Lewis acid-promoted reactions of ethenetricarboxylates with γ-CF3-substituted propargyl alcohols

Article abstract of DOI:10.1016/j.tet.2009.01.024

The Lewis acid-promoted reaction of an ethenetricarboxylate derivative (1) with CF₃-substituted propargyl alcohols has been examined. Reaction of γ-CF₃ propargyl alcohols in the presence of zinc bromide gave five-membered CF₃

Full text of DOI:10.1016/j.tet.2009.01.024

Tetrahedron 65 (2009) 1988–1994
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Lewis acid-promoted reactions of ethenetricarboxylates with
propargyl alcohols
g-CF3-substituted
,
a
b
Shoko Yamazaki a , Yuko Yamamoto , Yuji Mikata
*
a Department of Chemistry, Nara University of Education, Takabatake-cho, Nara 630-8528, Japan
b KYOUSEI Science Center, Nara Women’s University, Nara 630-8506, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The Lewis acid-promoted reaction of an ethenetricarboxylate derivative (1) with CF3-substituted
propargyl alcohols has been examined. Reaction of -CF3 propargyl alcohols in the presence of zinc
bromide gave five-membered CF3-containing tetrahydrofurans in 66–85% yield. The CF3 group acti-
vates alkyne as an electron-withdrawing group. On the other hand, reaction of -trifluoromethyl-
-aryl propargyl alcohols 2 with 1 in the presence of 1 equiv of SnCl4 gave cyclobutane derivatives 6
Received 12 September 2008
Received in revised form 25 December 2008
Accepted 6 January 2009
g
g
Available online 14 January 2009
a
in 29–49% yield. Formation of cyclobutane 6a arises from the [2þ2] cycloaddition between ethene-
tricarboxylate 1 and chloroallene 8, which is produced by the reaction of propargyl alcohol 2a and
SnCl4.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
derivative 1 with
found that reaction of
g
-CF3-substituted propargylic alcohols, it was
-CF3 propargyl alcohols with 1 in the
g
Fluorine-containing molecules are interesting because of
their biological activities.1 Introduction of fluorine atoms into
biologically important skeletons such as heterocycles and
carbocycles is expected to lead to various activities. Recently, the
synthesis of methylenetetrahydrofurans by one-pot formal [3þ2]
cycloadditions involving propargylic alcohols with electrophilic
alkenes has been developed.2 The synthetic methods provide
powerful tools to prepare highly functionalized tetrahydrofuran
rings. The reactions can be effectively promoted by base, base/
transition metals, and Lewis acids, depending on the substrates.
Efficient preparation of CF3-substituted propargylic alcohols has
been reported recently.3 The CF3 substituent is known as an
efficient electron-withdrawing group due to the inductive effect of
fluorine atoms.4 We have reported zinc and indium-promoted
formal [3þ2] cycloadditions of ethenetricarboxylates with prop-
argyl alcohol to afford tetrahydrofurans.2f The highly electrophilic
reactivity of ethenetricarboxylates led to an efficient one-pot
reaction. We have also reported a Lewis acid-catalyzed cyclization
presence of SnCl4 gave cyclobutane derivatives, via a chloro-
allene intermediate.
2. Results and discussion
The reaction of triethyl ethenetricarboxylate (1) and
g-CF3-
substituted propargyl alcohols 2a–e3,5 in the presence of ZnBr2
(0.2 equiv) was examined at first. Reaction of 1 and 2a–e in the
presence of ZnBr2 (0.2 equiv) at 110 ꢀC in toluene overnight gave 3a–e
in 66–85% yield, as diastereomer mixtures in a 1:1 to 1:1.3 ratio,
respectively (Eq.1). The result is in accord with the reported reaction
of propargyl alcohols.2f,g For the geometry of the alkene moiety,
Z-CF3-substituted methylenetetrahydrofurans were obtained
selectively.6 Although the low 2,5-substituent diastereoselectivity is
a general problem of tetrahydrofuran formation using a-substituted
propargyl alcohols,2 the diastereomers of certain derivatives (3c–e)
could be separated by column chromatography. The reaction of 1
and 1-(3,3,3-trifluoroprop-1-ynyl)cyclohexanol
4 with ZnBr2
of ethenetricarboxylate derivative 1 with
g-ester and silicon
(0.2 equiv) gave 5 in 32% yield (Eq. 2). The lower yield mayarise from
steric hindrance in the initial addition step.
substituted propargyl alcohols to give methylenetetrahydrofurans
stereoselectively.2g
The reaction of diethyl benzylidenemalonate with 2a in the
presence of ZnBr2 was also examined. The reaction gave the start-
ing material, diethyl benzylidenemalonate and a complex mixture
and the possible cycloadducts could not be isolated. Thus, the high
reactivity of 1 compared to benzylidenemalonate was shown by
this efficient cyclization reaction.
In this study, during examination of the applicability of
Lewis acid-catalyzed cyclization of the ethenetricarboxylate
* Corresponding author.
E-mail address: yamazaks@nara-edu.ac.jp (S. Yamazaki).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.024

S. Yamazaki et al. / Tetrahedron 65 (2009) 1988–1994
1989
EtO2C CO2Et
+
CF3
ZnBr2
EtO2C
EtO2C
CF3
(0.2 eq.)
toluene
110 °C
R
EtO2C
R
O
EtO2C
HO
2a: R = Ph
3a: R = Ph (66% trans:cis=1:1)
1
3b: R = C6H4-4-Me (67% trans:cis=1:1)
3c: R = C6H4-4-Br (85% trans:cis=1:1)
3d: R = C6H4-4-OMe (70% trans:cis=1.1:1)
3e: R = CH2CH2Ph (70% trans:cis=1:1.3)
2b: R = C6H4-4-Me
2c: R = C6H4-4-Br
2d: R = C6H4-4-OMe
2e: R = CH2CH2Ph
ð1Þ
CF3
EtO2C
EtO2C
EtO2C CO2Et
CF3
ZnBr2
(0.2 eq.)
+
EtO2C
ð2Þ
toluene
110 °C
O
EtO2C
HO
1
5
4
32%
Various Lewis acids such as AlCl3, InBr3, FeCl3, and TiCl4–Et3N7
were examined, however, they gave complex mixtures. SnCl4 was
expected to have different reactivity, and reaction of 1 with ester-
substituted propargyl alcohol gave the E-isomer tetrahydrofuran,
which is a different stereoisomer from that obtained with the other
Lewis acids, zinc, aluminum, and indium halides.2g Interestingly,
reaction of 4,4,4-trifluoro-1-phenylbut-2-yn-1-ol (2a) with 1 in the
presence of 1 equiv of SnCl4 gave a product 6a containing chlorine
in 29–33% yield (Eq. 3).8 The cyclobutane structure of 6a was
determined by X-ray analysis (Fig. 1).9 The reaction of 2b,f,g and 1
with SnCl4 gave 6b,f,g in 39–49% yield.10 The reaction of 4-Cl and
4-F substituted substrates 2h,i with 1 gave cyclobutanes 6h,i in low
yields, along with complex mixtures. The reaction of 2c,d (R0¼Br
and OMe) and 2j and 1 gave complex mixtures.11 The reaction of an
aliphatic derivative 2e and 1 gave a complex mixture along with
recovered 2e and the reaction of 4 and 1 did not proceed under
similar reaction conditions.
Figure 1. ORTEP drawing of the cyclobutane 6a (thermal ellipsoids are drawn at 50%
probability).
The reaction of the unstable allene 8 with 1 without SnCl4 did
not proceed. The reaction with SnCl4 gave cyclobutane 6a in 36%
yield (Eq. 5). Although the yields are not very good probably
because of the instability of the intermediate allene 8 under the
reaction conditions, a novel reaction involving the formation of
chloroallene and subsequent [2þ2] cycloaddition by SnCl4 was
found.
CF3
CF3 CF3
CF3
Cl
CF3
Ph
SnCl4
(1.0 eq.)
R'
+
+
CF3
EtO2C CO2Et
CH2Cl2
r.t.
SnCl4
(1.0 eq.)
CO2Et
CO2Et
HO
Ph
Ph
O
Ph
Cl
Ph
+
2a
CH2Cl2
r.t.
8
7
9
EtO2C
HO
F3C
ð4Þ
CO2Et
10-16%
10-14%
SNi
30-48% (dr 1:1)
SnCl4
1
Cl
R'
Cl
Sn
Cl
2a: R' = H
2b: R' = Me
2f: R' = Et
2g: R' = iPr
6a: R' = H (29-33%)
6b: R' = Me (39%)
6f: R' = Et (49%)
6g: R' = iPr (49%)
6h: R' = Cl (10%)
6i: R' = F (23%)
Cl
ð3Þ
2h: R' = Cl
2i: R' = F
2a
Cl
H
O
CF3
2a-SnCl4
Ph
HO
CF3
2j
SnCl4
(1.0 eq.)
6a
1
+
8
ð5Þ
Formation of 6a is speculated to arise from the [2þ2] cyclo-
addition between 1 and chloroallene 8.12 Chloroallene 8 is postu-
lated to be produced by the reaction of 2a and SnCl4.7,13 The
reaction of 2a in the presence of SnCl4 without 1 was thus per-
formed. The reaction gave propargyl chloride 7, chloroallene 8, and
ether derivative 9 in 10–14%, 10–16%, and 30–48% (dr 1:1) yields,
respectively (Eq. 4). Chloroallene 8 was found to be unstable and
decomposed in a concentrated state. Propargyl chloride 7 and
chloroallene 8 are formed by nucleophilic substitution reactions of
propargylic substrate 2a with SnCl4. Ether derivative 9 may be
formed by nucleophilic substitution reaction between 2a and
CH2Cl2
r.t.
36%
The regioselectivity of the [2þ2] cycloaddition may be explained
by larger HOMO of C2 (HOMO coefficients: C2, ꢁ0.41; C1, ꢁ0.27; C3,
þ0.04) in 3-chloro-4,4,4-trifluoro-1-phenylbuta-1,2-diene 8 in the
reaction with highly electrophilic olefin 1 coordinated with SnCl4
(Scheme 1).14 The possible zwitter-ion intermediates A may be also
stabilized by the Ph group. One stereoisomer of the cyclobutane
was isolated and its structure confirmed by X-ray analysis (Fig. 1).
Since the obtained yields were low, the preference for the obtained
stereochemistry in 6a is not clear.
SnCl4-activated propargyl alcohol 2a. The a-phenyl group of 2a may
facilitate these substitution reactions.

1990
S. Yamazaki et al. / Tetrahedron 65 (2009) 1988–1994
Cl4
Sn
3.1.3. Compound 2g
EtO
O
SnCl4
Rf¼0.4 (hexane–ether¼4:1); brown oil; 1H NMR (400 MHz,
Ph
Ph
O
1
O
O
CDCl3)
d
(ppm) 1.25 (d, J¼7.0 Hz, 6H), 2.90 (br s, 1H), 2.92 (septet,
+
OEt
CO2Et
2
3
J¼7.0 Hz, 1H), 5.41 (br q, J¼2.7 Hz, 1H), 7.26 (d, J¼8.1 Hz, 2H), 7.38
EtO
OEt
F3C
(d-like, J¼8.1 Hz, 2H); 13C NMR (100.6 MHz, CDCl3)
d (ppm) 23.92
Cl
CF3
Cl
(CH3), 33.98 (CH), 63.85 (CH), 73.28 (C, q, JFC¼53 Hz), 86.68 (C, q,
8
EtO2C
1-SnCl4
A
JFC¼7 Hz), 114.16 (C, q, JFC¼258 Hz), 126.82 (CH), 127.17 (CH), 135.38
(C), 150.33 (C); 19F NMR (376 MHz, CDCl3)
d
(ppm) ꢁ50.95 (d,
CO2Et
JFH¼3.1 Hz); IR (neat) 3303, 2965, 2277,1277,1146 cmꢁ1; MS (EI) m/z
242 (Mþ, 27), 227 (56), 199 (100%); HRMS Mþ 242.0914 (calcd for
C13H13F3O 242.0918). Anal. Calcd for C13H13F3O: C, 64.46; H, 5.41.
Found: C, 64.18; H, 5.40.
Ph
CO2Et
F3C
CO2Et
Cl
6a
3.1.4. Compound 2h
Scheme 1.
Rf¼0.3 (hexane–ether¼4:1); brown crystals, mp 46–47 ꢀC; 1H
NMR (400 MHz, CDCl3)
d (ppm) 2.83 (br s, 1H), 5.52 (br s, 1H), 7.38
(d-like, J¼8.6 Hz, 2H), 7.42 (d-like, J¼8.6 Hz, 2H); 13C NMR
In summary, a new reaction of
with 1 in the presence of SnCl4 to give cyclobutane derivatives 6
was found. Reaction of -CF3 propargyl alcohols in the presence of
g-CF3 a-aryl propargyl alcohols 2
(100.6 MHz, CDCl3)
d
(ppm) 63.32 (CH), 73.71 (C, q, JFC¼53 Hz),
g
86.01 (C, q, JFC¼6 Hz), 114.03 (C, q, JFC¼258 Hz), 128.02 (CH), 129.25
(CH), 135.28 (C), 136.39 (C); 19F NMR (376 MHz, CDCl3)
d
(ppm)
zinc bromide also gave five-membered CF3-containing tetra-
hydrofurans. CF3 moieties in both products would attract much
attention, because of the difficulty in preparation of CF3-containing
skeletons. Further improvement of the selectivity and elucidation
of the effects of the CF3 group in these reactions are under
investigation.
ꢁ51.13 (d, JFH¼2.7 Hz); IR (neat) 3336, 2279, 1598, 1490, 1276,
1146 cmꢁ1; MS (EI) m/z 234, 236 (Mþ); HRMS Mþ 234.0052
(calcd for C10H635ClF3O 234.0059), 236.0030 (calcd for C10H637ClF3O
236.0030).
3.1.5. Compound 2i
3. Experimental section
3.1. General methods
Rf¼0.7 (hexane–ether¼2:1); brown oil; 1H NMR (400 MHz,
CDCl3)
d
(ppm) 2.70 (br d, J¼4.9 Hz,1H), 5.55 (br s,1H), 7.10 (dd-like,
J¼8.7, 8.6 Hz, 2H), 7.48 (dd-like, J¼8.6, 5.2 Hz, 2H); 13C NMR
(100.6 MHz, CDCl3)
d
(ppm) 63.35 (CH), 73.64 (C, q, JFC¼53 Hz),
Melting points are uncorrected. IR spectra were recorded in the
FT-mode. 1H NMR spectra were recorded at 400 MHz. 13C NMR
spectra were recorded at 100.6 MHz. 19F NMR spectra were recor-
ded at 376 MHz. 1H chemical shifts are reported in parts per million
relative to Me4Si. 13C chemical shifts are reported in parts per
million relative to CDCl3 (77.1 ppm). 19F chemical shifts are reported
in parts per million relative to CFCl3. 13C multiplicities were
determined by DEPT and HSQC. Mass spectra were recorded at an
ionizing voltage of 70 eV by EI or FAB. All reactions were carried out
under a nitrogen atmosphere.
86.30 (C, q, JFC¼7 Hz), 114.08 (C, q, JFC¼258 Hz), 116.05 (CH, d,
JFC¼22 Hz), 128.63 (CH, d, JFC¼8 Hz), 133.91 (C, d, JFC¼3 Hz), 163.19
(C, JFC¼249 Hz); 19F NMR (376 MHz, CDCl3)
d
(ppm) ꢁ112.59 (m,
1ꢂF), ꢁ51.10 (d, JFH¼3.1 Hz, 3ꢂF); IR (neat) 3324, 2279, 1608, 1511,
1279, 1146 cmꢁ1; MS (EI) m/z 218 (Mþ, 38), 217 (71), 201 (91), 151
(100%); HRMS Mþ 218.0354 (calcd for C10H6F4O 218.0355).
3.2. Typical experimental procedure (Eq. 1)
To a solution of 1 (122 mg, 0.5 mmol) in toluene (0.9 mL)
was added 1-(4-bromophenyl)-4,4,4-trifluorobut-2-yn-1-ol (2c)
(140 mg, 0.5 mmol) and ZnBr2 (22 mg, 0.1 mmol). The mixture was
heated at 110 ꢀC and stirred for 16 h. The reaction mixture was
cooled to room temperature and quenched by water (1.5 mL) and
then saturated aqueous NaHCO3. The mixture was extracted with
dichloromethane and the organic phase was washed with water,
dried (Na2SO4), and evaporated in vacuo. The residue was purified
by column chromatography over silica gel with hexane–ether as
eluent to give trans-3c (108 mg, 41%) and cis-3c (115 mg, 44%).
g-CF3-substituted propargyl alcohols 2a,c,e,j and 4 were pre-
pared according to Refs. 3 and 5 and 2b,f–i were prepared
according to the reported procedure.3
3.1.1. Compound 2b
Rf¼0.6 (hexane–ether¼1:1); yellow oil; 1H NMR (400 MHz,
CDCl3)
d
(ppm) 2.37 (s, 3H), 2.53 (br s, 1H), 5.49 (qd, J¼2.7, 2.7 Hz,
1H), 7.22 (d, J¼8.1 Hz, 2H), 7.37 (d-like, J¼8.1 Hz, 2H); 13C NMR
(100.6 MHz, CDCl3)
d
(ppm) 21.26 (CH3), 63.94 (CH, q, JFC¼1.5 Hz),
73.31 (C, q, JFC¼53 Hz), 86.77 (C, q, JFC¼7 Hz), 114.16 (C, q,
JFC¼258 Hz), 126.67 (CH), 129.76 (CH), 135.20 (C), 139.38 (C); 19F
3.2.1. trans-3c
NMR (376 MHz, CDCl3)
d
(ppm) ꢁ50.98 (d, JFH¼3.1 Hz); IR (neat)
Rf¼0.4 (hexane–ether¼2:1); colorless crystals, mp 104.5–
3348, 2928, 2277, 1276, 1143 cmꢁ1; MS (EI) m/z 214 (Mþ, 70), 199
105.5 ꢀC; 1H NMR (400 MHz, CDCl3)
d
(ppm) 1.288 (t, J¼7.1 Hz, 3H),
(100%); HRMS Mþ 214.0602 (calcd for C11H9F3O 214.0605).
1.289 (t, J¼7.1 Hz, 3H), 1.37 (t, J¼7.1 Hz, 3H), 4.15–4.40 (m, 6H), 5.20
(s, 1H), 6.06 (qd, J¼2.6, 2.6 Hz, 1H), 6.29 (qd, J¼8.6, 2.4 Hz, 1H), 7.17
(d-like, J¼8.5 Hz, 2H), 7.47 (d-like, J¼8.5 Hz, 2H). Selected NOEs are
3.1.2. Compound 2f
Rf¼0.7 (hexane–ether¼2:1); yellow oil; 1H NMR (400 MHz,
between d 7.17 (o-H of C6H4-p-Br) and 5.20 (CHCO2Et), 6.06
CDCl3)
d
(ppm) 1.24 (t, J¼7.6 Hz, 3H), 2.66 (q, J¼7.6 Hz, 2H), 2.76 (br
(OCHC6H4-p-Br). 13C NMR (100.6 MHz, CDCl3)
d (ppm) 13.83 (CH3),
s, 1H), 5.46 (br s, 1H), 7.23 (d-like, J¼8.2 Hz, 2H), 7.38 (d-like,
13.98 (CH3),14.05 (CH3), 61.84 (CH2), 63.09 (CH2), 63.50 (CH2), 67.81
(C), 79.98 (CH), 82.00 (CH), 118.74 (CH, q, JFC¼36 Hz), 122.15 (C, q,
JFC¼272 Hz), 123.21 (C), 129.97 (CH), 131.74 (CH), 136.38 (C), 147.66
(C, q, JFC¼5 Hz), 165.31 (C), 165.97 (C), 168.14 (C). Selected HMBC
J¼8.2 Hz, 2H); 13C NMR (100.6 MHz, CDCl3)
d (ppm) 15.53 (CH3),
28.66 (CH2), 63.90 (CH, q, JFC¼1.5 Hz), 73.28 (C, q, JFC¼53 Hz), 86.74
(C, q, JFC¼7 Hz), 114.16 (C, q, JFC¼258 Hz), 126.78 (CH), 128.59 (CH),
135.35 (C), 145.71 (C); 19F NMR (376 MHz, CDCl3)
d
(ppm) ꢁ50.96
correlations are between
and between
(376 MHz, CDCl3)
2983, 1758, 1734, 1254, 1219, 1095 cmꢁ1; MS (EI) m/z 524 (Mþ, 9.9),
d 5.20 (CHCO2Et) and d 147.66 (C]CHCF3)
(d, JFH¼3.1 Hz); IR (neat) 3324, 2970, 2277, 1277, 1146 cmꢁ1; MS (EI)
m/z 228 (Mþ); HRMS Mþ 228.0765 (calcd for C12H11F3O 228.0762).
Anal. Calcd for C12H11F3O: C, 63.16; H, 4.86. Found: C, 63.53; H, 4.84.
d
6.06 (OCHC6H4-p-Br) and 79.98 (CHCO2Et). 19F NMR
(ppm) ꢁ60.13 (dd, JFH¼9.2, 3.1 Hz); IR (KBr)
d

S. Yamazaki et al. / Tetrahedron 65 (2009) 1988–1994
1991
522 (Mþ, 9.2), 451 (100), 449 (99%); HRMS Mþ 522.0505 (calcd for
C21H2279BrF3O7 522.0501), 524.0484 (calcd for C21H2281BrF3O7
524.0481). Anal. Calcd for C21H22BrF3O7: C, 48.20; H, 4.24. Found: C,
48.18; H, 4.26.
(CH, q, JFC¼37 Hz), 118.18 (CH, q, JFC¼37 Hz), 122.01 (C, q,
JFC¼272 Hz), 122.22 (C, q, JFC¼272 Hz), 128.03 (CH), 128.69 (CH),
128.90 (CH), 129.16 (CH), 133.85 (C), 134.30 (C), 138.71 (C), 138.74
(C), 148.24 (C, q, JFC¼5 Hz), 150.45 (C, q, JFC¼5 Hz), 165.25 (C), 165.52
(C), 165.95 (C), 166.63 (C), 167.20 (C), 168.20 (C). Selected HMBC
3.2.2. cis-3c
correlations are between
C]CHCF3) and 5.20 (trans CHCO2Et) and 148.24 (trans C]CHCF3).
19F NMR (376 MHz, CDCl3)
ꢁ60.32 (dd, JFH¼8.4, 2.8 Hz); IR (neat) 2985, 1742, 1254, 1213, 1129,
1024 cmꢁ1; MS (EI) m/z 458 (Mþ); HRMS Mþ 458.1554 (calcd for
C22H25F3O7 458.1552). Anal. Calcd for C22H25F3O7: C, 57.64; H, 5.50.
Found: C, 57.22; H, 5.50.
d 5.05 (cis CHCO2Et) and 150.45 (cis
Rf¼0.3 (hexane–ether¼2:1); pale yellow oil; 1H NMR
d
(400 MHz, CDCl3)
d
(ppm) 1.21 (t, J¼7.1 Hz, 3H), 1.28 (t, J¼7.1 Hz,
d
(ppm) ꢁ59.75 (dd, JFH¼9.0, 2.3 Hz),
3H), 1.34 (t, J¼7.1 Hz, 3H), 4.09–4.42 (m, 6H), 5.07 (s, 1H), 5.74 (qd,
J¼2.7, 2.7 Hz, 1H), 6.07 (qd, J¼8.7, 2.7 Hz, 1H), 7.24 (d-like,
J¼8.5 Hz, 2H), 7.46 (d-like, J¼8.5 Hz, 2H). Selected NOEs are
between
d 5.74 (OCHC6H4-p-Br) and 5.07 (CHCO2Et), 7.24 (o-H of
C6H4-p-Br). 13C NMR (100.6 MHz, CDCl3)
d (ppm) 13.79 (CH3),
13.90 (CH3), 13.95 (CH3), 61.65 (CH2), 63.07 (CH2), 63.31 (CH2),
68.38 (C), 80.58 (CH), 82.13 (CH), 118.14 (CH, q, JFC¼37 Hz), 121.92
(C, q, JFC¼272 Hz), 123.24 (C), 130.55 (CH), 131.49 (CH), 135.87 (C),
149.71 (C, q, JFC¼5 Hz), 165.26 (C), 166.39 (C), 167.04 (C). Selected
3.2.5. trans-3d
Rf¼0.4 (hexane–ether¼1:1); pale yellow oil; 1H NMR
(400 MHz, CDCl3)
d
(ppm) 1.28 (t, J¼7.1 Hz, 3H), 1.29 (t, J¼7.1 Hz,
3H), 1.34 (t, J¼7.1 Hz, 3H), 3.79 (s, 3H), 4.15–4.29 (m, 4H), 4.31–
4.42 (m, 2H), 5.21 (d, J¼0.7 Hz, 1H), 6.08 (qd, J¼2.7, 2.7 Hz, 1H),
6.25 (qd, J¼8.6, 2.4 Hz, 1H), 6.86 (d-like, J¼8.8 Hz, 2H), 7.21
HMBC correlations are between
(C]CHCF3) and between
19F NMR (376 MHz, CDCl3)
d
5.07 (CHCO2Et) and
d 149.71
d
6.07 (C]CHCF3) and 68.38 (C(CO2Et)2).
d
(ppm) ꢁ59.70 (dd, JFH¼7.6, 3.1 Hz); IR
(d-like, J¼8.8 Hz, 2H). Selected NOEs are between
d 7.21 (o-H of
(neat) 2984, 1740, 1490, 1259, 1215, 1120 cmꢁ1; MS (EI) m/z 524
(Mþ, 9.9), 522 (Mþ, 9.9), 451 (99), 449 (100%); HRMS Mþ 522.0494
(calcd for C21H2279BrF3O7 522.0501), 524.0479 (calcd for
C21H2281BrF3O7 524.0481). Anal. Calcd for C21H22BrF3O7: C, 48.20;
H, 4.24. Found: C, 48.03; H, 4.31.
C6H4-p-OMe) and 5.21 (CHCO2Et), 6.08 (OCHC6H4-p-OMe). 13C
NMR (100.6 MHz, CDCl3) (ppm) 13.82 (CH3), 13.98 (CH3), 14.05
d
(CH3), 55.28 (CH3), 61.71 (CH2), 62.97 (CH2), 63.34 (CH2), 67.91
(C), 79.65 (CH), 82.29 (CH), 113.86 (CH), 118.27 (CH, q, JFC¼36 Hz),
122.25 (C, q, JFC¼271 Hz), 129.51 (C), 129.59 (CH), 148.47 (C, q,
JFC¼5 Hz), 159.98 (C), 165.56 (C), 166.09 (C), 168.30 (C). Selected
3.2.3. Compound 3a
HMBC correlations are between
(C]CHCF3) and between
(CHCO2Et). 19F NMR (376 MHz, CDCl3)
d
d
5.21 (CHCO2Et) and
6.08 (OCHC6H4-p-OMe) and 79.65
(ppm) ꢁ60.22 (dd,
d 148.47
Rf¼0.4 (hexane–AcOEt¼3:1); pale yellow oil; 1H NMR
d
(400 MHz, CDCl3) 1:1 diastereomer mixture,
d
(ppm) 1.19–1.37 (m,
9H), 4.07–4.40 (m, 6H), 5.07 (s, 1ꢂ0.5H), 5.22 (d, J¼0.5 Hz,
1ꢂ0.5H), 5.78 (dq, J¼2.8, 2.8 Hz, 1ꢂ0.5H), 6.05 (dq, J¼8.8,
2.7 Hz, 1ꢂ0.5H), 6.11 (dq, J¼2.6, 2.6 Hz, 1ꢂ0.5H), 6.28 (dq, J¼8.8,
2.4 Hz, 1ꢂ0.5H), 7.27–7.34 (m, 5H). Selected NOEs are between
JFH¼9.2, 3.1 Hz); IR (neat) 2985, 1742, 1612, 1516, 1249, 1213, 1129,
1033 cmꢁ1; MS (EI) m/z 474 (Mþ, 5.0), 401 (84), 135 (100%);
HRMS (FAB) (MþNa)þ 479.1392 (calcd for C22H25F3O8Na
497.1399). Anal. Calcd for C22H25F3O8: C, 55.70; H, 5.31. Found: C,
55.35; H, 5.09.
d
5.07 (cis CHCO2Et) and 5.78 (cis OCHPh) and between d 5.22
(trans CHCO2Et) and 7.27–7.34 (trans o-H of Ph). 13C NMR
(100.6 MHz, CDCl3) (ppm) 13.83 (CH3), 13.95 (CH3), 13.97 (CH3),
d
3.2.6. cis-3d (including a small amount of impurity)
14.00 (CH3), 14.06 (CH3), 61.60 (CH2), 61.76 (CH2), 63.00 (CH2),
63.25 (CH2), 63.37 (CH2), 67.91 (C), 68.57 (C), 79.81 (CH), 80.57
(CH), 82.66 (CH), 82.96 (CH), 117.95 (CH, q, JFC¼37 Hz), 118.47 (CH,
q, JFC¼37 Hz), 122.03 (C, q, JFC¼272 Hz), 122.23 (C, q, JFC¼272 Hz),
128.21 (CH), 128.30 (CH), 128.55 (CH), 128.87 (CH), 128.93 (CH),
129.00 (CH), 136.79 (C), 137.25 (C), 148.09 (C, q, JFC¼5 Hz), 150.24
(C, q, JFC¼5 Hz), 165.31 (C), 165.54 (C), 166.01 (C), 166.66 (C), 167.23
Rf¼0.3 (hexane–ether¼1:1); pale yellow oil; 1H NMR (400 MHz,
CDCl3)
d
(ppm) 1.22 (t, J¼7.1 Hz, 3H), 1.30 (t, J¼7.1 Hz, 3H), 1.34
(t, J¼7.1 Hz, 3H), 3.79 (s, 3H), 4.09–4.41 (m, 6H), 5.04 (s, 1H), 5.73
(qd, J¼2.7, 2.7 Hz, 1H), 6.03 (qd, J¼8.8, 2.7 Hz, 1H), 6.83 (d-like,
J¼8.6 Hz, 2H), 7.26 (d, J¼8.6 Hz, 2H). Selected NOEs are between
d
5.04 (OCHC6H4-p-OMe) and 5.73 (CHCO2Et), 7.26 (o-H of C6H4-p-
OMe). 13C NMR (100.6 MHz, CDCl3)
d (ppm) 13.84 (CH3), 13.95
(C), 168.23 (C). Selected HMBC correlations are between
CHCO2Et) and 150.24 (cis C]CHCF3) and 5.22 (trans CHCO2Et)
and 148.09 (trans C]CHCF3). 19F NMR (376 MHz, CDCl3)
(ppm)
d
5.07 (cis
(CH3), 13.98 (CH3), 55.27 (CH3), 61.57 (CH2), 62.97 (CH2), 63.20
(CH2), 68.58 (C), 80.38 (CH), 82.61 (CH), 113.62 (CH), 117.74 (CH, q,
JFC¼37 Hz), 122.05 (C, q, JFC¼272 Hz), 129.06 (C), 130.27 (CH), 150.69
(C, q, JFC¼5 Hz), 160.08 (C), 165.39 (C), 166.67 (C), 167.28 (C).
d
d
ꢁ59.79 (dd, JFH¼7.5, 3.0 Hz), ꢁ60.28 (dd, JFH¼9.2, 3.2 Hz); IR (neat)
2986, 1774–1732, 1457, 1368, 1246, 1121 cmꢁ1; MS (EI) m/z 444
(Mþ, 8), 371 (100%); HRMS Mþ 444.1393 (calcd for C21H23F3O7
444.1396).
Selected HMBC correlations are between
150.69 (C]CHCF3) and between
(C(CO2Et)2). 19F NMR (376 MHz, CDCl3)
d
5.04 (CHCO2Et) and
d
d 6.03 (C]CHCF3) and 68.58
d
(ppm) ꢁ59.68 (dd, JFH¼9.2,
3.1 Hz); IR (neat) 2985, 1739, 1613, 1517, 1252, 1114, 1031 cmꢁ1; MS
(EI) m/z 474 (Mþ, 30), 401 (98), 327 (50), 281 (59), 213 (75), 135
(100%); HRMS (FAB) (MþNa)þ 497.1397 (calcd for C22H25F3O8Na
497.1399).
3.2.4. Compound 3b
Rf¼0.6 (hexane–ether¼4:1); pale yellow oil; 1H NMR (400 MHz,
CDCl3) 1:1 diastereomer mixture,
d
(ppm) 1.20 (t, J¼7.1 Hz, 3ꢂ0.5H),
1.279 (t, J¼7.1 Hz, 3ꢂ0.5H), 1.286 (t, J¼7.1 Hz, 3ꢂ0.5H), 1.294 (t,
J¼7.1 Hz, 3ꢂ0.5H), 1.33 (t, J¼7.1 Hz, 3ꢂ0.5H), 1.34 (t, J¼7.1 Hz,
3ꢂ0.5H), 2.32 (s, 3ꢂ0.5H), 2.33 (s, 3ꢂ0.5H), 4.07–4.40 (m, 6H), 5.05
(s, 1ꢂ0.5H), 5.20 (d, J¼0.7 Hz, 1ꢂ0.5H), 5.75 (dq, J¼2.8, 2.8 Hz,
1ꢂ0.5H), 6.03 (dq, J¼8.8, 2.7 Hz, 1ꢂ0.5H), 6.09 (dq, J¼2.6, 2.6 Hz,
1ꢂ0.5H), 6.26 (dq, J¼8.7, 2.4 Hz, 1ꢂ0.5H), 7.10–7.22 (m, 4H).
3.2.7. trans-3e
Rf¼0.3 (hexane–ether¼4:1); pale yellow oil; 1H NMR
(400 MHz, CDCl3)
d
(ppm) 1.26 (t, J¼7.1 Hz, 3H), 1.275 (t, J¼7.1 Hz,
3H), 1.281 (t, J¼7.1 Hz, 3H), 1.83–2.07 (m, 2H), 2.63–2.82 (m, 2H),
4.13–4.31 (m, 6H), 5.15–5.20 (m, 1H), 5.30 (d, J¼0.7 Hz, 1H), 6.13
(qd, J¼8.9, 2.4 Hz, 1H), 7.17–7.21 (m, 3H), 7.27–7.30 (m, 2H).
Selected NOEs are between
OCHAr) and between 5.20 (trans CHCO2Et) and 7.10–7.22 (trans
o-H of Ar). 13C NMR (100.6 MHz, CDCl3)
(ppm) 13.73 (CH3), 13.84
d 5.05 (cis CHCO2Et) and 5.75 (cis
d
Selected NOEs are between d 1.83–2.07 (OCHCH2CH2) and 5.15–
d
5.20 (OCHCH2CH2), 5.30 (OCHCO2Et). 13C NMR (100.6 MHz, CDCl3)
d (ppm) 13.81 (CH3), 13.91 (CH3), 14.02 (CH3), 31.81 (CH2), 36.22
(CH3), 13.88 (CH3), 13.89 (CH3), 13.96 (CH3), 21.13 (CH3), 21.16 (CH3),
61.48 (CH2), 61.63 (CH2), 62.90 (CH2), 63.14 (CH2), 63.25 (CH2), 67.87
(C), 68.56 (C), 79.62 (CH), 80.42 (CH), 82.41 (CH), 82.75 (CH), 117.56
(CH2, q, J¼1.5 Hz), 61.71 (CH2), 62.84 (CH2), 63.28 (CH2), 67.34 (C),
80.20 (CH), 116.31 (CH, q, JFC¼36 Hz), 122.74 (C, q, JFC¼271 Hz),

1992
S. Yamazaki et al. / Tetrahedron 65 (2009) 1988–1994
126.07 (CH), 128.46 (CH), 128.56 (CH), 141.06 (C), 149.48 (C, q,
JFC¼5 Hz), 165.33 (C), 166.00 (C), 168.68 (C). Selected HMBC cor-
(CH3), 13.95 (CH3), 14.11 (CH3), 50.80 (CH), 54.04 (CH), 58.71 (C),
61.90 (CH2), 62.32 (CH2), 62.42 (CH2), 118.12 (C, q, JFC¼41 Hz),119.84
(C, q, JFC¼273 Hz),128.11 (CH),128.13 (CH),128.38 (CH),135.44 (C, q,
JFC¼2 Hz), 142.31 (C, q, JFC¼3 Hz), 166.48 (C), 167.39 (C), 167.42 (C).
relations are between
d 5.30 (CHCO2Et) and d 149.48 (C]CHCF3)
and between
(376 MHz, CDCl3)
d
6.13 (C]CHCF3) and 67.34 (C(CO2Et)2). 19F NMR
d
(ppm) ꢁ59.79 (dd, JFH¼9.2, 3.1 Hz); IR (neat)
Selected HMBC correlations are between
(CHPh) and
5.43 (CHPh) and
d
4.82 (CHCO2Et), 5.43
4.82 (CHCO2Et),
58.71 (C(CO2Et)2). 19F NMR (376 MHz, CDCl3)
2985, 1744, 1369, 1254, 1213, 1123 cmꢁ1; MS (EI) m/z 472 (Mþ, 30),
399 (100), 279 (68%); HRMS Mþ 472.1705 (calcd for C23H27F3O7
472.1709). Anal. Calcd for C23H27F3O7: C, 58.47; H, 5.76. Found: C,
58.34; H, 5.73.
d 142.31 (C]CClCF3) and between d
d
d
(ppm) ꢁ65.82 (dd, JFH¼2.3, 2.3 Hz); IR (KBr) 2992, 1733, 1274,
1188, 1136 cmꢁ1; MS (EI) m/z 464 (Mþ, 9), 462 (Mþ, 26), 416 (49),
388 (43), 343 (43), 315 (100%); HRMS Mþ 462.1053 (calcd for
C21H2235ClF3O6 462.1057), 464.1032 (calcd for C21H2237ClF3O6
464.1028). Anal. Calcd for C21H22ClF3O6: C, 54.49; H, 4.79; Cl, 7.66; F,
12.31. Found: C, 54.55; H, 4.86; Cl, 7.59; F, 12.02.
3.2.8. cis-3e
Rf¼0.2 (hexane–ether¼4:1); pale yellow oil; 1H NMR (400 MHz,
CDCl3)
d
(ppm) 1.26 (t, J¼7.1 Hz, 3H), 1.29 (t, J¼7.1 Hz, 3H), 1.31 (t,
J¼7.1 Hz, 3H), 1.99–2.15 (m, 2H), 2.68–2.87 (m, 2H), 4.19–4.36 (m,
6H), 4.86–4.91 (m, 1H), 4.96 (s, 1H), 5.84 (qd, J¼8.8, 2.6 Hz, 1H),
7.16–7.21 (m, 3H), 7.26–7.30 (m, 2H). Selected NOEs are between
3.3.2. Compound 6b
Rf¼0.3 (hexane–ether¼4:1); yellow crystals, mp 73–74 ꢀC
d
4.86–4.91 (OCHCH2CH2) and 4.96 (OCHCO2Et), 1.99–2.15
(hexane–AcOEt); 1H NMR (400 MHz, CDCl3)
d (ppm) 0.756
(OCHCH2CH2). 13C NMR (100.6 MHz, CDCl3)
d
(ppm) 13.83 (CH3),
(t, J¼7.1 Hz, 3H), 1.25 (t, J¼7.1 Hz, 3H), 1.31 (t, J¼7.1 Hz, 3H), 2.30 (s,
3H), 3.52–3.61 (m, 1H), 3.70–3.78 (m, 1H), 4.12–4.32 (m, 4H), 4.82
(dq, J¼3.8, 2.2 Hz, 1H), 5.38 (dq, J¼3.5, 2.7 Hz, 1H), 7.05–7.10 (m,
13.97 (CH3), 14.05 (CH3), 31.69 (CH2), 35.96 (CH2, q, J¼1.5 Hz), 61.56
(CH2), 62.91 (CH2), 63.10 (CH2), 68.30 (C), 79.86 (CH), 80.73 (CH),
115.50 (CH, q, JFC¼36 Hz), 122.54 (C, q, JFC¼271 Hz), 126.03 (CH),
128.43 (CH), 128.64 (CH), 141.05 (C), 151.95 (C, q, JFC¼5 Hz), 165.42
(C), 166.55 (C), 167.70 (C). Selected HMBC correlations are between
4H). Selected NOEs are between
d 7.07–7.10 (Ar) and 4.82
(CHCO2Et), 5.38 (CHC6H4-4-Me). 13C NMR (100.6 MHz, CDCl3)
(ppm) 13.39 (CH3), 13.98 (CH3), 14.12 (CH3), 21.17 (CH3), 50.77
d
d
4.96 (CHCO2Et) and
d
151.95 (C]CHCF3), 79.86 (OCHCH2CH2). 19
F
(CH), 53.82 (CH), 58.76 (C), 61.88 (CH2), 62.28 (CH2), 62.38 (CH2),
117.96 (C, q, JFC¼41 Hz), 119.88 (C, q, JFC¼273 Hz), 128.02 (CH),
129.03 (CH), 132.42 (C, q, JFC¼1.5 Hz), 137.83 (C), 142.66 (C, q,
JFC¼2 Hz), 166.57 (C), 167.44 (C), 167.50 (C). Selected HMBC corre-
NMR (376 MHz, CDCl3)
d
(ppm) ꢁ59.52 (dd, JFH¼9.2, 3.1 Hz); IR
(neat) 2984, 1741, 1368, 1261, 1214, 1124 cmꢁ1; MS (EI) m/z 472 (Mþ,
30), 399 (100) 327 (42%); HRMS Mþ 472.1707 (calcd for C23H27F3O7
472.1709).
lations are between
d
4.82 (CHCO2Et), 5.38 (CHC6H4-4-Me) and
4.82 (CHCO2Et), 5.38 (CHC6H4-
58.76 (C(CO2Et)2). 19F NMR (376 MHz, CDCl3)
(ppm)
d
142.66 (C]CClCF3) and between d
3.2.9. Compound 5
4-Me) and
d
d
Rf¼0.6 (hexane–ether¼1:2); colorless oil; 1H NMR (400 MHz,
ꢁ65.78 (dd, JFH¼2.3, 2.3 Hz); IR (KBr) 2989, 1757, 1735, 1273, 1192,
1132, 1023 cmꢁ1; MS (EI) m/z 478 (Mþ, 11), 476 (Mþ, 28), 432 (66),
430 (86), 402 (95), 329 (100%); HRMS Mþ 476.1213 (calcd for
C22H2435ClF3O6 476.1214), 478.1210 (calcd for C22H2437ClF3O6
478.1184). Anal. Calcd for C22H24ClF3O6: C, 55.41; H, 5.07. Found: C,
55.39; H, 5.05.
CDCl3)
d
(ppm) 1.25 (t, J¼7.1 Hz, 3H), 1.28 (t, J¼7.1 Hz, 3H), 1.31
(t, J¼7.1 Hz, 3H), 1.24–1.33 (m, 1H), 1.54–1.95 (m, 9H), 4.14–4.37 (m,
6H), 5.06 (s,1H), 5.87 (q, J¼9.7 Hz,1H); 13C NMR (100.6 MHz, CDCl3)
d
(ppm) 13.82 (CH3), 13.97 (CH3), 14.07 (CH3), 21.87 (CH2), 22.11
(CH2), 24.76 (CH2), 32.56 (CH2, q, JFC¼3 Hz), 34.22 (CH2, q,
JFC¼3 Hz), 61.41 (CH2), 62.75 (CH2), 62.94 (CH2), 69.11 (C), 78.20
(CH), 85.95 (C), 115.60 (CH, q, JFC¼37 Hz), 122.46 (C, q, JFC¼271 Hz),
155.12 (C, q, JFC¼6 Hz), 165.99 (C), 166.84 (C), 168.27 (C). Selected
3.3.3. Compound 6f
Rf¼0.3 (hexane–ether¼4:1); yellow oil; 1H NMR (400 MHz,
HMBC correlations are between
d
5.06 (CHCO2Et) and
d
155.12
(ppm)
CDCl3)
d
(ppm) 0.712 (t, J¼7.1 Hz, 3H), 1.79 (t, J¼7.6 Hz, 3H), 1.25
(C]CHCF3), 85.95 (OC(CH2)5). 19F NMR (376 MHz, CDCl3)
d
(t, J¼7.1 Hz, 3H), 1.31 (t, J¼7.1 Hz, 3H), 2.60 (q, J¼7.6 Hz, 2H),
3.52–3.61 (m, 1H), 3.67–3.75 (m, 1H), 4.12–4.32 (m, 4H), 4.82 (dq,
J¼3.8, 2.2 Hz, 1H), 5.40 (dq, J¼3.6, 2.7 Hz, 1H), 7.08–7.12 (m, 4H).
ꢁ55.64 (d, JFH¼9.2 Hz); IR (neat) 2937, 1742, 1256, 1119 cmꢁ1; MS
(EI) m/z 436 (Mþ, 15), 363 (100%); HRMS Mþ 436.1715 (calcd for
C20H27F3O7 436.1709). Anal. Calcd for C20H27F3O7: C, 55.04; H, 6.24;
F, 13.06. Found: C, 55.22; H, 6.39; F, 12.73.
Selected NOEs are between
d 7.08–7.12 (Ar) and 4.82 (CHCO2Et),
5.40 (CHC6H4-4-Et). 13C NMR (100.6 MHz, CDCl3)
d (ppm) 13.32
(CH3), 13.92 (CH3), 14.07 (CH3), 15.63 (CH3), 28.57 (CH2), 50.72
(CH), 53.82 (CH), 58.72 (C), 61.84 (CH2), 62.25 (CH2), 62.34 (CH2),
117.91 (C, q, JFC¼40 Hz), 119.85 (C, q, JFC¼273 Hz), 127.81 (CH),
128.03 (CH), 132.61 (C, q, JFC¼1.5 Hz), 142.66 (C, q, JFC¼2 Hz),
144.23 (C), 166.53 (C), 167.41 (C), 167.45 (C). Selected HMBC
3.3. Reaction of 1 and 2a in the presence of SnCl4 (Eq. 3)
To a solution of 1 (122 mg, 0.5 mmol) in CH2Cl2 (0.9 mL) was
added
4,4,4-trifluoro-1-phenylbut-2-yn-1-ol
(2a)
(100 mg,
0.5 mmol) and SnCl4 (130 mg, 0.06 mL, 0.5 mmol). The mixture was
stirred at room temperature for 19 h. The reaction mixture was
quenched by water and then saturated aqueous NaHCO3. The
mixture was extracted with dichloromethane and the organic
phase was dried (Na2SO4), and evaporated in vacuo. The residue
was purified by column chromatography over silica gel with hex-
ane–ether as eluent to give 6a (77 mg, 33%) as an isolable product.
correlations are between
and 142.66 (C]CClCF3) and between
(CHC6H4-4-Et) and
d
4.82 (CHCO2Et), 5.40 (CHC6H4-4-Et)
d
d
4.82 (CHCO2Et), 5.40
d
58.72 (C(CO2Et)2). 19F NMR (376 MHz, CDCl3)
d
(ppm) ꢁ65.77 (dd, JFH¼2.5, 2.5 Hz). 19F/1H HOESY correlations
are between
d
ꢁ65.77 (CF3) and
d 5.40 (CHC6H4-4-Et) and 7.08–
7.12 (Ar–H). IR (neat) 2982, 1739, 1514, 1369, 1264, 1191,
1145 cmꢁ1; MS (EI) m/z 492 (Mþ, 3.4), 490 (Mþ, 6.6), 444 (27),
416 (42), 371 (49), 343 (100%); HRMS Mþ 490.1366 (calcd for
C23H2635ClF3O6 490.1370), 492.1351 (calcd for C23H2637ClF3O6
492.1341). Anal. Calcd for C23H26ClF3O6: C, 56.27; H, 5.34. Found:
C, 56.32; H, 5.14.
3.3.1. Compound 6a
Rf¼0.5 (hexane–ether¼1:1); pale yellow crystals, mp 76–78 ꢀC
(hexane); 1H NMR (400 MHz, CDCl3)
d
(ppm) 0.733 (t, J¼7.1 Hz, 3H),
1.25 (t, J¼7.1 Hz, 3H), 1.31 (t, J¼7.1 Hz, 3H), 3.49–3.57 (m, 1H), 3.68–
3.76 (m, 1H), 4.13–4.33 (m, 4H), 4.83 (dq, J¼3.8, 2.2 Hz, 1H), 5.43
(dq, J¼3.4, 2.7 Hz, 1H), 7.17–7.20 (m, 2H), 7.23–7.31 (m, 3H).
3.3.4. Compound 6g
Rf¼0.2 (hexane–ether¼4:1); pale yellow crystals, mp 56–58 ꢀC
Selected NOEs are between
d
7.17–7.20 (o-H of Ph) and 4.83
(ppm) 13.39
(hexane); 1H NMR (400 MHz, CDCl3)
1.196 (d, J¼7.0 Hz, 3H), 1.199 (d, J¼6.8 Hz, 3H), 1.24 (t, J¼7.1 Hz,
d
(ppm) 0.680 (t, J¼7.1 Hz, 3H),
(CHCO2Et), 5.43 (CHPh). 13C NMR (100.6 MHz, CDCl3)
d

S. Yamazaki et al. / Tetrahedron 65 (2009) 1988–1994
1993
3H), 1.31 (t, J¼7.1 Hz, 3H), 2.86 (septet, J¼6.9 Hz, 1H), 3.51–3.59 (m,
3.4. Reaction of 2a in the presence of SnCl4 (Eq. 4)
1H), 3.64–3.73 (m, 1H), 4.12–4.32 (m, 4H), 4.82 (dq, J¼3.7, 2.2 Hz,
1H), 5.39 (dq, J¼3.5, 2.7 Hz, 1H), 7.08–7.14 (m, 4H). Selected NOEs
To a solution of 4,4,4-trifluoro-1-phenylbut-2-yn-1-ol (2a)
(300 mg, 1.5 mmol) in CH2Cl2 (2.8 mL) was added SnCl4 (391 mg,
0.18 mL, 1.5 mmol). The mixture was stirred at room tempera-
ture for 17 h. The reaction mixture was quenched by water and
then saturated aqueous NaHCO3. The mixture was extracted
with dichloromethane and the organic phase was dried
(Na2SO4), and evaporated in vacuo. The residue was purified by
column chromatography over silica gel with hexane–ether as
eluent to give 7 (44 mg, 14%), 8 (49 mg, 15%), and 9 (120 mg,
42%).
are between
d 7.08–7.14 (Ar) and 4.82 (CHCO2Et), 5.39 (CHC6H4-
4-iPr). 13C NMR (100.6 MHz, CDCl3)
d (ppm) 13.36 (CH3), 13.97
(CH3), 14.12 (CH3), 23.96 (CH3), 33.85 (CH), 50.75 (CH), 53.87 (CH),
58.77 (C), 61.87 (CH2), 62.28 (CH2), 62.37 (CH2), 117.98 (C, q,
JFC¼41 Hz), 119.88 (C, q, JFC¼273 Hz), 126.37 (CH), 128.04 (CH),
132.73 (C), 142.62 (C, q, JFC¼3 Hz), 148.83 (C), 166.58 (C), 167.47 (C),
167.49 (C). Selected HMBC correlations are between
d
4.82
142.62 (C]CClCF3) and
4.82 (CHCO2Et), 5.39 (CHC6H4-4-iPr) and
58.77
(C(CO2Et)2). 19F NMR (376 MHz, CDCl3)
(ppm) ꢁ65.76 (dd, JFH¼2.4,
2.4 Hz). 19F/1H HOESY correlations are between
ꢁ65.76 (CF3) and
5.39 (CHC6H4-4-iPr) and 7.08–7.14 (Ar–H). IR (KBr) 2964, 1735,
(CHCO2Et), 5.39 (CHC6H4-4-iPr) and
between
d
d
d
d
d
3.4.1. Compound 7
d
Rf¼0.4 (hexane–ether¼2:1); pale yellow oil; 1H NMR (400 MHz,
1300, 1261, 1187, 1146 cmꢁ1; MS (EI) m/z 506 (Mþ, 20), 504 (Mþ, 41),
458 (87), 430 (98), 385 (91), 357 (100%); HRMS Mþ 504.1526 (calcd
for C24H2835ClF3O6 504.1527), 506.1505 (calcd for C24H2837ClF3O6
506.1497). Anal. Calcd for C24H28ClF3O6: C, 57.09; H, 5.59. Found: C,
57.14; H, 5.45.
CDCl3)
d
(ppm) 5.66 (q, J¼3.0 Hz, 1H), 7.40–7.46 (m, 3H), 7.50–7.53
(m, 2H); 13C NMR (100.6 MHz, CDCl3)
d (ppm) 47.15 (CH), 77.51 (C, q,
JFC¼53 Hz), 83.62 (C, q, JFC¼6 Hz), 114.01 (C, q, JFC¼258 Hz), 127.62
(CH), 129.31 (CH), 129.91 (CH), 135.91 (C); 19F NMR (376 MHz,
CDCl3)
d
(ppm) ꢁ51.28 (d, JFH¼3.1 Hz); IR (neat) 2265, 1457, 1284,
1264 cmꢁ1; MS (EI) m/z 220 (Mþ, 9), 218 (Mþ, 27), 183 (100%);
HRMS Mþ 218.0102 (calcd for C10H635ClF3 218.0110), 220.0056
(calcd for C10H637ClF3 220.0082).
3.3.5. Compound 6h (including a small amount of impurity)
Rf¼0.5 (hexane–ether¼1:1); brown oil; 1H NMR (400 MHz,
CDCl3)
d
(ppm) 0.799 (t, J¼7.1 Hz, 3H), 1.25 (t, J¼7.1 Hz, 3H), 1.31
(t, J¼7.1 Hz, 3H), 3.57–3.65 (m, 1H), 3.74–3.82 (m, 1H), 4.13–4.32 (m,
4H), 4.80 (dq, J¼3.8, 2.2 Hz, 1H), 5.40 (dq, J¼3.1, 2.8 Hz, 1H), 7.14
(d-like, J¼8.5 Hz, 2H), 7.28 (d-like, J¼8.5 Hz, 2H). Selected NOEs are
3.4.2. Compound 8
Rf¼0.3 (hexane–ether¼2:1); pale yellow oil; 1H NMR (400 MHz,
CDCl3)
(100.6 MHz,CDCl3)
d
(ppm) 6.93 (q, J¼2.7 Hz, 1H), 7.34–7.43 (m, 5H); 13C NMR
between
d
7.14 (Ar) and 4.80 (CHCO2Et), 5.40 (CHC6H4-4-Cl). 13C
d
(ppm)97.98(C,q,JFC¼45 Hz),108.54(CH),120.25
NMR (100.6 MHz, CDCl3)
d
(ppm) 13.48 (CH3), 13.98 (CH3), 14.13
(C, q, JFC¼273 Hz), 128.62 (CH), 129.26 (CH), 129.83 (C), 130.06 (CH),
(CH3), 50.78 (CH), 53.33 (CH), 58.62 (C), 62.03 (CH2), 62.52 (CH2),
62.55 (CH2), 118.53 (C, q, JFC¼41 Hz), 119.78 (C, q, JFC¼273 Hz),
128.62 (CH), 129.53 (CH), 133.96 (C), 134.10 (C), 141.74 (C, q, J¼2 Hz),
166.37 (C), 167.29 (2ꢂC). Selected HMBC correlations are between
201.73 (C, q, JFC¼2.3 Hz); 19F NMR (376 MHz, CDCl3)
(ppm) ꢁ66.68
d
(d, JFH¼3.1 Hz); IR (neat) 1963,1460,1400,1270,1131 cmꢁ1;MS(EI)m/z
220 (Mþ, 13), 218 (Mþ, 53), 183 (100%); HRMS Mþ 218.0108 (calcd
for C10H635ClF3 218.0110), 220.0085 (calcd for C10H637ClF3 220.0082).
d
4.80 (CHCO2Et), 5.40 (CHC6H4-4-Cl) and
between
(C(CO2Et)2). 19F NMR (376 MHz, CDCl3)
2.4 Hz). 19F/1H HOESY correlations are between
d
141.74 (C]CClCF3) and
58.62
(ppm) ꢁ65.71 (dd, JFH¼2.4,
ꢁ65.71 (CF3) and
d
4.80 (CHCO2Et), 5.40 (CHC6H4-4-Cl) and
d
3.4.3. Compound 9
d
Rf¼0.2 (hexane–ether¼2:1); colorless crystals, mp 52–55 ꢀC
d
(hexane); 1H NMR (400 MHz, CDCl3) obtained as 1:1 diastereomer
d
5.40 (CHC6H4-4-Cl) and 7.14 (Ar–H). IR (neat) 2985, 1736, 1493,
mixture,
d
(ppm) 5.31 (q, J¼2.9 Hz, 1ꢂ0.5H), 5.54 (q, J¼2.7 Hz,
1369, 1268, 1192, 1146 cmꢁ1; MS (EI) m/z 498 (Mþ, 4), 496 (Mþ, 6),
1ꢂ0.5H), 7.39–7.49 (m, 5H). Recrystallization from hexane changed
450 (33), 422 (51), 351 (68), 349 (100%); HRMS Mþ 496.0660 (calcd
the diastereomer ratio from 1:1 to 1.5:1. 13C NMR (100.6 MHz,
for
C21H2135Cl2F3O6
496.0667),
498.0629
(calcd
for
CDCl3)
d
(ppm) 69.10 (CH), 69.42 (CH), 75.01 (C, q, JFC¼53 Hz),
35
C21H21 Cl37ClF3O6 498.0638).
75.31 (C, q, JFC¼53 Hz), 83.97 (C, q, JFC¼6 Hz), 84.07 (C, q, JFC¼6 Hz),
113.97 (C, q, JFC¼258 Hz), 127.69 (CH), 127.83 (CH), 129.09 (CH),
129.23 (CH), 129.73 (CH), 129.92 (CH), 134.94 (C), 135.04 (C); 19F
3.3.6. Compound 6i
Rf¼0.2 (hexane–ether¼3:1); yellow oil; 1H NMR (400 MHz,
NMR (376 MHz, CDCl3)
d
(ppm) ꢁ51.02 (d, JFH¼3.1 Hz), ꢁ51.11 (d,
CDCl3)
d
(ppm) 0.798 (t, J¼7.1 Hz, 3H), 1.25 (t, J¼7.1 Hz, 3H), 1.31
JFH¼3.1 Hz); IR (KBr) 2265, 1282, 1144 cmꢁ1; MS (EI) m/z 382 (Mþ,
2), 304 (5), 183 (100%); HRMS Mþ 382.0793 (calcd for C20H12F6O
382.0792). Anal. Calcd for C20H12F6O: C, 62.83; H, 3.16. Found: C,
62.71; H, 3.24.
(t, J¼7.1 Hz, 3H), 3.56–3.64 (m, 1H), 3.74–3.82 (m, 1H), 4.13–4.33
(m, 4H), 4.80 (dq, J¼3.8, 2.2 Hz, 1H), 5.41 (dq, J¼3.1, 2.6 Hz, 1H),
6.99 (t-like, J¼8.8 Hz, 2H), 7.18 (dd-like, J¼8.3, 5.2 Hz, 2H). Selected
NOEs are between
d 7.18 (Ar) and 4.80 (CHCO2Et), 5.41 (CHC6H4-4-
F). 13C NMR (100.6 MHz, CDCl3)
d
(ppm) 13.51 (CH3), 13.97 (CH3),
Acknowledgements
14.12 (CH3), 50.74 (CH), 53.27 (CH), 58.68 (C, q, J¼1.5 Hz), 61.99
(CH2), 62.44 (CH2), 62.50 (CH2), 115.35 (CH, d, J¼21 Hz), 118.43 (C,
q, JFC¼41 Hz), 119.79 (C, q, JFC¼273 Hz), 129.91 (CH, d, J¼8 Hz),
131.32 (C, d, J¼1.5 Hz), 142.17 (C, q, J¼3 Hz), 162.50 (C, d,
J¼247 Hz), 166.46 (C), 167.35 (2ꢂC). Selected HMBC correlations
This work was supported by the Ministry of Education, Culture,
Sports, Science, and Technology of the Japanese Government. We
thank Mr. T. Matsuda and Mr. Y. Fukushima (Nara University of
Education) for experimental help. We thank Nara Institute of Sci-
ence and Technology (NAIST) and Prof. K. Kakiuchi (NAIST) for mass
spectra. We also thank to Prof. S. Umetani (Kyoto University) for
elemental analyses.
are between
d
4.80 (CHCO2Et), 5.41 (CHC6H4-4-F) and
d 142.17
(C]CClCF3) and between
d
d
4.80 (CHCO2Et), 5.41 (CHC6H4-4-F) and
58.68 (C(CO2Et)2). 19F NMR (376 MHz, CDCl3)
d
(ppm) ꢁ114.12 (tt,
JFH¼8.5, 5.2 Hz, 3ꢂF), ꢁ65.72 (dd, JFH¼2.3, 2.3 Hz, 1ꢂF). 19F/1H
HOESY correlations are between
d
ꢁ65.72 (CF3) and
d
5.41
6.99
(CHC6H4-4-F) and 7.18 (Ar) and between
d
ꢁ114.12 (CF3) and
d
Supplementary data
(Ar–H). IR (neat) 2985, 1737, 1607, 1511, 1270, 1192, 1146 cmꢁ1; MS
(EI) m/z 482 (Mþ, 3), 480 (Mþ, 6), 434 (34), 406 (45), 361 (35), 333
(100%); HRMS Mþ 480.0961 (calcd for C21H2135ClF4O6 480.0963),
482.0973 (calcd for C21H2137ClF4O6 482.0933).
Crystallographic data and 1H and 13C NMR data. Supplementary
data associated with this article can be found in the online version,
at doi:10.1016/j.tet.2009.01.024.

1994
S. Yamazaki et al. / Tetrahedron 65 (2009) 1988–1994
7. Recently, conversion of propargyl alcohols to chloroallenes using TiCl4/R3N has
References and notes
been reported Karunakar, G. V.; Periasamy, M. J. Org. Chem. 2006, 71, 7463.
8. The reaction of 1 and 2a in the presence of 0.2 equiv of SnCl4 gave starting
materials 1 and 2a along with a small amount of unidentified impurities.
9. Crystallographic data for 6a have been deposited with the Cambridge Crys-
tallographic Data Centre (no. CCDC 698776). Copies of the data can be obtained,
free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK,
(fax: þ44 (0)1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
1. (a) Welch, J. T. Tetrahedron 1987, 43, 3123; (b) Welch, J. T.; Eswarakrishnan, S.
Fluorine in Bioorganic Chemistry; John Wiley & Sons: New York; NY, 1991; (c)
Organofluorine Compounds in Medicinal and Biochemical Applications; Filler, R.,
Kobayashi, Y., Yagupolskii, L. M., Eds.; Elsevier: Amsterdam, 1993; (d) Resnati,
G.; Soloshnok, V. A. Fluoroorganic chemistry: synthetic challenges and bio-
medical rewards (Tetrahedron Symposium-in-Print Number 58). Tetrahedron
1996, 52, 1; (e) Fluorine-containing Amino Acids, Synthesis and Properties;
Kukhar, V. P., Soloshonok, V. A., Eds.; J. Wiley and Sons: New York, NY, 1995; (f)
Asymmetric Fluoroorganic Chemistry, Synthesis, Application and Future Directions;
Ramachandran, P. V., Ed.; American Chemical Society: Washington, DC, 2000.
2. (a) Yamazaki, S. Chem.dEur. J. 2008, 14, 6024; (b) Marat, X.; Monteiro, N.;
Balme, G. Synlett 1997, 845; (c) Cavicchioli, M.; Marat, X.; Monteiro, N.; Hart-
mann, B.; Balme, G. Tetrahedron Lett. 2002, 43, 2609; (d) Nakamura, M.; Liang,
C.; Nakamura, E. Org. Lett. 2004, 6, 2015; (e) Yakura, T.; Yamada, S.; Shiima, M.;
Iwamoto, M.; Ikeda, M. Chem. Pharm. Bull. 1998, 46, 744; (f) Morikawa, S.;
Yamazaki, S.; Furusaki, Y.; Amano, N.; Zenke, K.; Kakiuchi, K. J. Org. Chem. 2006,
71, 3540; (g) Morikawa, S.; Yamazaki, S.; Tsukada, M.; Izuhara, S.; Morimoto, T.;
Kakiuchi, K. J. Org. Chem. 2007, 72, 6459.
3. (a) Yamazaki, T.; Mizutani, K.; Kitazume, T. J. Org. Chem. 1995, 60, 6046; (b)
Yamazaki, T.; Yamamoto, T.; Ichihara, R. J. Org. Chem. 2006, 71, 6251.
4. Hammet constants of the CF3 group are sm¼0.46 and sp¼0.53 Exner, O. In
Correlation Analysis in Organic Chemistry; Chapman, N. B., Shorter, J., Eds.;
Plenum: New York, NY, 1978; Chapter 10.
5. Qing, F.-L.; Gao, W.-Z.; Ying, J. J. Org. Chem. 2000, 65, 2003.
6. The (Z)-structure of 3a–e was determined by the absence of NOE peaks
between ]CHCF3 and OCHR (in Eq. 1) in the NOESY spectra.
10. The stereochemistry of 6b, 6f–i was assigned by NOESY and 19F/1H HOESY (for
6f–i) spectra, along with similarity to 6a in the NMR spectra.
11. The alkyl groups (R0¼Me, Et, iPr) in 2b,f,g may stabilize the cationic
intermediate A (in Scheme 1) for the [2þ2] cycloaddition as electron-donating
groups. On the other hand, SnCl4 possibly coordinates to OMe and Br groups
(2d, 2c) and causes side reactions. However, at this stage it is difficult to discuss
on the electronic effects of substituents. Study on the detailed reaction mech-
anism is under investigation.
12. [2þ2] Cycloadditions of allene derivatives with Michael acceptors in the
presence of Lewis acids have been reported. (a) Narasaka, K.; Hayashi, Y.;
Shimadzu, H.; Niihata, S. J. Am. Chem. Soc. 1992, 114, 8869; (b) Engler, T. A.;
Agrios, K.; Reddy, J. P.; Iyengar, R. Tetrahedron Lett. 1996, 37, 327.
13. Chloroallenes have been also prepared from propargyl alcohols by treatment
with concentrated hydrochloric acid in the presence of cuprous and ammo-
nium chlorides, or calcium chloride. (a) Hennion, G. F.; Sheehan, J. J.; Maloney,
D. E. J. Am. Chem. Soc. 1950, 72, 3542; (b) Tseng, C. K.; Migliorese, K. G.; Miller, S.
I. Tetrahedron 1974, 30, 377; (c) Crandall, J. K.; Conover, W. W.; Komin, J. B.;
Machleder, W. H. J. Org. Chem. 1974, 39, 1723.
14. These calculations were performed at the RHF/STO-3G//B3LYP/6-31G
Gaussian 03.
*
with