Rhodium(i)-catalyzed 1,4-conjugate arylation toward β-fluoroalkylated electron-deficient alkenes: A new entry to a construction of a tertiary carbon center possessing a fluoroalkyl group

Article abstract of DOI:10.1039/c2ob26708j

Treatment of β-fluoroalkylated-α,β-unsaturated ketones with 1.2 equiv. of various arylboronic acids in the presence of 5 mol% of [Rh(COD)₂]BF₄ and 6 mol% of (S)-BINAP in toluene/H ₂O (v/v = 4/1) at the reflux temperature for 3 h gave the corresponding Michael adducts in high yields with over 90% enantioselectivity. Though other electron-deficient alkenes, such as vinylsulfone and vinylphosphonate, were found to be much less reactive in the rhodium-catalyzed conjugate addition with arylboronic acids, the reaction of various arylstannanes toward such electron-deficient alkenes took place very smoothly to afford the corresponding adducts in high yields.

Full text of DOI:10.1039/c2ob26708j

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ARTICLE TYPE
Rhodium(I)-Catalyzed 1,4-Conjugate Arylation toward β-
Fluoroalkylated Electron-Deficient Alkenes: A New Entry to a
Construction of a Tertiary Carbon Center Possessing a Fluoroalkyl
Group
5
Atsunori Morigakia, Tomoo Tanakab, Tomotsugu Miyabeb, Takashi Ishiharab and Tsutomu Konnob*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
Treatment of β-fluoroalkylated-α,β-unsaturated ketones with 1.2 equiv. of various arylboronic acids in
the presence of 5 mol% of [Rh(C8H12)2]BF4 and 6 mol% of (S)-BINAP in toluene/H2O (v/v=4/1) at the
10 reflux temperature for 3 h gave the corresponding Michael adducts in high yields with over 90%
enantioselectivity. Though other electron-deficient alkenes, such as vinyl sulfone and vinylphosphonate,
were found to be much less reactive in the rhodium-catalyzed conjugate addition with arylboronic acids,
the reaction of various arylstannanes toward such electron-deficient alkenes took place very smoothly to
afford the corresponding adducts in high yields.
conjugate additions toward β-fluoroalkylated α,β-unsaturated
15 Introduction
ketones,9 esters,10 sulfoxides,11 sulfones,12 and nitroalkenes13
using a variety of carbon nucleophiles, such as enolates,
45 stabilized carbanions, etc. However, very little attention has been
focused on the 1,4-conjugate arylation using arylmetals (Scheme
2, [eq. 2]),14 although some Friedel-Crafts arylations using
heteroaromatics have been reported so far.15 We report herein
that various arylboronic acids or arylstannanes react very
50 smoothly with fluorine-containing α,β-unsaturated compounds in
the presence of the rhodium catalyst, particularly in the former
case the high enantiocontrol being observed when the catalyst
coordinated with (S)-BINAP was used.16
1,4-Conjugate addition reactions of carbon nucleophiles to α,β-
unsaturated compounds are among the most widely used methods
for carbon-carbon bond formation in organic synthesis (Scheme
1).1 The versatility for this process is due to the wide variety of
20 donors (organometallic reagents, Michael donors, other
carbanions) and acceptors (α,β-unsaturated reagents) that can be
employed. In particular, numerous asymmetric version, like
copper-,2 nickel-,3 cobalt-,4 rhodium-,5 alkali metal-catalyzed
enantioselective reaction,6 and others,7 have been reported in
25 recent years.
R
Rf
OMet
R5
Many
examples
R
EWG
EWG
+
C
Met
EWG
R3
Rf
+
C
[eq. 1]
O
R3
R4
EWG
an electron-withdrawing
group
EWG =
Met = Li, Mg
Cu, Rh
R4
COR1, CO R1
SOR1, SO22R1
NO2
R5
EWG =
etc.
O
C
O
C
Scheme 1. 1,4-Conjugate addition reaction.
N
R2
R1
30 It has been well known that the incorporation of a fluoroalkyl
moiety to organic molecules can significantly modify its
physicochemical features and consequently its biological
properties.8 Therefore, fluoroalkylated compounds have played a
unique and significant role in agricultural and medicinal
35 chemistry.
Rf
Ar Met
EWG
This Work
[eq. 2]
Rare
examples
Ar
55
Scheme 2. Intended program.
Hence, it is not surprising that much effort has been devoted to
the development of 1,4-conjugate addition reactions of various
carbon nucleophiles toward β-fluoroalkylated electron-deficient
alkenes for the preparation of various types of fluorine-containing
40 molecules (Scheme 2, [eq. 1]).
Results and discussion
Initially, we investigated 1,4-conjugate arylation reaction using
60 (E)-4,4,4-trifluoro-1-phenyl-2-buten-1-one (1a) (Rf = CF3, R =
Ph in Scheme 3), prepared readily according to the reported
procedure,17 and phenylboronic acid as shown in Table 1. Thus,
To date, there have been considerable studies on the 1,4-
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[journal], [year], [vol], 00–00 | 1

Organic & Biomolecular Chemistry
Page 2 of 9
treatment of 1.0 equiv. of 1a with 1.2 equiv. of phenylboronic 40 Table 2. Conjugate addition of various boronic acids toward various
acid in the presence of 0.5 mol% of [Rh(COD)2]BF4 and 0.6
mol% of (S)-BINAP in toluene/H2O (v/v=4/1) at the reflux
temperature for 3 h gave the corresponding 1,4-conjugate
arylation product 2a with 55% enantiomeric excess in 60% yield
(Entry 1). In this case, the product with R absolute configuration
was afforded preferentially (vide infra). When 2.4 equiv. of
phenylboronic acid was used, the chemical yield and the
enantiomeric excess were both increased (Entry 2). Although the
10 employment of 1 mol% of rhodium catalyst did not cause any
influence of the reaction (Entry 3), 5 mol% of the catalyst led to a
significant improvement of the optical purity, the desired adduct
with 85% enantiomeric excess being obtained in 96% yield
(Entry 4). Eventually, the best yield was obtained when the
15 reaction was carried out by using 1.2 equiv. of phenylboronic
acid in the presence of 5 mol% of [Rh(COD)2]BF4 and 6 mol% of
(S)-BINAP (Entry 5). In this case, the product with 90%
enantiomeric excess was obtained in 96% yield.
As shown in Entries 6-11, we also examined the solvent effect on
20 the conjugate addition. As a result, hexane, THF, DMF, CH3OH,
and CH3NO2 were not the solvent of choice, the corresponding
adducts being obtained in very low yields (0−32%). Quite
interestingly, 1,4-dioxane, which is generally used in the Rh(I)-
catalyzed conjugate addition with nonfluorinated electron-
25 deficient olefins, resulted in the significant decrease of the optical
purity of 2a (23% ee), though the yield was good (Entry 10).
With the optimum reaction conditions (Table 1, Entry 5), we next
investigated the conjugate addition of various arylboronic acids.
The results are summarized in Table 2.
fluorinatd electron-deficient alkenes.a
Substrate
Product
2/%b
Ee/%c
Entry
1
View Online
5
CF3
O
O
90
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
2a
2b
2c
2d
2e
2f
96 (90)
F3
C
C
CF3
O
O
92
2
3
95 (91)
96 (89)
95 (94)
89 (81)
3
F3
Me
CF3
O
O
O
92
F3
C
C
MeO
CF3
O
F3
94
4
Cl
CF3
O
O
O
O
O
91
5
F3
F3
F3
C
C
C
Cl
CF3
Cl
N.D.d
90
6
CF3
O
2g
2h
2i
7
84 (80)
96 (95)
95 (80)
79 (65)
51[e]
F
CF3
O
O
O
93
8
F3
C
Me
O
CF3
O
O
92
9
F3
C
C
EtO
O
CF3
CF3
O
O
30
90
2j
10
11
12
13
14
15
16
17
18
F3
S
R1B(OH)2 (X eq.)
[Rh(COD)2]BF4 (Y mol%)
(S)-BINAP (1.2 eq. of Rh catalyst)
O
70
2k
2l
O
Rf
O
F3
C
Solvent/H2O (v/v=4/1), reflux, 3 h
Rf
R
R1
R
CF3
O
1
2
O
N.D.d
92
60[e]
OEt
F3
C
OEt
Scheme 3. Rhodium(I)-catalyzed 1,4-conjugate addition using
35 arylboronic acids.
CF3
O
O
2m
2n
2o
53 (46)
60 (45)
30 (27)
13
NMe2
F3
C
NMe2
CF3
NO2
NO2
5
F3
C
Table 1. Investigation of the reaction conditions (Rf = CF3, R, R1 = Ph)
Entry X/eq
Y/mol%
2a/%a
Ee/%b
Solvent
CF3
O2
S
SO2Ph
9
F3
C
1.2
2.4
2.4
2.4
1.2
Toluene
Toluene
Toluene
Toluene
Toluene
1
2
3
4
5
0.5
0.5
1.0
5.0
5.0
60
91
95
96
55
72
74
85
90
CF3
N.D.d
74
P(O)(OEt)2 1f
P(O)(OEt)2 2p
F3
C
96 (90)
CHF
CF3
O
2O
1g
2q
96 (92)
91
F2HC
6
7
8c
1.2
1.2
1.2
1.2
1.2
1.2
5.0
5.0
5.0
5.0
5.0
5.0
0
23
32
9
-
34
2
Hexane
THF
O
CF3
O
90
1h
2a
DMF
Ph
9
4
CH3OH
1,4-Dioxane
CH3NO2
a) All reaction was carried out by using 1.0 equiv. of the electron-
10
11
78
22
23
36
deficient alkene and 1.2 equiv. of boronic acid in the presence of 5 mol%
of [Rh(COD)2]BF4 and 6 mol% of (S)-BINAP in toluene/H2O (v/v=4/1)
at the reflux temperature for 3 h. b) Determined by 19F NMR. Values in
parentheses are of isolated yield. c) Determined by HPLC (Chiral pac
AD-H). d) Not determined. e) The product could not be purified due to
some impurities.
a) Determined by 19F NMR. Value in parentheses is of isolated yield.
b) Determined by HPLC (Chiralpac AD). c) Carried out at 100 °C
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Page 3 of 9
Organic & Biomolecular Chemistry
CF3 OH
Ph
CF3
O
As shown in Entries 2-4 and 7-9, various types of arylboronic
LiAlH4 (2.0 equiv.)
THF, 0 °C, 1 h
acids having an electron-donating (CH3, CH3O) or an electron-
withdrawing group (Cl, F, CH3CO, EtO2C) on the benzene ring
could participate nicely in the conjugate addition to give the
corresponding adducts 2b-d, 2g-i in excellent yields (84−96%
yield) with high enantioselectivity (90−94% ee). However, the
use of ortho-substituted arylboronic acid, such as o-chlorophenyl-
or 1-naphthylboronic acid, resulted in a significant decrease of
the reaction efficacy (3% or 51% yield in Entries 6 or 11), while
Ph
Ph
Ph
2a (84% ee)
3a
81% (d.r. = 1 : 1)
View Online
5
CF3
CuSO4-SiO2 (2.0 equiv.)
Hexane, reflux, 2 h
Ph
Ph
R
4a
26%
10 meta-substitution of the benzene ring of R1B(OH)2 did not
influence on the reaction at all (Entry 5). 2-Thienylboronic acid
was also found to be a good Michael donor in the reaction (Entry
10), though the yield decreased slightly.
[!]D24 = +47.4 (c, 0.6, CHCl3)
lit. for (S)-isomer (55% ee) [!]D21 = -36.4 (c, 2.7, CHCl3)
55
Scheme 5. Determination of the absolute configuration of 2a.
We also examined the conjugate addition reaction using various
15 types of fluorine-containing electron-deficient alkenes. As shown
in Entries 12-14, the reaction of various electron-deficient
alkenes, such as α,β-unsaturated ester 1b, amide 1c, or
nitroalkene 1d18, proceeded to give the corresponding adducts 2l-
n in good yields. Especially, the high enantioselectivity (92% ee)
20 was observed in the case of the amide (Entry 13). Unfortunately,
the vinyl sulfone 1e and the vinylphosphonate 1f19 did not give
the satisfactory results, the product being afforded in very low
yields as well as in a very low enantioselective manner (Entries
15 and 16). Changing the fluoroalkyl group from a CF3 group to
25 a CHF2 group also caused a decrease of the enantiomeric excess.
The use of (Z)-substrate 1h afforded the Michael adduct 2a with
the same absolute configuration as in the reaction of (E)-substrate
1a (Entry 1 vs Entry 18).
The proposed mechanism for the present reaction is outlined in
60 Scheme 6.5a, 5b, 5d, 5f
Thus, (E)-substrate (or which was produced via isomerization of
(Z)-isomer) may come close to arylrhodium species coordinated
with (S)-BINAP (Int-A), avoiding the phenyl group on
phosphorus atom. Then, si face of the alkene may coordinate
65 with aryl-rhodium species, followed by the attack of the aryl
group, affording the corresponding rhodium enolate (Int-B).
Finally, the enolate may react with H2O to give the corresponding
Michael adduct, and the rhodium species coordinated with (S)-
BINAP may be regenerated.
70
In order to reveal why the same product, (R)-stereoisomer 2a was
30 obtained preferentially in both (E)- and (Z)-substrates, we treated
1h with 5 mol% of [Rh(COD)2]BF4 and 6 mol% of (S)-BINAP in
toluene/H2O (v/v = 4/1) at the reflux temperature for 3 h. As a
result, 1h was completely comsumed, 1a being obtained
quantitatively (Scheme 4). This experimental result indicates that
35 rhodium catalyst coordinated with (S)-BINAP as a ligand
catalyzes the alkene-isomerizaiton much more rapidly than the
conjugate addition reaction.20
[Rh(I)] + (S)-BINAP
+
ArB(OH)2
CF3
O
Ph
O
P
P
Rh
Ar
F3C
Rh
P
P
O
Ar
F3C
Ph
H
CF3
O
O
[Rh(COD)2]BF4 (5 mol%)
(S)-BINAP (6 mol%)
F3C
Toluene/H2O (v/v=4/1)
reflux, 3 h
Int-A
1h
1a : quant.
40
Scheme 4. Rhodium(I)-catalyzed alkene-isomerization.
CF
P
3P
CF3
O
H2O
Rh
Ar
O
Ar
Ph
The stereochemical assignment of 2 was made as follows
H
45 (Scheme 5). Thus, treatment of optically active 2a with 2.0 equiv.
of LiAlH4 in THF at 0 °C for 1 h gave a 1 : 1 diastereomeric
mixture of the corresponding alcohol 3a in 81% yield, which
were subjected to 2.0 equiv. of CuSO4-SiO2 in hexane at the
reflux temperature for 2 h,21 giving the known compound 4a.
50 The comparison of the observed optical rotation of 4a with its
literature value made it possible to determine the absolute
configuration of 2a as R.22
Int-B
Scheme 6. A plausible reaction mechanism.
Next, our attention was directed toward the conjugate addition of
75 organostannanes into fluorine-containing electron-deficient
alkenes.
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Organic & Biomolecular Chemistry
Page 4 of 9
Initially, screening of the solvent was done in detail as shown in
Table 3. Thus, treatment of 1a (Rf = CF3, R = Ph) with 1.2 equiv.
With the best reaction conditions in hand (Table 3, Entry 2), we
next examined the reaction using various organostannanes as
shown in Table 4.
of phenyltributylstannane in the presence of
[Rh(COD)2]BF4 in toluene at 90 °C for
2
h
mol% of
gave the
2
View Online
5
correspponding adduct 2a in 76% yield (Entry 1). In this case,
any trace of the starting α,β-unsaturated ketone was not detected.
Changing the solvent from toluene to THF led to an increase of
the yield, the desired adduct being afforded in 86% yield (Entry
2). Acetonitrile as well as 1,2-dichloroethane were also found to
40
Table 4. Conjugate addition of various organostannanes toward
various fluorinated electron-deficient alkenes.
Entry
Substrate
Product
2/%a
1/%a
O
CF3 O
10 be the solvent of choice (Entries 3 and 4), while the use of DMF
and 1,4-dioxane caused a significant decrease of the yield
(Entries 5 and 6). In the absense of catalyst, the reation did not
proceed at all (Entry 7).
trace
1
F3
C
1a
1a
86 (68)
2a
CF3
O
O
O
2
3
F3C
2b 75
0
Me
Then, we next investigated the reaction under the influence of
15 various rhodium catalysts as shown in Entry 8-16. Addition of
phosphine ligand, such as PPh3, P(o-Tol)3, P(t-Bu)3, PCy3, did not
cause any significant change in the yield (Entries 8-11). In
addition, the use of [RhCl(COD)]2 afforded the desired adduct in
high yield (Entry 13). However, very disappointingly, the
20 catalyst, [Rh(COD)2]BF4 + (S)-BINAP, which is the catalyst of
choice in the conjugate addition with various boronic acids, was
found to be less reactive, the adduct being obtained in only 61%
yield. Additionally, no enantioselectivity was observed in this
case (Entry 12). Furthermore, all of [Rh(COD)(MeCN)2]BF4,
25 Willkinson catalyst, and Rh(acac)(C2H4)2 did not give
satisfactory results (Entries 14-16).
CF3
O
trace
F3C
1a
1a
2c 87 (56)
MeO
CF3
O
O
O
trace
4
F3C
87 (66)
31
2r
2s
OMe
CF3
O
O
F3C
1a
1a
26
0
5
6
OMe
CF3
O
F3C
2d 75 (67)
2h 89 (54)
Cl
CF3
O
O
O
O
0
0
7
8
F3C
F3C
F3C
1a
1a
Me
R1SnBu3 (1.2 eq.), Catalyst (2 mol%)
H2O (1.0 eq.)
O
O
Rf
O
CF3
O
Solvent, reflux, 2 h
Rf
R
R1
R
2i
78 (59)
EtO
1
2
O
30
CF3
O
Scheme 7. Rhodium(I)-catalyzed 1,4-conjugate addition using
arylstannanes.
9
1a
1a
39 (13)
14
38
29
2t
C
N
O
O
CF3
O
O
10
F3C
2u
Table 3. Investigation of the reaction conditions (Rf = CF3, R, R1 = Ph).
O
S
2a/%a
Entry
1b [Rh(COD)2]BF4
[Rh(COD)2]BF4
Catalyst
Solvent
CF3
76
86 (68)
64
66c
80
Toluene
THF
DMF
1,4-Dioxane
MeCN
ClCH2CH2Cl
THF
11
12
F3C
1a
1b
2j 10
2l 65
25
0
2
3b [Rh(COD)2]BF4
4b [Rh(COD)2]BF4
CF3
O
O
OEt
F3
C
OEt
5
[Rh(COD)2]BF4
6b [Rh(COD)2]BF4
87
0
CF3
O
O
13
1c
1d
1e
NMe2
23
19
20
16
8
2m
2n
7
None
F3
C
NMe2
CF3
8
9
[Rh(COD)2]BF4 + 2PPh3
[Rh(COD)2]BF4 + 2P(o-Tol)3
[Rh(COD)2]BF4 + 2P(t-Bu)3
[Rh(COD)2]BF4 + 2PCy3
[Rh(COD)2]BF4 + (S)-BINAP
1/2[RhCl(COD)2]
[Rh(COD)(MeCN)2]
RhCl(PPh3)3
Rh(acac)(C2H4)2
84
88
86
87
61d
88
41
0
THF
THF
THF
THF
THF
THF
THF
THF
THF
NO2
NO2
14
F3
C
10
11
12
13
14
15
16
CF3
O2
S
15b
2o 77 (61)
SO2Ph
F3
C
CF3
16b
17
1f
82 (47)
0
P(O)(OEt)2
P(O)(OEt)2
F3
C
2p
CHF2
O
0
O
trace
1g
2q
86 (60)
a) Determined by 19F NMR. Value in parentheses is of isolated yield.
b) Carried out at 90 °C (bath temp).
F2HC
Ph
c) The starting !,"-unsaturated ketone was recovered in 7% yield.
d) No enantioselectivity was observed.
a) Determined by 19F NMR. Values in parentheses are of isolatd yield.
b) Five mol% of rhodium catalyst were used.
35
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Organic & Biomolecular Chemistry
Notes and references
As shown in Entries 2, 3 and 6-8, various types of arylstannanes
aFunctional Materials Research Laboratories Research & Development
50 Headquarters LION CORPORATION, 7-2-1 Hirai, Edogawa-ku, Tokyo
having an electron-donating (CH3, CH3O) or an electron-
withdrawing group (Cl, EtO2C, CH3CO) on the benzene ring
could participate nicely in the conjugate addition to give the
corresponding adducts 2b-d, 2h, i in high yields (75-89% yield).
However, the use of ortho-substituted and para-cyano-substituted
arylstannanes resulted in a significant decrease of the reaction
efficacy (31% and 39% yield in Entries 5 and 9). Additionally, 2-
furyl and 2-thienyl functionalities were all found to be somewhat
132-0035, Japan
b
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Department of Chemistry and Materials Technology, Kyoto Institute of
Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan Fax: 81-75-
724-7580; Tel: 81-75-724-7517; E-mail:konno@chem.kit.ac.jp
55 † Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/b000000x/
5
10 less reactive, the desired adducts being afforded in less than 20%
yield (Entries 10 and 11).
Experimental
We also examined the conjugate addition reaction using various
types of fluorine-containing electron-deficient olefins. As shown
in Entry 12, the reaction with α,β-unsaturated ester 1b proceeded
15 smoothly to give the corresponding adducts 2l in good yields,
while α,β-unsaturated amide as well as nitroalkene did not give
any satisfactory results (Entries 13 and 14). It is noteworthy that
both trifluoromethylated vinyl sulfone and vinylphosphonate
could react with phenylstannane very smoothly to give the
20 corresponding 1,4-adducts 2o, 2p in high yields, because the
reaction with arylboronic acids did not afford the 1,4-adducts in
good yields (Entries 15 and 16 in Table 2). Changing a
fluoroalkyl group from a CF3 group to a CHF2 group did not
influence on the reaction at all (Entry 17).
25 As shown in Scheme 8, the reaction mechanism, which is similar
to that in the reaction with boronic acids, may be proposed.5c, 5e
Thus, the transmetalation of the cationic rhodium complex with
organostannane produces the organorhodium intermediate Rh-R1
and Bu3SnBF4. Addition of Rh-R1 toward electron-deficient
30 alkenes 1 leads to the η3-oxa-π-allylrhodium complex Int-C,
which then reacts with Bu3SnBF4 to afford stannyl enol ether Int-
D and to regenerate the cationic rhodium complex. The stannyl
enol ether Int-D is easily hydrolyzed to afford product 2.
60 General information: Infrared spectra (IR) were taken on a
JASCO FT/IR-4100typeA spectrometer as film on a NaCl plate.
1H and 13C NMR spectra were measured with a Bruker DRX-500
NMR spectrometer and
a JEOL JNM- AL 400 NMR
spectrometer in chloroform-d (CDCl3) solution with
a
65 tetramethylsilane (Me4Si) as an internal reference. A JEOL
JNM-EX90A (84.21 MHz) FT-NMR spectrometer and a JEOL
JNM-AL 400 NMR spectrometer were used for determining the
yield of the products with hexafluorobenzene (C6F6). 19F NMR
(376.05 MHz) spectra was measured with a JEOL JNM-AL 400
70 NMR spectrometer in a chloroform-d (CDCl3) solution with
trichlorofluoromethane (CFCl3) as an internal standard. High-
resolution mass spectra (HRMS) were taken on a Hitachi M-80B
mass spectrometer by electron impact (EI), chemical ionization
(CI), and fast atom bombardment (FAB) methods. Thin-layer
75 chromatography (TLC) was done on aluminium sheets coated
with silica gel (Merck 60 F254), and column chromatography was
carried out using silica gel (Wacogel C-200) as adsorbent. Liquid
choromatographic analysis were conducted on a Shimadzu LC-
10Avp instrument equipped with model SPD-10Avp
80 spectrometers as an ultra violet light (254 nm) and chiral column
(Daicel CHIRALPAC AD-H). Optical rotations were measured
on a Horiba high sensitive polarimeter SEPA-200. Specific
rotations, [α]D, were reported in degree and the concentration (c)
was given in gram per 100 mL of the indicated solvent.
Rf
O
Rf OSnBu3
H2O
R1-SnBu3
R1
R
R1
R
2
Int-D
-
Rh+BF4
85 All chemicals were of reagent grade and, if necessary, were
purified in the usual manner prior to use.
Bu3SnBF4
Rh-R1
Rh
O
R1
R
Typical experimental procedure for the conjugate addition of
90 aryl- and alkenylboronic acids to electron deficient ofefins
A mixture of phenylboronic acid (37 mg, 3.00 mmol), bis(1,5-
cyclooctadiene)rhodium tetrafluoroborate (5.00 mg, 5 mol%),
Int-C
Rf
O
R
Rf
1
35
(S)-2,2’-bis(diphenylphosphino)-1,1’-binaphtyl
[(S)-BINAP]
Scheme 8. A plausible reaction mechanism.
(9.00 mg, 6 mol%) and the 4,4,4-trifluoro-1-phenyl-2-butenone
95 (1a) (50 mg, 0.25 mmol) were placed in a flask and then a
distilled toluene/water mixture (4 mL/0.5 mL) was added at room
temperature. The flask was heated in a preheated oil bath at 120
oC and the mixture was stirred for 3 h. After filtration through
silica (eluting ethyl acetate), the solvent was removed under
100 reduced pressure. The residue was purified by silica gel column
chromatography to give 4,4,4-trifluoro-1,3-diphenylbutan-1-one
(2a) (63 mg, 90% yield). (Method A)
Conclusions
In summary, we have demonstrated the rhodium-catalyzed
conjugate addition reaction of various arylboronic acids as well
40 as arylstannanes toward various β-fluoroalkylated electron-
deficient olefins. As a result, α,β-unsaturated ketones and amide,
not vinylsulfone and vinylphosphonate, could participate in the
highly enantioselective conjugate addition very well. In sharp
contrast, organostannanes were found to be more reactive in the
45 case of vinylsulfone and vinylphosphonate as Michael donor, the
corresponding adducts being given in high yields.
105
Typical procedure for the 1,4-addition of aryl- and
alkenylstannanes to electron deficient ofefins
To a solution of [Rh(COD)2]BF4 (5.00 mg, 2 mol%) in THF (1
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 5

Organic & Biomolecular Chemistry
Page 6 of 9
mL) were added 4,4,4-trifluoro-1-phenyl-2-butenone (1a) (100
(3R)-3-(4-Chlorophenyl)-4,4,4-trifluoro-1-phenylbutan-1-one
mg, 0.50 mmol) and tributylphenylstannane (220 mg, 0.60 mmol)
and water (9.00 mg, 0.50 mmol). After addition was completed,
the reaction mixture was heated reflux temperature and stirred at
(2d)
Yield : 94%; [α]37. = +16.5 (c = 1.00, CCl4), ee = 94%, AD-H,
D
Hexane : i-PrOH = 99.6 : 0.4, 0.7 mL/m (Method A); M.P. : 66-
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1
5
that temperature for 2 h. After the reaction was quenched with 65 68 °C; H NMR (CDCl3) δ = 3.59 (dd, J = 3.86, 17.80 Hz, 1H),
sat. NH4Cl aq., the whole was extracted with ethyl acetate three
times, and combined organic layers were dried over andydrous
Na2SO4, concentrated in vacuo. The residue was purified by silica
gel column chromatography to give 4,4,4-trifluoro-1,3-
3.67 (dd, J = 9.47, 17.80 Hz, 1H), 4.18-4.26 (m, 1H), 7.28-7.35
(m, 4H), 7.45-7.48 (m, 2H), 7.57-7.60 (m, 1H), 7.91-7.93 (m,
2H); 13C NMR (CDCl3) δ = 38.14, 44.30 (q, J = 27.73 Hz),
126.68 (q, J = 279.31 Hz), 128.00, 128.75, 129.00, 130.34,
70 133.04 (q, J = 1.26 Hz), 133.67, 134.30, 136.11, 194.96; 19F
NMR (CDCl3) δ = −70.20 (d, J = 8.83 Hz, 3F); IR (KBr) 2963,
2956, 1670, 1595, 1580, 1497, 1450, 1425, 1319, 1310, 1281,
1250, 1207, 1184, 1157, 1103, 1092, 1069, 1015, 961, 924, 822,
804, 779 cm-1; HRMS calcd for C16H13ClF3O (M+H) 313.0607,
10 diphenylbutan-1-one (2a) (120 mg, 86% yield). (Method B)
(3R)-4,4,4-Trifluoro-1,3-diphenylbutan-1-one (2a)
Yield : 90%; [α]34 = +36.6 (c = 1.04, CCl4), ee = 90%, AD-H,
D
Hexane : i-PrOH = 99.6 : 0.4, 0.7 mL/m (Method A); M.P. : 61-
1
15 63 °C; H NMR (CDCl3) δ = 3.60 (dd, J = 4.01, 17.76 Hz, 1H), 75 found 313.0618.
3.70 (dd, J = 9.22, 17.76 Hz, 1H), 4.21-4.30 (m, 1H), 7.26-7.35
(m, 3H), 7.39-7.41 (m, 2H), 7.44-7.48 (m, 2H), 7.56-7.59 (m, 2H),
7.92-7.94 (m, 1H); 13C NMR (CDCl3) δ = 38.25, 44.77 (q, J =
27.45 Hz), 126.95 (q, J = 279.49 Hz), 128.01, 128.27, 128.67,
(3R)-3-(3-Chlorophenyl)-4,4,4-trifluoro-1-phenylbutan-1-one
(2e)
Yield : 81%; [α]34 = +13.3 (c = 1.10, CCl4), ee = 91% AD-H,
D
20 128.69, 129.00, 133.52, 134.71 (q, J = 1.38 Hz), 136.27, 195.25; 80 Hexane : i-PrOH = 99.6 : 0.4, 0.7 mL/m (Method A); 1H NMR
19F NMR (CDCl3) δ = −70.17 (d, J = 8.83 Hz 3F); IR (KBr) 3065,
3038, 2963, 2910, 1717, 1686, 1595, 1497, 1474, 1450, 1427,
1375, 1362, 1339, 1319, 1308, 1256, 1227, 1153, 1001, 961, 922,
880, 779 cm-1.; HRMS calcd for C16H13F3O (M+) 278.0918,
25 found 278.0923.
(CDCl3) δ = 3.62 (dd, J = 4.20, 17.92 Hz, 1H), 3.68 (dd, J = 9.05,
17.92 Hz, 1H), 4.21-4.29 (m, 1H), 7.20-7.67 (m, 7H), 7.90-8.03
(m, 2H); 13C NMR (CDCl3) δ = 38.13, 44.50 (q, J = 27.68 Hz),
126.62 (q, J = 279.44 Hz), 127.39, 128.00, 128.56, 128.74,
85 129.07, 129.93, 133.68, 134.51, 136.05, 136.54, 194.81; 19F
NMR (CDCl3) δ = −70.05 (d, J = 11.02 Hz, 3F); IR (neat) 3065,
2961, 1692, 1597, 1578, 1479, 1450, 1435, 1420, 1371, 1346,
1307, 1258, 1223, 1158, 1109 , 1001, 989, 972, 783, 756 cm-1.;
(3R)-4,4,4-Trifluoro-3-(4-methylphenyl)-1-phenylbutan-1-one
(2b)
Yield : 91%; [α]36 = +12.3 (c = 1.01, CCl4), ee = 92%, AD-H,
D
HRMS calcd for C16H13ClF3O (M+H) 313.0607, found 313.0607.
30 Hexane : i-PrOH = 99.6 : 0.4, 0.7 mL/m (Method A); M.P. : 80-
90
1
81 °C; H NMR (CDCl3) δ = 2.31 (s, 3H), 3.58 (dd, J = 3.94,
(3R)-4,4,4-Trifluoro-3-(4-fluorophenyl)-1-phenylbutan-1-one
17.73 Hz, 1H), 3.68 (dd, J = 9.33, 17.73 Hz, 1H), 4.15-4.26 (m,
1H), 7.14-7.15 (m, 2H), 7.26-7.29 (m, 2H), 7.44-7.47 (m, 2H),
7.56-7.59 (m, 1H), 7.92-7.94 (m, 2H); 13C NMR (CDCl3) δ =
(2g)
Yield : 80%; [α]35 = +6.4 (c = 0.85, CCl4), ee = 90%, AD-H,
D
Hexane : i-PrOH = 99 : 1, 0.7 mL/m (Method A); M.P. : 94-
1
35 21.01, 38.23, 44.42 (q, J = 27.37 Hz), 127.02 (q, J = 279.44 Hz), 95 95 °C; H NMR (CDCl3) δ = 3.51 (dd, J = 3.99, 17.76 Hz, 1H),
128.00, 128.66, 128.82, 129.37, 131.51, 133.46, 136.33, 138.02,
195.33; 19F NMR (CDCl3) δ = −70.29 (d, J = 11.02 Hz, 3F); IR
(KBr) 3036, 2963, 2907, 1686, 1595, 1578, 1520, 1508, 1423,
1373, 1306, 1259, 1200, 1153, 1119, 1097, 1020, 1003, 961, 885,,
3.59 (dd, J = 9.40, 17.76 Hz, 1H), 4.12-4.20 (m, 1H), 6.90-6.98
(m, 2H), 7.28-7.51 (m, 5H), 7.83-7.85 (m, 2H); 13C NMR
(CDCl3) δ = 38.30, 44.17 (q, J = 27.65 Hz), 115.66 (d, J = 21.38
Hz), 126.80 (q, J = 279.56 Hz), 127.99, 128.75, 130.63, 130.70,
40 814 cm-1.; HRMS calcd for C17H15F3O (M+) 292.1075, found 100 133.63, 136.21, 162.57 (d, J = 247.24 Hz), 195.10; 19F NMR
292.1068.
(CDCl3) δ = −69.88 (d, J = 8.83 Hz, 3F), −114.68 (s, 1F); IR
(KBr) 2926, 2856, 1693, 1659, 1599, 1580, 1514, 1448, 1423,
1350, 1306, 1259, 1165, 1109, 1067, 1016, 962, 922, 831, 791,
689 cm-1.; HRMS calcd for C16H13F4O (M+H) 297.0903, found
105 297.0905.
(3R)-4,4,4-Trifluoro-3-(4-methoxyphenyl)-1-phenylbutan-1-
one (2c)
45 Yield : 89%; [α]35 = +12.6 (c =1.00, CCl4), ee = 92% AD-H,
D
Hexane : i-PrOH = 99 : 1, 0.7 mL/m (Method A); M.P. : 65-
1
66 °C; H NMR (CDCl3) δ = 3.56 (dd, J = 3.93, 17.67 Hz, 1H),
(3R)-3-(4-Acetylphenyl)-4,4,4-trifluoro-1-phenylbutan-1-one
(2h)
3.66 (dd, J = 9.38, 17.67 Hz, 1H), 3.78 (s, 3H), 4.15-4.23 (m,
1H), 6.85-6.87 (m, 2H), 7.30-7.32 (m, 2H), 7.44-7.47 (m, 2H),
Yield ; 95%; [α]18 D= +32.4 (c = 0.98, CCl4), ee = 93%, AD-H,
50 7.56-7.59 (m, 1H), 7.92-7.93 (m, 2H); 13C NMR (CDCl3) δ = 110 Hexane : i-PrOH = 80 : 20, 0.7 mL/m (Method A); M.P. : 96-
1
38.31, 44.54 (q, J = 27.53 Hz), 55.16, 114.07, 126.50 (q, J = 1.38
Hz), 127.02 (q, J = 279.19 Hz), 128.00, 128.68, 130.04, 133.49,
136.34, 159.43, 195.41; 19F NMR (CDCl3) δ = −69.80 (d, J =
8.83 Hz, 3F); IR (KBr) 3026, 2961, 2839, 1682, 1614, 1595,
97 °C; H NMR (CDCl3) δ = 2.36 (s, 3H), 3.64 (dd, J = 3.73,
17.89 Hz, 1H), 3.74 (dd, J = 9.81, 17.89 Hz, 1H), 4.27-4.35 (m,
1H), 7.45-7.52 (m, 4H), 7.57-7.60 (m, 1H), 7.91-7.94 (m, 4H);
13C NMR (CDCl3) δ = 26.48, 37.98, 44.79 (q, J = 27.67 Hz),
55 1518, 1450, 1431, 1371, 1308, 1246, 1227, 1207, 1184, 1153, 115 126.57 (q, J = 279.44 Hz), 127.95, 128.58, 128.72, 129.28,
1121, 1099, 1036, 1001, 961, 883, 818, 764, 685 cm-1.; HRMS
calcd for C17H15F3O2 (M+) 308.1024, found 308.1026
133.68, 135.98, 136.90, 139.65 (q, J = 1.38 Hz), 194.84, 197.36;
19F NMR (CDCl3) δ = −69.82 (d, J = 9.04 Hz, 3F); IR (KBr)
2964, 1738, 1684, 1609, 1595, 1578, 1448, 1427, 1319, 1310,
1250, 1221, 1161, 1123, 1101, 1016, 945, 924, 831, 779, 687 cm-
60
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Organic & Biomolecular Chemistry
1.; HRMS calcd for C18H16F3O2 (M+H) 321.1102, found
321.1110.
Hexane : i-PrOH = 97 : 3, 0.7 mL/m (Method A); Yield : 61%
(Method B), M.P. : 91-92 °C; 1H NMR (CDCl3) δ = 3.74 (dd, J =
3.48, 14.69 Hz, 1H), 3.79 (dd, J = 9.93, 14.69 Hz, 1H), 3.93-4.02
(3R)-3-(4-Ethoxycarbonylphenyl)-4,4,4-trifluoro-1-
(m, 1H), 7.11-7.13 (m, 2H), 7.18-7.21 (m, 2H) 7.23-7.26 (m, 1H),
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5
phenylbutan-1-one (2i)
65 7.33-7.36 (m, 2H), 7.49-7.52 (m, 1H), 7.58-7.60 (m, 2H); 13C
Yield : 80%; [α]19 = +31.6 (c = 0.77, CCl4), ee = 92%, AD-H,
D
NMR (CDCl3) δ = 45.81 (q, J = 28.64 Hz), 55.34, 125.37 (q, J =
280.44 Hz), 127.79, 128.73, 128.88, 129.05, 129.08, 131.00,
133.63, 138.95; 19F NMR (CDCl3) δ = −70.55 (d, J = 6.64 Hz,
3F); IR (KBr) 2986, 1558, 1418, 1310, 1259, 1188, 1157, 1142,
70 1105, 1082, 1030, 870, 795, 754, 698, 689, 592, 550 cm-1; HRMS
calcd for C15H13F3O2S (M+) 314.0588, found 314.0593.
Hexane : i-PrOH = 95 : 5, 0.7mL/m (Method A); M.P. : 85-
86 °C; 1H NMR (CDCl3) δ = 1.37 (t, J = 7.12 Hz, 3H), 3.62 (dd, J
= 3.82, 17.86 Hz, 1H) , 3.72 (dd, J = 9.53, 17.86 Hz, 1H), 4.25-
10 4.35 (m, 1H), 4.36 (q, J = 7.12 Hz, 2H), 7.40-7.52 (m, 4H), 7.53-
7.61 (m, 1H), 7.86-7.94 (m, 2H), 7.96-8.04 (m, 2H); 13C NMR
(CDCl3) δ = 14.26, 38.10, 44.85 (q, J = 27.79 Hz), 61.01, 126.62
(q, J = 279.69 Hz), 128.00, 128.76, 129.07, 129.87, 130.55,
133.69, 136.10, 139.41, 166.05, 194.92; 19F NMR (CDCl3) δ = −
15 69.73 (d, J = 8.83 Hz, 3F); IR (KBr) 2963, 1711, 1684, 1614,
1450, 1433, 1369, 1311, 1286, 1250, 1207, 1168, 1151, 1103,
1022, 964, 851, 766, 754, 714, 690, 644, 629, 594 cm-1.; HRMS
calcd for C19H18F3O3 (M+H) 351.1208, found 351.1214.
Diethyl (2-phenyl-2-trifluoromethylethyl)phosphonate (2p)
Yield : 47% (Method B), 1H NMR (CDCl3) δ = 1.01 (t, J = 7.06
75 Hz, 3H), 1.13 (t, J = 7.05 Hz 3H), 2.31-2.44 (m, 2H), 3.53-3.60
(m, 1H), 3.70-3.96 (m, 4H), 7.53 (s, 5H); 13C NMR (CDCl3) δ =
15.97 (d, J = 6.29 Hz), 16.02 (d, J = 6.54 Hz), 26.03 (dq, J =
147.48, 1.46 Hz), 45.09 (dq, J = 28.37, 1.92 Hz), 61.63 (d, J =
5.85 Hz), 61.67 (d, J = 5.33 Hz), 126.28 (dq, J = 280.19, 22.89
80 Hz), 128.51, 128.52, 129.17, 133.58; 19F NMR (CDCl3) δ = −
71.55 (d, J = 9.78 Hz, 3F). IR (neat) 3037, 2984, 2932, 1723,
1497, 1457, 1416, 1393, 1367, 1257, 1176, 1147, 1109, 1061,
1026, 969, 900, 864, 812, 752 cm-1.
20 (3S)-4,4,4-Trifluoro-1-phenyl-3-(2-thienyl)butan-1-one (2j)
Yield : 65%; [α]36 = −4.4 (c = 0.98, CCl4), ee = 90%, AD-H,
D
Hexane : i-PrOH = 99.6 : 0.4, 0.7 mL/m (Method A); M.P. : 89-
1
91 °C; H NMR (CDCl3) δ = 3.54 (dd, J = 4.12, 17.60 Hz, 1H),
3.62 (dd, J = 9.03, 17.60 Hz, 1H), 4.38-4.46 (m, 1H), 7.11-7.12
25 (m, 1H), 7.28-7.30 (m, 2H), 7.45-7.48 (m, 2H), 7.59-7.60 (m, 1H),
7.92-7.94 (m, 2H); 13C NMR (CDCl3) δ = 38.58, 40.26 (q, J =
28.37 Hz), 124.16, 126.02, 126.66 (q, J = 279.19 Hz), 127.42,
128.00, 128.70, 133.54, 134.75, 136.25, 195.19; 19F NMR
(CDCl3) δ = −70.64 (d, J = 8.75 Hz, 3F); IR (KBr) 3749, 3107,
30 3090, 3061, 2964, 2941, 1717, 1684, 1595, 1578, 1541, 1448,
1433, 1331, 1308, 1295, 1219, 1146, 1094, 1016, 978 cm-1.;
HRMS calcd for C14H12F3OS (M+H) 285.0561, found 285.0555.
85 (3R)-4,4-Difluoro-1,3-diphenylbutan-1-one (2q)
Yield : 92%; [α]36 = −12.6 (c = 0.99, CCl4), ee = 74%, AD-H,
D
Hexane : i-PrOH = 99 : 1, 0.7 mL/m (Method A); M.P. : 56-
1
58 °C; H NMR (CDCl3) δ = 3.54 (dd, J = 7.99, 17.82 Hz, 1H),
3.62 (dd, J = 5.47, 17.82 Hz, 1H), 3.91-4.00 (m, 1H), 6.05 (dt, J
90 = 2.81, 56.61 Hz, 1H), 7.26-7.59 (m, 8H), 7.95-7.97 (m, 2H); 13
C
NMR (CDCl3) δ = 37.37 (t, J = 2.82 Hz), 44.56 (t, J = 19.97 Hz),
117.24 (t, J = 244.35 Hz), 127.75, 128.01, 128.64, 128.68, 128.90,
133.35, 136.44 (m), 136.65, 196.72; 19F NMR (CDCl3) δ = −
120.18 (ddd, J = 14.12, 56.61, 276.75 Hz, 1F), -123.34 (ddd, J =
95 18.36, 56.61, 276.75, 1F); IR (KBr) 3064, 2963, 2926, 1693,
1597, 1477, 1435, 1418, 1348, 1298, 1258, 1223, 1157, 1084,
1065, 1001, 989, 974, 783, 756, 714, 648 cm-1.; HRMS calcd for
C16H14F2O (M+H) 261.1091, found 261.1088.
(3R)-N,N-Dimethyl-4,4,4-trifluoro-3-phenylbutanamide (2m)
35 Yield : 46%; [α]35 = −44.0 (c = 1.01, CCl4), ee = 92% AD-H,
D
Hexane : i-PrOH = 97 : 3, 0.7 mL/m (Method A); M.P. : 68-
1
69 ℃; H NMR (CDCl3) δ = 2.87 (s, 3H), 2.94 (d, J = 6.72 Hz,
2H), 2.97 (s, 3H), 4.10-4.18 (m, 1H), 7.29-7.37 (m, 5H); 13C
NMR (CDCl3) δ = 33.11 (q, J = 1.50 Hz), 35.60, 37.03, 46.01 (q,
40 J = 27.13 Hz), 127.00 (q, J = 279.52 Hz), 128.13, 128.58, 128.93,
134.95 (q, J = 1.51 Hz), 168.72; 19F NMR (CDCl3) δ = −70.19 (d,
J = 8.83 Hz, 3F); IR (KBr) 2928, 1637, 1499, 1458, 1354, 1286,
1256, 1211, 1163, 1101, 1059, 966, 880, 804, 783, 758, 706, 687,
613 cm-1; HRMS calcd for C12H15F3NO (M+H) 246.1107, found
45 246.1102.
100 4,4,4-Trifluoro-3-(3-methoxyphenyl)-1-phenylbutan-1-one
(2r)
Yield : 66% (Method B); M.P. : 69-70 °C; 1H NMR (CDCl3) δ =
3.58 (dd, J = 4.10, 17.73 Hz, 1H), 3.68 (dd, J = 9.12, 17.73 Hz,
1H), 3.80 (s, 3H), 4.19-4.27 (m, 1H), 6.83-6.85 (m, 1H), 6.93 (s,
105 1H), 6.98 (d, J = 22.70 Hz, 1H), 7.25 (t, J = 8.16 Hz, 1H), 7.46
(m, 2H), 7.57 (m, 1H), 7.93 (m, 2H); 13C NMR (CDCl3) δ =
38.28, 44.77 (q, J = 27.54 Hz), 55.21, 113.39, 115.18, 121.29,
126.91 (q, J = 284.09 Hz), 128.04, 128.71, 129.65, 133.53,
136.05 (q, J = 1.63 Hz), 136.32, 159.65, 195.24; 19F NMR
110 (CDCl3) δ = −70.08 (d, J = 9.78 Hz, 3F); IR (KBr) 3073, 3007,
2969, 2942, 2842, 1686, 1602, 1496, 1466, 1450, 1440, 1376,
1317, 1304, 1265, 1251, 1222, 1199, 1160, 1105 cm-1.; HRMS
calcd for C17H16F3O2 (M+H) 309.1102, found 309.1109.
3,3,3-Trifluoro-1-nitro-2-phenylpropane (2n)
Yield : 45%; [α]26 = +2.8 (c = 0.85, CCl4), ee = 5% , AD-H,
D
1
Hexane : i-PrOH = 99.6 : 0.4, 0.5 mL/m (Method A); H NMR
50 (CDCl3) δ = 4.29-4.37 (m, 1H), 4.84 (dd, J = 8.98, 13.76 Hz, 1H),
4.98 (dd, J = 5.73, 13.76 Hz, 1H), 7.30-7.36 (m, 2H), 7.37-7.44
(m, 3H); 13C NMR (CDCl3) δ = 48.06 (q, J = 28.47 Hz), 73.84,
124.95 (q, J = 280.30 Hz), 128.75, 129.26, 129.57, 129.99; 19F
NMR (CDCl3) δ = −69.47 (d, J = 8.75 Hz, 3F); IR (neat) 3040,
55 2961, 1568, 1458, 1437, 1377, 1304, 1259, 1177, 1119, 1005,
984, 795, 762, 698, 665, 500 cm-1; HRMS calcd for C9H8F3NO2
(M+) 219.0507, found 219.0503.
115 4,4,4-Trifluoro-3-(4-cyanophenyl)-1-phenylbutan-1-one (2t)
1
Yield : 13% (Method B); H NMR (CDCl3) δ = 3.64 (dd, J =
3.96, 18.00 Hz, 1H), 3.70 (dd, J = 9.47, 18.00 Hz, 1H), 4.25-4.33
(m, 1H), 7.47 (t, J = 7.59 Hz, 2H), 7.52 (d, J = 8.21 Hz, 2H),
Phenyl 3,3,3-trifluoro-2-phenylsulfone (2o)
60 Yield : 27%; [α]35D= −6.1 (c = 1.09, CCl4), ee = 9%, AD-H,
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Organic & Biomolecular Chemistry
Page 8 of 9
7.57-7.64 (m, 3H), 7.91 (d, J = 7.59 Hz, 2H); 13C NMR (CDCl3)
δ = 37.99, 44.98 (q, J = 28.06 Hz), 118.25, 126.37 (q, J = 279.69
Hz), 127.99, 128.84, 129.90, 132.44, 133.04, 133.90, 135.85,
139.81, 194.60; 19F NMR (CDCl3) δ = −69.71 (d, J = 9.78 Hz,
3F); IR (neat) 3063, 2927, 2231, 1691, 1597, 1581, 1507, 1449,
1421, 1369, 1307, 1257, 1225, 1159, 1108, 1066, 1022, 1002,
961, 925 cm-1.
Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics
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Determination of the absolute stereochemistry
10 To a suspension of lithium aluminium hydride (19 mg, 0.50
mmol) in THF (2 mL) was dropwise added a THF solution of 2a
(69 mg, 0.25 mmol) at 0 °C. The reaction mixture was stirred at
that temperature for 1 h, and then the reaction was quenched with
sturated aqueous NH4Cl. The whole was extracted with EtOAc
15 three times. The combined organic layers were dried over
anhydrous Na2SO4, filtered, and concentrated in vacuo. The
residue was purified by silica gel column chromatography to give
the corresponding alcohols 3a as a diastereomeric mixture in a
ratio of 1 : 1 (57 mg, 0.20 mmol, 81% yield).
75
80
20 To a suspension of CuSO4-SiO2 (136 mg)21 in hexane (2 mL) was
added the alcohols 4a (56 mg, 0.20 mmol) at room temperature.
Then the reaction was refluxed for 1 h. After the reaction was
allowed to cool to roomtemperature, the mixture was fitered, and
concentrated in vacuo. The residue was purified by silica gel
25 column chromatography to afford the dehydrated product 4a
(known compound) in 26% yield (14 mg, 0.052 mmol).
(8)
85
90
Acknowledgment
30 We greatly acknowledge TOSOH F-TECH, INC. for supplying
trifluoroacetaldehyde ethyl hemiacetal and ethyl 4,4,4-
trifluorocrotonate.
95
References and notes
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Organic & Biomolecular Chemistry
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Lewis acid to promote the isomerization. However, the
30
detailed reaction mechanism for the isomerization
remains unclear at present and an exact explanation for
the mechanism awaits further investigation.
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