A kinetic separation method for the stereoselective preparation of (Z)- and (E)-monofluoroenynes from E/Z mixtures of 1-bromo-1-fluoroolefins

Article abstract of DOI:10.1016/S0022-1139(01)00529-2

Reaction of E/Z mixtures of 1-bromo-1-fluoroolefins with 1-alkynes and catalytic Pd(PPh₃)₂Cl₂ and CuI in triethylamine at room temperature gave (after 16-24h) predominately the (Z)-monofluoroenyne (Z/E>92/8) in good yields. Pure (Z)-monofluoroenyne could generally be obtained by chromatographic separation of the crude Z/E mixture. Pure (Z)-1-bromo-1-fluoroolefin could he recovered and reacted with 1-alkynes under similar conditions and longer reaction times (48h) to give pure (E)-monofluoroenynes in excellent yields (78-89%). Thus, E/Z mixtures of 1-bromo-1-fluoroolefins could be kinetically separated into (Z)- and (E)-monofluoroenynes. This methodology provides a simple one-step unequivocal route to the isomerically pure (Z)- and (E)-monofluoroenynes from the readily available 1-bromo-1-fluoroolefins.

Full text of DOI:10.1016/S0022-1139(01)00529-2

Journal of Fluorine Chemistry 112 ꢀ2001) 317±324
A kinetic separation method for the stereoselective preparation
of ꢀZ)- and ꢀE)-mono¯uoroenynes from E/Z mixtures
of 1-bromo-1-¯uoroole®ns
*
Xin Zhang,Donald J. Burton
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
Received 6 June 2001; accepted 31 August 2001
Abstract
Reaction of E/Z mixtures of 1-bromo-1-¯uoroole®ns with 1-alkynes and catalytic PdꢀPPh3)2Cl2 and CuI in triethylamine at room
temperature gave ꢀafter 16±24 h) predominately the ꢀZ)-mono¯uoroenyne ꢀZ=E > 92=8) in good yields. Pure ꢀZ)-mono¯uoroenyne could
generally be obtained by chromatographic separation of the crude Z/E mixture. Pure ꢀZ)-1-bromo-1-¯uoroole®n could he recovered and
reacted with 1-alkynes under similar conditions and longer reaction times ꢀ48 h) to give pure ꢀE)-mono¯uoroenynes in excellent yields ꢀ78±
89%). Thus, E/Z mixtures of 1-bromo-1-¯uoroole®ns could be kinetically separated into ꢀZ)- and ꢀE)-mono¯uoroenynes. This methodology
provides a simple one-step unequivocal route to the isomerically pure ꢀZ)- and ꢀE)-mono¯uoroenynes from the readily available 1-bromo-1-
¯uoroole®ns. # 2001 Elsevier Science B.V. All rights reserved.
Keywords: Enynes; Mono¯uoroenynes; Kinetic separation; Palladium catalysis
1. Introduction
[16,17]. This route was limited to aryl substituents on the
ole®nic carbon and required several steps to the 1-bromo-1-
¯uoro-arylethene. Similar palladium-catalyzed condensa-
tion of 1-halo-2-¯uoroalkenes with 1-alkynes provided a
route to 1-¯uoro-1-en-3-yne derivatives [18]. a-Fluoropro-
pargyl phosphonate ester condensation with aldehydes has
also been successfully utilized for the preparation of con-
jugated ¯uoroenynes [19,20], and the addition±elimination
sequence of acetylenic lithium reagents with 1,1-dichloro-
2,2-di¯uoroethene also provided several mono¯uoroenynes
[21].
Recently,we reported a stereoselective preparation of
pure ꢀE)- and ꢀZ)-1-¯uorovinylphosphonates via a kinetic
separation,utilizing a palladium-catalyzed phosphorylation
reaction of E/Z mixtures of 1-bromo-1-¯uoroole®ns with
dialkyl phosphites and triethylamine [22,23].
The chemistry and biology of conjugated enynes has
recently received extensive attention [1,2]. Methods for
the synthesis of ¯uorinated analogs have received increased
attention,since many of these ¯uorinated analogs exhibit
interesting biological activity [3±8]. The most popular
approach to di¯uorinated enynes has been via palladium-
catalyzed cross-coupling reactions of 1-alkynes with ¯uori-
nated vinyl bromides or iodides [9±14]. In contrast to the
many examples of di¯uorinated or tri¯uorinated enynes,
only a few reports of mono¯uoroenynes have been docu-
mented. Camps introduced ¯uorine to a pre-existing enyne
via a multi-step sequence [15]. Rolando and co-workers
employed a palladium-catalyzed cross-coupling reaction
of 1-bromo-1-¯uoro-2-arylethene with a terminal alkyne
* Corresponding author. Tel.:‡1-319-335-1363; fax:‡1-319-335-1270.
E-mail address: donald-burton@uiowa.edu ꢀD.J. Burton).
The recovered ꢀZ)-C6H5CH=CFBr could be stereospecifi-
cally converted to the ꢀZ)-1-fluoro-vinylphosphonate by a
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ꢀ 0 1 ) 0 0 5 2 9 - 2

318
X. Zhang, D.J. Burton / Journal of Fluorine Chemistry 112 +2001) 317±324
similar phosphorylation reaction at 70±80 8C [22]. Mechan-
istic experiments indicated that the kinetic separation
occurred in the oxidative addition step of the vinyl bromide
to Pdꢀ0). Consequently,we reasoned that other Pdꢀ0)-cata-
However,when an E/Z mixture of 1-bromo-1-¯uorostyr-
ene was reacted with phenylacetylene under similar cou-
pling conditions,a signi®cantly better kinetic separation was
observed,as outlined below:
lyzed cross-coupling reactions of the E/Z mixture of the 1-
bromo-1-fluoroolefins controlled by the rate of the oxidative
addition step could also provide a novel utilization of both
the ꢀE)- and ꢀZ)-olefins of the E/Z mixture for the stereo-
selective preparation of multi-functionalized derivatives.
Herein,we report the extension of this kinetic separation
methodology for the stereoselective synthesis of monofluor-
oenynes [23].
At room temperature,the reaction was monitored ꢀby 19F
NMR) until all the ꢀE)-olefin had been consumed ꢀꢀ16 h).
The reaction was stopped at this stage,and the products
separated by silica gel chromatography. Pure ꢀZ)-
C6H5CH=CFBr was recovered,and C 6H5CH=CFCBCC6H5
ꢀZ=E ˆ 93=7) was obtained,which on further purification
ꢀby recrystallization from pentane) gave 38% of pure ꢀZ)-
C6H5CH=CFCBCC6H5,characterized by 1H, 19F and 13C
NMR and mass spectroscopy ꢀboth LRMS and HRMS). The
ꢀZ)- or ꢀE)-configuration was assigned on the magnitude of
3
2. Results and discussion
trans JHF > cis3JHF, cf. [16,17,22]. Thus, kinetic separa-
tion significantly enhances the formation of the ꢀZ)-enyne.
We chose to monitor the reaction until all the ꢀE)-olefin had
reactedÐin order to maximize the amount and purity of the
recovered ꢀZ)-olefinꢀwhich,with longer reactiontimes) could
be similarly coupled to give the ꢀE)-enyne. If one wished only
the ꢀZ)-enyne,the reaction could be terminated earlier to
increase the Z/E ratio of enyne product. When E/Z mixtures of
1-bromo-1-fluorostyrenes were treated similarly with a vari-
ety of 1-alkynes,the corresponding ꢀ Z)-enynes could be
obtained in reasonable yields and high purity after chromato-
graphic separation. These results are summarized in Table 1
ꢀcompounds 1±6). Similar kinetic separation was achieved
with the p-chlorostyrene analog ꢀcompounds 7±8),as well as
Our initial preparation of mono¯uorinated enynes utilized
the palladium-catalyzed coupling reaction of 1-alkynes with
an E/Z mixture of 1-¯uoro-1-iodostyrene as a model reac-
tion. The styrene was prepared via a Wittig±Horner reaction
as outlined below [24]:
The 1-fluoro-1-iodostyrene reacted smoothly with phenyla-
cetylene at room temperature in the presence of PdꢀPPh3)2-
Cl2,CuI and Et N.
3
Although the Z/E ratio ꢀ1:1) improved after a modest reac-
tion time ꢀZ=E ˆ 7=3),it was obvious that both isomers of
the vinyl iodide had reacted and eventually a 1:1 Z/E mixture
was obtained after 16 h at room temperature. Similar results
were obtained with 1-heptyne and ꢀÆ) acetaldehyde ethyl
propargyl acetal. Thus,although some kinetic separation
was observed,the relative rate of the E/Z-olefin isomers with
the 1-alkynes was not sufficiently different to be of practical
value and paralleled similar observations in the attempted
kinetic separation of 1-fluoro-1-iodoolefins via Pdꢀ0)-cata-
lyzed phosphorylation reactions [22].
with alkyl substituted 1-bromo-1-fluoroolefins ꢀcompounds
9±12). The recovered ꢀZ)-1-bromo-1-fluoroolefins were sub-
sequently coupled ꢀwith longer reaction times) to yield the
corresponding ꢀE)-monofluorinated enynes in excellent
yields and high stereochemical purity ꢀcompounds 13±19).
The reactive Pdꢀ0) is usually generated in situ,but one can
also catalyze the reaction with PdꢀPPh3)4 ꢀcf. compound 6)
in DMF/Et3N. With the normal PdꢀPPh3)2Cl2/CuI/Et3N
system,the CuI is necessary for rapid reaction. In the
absence of CuI,the conversion of ꢀ E)-ole®ns to ꢀZ)-enynes
takes ꢀ1 week for total consumption of the ꢀE)-ole®n.

X. Zhang, D.J. Burton / Journal of Fluorine Chemistry 112 +2001) 317±324
319
Table 1
The Pdꢀ0)-catalyzed reaction of E/Z-1-bromo-1-fluoroolefins with 1-alkynes
E=Z-RCHˆCFBr ‡ HCBCR0PdꢁPPh3† Cl2
!
RCHˆCFCBCR0
2
CuI=Et3N=RT
Compound no.
R
R0
E/Z ratio of olefin
Reaction conditions
Isolated yield ꢀ%)a Z/E ratio enyne
1
2
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
6/5
1/1
RT,16 h
RT,24 h
RT,24 h
RT,16 h
RT,24 h
RT,24 h
RT,24 h
RT,24 h
RT,24 h
RT,24 h
RT,24 h
RT,24 h
RT,48 h
RT,48 h
RT,48 h
RT,48 h
RT,48 h
RT,48 h
RT,48 h
38 ꢀ100:0)
46 ꢀ98:2)
54 ꢀ95:5)
23 ꢀ99:1)
49 ꢀ95:5)
45 ꢀ99:1)
48 ꢀ99:1)
49 ꢀ99:1)
64 ꢀ90:10)
43 ꢀ98:2)
46 ꢀ93:7)
53 ꢀ92:8)
88 ꢀ3:97)
87 ꢀ0:100)
89 ꢀ>2:98)
89 ꢀ>1:99)
77 ꢀ0:100)
89 ꢀ0:100)
78 ꢀ0:100)
C5H11
Acetalb
3
3/2
4
SiꢀCH3)3
CHꢀOH)CH3
Cyclohexanol
CHꢀOH)CH3
Acetalb
6/5
5
1/1
1/1
6
7
p-ClC6H4
p-ClC6H4
C7H15
1/1
8
1/1
9
C6H5
CHꢀOH)CH3
Acetalb
7/3
1/1
10
11
12
13
14
15
16
17
18
19
C7H15
C7H15
1/1
C6H5ꢀCH3)CH
C6H5
C6H5
CHꢀOH)CH3
C6H5
C5H11
Acetalb
7/3
3/97
0/100
>2/98
0/100
0/100
0/100
0/100
C6H5
C6H5
CHꢀOH)CH3
CHꢀOH)CH3
Acetalb
p-ClC6H4
p-ClC6H4
C6H5ꢀCH3)CH
CHꢀOH)CH3
a Z/E ratio and yield of enyne after chromatography; yield is based on the amount of olefin consumed.
b Acetal,R ˆ CH2OCHꢁOCH2CH3†CH3.
3. Conclusions
performed at 70 eV in the electron-impact mode on a single-
quadrapole instrument interfaced to a gas chromatograph
®tted with an OV-101 column. High resolution mass spectral
analyses were performed by the High Resolution Mass
Spectroscopy Facility,University of Iowa,at 70 eV in the
electron-impact mode. GLPC analyses were performed on a
5% OV-101 column with a thermal conductivity detector.
This work demonstrates another useful practical applica-
tion of kinetic separation in reactions of E/Z-1-bromo-1-
¯uoroole®ns mediated by palladium catalysis [22]. By
utilizing the difference in reactivity of the ꢀE)- and ꢀZ)-
ole®ns,the conversion to ꢀ Z)-mono¯uorinated enynes can he
achieved. In addition,the less reactive ꢀ Z)-ole®n can he
recovered and selectively converted to the corresponding
ꢀE)-mono¯uorinated enynes in high yields and high stereo-
selectivity. Consequently,the E/Z-1-bromo-1-¯uoroole®ns,
which are readily prepared from aldehydes and the bromo-
¯uoromethylene ylide [25] can he employed to produce both
the ꢀZ)- and ꢀE)-mono¯uorinated enynes,thus,providing a
simple one-step route to both isomers of these useful com-
pounds. Further applications of kinetic separation utilizing
E/Z mixtures of 1-bromo-1-¯uoroole®ns are in progress and
will he reported in due course.
4.2. Materials
The E/Z mixtures of 1-bromo-1-¯uoroole®ns were pre-
pared from the corresponding aldehydes and [Ph3P=CFBr] as
described in the literature [25]. The E/Z mixtures of 1-¯uoro-
1-iodo¯uoroole®ns were prepared from the corresponding
aldehydes and [ꢀEtO)2PꢀO)CFI] [24]. ꢀEtO)2PꢀO)CFHI
was prepared by iodination of ꢀEtO)2PꢀO)CFHZnBr [26].
Tetrakis ꢀtriphenylphosphine) palladium was prepared by
Coluson's procedure [27]. The aldehydes and 1-alkynes
were commercial samples and were either distilled prior
to use or used directly. Et3N was dried over NaH and
distilled from CaH2. CuI was puri®ed by the literature
procedure [28]. PdꢀPPh3)2Cl2 was prepared by King and
Negishi's procedure [29].
4. Experimental
4.1. General
All reactions were monitored by 19F NMR analysis of the
reaction mixture on a 90 or 300 MHz spectrometer. The 1H,
19F and 13C NMR spectra of ®nal products were obtained on
a 300 MHz spectrometer ꢀCDCl3,CFCl 3 or TMS as internal
references). FT-IR spectra were recorded on the pure sample
on NaCl plates. Low resolution mass spectra analyses were
4.2.1. +Z)-1,4-diphenyl-3-fluoro-3-buten-1-yne +1)
To a mixture of 0.01 g ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01 g
ꢀ0.05 mmol) CuI,0.21 g ꢀ2.0 mmol) C 6H5CBCH and 2.0 ml
of Et3N was added 0.41 g ꢀ2.0 mmol) of an E/Z mixture
ꢀE=Z ˆ 6=5) of C6H5CH=CFBr. The resulting mixture was
stirred at room temperature until no ꢀE)-ole®n remained by

320
X. Zhang, D.J. Burton / Journal of Fluorine Chemistry 112 +2001) 317±324
19F NMR analysis of the reaction mixture ꢀꢀ16 h). The
reaction mixture was directly puri®ed by silica gel chromato-
graphy ꢀhexane as eluant); 0.20 g of pure ꢀZ)-C6H5CH=CFBr
was recovered ꢀ0.21 g ole®n consumed) and 0.24 g of a white
solid was obtained ꢀZ=E ˆ 93=7). Recrystallization from
ꢀm,2H),1.36 ꢀd, J ˆ 5:3 Hz,3H),1.23 ꢀt, J ˆ 7:0 Hz,3H)
ppm. 19F NMR ꢀCDCl3): À105.2 ꢀdt, J ˆ 34:3 Hz, J ˆ 4:5
Hz) ppm. 13C NMR ꢀCDCl3): 140.4 ꢀd, J ˆ 248:7 Hz),
132.6 ꢀd, J ˆ 6:1 Hz),129.1 ꢀd, J ˆ 8:0 Hz),128.6,128.2
ꢀd, J ˆ 2:8 Hz),116.3 ꢀd, J ˆ 12:2 Hz),98.8,89.2 ꢀd, J ˆ
6:1 Hz),78.8 ꢀd, J ˆ 42:1 Hz),60.8,52.7 ꢀd, J ˆ 1:9 Hz),
1
pentane gave 0.17 g ꢀ38%) of pure ꢀ1). H NMR ꢀCDCl3)
‡
7.21±7.55 ꢀm,10H),6.13 ꢀd, J ˆ 34:9 Hz,1H) ppm. 19F
NMR ꢀCDCl3): À104.7 ꢀd, J ˆ 34:9 Hz) ppm. 13C NMR
ꢀCDCl3): 141.2 ꢀd, J ˆ 248:5 Hz),132.9 ꢀd, J ˆ 6:1 Hz),
131.7 ꢀd, J ˆ 2:1 Hz),129.2 ꢀd, J ˆ 4:3 Hz),129.1,128.5,
128.4,128.1 ꢀd, J ˆ 2:6 Hz),121.4 ꢀd, J ˆ 2:1 Hz),116.1 ꢀd,
J ˆ 12:8 Hz),92.4 ꢀd, J ˆ 6:4 Hz),82.3 ꢀd, J ˆ 41:8 Hz)
19.6,15.2 ppm. GC±MS: 248 ꢀ M ,3),233 ꢀ10),185 ꢀ6),176
ꢀ39),159 ꢀ100),146 ꢀ46),133 ꢀ54),72 ꢀ28). FT-IR ꢀneat,
NaCl plate): 3319 ꢀs),3027 ꢀs),2935 ꢀvs),2875 ꢀs),1664 ꢀs),
1646 ꢀvs). TLC: Rf ˆ 0:3 ꢀhexanes:ethyl acetate ˆ 1:4).
4.2.4. +3Z)-3-fluoro-4-phenyl-1-trimethylsilyl-
3-buten-1-yne +4)
‡
ppm. GC±MS: 222 ꢀM ,83),220 ꢀ100),202 ꢀ98),194 ꢀ11),
110 ꢀ36),98 ꢀ18). HRMS: Calcd for C 16H11F: 222.0845;
Found: 222.0859.
Similarly,0.40 g ꢀ2.0 mmol) of an E/Z mixture of
C6H5CH=CFBr ꢀE=Z ˆ 6=5) was reacted with 0.20 g
ꢀ2.0 mmol) of Me3SiCBCH in the presence of 0.01 g
ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01 g ꢀ0.05 mmol) CuI and
2.0 ml Et3N at room temperature until no ꢀE)-ole®n
remained by 19F NMR analysis of the reaction mixture
ꢀꢀ16 h). The reaction mixture was directly puri®ed by silica
gel chromatography ꢀhexanes,100%); 0.15 g of crude enyne
ꢀZ=E ˆ 85=15) was obtained; after a second silica gel
chromatography,0.10 g of ꢀ 4) ꢀZ=E ˆ 99=1) ꢀ23%) was
4.2.2. +Z)-2-fluoro-1-phenyl-1-nonen-3-yne +2)
To a mixture of 0.01 g ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01 g
ꢀ0.05 mmol) CuI,0.19 g ꢀ2.0 mmol) CH ꢀCH2)4CBCH and
3
2.0 mlofEt3Nwasadded0.40 gꢀ2.0 mmol)ofanE/Zmixture
of C6H5CH=CFBr ꢀE=Z ˆ 1=1). The reaction mixture was
stirred at room temperature until no ꢀE)-ole®n remained by
19F NMR analysis of the reaction mixture ꢀꢀ24 h). The
reaction mixture was directly puri®ed by silica gel chroma-
tography ꢀhexanes). After solvent removal via rotary eva-
poration,excess ole®n was removed under vacuum ꢀ0.02 mm
Hg) and 0.20 g ꢀ46%) of ꢀ2) ꢀZ=E ˆ 98=2) was obtained. 1H
NMR ꢀCDCl3): 7.21±7.51 ꢀm,5H),5.93 ꢀd, J ˆ 35:2 Hz,
1H),2.39 ꢀtd, J ˆ 7:1 Hz, J ˆ 5:0 Hz,2H),1.29±1.64 ꢀm,
6H),0.92 ꢀt, J ˆ 6:9 Hz,3H),ppm. 19F NMR ꢀCDCl3):
À102.3 ꢀdt, J ˆ 35:0 Hz, J ˆ 5:0 Hz) ppm. 13C NMR
ꢀCDCl3): 141.4 ꢀd, J ˆ 248:5 Hz),133.1 ꢀd, J ˆ 6:1 Hz),
128.9 ꢀd, J ˆ 8:3 Hz),128.5,127.7 ꢀd, J ˆ 2:4 Hz),114.3 ꢀd,
J ˆ 13:4 Hz),94.4 ꢀd, J ˆ 6:0 Hz),74.1 ꢀd, J ˆ 41:5 Hz),
31.0 ꢀd, J ˆ 3:6 Hz),27.8 ꢀd, J ˆ 1:6 Hz),22.1,19.2 ꢀd,
1
obtained. H NMR ꢀCDCl3): 7.25±7.50 ꢀm,5H),6.06 ꢀd,
J ˆ 35:0 Hz,1H),0.25 ꢀs,9H) ppm.
19F NMR ꢀCDCl3):
À105.8 ꢀd, J ˆ 35:0 Hz) ppm. 13C NMR ꢀCDCl3): 140.8 ꢀd,
J ˆ 249:0 Hz),132.7 ꢀd, J ˆ 6:1 Hz),129.1 ꢀd, J ˆ 8:6 Hz),
128.6,128.2 ꢀd, J ˆ 2:5 Hz),116.3 ꢀd, J ˆ 12:2 Hz),99.0
ꢀd, J ˆ 4:9 Hz),97.0 ꢀd, J ˆ 40:3 Hz), À0.48 ppm. GC±
‡
MS: 218 ꢀM ,49); 203 ꢀ20),183 ꢀ11),163 ꢀ5),141 ꢀ36),101
ꢀ100),87 ꢀ5),77 ꢀ36). FT-IR ꢀneat,NaCl plate): 3056 ꢀs),
3027 ꢀs),2962 ꢀm),2900 ꢀs),1643 ꢀm).
4.2.5. +5Z)-5-fluoro-6-phenyl-5-hexen-3-yn-2-ol +5)
Similarly,0.61 g ꢀ3.0 mmol) of an E/Z mixture of
C6H5CH=CFBr ꢀE=Z ˆ 1=1) was reacted with 0.21 g
ꢀ3.0 mmol) of 1-butyn-3-ol in the presence of 0.01 g
ꢀ0.014 mmol) of PdꢀPPh3)2Cl2,0.01 g ꢀ0.05 mmol) CuI
and 2.0 ml Et3N at room temperature until no ꢀE)-ole®n
remained by 19F NMR analysis of the reaction mixture
ꢀꢀ24 h). The reaction mixture was directly puri®ed by silica
gel chromatography ꢀhexanes,100%; then 5:95 ethyl acet-
ate:hexanes); 0.28 g of pure ꢀZ)-ole®n was recovered
ꢀ0.33 g,1.64 mmol of ole®n consumed) and 0.28 g ꢀ49%)
of ꢀ5) ꢀZ=E > 95=5) was obtained. 1H NMR ꢀCDCl3): 7.22±
7.52 ꢀm,5H),6.03 ꢀd, J ˆ 35:0 Hz,1H),4.73 ꢀm,1H),2.51
ꢀs,1H),1.52 ꢀd, J ˆ 6:7 Hz,3H) ppm. 19F NMR ꢀCDCl3):
À105.2 ꢀdd, J ˆ 34:9 Hz, J ˆ 4:4 Hz) ppm. 13C NMR
ꢀCDCl3): 140.4 ꢀd, J ˆ 248:4 Hz),132.6 ꢀd, J ˆ 6:1 Hz),
129.1 ꢀd, J ˆ 8:3 Hz),128.6,128.2 ꢀd, J ˆ 2:2 Hz),116.2
ꢀd, J ˆ 12:5 Hz),94.1 ꢀd, J ˆ 6:5 Hz),77.2 ꢀd, J ˆ 42:1
Hz),58.4 ꢀd, J ˆ 1:9 Hz),23.7 ꢀd, J ˆ 1:5 Hz) ppm. GC±
‡
J ˆ 2:2 Hz),13.9 ppm. GC±MS: 216 ꢀ M ,53),201 ꢀ2),173
ꢀ12),159 ꢀ100),146 ꢀ50),133 ꢀ63),109 ꢀ12),91 ꢀ21). FT-IR
ꢀneat,NaCl plate): 3091 ꢀs),3052 ꢀs),3025 ꢀs),2956 ꢀw),
2221 ꢀs),1648 ꢀm),1467 ꢀs). TLC: Rf ˆ 0:4 ꢀhexanes).
HRMS: Calcd for C15H17F: 216.1314; Found: 216.1317.
4.2.3. +Æ) Acetaldehyde ethyl {+4Z)-4-fluoro-5-phenyl-
4-penten-2-ynyl}acetal +3)
Similarly,0.40 g ꢀ2.0 mmol) of an E/Z mixture of
C6H5CH=CFBr ꢀE=Z ˆ 3=2) was reacted with 0.26 g
ꢀ2.0 mmol) of ꢀÆ) acetaldehyde ethyl propargyl acetal in
the presence of 0.01 g ꢀ0.014 mmol) of PdꢀPPh3)2Cl2,0.01 g
ꢀ0.05 mmol) CuI and 2.0 ml Et3N at room temperature until
no ꢀE)-ole®n remained by 19F NMR analysis of the reaction
mixture ꢀꢀ24 h). The reaction mixture was directly puri®ed
by silica gel chromatography ꢀhexanes,100%; then 5:95
ethyl acetate:hexanes); 0.16 g of pure ꢀZ)-ole®n was recov-
ered ꢀ0.24 g,1.2 mmol of ole®n consumed) and 0.27 g
ꢀ54%) of ꢀ3) ꢀZ=E ˆ 95=5) was obtained. 1H NMR ꢀCDCl3):
‡
MS: 190 ꢀM ,69),175 ꢀ18),155 ꢀ40),146 ꢀ100),133 ꢀ15),
127 ꢀ45). FT-IR ꢀneat,NaCl plate): 3110 ꢀs),3091 ꢀs),
3027 ꢀm),1683 ꢀs),1646 ꢀw),1496 ꢀm). TLC:
7.24±7.51 ꢀm,5H),6.05 ꢀd,
ꢀq, J ˆ 5:3 Hz,1H),4.40 ꢀd, J ˆ 4:9 Hz,2H),3.47±3.73
J ˆ 34:9 Hz,1H),4.88
Rf ˆ 0:25
ꢀhexanes:ethyl acetate ˆ 9:1).

X. Zhang, D.J. Burton / Journal of Fluorine Chemistry 112 +2001) 317±324
321
4.2.6. +30Z)-+30-fluoro-40-phenyl-30-buten-10-ynyl)-
1-cyclohexanol +6)
ꢀ2.0 mmol) of ꢀÆ) acetaldehyde ethyl propargyl acetal in
the presence of 0.01 g ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01 g
ꢀ0.05 mmol) CuI and 2.0 ml Et3N at room temperature until
no ꢀE)-ole®n remained by 19F NMR analysis of the reaction
mixture ꢀꢀ24 h). The reaction mixture was directly puri®ed
by silica gel chromatography ꢀhexanes; 100%,then 5:95
ethyl acetate:hexanes); 0.19 g of pure ꢀZ)-ole®n was recov-
ered ꢀ0.28 g,1.12 mmol of ole®n was consumed) and 0.28 g
ꢀ49%) of ꢀ8) was obtained ꢀZ=E > 99/1). 1H NMR ꢀCDCl3):
To a mixture of 0.05 g ꢀ0.043 mmol) PdꢀPPh3)4,0.37 g
ꢀ3.0 mmol) of 1-ethynyl-1-cyclohexanol,DMF ꢀ5 ml) and
Et3N ꢀ1 ml) was added 0.61 g ꢀ3.0 mmol) of an E/Z mixture
of C6H5CH=CFBr ꢀE=Z ˆ 1=1). The resulting mixture was
stirred at room temperature until no ꢀE)-ole®n remained by
19F NMR analysis of the reaction mixture ꢀꢀ24 h). The
reaction mixture was then diluted with 100 ml of ether; the
organic fraction was washed with saturated NH4Cl solution
ꢀ30 ml),water ꢀ3 Â 20 ml) and brine solution ꢀ20 ml) and
dried over anhydrous MgSO4. Ether was removed via rotary
evaporation and the residue was puri®ed by silica gel
chromatography ꢀhexanes,100%; then 50:50 ethyl acetate:-
hexanes); 0.20 g of pure ꢀZ)-ole®n was recovered ꢀ0.41 g,
2.0 mmol of ole®n consumed) and 0.33 g ꢀ45%) of ꢀ6) was
7.18±7.35 ꢀm,4H),5.90 ꢀd,
J ˆ 34:3 Hz,1H),4.78 ꢀq,
J ˆ 5:4 Hz,1H),4.31 ꢀd, J ˆ 4:9 Hz,2H),3.40±3.64 ꢀm,
2H),1.27 ꢀd, J ˆ 5:4 Hz,3H),1.15 ꢀt, J ˆ 7:1 Hz,3H) ppm.
19F NMR ꢀCDCl3): À104.1 ꢀdt, J ˆ 34:3 Hz, J ˆ 5:1 Hz)
ppm. 13C NMR ꢀCDCl3): 140.8 ꢀd, J ˆ 249:2 Hz),133.9 ꢀd,
J ˆ 4:4 Hz),131.0 ꢀd, J ˆ 6:5 Hz),130.3 ꢀd, J ˆ 8:0 Hz),
128.7,115.2 ꢀd, J ˆ 12:3 Hz),98.8,88.7 ꢀd, J ˆ 5:8 Hz),
78.4 ꢀd, J ˆ 42:1 Hz),60.7,52.6 ꢀd, J ˆ 1:4 Hz),19.6,15.2
1
obtained ꢀZ=E > 99=1). GLPC > 99%. H NMR ꢀCDCl3):
‡
7.15±7.46 ꢀm,5H),5.96 ꢀd, J ˆ 34:9 Hz,1H),2.01 ꢀs,1H),
1.92 ꢀm,2H),1.47±1.69 ꢀm,7H),1.13±1.25 ꢀm,1H) ppm.
19F NMR ꢀCDCl3): À104.5 ꢀd, J ˆ 35:6 Hz) ppm. 13C NMR
ꢀCDCl3): 140.7 ꢀd, J ˆ 249:2 Hz),132.7 ꢀd, J ˆ 5:9 Hz),
129.1 ꢀd, J ˆ 8:0 Hz),128.6,128.1 ꢀd, J ˆ 2:9 Hz),115.9
ꢀd, J ˆ 12:3 Hz),96.1 ꢀd, J ˆ 6:5 Hz),77.5 ꢀd, J ˆ 52:3
ppm. DIP±MS: 282 ꢀM ,6),284 ꢀ2),267 ꢀ10),239 ꢀ5),210
ꢀ74),193 ꢀ53),157 ꢀ79),146 ꢀ100),127 ꢀ51). FT-IR ꢀneat,
NaCl plate): 2980 ꢀm),2927 ꢀm),2868 ꢀs),1649 ꢀm),1223
ꢀs),1150 ꢀm). Rf ˆ 0:33 ꢀhexanes:ethyl acetate ˆ 9:1).
4.2.9. +3Z)-3-fluoro-1-phenyl-3-undecen-1-yne +9)
‡
Hz),69.0,39.5,25.0,23.1 ppm. GC±MS: 244 ꢀ M ,43),226
Similarly,0.45 g ꢀ2.0 mmol) of an E/Z mixture of
C7H15CH=CFBr ꢀE=Z ˆ 7=3) was reacted with 0.20 g
ꢀ2.0 mmol) phenyl acetylene in the presence of 0.01 g
ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01 g ꢀ0.05 mmol) CuI and
3.0 ml Et3N at room temperature until no ꢀE)-ole®n
remained by 19F NMR analysis of the reaction mixture
ꢀꢀ24 h). The reaction mixture was directly puri®ed by silica
gel chromatography ꢀhexane),and 0.31 g ꢀ64%) of ꢀ 9)
ꢀZ=E ˆ 90=10) was obtained. 1H NMR ꢀCDCl3): 7.25±
ꢀ84),196 ꢀ31),183 ꢀ53),159 ꢀ41),146 ꢀ100),133 ꢀ49),125
ꢀ30). TLC: Rf ˆ 0:2 ꢀhexane:ethyl acetate ˆ 9:1).
4.2.7. +5Z)-5-fluoro-6-+40-chlorophenyl)-
5-hexen-3-yn-2-ol +7)
Similarly,0.71 g ꢀ3.0 mmol) of an E/Z mixture of p-
ClC6H4CH=CFBr ꢀE=Z ˆ 1=1) was reacted with 0.21 g
ꢀ3.0 mmol) of 1-butyn-3-ol in the presence of 0.01 g
ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01 g ꢀ0.05 mmol) CuI and
2.0 ml Et3N at room temperature until no ꢀE)-ole®n
remained by 19F NMR analysis of the reaction mixture
ꢀꢀ24 h). The reaction mixture was directly puri®ed by silica
gel chromatography ꢀhexanes,100%; then 10:90 ethyl acet-
ate:hexanes); 031 g of pure ꢀZ)-ole®n was recovered ꢀ0.41 g,
1.7 mmol of ole®n was consumed) and 0.32 g ꢀ48%) of ꢀ7)
7.51 ꢀm,5H),5.31 ꢀdt,
2.22 ꢀm,2H),1.29±1.44 ꢀm,10H),0.88 ꢀm,3H) ppm.
J ˆ 33:5 Hz, J ˆ 7:8 Hz,1H),
19F
NMR ꢀCDCl3): À111.6 ꢀd, J ˆ 33:7 Hz) ppm. 13C NMR
ꢀCDCl3): 141.0 ꢀd, J ˆ 235:3 Hz),131.6 ꢀd, J ˆ 1:8 Hz),
128.9,128.4,121.7 ꢀd, J ˆ 2:5 Hz),118.1 ꢀd, J ˆ 20:1 Hz),
90.1 ꢀd, J ˆ 7:0 Hz),81.5 ꢀd, J ˆ 43:7 Hz),31.8,29.1,29.0,
28.9 ꢀd, J ˆ 1:8 Hz),24.6 ꢀd, J ˆ 0:6 Hz),22.6,14.1 ppm.
‡
1
was obtained ꢀZ=E > 99=1). H NMR ꢀCDCl3): 7.20±7.33
GC±MS: 244 ꢀM ,21),215 ꢀ5),173 ꢀ10),159 ꢀ87),146
ꢀm,4H),5.89 ꢀd, J ˆ 33:5 Hz,1H),4.64 ꢀm,1H),2.33 ꢀs,
1H),1.45 ꢀd, J ˆ 6:7 Hz,3H) ppm. 19F NMR ꢀCDCl3):
À104.3 ꢀdd, J ˆ 34:3 Hz, J ˆ 4:5 Hz) ppm. 13C NMR
ꢀCDCl3): 140.7 ꢀd, J ˆ 249:2 Hz),133.9 ꢀd, J ˆ 4:1 Hz),
131.0 ꢀd, J ˆ 5:8 Hz),130.3 ꢀd, J ˆ 8:3 Hz),128.8,115.1
ꢀ100),133 ꢀ38). FT-IR ꢀneat,NaCl plate): 3058 ꢀs),3035
ꢀvs),3021 ꢀs),2219 ꢀs),1708 ꢀm),1666 ꢀm). HRMS: Calcd
for C17H21F: 244.1627; Found: 244.1625.
4.2.10. +5Z)-5-fluoro-5-tridecen-3-yn-2-ol +10)
ꢀd, J ˆ 12:3 Hz),94.5 ꢀd,
J ˆ 6:2 Hz),77.0 ꢀd,
Similarly,0.45 g ꢀ2.0 mmol) of an E/Z mixture of
C7H15CH=CFBr ꢀE=Z ˆ 1=1) was reacted with 0.20 g
ꢀ2.5 mmol) of 1-butyn-3-ol in the presence of 0.01 g
ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01 g ꢀ0.05 mmol) CuI and
2.0 ml Et3N at room temperature until no ꢀE)-ole®n
remained by 19F NMR analysis of the reaction mixture
ꢀꢀ24 h). The reaction mixture was directly puri®ed by silica
gel chromatography ꢀhexanes,100%; then 5:95 ethyl acet-
ate:hexanes); 0.22 g of pure ꢀZ)-ole®n was recovered
ꢀ0.23 g,1.03 mmol of ole®n consumed) and 0.18 g ꢀ43%)
of ꢀ10) ꢀZ=E > 98=2) was obtained. 1H NMR ꢀCDCl3): 5.13
J ˆ 41:8 Hz),58.5 ꢀd, J ˆ 1:8 Hz),23.7 ꢀd, J ˆ 1:8 Hz)
‡
ppm. GC±MS: 224 ꢀM ,44),226 ꢀ11),209 ꢀ22),189 ꢀ22),
169 ꢀ14),145 ꢀ100),141 ꢀ8),133 ꢀ5),125 ꢀ17),113 ꢀ4). TLC:
Rf ˆ 0:2 ꢀhexanes:ethyl acetate ˆ 9:1). HRMS: Calcd for
C12H10F37C10: 226.0375; Found: 226.0379.
4.2.8. +Æ) Acetaldehyde ethyl{+4Z)-4-fluoro-5-
+40-chlorophenyl)-4-penten-2-ynyl}acetal +8)
Similarly,0.47 g ꢀ2.0 mmol) of an E/Z mixture of p-
ClC6H4CH=CFBr ꢀE=Z ˆ 1=1) was reacted with 0.26 g

322
X. Zhang, D.J. Burton / Journal of Fluorine Chemistry 112 +2001) 317±324
ꢀdt, J ˆ 33:5 Hz, J ˆ 7:8 Hz,1H),4.58 ꢀm,1H),2.04±2.12
ꢀm,3H),1.41 ꢀd, J ˆ 6:7 Hz,3H),1.12±1.33 ꢀm,10H),0.81
ꢀt, J ˆ 6:4 Hz,3H) ppm. 19F NMR ꢀCDCl3): À112.1 ꢀd, J ˆ
33:1 Hz) ppm. 13C NMR ꢀCDCl3): 140.4 ꢀd, J ˆ 235:5 Hz),
118.3 ꢀd, J ˆ 19:6 Hz),91.9 ꢀd, J ˆ 7:3 Hz),77.5 ꢀd, J ˆ
43:5 Hz),58.4 ꢀd, J ˆ 1:4 Hz),31.8,29.1,28.9,28.7 ꢀd, J ˆ
1:5 Hz),24.4,23.8 ꢀd, J ˆ 1:4 Hz),22.6,14.0 ppm. GC±
144.3 ꢀd, J ˆ 1:8 Hz),139.3 ꢀd, J ˆ 237:4 Hz),128.6,
126.8,126.5,122.5 ꢀd,
J ˆ 18:9 Hz),92.6 ꢀd, J ˆ 6:8
Hz),76.3 ꢀd, J ˆ 43:3 Hz),58.4 ꢀd, J ˆ 1:2 Hz),35.2 ꢀd,
J ˆ 1:9 Hz),23.7 ꢀd, J ˆ 1:8 Hz),21.1 ꢀd, J ˆ 1:9 Hz) ppm.
‡
GC±MS: 218 ꢀM ,4),203 ꢀ13),185 ꢀ23),170 ꢀ12),165 ꢀ23),
155 ꢀ23),133 ꢀ15),77 ꢀ20),43 ꢀ100). FT-IR ꢀneat,NaCl
plate): 3380 ꢀm),3029 ꢀs),2977 ꢀm),1664 ꢀm),1236 ꢀs).
TLC: Rf ˆ 0:20 ꢀhexanes:ethyl acetate ˆ 9:1).
‡
MS: 212 ꢀM ,9),165 ꢀ4),141 ꢀ6),121 ꢀ6),109 ꢀ16),99 ꢀ26),
79 ꢀ15),55 ꢀ28),43 ꢀ100). FT-IR ꢀneat,NaCl plate): 3573 ꢀs),
3373 ꢀm),3052 ꢀm),1667 ꢀm),1721 ꢀs). TLC:
Rf ˆ 0:25
4.2.13. +E)-1,4-diphenyl-3-fluoro-3-buten-1-yne +13)
ꢀhexanes:ethyl acetate ˆ 9:1).
To a mixture of 0.01 g ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01 g
ꢀ0.05 mmol) CuI and 0.21 g ꢀ2.0 mmol) C6H5CBCH and
2.0 ml Et3N was added 0.41 g ꢀ2.0 mmol) of C6H5CH=CFBr
ꢀZ=E ˆ 97=3),and the reaction mixture was stirred at room
temperature for 48 h. The reaction mixture was directly
puri®ed by silica gel chromatography ꢀhexanes),followed
by recrystallization from pentane to give 0.39 g ꢀ88%) of
ꢀ13) ꢀE=Z > 97=3). 1H NMR ꢀCDCl3): 7.21±7.67 ꢀm,10H),
6.61 ꢀd, J ˆ 16:1 Hz,1H) ppm. 19F NMR ꢀCDCl3): À102.8
ꢀd, J ˆ 16:6 Hz) ppm. 13C NMR ꢀCDCl3): 141.1 ꢀd, J ˆ
232:2 Hz),132.2 ꢀd, J ˆ 9:5 Hz),131.7 ꢀd, J ˆ 2:6 Hz),
129.6,128.5 ꢀd, J ˆ 5:1 Hz),128.2 ꢀd, J ˆ 2:1 Hz),128.1
ꢀd, J ˆ 3:3 Hz),121.3 ꢀd, J ˆ 2:6 Hz),117.5 ꢀd, J ˆ 33:1
Hz),97.3 ꢀd, J ˆ 6:9 Hz),81.2 ꢀd, J ˆ 41:1 Hz) ppm. GC±
4.2.11. +Æ) Acetaldehyde ethyl{+4Z)-4-fluoro-
4-dodecen-2-ynyl}acetal +11)
Similarly,0.45 g ꢀ2.0 mmol) of an E/Z mixture of
C7H15H=CFBr ꢀE=Z ˆ 1=1) was reacted with 0.26 g
ꢀ2.0 mmol) of ꢀÆ) acetaldehyde ethyl propargyl acetal in
the presence of 0.01 g ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01 g
ꢀ0.05 mmol) CuI and 2.0 ml Et3N at room temperature until
no ꢀE)-ole®n remained by 19F NMR analysis of the reaction
mixture ꢀꢀ24 h). The reaction mixture was directly puri®ed
by silica gel chromatography ꢀhexanes,100%; then 5:95
ethyl acetate:hexanes): 0.20 g of pure ꢀZ)-ole®n was recov-
ered ꢀ0.25 g,1.11 mmol of ole®n was consumed) and 0.25 g
ꢀ46%) of ꢀ11) ꢀZ=E ˆ 93=7) was obtained. 1H NMR
ꢀCDCl3): 5.15 ꢀdt, J ˆ 33:5 Hz, J ˆ 7:8 Hz,1H),4.78
ꢀq, J ˆ 5:3 Hz,1H),4.27 ꢀd, J ˆ 4:9 Hz,2H),3.40±3.64
ꢀm,2H),2.08 ꢀqd, J ˆ 6:6 Hz, J ˆ 1:8 Hz,2H),1.12±1.32
ꢀm,16H),0.81 ꢀt, J ˆ 6:5 Hz,3H) ppm. 19F NMR ꢀCDCl3):
À112.1 ꢀd, J ˆ 33:5 Hz) ppm. 13C NMR ꢀCDCl3): 140.4
ꢀd, J ˆ 235:6 Hz),118.3 ꢀd, J ˆ 19:8 Hz),98.7,86.9 ꢀd, J ˆ
7:0 Hz),78.0 ꢀd, J ˆ 44:0 Hz),60.7,52.6 ꢀd, J ˆ 1:8 Hz),
‡
MS: 222 ꢀM ,90),220 ꢀ100),202 ꢀ16),194 ꢀ4),150 ꢀ2),110
ꢀ12),98 ꢀ6),85 ꢀ3),74 ꢀ3).
4.2.14. +E)-2-fluoro-1-phenyl-1-nonen-3-yne +14)
Similarly,the reaction of 0.40 g ꢀ2.0 mmol) of ꢀ Z)-
C6H5CH=CFBr with 0.19 g ꢀ2.0 mmol) CH3ꢀCH2)4CBCH
in the presence of 0.01 g ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01 g
ꢀ0.05 mmol) CuI and 2.0 ml Et3N at room temperature for
1
31.7,28.9 ꢀd, J ˆ 4:6 Hz),28.7 ꢀd, J ˆ 1:8 Hz),24.4 ꢀd, J ˆ
48 h gave 0.37 g ꢀ87%) of ꢀ14),GLPC > 99%. H NMR
‡
0:9 Hz),22.6,19.6,15.2,14.0 ppm. GC±MS: no
observed,211 ꢀ2),183 ꢀ10),170 ꢀ8),155 ꢀ5),143 ꢀ8),
138 ꢀ100),111 ꢀ26),91 ꢀ36). FT-IR ꢀneat,NaCl plate):
M
ꢀCDCl3): 7.20±7.58 ꢀm,5H),6.48 ꢀd, J ˆ 17:0 Hz,1H),2.46
ꢀtd, J ˆ 7:0 Hz, J ˆ 5:3 Hz,2H),1.26±1.67 ꢀm,6H),0.91 ꢀt,
J ˆ 7:0 Hz,3H) ppm. 19F NMR ꢀCDCl3): À99.9 ꢀdt,
J ˆ 17:1 Hz, J ˆ 5:0 Hz) ppm. 13C NMR ꢀCDCl3): 141.3
ꢀd, J ˆ 232:2 Hz). 132.4 ꢀd, J ˆ 9:8 Hz),128.3,127.8,
127.7,115.7 ꢀd, J ˆ 33:8 Hz),99.9 ꢀd, J ˆ 6:5 Hz), 73.0
ꢀd, J ˆ 41:1 Hz),31.0,27.6 ꢀd, J ˆ 1:8 Hz),22.1,19.5,
2955 ꢀs),2857 ꢀs),1666 ꢀs),1128 ꢀs). TLC:
ꢀhexane:ethyl acetate ˆ 9:1).
Rf ˆ 0:33
4.2.12. +5Z)-5-fluoro-6-phenyl-5-octen-3-yn-2-ol +12)
Similarly,0.69 g ꢀ3.0 mmol) of an E/Z mixture of
PhꢀCH3)CHCH=CFBr ꢀE=Z ˆ 7=3) was reacted with
0.21 g ꢀ3.0 mmol) of 1-butyn-3-ol in the presence of
0.01 g ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01 g ꢀ0.05 mmol)
CuI and 3.0 ml Et3N at room temperature until no ꢀE)-ole®n
remained by 19F NMR analysis of the reaction mixture
ꢀꢀ24 h). The reaction mixture was directly puri®ed by silica
gel chromatography ꢀhexanes,100%; then 50:50 ethyl acet-
ate:hexanes); 0.23 g of pure ꢀZ)-ole®n was recovered
ꢀ0.46 g,2.0 mmol of ole®n was consumed) and 0.23 g
ꢀ53%) of ꢀ12) ꢀZ=E ˆ 92=8) was obtained. 1H NMR
ꢀCDCl3): 7.18±7.34 ꢀm,5H),5.36 ꢀdd, J ˆ 32:6 Hz, J ˆ
9:8 Hz,1H),4.59±4.67 ꢀm,1H),3.96±4.04 ꢀm,1H),
‡
13.9 ppm. GC±MS: 216 ꢀM ,76),201 ꢀ3),187 ꢀ8),173 ꢀ13),
159 ꢀ100),146 ꢀ54),133 ꢀ76),109 ꢀ12). FT-IR ꢀneat,NaCl
plate): 3060 ꢀs),3027 ꢀs),2958 ꢀw),2933 ꢀw),2861 ꢀm),
2225 ꢀm),1641 ꢀw),1448 ꢀm). HRMS: Calcd for C 15H17F:
216.1314; Found: 216.1319.
4.2.15. +Æ) Acetaldehyde ethyl{+4E)-4-fluoro-5-
phenyl-4-penten-2-ynyl}acetal +15)
Similarly,the reaction of 0.40 g ꢀ2.0 mmol) of C 6H5-
CH=CFBr ꢀZ=E > 98=2) with 0.26 g ꢀ2.0 mmol) of ꢀÆ)
acetaldehyde ethyl propargyl acetal in the presence of
0.01 g ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01 g ꢀ0.05 mmol)
CuI and 2.0 ml Et3N at room temperature for 48 h gave
0.44 g ꢀ89%) of ꢀ15) ꢀE=Z > 98=2). 1H NMR ꢀCDCl3):
2.08 ꢀs,1H),1.46 ꢀdd, J ˆ 6:6 Hz, J ˆ 0:4 Hz,3H),1.37
ꢀd, J ˆ 7:1 Hz,3H) ppm. 19F NMR ꢀCDCl3): À111.4
ꢀdt, J ˆ 33:1 Hz, J ˆ 3:1 Hz) ppm. 13C NMR ꢀCDCl3):
7.24±7.60 ꢀm,5H),6.59 ꢀd,
ꢀq, J ˆ 5:4 Hz,1H),4.47 ꢀdd,
J ˆ 17:0 Hz,1H),4.88
J ˆ 5:1 Hz, J ˆ 1:6 Hz,

X. Zhang, D.J. Burton / Journal of Fluorine Chemistry 112 +2001) 317±324
323
2H),3.47±3.71 ꢀm,2H),1.36 ꢀd, J ˆ 5:3 Hz,3H),1.21 ꢀt,
J ˆ 7:0 Hz,3H) ppm. 19F NMR ꢀCDCl3): À103.1 ꢀdt,
J ˆ 17:2 Hz, J ˆ 5:1 Hz) ppm. 13C NMR ꢀCDCl3): 140.5
ꢀd, J ˆ 232:5 Hz),131.7 ꢀd, J ˆ 8:7 Hz),128.4,128.2 ꢀd,
J ˆ 2:1 Hz),128.0,117.8 ꢀd, J ˆ 32:7 Hz),98.9,94.3 ꢀd,
ethyl propargyl acetal in the presence of 0.01 g
ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01 g ꢀ0.05 mmol) CuI and
2.0 ml of Et3N at room temperature for 48 h gave 0.25 g
1
ꢀ89%) of ꢀ18). H NMR ꢀCDCl3): 7.18±7.46 ꢀm,4H),6.45
ꢀd, J ˆ 16:4 Hz,1H),4.79 ꢀq, J ˆ 5:3 Hz,1H),4.37 ꢀd,
J ˆ 7:3 Hz),76.8 ꢀd, J ˆ 41:5 Hz),61.0,52.7 ꢀd,
J ˆ
J ˆ 5:1 Hz,2H),3.38±3.62 ꢀm,2H),1.27 ꢀd,
J ˆ 5:4 Hz,
‡
2:2 Hz),19.6,15.2 ppm. GC±MS: 248 ꢀ M ,3),233 ꢀ16),
219 ꢀ5),205 ꢀ8),185 ꢀ10),176 ꢀ23),159 ꢀ100),146 ꢀ35),133
ꢀ52),128 ꢀ27). FT-IR ꢀneat,NaCl plate): 3060 ꢀs),3027 ꢀs),
2979 ꢀm),2931 ꢀm),1643 ꢀm),1448 ꢀm),1216 ꢀm).
3H),1.12 ꢀt, J ˆ 7:1 Hz,3H) ppm. 19F NMR ꢀCDCl3):
À101.9 ꢀdt, J ˆ 16:9 Hz, J ˆ 5:1 Hz) ppm. 13C NMR
ꢀCDCl3): 140.8 ꢀd, J ˆ 234:4 Hz),133.8 ꢀd, J ˆ 2:5 Hz),
130.3 ꢀd, J ˆ 9:2 Hz),129.1 ꢀd, J ˆ 3:1 Hz),128.6,116.7
ꢀd, J ˆ 32:9 Hz),98.9,95.0 ꢀd,
J ˆ 6:7 Hz),77.1 ꢀd,
4.2.16. +5E)-5-fluoro-6-phenyl-5-hexen-3-yn-2-ol +16)
Similarly,the reaction of 0.40 g ꢀ2.0 mmol) of ꢀ Z)-
C6H5CH=CFBr with 0.21 g ꢀ3.0 mmol) of 1-butyn-3-ol in
the presence of 0.01 g ꢀ0.014 mmol) PdꢀPPh3)2Cl2,0.01
ꢀ0.05 mmol) CuI and 2.0 ml Et3N at room temperature
for 48 h gave ꢀafter silica gel chromatography,50:50 ethyl
J ˆ 43:4 Hz),60.9,52.6 ꢀd, J ˆ 1:8 Hz),19.6,15.1 ppm.
‡
DIP±MS: 282 ꢀM ,4),284 ꢀ1.3),267 ꢀ10),239 ꢀ8),210 ꢀ55),
193 ꢀ70),157 ꢀ100),146 ꢀ96),127 ꢀ49). FT-IR ꢀneat,NaCl
plate): 2980 ꢀs),2930 ꢀs),1642 ꢀs),1491 ꢀs),1150 ꢀs). TLC:
Rf ˆ 0:34 ꢀhexanes:ethyl acetate ˆ 9:1). HRMS: Calcd for
C15H1635ClFO2,282.0823; Found: 282.0815.
1
acetate:hexanes) 0.34 g ꢀ89%) of ꢀ16),GLPC > 99%. H
NMR ꢀCDCl3): 7.23±7.59 ꢀm,5H),6.58 ꢀd, J ˆ 17:0 Hz,
4.2.19. +5E)-5-fluoro-6-phenyl-5-octen-3-yn-2-ol +19)
Similarly,the reaction of 0.23 g ꢀ1.0 mmol) of ꢀ Z)-
C6H5ꢀCH3)CHCH=CFBr with 0.10 g ꢀ1.3 mmol) of 1-
butyn-3-ol in the presence of 0.01 g ꢀ0.014 mmol)
1H),4.75 ꢀm,1H),2.39 ꢀs,1H),1.54 ꢀd,
J ˆ 6:6 Hz,3H)
ppm. 19F NMR ꢀCDCl3): À103.2 ꢀdd, J ˆ 16:5 Hz, J ˆ 4:4
Hz) ppm. 13C NMR ꢀCDCl3): 140.4 ꢀd, J ˆ 232:9 Hz),
131.7 ꢀd, J ˆ 9:4 Hz),128.4,128.3 ꢀd, J ˆ 1:8 Hz),127.9
ꢀd, J ˆ 3:2 Hz),117.7 ꢀd, J ˆ 32:3 Hz),99.1 ꢀd, J ˆ 6:9
Hz),76.0 ꢀd, J ˆ 41:4 Hz),58.6 ꢀd, J ˆ 1:8 Hz),23.5 ꢀd,
PdꢀPPh3)2Cl2,0.01 g ꢀ0.05 mmol) CuI and 3.0 ml Et N at
3
1
room temperature for 48 h gave 0.17 g ꢀ78%) of ꢀ19). H
NMR ꢀCDCl3): 7.18±7.34 ꢀm,5H),5.73 ꢀdd, J ˆ 14:3 Hz,
J ˆ 10:5 Hz,1H),4.66±4.77 ꢀm,1H),3.66±3.77 ꢀm,1H),
2.22 ꢀs,1H),1.51 ꢀd, J ˆ 6:3 Hz,3H),1.39 ꢀdd, J ˆ 6:8 Hz,
J ˆ 0:8 Hz,3H) ppm. 19F NMR ꢀCDCl3): À109.7 ꢀd, J ˆ
14:6 Hz) ppm. 13C NMR ꢀCDCl3): 144.5,140.5 ꢀ J ˆ 233:7
Hz) 128.5,126.6 ꢀd, J ˆ 23:3 Hz),122.3 ꢀdd, J ˆ 22:6 Hz,
J ˆ 3:7 Hz),97.7 ꢀd, J ˆ 6:7 Hz),74.4 ꢀd, J ˆ 43:3 Hz),
58.5,37.2 ꢀd, J ˆ 4:3 Hz),23.8,21.4 ꢀd, J ˆ 2:5 Hz) ppm.
‡
J ˆ 2:2 Hz) ppm. GC±MS: 190 ꢀM ,64),175 ꢀ16),155
ꢀ51),146 ꢀ100),133 ꢀ19),127 ꢀ58),122 ꢀ1),107 ꢀ3),94 ꢀ3),
75 ꢀ11). FT-IR ꢀneat,NaCl plate): 3106 ꢀs),3085 ꢀs),2985
ꢀm),2935 ꢀs),2877 ꢀs),1675 ꢀs),1448 ꢀm). TLC: Rf ˆ 0:25
ꢀhexanes:ethyl acetate ˆ 9:1).
4.2.17. +5E)-5-fluoro-6-+40-chlorophenyl)-
5-hexen-3-yn-2-ol +17)
‡
GC±MS: 218 ꢀM ,1),203 ꢀ3),185 ꢀ9),170 ꢀ5),165 ꢀ7),155
Similarly,the reaction of 0.24 g ꢀ1.0 mmol) of ꢀ Z)-p-
ClC6H4CH=CFBr with 0.1 g ꢀ1.3 mmol) of 1-butyn-3-ol
in the presence of 0.01 g ꢀ0.014 mmol) PdꢀPPh3)2Cl2,
0.01 g ꢀ0.05 mmol) CuI and 3.0 ml Et3N at room tempera-
ture for 48 h gave ꢀafter silica gel chromatography,hexanes,
100%; then 50:50 ethyl acetate:hexanes) 0.17 g ꢀ77%) of
ꢀ17). 1H NMR ꢀCDCl3): 7.18±7.47 ꢀm,4H),6.47 ꢀd,
J ˆ 16:5 Hz,1H),4.64±4.75 ꢀm,1H),2.08 ꢀs,1H),1.49
ꢀd, J ˆ 6:6 Hz,3H) ppm. 19F NMR ꢀCDCl3): À102.2 ꢀdd,
J ˆ 17:6 Hz, J ˆ 3:8 Hz) ppm. 13C NMR ꢀCDCl3): 140.7
ꢀ8),133 ꢀ45),115 ꢀ9),77 ꢀ23),43 ꢀ100). FT-IR ꢀneat,NaCl
plate): 3334 ꢀm),3085 ꢀs),3029 ꢀs),2979 ꢀm),1654 ꢀm),
1288 ꢀw). TLC: Rf ˆ 0:20 ꢀhexanes:ethyl acetate ˆ 9:1).
HRMS: Calcd for C14H15FO,218.1107; Found: 218.1094.
Acknowledgements
We thank the National Science Foundation for ®nancial
support of this work. Xin Zhang would like to thank Dr.
Long Lu for his help and discussions during the course of
this work.
ꢀd, J ˆ 234:4 Hz),133.9 ꢀd,
J ˆ 2:2 Hz),130.3 ꢀd,
J ˆ 9:4 Hz),129.2 ꢀd,
J ˆ 2:9 Hz),128.7,116.7 ꢀd,
J ˆ 33:4 Hz),99.6 ꢀd, J ˆ 6:5 Hz),75.8 ꢀd, J ˆ 41:7 Hz),
58.6 ꢀd, J ˆ 2:1 Hz),23.6 ꢀd, J ˆ 1:8 Hz) ppm. GC±MS:
‡
224 ꢀM ,35),226 ꢀ11),209 ꢀ16),189 ꢀ16),169 ꢀ9),145 ꢀ55),
References
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for C12H10F35ClO,224.0404; Found: 224.0427.
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