B -(3,3-Difluoroallyl)diisopinocampheylborane for the enantioselective fluoroallylboration of aldehydes

Article abstract of DOI:10.1021/jo300970z

The fluoroallylboration of aldehydes with B-(3,3-difluoroallyl) diisopinocampheylborane, which was prepared via the hydroboration of 1,1-difluoroallene, provides chiral 2,2-gem-difluorinated homoallylic alcohols in good yields and 91-97% ee.

Full text of DOI:10.1021/jo300970z

Note
pubs.acs.org/joc
B‑(3,3-Difluoroallyl)diisopinocampheylborane for the
Enantioselective Fluoroallylboration of Aldehydes
P. Veeraraghavan Ramachandran,* Agnieszka Tafelska-Kaczmarek,‡ and Anamitra Chatterjee
Herbert C. Brown Center for Borane Research, Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette,
Indiana 47907-2084, United States
S
* Supporting Information
ABSTRACT: The fluoroallylboration of aldehydes with B-(3,3-difluoroallyl)-
diisopinocampheylborane, which was prepared via the hydroboration of 1,1-
difluoroallene, provides chiral 2,2-gem-difluorinated homoallylic alcohols in good
yields and 91−97% ee.
luorine substitution often alters the reactivity and reaction
iodomethylboronate16 (Scheme 1) was found to be unstable for
storage. Hence, the difluoroallylboration of benzaldehyde (5a)
1
Fmechanism of organic molecules.
Medicinal chemists
undertake this exercise to alter the biological properties of such
molecules, with the aim of identifying more potent and
bioavailable molecules.2 Geminal difluorinated aliphatic fluoro-
organic molecules are particularly attractive due to their unique
pharmacological properties.3 As part of our program involving
fluoro-organic synthesis via boranes,4 we had reported the
preparation and reactions of racemic and chiral 2-benzyloxy-
(3,3-difluoroallyl)boronates 1 and 2, respectively (Figure 1), for
the synthesis of 2,2-gem-difluorinated homoallyl alcohols and
derivatives.5
Scheme 1. Preparation of (3,3-Difluoroallyl)boronates 3 and
4
was examined with in situ generated reagents, and the optimal
conditions were identified (Table 1).
Figure 1. (3,3-Difluoroallyl)boronates.
The allylboration of benzaldehyde (5a) with 3 in THF at
room temperature, monitored by 11B NMR spectroscopy
(chemical shift change from δ 30 to 18 ppm), furnished 2,2-
difluoro-1-phenylbut-3-en-1-ol (6a) in only 15% yield. On the
basis of Lewis acid catalyzed allylboration with allylboronates,17
the reaction was examined in the presence of 10 mol %
Sc(OTf)3, which improved the yield to 43%. Raising the
temperature to reflux further improved the yield to 67%.
Increasing the catalyst loading to 20 mol % and the reaction
time to 48 h did not improve the yield. Changing the catalyst to
In(OTf)3 (10 mol %) yielded 38% of the homoallylic alcohol.
The influence of the solvent was then examined. Unlike the
benzyloxy reagent 1, the parent reagent 3 was only sparingly
soluble in pentane. The reaction failed in refluxing dichloro-
methane (48 h); refluxing in toluene decomposed the reagent.
With the standardized reaction conditions, the fluoroallylbo-
ration of additional aldehydes was carried out (Table 2).
We had also reported a low yield (≤20%) synthesis of the
parent camphanediol (3,3-difluoroallyl)boronate 45b from 2,2-
difluorovinyllithium6 and the corresponding camphanediol
iodomethylboronate.7 The importance of the products 2,2-
difluoro-1-aryl/alkylbut-3-en-1-ols as useful building blocks for
the synthesis of bioactive molecules,8 led us to re-examine the
synthesis of racemic and chiral (3,3-difluoroallyl)boronate
reagents 3 and 4. While racemic 2,2-difluoro-1-aryl/alkylbut-
3-en-1-ols have been reported via the addition of gem-
difluoroallylmetals (Si,9 In,10 Li,11 Sn,12 Zn13) to aldehydes
and ketones, to the best of our knowledge, chiral 2,2-gem-
difluorohomoallyl alcohols are accessed via a lipase-mediated
enzymatic resolution of racemic alcohols.14 Reported herein are
the improved synthesis of asymmetric (3,3-difluoroallyl)-
boronate, the failed asymmetric allylboration with 4, and
finally, the successful preparation and reactions of difluor-
oallylborane-derived from α-pinene.
Diisopropyl (3,3-difluoroallyl)boronate (3) prepared via the
Received: May 22, 2012
Published: September 13, 2012
homologation15 of 2,2-difluorovinyllithium6 with diisopropyl
© 2012 American Chemical Society
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The Journal of Organic Chemistry
Note
were monitored by the 11B NMR spectroscopy (chemical shift
change from δ 33 to 22 ppm).
Table 1. Difluoroallylboration of Benzaldehyde (5a) with 3;
Optimization of Conditions
a
As in the case of the racemic fluoroallylboration (Table 1),
no reaction took place in dichloromethane and decomposition
was observed in toluene. Allylboration of benzaldehyde (5a)
afforded the chiral homoallyl alcohol (R)-6a in 38% yield and
surprisingly low 20% ee, as was determined by H and 19F
1
b
c
entry
L.A.
solvent
temp (°C)
time (h)
yield (%)
NMR analysis of the corresponding α-methoxy α,α,α-
trifluoromethylphenyl acetates (Mosher esters).19 The config-
uration of the alcohol was assigned on the basis of the sign of
the optical rotation of the alcohol, as reported in the
literature.14
The use of In(OTf)3 (20 mol %) decreased the ee to 12%,
but with similarly poor yield (37%). Low enantioselectivity
(20%) was also observed for p-anisaldehyde (5b), where the
reaction required 4.5 days (11B NMR).
The disappointing results from chiral (3,3-difluoroallyl)-
boronates and the established success of pinane-mediated allyl-,
crotyl-, and alkoxyallylborations20 prompted the preparation of
B-(3,3-difluoroallyl)diisopinocampheylborane and fluoroallyl-
boration of aldehydes. Hydroboration of substituted allenes
have been utilized for the preparation of novel achiral and chiral
allylboranes.21 Accordingly, we examined the hydroboration of
1,1-difluoroallene with racemic and chiral diisopinocampheyl-
borane (Ipc2BH) (Scheme 3).
1
2
3
4
5
6
7
THF
rt
24
24
24
24
48
24
15
43
67
38
d
Sc(OTf)3
Sc(OTf)3
In(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
THF
rt
THF
reflux
reflux
reflux
reflux
f
THF
CH2Cl2
toluene
pentane
e
a
b
Reactions were carried out with 1.5 equiv of crude reagent. 10 mol
% of the Lewis acid was used, unless otherwise stated. Isolated yields
of pure products. No reaction observed. Decomposition of reagent
3. No reaction due to the poor solubility of the reagent.
c
d
e
f
a
Table 2. Difluoroallylboration of Aldehydes 5 with 3
b
entry
RCHO (5)
R
6
time (h)
yield (%)
1
2
3
4
5a
5b
5c
5d
C6H5
6a
6b
6c
6d
24
48
38
48
67
33
25
62
p-MeO-C6H4
2-Naphthyl
The successful, reagent-dependent, and regioselective hydro-
boration of a variety of fluoroolefins have been described by us
earlier.22 Hydroboration of fluoroalkynes have also been
reported in the literature.23 However, there has been no report
on the hydroboration of fluoroallenes. Accordingly, freshly
prepared 1,1-difluoroallene,24 was added to a suspension of
(−)-Ipc2BH in diethyl ether at −78 °C and was warmed to 0
°C over 3 h, whereafter the reaction medium became
homogeneous. The 11B NMR spectrum revealed two peaks at
δ 79 and 49 ppm in a 7:3 ratio, presumably corresponding to
the difluoroallylborane 7 and (2,2-difluoro-1-methylvinyl)-
borane (on the basis of 11B NMR of vinylboranes) (Scheme 3).
Benzaldehyde (5a) was added to the above mixture at −78
°C, and the reaction, which was monitored by 11B NMR
spectroscopy, was complete within 4 h. The NMR spectrum
revealed a broad peak at δ 50 ppm, along with a shoulder peak,
presumably due to the unreacted vinylborane. Alkaline
oxidative workup with hydrogen peroxide over 12 h at rt,
provided the expected 2,2-difluoro-1-phenylbut-3-en-1-ol (6a)
in 43% yield, based on the allylborane present in the medium.
Since allylboration has been shown to be a fast reaction even at
low temperatures,25 the yield of 6a is most likely limited by the
C6H5(CH2)2
a
Reactions were carried out in THF at reflux with 1.5 equiv of crude
reagent and 10 mol % of Sc(OTf)3. Isolated yields of pure products.
b
Surprisingly, low yields, 33% and 25%, respectively, were
obtained for the allylboration of p-anisaldehyde (5b) and 2-
naphthaldehyde (5c). Hydrocinnamaldehyde (5d) afforded the
product in 62% isolated yield. The factors influencing the low
yield are not clear at this point, although similar homoallylic
alcohols have been found to undergo the elimination of fluoride
under basic conditions.18 It is noteworthy that diisopropyl (3,3-
difluoroallyl)boronate (3) is less reactive than the 2-benzyloxy-
substituted reagent 1. This could be due to increased electron
density of the vinylic ether, a fact which should favor the allyl
transfer.
We were able to significantly improve upon our previous
results,5b enhancing the yield of (1R,3S)-1,2,2-trimethylcyclo-
pent-1,3-diyl (4R)-2-(3,3-difluoroprop-2-enyl)-4-phenyl-1,3,2-
dioxaborolane (4) from ≤20% to 80%, simply by decreasing
the reaction temperature. Unlike the achiral reagent, 4 is stable
to silica gel chromatography and the yield represents isolated
yield of the pure reagent and further reactions were carried out
using pure reagent. The fluoroallylboration of aldehydes with 4
was also facilitated by the presence of a Lewis acid, higher
reaction temperature, and longer reaction times (Scheme 2).
Allylborations were carried out with 1.25 equiv of reagent 4 in
the presence of 10 mol % of Sc(OTf)3 at reflux in THF and
1
formation of the allylborane from hydroboration. H and 19F
NMR analysis of the Mosher ester derivative of 6a revealed an
enantiomeric excess of 94%, and a configurational assignment
of R.14 It is observed that the stereochemistry of the product of
the reaction with difluoroallylborane 7 is the same as that of the
nonfluorinated analogue.25
Solvents such as THF, pentane, and CH2Cl2 decreased the
yield of the reaction. Although there was no change in the
enantioselectivity, lowering the allylboration temperature to
−100 °C improved the yield to 72%. The use of catalytic
Sc(OTf)3 did not improve the yield or enantioselectivity.
Accordingly, further difluoroallylboration of a series of
aldehydes with 7 was carried out at this temperature (Table
3). p-Anisaldehyde (5b) provided (R)-6b in 71% yield and 93%
ee. Similarly, high ee (94%) was obtained for 2-naphthaldehyde
(5c) as well. While α,β-unsaturated aldehyde, cinnamaldehyde
Scheme 2. Asymmetric Difluoroallylboration of Aldehydes 5
with 4
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The Journal of Organic Chemistry
Note
Scheme 3. Preparation and Reaction of B-(3,3-Difluoroallyl)diisopinocampheylborane (7)
Preparation of diisopropyl iodomethylboronate,16 (1R,2R,3R,4S)-4-
iodomethyl-1,10,10-trimethyl-2-phenyl-3,5-dioxa-4-boratricyclo-
[5.2.1.00,0]decane,7 1,1-difluoropropa-1,2-diene,24 (-)-diisopinocam-
pheylborane26 were achieved as reported.
Table 3. Asymmetric Difluoroallylboration of Aldehydes 5
with 7 in Et2O
a
c
d
temp
(°C)
(R)-
b
yield
(%)
ee
entry
5
R
6
(%)
1. General Procedure for the One-Pot Synthesis of Diisopropyl
(3,3-Difluoroallyl)Boronate (3) and Procedure for the Difluoroallyl-
boration of Aldehydes for the Preparation of 6a−d. To a solution of
1,1-difluoroethene (1.14 mL, 10.64 mmol) in THF (10 mL) and
diethyl ether (2.5 mL) at −110 °C was added dropwise s-BuLi (3.80
mL, 1.4 M in cyclohexane, 5.32 mmol). The reaction mixture was
stirred at the same temperature for 15 min and then diisopropyl
iodomethylboronate (1.58 g, 5.85 mmol) was slowly added at −100
°C. After 40 min at this temperature, the mixture was stirred at rt for 2
h and filtered through a short bed of Celite. The solvents were
removed under vacuum and the crude difluoroallylboronate 3 was then
dissolved in THF (3.5 mL), aldehyde (3.52 mmol), and Sc(OTf)3
(0.17 g, 0.35 mmol) were added, and the reaction mixture was refluxed
for 24 h (11B NMR shift from δ 29.5 to 18 ppm). The reaction was
quenched with satd aq NH4Cl solution (5 mL), and the product was
extracted with diethyl ether, washed with brine, dried (anhyd MgSO4),
filtered, and concentrated. The residue was purified by flash silica gel
chromatography (hexane/ethyl acetate = 8:1) to yield homoallyl
alcohols 6a−d. The spectral data were consistent with those reported
in the literature.8c,12,14,27
1
2
3
3
5
6
7
5a
5a
5b
5c
5d
5e
5f
C6H5
C6H5
−78
−100
−100
−100
−100
−100
−100
6a
6a
6b
6c
6d
6e
6f
43
72
71
70
76
70
69
94
94
93
94
97
91
92
p-MeO-C6H4
2-Naphthyl
C6H5(CH2)2
E-C6H5CHCH
2-Furyl
a
Reactions were carried out with 1 equiv of crude reagent over 4 h.
b
Determined by comparison of the optical rotation with those of
known compounds.14 Yields of pure products based on the number of
c
d
equivalents of reagent in the mixture. Determined by H and 19F
1
NMR analysis of Mosher esters.
(5e) afforded the product in 91% ee, hydrocinnamaldehyde
(5d) afforded the highest ee, 97%, for the homoallylic alcohol
in 76% yield. A heteroaromatic aldehyde, 2-furaldehyde (5f),
provided the product in 69% yield and 92% ee. It is gratifying to
note that pinane-derived reagent 7 provides very high ee for the
allylboration, even with the presence of the fluorine atoms. In
comparison, the camphor-derived allylboronate reagent 4
provides poor ee.
In conclusion, higher yields were achieved for the synthesis
of racemic and chiral (3,3-difluoroallyl)boronates, although the
allylboration results in poor yields and ee of the homoallyl
alcohols. The hydroboration of 1,1-difluoroallene with
diisopinocampheylborane provides a 7:3 mixture of the
corresponding (3,3-difluoroallyl)- and (2,2-difluoro-1-methyl-
vinyl) borane. Difluoroallylboration of representative aldehydes
with B-(3,3-difluoroallyl)diisopinocampheylborane provides
2,2-gem-difluorinated homoallyl alcohols in good yields and
high ee.
2. General Procedure for the Synthesis of (1R,3S)-1,2,2-
Trimethylcyclopent-1,3-diyl (4R)-2-(3,3-difluoroprop-2-enyl)-4-phe-
nyl-1,3,2-dioxaborolane (4). To a solution of 1,1-difluoroethene (0.85
mL, 7.96 mmol) in THF (7.5 mL) and diethyl ether (1.9 mL) at −110
°C was added dropwise s-BuLi (2.85 mL, 1.4 M in cyclohexane, 3.98
mmol). The reaction mixture was stirred at the same temperature for
15 min, and then (1R,2R,3R,4S)-4-iodomethyl-1,10,10-trimethyl-2-
phenyl-3,5-dioxa-4-boratricyclo[5.2.1.00,0]decane7 (1.74 g, 4.38 mmol)
was slowly added at −100 °C. After 40 min at this temperature, the
mixture was stirred at rt for 2 h and filtered through a short bed of
Celite. The solvents were removed and the residue was purified by
flash silica gel chromatography (hexane/ethyl acetate = 8:1) to yield
difluoroallylboronate 4 as a light yellow oil (1.06 g, 80%). Rf: 0.55
1
(hexane/ethyl acetate = 8:1). H NMR (300 MHz, CDCl3): δ 7.44−
7.29 (m, 5H), 4.75 (s, 1H), 4.19 (dtd, J = 25.5, 7.8, and 2.4 Hz, 1H),
2.16 (d, J = 5.1 Hz, 1H), 1.89−1.81 (m, 1H), 1.51 (d, J = 7.8 Hz, 1H),
1.22 (s, 3H), 1.20−1.15 (m, 2H), 1.10−1.00 (m, 1H), 0.97 (s, 3H),
0.94 (s, 3H). 19F NMR (282 MHz, CDCl3): δ −91.73 (d, J = 50.5 Hz,
1F), −94.62 (dd, J = 50.5 and 25.4 Hz, 1F). 13C NMR (75 MHz,
CDCl3): δ 155.9 (t, J = 282.5), 141.4, 127.4, 127.2, 126.5, 95.9, 88.7,
73.3 (t, J = 23.3 Hz), 51.9, 50.1, 48.7, 29.4, 24.6, 23.4, 20.5, 9.2. 11B
NMR (96 MHz, CDCl3): δ 33.2. MS EI: m/z = 332 [M+]. HRMS
(ESI): calcd for C19H23BF2O2 332.1759, found 332.1765.
EXPERIMENTAL SECTION
■
General Information. Unless otherwise noted, all manipulations
were carried out under inert atmosphere in flame-dried glassware.
Tetrahydrofuran (THF) was freshly distilled before use from sodium
benzophenone ketyl. All other chemicals and solvents were purchased
commercially and used without further purification, unless otherwise
noted.
General Procedure for the Difluoroallylboration of Alde-
hydes Using Reagent 4. To a solution of chiral (3,3-difluoroallyl)-
boronate 4 (1.25 mmol) in THF (1 mL) were added aldehyde 5 (1.00
mmol) and Sc(OTf)3 (0.10 mmol), and the reaction mixture was
refluxed for the desired time (shown in Table 3) (11B NMR shift from
δ 33.2 to 22.4 ppm). The reaction was quenched with satd aq NH4Cl
solution (1.5 mL), and the product was extracted with diethyl ether,
washed with brine, dried (anhyd. MgSO4), filtered, and concentrated.
The residue was purified by flash silica gel chromatography to yield
homoallyl alcohol 6.
The 1H, 19F, 13C, and 11B nuclear magnetic resonance (NMR)
spectra were plotted on 300 MHz spectrometer with Nalorac-quad
probes using CDCl3 as a solvent at room temperature. The NMR
chemical shifts (δ) are reported in ppm. Abbreviations for H and 19
F
1
NMR: s = singlet, d = doublet, m = multiplet, b = broad, t = triplet, q =
quartet. High-resolution mass spectra were obtained by electro spray
impact ionization in combination with a single quadrupole mass
analyzer. The reactions were monitored by TLC using silica gel F254
precoated plates. Flash chromatography was performed using flash
grade silica gel (particle size: 40−63 μm, 230 × 400 mesh). Optical
rotations were measured on an automatic polarimeter at the Na D line
(λ = 589 nm) using a 1 dm cell.
3. General Procedure for the One Pot Synthesis of B-(3,3-
Difluoroallyl)Diisopinocampheylborane (7) and Representative
Procedure for the Difluoroallylboration of Aldehydes for the
Preparation of (R)-2,2-Difluoro-1-phenylbut-3-en-1-ol [(R)-6a]. To
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The Journal of Organic Chemistry
Note
a suspension of (−)-Ipc2BH26 (1.25 g, 4.38 mmol) in Et2O (10 mL) at
−78 °C was added 1,1-difluoropropa-1,2-diene24 (0.50 g, 6.57 mmol).
After the mixture was stirred for 3 h at 0 °C, the solid dissolved
completely, indicating the completion of hydroboration (11B NMR δ
79 and 49 ppm, ratio 7:3). The reaction mixture was cooled to −100
°C, and benzaldehyde (5a) (0.46 g, 4.38 mmol) was added dropwise.
The mixture was stirred at this temperature for 4 h (11B NMR: δ 79
ppm to 50 ppm), oxidized with 3 M NaOH (3.2 mL) and 30% H2O2
(3.2 mL), and stirred at rt for 12 h. The product was extracted with
diethyl ether, washed with brine, dried (anhyd. MgSO4), filtered, and
concentrated. The residue was purified by flash silica gel
chromatography (hexane/ethyl acetate = 8:1) to yield homoallyl
alcohol (R)-6a as a colorless viscous liquid (0.36 g, 45%, calculated to
72% on the basis of 7:3 mixture of the reagents). Rf = 0.21 (hexane/
mixture of the reagents). Rf 0.15 (hexane/ethyl acetate = 9:1). [α]23
=
D
1
+7.22 (c 1.15, CHCl3), 91% ee, determined by H and 19F NMR
1
analysis of Mosher ester. H NMR (300 MHz, CDCl3): δ 7.43−7.28
(m, 5H), 6.78 (d, J = 15.6 Hz, 1H), 6.20 (dd, J = 15.6 and 5.7 Hz, 1H),
6.01 (ddd, J = 23.1, 17.4, and 11.1 Hz, 1H), 5.75 (dtd, J = 17.4 Hz, 2.1
and 0.9 Hz, 1H), 5.57 (d, J = 11.1 Hz, 1H), 4.57−4.46 (m, 1H), 2.23
(d, J = 5.1 Hz, 1H). 19F NMR (282 MHz, CDCl3): δ −109.99 (dt, J =
247.8 and 10.1 Hz, 1F), −112.10 (dt, J = 247.8 and 10.1 Hz, 1F). 13C
NMR (75 MHz, CDCl3): δ 135.8, 134.5, 129.5 (t, J = 25.4 Hz), 128.5,
128.2, 126.6, 123.0, 121.6 (t, J = 9.0 Hz), 119.3 (t, J = 242.5 Hz), 74.4
(td, J = 29.8 and 4.8 Hz). MS EI: m/z = 210 [M+]. HRMS (ESI): calcd
for C12H12F2O 210.0856, found 210.0859.
(R)-2,2-Difluoro-1-(furan-2-yl)but-3-en-1-ol [(R)-6f]. A light
yellow oil, 0.25 g, yield 42% (calculated to 69% on the basis of 7:3
mixture of the reagents). Rf 0.80 (hexane/ethyl acetate = 8:1). [α]23
=
ethyl acetate = 8:1). [α]23 = −16.96 (c 1.25, CHCl3), 94% ee,
D
D
determined by 1H and 19F NMR analysis of Mosher ester (lit.14 [α]23
= −14.7 (c 1.13, CHCl3), 79% ee). H NMR (300 MHz, CDCl3): δ
−1.88 (c 1.17, CHCl3), 92% ee, determined by H and 19F NMR
analysis of Mosher ester. 1H NMR (300 MHz, CDCl3): δ 7.50 (d, J =
1.8 Hz, 1H), 6.51−6.50 (m, 1H), 6.47−6.45 (m, 1H), 6.13−5.96 (m,
1H), 5.78 (dt, J = 17.7 and 2.4 Hz, 1H), 5.60 (d, J = 11.1 Hz, 1H),
4.97 (td, J = 9.3 and 6.6 Hz, 1H), 2.86 (d, J = 6.6 Hz, 1H). 19F NMR
(282 MHz, CDCl3): δ −108.90 (t, J = 10.8 Hz, 2F). 13C NMR (75
MHz, CDCl3): δ 149.4, 143.0, 129.5 (t, J = 25.2 Hz), 121.8 (t, J = 8.5
Hz), 118.7 (t, J = 240.0 Hz), 110.6, 109.6, 70.4 (t, J = 31.6 Hz). MS
EI: m/z = 174 [M+]. HRMS (ESI): calcd for C8H8F2O2 174.0492,
found 174.0488.
1
D
1
7.42−7.35 (m, 5H), 5.86 (ddd, J = 23.1, 17.4, and 11.1 Hz, 1H), 5.59
(d, J = 17.4 Hz, 1H), 5.46 (d, J = 11.1 Hz, 1H), 4.88 (t, J = 9.6 Hz,
1H), 2.81 (bs, 1H). 19F NMR (282 MHz, CDCl3): δ −109.32 (dt, J =
246.4 and 10.4 Hz, 1F), −110.99 (dt, J = 246.4 and 10.4 Hz, 1F). 13C
NMR (75 MHz, CDCl3): δ 135.9, 129.2 (t, J = 25.5 Hz), 128.6, 128.1,
127.5, 121.5 (t, J = 8.7 Hz), 119.5 (t, J = 243.1 Hz), 75.7 (td, J = 29.6
and 5.8 Hz). MS EI: m/z = 184 [M+]. HRMS (ESI): calcd for
C10H10F2O 184.0700, found 184.0711.
(R)-2,2-Difluoro-1-(4-methoxyphenyl)but-3-en-1-ol [(R)-6b].
A colorless viscous liquid, 0.50 g, 44% (calculated to 71% on the
basis of 7:3 mixture of the reagents). Rf 0.09 (hexane/ethyl acetate =
8:1). [α]23D = −19.75 (c 1.55, CHCl3), 93% ee, determined by 1H and
ASSOCIATED CONTENT
* Supporting Information
Copies of the NMR spectra of the products. This material is
available free of charge via the Internet at http://pubs.acs.org.
■
S
19F NMR analysis of Mosher ester (lit.14 [α]23 = −20.2 (c 1.01,
D
CHCl3), 94% ee). 1H NMR (300 MHz, CDCl3): δ 7.33 (d, J = 8.7 Hz,
2H), 6.91−6.86 (m, 2H), 5.86 (ddd, J = 23.4, 17.4, and 11.1 Hz, 1H),
5.59 (dtd, J = 17.4, 2.4, and 0.9 Hz, 1H), 5.46 (d, J = 11.1 Hz, 1H),
4.84 (td, J = 9.6 and 3.0 Hz, 1H), 3.81 (s, 3H), 2.63 (d, J = 3.6 Hz,
1H). 19F NMR (282 MHz, CDCl3): δ −109.59 (dt, J = 245.9 and 10.4
Hz, 1F), −111.17 (dt, J = 245.9 and 10.4 Hz, 1F). 13C NMR (75 MHz,
CDCl3): δ 159.7, 129.4 (t, J = 25.5 Hz), 128.8, 128.1, 121.3, 119.5 (t, J
= 242.8 Hz), 113.4, 75.4 (td, J = 29.6 and 7.3 Hz), 55.1. MS EI: m/z =
214 [M+]. HRMS (ESI): calcd for C11H12F2O2 214.0805, found
214.0811.
AUTHOR INFORMATION
Corresponding Author
*E-mail: chandran@purdue.edu.
■
Present Address
‡Department of Chemistry, Nicolaus Copernicus University,
́
Gagarina 7, 87−100 Torun, Poland.
Notes
The authors declare no competing financial interest.
(R)-2,2-Difluoro-1-(naphthalen-2-yl)but-3-en-1-ol [(R)-6c]. A
light yellow oil, 0.53 g, 48% (calculated to 70% on the basis of 7:3
mixture of the reagents). Rf 0.33 (hexane/ethyl acetate = 8:2). [α]23
=
D
1
−15.56 (c 1.08, CHCl3), 94% ee, determined by H and 19F NMR
ACKNOWLEDGMENTS
We thank the Herbert C. Brown Center for Borane Research
for financial assistance of this project.
■
1
analysis of Mosher ester. H NMR (300 MHz, CDCl3): δ 7.89−7.83
(m, 4H), 7.55−7.49 (m, 3H), 5.88 (ddd, J = 23.4, 17.4, and 11.1 Hz,
1H), 5.61 (dt, J = 17.1 and 2.0 Hz, 1H), 5.46 (d, J = 10.8 Hz, 1H),
5.09 (t, J = 9.3 Hz, 1H), 2.62 (bs, 1H). 19F NMR (282 MHz, CDCl3):
δ −109.03 (dt, J = 246.7 and 10.4 Hz, 1F), −110.46 (dt, J = 246.7 and
10.4 Hz, 1F). 13C NMR (75 MHz, CDCl3): δ 133.3, 132.8, 129.2 (t, J
= 25.5 Hz), 128.1, 127.8, 127.6, 127.0, 126.3, 126.2, 124.9, 121.6,
119.6 (t, J = 243.4 Hz), 75.9 (td, J = 29.7 and 6.7 Hz). MS EI: m/z =
234 [M+]. HRMS (ESI): calcd for C14H12F2O 234.0856, found
234.0859.
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■
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