Phosphine catalyst-controlled cycloaddition or dienylation reactions of trifluoromethyl aryl ketones with bis-substituted allenoates

Article abstract of DOI:10.1021/jo401462c

A chemoselective phosphine-catalyzed cycloaddition or dienylation reaction between trifluoromethyl-substituted ketones and bis-substituted allenoates was described. Under the catalysis of triarylphosphine, the reaction gave a range of trifluoromethylated tetrahydrofurans with broad substrate tolerance and good to excellent stereoselectivity, while the use of trialkylphosphine switched the reaction pathway to furnish CF₃-substituted dienyl tertiary alcohols chemoselectively. Moreover, a preliminary study on the asymmetric version of the reaction was also performed, which represents the first example of a phosphine-catalyzed asymmetric reaction between allenoates and carbonyl compounds.

Full text of DOI:10.1021/jo401462c

Article
pubs.acs.org/joc
Phosphine Catalyst-Controlled Cycloaddition or Dienylation
Reactions of Trifluoromethyl Aryl Ketones with Bis-Substituted
Allenoates
Hua Xiao,*,†,‡ Zhuo Chai,† Ri-Sheng Yao,‡ and Gang Zhao*,†
†Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, China
‡School of Medical Engineering, Hefei University of Technology, Hefei 230009, China
S
* Supporting Information
ABSTRACT: A chemoselective phosphine-catalyzed cyclo-
addition or dienylation reaction between trifluoromethyl-
substituted ketones and bis-substituted allenoates was
described. Under the catalysis of triarylphosphine, the reaction
gave a range of trifluoromethylated tetrahydrofurans with
broad substrate tolerance and good to excellent stereo-
selectivity, while the use of trialkylphosphine switched the
reaction pathway to furnish CF3-substituted dienyl tertiary alcohols chemoselectively. Moreover, a preliminary study on the
asymmetric version of the reaction was also performed, which represents the first example of a phosphine-catalyzed asymmetric
reaction between allenoates and carbonyl compounds.
In 2009, He and co-workers10 reported the [3 + 2]
annulation between γ-substituted allenoates and aromatic
The trifluoromethyl-substituted quaternary carbon center is an
aldehyde,11,12 which served as a facile entry to tetrahydrofurans
important structural motif occurring in a range of pharmaceut-
with modest stereoselectivities. The chemoselective formation
of tetrahydrofurans was achieved in refluxing xylene. Herein we
efavirenz,1a antimalarial agent dihydroartemisinin (DHA),1b
disclosed a novel catalyst-dependent13 chemoselective cyclo-
INTRODUCTION
■
icals and drug candidate molecules such as anti-HIV agent
and nonsteroidal selective glucocorticoid receptor (GR) agonist
addition or dienylation reaction between bis-substituted
allenoates and trifluoromethyl ketones. In this system, two
ZK216348.1c Particularly, the CF3-substituted tetrahydrofuran
and tertiary alcohol are substructures present in some bioactive
molecules with great potential value in medicinal chemistry.2
Owing to the higher electrophilicity of α-trifluoromethyl
ketones as compared with their nonfluorinated counterparts,
they are more prone to attack by carbon nucleophiles, which
constitutes a simple and direct way to the CF3-substituted
tertiary alcohols and their analogues.3 On the other hand, the
phosphine-catalyzed cycloaddition reactions of allenoates or
their surrogates with various electrophiles have emerged as a
versatile platform for the synthesis of valuable five- and six-
membered cyclic structures.4,5 Unlike the widely studied
electron-deficient olefins,6a imines,6b and aldehydes,7,8 the use
of CF3-activated ketones as electrophiles in the allenoate
reaction was not disclosed until recently by Ye et al.9 The
products of the reaction with α-trifluoromethyl ketones are
highly dependent on the structures of the allenoates: the use of
simple allenoates gave CF3-substituted 1,2-dihydrofurans
(under phosphine catalysis) or oxetanes (under tertiary amine
catalysis), while the use of α-branched allenoates provided CF3-
substituted dihydropyrans and the use of Morita−Baylis−
Hillman adducts furnished dienes (Scheme 1). Up to now, the
nucleophile-catalyzed γ- or bis-substituted allenoate reaction
with trifluoromethyl ketone had remained unexplored.
skeletally different products, CF3-substituted tetrahydrofurans
and dienyl tertiary alcohols, could be obtained chemoselectively
by judicious choice of the phosphine catalyst (Scheme 1).
Moreover, the presented cycloaddition reaction using α-
trifluoromethyl ketones also enables satisfying improvement
in substrate generality and chemo- and stereoselectivity as
compared with analogous examples.10a,c
RESULTS AND DISCUSSION
■
Initially, γ-methyl allenoate 2a was reacted with CF3-substituted
acetophenone 1a in the presence of (p-CH3OC6H4)3P, giving a
mixture of [3 + 2] cycloadduct 3aa and tertiary alcohol 4aa in
poor product ratio and E,E/Z,E ratio (Scheme 2, eq 1). To our
surprise, the use of α,γ-bis-substituted allenoate 2b led to
excellent chemo- and stereoselectivity: the use of (p-
CH3OC6H4)3P gave [3 + 2] cycloadduct 3a as the sole
product with 93% yield (E/Z > 15/1) under the optimized
reaction conditions (for details, see the Supporting Informa-
tion), and the use of tributylphosphine provided CF3-
substituted dienyl tertiary alcohol 4a with excellent chemo-
Received: July 12, 2013
© XXXX American Chemical Society
A
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Scheme 1. Nucleophilic Phosphine-Catalyzed Reactions of α-Trifluoromethyl Ketones and Allenoates or Their Surrogates
Scheme 2. Chemoselective Reaction between Bis-Substituted Allenoate and Trifluoromethyl Ketone
Table 1. Catalytic [3 + 2] Cycloadditions of Trifluoromethyl Aryl Ketones 1 with Allenoates 2 Catalyzed by Tris(4-
a
methoxyphenyl)phosphine
b
c
entry
1, Ar
1a, Ph
2, R
product
3a
yield (%)
E/Z
1
2
2b, H
2b, H
2b, H
2b, H
2b, H
2b, H
2b, H
2b, H
2b, H
2b, H
2b, H
2c, Me
2b, H
93
83
90
85
69
71
70
64
70
89
77
69
64
15/1
12/1
11/1
19/1
9/1
1b, 4-BrC6H4
1c, 4-FC6H4
1d, 4-ClC6H4
1e, 4-MeOC6H4
1f, 3-MeOC6H4
1g, 4-EtOC6H4
1h, 4-EtC6H4
1i, 4-MeC6H4
1j, 2-thienyl
3b
3
3c
4
3d
5
3e
6
3f
8/1
7
3g
15/1
9/1
8
3h
9
3i
8/1
10
11
3j
12/1
11/1
19/1
8/1
1k, 1-naphthyl
1a, Ph
3k
d
12
e
3ac, 3ac′
3l
13
1l, 4-MeSC6H4
a
Unless otherwise noted, all reactions were carried out with 1 (0.1 mmol) and 2 (0.15 mmol) in the presence of phosphine (0.02 mmol) in CH2Cl2
b
c
d
(1.0 mL) for 3 h at rt. Yields of isolated E isomer. Determined by 1H NMR analysis of crude products. The diastereoselectivity ratio of 3ac and
e
3ac′ was determined as 56/44 by isolated yield. The double bond migration product 3l′ was obtained in 28% yield and with 1.2/1
diastereoselectivity concurrently.
selectivity and moderate E,E selectivity, which may be viewed as
a double vinylic analogue of Mosher’s ester (Scheme 2, eq 2).
The presence of Bu3P also gave the isomerization product of
allenoate 2b itself concomitantly (for details, see the
Supporting Information). Notably, in all cases examined
above, 1,3-dioxane derivatives (common byproduct in aldehyde
B
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Article
reactions; see Kwon and He’s reports7d,10a) was not detected,
which may be ascribed to the steric hindrance of the CF3 group.
The reaction scope under the catalysis of tris(4-
methoxyphenyl)phosphine was first examined (Table 1). The
[3 + 2] cycloaddition reaction between bis-substituted allenoate
2b and various aryl trifluoromethyl ketones proceeded
smoothly to provide a range of synthetically valuable
tetrahydrofurans containing a CF3-substituted quaternary
stereogenic center in 64−93% yields and with good to excellent
E selectivities as the only products. An obvious electronic effect
on the reactivity was observed: aromatic ketones containing
electron-withdrawing substituents in general gave higher yields
and stereoselectivities than those with electron-donating
substituents. The heteroaryl ketone 1j and the sterically
demanding substrate 1k were also well-tolerated in the
cycloaddition (entries 10 and 11). However, aliphatic substrates
were totally unsuitable (the aliphatic ketones generally
remained unreacted under the typical reaction conditions).
The reaction proceeded uneventfully when γ-ethyl allenoate 2c
was employed as the substrate, albeit with a poor diaster-
eoselectivity (entry 12). To our surprise, the relatively electron-
rich ketone 1l was reactive enough to achieve full conversion,
furnishing the normal cycloadduct in 72% yield with a
moderate E/Z ratio. Meanwile, an unprecedented double
bond migration product, 3l′, was also isolated in 28% yield with
statistically random diastereoselectivity (entry 13). Further
study revealed such migration of an exocyclic double bond is
thermodynamically favored: when the reaction time was
prolonged, all tested aryl ketones yielded a trace amount of
migrated products.
interest.14 Different from the observation in the (p-
CH3OC6H4)3P catalysis, the Bu3P-catalyzed reaction of
substrates 1b, 1c, and 1d bearing electron-withdrawing
substituents required a higher reaction temperature in toluene
to give high yields of the diene products, albeit with low E,E/
Z,E selectivities (entries 2−4). Similar results were also
observed with heteroaryl ketone 1j and 1-naphthyl ketone 1k
(entries 10 and 11). In comparison, the reaction of substrates
with electron-neutral or electron-donating substitutents could
be run at rt to provide higher yields and E,E/Z,E selectivities.
The configuration of diene 4a was assigned by comparison with
literature analogues15 via 1H NMR analysis, and the
configurations of the others were assigned accordingly. Notably,
in the cases examined, small amounts of tetrahydrofuran
products 3 were also formed concomitantly.
Recently, significant advances have been made in the
applications of chiral phosphines for asymmetric allenoate
reaction. However, the development of P-catalyzed enantiose-
lective reactions involving carbonyl electrophiles or γ-
substituted allenoate (in the case in which the γ-substitutents
participate in the reaction) has not been reported.16 The
stereocontrolled δ addition of a phosphine−allenoate inter-
mediate was still a challenging goal due to the remote distance
between the chiral center of the catalyst and the δ carbon of the
allenoate. Herein we also performed some preliminary research
on the enantioselective cycloaddition with activated ketones
catalyzed by our previously developed chiral bifunctional
phosphines (Scheme 3).17 With the trifluoromethyl ketone 1a
in the presence of catalyst 5a, the reaction with allenoates 2a
and 2b proceeded uneventfully to provide the diene and
tetrahydrofuran products in moderate yields (for details on
chiral catalyst screening, see the Supporting Information), albeit
with poor enantioselectivities (Scheme 3, eq 1). To our delight,
the reaction with another type of activated carbonyl, α-keto
ester 1a′, worked well to give the corresponding tetrahydrofur-
an 3ad with superior ee with catalyst 5b. To our knowledge,
this is the first example of enantioselective P-catalyzed reaction
between allenoate or its surrogate and carbonyl compounds.
Moreover, the investigation of asymmetric catalysis revealed
that the reaction pathway was also tunable by changing the α-
substituent patterns of γ-methyl allenoates (Scheme 3, eq 1).
Notably, chemoselectivities in these asymmetric reactions were
generally excellent with no byproducts detected.
Subsequently, the scope of Bu3P-catalyzed dienylation
reaction of trifluoromethyl ketone was tested, and the results
are summarized in Table 2. The reaction provided facile access
to CF3-substituted dienyl tertiary alcohols with generally high
yields, which could also be a unique complement to the current
strategies for accessing the diene motif of high synthetic
Table 2. Catalytic Additions of Trifluoromethyl Aryl Ketones
a
1 with Allenoate 2b Catalyzed by Tributylphosphine
On the basis of previous reports18,10a and our own
observation, a tentative mechanistic rationale for the chemo-
selective reaction is illustrated in Scheme 4. Upon the
nucleophilic addition of phosphine, the allenoate is first
converted to zwitterionic intermediate A, which undergoes
1,4-H migration immediately to give intermediate B. The
vinylic phosphonium B, stabilized by its phosphorus ylide
resonance form, attacks the carbonyl group of the trifluor-
omethyl ketone to furnish intermediate C1 or C2. Depending
on the phosphine catalysts used, two pathways are possible: (1)
due to the P−O interaction,18d triarylphosphine-derived
zwitterions might form a six-membered ring, C2, which is
suitable for ring closure after a double bond migration to give
intermediate D, and the latter would undergo a 5-exo-trig
process to produce the tetrahydrofuran product 3 with release
of the phosphine; (2) for trialkylphosphine-derived zwitterions,
the more electron-rich substituent (n-butyl group) on the
phosphorus center could stabilize its positive charge more
efficiently, and less P−O interaction might be expected.18a
Thus, in this case, together with steric factors, the open-chained
b
d
yield of 4
yield of 3
c
entry
1
1, Ar
1a, Ph
4
(%)
E,E/Z,E
(%)
4a
4b
4c
4d
90
86
88
80
88
93
83
88
84
80
70
82
7/1
5
10
8
e
2
1b, 4-BrC6H4
1c, 4-FC6H4
1d, 4-ClC6H4
2/1
e
3
e
2.3/1
2/1
4
12
5
5
6
7
8
9
1e, 4-MeOC6H4 4e
6/1
1f, 3-MeOC6H4
1g, 4-EtOC6H4
1h, 4-EtC6H4
1i, 4-MeC6H4
1j, 2-thienyl
4f
4g
4h
4i
6/1
5
6.5/1
6.5/1
7/1
4
5
4
e
10
4j
3/1
12
12
4
e
11
1k, 1-naphthyl
1l, 4-MeSC6H4
4k
4l
3/1
12
6/1
a
Unless otherwise noted, all reactions were carried out with 1 (0.1
mmol) and 2 (0.12 mmol) in the presence of phosphine (0.015
mmol) in CH2Cl2 (2.0 mL) for 3 h at rt. Isolated yields of E,E and
Z,E isomers. Determined by H NMR analysis of crude products.
b
c
1
d
e
Isolated yields of E isomers. The reaction was run at 60 °C for 2 h.
C
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Scheme 3. Exploration of the Asymmetric Annulation of Activated Ketone and γ-Substituted Allenoate
Scheme 4. Plausible Reaction Mechanism
C1 would be favored, which was transformed to intermediate G
through some internal proton transfer processes (via E and F)
to provide the diene compound. A full understanding of the
intrinsic factors determining such chemoselectivity of this
reaction still requires further study.
EXPERIMENTAL SECTION
■
General Methods. Unless otherwise indicated, chemicals and
solvents were purchased from commercial suppliers or purified by
standard techniques. All reactions were carried out employing oven-
dried glassware. Various γ-substituted allenoates were prepared
according to a modificated version of the literature procedure8e,19a
and stored at 4 °C prior to use. All trifluoromethyl aryl ketones were
prepared following reported procedures19b,c or purchased from
commercial suppliers. All acyl-protected aminophosphines were
synthesized according to procedures reported previously.17a
Representative Procedure for the Triarylphosphine-Cata-
lyzed Cycloadditions. To a stirred solution of trifluoromethyl
ketone 1 (0.1 mmol) and phosphine (0.02 mmol) in CH2Cl2 (1 mL)
was added γ-substituted allenoate (0.15 mmol) via a microsyringe in
one portion. Then the resulting mixture was vigorously stirred at rt
and monitored by TLC. After the reaction was complete, the mixture
was directly purified by column chromatography on silica gel
(petroleum ether/ethyl acetate (10/1) as the eluent) to furnish the
corresponding product. The E/Z geometries of the main products
were determined by comparison of 1H NMR data with those of
cycloadduct 3aa, which were compared with those of known
analogues.10a
CONCLUSION
■
In conclusion, we have demonstrated a catalyst-controlled
chemoselective cycloaddition or dienylation reaction between
trifluoromethyl ketone and bis-substituted allenoate with
commercially available simple phosphine catalysts. These
findings not only enrich the chemistry of reactions of allenoates
under nucleophilic catalysis, but also enable easy access to two
sets of skeletally diverse products bearing CF3 quarternary
stereogenic centers, namely, trifluoromethylated tetrahydrofur-
ans and dienyl tertiary alcohols, in good yields and E selectivity.
Furthermore, a preliminary study on the first asymmetric P-
catalyzed annulation reaction of allenoate with carbonyls was
also performed with promising results for further research.
Efforts toward a highly enantioselective version of the reaction
are currently under way in our laboratories.
Data for (E)-diethyl 2-(5-phenyl-5-(trifluoromethyl)dihydrofuran-
2(3H)-ylidene)succinate (3a): 36 mg, 93% yield; Rf = 0.4 (petroleum
ether/ethyl acetate, 80/20); viscous, colorless oil; 1H NMR (400
MHz, CDCl3) δ = 7.47−7.46 (m, 2H), 7.41−7.39 (m, 3H), 4.17 (q, J
= 7.0 Hz, 4H), 3.55 (d, JAB = 16.8 Hz, 1H), 3.49 (d, JAB = 16.8 Hz,
D
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1H), 3.42−3.33 (m, 1H), 3.21−3.13 (m, 1H), 2.90−2.83 (m, 1H),
2.55−2.47 (m, 1H), 1.27 (t, J = 7.0 Hz, 3H), 1.26 (t, J = 7.0 Hz, 3H);
13C NMR (CDCl3, 100 MHz) δ = 171.6, 169.8, 167.4, 135.4, 129.3,
0.35 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.34 (dd, J = 8.2, 8.1 Hz, 1H), 7.01 (d, J
= 8.2 Hz, 2H), 6.95 (m, 1H), 4.20 (q, J = 7.0 Hz, 4H), 3.85 (s, 3H),
3.57 (d, JAB = 16.8 Hz, 1H), 3.52 (d, JAB = 16.8 Hz, 1H), 3.45−3.36
(m, 1H), 3.22−3.14 (m, 1H), 2.90−2.83 (m, 1H), 2.57−2.50 (m, 1H),
1.29 (t, J = 7.0 Hz, 6H); 13C NMR (CDCl3, 100 MHz) δ = 171.6,
169.8, 167.4, 159.7, 136.9, 127.3, 124.4 (q, JC−F = 284 Hz), 118.5,
114.4, 112.6, 99.1, 88.7 (q, JC−F = 30.1 Hz), 60.6, 60.2, 55.3, 32.2, 32.0,
30.1, 14.3, 14.2; 19F NMR (CDCl3, 282 MHz) δ = −79.4; IR (film,
cm−1) 2981, 2936, 2851, 1738, 1712, 1657, 1604, 1586, 1493, 1465,
1369, 1295, 1178, 1101, 1047, 883, 784, 728; HRMS (MALDI) m/z
calcd for C20H23F3O6Na [M + Na]+ 439.1344, found 439.1339.
Data for (E)-diethyl 2-(5-(4-ethoxyphenyl)-5-(trifluoromethyl)-
dihydrofuran-2(3H)-ylidene)succinate (3g): 30 mg, 70% yield; Rf =
0.36 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.39 (d, J = 8.7 Hz, 2H), 6.93 (d, J = 8.8
Hz, 2H), 4.20 (q, J = 7.3 Hz, 4H), 4.07 (q, J = 7.0 Hz, 2H), 3.56 (d,
JAB = 16.8 Hz, 1H), 3.51 (d, JAB = 16.8 Hz, 1H), 3.44−3.35 (m, 1H),
3.23−3.14 (m, 1H), 2.89−2.81 (m, 1H), 2.55−2.48 (m, 1H), 1.44 (t, J
= 7.0 Hz, 3H), 1.29 (t, J = 7.2 Hz, 6H); 13C NMR (CDCl3, 100 MHz)
δ = 171.6, 169.9, 167.5, 127.6, 127.1, 124.5 (q, JC−F = 285 Hz), 114.4,
99.0, 88.7 (q, JC−F = 30.1 Hz), 63.6, 60.6, 60.2, 32.0, 30.2, 29.7, 14.7,
14.3, 14.2; 19F NMR (CDCl3, 282 MHz) δ = −76.6; IR (film, cm−1)
2982, 2935, 1740, 1713, 1653, 1514, 1300, 1252, 1172, 1118, 1047,
898, 834, 808; HRMS (MALDI) m/z calcd for C21H25F3O6Na [M +
Na]+ 453.1501, found 453.1496.
Data for (E)-diethyl 2-(5-(4-ethylphenyl)-5-(trifluoromethyl)-
dihydrofuran-2(3H)-ylidene)succinate (3h): 26 mg, 69% yield; Rf =
0.38 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (300 MHz, CDCl3) δ = 7.37 (d, J = 8.2 Hz, 2H), 7.22 (d, J = 8.2
Hz, 2H), 4.16 (q, J = 7.0 Hz, 2H), 4.15 (q, J = 7.1 Hz, 2H), 3.53 (d,
JAB = 16.7 Hz, 1H), 3.47 (d, JAB = 17.0 Hz, 1H), 3.39−3.31 (m, 1H),
3.23−3.09 (m, 1H), 2.88−2.78 (m, 1H), 2.65 (q, J = 7.6 Hz, 2H),
2.54−2.45 (m, 1H), 1.26−1.24 (m, 9H); 13C NMR (CDCl3, 100
MHz) δ = 171.6, 169.9, 167.5, 145.5, 132.6, 128.0, 126.3, 124.5 (q,
JC−F = 284 Hz), 99.0, 88.8 (q, JC−F = 30.1 Hz), 60.6, 60.2, 32.1, 30.1,
29.7, 28.5, 15.3, 14.3, 14.2; 19F NMR (CDCl3, 282 MHz) δ = −79.6;
IR (film, cm−1) 2969, 2930, 2855, 1741, 1713, 1656, 1515, 1462, 1415,
1369, 1316, 1175, 1090, 1047, 830, 785; HRMS (MALDI) m/z calcd
for C21H25F3O5Na [M + Na]+ 437.1552, found 437.1546.
Data for (E)-diethyl 2-(5-(p-tolyl)-5-(trifluoromethyl)-
dihydrofuran-2(3H)-ylidene)succinate (3i): 28 mg, 70% yield; Rf =
0.36 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.38 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.1
Hz, 2H), 4.20 (q, J = 7.0 Hz, 4H), 3.57 (d, JAB = 16.8 Hz, 1H), 3.52 (d,
JAB = 16.8 Hz, 1H), 3.44−3.36 (m, 1H), 3.23−3.14 (m, 1H), 2.90−
2.83 (m, 1H), 2.56−2.49 (m, 1H), 2.39 (s, 3H), 1.30 (t, J = 7.0 Hz,
3H), 1.29 (t, J = 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ =
171.6, 169.9, 167.5, 139.3, 132.4, 129.2, 126.2, 124.4 (q, JC−F = 285
Hz), 99.0, 88.8 (q, JC−F = 30.1 Hz), 60.6, 60.2, 32.0, 30.1, 29.7, 21.1,
14.3, 14.2; 19F NMR (CDCl3, 282 MHz) δ = −79.7; IR (film, cm−1)
2982, 2933, 1740, 1713, 1658, 1515, 1461, 1369, 1315, 1174, 1121,
1088, 1048, 899, 815; HRMS (MALDI) m/z calcd for C20H23F3O5Na
[M + Na]+ 423.1395, found 423.1390.
Data for (E)-diethyl 2-(5-(thiophene-2-yl)-5-(trifluoromethyl)-
dihydrofuran-2(3H)-ylidene)succinate (3j): 35 mg, 89% yield; Rf =
0.33 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.39 (dd, J = 5.0, 1.0 Hz, 1H), 7.18 (d, J
= 3.5 Hz, 1H), 7.06 (dd, J = 5.0, 3.7 Hz, 1H), 4.19 (q, J = 7.0 Hz, 4H),
3.51 (d, JAB = 17.1 Hz, 1H), 3.48 (d, JAB = 16.8 Hz, 1H), 3.46−3.42
(m, 1H), 3.25−3.17 (m, 1H), 2.86−2.79 (m, 1H), 2.63−2.56 (m, 1H),
1.29 (t, J = 7.0 Hz, 6H); 13C NMR (CDCl3, 100 MHz) δ = 171.4,
169.3, 167.3, 137.9, 127.2, 127.0, 126.8, 123.8 (q, JC−F = 284 Hz), 99.7,
87.5 (q, JC−F = 30.4 Hz), 60.6, 60.3, 33.2, 31.9, 30.1, 14.3, 14.2; 19F
NMR (CDCl3, 282 MHz) δ = −76.8; IR (film, cm−1) 3107, 2982,
2936, 2358, 1740, 1713, 1462, 1369, 1299, 1175, 1089, 1046, 883, 843,
781, 710; HRMS (MALDI) m/z calcd for C17H19F3O5SNa [M + Na]+
415.0803, found 415.0798.
128.5, 126.3, 124.4 (q, JC−F = 248 Hz), 99.1, 88.8 (q, JC−F = 30.1 Hz),
60.6, 60.2, 32.1, 32.0, 30.1, 14.3, 14.2; 19F NMR (CDCl3, 282 MHz) δ
= −79.6; IR (film, cm−1) 2983, 1738, 1656, 1454, 1370, 1309, 1186,
1101, 1042, 891, 768, 723; HRMS (ESI) m/z calcd for C19H21F3O5Na
[M + Na]+ 409.1239, found 409.1238. Data for the chiral product
(best ee obtained with a trifluoromethyl ketone, catalyzed by
phenylalanine-derived phosphine 5i; for details, see Table 4S in the
Supporting Information): enantiometric excess 33%; HPLC analysis
(Chiralpak AD-H column, hexane/i-PrOH, 90/10, flow rate 0.60 mL/
min) tmajor = 14.6 min, tminor = 10.6 min, λ = 254 nm.
Data for (E)-diethyl 2-(5-(4-bromophenyl)-5-(trifluoromethyl)-
dihydrofuran-2(3H)-ylidene)succinate (3b): 38 mg, 83% yield; Rf =
1
0.38 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; H
NMR (400 MHz, CDCl3) δ = 7.54 (d, J = 8.5 Hz, 2H), 7.35 (d, J = 8.5
Hz, 2H), 4.17 (q, J = 7.0 Hz, 4H), 3.53 (d, JAB = 16.8 Hz, 1H), 3.47 (d,
JAB = 16.8 Hz, 1H), 3.42−3.33 (m, 1H), 3.21−3.13 (m, 1H), 2.89−
2.82 (m, 1H), 2.50−2.42 (m, 1H), 1.27 (t, J = 7.0 Hz, 3H), 1.26 (t, J =
7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ = 171.5, 169.4, 167.3,
134.5, 131.8, 128.1, 124.1 (q, JC−F = 285 Hz), 99.5, 88.5 (q, JC−F = 30.1
Hz), 60.7, 60.3, 32.1, 32.0, 30.0, 14.3, 14.2; 19F NMR (CDCl3, 282
MHz) δ = −79.6; IR (film, cm−1) 2982, 2935, 1739, 1713, 1658, 1490,
1369, 1312, 1173, 1113, 1048, 1009, 898, 821, 781, 736; HRMS
(MALDI) m/z calcd for C19H20BrF3O5Na [M + Na]+ 487.0338, found
487.0344.
Data for (E)-diethyl 2-(5-(4-fluorophenyl)-5-(trifluoromethyl)-
dihydrofuran-2(3H)-ylidene)succinate (3c): 36 mg, 90% yield; Rf =
1
0.4 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; H
NMR (400 MHz, CDCl3) δ = 7.48 (dd, J = 8.5, 6.0 Hz, 2H), 7.12 (dd,
J = 8.8, 8.5 Hz, 2H), 4.20 (q, J = 7.0 Hz, 2H), 4.19 (q, J = 7.0 Hz, 2H),
3.55 (d, JAB = 16.8 Hz, 1H), 3.50 (d, JAB = 16.8 Hz, 1H), 3.45−3.36
(m, 1H), 3.25−3.16 (m, 1H), 2.92−2.85 (m, 1H), 2.54−2.47 (m, 1H),
1.29 (t, J = 7.0 Hz, 3H), 1.28 (t, J = 7.0 Hz, 3H); 13C NMR (CDCl3,
100 MHz) δ = 171.5, 169.5, 167.3, 163.23 (d, JC−F = 249 Hz), 131.3
(d, JC−F = 3.6 Hz), 128.3 (d, JC−F = 8.1 Hz), 124.3 (q, JC−F = 284 Hz),
115.5 (d, JC−F = 22 Hz), 99.3, 88.4 (q, JC−F = 30 Hz), 60.6, 60.3, 32.2,
32.0, 30.1, 14.3, 14.2; 19F NMR (CDCl3, 282 MHz) δ = −76.5,
−109.3; IR (film, cm−1) 2983, 2937, 1738, 1702, 1657, 1513, 1370,
1312, 1238, 1176, 1128, 1048, 837, 781; HRMS (MALDI) m/z calcd
for C19H20F4O5Na [M + Na]+ 427.1145, found 427.1139.
Data for (E)-diethyl 2-(5-(4-chlorophenyl)-5-(trifluoromethyl)-
dihydrofuran-2(3H)-ylidene)succinate (3d): 36 mg, 85% yield; Rf =
1
0.38 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; H
NMR (400 MHz, CDCl3) δ = 7.43−7.37 (m, 4H), 4.17 (q, J = 7.0 Hz,
4H), 3.53 (d, JAB = 16.8 Hz, 1H), 3.48 (d, JAB = 16.8 Hz, 1H), 3.42−
3.34 (m, 1H), 3.22−3.13 (m, 1H), 2.89−2.82 (m, 1H), 2.50−2.43 (m,
1H), 1.27 (t, J = 7.0 Hz, 3H), 1.26 (t, J = 7.0 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) δ = 171.5, 169.4, 167.3, 135.6, 134.0, 128.8, 127.8,
124.2 (q, JC−F = 285 Hz), 99.4, 88.3 (q, JC−F = 30.1 Hz), 60.7, 60.3,
32.1, 32.0, 30.0, 14.3, 14.2; 19F NMR (CDCl3, 282 MHz) δ = −79.6;
IR (film, cm−1) 2982, 2936, 1720, 1660, 1494, 1463, 1369, 1311, 1255,
1175, 1086, 1048, 1012, 826, 738; HRMS (MALDI) m/z calcd for
C19H20ClF3O5Na [M + Na]+ 443.0849, found 443.0844.
Data for (E)-diethyl 2-(5-(4-methoxyphenyl)-5-(trifluoromethyl)-
dihydrofuran-2(3H)-ylidene)succinate (3e): 28 mg, 69% yield; Rf =
1
0.35 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; H
NMR (300 MHz, CDCl3) δ = 7.42 (d, J = 8.5 Hz, 2H), 6.91 (d, J = 8.5
Hz, 2H), 4.16 (q, J = 7.0 Hz, 4H), 3.81 (s, 3H), 3.54 (d, JAB = 16.8 Hz,
1H), 3.47 (d, JAB = 16.8 Hz, 1H), 3.39−3.30 (m, 1H), 3.20−3.09 (m,
1H), 2.86−2.76 (m, 1H), 2.53−2.43 (m, 1H), 1.27 (m, 6H); 13C
NMR (CDCl3, 100 MHz) δ = 171.6, 169.9, 167.5, 160.3, 127.7, 127.3,
124.4 (q, JC−F = 284 Hz), 113.9, 99.0, 88.7 (q, JC−F = 30.1 Hz), 60.6,
60.2, 55.3, 32.0, 30.2, 29.7, 14.3, 14.2; 19F NMR (CDCl3, 282 MHz) δ
= −79.8; IR (film, cm−1) 2981, 2937, 2843, 1736, 1655, 1612, 1516,
1463, 1369, 1302, 1254, 1172, 1087, 1047, 897, 832; HRMS (MALDI)
m/z calcd for C20H23F3O6Na [M + Na]+ 439.1344, found 439.1339.
Data for (E)-diethyl 2-(5-(3-methoxyphenyl)-5-(trifluoromethyl)-
dihydrofuran-2(3H)-ylidene)succinate (3f): 29 mg, 71% yield; Rf =
Data for (E)-diethyl 2-(5-(naphthalen-1-yl)-5-(trifluoromethyl)-
dihydrofuran-2(3H)-ylidene)succinate (3k): 33 mg, 77% yield; Rf =
E
dx.doi.org/10.1021/jo401462c | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1
0.33 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; H
NMR (400 MHz, CDCl3) δ = 8.31 (br, 1H), 7.93 (dd, J = 8.1, 7.5 Hz,
2H), 7.82 (br, 1H), 7.59 (m, 1H), 7.53 (m, 2H), 4.25−4.17 (m, 4H),
3.64 (d, JAB = 16.9 Hz, 1H), 3.59 (d, JAB = 16.8 Hz, 1H), 3.44−3.40
(m, 2H), 3.34−3.29 (m, 1H), 2.94−2.86 (m, 1H), 1.30 (m, 6H); 13C
NMR (CDCl3, 100 MHz) δ = 171.5, 167.5, 134.5, 131.5, 130.9, 129.3,
127.1, 126.5, 125.7, 124.7, 123.7, 98.9, 60.7, 60.2, 32.3, 29.7, 14.3, 14.2;
19F NMR (CDCl3, 282 MHz) δ = −75.1; IR (film, cm−1) 2982, 2934,
(CDCl3, 100 MHz) δ = 171.6, 168.8, 167.5, 136.5, 129.1, 128.5, 125.7,
99.0, 60.6, 60.2, 42.0, 39.2, 31.9, 15.4, 14.3, 14.2; 19F NMR (CDCl3,
282 MHz) δ = −73.4; IR (film, cm−1) 2983, 2937, 1739, 1712, 1657,
1369, 1312, 1168, 1111, 1052, 1029, 724, 699; HRMS (MALDI) m/z
calcd for C20H23F3O5Na [M + Na]+ 423.1395, found 423.1390.
Data for (E)-diethyl 2-(5-(4-(methylthio)phenyl)-5-
(trifluoromethyl)dihydrofuran-2(3H)-ylidene)succinate (3l): 28 mg,
64% yield; Rf 1= 0.35 (petroleum ether/ethyl acetate, 80/20); viscous,
colorless oil; H NMR (400 MHz, CDCl3) δ = 7.37 (d, J = 8.3 Hz,
1738, 1712, 1653, 1463, 1369, 1311, 1178, 1129, 1098, 1078, 1049,
962, 803, 777; HRMS (MALDI) m/z calcd for C23H23F3O5Na [M +
Na]+ 459.1390, found 459.1395.
2H), 7.26 (d, J = 8.5 Hz, 2H), 4.17 (q, J = 7.0 Hz, 4H), 3.53 (d, JAB
=
16.8 Hz, 1H), 3.48 (d, JAB = 16.9 Hz, 1H), 3.42−3.33 (m, 1H), 3.20−
3.11 (m, 1H), 2.87−2.80 (m, 1H), 2.49 (m, 4H), 1.27 (t, J = 7.3 Hz,
3H), 1.26 (t, J = 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ =
171.6, 169.7, 167.4, 140.5, 131.9, 126.7, 126.1, 124.3 (q, JC−F = 285
Hz), 99.2, 88.6 (q, JC−F = 30.1 Hz), 60.6, 60.2, 32.0, 30.1, 29.7, 15.4,
14.3, 14.2; 19F NMR (CDCl3, 282 MHz) δ = −79.6; IR (film, cm−1)
2982, 2935, 1740, 1713, 1653, 1514, 1300, 1252, 1172, 1118, 1047,
898, 834, 808; HRMS (MALDI) m/z calcd for C20H23F3O5SNa [M +
Na]+ 455.1116, found 455.1111.
Data for (E)-ethyl 2-(5-phenyl-5-(trifluoromethyl)dihydrofuran-
2(3H)-ylidene)acetate (3aa): 6 mg, 21% yield; Rf = 0.4 (petroleum
ether/ethyl acetate, 80/20); viscous, colorless oil; 1H NMR (400
MHz, CDCl3) δ = 7.53 (m, 2H), 7.44 (m, 3H), 5.63 (m, 1H), 4.18 (q,
J = 7.0 Hz, 2H), 3.37 (m, 1H), 3.15 (m, 1H), 2.88 (m, 1H), 2.53 (m,
1H), 1.30 (t, J = 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ =
173.7, 135.5, 129.3, 128.5, 126.3, 92.4, 59.6, 31.7, 29.4, 14.2; 19F NMR
(CDCl3, 282 MHz) δ = −72.7; IR (film, cm−1) 3027, 2939, 1718,
1653, 1621, 1481, 1387, 1345, 1261, 1129, 1035, 1001, 956, 821;
HRMS (MALDI) m/z calcd for C15H15F3O3Na [M + Na]+ 323.0871,
found 323.0873.
Data for (Z)-ethyl 2-(5-phenyl-5-(trifluoromethyl)dihydrofuran-
2(3H)-ylidene)acetate (3aa′): 5 mg, 17% yield; Rf = 0.25 (petroleum
ether/ethyl acetate, 80/20); viscous, colorless oil; 1H NMR (400
MHz, CDCl3) δ = 7.60 (m, 2H), 7.41 (m, 3H), 4.98 (m, 1H), 4.21 (q,
J = 7.0 Hz, 2H), 2.99 (m, 1H), 2.83 (m, 1H), 2.73 (m, 1H), 2.43 (m,
1H), 1.32 (t, J = 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ =
165.2, 135.6, 129.3, 128.5, 126.5, 91.2, 59.6, 30.7, 29.7, 14.4; 19F NMR
(CDCl3, 282 MHz) δ = −73.1; IR (film, cm−1) 3031, 2899, 1724,
1619, 1601, 1487, 1347, 1325, 1274, 1131, 1045, 1015, 959, 764;
HRMS (MALDI) m/z calcd for C15H15F3O3Na [M + Na]+ 323.0871,
found 323.0875.
Data for diethyl 2-(5-(4-(methylthio)phenyl)-5-(trifluoromethyl)-
4,5-dihydrofuran-2-yl)succinate (3l′): 12 mg, 28% yield; Rf = 0.38
(petroleum ether/ethyl acetate, 80/20); dr = 1.18/1, the mixture of
diastereoisomers was unseparable by column chromatography; viscous,
1
colorless oil; H NMR (400 MHz, CDCl3) δ = 7.41−7.38 (m, 2H),
7.27−7.24 (m, 2H), 4.85 (m, 1H), 4.21−4.13 (m, 4H), 3.84−3.81 (m,
1H), 3.38 (dd, J = 16.8, 7.0 Hz, 1H), 3.09−2.98 (m, 2H), 2.71 (ddd, J
= 16.8, 9.3, 5.5 Hz, 1H), 2.49 (s, 3H), 1.27−1.24 (m, 6H); 13C NMR
(CDCl3, 100 MHz) δ = 171.1, 170.2, 139.8, 134.4, 126.8, 126.7, 126.1,
96.7, 96.5, 61.6, 61.5, 60.9, 41.0, 40.9, 39.5, 34.3, 34.1, 29.7, 15.5, 14.1,
14.0; 19F NMR (CDCl3, 282 MHz) δ = −81.9, −82.0; IR (film, cm−1)
2983, 2928, 1740, 1599, 1495, 1446, 1373, 1306, 1253, 1165, 1069,
1030, 863, 818, 736, 688; HRMS (MALDI) m/z calcd for
C20H23F3O5SNa [M + Na]+ 455.1116, found 455.1111.
Data for (E)-diethyl 2-(5-(ethoxycarbonyl)-5-phenyldihydrofur-
an-2(3H)-ylidene)succinate (3ab): 20 mg, 51% yield; Rf = 0.34
(petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.48 (m, 2H), 7.35 (m, 3H), 4.17 (q, J =
7.1 Hz, 6H), 3.58 (d, JAB = 16.8 Hz, 1H), 3.51 (d, JAB = 16.8 Hz, 1H),
3.22 (m, 1H), 3.16 (m, 1H), 2.97 (m, 1H), 2.38 (dt, J = 12.6, 8.5 Hz,
1H), 1.26 (m, 6H), 1.21 (t, J = 7.1 Hz, 3H); 13C NMR (CDCl3, 100
MHz) δ = 171.9, 170.7, 170.2, 167.8, 138.6, 128.5, 128.4, 125.1, 98.3,
90.6, 62.1, 60.5, 60.0, 35.4, 32.0, 30.3, 14.4, 14.3, 13.9; IR (film, cm−1)
2981, 2932, 2854, 1736, 1650, 1449, 1368, 1304, 1259, 1176, 1094,
1058, 887, 860, 781; HRMS (MALDI) m/z calcd for C21H26O7Na [M
+ Na]+ 413.1576, found 413.1558. Data for the chiral product:
enantiometric excess 48%; HPLC analysis (Chiralpak AD-H column,
hexane/i-PrOH, 90/10, flow rate 0.60 mL/min) tmajor = 15.5 min, tminor
= 14.4 min, λ = 254 nm.
Data for (2E,4E)-ethyl 7,7,7-trifluoro-6-hydroxy-6-phenylhepta-
2,4-dienoate (4aa): 7 mg, 24% yield; Rf = 0.3 (petroleum ether/ethyl
acetate, 80/20); viscous, colorless oil; 1H NMR (300 MHz, CDCl3) δ
= 7.58−7.56 (m, 2H), 7.41−7.37 (m, 3H), 7.30 (dd, J = 15.6, 5.0 Hz,
1H), 6.64 (dd, J = 15.2, 10.3 Hz, 1H), 6.56 (d, J = 15.5 Hz, 1H), 5.96
(d, J = 15.3 Hz, 1H), 4.20 (q, J = 7.0 Hz, 2H), 3.04 (br, 1H), 1.29 (t, J
= 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ = 166.5, 142.3, 137.5,
136.7, 130.8, 129.1, 128.6, 126.6, 126.1, 124.3, 60.6, 14.2; 19F NMR
(CDCl3, 282 MHz) δ = −76.3; IR (film, cm−1) 3427, 2984, 1698,
1645, 1619, 1451, 1370, 1305, 1241, 1166, 1077, 1001, 941, 706;
HRMS (MALDI) m/z calcd for C15H15F3O3Na [M + Na]+ 323.0871,
found 323.0875. Data for the chiral product from the catalysis of
phosphine 5i: yield 50%; enantiometric excess 26%; HPLC analysis
(Chiralpak OD column, hexane/i-PrOH, 90/10, flow rate 0.70 mL/
min) tmajor = 19.7 min, tminor = 12.3 min, λ = 254 nm.
Data for (E)-ethyl 5-(3-cyano-1-ethoxy-1-oxopropan-2-ylidene)-
2-phenyltetrahydrofuran-2-carboxylate (3ad): 26 mg, 75% yield; Rf
= 0.34 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil;
1H NMR (400 MHz, CDCl3) δ = 7.55 (m, 2H), 7.42 (m, 3H), 4.25
trans-(E)-Diethyl 2-(4-Methyl-5-phenyl-5-(trifluoromethyl)-
dihydrofuran-2(3H)-ylidene)succinate (3ac). The diastereoisomers
were separable by silica gel chromatography, which could be
discriminated by 1H NMR data. The diagnostic feature is the chemical
shift differences of the methyl group caused by the shielding effect of
the adjacent phenyl group. Data for 3ac: 15 mg, 38% yield; Rf = 0.35
(petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.45−7.43 (m, 5H), 4.22 (q, J = 7.3 Hz,
2H), 4.20 (q, J = 7.0 Hz, 2H), 3.65−3.49 (m, 3H), 3.13−3.04 (m,
1H), 2.86 (dd, J = 18.1, 6.3 Hz, 1H), 1.30 (m, 6H), 0.86 (d, J = 7.1 Hz,
3H); 13C NMR (CDCl3, 100 MHz) δ = 171.6, 169.2, 167.6, 132.4,
129.0, 128.4, 126.4, 126.3, 123.6, 99.2, 91.1 (q, JC−F = 30.1 Hz), 60.6,
60.2, 38.6, 36.7, 31.9, 17.3, 14.3, 14.2; 19F NMR (CDCl3, 282 MHz) δ
= −76.6; IR (film, cm−1) 2982, 2936, 1739, 1712, 1657, 1450, 1369,
1314, 1298, 1178, 1101, 1071, 1051, 934, 729; HRMS (MALDI) m/z
calcd for C20H23F3O5Na [M + Na]+ 423.1395, found 423.1390.
Data for cis-(E)-diethyl 2-(4-methyl-5-phenyl-5-(trifluoromethyl)-
dihydrofuran-2(3H)-ylidene)succinate (3ac′): 12 mg, 31% yield; Rf =
(m, 4H), 3.61 (d, JAB = 16.8 Hz, 1H), 3.58 (d, JAB = 16.8 Hz, 1H), 3.29
(m, 1H), 3.16 (m, 1H), 3.03 (m, 1H), 2.47 (dt, J = 12.5, 9.1 Hz, 1H),
1.35 (t, J = 7.0 Hz, 3H), 1.21 (t, J = 7.0 Hz, 3H); 13C NMR (CDCl3,
100 MHz) δ = 171.9, 170.3, 166.3, 137.8, 128.8, 128.7, 125.1, 118.3,
94.6, 91.6, 62.4, 60.7, 35.1, 30.8, 29.7, 15.0, 14.4, 13.9; IR (film, cm−1)
2998, 2936, 2812, 2230, 1741, 1622, 1519, 1327, 1291, 1252, 1186,
1095, 1027, 897, 856, 763; HRMS (MALDI) m/z calcd for
C19H21O5NNa [M + Na]+ 366.1317, found 366.1313. Data for the
chiral product: enantiometric excess 52%; HPLC analysis (Chiralpak
OD column and AD-H column in series, hexane/i-PrOH, 90/10, flow
rate 0.50 mL/min) tmajor = 41.4 min, tminor = 39.7 min, λ = 254 nm.
General Procedure for the Tributylphosphine-Catalyzed
Alkenylations. Conditions at rt. To a stirred solution of
trifluoromethyl ketone 1 (0.1 mmol) and bis-substituted allenoate
2b (0.12 mmol) in CH2Cl2 (2 mL) was added tributylphosphine
(0.015 mmol) via a microsyringe in one portion. Then the resulting
mixture was vigorously stirred at rt and monitored by TLC. After the
reaction was complete, the mixture was directly purified by column
1
0.33 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; H
NMR (400 MHz, CDCl3) δ = 7.58−7.56 (m, 2H), 7.44−7.42 (m,
3H), 4.20 (m, 4H), 3.60−3.46 (m, 3H), 3.07−2.98 (m, 1H), 2.93−
2.85 (m, 1H), 1.53 (dd, J = 7.1, 1.8 Hz, 3H), 1.30 (m, 6H); 13C NMR
F
dx.doi.org/10.1021/jo401462c | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
chromatography on silica gel (petroleum ether/ethyl acetate (10/1) as
the eluent) to furnish the corresponding product.
138.1, 137.1, 132.7, 129.6, 128.8, 128.7, 127.6, 127.4, 126.9, 115.5,
115.4, 115.3, 115.2, 61.3, 61.2, 61.1, 60.0, 40.2, 32.7, 29.7, 14.2, 14.1,
14.0; 19F NMR (CDCl3, 282 MHz) δ = −79.0 (CF3, minor), −79.1
(CF3, major), −113.2 (ArF, major), −113.6 (ArF, minor); IR (film,
cm−1) 3440 (br), 2985, 2936, 1714, 1645, 1604, 1466, 1447, 1371,
1240, 1179, 1096, 1029, 839, 731; HRMS (ESI) m/z calcd for
C19H20F4O5Na [M + Na]+ 427.1145, found 427.1141.
Conditions at 60 °C. The solution of trifluoromethyl ketone 1 (0.1
mmol) in toluene (2 mL) was warmed to 60 °C before the bis-
substituted allenoate 2b (0.12 mmol) and tributylphosphine (0.015
mmol) were added sequentially via a microsyringe in one portion.
Then the resulting mixture was vigorously stirred at 60 °C and
monitored by TLC. After the reaction was complete, the mixture was
allowed to cool to rt and directly purified by column chromatography
on silica gel (petroleum ether/ethyl acetate (10/1) as the eluent) to
furnish the corresponding product.
Data for (E)-diethyl 2-((E)-5,5,5-trifluoro-4-hydroxy-4-phenyl-
pent-2-en-1-ylidene)succinate (4a): mixture of E,E/Z,E isomers
(major and minor), E,E/Z,E = 7/1; 35 mg, 90% yield; Rf = 0.3
(petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.66 (dd, J = 15.6, 11.3 Hz, 1H; minor,
CHCHCH), 7.60 (m, 2H; both isomers, ArH), 7.45−7.44 (m, 1H;
major, CHCHCH), 7.43−7.40 (m, 3H; both isomers, ArH), 6.84
(dd, J = 15.1, 11.3 Hz, 1H; major, CHCHCH), 6.66 (d, J = 15.0 Hz,
1H; major, CHCHCH), 6.57 (d, J = 11.0 Hz, 1H; minor, CH
CHCH), 6.46 (d, J = 15.6 Hz, 1H; minor, CHCHCH), 4.28−4.22
(m, 2H; both isomers, CH2CO2CH2CH3), 4.17−4.11 (m, 2H; both
isomers, OCH2CH3), 3.46 (s, 2H; major, CH2CO), 3.36 (s, 2H;
minor, CH2CO), 3.33 (s, 1H; major, OH), 3.23 (s, 1H; minor, OH),
1.34−1.30 (t, J = 7.0 Hz, 3H; both isomers, CH2CO2CH2CH3), 1.26−
1.23 (t, J = 7.3 Hz, 3H; both isomers, OCH2CH3); 13C NMR (CDCl3,
100 MHz) δ = 170.5, 166.9, 138.6, 138.4, 138.3, 136.9, 136.8, 129.0,
128.8, 128.5, 128.4, 127.4, 126.6, 61.2, 61.1, 32.7, 14.2, 14.1 (additional
peaks and line broadenings are observed due to diastereoisomers); 19F
NMR (CDCl3, 282 MHz) δ = −78.8 (minor), −78.9 (major); IR
(film, cm−1) 3441, 2985, 2940, 1714, 1644, 1614, 1450, 1371, 1162,
1028, 1004, 979, 769, 710; HRMS (ESI) m/z calcd for C19H21F3O5Na
[M + Na]+ 409.1239, found 409.1231.
Data for (E)-diethyl 2-((E)-4-(4-chlorophenyl)-5,5,5-trifluoro-4-
hydroxypent-2-en-1-ylidene)succinate (4d): mixture of E,E/Z,E
isomers (major and minor), E,E/Z,E = 2.2/1; 33 mg, 80% yield; Rf
= 0.3 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.63 (dd, J = 15.6, 11.3 Hz, 1H; minor,
CHCHCH), 7.54 (m, 2H; both isomers, ArH), 7.42 (d, J = 11.5 Hz,
1H; major, CHCHCH), 7.38 (m, 2H; both isomers, ArH), 6.82 (dd,
J = 15.1, 11.3 Hz, 1H; major, CHCHCH), 6.62 (d, J = 15.3 Hz, 1H;
major, CHCHCH), 6.56 (d, J = 11.1 Hz, 1H; minor, CH
CHCH), 6.42 (d, J = 15.6 Hz, 1H; minor, CHCHCH), 4.28−4.23
(m, 2H; both isomers, CH2CO2CH2CH3), 4.16−4.11 (m, 2H; both
isomers, OCH2CH3), 3.46 (s, 2H; major, CH2CO), 3.35 (s, 2H;
minor, CH2CO), 1.34−1.30 (t, J = 7.2 Hz, 3H; both isomers,
CH2CO2CH2CH3), 1.26−1.22 (t, J = 7.0 Hz, 3H; both isomers,
OCH2CH3); 13C NMR (CDCl3, 100 MHz) δ = 170.9, 170.6, 166.8,
165.9, 140.3, 138.5, 137.8, 136.8, 135.5, 135.4, 135.2, 135.0, 129.7,
128.8, 128.6, 128.5, 128.2, 127.8, 127.6, 127.0, 126.0, 123.1, 61.3, 61.2,
61.1, 40.2, 32.7, 29.7, 14.2, 14.1, 14.0, 13.9; 19F NMR (CDCl3, 282
MHz) δ = −79.0 (minor), −79.1 (major); IR (film, cm−1) 3437 (br),
2984, 2937, 1713, 1645, 1498, 1371, 1241, 1162, 1097, 1029, 979, 932,
830, 732; HRMS (ESI) m/z calcd for C19H20ClF3O5Na [M + Na]+
443.0849, found 443.0843.
Data for (E)-diethyl 2-((E)-5,5,5-trifluoro-4-hydroxy-4-(4-
methoxyphenyl)pent-2-en-1-ylidene)succinate (4e): mixture of
E,E/Z,E isomers (major and minor), E,E/Z,E = 6/1; 37 mg, 88%
yield; Rf = 0.28 (petroleum ether/ethyl acetate, 80/20); viscous,
colorless oil; 1H NMR (400 MHz, CDCl3) δ = 7.64 (dd, J = 15.6, 11.3
Hz, 1H; minor, CHCHCH), 7.51 (d, J = 8.8 Hz, 2H; both isomers,
ArH), 7.44 (d, J = 11.3 Hz, 1H; major, CHCHCH), 6.94 (d, J = 9.0
Hz, 2H; both isomers, ArH), 6.84 (dd, J = 15.1, 11.3 Hz, 1H; major,
CHCHCH), 6.64 (d, J = 15.1 Hz, 1H; major, CHCHCH), 6.57
(d, J = 11.0 Hz, 1H; minor, CHCHCH), 6.44 (d, J = 15.5 Hz, 1H;
minor, CHCHCH), 4.26 (q, J = 7.0 Hz, 2H; both isomers,
CH2CO2CH2CH3), 4.14 (q, J = 7.1 Hz, 2H; both isomers,
OCH2CH3), 3.84 (s, 3H; major, OCH3), 3.47 (s, 2H; major,
CH2CO), 3.36 (s, 2H; minor, CH2CO), 3.33 (br, 1H; major, OH),
1.33 (t, J = 7.0 Hz, 3H; both isomers, CH2CO2CH2CH3), 1.25 (t, J =
7.0 Hz, 3H; both isomers, OCH2CH3); 13C NMR (CDCl3, 100 MHz)
δ = 170.5, 166.9, 160.0, 138.7, 138.5, 128.9, 128.0, 127.2, 127.1, 113.9,
113.8, 61.2, 61.1, 55.3, 32.7, 29.7, 14.2, 14.1 (additional peaks and line
broadenings are observed due to diastereoisomers); 19F NMR (CDCl3,
282 MHz) δ = −78.9 (minor), −79.0 (major); IR (film, cm−1) 3443
(br), 2983, 2937, 2842, 1714, 1644, 1611, 1514, 1465, 1371, 1254,
1160, 1031, 1000, 979, 834, 736; HRMS (ESI) m/z calcd for
C20H23F3O6Na [M + Na]+ 439.1344, found 439.1341.
Data for (E)-diethyl 2-((E)-4-(4-bromophenyl)-5,5,5-trifluoro-4-
hydroxypent-2-en-1-ylidene)succinate (4b): mixture of E,E/Z,E
isomers (major and minor), E,E/Z,E = 2/1; 40 mg, 86% yield; Rf =
1
0.3 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; H
NMR (400 MHz, CDCl3) δ = 7.63 (dd, J = 15.6, 11.3 Hz, 1H; minor,
CHCHCH), 7.54 (d, J = 8.7 Hz, 2H; both isomers, ArH), 7.47 (d, J
= 8.6 Hz, 2H; both isomers, ArH), 7.42 (d, J = 11.3 Hz, 1H; major,
CHCHCH), 6.82 (dd, J = 15.1, 11.3 Hz, 1H; major, CHCHCH),
6.61 (d, J = 15.2 Hz, 1H; major, CHCHCH), 6.56 (d, J = 11.0 Hz,
1H; minor, CHCHCH), 6.41 (d, J = 15.6 Hz, 1H; minor, CH
CHCH), 4.28−4.22 (m, 2H; both isomers, CH2CO2CH2CH3), 4.17−
4.11 (m, 2H; both isomers, OCH2CH3), 3.46 (s, 2H; major, CH2CO),
3.35 (s, 2H; minor, CH2CO), 1.34−1.30 (t, J = 7.0 Hz, 3H; both
isomers, CH2CO2CH2CH3), 1.26−1.22 (t, J = 7.3 Hz, 3H; both
isomers, OCH2CH3); 13C NMR (CDCl3, 100 MHz) δ = 170.9, 170.5,
166.8, 165.9, 140.2, 138.5, 137.8, 136.7, 135.9, 131.6, 131.5, 129.8,
128.6, 128.5, 127.8, 127.6, 127.1, 125.9, 123.4, 123.2, 61.3, 61.2, 61.1,
40.2, 32.7, 29.7, 14.2, 14.1, 14.0; 19F NMR (CDCl3, 282 MHz) δ =
−79.6 (major), −79.7 (minor); IR (film, cm−1) 3425 (br), 2985, 2936,
1713, 1645, 1466, 1371, 1095, 1029, 978, 901, 853, 714; HRMS (ESI)
m/z calcd for C19H20BrF3O5Na [M + Na]+ 487.0344, found 487.0339.
Data for (E)-diethyl 2-((E)-5,5,5-trifluoro-4-(4-fluorophenyl)-4-
hydroxypent-2-en-1-ylidene)succinate (4c): mixture of E,E/Z,E
isomers (major and minor), E,E/Z,E = 2.3/1; 36 mg, 88% yield; Rf
= 0.3 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.63 (dd, J = 15.5, 11.0 Hz, 1H; minor,
CHCHCH), 7.58 (m, 2H; both isomers, ArH), 7.43 (d, J = 11.6 Hz,
1H; major, CHCHCH), 7.09 (m, 2H; both isomers, ArH), 6.82 (dd,
J = 15.1, 11.3 Hz, 1H; major, CHCHCH), 6.63 (d, J = 15.1 Hz, 1H;
major, CHCHCH), 6.57 (d, J = 11.1 Hz, 1H; minor, CH
CHCH), 6.43 (d, J = 15.5 Hz, 1H; minor, CHCHCH), 4.28−4.23
(m, 2H; both isomers, CH2CO2CH2CH3), 4.16−4.11 (m, 2H; both
isomers, OCH2CH3), 3.69 (br, 1H; major, OH), 3.53 (br, 1H; minor,
OH), 3.46 (s, 2H; major, CH2CO), 3.36 (s, 2H; minor, CH2CO),
1.34−1.30 (t, J = 7.0 Hz, 3H; both isomers, CH2CO2CH2CH3), 1.26−
1.22 (t, J = 7.3 Hz, 3H; both isomers, OCH2CH3); 13C NMR (CDCl3,
100 MHz) δ = 170.9, 170.6, 166.8, 165.9, 164.2, 161.8, 140.4, 138.5,
Data for (E)-diethyl 2-((E)-5,5,5-trifluoro-4-hydroxy-4-(3-
methoxyphenyl)pent-2-en-1-ylidene)succinate (4f): mixture of E,E/
Z,E isomers (major and minor), E,E/Z,E = 6/1; 39 mg, 93% yield; Rf =
0.28 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.64 (dd, J = 15.5, 11.0 Hz, 1H; minor,
CHCHCH), 7.42 (d, J = 11.5 Hz, 1H; major, CHCHCH), 7.33
(m, 1H; both isomers, ArH), 7.17 (m, 2H; both isomers, ArH), 6.93
(dd, J = 8.0, 2.3 Hz, 1H; both isomers, ArH), 6.84 (dd, J = 15.3, 11.6
Hz, 1H; major, CHCHCH), 6.63 (d, J = 15.3 Hz, 1H; major, CH
CHCH), 6.56 (d, J = 11.0 Hz, 1H; minor, CHCHCH), 6.43 (d, J =
15.6 Hz, 1H; minor, CHCHCH), 4.25 (q, J = 7.0 Hz, 2H; both
isomers, CH2CO2CH2CH3), 4.13 (q, J = 7.1 Hz, 2H; both isomers,
OCH2CH3), 3.84 (s, 3H; major, OCH3), 3.59 (br, 1H; major, OH),
3.46 (s, 2H; major, CH2CO), 3.35 (s, 2H; minor, CH2CO), 1.32 (t, J =
7.0 Hz, 3H; both isomers, CH2CO2CH2CH3), 1.24 (t, J = 7.0 Hz, 3H;
both isomers, OCH2CH3); 13C NMR (CDCl3, 100 MHz) δ = 170.6,
166.9, 159.7, 138.7, 138.4, 138.3, 129.5, 127.3, 127.2, 118.9, 114.2,
112.7, 61.2, 61.1, 55.3, 32.7, 29.7, 14.2, 14.0 (additional peaks and line
G
dx.doi.org/10.1021/jo401462c | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
broadenings are observed due to diastereoisomers); 19F NMR (CDCl3,
282 MHz) δ = −78.6 (minor), −78.7 (major); IR (film, cm−1) 3444
(br), 2984, 2939, 2839, 1730, 1713, 1644, 1604, 1491, 1466, 1370,
1241, 1085, 1031, 979, 853, 785, 721; HRMS (ESI) m/z calcd for
C20H23F3O6Na [M + Na]+ 439.1344, found 439.1339.
166.9, 139.0, 138.7, 138.5, 133.9, 129.2, 129.1, 127.2, 126.5, 124.7 (q,
JC−F = 286 Hz), 61.2, 61.1, 40.3, 32.7, 29.7, 21.1, 14.2, 14.1, 14.0
(additional peaks and line broadenings are observed due to
diastereoisomers); 19F NMR (CDCl3, 282 MHz) δ = −78.8
(minor), −78.9 (major); IR (film, cm−1) 3444 (br), 2984, 2930,
1730, 1644, 1613, 1514, 1447, 1371, 1158, 1029, 978, 932, 818;
HRMS (ESI) m/z calcd for C20H23F3O5Na [M + Na]+ 423.1395,
found 423.1392.
Data for (E)-diethyl 2-((E)-4-(4-ethoxyphenyl)-5,5,5-trifluoro-4-
hydroxypent-2-en-1-ylidene)succinate (4g): mixture of E,E/Z,E
isomers (major and minor), E,E/Z,E = 6.5/1; 35 mg, 83% yield; Rf
= 0.3 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.64 (dd, J = 15.6, 11.1 Hz, 1H; minor,
CHCHCH), 7.33 (d, J = 8.8 Hz, 2H; both isomers, ArH), 7.43 (d, J
= 11.3 Hz, 1H; major, CHCHCH), 6.91 (d, J = 8.8 Hz, 2H; both
isomers, ArH), 6.84 (dd, J = 15.3, 11.6 Hz, 1H; major, CHCHCH),
6.63 (d, J = 15.0 Hz, 1H; major, CHCHCH), 6.58 (d, J = 11.3 Hz,
1H; minor, CHCHCH), 6.43 (d, J = 15.5 Hz, 1H; minor, CH
CHCH), 4.25 (q, J = 7.0 Hz, 2H; both isomers, CH2CO2CH2CH3),
4.15 (q, J = 7.3 Hz, 2H; both isomers, OCH2CH3), 4.06 (q, J = 7.1 Hz,
2H; both isomers, ArOCH2CH3), 3.46 (s, 2H; major, CH2CO), 3.35
(s, 2H; minor, CH2CO), 1.44 (t, J = 7.0 Hz, 3H; both isomers,
ArOCH2CH3), 1.32 (t, J = 7.0 Hz, 3H; both isomers,
CH2CO2CH2CH3), 1.24 (t, J = 7.3 Hz, 3H; both isomers,
OCH2CH3); 13C NMR (CDCl3, 100 MHz) δ = 170.6, 166.9, 159.4,
138.8, 138.6, 137.6, 128.7, 128.0, 127.2, 127.1, 126.2, 123.4, 114.4,
63.5, 61.2, 61.1, 32.7, 29.7, 14.7, 14.2, 14.0 (additional peaks and line
broadenings are observed due to diastereoisomers); 19F NMR (CDCl3,
282 MHz) δ = −78.9 (minor), −79.0 (major); IR (film, cm−1) 3449,
2983, 2936, 1731, 1716, 1643, 1611, 1512, 1393, 1297, 1242, 1154,
1117, 1031, 1000, 924, 837; HRMS (ESI) m/z calcd for
C21H25F3O6Na [M + Na]+ 453.1501, found 453.1496.
Data for (E)-diethyl 2-((E)-4-(4-ethylphenyl)-5,5,5-trifluoro-4-
hydroxypent-2-en-1-ylidene)succinate (4h): mixture of E,E/Z,E
isomers (major and minor), E,E/Z,E = 6.5/1; 36 mg, 88% yield; Rf
= 0.3 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.64 (dd, J = 15.5, 11.3 Hz, 1H; minor,
CHCHCH), 7.50 (d, J = 8.0 Hz, 2H; both isomers, ArH), 7.44 (d, J
= 11.3 Hz, 1H; major, CHCHCH), 7.25 (d, J = 8.2 Hz, 2H; both
isomers, ArH), 6.85 (dd, J = 15.1, 11.5 Hz, 1H; major, CHCHCH),
6.65 (d, J = 15.1 Hz, 1H; major, CHCHCH), 6.57 (d, J = 11.0 Hz,
1H; minor, CHCHCH), 6.45 (d, J = 15.3 Hz, 1H; minor, CH
CHCH), 4.25 (q, J = 7.3 Hz, 2H; both isomers, CH2CO2CH2CH3),
4.14 (q, J = 7.1 Hz, 2H; both isomers, OCH2CH3), 3.47 (s, 2H; major,
CH2CO), 3.44 (br, 1H; major, OH), 3.35 (s, 2H; minor, CH2CO),
3.31 (br, 1H; minor, OH), 2.68 (q, J = 7.5 Hz, 2H; both isomers,
Data for (E)-diethyl 2-((E)-5,5,5-trifluoro-4-hydroxy-4-(thio-
phene-2-yl)pent-2-en-1-ylidene)succinate (4j): mixture of E,E/Z,E
isomers (major and minor), E,E/Z,E = 3/1; 31 mg, 80% yield; Rf =
0.28 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.70 (dd, J = 15.5, 11.3 Hz, 1H; minor,
CHCHCH), 7.44 (d, J = 11.5 Hz, 1H; major, CHCHCH), 7.38
(m, 1H; both isomers, ArH), 7.21 (m, 1H; both isomers, ArH), 7.06
(m, 1H; both isomers, ArH), 6.92 (dd, J = 14.8, 11.6 Hz, 1H; major,
CHCHCH), 6.58 (d, J = 11.3 Hz, 1H; minor, CHCHCH), 6.55
(d, J = 14.8 Hz, 1H; major, CHCHCH), 6.37 (d, J = 15.3 Hz, 1H;
minor, CHCHCH), 4.25 (q, J = 7.0 Hz, 2H; both isomers,
CH2CO2CH2CH3), 4.15 (q, J = 7.3 Hz, 2H; both isomers,
OCH2CH3), 3.49 (s, 2H; major, CH2CO), 3.36 (s, 2H; minor,
CH2CO), 1.33 (t, J = 7.0 Hz, 3H; both isomers, CH2CO2CH2CH3),
1.25 (t, J = 7.3 Hz, 3H; both isomers, OCH2CH3); 13C NMR (CDCl3,
100 MHz) δ = 171.0, 170.6, 166.9, 165.9, 140.5, 140.3, 140.1, 138.4,
136.9, 136.0, 129.6, 127.6, 127.2, 127.1, 126.9, 126.7, 126.6, 126.5,
126.6, 61.2, 61.1, 61.0, 40.3, 32.8, 29.7, 14.2, 14.1, 14.0 (additional
peaks and line broadenings are observed due to diastereoisomers); 19F
NMR (CDCl3, 282 MHz) δ = −78.9 (minor), −79.0 (major); IR
(film, cm−1) 3434, 2983, 2935, 1714, 1645, 1489, 1371, 1240, 1162,
1077, 1028, 1010, 932, 823; HRMS (ESI) m/z calcd for
C17H19F3O5NaS [M + Na]+ 415.0803, found 415.0803.
Data for (E)-diethyl 2-((E)-5,5,5-trifluoro-4-hydroxy-4-(naphtha-
len-1-yl)pent-2-en-1-ylidene)succinate (4k): mixture of E,E/Z,E
isomers (major and minor), E,E/Z,E = 3/1; 31 mg, 70% yield; Rf =
0.28 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 8.49−8.47 (m, 1H; both isomers, ArH),
7.92−7.87 (m, 2H; both isomers, ArH), 7.82−7.80 (m, 1H; both
isomers, ArH), 7.51−7.47 (m, 3H; both isomers, ArH), 7.40 (d, J =
10.5 Hz, 1H; major, CHCHCH), 6.73 (dd, J = 15.6, 10.8 Hz, 1H;
major, CHCHCH), 6.68 (d, J = 15.3 Hz, 1H; major, CHCHCH),
6.55 (d, J = 11.3 Hz, 1H; minor, CHCHCH), 6.50 (d, J = 15.8 Hz,
1H; minor, CHCHCH), 4.22 (q, J = 7.0 Hz, 2H; major,
CH2CO2CH2CH3), 4.14 (q, J = 7.0 Hz, 2H; minor, CH2CO2CH2CH3
and OCH2CH3), 4.05 (q, J = 7.0 Hz, 2H; major, OCH2CH3), 3.35 (s,
2H; major, CH2CO), 3.31 (s, 2H; minor, CH2CO), 1.30 (t, J = 7.3 Hz,
3H; both isomers, CH2CO2CH2CH3), 1.19 (t, J = 7.1 Hz, 3H; major,
OCH2CH3), 1.10 (t, J = 7.0 Hz, 3H; minor, OCH2CH3); 13C NMR
(CDCl3, 100 MHz) δ = 170.9, 170.3, 166.9, 166.0, 140.1, 139.2, 138.7,
137.9, 134.9, 132.4, 132.1, 131.1, 130.8, 130.6, 129.1, 129.0, 128.9,
127.3, 127.1, 126.1, 126.0, 125.8, 125.7, 124.5, 61.2, 61.0, 60.9, 40.2,
32.7, 29.7, 14.2, 14.0, 13.8 (additional peaks and line broadenings are
observed due to diastereoisomers); 19F NMR (CDCl3, 282 MHz) δ =
−75.6 (minor), −75.8 (major); IR (film, cm−1) 3431 (br), 2983, 2934,
1716, 1643, 1465, 1370, 1266, 1088, 1055, 1029, 978, 802; HRMS
(ESI) m/z calcd for C23H23F3O5Na [M + Na]+ 459.1395, found
459.1395.
ArCH2CH3), 1.32 (t,
J = 7.0 Hz, 3H; both isomers,
CH2CO2CH2CH3), 1.28−1.23 (m, 6H; both isomers, and
OCH2CH3 and ArCH2CH3); 13C NMR (CDCl3, 100 MHz) δ =
170.5, 166.9, 145.2, 138.8, 138.6, 134.2, 128.0, 127.9, 127.1, 126.6,
124.8 (q, JC−F = 286 Hz), 61.2, 61.1, 61.0, 60.9, 40.3, 32.7, 29.7, 28.4,
15.3, 14.2, 14.1, 14.0 (additional peaks and line broadenings are
observed due to diastereoisomers); 19F NMR (CDCl3, 282 MHz) δ =
−78.7 (minor), −78.8 (major); IR (film, cm−1) 3451, 2970, 2953,
2875, 1730, 1713, 1643, 1514, 1464, 1371, 1163, 1030, 1001, 933, 834,
777; HRMS (ESI) m/z calcd for C21H25F3O5Na [M + Na]+ 437.1552,
found 437.1548.
Data for (E)-diethyl 2-((E)-5,5,5-trifluoro-4-hydroxy-4-(p-tolyl)-
pent-2-en-1-ylidene)succinate (4i): mixture of E,E/Z,E isomers
(major and minor), E,E/Z,E = 7/1; 34 mg, 84% yield; Rf = 0.3
(petroleum ether/ethyl acetate, 80/20); viscous, colorless oil; 1H
NMR (400 MHz, CDCl3) δ = 7.64 (dd, J = 15.6, 11.3 Hz, 1H; minor,
CHCHCH), 7.47 (d, J = 8.0 Hz, 2H; both isomers, ArH), 7.43 (d, J
= 11.3 Hz, 1H; major, CHCHCH), 7.23 (d, J = 8.3 Hz, 2H; both
isomers, ArH), 6.84 (dd, J = 15.1, 11.6 Hz, 1H; major, CHCHCH),
6.64 (d, J = 15.1 Hz, 1H; major, CHCHCH), 6.57 (d, J = 11.3 Hz,
1H; minor, CHCHCH), 6.44 (d, J = 15.5 Hz, 1H; minor, CH
CHCH), 4.25 (q, J = 7.0 Hz, 2H; both isomers, CH2CO2CH2CH3),
4.15 (q, J = 7.3 Hz, 2H; both isomers, OCH2CH3), 3.46 (s, 2H; major,
CH2CO), 3.35 (s, 2H; minor, CH2CO), 3.27 (s, 1H; major, OH), 3.17
(s, 1H; minor, OH), 2.39 (s, 3H; both isomers, ArCH3), 1.33 (t, J =
7.0 Hz, 3H; both isomers, CH2CO2CH2CH3), 1.25 (t, J = 7.0 Hz, 3H;
both isomers, OCH2CH3); 13C NMR (CDCl3, 100 MHz) δ = 170.5,
Data for (E)-diethyl 2-((E)-5,5,5-trifluoro-4-hydroxy-4-(4-
(methylthio)phenyl)pent-2-en-1-ylidene)succinate (4l): mixture of
E,E/Z,E isomers (major and minor), E,E/Z,E = 6/1; 34 mg, 82% yield;
Rf = 0.3 (petroleum ether/ethyl acetate, 80/20); viscous, colorless oil;
1H NMR (400 MHz, CDCl3) δ = 7.63 (dd, J = 15.5, 11.1 Hz, 1H;
minor, CHCHCH), 7.50 (d, J = 8.3 Hz, 2H; both isomers, ArH),
7.43 (d, J = 11.3 Hz, 1H; major, CHCHCH), 7.27 (d, J = 8.5 Hz,
2H; both isomers, ArH), 6.83 (dd, J = 15.0, 11.3 Hz, 1H; major, CH
CHCH), 6.62 (d, J = 15.1 Hz, 1H; major, CHCHCH), 6.56 (d, J =
11.1 Hz, 1H; minor, CHCHCH), 6.42 (d, J = 15.5 Hz, 1H; minor,
CHCHCH), 4.25 (q, J = 7.0 Hz, 2H; both isomers,
CH2CO2CH2CH3), 4.13 (q, J = 7.3 Hz, 2H; both isomers,
OCH2CH3), 3.57 (br, 1H; major, OH), 3.46 (s, 2H; major,
CH2CO), 3.35 (s, 2H; minor, CH2CO), 2.51 (s, 3H; major,
H
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ArSCH3), 1.32 (t, J = 7.0 Hz, 3H; both isomers, CH2CO2CH2CH3),
1.24 (t, J = 7.3 Hz, 3H; both isomers, OCH2CH3); 13C NMR (CDCl3,
100 MHz) δ = 171.0, 170.6, 166.9, 166.0, 140.5, 140.1, 139.7, 138.7,
137.2, 133.4, 129.4, 127.4, 127.3, 127.1, 127.0, 126.1, 123.3, 61.2, 61.1,
61.0, 32.7, 29.7, 15.4, 14.7, 14.2, 14.0 (additional peaks and line
broadenings are observed due to diastereoisomers); 19F NMR (CDCl3,
282 MHz) δ = −78.8 (minor), −78.9 (major); IR (film, cm−1) 3438,
2983, 2927, 1739, 1713, 1644, 1598, 1495, 1466, 1370, 1240, 1095,
979, 931, 819; HRMS (ESI) m/z calcd for C20H23F3O5NaS [M + Na]+
455.1116, found 455.1111.
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ASSOCIATED CONTENT
■
S
* Supporting Information
Tables giving information on the screening of phosphine
catalysts for the reaction of trifluoromethyl ketone and catalyst
screening for asymmetric cycloaddition reaction and condition
1
surveys for cycloaddition and dienylation reactions, H NMR
and 13C NMR spectra for 3a−3l, 3aa, 3aa′, 3ac, 3ac′, 3l′, 3ab,
3ad, 4aa, and 4a−4l, and chiral HPLC spectra of 3a, 3ab, 3ad,
and 4aa. This material is available free of charge via the Internet
at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Authors
*Fax: (+86) 21-64166128. E-mail: xiaohua@mail.sioc.ac.cn.
*Fax: (+86) 21-64166128. E-mail: zhaog@mail.sioc.ac.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from the National
Basic Research Program of China (973 Program, Grant
2010CB833200), the National Natural Science Foundation of
China (Grants 21032006 and 21272247), the Science and
Technology Commission of Shanghai Municipality (Grant
11XD1406400), the Excellent Young Scholars Foundation of
the National Natural Science Foundation of China (Grant
20525208), and the supporting fund for young researchers of
the Hefei University of Technology (to H.X.).
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