Stereoselective synthesis of monofluoroalkyl α,β-unsaturated ketones from allenyl carbinol esters mediated by gold and selectfluor

Article abstract of DOI:10.1021/jo301239p

Allenyl carbinol ester 3 isomerizes to an E,Z mixture of the corresponding diene 2 in the presence of gold catalyst 4, but the resulting mixture yields monofluoroalkyl α,β-unsaturated ketone 1 with exclusive E selectivity and in high yields after reaction

Full text of DOI:10.1021/jo301239p

Note
pubs.acs.org/joc
Stereoselective Synthesis of Monofluoroalkyl α,β-Unsaturated
Ketones From Allenyl Carbinol Esters Mediated by Gold and
Selectfluor
Zhuang Jin, Rachel S. Hidinger, Bo Xu,* and Gerald B. Hammond*
Department of Chemistry, University of Louisville, Louisville, Kentucky 40292, United States
S
* Supporting Information
ABSTRACT: Allenyl carbinol ester 3 isomerizes to an E,Z
mixture of the corresponding diene 2 in the presence of gold
catalyst 4, but the resulting mixture yields monofluoroalkyl α,β-
unsaturated ketone 1 with exclusive E selectivity and in high
yields after reaction with Selectfluor.
onofluoroalkyl α,β-unsaturated ketones 1 are important
Scheme 1. Literature Syntheses of Monofluoroalkyl α,β-
Unsaturated Ketones Using Fluorine-Containing Building
Blocks (Top) or through Fluorination of Specific Ketones
(Bottom)
M
molecular synthons, as showcased by their widespread
use in the syntheses of bioactive compounds (Figure 1).1
Figure 1. Monofluoroalkyl (E)-α,β-unsaturated ketones A,1a B,1b and
C1c are important building blocks for bioactive agents.
Fluoroketone 1 is most commonly synthesized either by using a
fluorine containing building block2 or through fluorination of
an unsaturated ketone.3 But these methodologies have
limitations. The former relies on a shallow pool of fluorine
containing moieties (Scheme 1, top), whose preparation is not
always trivial; a case in point is the synthesis of fluorine-
containing Wittig reagents.2a,b,4
The fluorination of an unsaturated ketone is hampered
because the regioselective fluorination of the starting
unsaturated ketone is case specific (Scheme 1, bottom).
Because of these limitations, it is not trivial to build libraries
of fluoroalkyl α,β-unsaturated ketones.
the C−F bond formation did not involve gold catalysis. Instead,
gold facilitated the isomerization of propargylic esters to give
alleny acetate, which reacted with electrophilic fluorine
followed by hydrolysis to give α-fluoroenone.
We posited that an electron rich 1,3-butadien-2-ol ester 2
could be a suitable substrate for electrophilic fluorination
(Scheme 2, bottom) because it is readily made by the gold-
catalyzed isomerization of allenyl carbinol ester 3 using Gagosz’
methodology.7 We are pleased to report that a stereomixture of
Inspired by the works of Gouverneur5 and Nevado6 (Scheme
2, top), we envisioned a more efficient fluorination process to
overcome the aforementioned drawbacks. Nevado and co-
workers reported that propargyl acetate and Selectfluor, in the
presence of gold catalyst, delivered α-fluoroenone (mixture of E
and Z), and proposed that gold facilitated the 3,3-sigmatropic
rearrangement of propargyl acetate, and that C−F bond may be
formed through gold(III) reductive elimination. Gouverneur
and co-workers researched a similar reaction and reported that
Received: June 20, 2012
Published: August 16, 2012
© 2012 American Chemical Society
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The Journal of Organic Chemistry
Note
Scheme 2. Gold Catalyzed Isomerization of Alkyne and
Allene and Subsequent Fluorination Strategy
Table 1. Preparation of Monofluoroalkyl α,β-Unsaturated
Ketones 1 from in Situ Generated Dienes 2
a
2 can be fluorinated at room temperature by Selectfluor to give
fluoroalkyl α,β-unsaturated ketone 1 in high yields and with
exclusive E stereoselectivity.
Our results are shown in Table 1. Gagosz and co-workers
had reported that terminal allenyl carbinol ester 3 isomerizes to
1,3-butadien-2-ol ester 2 with moderate to good stereo-
selectivity in the presence of gold catalyst 4. Indeed, in our
hands carbinol ester 3a isomerized to diene 2a in CDCl3 in the
presence of catalyst 4,8 reacting readily with Selectfluor in
MeCN to yield the corresponding fluorinated ketone 1a in
excellent yield and with exclusive E stereoselectivity.9 It is
noteworthy that diene 2a (E:Z = 95:5) isomerizes to 1a during
the fluorination process, yielding exclusively the E isomer.
Similarly, aromatic substrates 3b, 3c and 3d isomerized to their
corresponding dienes 2 as mixture of E/Z isomers, but upon
fluorination, they afforded 1a with high stereoselectivity and
excellent chemical yields, regardless of the type of carboxylic
acid derivative used. Aliphatic allenyl esters 3e (entry 5), 3f
(entry 6) and 3g (entry 7) were also examined. All of them
isomerized efficiently and were fluorinated to give 1e (E:Z =
99:1) (entries 5 and 6)10 and 1g (E:Z = 99:1) (entry 7) in very
good yield. We were curious to know if an internal allenyl ester
such as 3h (entry 8) would behave similarly to terminal allene
under our reaction conditions. We were pleasantly surprised to
discover that even though 3h isomerized readily to give a
complex mixture of stereoisomers 2h (1:0.41:0.68:0.87), this
mixture still produced the desired 1h in good yield, as a single
E-isomer. Benzoate and acetate derivatives of 1,1-disubstituted
allenyl esters 3i and 3j were also tested. Again, their
isomerizations produced diene mixtures 2i and 2j, respectively,
but after fluorination, only 1i was obtained in very good yield
and with exclusive E selectivity.
We decided to investigate the preparation of fluoroalkyl E,E-
α,β,γ,δ-unsaturated ketone 1k using our protocol, but
unfortunately, this attempt failed because no isomerization of
the two substrates tested, 3k and 3l, took place in the presence
of gold catalyst 4 (Scheme 3).
A plausible mechanism for the isomerization of our diene
mixture is proposed in Scheme 4. The electron-rich double
bond of diene 2 attacks the electrophilic fluorine in Selectfluor
to form cationic intermediate C, which immediately isomerizes
to form the more stable intermediate D, and after hydrolysis
with trace amounts of water present in the reaction media, it
yields fluoroalkyl E-α,β-unsaturated ketone 1. The reported
electrophilic fluorination-nucleophilic addition reactions of
glycals11 and other substrates5,6 using Selectfluor lend support
to our proposed mechanism.
a
Reaction conditions: allenyl carbinol ester (3) (0.25 mmoL) and gold
catalyst 4 (1.0 mol %) were dissolved in CDCl3 (1 mL), stirred, and
monitored by H NMR until the reaction showed no more progress.
After CDCl3 removal under vacuum, Selectfluor (1.2 equiv) and
acetonitrile (1.5 mL) were added to the diene mixture 2 and stirred for
1
b
3 h at rt. Yield was calculated on starting allenyl carbinol ester (3).
c
19F NMR yield due to their volatility, α,α,α-trifluorotoluene as
d
internal standard. Yield of allylic alcohol. Ketones were reduced to
the corresponding allylic alcohol because of their instability toward
silica gel. Allylic alcohols of 1g and 1h contain less than 3% of
corresponding saturated alcohol; dr of the allylic alcohol (from 1h) is
4:1.
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The Journal of Organic Chemistry
Note
Typical Procedure for Ma’s Methodology. Hex-1-yn-3-ol
(556.2 μL, 5.0 mmol), octanal (779.5 μL, 5.0 mmol), morpholine
(691.2 μL, 8.0 mmol), ZnI2 (1276 mg, 4.0 mmol) and toluene (20
mL) were added into a 50 mL round-bottom reaction flask containing
a stir bar, and the flask was equipped with refluxing condenser. The
reaction mixture was refluxed for 8 h in oil bath, cooled to room
temperature, filtered through silica gel (about 20 g), and washed by
mixture of hexanes and ethyl acetate (120 mL, ratio is 4:1). The
solvent was removed in a vacuum and the resulting residue was
purified on a silica gel column, which was eluted by hexanes and ethyl
acetate to give tetradeca-5,6-dien-4-ol (262.5 mg, 25%).
Scheme 3. Limitations of Our Protocol
Scheme 4. Proposed Mechanism for the Isomerization
Typical Procedure for Harada’s Methodology. Stannous
chloride (568.8 mg, 3.0 mmol), 1-bromo-2-butyne (262.56 μL, 3.0
mmol), sodium iodide (450.0 mg, 3.0 mmol) and DMF (5 mL) were
added into a 10 mL reaction flask containing a stir bar, and the
reaction mixture was stirred for 1.5 h at room temperature. Then the
reaction mixture was cooled at 0 °C, and benzaldehyde (305.7 μL, 3.0
mmol) in DMF (1 mL) was added dropwise and stirred for overnight.
The reaction mixture was quenched by saturated ammonium chloride
(20 mL), followed by diethyl ether extraction (25 mL × 4). The ether
layers were combined and dried over anhydrous Na2SO4, filtered and
evaporated under reduced pressure; the resulting residue was
subjected to silica gel chromatography eluted by hexanes and ethyl
acetate system to yield 2-methyl-1-phenylbuta-2,3-dien-1-ol (384.0
mg, 80%).
Typical Procedure for Esterification of Allenyl Alcohol:
Synthesis of 3a. 1-Phenylbuta-2,3-dien-1-ol (292.1 mg, 2.0 mmol)
and triethylamine (417 μL, 3 mmol) were dissolved in dry
dichloromethane (5.0 mL) at 0 °C, in which the acetyl chloride
(213 μL, 3 mmol) was added slowly over a 5 min period, and the
mixture was stirred for 10 min at 0 °C. The resulting solution was
stirred for 5 h at room temperature, and then saturated ammonium
chloride solution (20 mL) was added to the reaction mixture, followed
by diethyl ether extraction (25 mL × 3). The ether layers were
combined and dried over anhydrous Na2SO4, filtered and evaporated
under reduced pressure to yield 3a (357.2 mg, 95%).
In summary, our protocol can efficiently fluorinate a mixture
of dienes 2 under mild conditions to give fluoroalkyl E-α,β-
unsaturated ketones in good to excellent yield. Because the
starting allenyl alcohols can be readily prepared using literature
methodologies,12 our protocol can be employed in the
synthesis of a variety of fluoroalkyl E-α,β-unsaturated ketones.
These ketones can, in turn, be further functionalized; for
example, they can be converted into a fluorosugar precursor,13
through dihydroxylation of its double bond.2a
Spectroscopic Data for 3. 1-Phenylbuta-2,3-dien-1-yl acetate
(3a).7 (357.2 mg, 95%), colorless liquid: 1H NMR (400 MHz, CDCl3)
δ 7.36 (m, 5H), 6.31 (m, 1H), 5.45 (q, J = 6.8 Hz, 1H), 4.86 (m, 2H),
2.10 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 208.5, 171.2, 138.9,
128.5, 128.2, 126.9, 91.5, 77.8, 73.4, 21.1.
EXPERIMENTAL SECTION
■
General Methods. The gold complex (4) and Selectfluor were
purchased from Aldrich. All air and/or moisture sensitive reactions
were carried out under argon atmosphere. Solvents (tetrahydrofuran,
ether, dichloromethane and DMF) were chemically dried using a
commercial solvent purification system. All other reagents and solvents
1-Phenylbuta-2,3-dien-1-yl benzoate (3b).7 (450.2 mg, 90%),
colorless liquid: 1H NMR (400 MHz, CDCl3) δ 8.11 (dd, J = 1.4, 7.1
Hz, 2H), 7.58 (dd, J = 1.3, 7.4 Hz, 1H), 7.48 (t, J = 7.5 Hz, 2H), 7.45
(d, J = 7.5 Hz, 2H), 7.40 (t, J = 7.0 Hz, 2H), 7.33 (t, J = 7.2 Hz, 1H),
6.56 (dt, J = 2.2, 6.7 Hz, 1H), 5.56 (q, J = 6.6 Hz, 1H), 4.90 (m, 2H);
13C NMR (175 MHz, CDCl3) δ 208.7, 165.5, 139.3, 133.0, 130.3,
were employed without further purification. H, 13C and 19F NMR
1
spectra were recorded at 500 (or 400), 126 (or 100) and 470 (or 376)
MHz, respectively, using CDCl3 (or CD3CN) as a solvent. The
chemical shifts are reported in δ (ppm) values relative to CHCl3 (7.26
ppm for 1H NMR and 77.0 ppm for 13C NMR) and CFCl3 (0 ppm for
19F NMR). Multiplicities are indicated by s (singlet), d (doublet), t
(triplet), q (quartet), p (pentet), h (hextet), m (multiplet) and br
(broad). Coupling constants, J, are reported in Hertz. FTIR spectra
were recorded in ATR (attenuated total reflection) solid mode. Exact
molecular weight of new compound was obtained by high-resolution
mass spectrometry (TOF).
129.7, 128.5, 128.3, 128.2, 126.8, 91.7, 77.9, 74.0.
1-Phenylbuta-2,3-dien-1-yl pivalate (3c).7 (425.5 mg, 93%),
colorless liquid: 1H NMR (400 MHz, CDCl3) δ 7.41−7.29 (m,
5H), 6.28 (dt, J = 2.4, 6.6 Hz, 1H), 5.41 (q, J = 6.6 Hz, 1H), 4.88 (m,
2H), 1.24 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 208.5, 177.4,
139.6, 128.4, 128.0, 126.9, 91.9, 77.5, 72.7, 38.9, 27.3.
1-Phenylbuta-2,3-dien-1-yl ethylcarbamate (3d). (386.3 mg,
89%), colorless liquid: 1H NMR (400 MHz, CDCl3) δ 7.36 (m,
5H), 6.23 (brs, 1H), 5.43 (q, J = 6.8 Hz, 1H), 4.84 (m, 2H), 3.21 (m,
2H), 1.12 (t, J = 6.8 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 208.47,
155.43, 139.75, 128.41, 128.06, 126.79, 92.06, 77.64, 73.72, 35.91,
15.17; HRMS (TOF) m/z (ES+) calcd for C13H15NNaO2 ([M +
Na]+) 240.0995, found 240.1000.
Preparation of Allenyl Alcohol. Allenyl alcohols precursor of 3a,
3e and 3g were prepared by Crabbe reaction.12b Allenyl alcohol
precursor of 3h was prepared by Ma’s methodology.12a Allenyl alcohol
precursor of 3i was prepared by Harada’s methodology.12c
Typical Procedure for Crabbe Reaction. 1-Phenylprop-2-yn-1-
ol (396.0 mg, 3.0 mmol), paraformaldehyde (180.0 mg, 6.0 mmol),
diisopropylamine (834.0 μL, 6.0 mmoL), CuBr (257.4 mg, 1.8 mmol)
and 1,4-dioxane (20 mL) were added into a 50 mL round-bottom
reaction flask containing a stir bar, and the flask was equipped with
reflux condenser. The reaction mixture was refluxed in oil bath for 2 h,
cooled to room temperature, filtered through silica gel (about 15 g),
and washed by mixture of hexanes and ethyl acetate (100 mL, ratio is
4:1). The solvent was removed in a vacuum, and the resulting residue
was purified on a silica gel column, which was eluted by hexanes and
ethyl acetate to give 1-phenylbuta-2,3-dien-1-ol (292.0 mg, 67%).
Hepta-1,2-dien-4-yl benzoate (3e).7 (386.3 mg, 89%), colorless
1
liquid: H NMR (400 MHz, CDCl3) δ 8.08−8.05 (m, 2H), 7.55 (d, J
= 7.5 Hz, 1H), 7.44 (dd, J = 7.8 Hz, 2H), 5.55 (m, 1H), 5.40 (q, J =
6.6 Hz, 1H), 4.92−4.82 (m, 2H), 1.91−1.70 (m, 2H), 1.59−1.42 (m,
2H), 0.99 (t, J = 7.4 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 208.5,
165.92, 132.8, 130.6, 129.6, 128.4, 91.1, 77.3, 72.1, 36.4, 18.6, 13.9.
Hepta-1,2-dien-4-yl ethylcarbamate (3f). (351.4 mg, 96%),
1
colorless liquid: H NMR (500 MHz, CDCl3) δ 5.24 (m, 2H), 4.86
(m, 2H), 4.61 (brs, 1H), 3.23 (m, 2H), 1.64 (m, 2H), 1.38 (m, 2H),
1.14 (t, J = 7.0 Hz, 3H), 0.93 (t, J = 7.0 Hz, 3H); 13C NMR (125
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The Journal of Organic Chemistry
Note
MHz, CDCl3) δ 208.2, 155.9, 91.5, 76.8, 71.7, 36.5, 35.8, 18.5, 15.2,
13.8; HRMS (TOF) m/z (ES+) calcd for C10H17NNaO2 ([M + Na]+)
206.1151, found 206.1154.
6.6 Hz, 1H), 6.37 (d, J = 16.0 Hz, 1H), 4.97 (d, J = 47.5 Hz, 2H), 2.26
(m, 2H); 19F NMR (470 MHz) δ −229.53 (t, J = 47.9 Hz).
(E)-1-Fluoropentadec-3-en-2-ol, derived from (1g). (50.6 mg,
1
Pentadeca-1,2-dien-4-yl benzoate (3g). (577.4 mg, 88%), color-
83%), colorless liquid. Contains less than 3% saturated alcohol: H
1
NMR (400 MHz, CDCl3) δ 5.83 (dt, J = 15.2, 8.0 Hz, 1H), 5.41 (dd, J
= 15.6, 6.4 Hz, 1H), 4.45 (m, 0.5H), 4.34 (m, 2H), 4.20 (m, 0.5H),
2.04 (q, J = 6.8 Hz,1H), 1.25−1.39 (m, 18H), 0.87 (t, J = 7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 135.5 (d, J = 1.5 Hz), 125.8 (d, J = 8.5
Hz), 86.4 (d, J = 171.2 Hz), 71.5 (d, J = 19.4 Hz), 32.3, 31.9, 29.6,
29.6, 29.6, 29.4, 29.3, 29.1, 28.9, 22.7, 14.1; 19F NMR (376 MHz) δ
−225.54 (dt, J = 48.1, 17.7 Hz); FTIR (ATR)/cm−1 3420, 2924, 2854,
1466, 1012; HRMS (TOF) m/z (ES+) calcd for C15H29FNaO ([M +
Na]+) 267.2095, found 267.2095.
less liquid: HNMR (400 MHz, CDCl3) δ 8.05 (d, J = 7.6 Hz, 2H),
7.53 (t, J = 7.2 Hz, 1H), 7.43 (t, J = 8.0 Hz, 2H), 5.49 (q, J = 7.6 Hz,
1H), 5.32 (q, J = 6.4 Hz, 1H), 4.86 (m, 2H), 1.79 (m, 2H), 1.34 (m,
18H), 0.87 (t, J = 6.4 Hz, 3H); 13CNMR (125 MHz, CDCl3) δ 208.5,
165.9, 132.8, 130.6, 129.6, 128.3, 90.9, 77.3, 72.4, 34.3, 31.9, 29.6, 29.6,
29.6, 29.5, 29.4, 25.3, 22.6, 22.6, 14.1; HRMS (TOF) m/z (ES+) calcd
+
for C22H32NaO2 ([M + Na]+) 351.2295, found 351.2294.
Tetradeca-5,6-dien-4-yl benzoate (3h). (609.2 mg, 97%), yellow
liquid: 1HNMR (400 MHz, CDCl3) δ 8.04 (d, J = 7.6 Hz, 2H), 7.53 (t,
J = 7.2 Hz, 1H), 7.41 (t, J = 6.4 Hz, 2H), 5.47 (m, 1H), 5.27 (m, 2H),
1.99 (m, 2H), 1.82 (m, 2H), 1.33 (m, 12H), 0.95 (t, J = 7.2 Hz, 3H),
0.86 (m, 3H); 13CNMR (100 MHz, CDCl3) δ 203.99 (203.92), 165.9,
132.7 (132.6), 130.74 (130.72), 129.5, 128.3 (128.2), 93.8 (93.7), 91.6
(91.5), 72.8 (72.5), 36.5 (36.4), 31.8 (31.7), 29.1 (29.0), 29.07
(29.04), 29.0, 28.9 (28.5), 22.6 (22.5), 18.6, 14.1, 13.9 (13.8); HRMS
(E)-7-Fluorotetradec-4-en-6-ol (dr = 4:1), derived from (1h). (41.4
mg, 72%), colorless liquid, containing less than 3% saturated alcohol.
1
Major diastereomers: H NMR (400 MHz, CDCl3) δ 5.79 (dt, J =
15.2, 7.2 Hz, 1H), 5.42 (dd, J = 15.6, 7.6 Hz, 1H), 4.37 (m, 0.5H), 4.23
(m, 0.5H), 4.05 (m, 1H), 2.04 (m, 2H), 1.26−1.62 (m, 14H), 0.87 (m,
6H); 13C NMR (100 MHz, CDCl3) δ 135.5, 127.3 (d, J = 7.0 Hz),
96.6 (d, J = 171.1 Hz), 74.7 (d, J = 20.9 Hz), 34.4, 31.7, 30.9, 29.3,
29.1, 24.9, 22.6, 22.1, 14.0, 13.6; 19F NMR (376 MHz) δ −192.30
(m); FTIR (ATR)/cm−1 3427, 2926, 2857, 1464, 970; HRMS (TOF)
m/z (ES+) calcd for C14H27FNaO ([M + Na]+) 253.1938, found
253.1940.
+
(TOF) m/z (ES+) calcd for C21H30NaO2 ([M + Na]+) 337.2138,
found 337.2140.
2-Methyl-1-phenylbuta-2,3-dien-1-yl benzoate (3i). (477.8 mg,
81%), colorless liquid: 1HNMR (400 MHz, CDCl3) δ 8.13 (d, J = 7.6
Hz, 2H), 7.57 (t, J = 7.6 Hz, 1H), 7.44 (m, 4H), 7.38 (t, J = 7.8 Hz,
2H), 7.32 (t, J = 7.2 Hz, 1H), 6.46 (s, 1H), 4.84 (m, 2H), 1.73 (t, J =
3.2 Hz, 3H); 13CNMR (100 MHz, CDCl3) δ 206.6, 165.4, 138.6,
133.1, 130.3, 129.7, 128.4, 128.1, 126.9, 99.2, 76.7, 76.5, 14.9; HRMS
(E)-1-Fluoro-3-methyl-4-phenylbut-3-en-2-ol, derived from (1i).
1
(35.6 mg, 79% for entry 9), colorless liquid: H NMR (500 MHz,
CDCl3) δ 7.37 (m, 2H), 7.27 (m, 3H), 6.67 (s, 1H), 4.61 (dd, J = 9.0,
2.5 Hz, 0.5H), 4.51 (m, 2H), 4.39 (t, J = 7.5 Hz, 0.5H), 1.92 (d, J = 1.5
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 136.9, 134.7 (d, J = 7.0 Hz),
128.9, 128.2, 127.7 (d, J = 1.6 Hz), 126.8, 85.7 (d, J = 172.2 Hz), 75.8
(d, J = 19.4 Hz), 14.6; 19F NMR (470 MHz) δ −225.33 (dt, J = 47.5,
17.4 Hz); FTIR (ATR)/cm−1 3397, 2977, 1723, 1448, 1055, 903, 751,
698; HRMS (TOF) m/z (ES+) calcd for C11H13FNaO ([M + Na]+)
203.0843, found 203.0841. Stereochemistry was determined by
ROSEY spectra.
+
(TOF) m/z (ES+) calcd for C18H16NaO2 ([M + Na]+) 287.1043,
found 287.1050.
2-Methyl-1-phenylbuta-2,3-dien-1-yl acetate (3j).14 (354.4 mg,
1
86%), colorless liquid: HNMR (400 MHz, CDCl3) δ 7.35 (m, 5H),
6.18 (s, 1H), 4.79 (s, 2H), 2.12 (s, 3H), 1.62 (t, J = 3.2 Hz, 3H);
13CNMR (100 MHz, CDCl3) δ 206.4, 169.9, 138.4, 128.5, 128.3,
127.4, 99.1, 76.7, 76.0, 21.1, 14.8; HRMS (TOF) m/z (ES+) calcd for
+
C13H14NaO2 ([M + Na]+) 225.0886, found 225.0890.
Isomerization of Allenyl Carbinol Esters (3) by Gold
Complex (4). Allenyl carbinol esters (3) (0.25 mmol) and gold
complex (4) (2.40 mg, 1 mol %) were dissolved in CDCl3 (1 mL),
stirred at room temperature, and monitored by H NMR until no
progress. All allenyl carbinol esters (3a−3j) efficiently isomerized into
dienes (2), and NMR yield was at least 95%.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
1H, 13C NMR, and IR spectra of new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
Fluorination of Dienes (2) with Selectfluor. CDCl3 of the
above reaction was carefully dried by rotary evaporator, and Selectfluor
(106 mg, 0.3 mmol) and acetonitrile (1.5 mL) were added into the
diene mixture (2) and stirred at room temperature for 3 h.
As for 1a, the reaction mixture was subjected to short silica gel
chromatography separation, which was eluted by gradient elution of
hexanes and ethyl acetate.
AUTHOR INFORMATION
Corresponding Author
*E-mail: Gb.hammond@louisville.edu; bo.xu@louisville.edu.
Notes
■
The authors declare no competing financial interest.
As for 1e, α,α,α-trifluorotoluene (0.1 mmoL) and 0.5 mL of
ACKNOWLEDGMENTS
CD3CN were added into reaction mixture for 19F NMR.
■
As for 1g, 1h and 1i, the reaction mixture was filtered through silica
gel (10 g), and washed by mixture of hexanes and ethyl acetate (4:1,
70 mL). Then, the solution was concentrated, and the remaining
residue was dissolved in 2−3 mL of methanol. CeCl3·7H2O (186 mg,
0.4 mmol) was added into the methanol solution, the solution was
placed at 0 °C (ice bath), and NaBH4 (15 mg, 0.4 mmol) was added
over 15 min. The reaction was stirred for another 20 min at room
temperature. Then, the mixture was directly subjected to silica gel
column separation eluted by hexane and ethyl acetate system.
(E)-1-Fluoro-4-phenylbut-3-en-2-one (1a).2h (37.0 mg, 90% for
entry 1), amorphous solid: 1H NMR (500 MHz, CDCl3) δ 7.77 (d, J =
16.5 Hz, 1H), 7.61 (m, 2H), 7.44 (m, 3H), 7.03 (dt, J = 16.0, 2.0 Hz,
1H), 5.05 (dd, J = 47.5, 1.0 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ
194.8 (d, J = 18.3 Hz), 145.1 (d, J = 3.1 Hz), 134.1, 131.2, 129.1,
128.7, 119.8, 84.8 (J = 184.1 Hz); 19F NMR (470 MHz) δ −228.68
(dt, J = 47.5, 2.4 Hz); FTIR/cm−1 3029, 2927, 1709, 1689, 1607, 1576,
1495, 1450, 1333, 1202, 1167, 1036, 998, 977, 748, 688.
We are grateful to the NSF (CHE-1111316) for financial
support and to the Center for Regulatory and Environmental
Analytical Metabolomics (CREAM) Mass Spectrometry
Facility (University of Louisville) funded by NSF/EPSCoR
(EPS-0447479). The authors also appreciate the help provided
by Deepika Malhotra in the acquisition of HRESIMS data.
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