Organocatalytic asymmetric direct aldol reactions of trifluoroacetaldehyde ethyl hemiacetal with aromatic methyl ketones

Article abstract of DOI:10.1021/jo200020z

The organocatalytic asymmetric direct aldol reaction of trifluoroacetaldehyde ethyl hemiacetal with aromatic methyl ketones in the presence of a catalytic amount of (S)-5-(pyrrolidin-2-yl)-1H-tetrazole in dichloroethane at 40 °C proceeds smoothly to produ

Full text of DOI:10.1021/jo200020z

NOTE
pubs.acs.org/joc
Organocatalytic Asymmetric Direct Aldol Reactions
of Trifluoroacetaldehyde Ethyl Hemiacetal with Aromatic
Methyl Ketones
Kazumasa Funabiki,* Yuya Itoh, Yasuhiro Kubota, and Masaki Matsui
Department of Materials Science and Technology, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
S Supporting Information
b
ABSTRACT: The organocatalytic asymmetric direct aldol reaction of
trifluoroacetaldehyde ethyl hemiacetal with aromatic methyl ketones in the
presence of a catalytic amount of (S)-5-(pyrrolidin-2-yl)-1H-tetrazole in
dichloroethane at 40 °C proceeds smoothly to produce (R)-4,4,4-trifluoro-
1-aryl-3-hydroxy-1-butanones in high yields with up to 90% ee.
n the decade since List and Barbas reported the L-proline-
catalyzed asymmetric direct aldol reaction of aliphatic ketones
pyrrolidine-catalyzed direct aldol reaction of CF3CHO ethyl
hemiacetal with a few aromatic methyl ketones, the trifluoro-
methylated aldol products, 4,4,4-trifluoro-1-aryl-3-hydroxy-1-bu-
tanones, were obtained only as racemic compounds.12
We report here, for the first time, the (S)-5-(pyrrolidin-2-yl)-
1H-tetrazole catalyzed asymmetric direct aldol reaction of not
only various aromatic methyl ketones but also aliphatic methyl
ketones with CF3CHO ethyl hemiacetal, which provides (R)-
4,4,4-trifluoro-1-aryl- and 1-alkyl-3-hydroxy-1-butanones in high
yields with up to 94% ee.
I
with aldehydes,1 tremendous attention has been paid to organo-
catalytic asymmetric reactions.2 Most notably, there are many
successful examples of organocatalytic asymmetric direct aldol
reactions of aliphatic ketones and aldehydes as donor carbonyl
compounds.3 However, only a few reports have described the
organocatalytic direct aldol reactions of aromatic methyl ketones
with aldehydes by chiral pyrrolidine derivatives4 or H8-BINOL-
derived phosphoric acid5 catalysts.
Catalytic asymmetric syntheses of fluorine-containing mol-
ecules have also attracted a great deal of attention in organo-
fluorine chemistry.6 Among these, trifluoroacetaldehyde
(CF3CHO)7 and trifluoromethyl ketones8 are the most attrac-
tive acceptor carbonyl compounds in the aldol reaction, like
fluorine-free aldehydes and ketones, for the construction of
R-trifluoromethylated alcohol moieties, which are commonly
found as subunits in chiral drugs or materials.9 However, in the
case of CF3CHO, it should be generated from its hemiacetal or
hydrate using an excess amount of concentrated. sulfuric acid
under a high reaction temperature just before the use of
CF3CHO,10 since CF3CHO normally exists as a hemiacetal or
hydrate due to the strong electron-withdrawing property of the
trifluoromethyl group. Moreover, CF3CHO must be handled
carefully because of its troublesome properties such as the fact
that it is a gas at room temperature, is very miscible with
moisture, and is highly reactive, leading to self-polymerization.
Recently, we11 and Yamamoto4a have developed organocata-
lytic asymmetric direct aldol reactions of CF3CHO ethyl
hemiacetal with acetone and cyclic ketones, to produce 5,5,5-
trifluoro-4-hydroxypentan-2-one and 2-(2,2,2-trifluoro-1-hydro-
xyethyl)cycloalkanes in good yields with high diastereoselectiv-
ities and enantioselectivities. Notably, these reactions do not
require a step for the generation of CF3CHO, in contrast to
other methods for the catalytic asymmetric aldol reaction of
CF3CHO.7 However, these organocatalytic asymmetric direct
aldol reactions of CF3CHO hemiacetal include only limited
examples of aliphatic ketones.4a,11 Although Gong reported a
The direct asymmetric aldol reaction of 1-phenylethanone
(acetophenone) (2a) with 3 equiv of CF3CHO ethyl hemiacetal
1a in the presence of 30 mol % of (S)-5-(pyrrolidin-2-yl)-1H-
tetrazole (3a) in dichloroethane (ClCH2CH2Cl) at 40 °C for 7 d
gave (R)-4,4,4-trifluoro-3-hydroxy-1-phenyl-1-butanone (4a) in
88% yield with 86% ee (Table 1, entry 2). The results of these
reactions under various conditions are summarized in Table 1.
The direct aldol reaction at room temperature gave the aldol
product 4a in only 24% yield with the same enantioselectivity
(entry 1). A decrease in the amount of catalyst 3a to 5 mol %
resulted in a significant decrease in the yield (45%) with a similar
enantioselectivity (entry 3). The reaction of hemiacetal 1a with
acetophenone 2a at reflux temperature for a shorter reaction time
(3 d) gave the aldol product 4a in 20% yield with very low
enantioselectivity (66% ee) (entry 4). Other solvents, such as
hexane, toluene, and acetonitonile (MeCN), did not give better
results than ClCH2CH2Cl (entries 5ꢀ7). Dimethyl formamide
(DMF) gave a much lower yield with a lower enantioselectivity
than the other solvents (entry 8). The reaction by the use of other
organocatalysts, such as L-proline (3b) and L-prolinamide (3c),
did not occur at all due to their weaker acidic protons of the
carboxyl and amide groups compared to that of the tetrazole
group.13
Scheme 1 summarizes the organocatalytic direct asymmetric
aldol reactions of the hemiacetal of CF3CHO 1a with various
Received: January 6, 2011
Published: March 17, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo200020z J. Org. Chem. 2011, 76, 3545–3550
|

The Journal of Organic Chemistry
NOTE
Table 1. Screening of the Reaction Conditions
Scheme 1. Organocatalytic Direct Asymmetric Aldol
Reactions of CF3CHO Hemiacetal 1a with Various Methyl
Ketones 2
entrya catalyst
solvent
conditions yieldb(%) (R:S, % ee)c
1
2
3a
3a
3ad
3a
3a
3a
3a
3a
3b
3c
ClCH2CH2Cl rt, 7 d
24
88
45
20
60
50
54
44
0
(93:7, 86)
(93:7, 86)
(91:9, 82)
(83:13, 66)
(90:10, 80)
(91:9, 82)
(92:8, 84)
(82:18, 64)
ClCH2CH2Cl 40 °C, 7 d
ClCH2CH2Cl 40 °C, 7 d
ClCH2CH2Cl reflux, 3 d
3
4
5
hexane
toluene
MeCN
DMF
40 °C, 7 d
40 °C, 7 d
40 °C, 7 d
40 °C, 7 d
6
7
8
9
ClCH2CH2Cl 40 °C, 7 d
ClCH2CH2Cl 40 °C, 7 d
10
0
a All of the reactions were carried out with trifluoroacetaldehyde ethyl
hemiacetal la (1.5 mmol) and acetophenone 2a (0.5 mmol) in solvent
(1 mL). b Yields of isolated products. c Determined by HPLC. d 5 mol %
of 3a was used.
aromatic, heteroaromatic, and aliphatic methyl ketones 2 under
the optimized conditions. The reaction of the hemiacetal 1a with
aromatic methyl ketones 2bꢀg, which have not only various
substituents on the phenyl group, such as methyl, methoxy,
fluoro, chloro, and nitro groups at the 4- and 3-positions, but also
naphthyl and biphenyl groups, afforded (R)-4,4,4-trifluoro-1-
aryl-3-hydroxy-1-butanones (4bꢀg,i,j) in 61ꢀ83% yields with
82ꢀ90% ee. Although use of the ketone 2h with a 2-methylphe-
nyl group provided the aldol product 4h in only 19% yield with
86% ee under the optimized reaction conditions, probably due to
the steric hindrance of the methyl group at 2-position on the
phenyl group, the reaction of the ketone 2h in the presence of
100 mol % of (S)-5-(pyrrolidin-2-yl)-1H-tetrazole (3a) pro-
ceeded smoothly to give 4h in good yield (61%) but with slightly
lower ee (79% ee). A couple of methyl ketones with heteroaro-
matic groups, such as 2-furyl and 2-pyridyl groups, also partici-
pated in the organocatalytic direct asymmetric aldol reactions
with the hemiacetal 1a under the optimized conditions to
produce 4,4,4-trifluoro-1-(2-furyl- and 2-pyridyl-)-3-hydroxy-1-
butanones (4k,l) in 60ꢀ87% yields with 64ꢀ86% ee. The
reaction of CF3CHO ethyl hemiacetal 1a with 1-cyclohexyletha-
none (2m) and 4-phenylbutan-2-one (2n) also proceeded
smoothly to give 1-cyclohexyl-4,4,4-trifluoro-3-hydroxybutan-1-
one (4m) in 85% yield with the highest enantioselectivity (94%
ee) due to the bulkiness of the cyclohexyl group and 6,6,6-
trifluoro-5-hydroxy-1-phenylhexan-3-one (4n) in 76% yield with
very low enantioselectivity (44% ee), without formation of the
regioisomer 5,5,5-trifluoro-4-hydroxy-3-phenethylpentan-2-one.
Notice that (S)-5-(pyrrolidin-2-yl)-1H-tetrazole (3a)-cata-
lyzed direct asymmetric aldol reactions of the hemiacetal of
CF3CHO 1a with cyclohexanone (2o) smoothly occurred in
much shorter reaction time (3 h) to give the corresponding aldol
product 4o in 89% yield with highly diastereo- (88% de) and
enantioselectivity (>99% ee). The reaction with 2-methyl-1-
a All of the reactions were carried out with CF3CHO enthyl hemiacetal
1a (1.5 mmol), ketone 2 (0.5 mmol), and organocatalyst 3a (30 mol%)
in dichloroethane (1 ml). b Yields of isolated products. c Determined by
HPLC. d Organocatalyst 3a (100 mol%) was used. e Determined by GC.
f Carried out for 3h.
phenylpropan-1-one (2p) as an R,R-disubstituted ketone did
not occur at all, and the ketone 2p was recovered in
quantitative yield.
The results with CF3CHO hydrate 1b, difluoroacetaldehyde
(CHF2CHO) ethyl hemiacetal 1c, and pentafluoropropionalde-
hyde (CF3CF2CHO) hydrate 1d are given in Scheme 2.
The use of CF3CHO hydrate 1b and CF3CF2CHO hydrate 1d
gave yields lower (46ꢀ60%) than that of the hemiacetal of
CF3CHO 1a with almost the same enantioselectivities (84ꢀ86%
ee). The lower yields are probably due to the presence of a large
amount of water. CHF2CHO ethyl hemiacetal 1c also reacts
with acetophenone 2a in the presence of the asymmetric
organocatalyst 3a under the optimized reaction conditions to
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NOTE
Scheme 2. Organocatalyst 3a-Catalyzed Asymmetric Direct
Aldol Reactions of Other Fluoroalkylaldehyde Hemiacetal
and Hydrates 1b,c,d with Acetophenone 2a
Figure 2. Proposed transition state.
Scheme 3. Microwave-Assisted Organocatalyst 3a-Catalyzed
Asymmetric Direct Aldol Reaction of CF3CHO Hemiacetal 1a
with Methyl Ketones 2
comparison to the optical rotation of 4a, stereochemical assign-
ments of the stereogenic center of other aldol products 4, 5, and 6
were made as R.
A proposed reaction mechanism is as follows (Figure 1). (S)-
5-(Pyrrolidin-2-yl)-1H-tetrazole (3a) reacts with methyl ke-
tones 2 to give chiral enamine. The reaction of the enamine with
CF3CHO hemiacetal gives the ammonium alchoxide, followed
by elimination of the ethoxide, which leads to the in situ gene-
ration of CF3CHO.17CF3CHO reacts with regenerated enam-
ine 2 through the reaction of iminium ion with the ethoxide via
successive asymmetric carbonꢀcarbon bond formation to
produce the intermediate. Hydrolysis of the intermediate gives
(R)-4,4,4-trifluoro-1-aryl- or 1-alkyl-3-hydroxy-1-butanones
(4) with high enantioselectivities and asymmetric organo-
catalyst 3a.
As described in Figure 2, the in situ generated CF3CHO reacts
with the chiral enamine through the transition state (TS-1).
According to the literature, in TS-1 it is important that (1) there
is an antiperiplanar relationship between the trifluoromethyl
group and the carbonꢀcarbon double bond of enamine, due to
the electrostatic interaction of the trifluoromethyl group14 and
(2) there is hydrogen bonding between the oxygen atom of
CF3CHO and the hydrogen atom of the tetrazole group.18
Finally, to reduce the reaction time, a microwave-assisted
organocatalytic asymmetric direct aldol reaction was examined
(Scheme 3).
Figure 1. Catalytic cycle of 3a.
give (R)-4,4-difluoro-3-hydroxy-1-phenylbutan-1-one (5a) in
52% yield with similar enantioselectivity (86% ee). The low yield
seems to be due to the weak electron-withdrawing property of
the difluoromethyl group or the higher LUMO level of
CHF2CHO, compared with CF3CHO. In fact, the (S)-
5-(pyrrolidin-2-yl)-1H-tetrazole (3a)-catalyzed direct aldol reac-
tion of ethyl glyoxalate (EtO2CCHO), which has a higher
LUMO level than CF3CHO,14 with the acetophenone 2a under
the same optimized reaction conditions gives only a trace amount
of the product with the quantitative recovery of 2a.
The stereogenic center of 4,4,4-trifluoro-1-phenyl-3-hydroxy-
1-butanones (4a), which was generated by (S)-5-(pyrrolidin-2-
yl)-1H-tetrazole (3a)-catalyzed direct asymmetric aldol reactions
of the hemiacetal of CF3CHO 1a, was determined as R by the
comparison to the reported values such as the optical rotation15
and the retention time of HPLC using a chiral stationary phase.16
In the literature,16 the absolute configuration of 4,4,4-trifluoro-1-
phenyl-3-hydroxy-1-butanones (4a) was established by single
crystal X-ray crystallography. The absolute configuration of
6,6,6-trifluoro-5-hydroxy-1-phenylhexan-3-one (4n) was also
determined by the optical rotation and comparison to the
reported value.15 On the basis of not only these results but also
Surprisingly, the organocatalytic asymmetric direct aldol reac-
tion of the CF3CHO hemiacetal 1a with the ketone 2a under
microwave heating conditions (multimode, 50 W, preset temp
80 °C, maximum temp 85 °C) in a shorter reaction time (3 h)
proceeded smoothly to give the aldol product 4a in 64% yield
with a slightly lower enantioselectivity (80% ee). The use of
DMF as a solvent in the microwave-assisted reaction was not
effective, giving only trace amount of 4a. The microwave-assisted
direct aldol reaction of 1a with other ketones, such as 2c,k
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NOTE
carrying the 4-methoxyphenyl and 2-furyl groups, gave the
corresponding products 4c,k in 38% and 53% yields with 80%
ee and 60% ee, respectively. The reason for the reduction in time
with a slightly lower enantioselectivity by microwave heating is
not yet clear at the present time.19
3F). HRMS (EI) Found: m/z 218.0553. Calcd for C10H9F3O2: M,
218.0555. Anal. Found: C, 54.99; H, 4.21. Calcd: C, 55.05; H, 4.16.
(R)-4,4,4-Trifluoro-3-hydroxy-1-p-tolylbutan-1-one (4b).
Rf 0.30 (dichloromethane); mp 66.0ꢀ67.7 (87% ee (R)),
108.4ꢀ108.8 (racemate, hexane/ethyl acetate); IR (KBr) 1682
(CdO), 3464 (OH) cmꢀ1; [R]18 = þ21.0° (88% ee (R), c = 1.4,
In conclusion, we have developed an organocatalytic asym-
metric direct aldol reaction of CF3CHO hemiacetal 1a with
various aromatic and aliphatic methyl ketones 2 to produce (R)-
4,4,4-trifluoro-1-aryl- and 1-alkyl-3-hydroxy-1-butanones (4) in
high yields with up to 94% ee. In this method, a single
manipulation includes multiple steps, such as (1) the ready for-
mation of enamine from aromatic and aliphatic methyl ketones,
(2) the enamine-assisted in situ generation of CF3CHO,17 (3)
successive asymmetric carbonꢀcarbon bond-formation reaction
of CF3CHO, and (4) hydrolysis of the intermediates, to give not
only (R)-4,4,4-trifluoro-1-aryl- or 1-alkyl-3-hydroxy-1-butanones
(4) with high enantioselectivities but also reproduction of
asymmetric organocatalyst. The present method is the first
example of the organocatalytic asymmetric direct aldol reaction
of CF3CHO hemiacetal 1a with various aromatic methyl ketones
and offers several advantages, such as no need for a step to
generate CF3CHO, the use of only a catalytic amount of
asymmetric organocatalyts, and no need for complicated
manipulations.
589
CHCl3); HPLC retention time (DAICEL CHIRALCEL AS-H), tR
=
1
11.4 min ((S)-isomer), tR = 17.5 min ((R)-isomer) min; H NMR
(CDCl3) δ 2.31 (s, 3H), 3.14 (dd, J = 17.69, 2.42 Hz, 1H), 3.25 (dd, J =
17.69, 9.54 Hz, 1H), 4.01 (br s, 1H), 4.57ꢀ4.64 (m, 1H), 7.16 and 7.74
(AB quartet, J = 8.09 Hz, 4H); 13C NMR (CDCl3) δ 21.6 (s), 38.1 (s),
66.8 (q, J = 32.0 Hz), 124.9 (q, J = 280.7 Hz), 128.3 (s), 129.5 (s), 133.5
(s), 145.2 (s), 197.1 (s); 19F NMR (CDCl3) δ ꢀ1.4 (d, J = 6.9 Hz, 3F).
HRMS (EI) Found: m/z 232.0710. Calcd for C11H11F3O2: M,
232.0711. Anal. Found: C, 56.83; H, 4.72. Calcd: C, 56.90; H, 4.77.
(R)-4,4,4-Trifluoro-3-hydroxy-1-(4-methoxyphenyl)butan-
1-one (4c). Rf 0.18 (dichloromethane); mp 77.1ꢀ79.1 °C (85% ee
(R)), 104.5ꢀ105.1 (racemate, hexane/ethyl acetate); IR (KBr) 1678
(CdO), 3460 (OH) cmꢀ1; [R]17 = þ25.5° (85% ee (R), c = 1.1,
589
CHCl3); HPLC retention time (DAICEL CHIRALCEL OD-H),
tR =24.8 min ((R)-isomer), tR = 33.4 min ((S)-isomer); 1H NMR
(CDCl3) δ 3.24 (dd, J = 17.45, 2.54 Hz, 1H), 3.34 (dd, J = 17.45, 9.42
Hz, 1H), 3.88 (s, 3H), 3.99 (br s, 1H), 4.67ꢀ4.70 (m, 1H), 6.95 and 7.93
(AB quartet, J = 9.18 Hz, 4H); 13C NMR (CDCl3) δ 37.7 (s), 55.5 (s),
67.0 (q, J = 32.0 Hz), 114.0 (s), 124.9 (q, J = 280.6 Hz), 129.0 (s), 130.6
(s), 164.3 (s), 196.0 (s); 19F NMR (CDCl3) δ ꢀ1.4 (d, J = 6.9 Hz, 3F).
HRMS (EI) Found: m/z 248.0663. Calcd for C11H11F3O3: M, 248.0660.
Anal. Found: C, 53.11; H, 4.44. Calcd: C, 53.23; H, 4.47.
’ EXPERIMENTAL SECTION
1
(R)-4,4,4-Trifluoro-1-(4-fluorophenyl)-3-hydroxybutan-1-
one (4d). Rf 0.25 (dichloromethane); mp 45.1ꢀ46.5 (83% ee (R)),
74.0ꢀ75.2 (racemate, CH2Cl2); IR (KBr) 1686 (CdO), 3472
(OH) cmꢀ1; [R]17589 = þ26.7° (83% ee (R), c = 1.3, CHCl3); HPLC
retention time (DAICEL CHIRALCEL AS-H), tR = 12.1 min ((S)-
isomer), tR = 17.8 min ((R)-isomer); 1H NMR (CDCl3) δ 3.17 (dd, J =
17.57, 2.17 Hz, 1H), 3.31 (dd, J = 17.57, 9.54 Hz, 1H), 3.78 (br s, 1H),
4.60ꢀ4.67 (m, 1H), 7.08 (dd, J = 8.75, 8.69 Hz, 2H), 7.91 (dd, J = 8.75,
5.19 Hz, 2H); 13C NMR (CDCl3) δ 38.3 (s), 66.7 (q, J = 32.2 Hz), 116.0
(d, J = 22.1 Hz), 124.8 (q, J = 280.7 Hz), 131.0 (d, J = 9.8 Hz), 132.5 (d,
J = 3.3 Hz), 166.3 (d, J = 256.4 Hz), 195.8 (s); 19F NMR (CDCl3)
δ ꢀ1.6 (d, J = 6.9 Hz, 3F), ꢀ25.36ꢀ ꢀ25.43 (m, 1F). HRMS (EI)
Found: m/z 236.0458. Calcd for C10H8F4O2: M, 236.0460.
Measurement. H NMR spectra were measured at 400 MHz in
deuterochloroform (CDCl3) or hexadeuteroacetone (CD3COCD3)
solutions with tetramethylsilane (Me4Si) as an internal standard. 13C
NMR spectra were obtained at 100 MHz in CDCl3 or CD3COCD3
solution with Me4Si as an internal standard. 19F NMR spectra were
recorded at 376 or 372 MHz in CDCl3 or CD3COCD3 solutions using
trifluoroacetic acid as an external standard.
Materials. Pure products were isolated by column chromatography
using Wakogel C-200 (100ꢀ200 mesh) or silica gel 60 (spherical,
40ꢀ50 μm). Analytical TLC was performed on Merck precoated (0.25
mm) silica gel 60 F254 plates. Hexane, 1,2-dichloroethane, toluene,
MeCN, and DMF were distilled over calcium hydride under argon or
purchased from Kanto Chemical Co. All chemicals were of reagent grade
and, if necessary, were purified in the usual manner prior to use.
Typical Procedure. A mixture of (S)-5-(pyrrolidin-2-yl)-1H-tetra-
zole (3a) (96 wt %, 0.022 g, 0.15 mmol), acetophenone 2a (0.060 g, 0.5
mmol), and CF3CHO ethyl hemiacetal 1a (96 wt %, 0.225 g, 1.5 mmol)
in ClCH2CH2Cl (1 mL) was stirred at 40 °C for 7 d. The reaction
mixture was quenched with brine (50 mL), extracted with dichloro-
methane (30 mL ꢁ 3), dried over Na2SO4, and concentrated under
vacuum to give the residue. Purification of the residue by flash
chromatography on silica gel (dichloromethane) gave 4,4,4-trifluoro-
3-hydroxy-1-phenyl-1-butanone (4a) (88%, 0.096 g) in an R:S ratio
of 93:7.
(R)-1-(4-Chlorophenyl)-4,4,4-trifluoro-3-hydroxybutan-1-
one (4e). Rf 0.33 (dichloromethane); mp 60.3ꢀ62.0 (84% ee (R)),
109.3ꢀ110.0 (racemate, hexane/ethyl acetate); IR (KBr) 1690 (CdO),
3464 (OH) cmꢀ1; [R]17 = þ14.3° (84% ee (R), c = 1.2, CHCl3);
589
HPLC retention time (DAICEL CHIRALCEL AS-H), tR = 12.2 min
1
((S)-isomer), tR = 15.8 min ((R)-isomer); H NMR (CDCl3) δ 3.17
(dd, J = 17.69, 2.17 Hz, 1H), 3.30 (dd, J = 17.69, 9.30 Hz, 1H),
3.66ꢀ3.72 (m, 1H), 4.61ꢀ4.69 (m, 1H), 7.18 and 7.86 (AB quartet, J =
7.18 Hz, 4H); 13C NMR (CDCl3) δ 38.3 (s), 66.7 (q, J = 32.2 Hz), 124.8
(q, J = 280.5 Hz), 129.2 (s), 129.6 (s), 134.3 (s), 140.7 (s), 196.1 (s); 19F
NMR (CDCl3) δ ꢀ1.5 (d, J = 6.9 Hz, 3F). HRMS Found: m/z
254.0138. Calcd for C10H837ClF3O2: M, 254.0135. Anal. Found: C,
47.54 ; H, 3.30. Calcd: C, 47.55; H, 3.19.
4,4,4-Trifluoro-3-hydroxy-1-phenyl-1-butanone (4a)15. Rf
0.2 (dichloromethane); mp 43.0ꢀ45.0 °C (86% ee (R)), 79.4ꢀ79.8 °C
(racemate, hexane/ethyl acetate); IR (KBr) 1694 (CdO), 3422
(R)-4,4,4-Trifluoro-3-hydroxy-1-(4-nitrophenyl)butan-1-
one (4f). Rf 0.20 (dichloromethane); mp 69.7ꢀ71.5 °C (86% ee (R)),
71.3ꢀ71.7 °C (racemate, hexane/ethyl acetate); IR (KBr) 1701
(OH) cmꢀ1; [R]17589 þ26.3° (86% ee (R), c = 1.0, CHCl3), [R]32
589
þ1.9° (84% ee (R), c = 1.5, MeOH), (ref [R]D þ2.6° (92% ee (R), c =
1.7, MeOH));14 HPLC retention time (DAICEL CHIRALCEL OD-H),
(CdO), 3487 (OH) cmꢀ1; [R]20 = þ25.2° (86% ee (R), c = 1.2,
589
1
tR = 10.3 min ((S)-isomer), tR = 11.6 min ((R)-isomer); H NMR
CHCl3); HPLC retention time (DAICEL CHIRALCEL OD-H), tR =
51.4 min ((R)-isomer), tR = 55.9 min ((S)-isomer); 1H NMR (CDCl3)
δ 3.24 (d, J = 17.63 Hz, 1H), 3.38ꢀ3.45 (m, 2H), 4.68 (br s, 1H), 8.07
and 8.27 (AB quartet, J = 8.45 Hz, 4H); 13C NMR (CDCl3) δ 39.0 (s),
66.6 (q, J = 32.5 Hz), 124.0 (s), 124.6 (q, J = 280.7 Hz), 129.3 (s), 140.3
(s), 150.8 (s), 195.6 (s); 19F NMR (CDCl3) δ ꢀ1.5 (d, J = 6.9 Hz, 3F).
(CDCl3) δ 3.33 (dd, J = 17.93, 3.17 Hz, 1H), 3.39 (dd, J = 17.93, 8.79
Hz, 1H), 3.74 (s, 1H), 4.69ꢀ4.75 (m, 1H), 7.49ꢀ7.53 (m, 2H),
7.62ꢀ7.66 (m, 1H), 7.97ꢀ7.99 (m, 2H); 13C NMR (CDCl3) δ 38.3
(s), 66.8 (q, J = 32.0 Hz), 124.8 (q, J = 280.7 Hz), 128.2 (s), 128.8 (s),
134.1 (s), 136.0 (s), 197.5 (s); 19F NMR (CDCl3) δ ꢀ1.5 (d, J = 6.9 Hz,
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The Journal of Organic Chemistry
NOTE
HRMS (EI) Found: m/z 263.0403. Calcd for C10H8F3NO4: M,
263.0405. Anal. Found: C, 45.68; H; 3.13; N, 5.41. Calcd for
C11H11F3O2: C, 45.64; H; 3.06; N; 5.32.
isomer), tR = 20.1 min ((R)-isomer); 1H NMR (CDCl3) δ 3.08 (d, J =
17.27 Hz, 1H), 3.21 (d, J = 17.27, 9.42 Hz, 1H), 3.65ꢀ3.69 (m, 1H),
4.60 (br s, 1H), 6.52 (br s, 1H), 7.22ꢀ7.23 (m, 1H), 7.57 (br s, 1H); 13C
NMR (CDCl3) δ 38.1 (s), 66.5 (q, J = 32.2 Hz), 112.7 (s), 118.7 (s),
124.7 (q, J = 281.0 Hz), 147.4 (s), 151.9 (s), 185.8 (s); 19F NMR
(CDCl3) δ ꢀ4.0 (d, J = 6.9 Hz, 3F). HRMS (ESI) Found: m/z
231.0241. Calcd for C8H7F3NaO3: M þ Na, 231.0245.
(R)-4,4,4-Trifluoro-3-hydroxy-1-m-tolylbutan-1-one (4g).
Rf 0.33 (dichloromethane); mp 44.8ꢀ46.3 °C (87% ee (R)),
81.1ꢀ81.6 °C (racemate, hexane/ethyl acetate); IR (KBr) 1682
(CdO), 3480 (OH) cmꢀ1; [R]18 = þ22.9° (87% ee (R), c = 1.7,
589
CHCl3); HPLC retention time (DAICEL CHIRALCEL OD), tR = 11.1
(R)-4,4,4-Trifluoro-3-hydroxy-1-(pyridin-2-yl)butan-1-
one (4l). Rf 0.10 (dichloromethane); mp 46.0ꢀ47.8 °C (86% ee (R),
CHCl2), 81.7ꢀ85.2 °C (racemate); IR (KBr) 1701 (CdO), 3456
(OH) cmꢀ1; [R]19589 = þ16.2° (86% ee (R), c = 1.7, CHCl3); HPLC
retention time (DAICEL CHIRALCEL AD-H), tR = 18.9 min ((R)-
isomer), tR = 22.8 min ((S)-isomer); 1H NMR (CD3COCD3) δ 3.24
(dd, J = 17.20, 2.42 Hz, 1H), 3.62 (dd, J = 17.20, 9.78 Hz, 1H),
4.62ꢀ4.69 (m, 1H), 5.41 (br s, 1H), 7.51 (d, J = 4.83 Hz, 1H),
7.84ꢀ7.90 (m, 2H), 8.59 (d, J = 4.10 Hz, 1H); 13C NMR
(CD3COCD3) δ 39.3 (s), 66.9 (q, J = 31.4 Hz), 122.4 (s), 126.8 (q,
J = 281.0 Hz), 128.6 (s), 138.2 (s), 150.0 (s), 153.7 (s), 197.7 (s); 19F
NMR (CD3COCD3) δ ꢀ1.7 (d, J = 6.9 Hz, 3F). HRMS (ESI) Found:
m/z 242.0398. Calcd for C9H8F3NNaO2: M þ Na, 242.0405.
1
min ((S)-isomer), tR = 13.2 min ((R)-isomer); H NMR (CDCl3) δ
2.31 (s, 3H), 3.17 (dd, J = 17.87, 2.42 Hz, 1H), 3.30 (dd, J = 17.87, 9.42
Hz, 1H), 3.90 (br s, 1H), 4.57ꢀ4.66 (m, 1H), 7.26 (t, J = 7.49 Hz, 1H),
7.32 (d, J = 7.49 Hz, 1H), 7.64ꢀ7.66 (m, 2H); 13C NMR (CDCl3) δ
21.2 (s), 38.3 (s), 66.9 (q, J = 32.2 Hz), 124.8 (q, J = 280.5 Hz), 125.4 (s),
128.7 (s), 134.86 (s), 134.87 (s) 136.0 (s), 138.7 (s), 197.7 (s); 19F
NMR (CDCl3) δ ꢀ1.5 (d, J = 6.9 Hz, 3F); MS (EI) m/z (rel intensity)
232 (Mþ; 11.0). Anal. Found: C, 56.67; H, 5.04. Calcd for C11H11F3O2:
C, 56.90; H, 4.77.
(R)-4,4,4-Trifluoro-3-hydroxy-1-o-tolylbutan-1-one (4h).
Rf 0.40 (dichloromethane); mp 65.4ꢀ66.5 °C (79% ee (R)),
81.1ꢀ81.6 °C (racemate, hexane/ethyl acetate); IR (KBr) 1685
(CdO), 3410 (OH) cmꢀ1; [R]28 þ20.4° (79% ee (R), c = 0.6,
(R)-1-Cyclohexyl-4,4,4-trifluoro-3-hydroxybutan-1-one
589
2
(4m). Rf 0.28 (dichloromethane); mp oil (95% ee (R), CH Cl2),
CHCl3); HPLC retention time (DAICEL CHIRALCEL OD), tR = 12.5
1
40.9ꢀ41.6 °C (racemate, hexane/ethyl acetate); IR (KBr) 1682
min ((S)-isomer), tR = 16.6 min ((R)-isomer); H NMR (CDCl3) δ
(CdO), 3464 (OH) cmꢀ1; [R]18 = þ23.9° (95% ee (R), c = 1.2,
2.47 (s, 3H), 3.19 (dd, J = 17.63, 3.02 Hz, 1H), 3.29 (dd, J = 17.63, 8.81
Hz, 1H), 3.48 (br s, 1H), 4.60 (m, 1H), 7.21ꢀ7.26 (m, 2H), 7.37 (t, J =
7.22 Hz, 1H), 7.14 (d, J = 7.22 Hz, 1H); 13C NMR (CDCl3) δ 21.5 (s),
40.6 (s), 67.1 (q, J = 32.0 Hz), 124.4 (q, J = 281.3 Hz), 125.9 (s), 129.1
(s), 132.3 (s), 132.4 (s), 136.2 (s), 139.1 (s), 200.8 (s); 19F NMR
(CDCl3) δ ꢀ1.4 (d, J = 6.9 Hz, 3F). HRMS (EI) Found: m/z 232.0711.
Calcd for C11H11F3O2: M, 232.0711. Anal. Found: C, 56.94; H, 4.77.
Calcd: C, 56.90; H, 4.77.
589
CHCl3); GC retention time (VARIAN CP-CHIRALSIL-D-VAL), tR =
13.9 min ((R)-isomer), tR = 14.2 min ((S)-isomer); 1H NMR (CDCl3) δ
1.16ꢀ1.41 (m, 5H), 1.67ꢀ1.90 (m, 5H), 2.78 (dd, J = 11.89, 2.66 Hz,
1H), 2.87 (dd, J = 11.89, 9.42 Hz, 1H), 3.93 (br s, 1H), 4.45ꢀ4.53 (m,
1H); 13C NMR (CDCl3) δ 25.31 (s), 25.33 (s), 25.6 (s), 27.9 (s), 28.0
(s), 39.9 (s), 51.3 (s), 66.3 (q, J = 32.2 Hz), 124.8 (q, J = 280.7 Hz), 211.9
(s); 19F NMR (CDCl3) δ ꢀ2.0 (d, J = 6.9 Hz, 3F); MS (EI) m/z (rel
intensity) 224 (Mþ; 3.7). Anal. Found: C, 53.54; H, 6.64. Calcd for
C10H15F3O2: C, 53.57; H, 6.74.
(R)-4,4,4-Trifluoro-3-hydroxy-1-(naphthalen-2-yl)butan-
1-one (4i). Rf 0.29 (hexane/ethyl acetate =7/3); mp 83.5ꢀ85.2 °C
(83% ee (R), CHCl2), 93.1ꢀ94.9 °C (racemate, hexane/ethyl acetate);
IR (KBr) 1670 (CdO), 3395 (OH) cmꢀ1; [R]19589 = þ17.4° (83% ee
(R), c = 1.2, CHCl3); HPLC retention time (DAICEL CHIRALCEL
(R)-6,6,6-Trifluoro-5-hydroxy-1-phenylhexan-3-one (4n)15.
Rf 0.23 (hexane/ethyl acetate =9/1); mp 66.6ꢀ68.5 °C (44% ee (R)),
72.8ꢀ73.4 °C (racemate, hexane/ethyl acetate); IR (KBr) 1717 (CdO),
3460 (OH) cmꢀ1; [R]19589 = þ10.7° (44% ee (R), c = 1.5, CHCl3); HPLC
retention time (DAICEL CHIRALCEL AS-H), tR =9.5min((S)-isomer), tR
=10.5min((R)-isomer);1HNMR(CDCl3) δ2.56ꢀ2.83 (m, 6H), 3.79 (br
s, 1H), 4.38ꢀ4.42 (m, 1H), 7.06ꢀ7.08 (m, 1H), 7.10ꢀ7.12 (m, 1H),
7.17ꢀ7.21 (m, 1H); 13C NMR (CDCl3) δ 29.3 (s), 42.1 (s), 45.0 (s), 66.5
(q, J= 32.2 Hz), 124.6 (q, J= 280.7 Hz), 126.3 (s), 128.2 (s), 128.6 (s), 140.2
(s), 207.6 (s); 19F NMR (CDCl3) δ ꢀ1.8 (d, J = 6.9 Hz, 3F). HRMS (ESI)
Found: m/z 269.0763. Calcd for C12H13F3NaO2: M þ Na, 269.0765.
(S)-2-((R)-2,2,2-Trifluoro-1-hydroxyethyl)cyclohexanone
(4o). Rf 0.28 (dichloromethane); oil (>99% ee), oil (racemate); IR
(KBr) 1701 (CdO), 3437 (OH) cmꢀ1; [R]28589 = ꢀ22.4° (>99% ee
(2S, 10R), c = 1.8, CHCl3); GC retention time (InterCap CHIRAMIX),
tR = 32.6 ((2S, 10R)-isomer), tR = 33.1 ((2R, 10S)-isomer) min; 1H NMR
(CDCl3) δ 1.67ꢀ1.81 (m, 3H), 1.95ꢀ1.99 (m, 1H), 2.13ꢀ2.16 (m,
2H), 2.37ꢀ2.49 (m, 2H), 2.74ꢀ2.80 (m, 1H), 4.02ꢀ4.11 (m, 1H), 4.47
(d, J = 6.52 Hz, 1H); 13C NMR (CDCl3) δ 24.8 (s), 28.0 (s), 31.5 (q, J =
1.6 Hz), 42.9 (s), 50.3 (s), 71.6 (q, J = 30.9 Hz), 124.7 (q, J = 282.5 Hz),
129.0 (s); 19F NMR (CDCl3) δ ꢀ1.9 (d, J = 7.6 Hz, 3F). HRMS (EI)
Found: m/z 196.0711. Calcd for C8H11F3O2: M, 196.0711.
1
OD-H), tR = 13.7 min ((S)-isomer), tR = 23.7 min ((R)-isomer); H
NMR (CDCl3) δ 3.42 (dd, J = 17.81, 2.54 Hz, 1H), 3.52 (dd, J = 17.81,
9.42 Hz, 1H), 3,70 (d, J = 4.35 Hz, 1H), 4.71ꢀ4.80 (m, 1H), 7.54ꢀ7.64
(m, 2H), 7.86ꢀ7.90 (m, 2H), 7.95ꢀ8.00 (m, 2H), 8.45 (s, 1H); 13C
NMR (CDCl3) δ 38.3 (s), 67.0 (q, J = 32.2 Hz), 123.3 (s), 124.9 (q, J =
280.5 Hz), 127.0 (s), 127.8 (s), 128.7 (s), 129.0 (s), 129.7 (s), 130.3 (s),
132.3 (s), 133.2 (s), 135.9 (s), 197.4 (s); 19F NMR (CDCl3) δ ꢀ1.4 (d,
J = 6.9 Hz, 3F). HRMS (ESI) Found: m/z 291.0602. Calcd for
C14H11F3NaO2: MþNa, 291.0609.
(R)-1-(Biphenyl-4-yl)-4,4,4-trifluoro-3-hydroxybutan-1-
one (4j). Rf 0.1 (hexane/ethyl acetate =9/1); mp 129.8ꢀ132.2 °C
(86% ee (R)), 133.9ꢀ136.8 °C (racemate, hexane/ethyl acetate); IR
(KBr) 1682 (CdO), 2967 (OH) cmꢀ1; [R]30589 þ11.5° (86% ee (R),
c = 1.3, CHCl3); HPLC retention time (DAICEL CHIRALCEL OD-H),
1
tR = 13.6 min ((R)-isomer), tR = 21.3 min ((S)-isomer); H NMR
(CDCl3) δ 3.32 (dd, J = 17.75, 2.42 Hz, 1H), 3.43 (dd, J = 17.75, 9.42
Hz, 1H), 3.76 (d, J = 4.59 Hz, 1H), 4.68ꢀ4.78 (m, 1H), 7.41 (t, J = 7.12
Hz, 1H), 7.47 (t, J = 7.12 Hz, 2H), 7.62 (d, J = 7.12, 2H), 7.70 and 8.02
(AB quartet, J = 8.09 Hz, 4H); 13C NMR (CDCl3) δ 38.3 (s), 67.0 (q, J =
32.0 Hz) 124.8 (q, J = 280.2 Hz), 127.3 (s), 127.4 (s), 128.5 (s), 128.8
(s), 129.0 (s), 134.6 (s), 139.5 (s), 146.8 (s), 197.1 (s); 19F NMR
(CDCl3) δ ꢀ1.5 (d, J = 6.9 Hz, 3F). HRMS (ESI) Found: m/z
317.0761. Calcd for C16H13F3NaO2: MþNa, 317.0765.
(R)-4,4-Difluoro-3-hydroxy-1-phenylbutan-1-one (5a). Rf
0.20 (dichloromethane); oil (86% ee (R)), oil (racemate); IR (KBr)
1686 (CdO), 3460 (OH) cmꢀ1; [R]20589 = þ38.7° (86% ee (R), c =
1.3, CHCl3); HPLC retention time (DAICEL CHIRALCEL AS-H),
1
(R)-4,4,4-Trifluoro-1-(furan-2-yl)-3-hydroxybutan-1-one
(4k). Rf 0.28 (dichloromethane); oil (64% ee (R)), 47.5ꢀ48.8 °C
(racemate, hexane/ethyl acetate); IR (KBr) 1670 (CdO), 3422
(OH) cmꢀ1; [R]18589 = þ20.4° (64% ee (R), c = 1.0, CHCl3); HPLC
retention time (DAICEL CHIRALCEL AS-H), tR = 16.1 min ((S)-
tR = 17.1 min ((S)-isomer), tR = 22.5 min ((R)-isomer); H NMR
(CDCl3) δ 3.33ꢀ3.25 (m, 2H), 3.52 (d, J = 4.11 Hz, 1H), 4.40ꢀ4.51
(m, 1H), 5.90 (td, J = 55.74, 3.46 Hz, 1H),7.47ꢀ7.51 (m, 2H),
7.60ꢀ7.63 (m, 1H), 7.96ꢀ7.98 (m, 2H); 13C NMR (CDCl3) δ 37.7
(t, J = 2.9 Hz), 67.7 (dd, J = 26.2, 23.8 Hz), 115.5 (t, J = 243.7 Hz), 128.2
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NOTE
(s), 128.8 (s), 133.9 (s), 136.2 (s), 198.8 (s); 19F NMR (CDCl3)
δ ꢀ50.9 (ddd, J = 287.9, 56.0, 9.7 Hz, 1F), ꢀ53.8 (ddd, J = 287.0, 56.0,
14.1 Hz, 1F). HRMS (EI) Found: m/z 200.0620. Calcd for
C10H10F2O2: M, 200.0649.
Fluoro-organic Compounds; Soloshonok, V. A., Ed.; John Wiley & Sons:
Chichester, 2004.
(7) (a) Ishii, A.; Soloshonok, A. V.; Mikami, K. J. Org. Chem. 2000,
65, 1597. (b) Ishii, A.; Kojima, J.; Mikami, K. Org. Lett. 1999, 1, 2013.
(c) Ishii, A.; Mikami, K. J. Fluorine Chem. 1999, 97, 51. (d) Iseki, K.;
Kobayashi, Y. Chem. Pharm. Bull. 1996, 44, 2003. (e) Iseki, K.; Oishi, S.;
Kobayashi, Y. Tetrahedron 1996, 52, 71. (f) Mikami, K.; Yajima, T.;
Takasaki, T.; Matsukawa, S.; Terada, M.; Uchimaru, T.; Maruta, M.
Tetrahedron 1996, 52, 85. (g) Mikami, K.; Yajima, T.; Siree, N.; Terada,
M.; Suzuki, Y.; Kobayashi, I. Synlett 1996, 837.
(8) For selected examples, see: (a) Zhang, D.; Yuan, C. Tetrahedron
2008, 64, 2480. (b) Wang, X.-J.; Zhao, Y.; Liu, J.-T. Org. Lett. 2007,
9, 1343. (c) Song, J. J.; Xu, J.; Tan, Z.; Reeves, J. T.; Grinberg, N.; Lee,
H.; Kuzmich, K.; Feng, X.; Yee, N. K.; Senanayake, C. H. Org. Process Res.
Dev. 2007, 11, 534. (d) Qiu, L.-H.; Shen, Z.-X. ; Shi, C.-Q.; Liu, Y.-H.;
Zhang, Y.-W. Chin. J. Chem. 2005, 23, 584.
(R)-4,4,5,5,5-Pentafluoro-3-hydroxy-1-phenylpentan-1-
one (6a). Rf 0.30 (dichloromethane); mp 72.8ꢀ74.0 °C (90% ee (R)),
98.0ꢀ99.0 °C (racemate, hexane/ethyl acetate); IR (KBr) 1682
(CdO), 3406 (OH) cmꢀ1; [R]27 þ23.1° (90% ee (R), c = 1.3,
589
CHCl3); HPLC retention time (DAICEL CHIRALCEL OD), tR = 9.8
1
min ((S)-isomer), tR = 12.3 min ((R)-isomer); H NMR (CDCl3) δ
3.25 (d, J = 17.75 Hz, 1H), 3.36 (dd, J = 17.75, 9.10 Hz, 1H), 3.88 (s,
1H), 4.71ꢀ4.79 (m, 1H), 7.40 (t, J = 7.81 Hz, 2H), 7.54 (td, J = 7.81,
0.97 Hz, 1H), 7.87 (td, J = 7.81, 0.97 Hz, 2H); 13C NMR(CDCl3) δ 37.4
(s), 66.4 (dd, J = 23.5, 7.6 Hz), 113.6 (ddt, J = 256.5, 251.8, 36.6 Hz),
119.0 (qt, J = 286.0, 35.4 Hz), 128.2 (s), 128.9 (s), 134.2 (s), 136.0 (s),
198.0 (s) ; 19F NMR (CDCl3) δ ꢀ3.8 (s, 3F), ꢀ44.4 (dd, J = 276.6, 5.7
Hz, 1F), ꢀ53.0 (dd, J = 276.6, 18.7 Hz, 1F); MS (EI) m/z (rel intensity)
268 (Mþ; 1.3). Anal. Found: C, 49.28; H, 3.35. Calcd for C11H9F5O2: C,
49.26; H, 3.38.
(9) For a drug, see: Wouters, J.; Moureau, F.; Evrard, G.; Koenig,
J.-J.; Jegham, S.; George, P.; Durant, F. Bio. Med. Chem. 1999, 7, 1683
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Chem., Int. Ed. 1999, 38, 2354 and references therein.
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1950, 72, 3370. (d) Shechter, H.; Conrad, F. J. Am. Chem. Soc. 1950,
72, 3371.
(11) (a) Funabiki, K.; Yamamoto, H.; Nagaya, H.; Matsui, M.
Tetrahedron Lett. 2006, 47, 5507.(b) Funabiki, K.; Matsui, M. Current
Fluoroorganic Chemistry; Soloshonok,V., Mikami, K., Yamazaki, T.,
Welch, J. T., Honek, J. F., Eds.; ACS Symposium Series 949; Oxford
University Press/American Chemical Society: Washington, DC, 2007;
p 141.
’ ASSOCIATED CONTENT
Supporting Information. 1H and 13C NMR spectra and
S
b
enantiomer separation by HPLC or GC for 4, 5, and 6. This
material is available free of charge via the Internet at http://pubs.
acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: funabiki@gifu-u.ac.jp.
(12) Zhang, F.; Peng, Y.; Liao, S.; Gong, Y. Tetrahedron 2007,
63, 4636.
(13) Taft, R. W.; Dordwell, F. G. Acc. Chem. Res. 1988, 21, 463.
(14) Makino, M.; Iseki, K.; Fujii, K.; Oishi, S.; Hirano, T.; Kobayashi,
Y. Tetrahedron Lett. 1995, 36, 6527.
’ ACKNOWLEDGMENT
(15) Lin, J. T.; Yamazaki, T.; Kitazume, T. J. Org. Chem. 1987,
52, 3211.
(16) Ishii, A.; Kanai, M.; Higashiyama, K.; Mikami, K. Chirality 2002,
14, 709.
This work was supported in part by a Grant-in-Aid for
Scientific Research (C) (19550104) and Young Scientists (B)
(14750665) from the Japan Society for the Promotion of Science
and by the Japan Science and Technology Agency (JST) (08-
077). We are grateful to Central Glass Co., Ltd. for the gift of
CF3CHO ethyl hemiacetal as well as financial support. We thank
Professors T. Ishihara and T. Konno of the Kyoto Institute of
Technology and Dr. Tomoko Yajima of Ochanomizu University
for the HRMS measurement.
(17) (a) Funabiki, K.; Nojiri, M.; Matsui, M.; Shibata, K. Chem.
Commun. 1998, 2051. (b) Funabiki, K.; Matsunaga., K.; Matsui, M.;
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M.; Hashimoto, W.; Yamamoto, H.; Matsui, M.; Shibata, K. J. Org. Chem.
2003, 68, 2853.(d) Funabiki, K. In Fluorine-Containing Synthons; So-
loshonok, V., Ed.; ACS Symposium Series 911; Oxford University
Press/American Chemical Society: Washington, DC, 2005; p 342.
(18) For a recent review, see: Longbottom, D. A.; Franckevicius, V.;
Kumarn, S.; Oelke, A. J.; Wascholowski, V.; Ley, S. V. Aldrichimica Acta
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