some transition metal
salts and complexes work as effective catalysts of this tan-
dem process. All catalytic systems except those reported
by Krische’s group5,7 were utilized only for reductive al-
dol reactions of a-enones with aldehydes. We herein dis-
close that In(OAc)3 efficiently catalyzes the 1,4-reduction
of certain a-enones with PhSiH3, and the intermediary
enolates can be used for carbon-carbon bond-forming re-
actions with aldehydes, ketones, and a-enones.8,9
+
Ph
PhC(O)
Ph
Ph
Ph
2a
Ph
3a
Entry
Solvent Additive Temp
(°C)
Time
Isolated yield (%)
(h)
24
24
3
2a
56
67
76
90
0
3a
1
THF
THF
THF
EtOH
EtOH
None
H2Ob
70
70
26
2
Trace
Trace
0
3
EtOHb 70
4
None
None
r.t.
r.t.
1.5
1.5
5c
0
The reduction of (E)-1,3-diphenyl-2-propen-1-one (chal-
cone, 1a) with PhSiH3 was initially examined for optimi-
zation of the reaction conditions (Table 1). The In(OAc)3-
catalyzed reaction in THF at 70 °C gave the desired ke-
tone 2a as the major product; however, a significant
amount of dimerization product 3a was also obtained (en-
try 1).10 The formation of 3a is attributable to the Michael
addition of indium enolate intermediate 4a to 1a. Proton
sources such as water and EtOH were used to suppress
this side reaction by protonation of 4a (entries 2 and 3). As
a result, the addition of EtOH was found to be effective
not only in suppressing the formation of 3a but also in ac-
celerating the 1,4-reduction of 1a. The use of EtOH as sol-
vent further enhanced the reaction rate to enable the
reduction at room temperature (entry 4).11 Thus the
In(OAc)3-catalyzed reduction of 1a in EtOH was com-
pleted in 1.5 hours at room temperature to give 2a in 90%
yield.12 Indium metal was deposited under these reaction
conditions. Since indium trihydride is known to easily de-
compose to indium metal and H2,13 this observation is in-
dicative of the formation of indium hydride species.
a Unless otherwise noted, all reactions were carried out with 1a (208
mg, 1.00 mmol), PhSiH3 (108 mg, 1.00 mmol), and In(OAc)3 (30 mg,
0.10 mmol) in solvent (2.0 mL).
b One equivalent (1.00 mmol) of H2O or EtOH was used.
c Without In(OAc)3.
Without In(OAc)3, the reduction of 1a did not proceed at
all (entry 5). Accordingly, indium hydride species would
act as the actual reductant.
The In(OAc)3-catalyzed system using EtOH as solvent
was applied to the reduction of some a,b-unsaturated car-
bonyl compounds (Table 2).14 Similar to 1a, (E)-1-phe-
nyl-2-buten-1-one (1b), 1-phenyl-2-propen-1-one (1c),
and (E,E)-1,5-diphenyl-1,4-pentadien-3-one (1d) under-
went 1,4-reduction to give the corresponding ketones 2 in
good yields (entries 1–4). In the case of 1d, a small
amount of 1,5-diphenyl-3-pentanone was formed by dou-
ble 1,4-reduction. The reduction of (E)-4-phenyl-3-buten-
2-one (1e) gave 1,4- and 1,2-reduction products, 2e and
5e, in low yields and 1e was recovered in 75% yield (entry
5). Similarly, (E)-3-decen-2-one (1f) was less reactive
than 1a–d. Slow addition of PhSiH3 slightly improved the
yield of 2f (entry 6). 5-Phenyl-1-penten-3-one (1g), a vi-
nyl ketone, showed high reactivity, but low chemoselec-
SYNLETT 2004, No. 11, pp 1985–1989
0
6
.0
9
.2
0
0
4
Advanced online publication: 06.08.2004
DOI: 10.1055/s-2004-830862; Art ID: U13104ST
© Georg Thieme Verlag Stuttgart · New York

1986
K. Miura et al.
LETTER
Table 2 In(OAc)3-Catalyzed Reduction of a,b-Unsaturated
solvolysis of 4 gives the 1,4-reduction product 2 and InL3,
(4) transmetalation between InL3 and PhSiH3 regenerates
HInL2.
a
Carbonyl Compounds with PhSiH3
O
In(OAc)3 (10 mol%)
+
PhSiH3
R1
R2
EtOH, r.t., 1.5 h
(1 equiv)
O
D
1
In(OAc)3 (10 mol%)
EtOH, r.t., 1.5 h
O
OH
+
+
PhSiD3
1a
1a
Ph
Ph
Ph
Ph
+
2a-d
(1 equiv)
R1
R2
R1
R2
92%, 91%d
2
5
O
Entry Substrate
R1
Isolated yield (%)
In(OAc)3 (10 mol%)
EtOD, r.t., 1.5 h
PhSiH3
R2
2
5
D
(1 equiv)
2a'-d
89%, 91%d
1
2
3
4
5
6
Ph
Ph
Ph
Ph
(1a)
(1b)
(1c)
(1d)
(1e)
(1f)
90
84
93
72b
15c
0
0
0
0
8c
0
Me
H
Scheme 1
In(OAc)3
PhSiH3
(E)-PhCH=CH
Ph
Me
Me
Ph
PhSiH2L
1
30c,d
54c,e
L2InH
n-Hex
PhSiH3
OInL2
7
8
9
PhCH2CH2
H
(1g)
(1h)
(1i)
63
0
23
0
InL3
R1
R2
EtO
H
Ph
Ph
4
2
EtOH
L = OAc, OEt
0
80
Scheme 2
a Unless otherwise noted, all reactions were carried out with 1 (0.50
mmol), PhSiH3 (54 mg, 0.50 mmol), and In(OAc)3 (15 mg, 0.05
mmol) in EtOH (1.0 mL) at r.t. for 1.5 h.
The mechanistic consideration induced us to utilize the in-
dium enolate intermediate 4 for carbon-carbon bond for-
mation. We thus examined the In(OAc)3-catalyzed
reductive aldol reaction of a-enones, aldehydes, and
PhSiH3. Initially, enone 1b and 1-naphthaldehyde (6a)
were selected as the substrates for optimization of the re-
action conditions (Table 3). Expectedly, the reaction of
1b, 6a, and PhSiH3 (molar ratio = 1:1:1) at room temper-
ature gave the desired aldol 7ba in 65% yield along with
2b (32%) and 1-naphthylmethanol (ca. 30%, entry 1).16
This result indicates that the In(OAc)3-catalyzed reduc-
tion of 1b is faster than that of 6a.17 The use of an excess
amount of 6a improved the yield of 7ba (entry 2). Lower-
ing the reaction temperature brought about high syn-selec-
tivity although the reaction rate became much slower
(entry 3). With a decreased amount of EtOH, 7ba was ob-
tained in high yield with high syn-diastereoselectivity (en-
tries 4 and 5).18
b 1,5-Diphenyl-3-pentanone also was obtained in 14% yield.
c The yield was determined by 1H NMR analysis using benzyl acetate
as the internal standard.
d The reaction was run for 24 h.
e The enhanced yield was obtained by the following method: PhSiH3
was added dropwise to the mixture of 1f, In(OAc)3, and EtOH over 1
h. The resultant mixture was stirred for 24 h.
tivity (entry 7). The present catalytic system was
ineffective in the reduction of ethyl cinnamate (1h, entry
8). In the case of cinnamaldehyde (1i), only the 1,2-reduc-
tion was observed (entry 9).
Dichloroindium hydride (Cl2InH) has been reported to be
valuable for radical reduction of alkyl halides.15 The
In(OAc)3-catalyzed reaction of 1a with PhSiH3 gave 2a
efficiently even in the presence of galvinoxyl, a radical
scavenger. The present 1,4-reduction would therefore not
involve a radical chain mechanism although the deposi-
tion of indium metal suggests the presence of indium hy-
dride species. In the 1,4-reduction of 1a, the use of PhSiD3
instead of PhSiH3 provided 2a-d by b-deuteration, while
the use of EtOD as solvent resulted in a-deuteration
(Scheme 1). Judging from these results, the present 1,4-
reduction could proceed via the following mechanism
(Scheme 2): (1) transmetalation between In(OAc)3 and
PhSiH3 in EtOH forms an indium hydride species (HInL2,
L = OAc, OEt), (2) 1,4-addition of the hydride to an a-
enone 1 leads to the corresponding indium enolate 4, (3)
The optimized conditions were applied to other combina-
tions of enones 1 and aldehydes 6 (Table 4).19 The reduc-
tive aldol reaction of phenyl ketones 1a–c with aromatic
aldehydes proceeded in high yields with high syn-diaste-
reoselectivity except the case with p-cyanobenzaldehyde
(entries 1–4, 7, 8, and 11). The use of aliphatic aldehydes
lowered the reaction efficiency and the syn-selectivity
(entries 5, 6, 9, and 10).20 Aliphatic a-enones also under-
went the reductive coupling to give the corresponding al-
dol products in moderate yields (entries 12–14).
Synlett 2004, No. 11, 1985–1989 © Thieme Stuttgart · New York

LETTER
1,4-Reduction and Reductive Aldol Reactions of a-Enones
Table 4 In(OAc)3-Catalyzed Reductive Aldol Reaction of a-
1987
Table 3 Optimization of Reaction Conditions for In(OAc)3-Cata-
a
lyzed Reductive Aldol Reactiona
Enones 1, Aldehydes 6, and PhSiH3
In(OAc)3
O
OH
O
In(OAc)3 (10 mol%)
O
+
+
(10 mol%)
1-NpCHO
PhSiH3
EtOH
RCHO
R1
R
+
+
PhSiH3
Ph
Me
6a
R1
R2
EtOH
1b
6
R2
1
0 °C, 36 h
7
O
OH
O
OH
Yieldb syn:anti
+
Entry Substrates
Ph
1-Np
Ph
1-Np
R1
R2
R
(%)
Et
Et
anti-7ba
syn-7ba
1
2c
3
Ph
Me
(1b)
1-Np
Ph
83
84
92:8
Entry
EtOH
(mL)
Temp
(°C)
Time
(h)
Isolated yield syn:anti
92:8
(%)
p-MeOC6H4 96
96:4
1b
2
1.0
1.0
1.0
0.5
0.25
r.t.
r.t.
0
24
13
60
60
36
65
82
45
82
83
74:26
84:16
92:8
4
p-NCC6H4
n-C7H15
c-Hex
1-Np
85
66
37
86
94
71
53
92
49
47
60
69:31
77:23
72:28
86:14
87:13
70:30
71:29
92:8
5c
6
3
4
0
92:8
7
Ph
Ph
(1a)
(1c)
5
0
92:8
8c
9c
10c
11
12c
13
14
Ph
a Unless otherwise noted, all reactions were carried out with 1b (73
mg, 0.50 mmol), 6a (102 mg, 0.65 mmol), PhSiH3 (54 mg, 0.50
mmol), and In(OAc)3 (15 mg, 0.05 mmol) in EtOH.
b With 6a (0.50 mmol).
n-C7H15
c-Hex
1-Np
Ph
H
Me
Me
n-Hex (1f)
(1j)
1-Np
87:13
88:12
85:15
Our attention was next focused on intramolecular reduc-
tive coupling by the In(OAc)3–PhSiH3 system. The
In(OAc)3-catalyzed reaction of a-enone 8,21 bearing a
formyl group, with PhSiH3 was performed under similar
conditions as those used for the intermolecular reductive
aldol reaction (Scheme 3, method A). However, the de-
sired cyclized product 9 was obtained in only a poor yield.
The formation of reduction products 10 and 11 was fa-
vored over the intramolecular aldol reaction. As the result
of various attempts, it was found that the reaction of 8 in
THF containing EtOH at reflux gave cis-9 in 77% yield
(Scheme 3, method B).22,23 The trans isomer of 9 was not
obtained.
H
1-Np
Ph
a Unless otherwise noted, all reactions were carried out with 1 (0.50
mmol), 6 (0.65 mmol), PhSiH3 (54 mg, 0.50 mmol), and In(OAc)3 (15
mg, 0.05 mmol) in EtOH (0.25 mL) at 0 °C for 36 h.
b Isolated yield.
c The reaction time is 72 h.
The cyclizations of enones 12 and bis-enones 14 also were
efficiently promoted by method B (Scheme 4).21,22 The re-
ductive aldol reaction of 12a afforded cis-13a with com-
plete stereocontrol.23 Enone 12b showed much higher
reactivity than 12a, but the cyclization resulted in low dia-
stereoselectivity. The reductive Michael reaction of 14
leading to 1,5-diketones 15 proceeded with complete
trans selectivity.23
O
O
In(OAc)3 (10 mol%)
+
PhSiH3
Ph
In conclusion, we have found that the combination of
In(OAc)3 and PhSiH3 is quite useful for both 1,4-reduc-
tion of certain a-enones and their intermolecular reductive
aldol reaction under mild conditions.9 The In(OAc)3–
PhSiH3 system is rather neutral (less Lewis acidic) and it
works well in EtOH, a less harmful solvent, at room tem-
perature or 0 °C. This catalytic system is applicable to in-
tramolecular reductive aldol and Michael reactions with
some modifications of the reaction conditions. We are
now studying further application of the In(OAc)3–PhSiH3
system, and the results will be reported in due course.
8
O
OH
O
O
O
OH
+
+
Ph
Ph
Ph
cis-9
10
11
Method A:
Method B:
11%
77%
15%
–
26%
–
Method A: EtOH (0.1 M), r.t., 4 h.
Method B: THF (0.1 M), EtOH (1 equiv), reflux, 8.5 h.
Scheme 3
Synlett 2004, No. 11, 1985–1989 © Thieme Stuttgart · New York

1988
K. Miura et al.
LETTER
(7) (a) Baik, T.-G.; Luis, A. L.; Wang, L.-C.; Krische, M. J. J.
Am. Chem. Soc. 2001, 123, 5112. (b) Wang, L.-C.; Jang, H.-
Y.; Roh, Y.; Lynch, V.; Schultz, A. J.; Wang, X.; Krische,
M. J. J. Am. Chem. Soc. 2002, 124, 9448. (c) Jang, H.-Y.;
Huddleston, R. R.; Krische, M. J. J. Am. Chem. Soc. 2002,
124, 15156. (d) Huddleston, R. R.; Krische, M. J. Org. Lett.
2003, 5, 1143.
In(OAc)3
(10 mol%)
O
O
O
OH
+
PhSiH3
Ph
Ph
Method B
( )n
( )n
12a: n = 1
12b: n = 0
45 h 13a, 90%, cis : trans = >99 : 1
4.5 h 13b, 85%, cis : trans = 62 : 38
(8) Ranu et al. have reported the InCl3-catalyzed 1,4-reduction
of electron-deficient alkenes with NaBH4. See: (a) Ranu, B.
C.; Samanta, S. Tetrahedron Lett. 2002, 43, 7405. (b)Ranu,
B. C.; Samanta, S. J. Org. Chem. 2003, 68, 7130.
(9) Quite recently, Baba et al. have reported a similar catalytic
system for reductive aldol reaction, in which InBr3 and
Et3SiH are used as catalyst and reducing agent, respectively.
See: Shibata, I.; Kato, H.; Ishida, T.; Yasuda, M.; Baba, A.
Angew. Chem. Int. Ed. 2004, 43, 711.
C(O)Ph
C(O)Ph
In(OAc)3
(10 mol%)
O
O
+
PhSiH3
Ph
Ph
Method B
( )n
( )n
14a: n = 1
14b: n = 0
4.5 h
3.5 h
trans-15a, 75%
trans-15b, 89%
(10) The use of In(acac)3 (acac = acetylacetonate) instead of
In(OAc)3 gave 2a and 3a in 34% and 65% yields,
respectively. InCl3 also promoted the reaction of 1a with
PhSiH3 in Et2O at r.t. (2a, 29%; 3a, 49%).
(11) The use of other hydrosilanes [Et3SiH, PhMe2SiH,
poly(methylhydrosiloxane)] instead of PhSiH3 resulted in no
reduction under the same conditions.
(12) The use of a half amount of PhSiH3 lowered the yield to
62%.
(13) Abernethy, C. D.; Cole, M. L.; Jones, C. Organometallics
2000, 19, 4852.
Scheme 4
Acknowledgment
This work was partly supported by Grants-in-Aid for Scientific Re-
search from the Ministry of Education, Culture, Sports, Science,
and Technology, Government of Japan and by Banyu Pharmaceuti-
cal Co. Ltd. We thank Dow Corning Toray Silicone Co. Ltd. and
Shin-Etsu Chemical Co. Ltd. for a gift of organosilicon compounds.
(14) General Procedure for the In(OAc)3-Catalyzed 1,4-
Reduction of a-Enones with PhSiH3: Under N2, a-enone 1
(0.50 mmol) and PhSiH3 (54 mg, 0.50 mmol) were added to
a suspension of In(OAc)3 (15 mg, 0.05 mmol) in EtOH (1.0
mL). The mixture was stirred at r.t. for 1.5 h and quenched
with sat. aq NaHCO3. The extract with t-BuOMe was dried
over Na2SO4 and evaporated. The residual oil was purified
by silica gel column chromatography.
(15) (a) Inoue, K.; Sawada, A.; Shibata, I.; Baba, A. J. Am. Chem.
Soc. 2002, 124, 906. (b) Inoue, K.; Sawada, A.; Shibata, I.;
Baba, A. Tetrahedron Lett. 2001, 42, 4661. (c) Takami, K.;
Mikami, S.; Yorimitsu, H.; Shinokubo, H.; Oshima, K.
Tetrahedron 2003, 59, 6627.
References
(1) 1,4-Hydrosilylation: (a) Speier, J. L.; Webster, J. A.; Barnes,
G. H. J. Am. Chem. Soc. 1957, 79, 974. (b) Bourhis, R.;
Frainnet, E.; Moulines, F. J. Organomet. Chem. 1977, 141,
157. (c) Barlow, A. P.; Boag, N. M.; Stone, G. A. J.
Organomet. Chem. 1980, 191, 39. (d) Kogure, T.; Ojima, I.
Organometallics 1982, 1, 1390. (e) Mahoney, W. S.;
Stryker, J. M. J. Am. Chem. Soc. 1989, 111, 8818. (f) Hilty,
T. K.; Revis, A. J. Org. Chem. 1990, 55, 2972. (g) Chan, T.
H.; Zheng, G. Z. Tetrahedron Lett. 1993, 34, 3095.
(h) Johnson, C. R.; Raheja, R. K. J. Org. Chem. 1994, 59,
2287. (i) Lipshutz, B. H.; Keith, J.; Papa, P.; Vivian, R.
Tetrahedron Lett. 1998, 39, 4627. (j) Appella, D. H.;
Moritani, Y.; Shintani, R.; Ferreira, E. M.; Buchwald, S. L.
J. Am. Chem. Soc. 1999, 121, 9473. (k) Lipshutz, B. H.;
Chrisman, W.; Noson, K.; Papa, P.; Sclafani, J. A.; Vivian,
R. W.; Keith, J. M. Tetrahedron 2000, 56, 2779.
(16) As shown here, the reductive aldol reaction is much slower
than the 1,4-reduction. This observation is attributable to
slow regeneration of the indium hydride species from the
indium aldolate intermediate.
(17) The In(OAc)3-catalyzed reduction of 6a with PhSiH3 (r.t.,
1.5 h) gave 1-naphthylmethanol in 82% yield.
(18) As proposed by Baba et al. (ref.9), the syn-selectivity can be
attributed by the formation of Z-4b by a concerted
hydroindation and the subsequent aldol addition via a cyclic
transition state. However, we have no evidence of the
selective formation of Z-4b.
(2) 1,4-Hydroboration: Evans, D. A.; Fu, G. C. J. Org. Chem.
1990, 55, 5678.
(3) 1,4-Hydroalumination: (a) Tsuda, T.; Hayashi, T.; Satomi,
H.; Kawamoto, T.; Saegusa, T. J. Org. Chem. 1986, 51, 537.
(b) Ikeno, T.; Kimura, T.; Ohtsuka, Y.; Yamada, T. Synlett
1999, 96.
(19) Typical Procedure for the In(OAc)3-Catalyzed
Reductive Aldol Reaction of a-Enones with Aldehydes:
Under N2, a-enone 1b (73 mg, 0.50 mmol), 6a (102 mg, 0.65
mmol), and PhSiH3 (54 mg, 0.50 mmol) were added to a
suspension of In(OAc)3 (15 mg, 0.05 mmol) in EtOH (0.25
mL). The mixture was stirred at 0 °C for 36 h. The work-up
and purification were performed by the procedure described
in ref.14. Compound 7ba (syn:anti = 92:8): IR (neat): 3540
(br s, OH), 1680 (C=O) cm–1. 1H NMR (270 MHz, CDCl3):
d = 0.69 (t, J = 7.6 Hz, 2.76 H), 0.86 (t, J = 7.6 Hz, 0.24 H),
1.63–1.79 (m, 1 H), 1.89–2.08 (m, 1 H), 3.52 (d, J = 5.9 Hz,
0.08 H), 3.80 (d, J = 1.7 Hz, 0.92 H), 3.96 (ddd, J = 9.1, 3.8,
3.6 Hz, 0.92 H), 4.11 (ddd, J = 8.2, 6.2, 5.9 Hz, 0.08 H), 5.82
(dd, J = 6.2, 5.9 Hz, 0.08 H), 5.85 (br s, 0.92 H), 7.31–7.96
(m, 12 H). 13C NMR (68 MHz, CDCl3) for the major isomer:
d = 12.25 (CH3), 20.17 (CH2), 51.62 (CH), 70.12 (CH),
(4) 1,4-Hydrostannylation: (a) Four, P.; Guibe, P. Tetrahedron
Lett. 1982, 23, 1825. (b) Keinan, E.; Gleize, P. A.
Tetrahedron Lett. 1982, 23, 477.
(5) Huddleston, R. R.; Krische, M. J. Synlett 2003, 12.
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Tetrahedron Lett. 1998, 39, 5237. (e) Taylor, S. J.; Morken,
J. P. J. Am. Chem. Soc. 1999, 121, 12202. (f) Ooi, T.; Doda,
K.; Sakai, D.; Maruoka, K. Tetrahedron Lett. 1999, 40,
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Chem. Soc. 2000, 122, 4528. (h) Zhao, C.-X.; Duffey, M.
O.; Taylor, S. J.; Morken, J. P. Org. Lett. 2001, 3, 1829.
Synlett 2004, No. 11, 1985–1989 © Thieme Stuttgart · New York

LETTER
122.49 (CH), 124.51 (CH), 125.28 (CH), 125.34 (CH),
1,4-Reduction and Reductive Aldol Reactions of a-Enones
1989
the subsequent Wittig olefination with Ph3PCHC(O)Ph. This
method was used also for the preparation of 12a, 12b, and
14b from 1-methylcyclopentene, 1,5-dimethyl-1,5-
cyclooctadiene, and 1,5-cyclooctadiene, respectively. See:
(a) Montgomery, J.; Savchenko, A. V.; Zhao, Y. J. Org.
Chem. 1995, 60, 5699. (b) See also the following paper for
the preparation of 12a and 12b: Huddleston, R. R.; Cauble,
D. F.; Krische, M. J. J. Org. Chem. 2003, 68, 11.
126.04 (CH), 127.94 (CH), 128.38 (CH × 2), 128.75 (CH ×
2), 129.14 (CH), 129.86 (C), 133.63 (CH), 133.73 (C),
136.69 (C), 137.22 (C), 206.37 (C). For the minor isomer
(only well-resolved peaks): d = 11.88 (CH3), 24.18 (CH2),
53.14 (CH), 72.85 (CH), 123.01 (CH), 124.37 (CH), 125.48
(CH), 126.17 (CH), 128.07 (CH), 128.43 (CH), 129.03
(CH), 130.53 (C), 133.16 (CH), 138.15 (C), 206.08 (C).
(20) The reaction of 1b with octanal was carried out in THF
containing an equimolar amount of EtOH at 70 °C.
However, both the yield of 7 and the syn-selectivity dropped
to 52% and 56% syn, respectively.
(21) According to the method reported by Montgomery et al., 8
and 14a were prepared by ozonolysis of cyclopentene and
(22) For the stereochemical assignment of 9, 15a, and 15b, see
ref.7a. The relative configurations of 13a and 13b were
determined by their NMR data reported in ref.21b
.
(23) Krische et al. have reported cis-selective reductive aldol
reactions of 8 and 12a, and trans-selective reductive Michael
reaction of 14. See ref.7 and ref.21b
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