Synthesis of new α,α,β,β-tetrafluoroesters

Article abstract of DOI:10.1016/j.jfluchem.2004.01.001

Substituted phenyl iodides or diiodides reacted with ethyl iodotetrafluoroproponylate ICF₂CF₂CO₂ Et, 1 in the presence of copper powder to give the coupled products 2 or 3 in good yields. Addition of 1 to ethylene and ally

Full text of DOI:10.1016/j.jfluchem.2004.01.001

Journal of Fluorine Chemistry 125 (2004) 763–765
Synthesis of new a,a,b,b-tetrafluoroesters
Zhen-Yu Yang*
DuPont Central Research & Development, Experimental Station, Wilmington, DE 19880-0328, USA
Received 6 January 2004; received in revised form 6 January 2004; accepted 7 January 2004
Available online 17 March 2004
Abstract
Substituted phenyl iodides or diiodides reacted with ethyl iodotetrafluoroproponylate ICF2CF2CO2Et, 1 in the presence of copper powder to
give the coupled products 2 or 3 in good yields. Addition of 1 to ethylene and allyl acetate proceeded smoothly under thermal and radical
conditions to give the corresponding adducts, which underwent elimination reaction to give b-vinyl and b-allyl a,a,b,b-tetrafluoroesters,
CH2¼CHCF2CF2CO2Et, 4 and CH2¼CHCH2CF2CF2CO2Et, 5, respectively. 1 also readily reacted with 1,5-hexadiene and 1-hexene with
copper or palladium complex, followed by reduction to remove iodine to produce o-alkenyl-a,a,b,b-tetrafluoroester CH2¼CH(CH2)4CF2-
CF2CO2Et 6 and a,a,b,b-tetrafluoroester C4H9CH2CHICF2CF2CO2Et.
# 2004 Elsevier B.V. All rights reserved.
Keywords: Iodotetrafluoroproponylate; a,a,b,b-Tetrafluoroesters; Coupling reaction
Partially fluorinated compounds have been widely uti-
lized in the areas of agrochemicals and pharmaceuticals or
as probes for investigating biochemical processes, since the
introduction of fluorine into organic molecules leads to
significant changes in biological activities [1]. Recently,
the introduction of the difluoromethylene functionality into
organic compounds has been growing attentions since it
was discovered that selected difluoromethylene containing
molecules have inhibited one or more enzymes or been
partially metabolized into a more active substance [2]. It has
been argued that the difluoromethylene group could be
regarded as an isopolar-isosteric replacement for oxygen
[3]. Among many building blocks, a-halo-a,a-difluoroace-
tates have been most widely used as synthones for making
a,a-difluoromethylene containing compounds [4]. How-
ever, a,a,b,b-tetrafluoroesters are difficult to prepare and
their properties are virtually unknown since the suitable
precursors for the preparation are not available previously.
We now report the preparations of various types of a,a,b,b-
tetrafluoroesters.
[5]. When reaction of perfluoromethoxylcyclopropane
with iodine at 240 8C, iodotetrafluoroproponyl fluoride
was obtained in high yield along with perfluoroalkyl
iodides [6]. The iodotetrafluoroproponyl fluoride can be
quenched with ethanol in the presence of sodium or
potassium fluoride to give the ethyl iodotetrafluoropropo-
nylate 1 in 75–90% yields from fluorinated cyclopropane
derivatives.
With 1 in hand, we tried to prepare various aryl substituted
a,a,b,b-tetrafluoroesters from 1. It was reported that per-
fluoroalkyl iodides coupled with aryl iodides in the presence
of copper to give perfluoroalkylated aromatics via a per-
fluoroalkylcopper intermediate [7]. Kobayashi extend the
reaction to iododdifluoroacetate and aryl iodies to give
aryldifluoroesters. Although the reaction worked well in
DMSO at room temperature, the only decomposition pro-
ducts were obtained when the reaction was carried out at
We previously discovered ring-opening reaction of
highly fluorinated cyclopropanes with halogenes to give
the corresponding 1,3-dihalofluoropropane derivatives
* Tel.: þ1-302-695-2461; fax: þ1-302-695-9799.
E-mail address: zhenyu.yang-1@usa.dupont.com (Z.-Y. Yang).
0022-1139/$ – see front matter # 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2004.01.001

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Z.-Y. Yang / Journal of Fluorine Chemistry 125 (2004) 763–765
above 60 8C [8]. I found that 1 coupled with aryl iodides and
copper powder in DMF at 80–110 8C to give the correspond-
ing a,a,b,b-tetrafluoroesters 2.
suitable base in an aprotic solvent should be selected to
prevent the hydrolysis of the ester. DBU has been demon-
strated to be an effective base in the elimination reaction.
The reaction was carried in dry ether or CH2Cl2 at room
temperature to afford b-vinyl-a,a,b,b-tetrafluoroester 4 in
high yield.
Although phenyl iodides gave the products in good yields,
phenyl bromide containing an electron-withdrawing also
worked well in the coupling reaction. For example phenyl
bromide substituted with acyl group formed the coupled
product 2e in 80%. The coupling reaction also worked well
with phenylene diiodide. Upon the reaction of ICF2CF2-
CO2Et with 1,3-diiodobenzene or 1,4-diiodobenzene and
copper powder in the presence of 2,20-dipridyl in DMF, the
corresponding bis-coupled products 3 were isolated in 82–
87% yields. However, with 1,4-diiodobiphenyl (IC6H4-
C6H4I), only 48% yield of product (EtO2CCF2CF2C6H4)2
3c was formed under similar conditions and substantial
starting material was recovered.
Preparation of b-allyl-a,a,b,b-tetrafluoroesters is also
achieved from 1. Addition of 1 to allyl acetate can be
initiated with copper powder or radical initiators, but the
radical initiator such as benzoyl peroxide gave better yields
of product. When copper used as an initiator, one to two
adduct was also formed although one to one adduct was
major product. One to one adduct was obtained in 89% yield
when benzoyl peroxide was added to the reaction mixture
portion by portion in the absence of solvent. The adduct was
treated with zinc powder in DMF to produce allyl substituted
a,a,b,b-tetrafluoroester 5 [9].
1 can be used to prepare o-alkenyl-a,a,b,b-tetrafluoroe-
sters. A general method for the preparation of these com-
pounds is selective addition of 1 to appropriate dienes,
followed by reduction to remove iodine. To minimize the
formation of a bis adduct, large excesses diene are required.
For example, upon the reaction of 1 to 2 mole excess1,5-
hexadiene and copper powder, the corresponding mono-
adduct was isolated in 71% yield. Reduction of the adduct
was achieved with Bu3SnH to produce the o-alkenyl-
a,a,b,b-tetrafluoroester 6 [9]. Although a small amount of
bis-adduct was also formed, no five membered ring adduct
was detected. In contrast, reaction of perfluoroalkyl iodides
with 1,6-heptadiene or its derivatives gives a cyclic adduct as
a major product [10]. It would be expected that 1 reacts with
1,6-heptadiene to produce the corresponding cyclic adduct.
b-Vinyl-a,a,b,b-tetrafluoroesters also can be prepared
from 1. Although a coupling reaction of vinyl iodides and
1 in the presence of copper powder could produce b-vinyl-
a,a,b,b-tetrafluoroesters, an addition–elimination method is
more cost effective and easy to scale up. 1 was readily added
to ethylene at 200 8C in an autoclave to give the correspond-
ing adduct. The high temperature addition is believed to be a
radical reaction. To prevent polymerization of ethylene, a
small amount of polymerization inhibitor such as D-limo-
nene is usually added to the reaction mixture. The formation
of product in high yield indicated the absence of side
reactions such as thermal elimination of ethylene from 1
or the adduct. When elimination of HI from the adduct, a

Z.-Y. Yang / Journal of Fluorine Chemistry 125 (2004) 763–765
765
The addition–reduction strategy can be applied to the
synthesis of saturated a,a,b,b-tetrafluoroesters. There are
numerous initiators to initiate the addition of perfluoroalkyl
iodides or functional fluorinated iodides to olefins and
various functional groups can be tolerated in the addition
as reported in our previous papers [11,12]. I anticipated that
these initiators could initiate the addition of 1 to olefins. I
have demonstrated an example of addition of 1 to 1-hexene
with Pd(PPh3)4 as an initiator to give the corresponding
adduct C4H6CHICH2CF2CF2CO2Et in 89% yield.
In conclusion, I have developed efficient methods for the
synthesis of various aryl-, vinyl-, allyl-, o-alkenyl-, and
alkyl a,a,b,b-tetrafluoroesters that previously were not read-
ily accessible from now available precursor 1. These new
fluorinated esters may have interesting properties them-
selves or are important and useful compounds for making
other more complex materials.
Typical procedure for 2a: A mixture of 5.7 g (28 mmol) of
iodobenzene, 9.0 g of (30 mmol) of ICF2CF2CO2Et, 4.8 g
(75 mmol) of Cu powder and 0.3 g of 2,20-bipyridyl in 25 ml
of DMF was stirred at 100 8C for 6 h under N2. After being
cooled to room temperature, the mixture was diluted with
100 ml of ether. Solids were removed by filtration and
washed with ether. The filtrate was poured to water and
the ether lay was separated, and then washed with diluted
HCl, water, NaCl solution and dried over MgSO4. After
removal of the ether, residue was distilled to give 5.6 g
(80%) of product, b.p. 95–96 8C/5 mmHg. 1H NMR: 7.58–
7.25 (m, 5H), 4.37 (q, J ¼ 7:5 Hz, 2H), 1.35 (t, J ¼ 7:5 Hz,
3H), 19F NMR: ꢀ112.0 (t, J ¼ 6:0 Hz, 2F), ꢀ119.3 (t, J ¼
6:0 Hz, 2F). HRMS: calcd for C11H10F4O2: 250.0617.
Found: 250.0596.
19F NMR: ꢀ113.6 (ddd, J ¼ 266:8 Hz, J ¼ 27 Hz, J ¼
10:7 Hz, 1F), ꢀ115.2 (ddd, J ¼ 266:8 Hz, J ¼ 24:5 Hz,
J ¼ 14:2 Hz, 1F), ꢀ120.6 (s, 2F). Anal: calcd for
C10H13F4IO4: C, 30.02; H, 3.27; F, 18.99; I, 31.72. Found:
C, 30.12; H, 3.25; F, 19.83; I, 30.57. To a stirred mixture of
75 g (1.15 mol) of Zn and 500 ml of DMF was dropwise
added 344 g (0.85 mol) of AcOCH2CHICH2CF2CF2CO2Et
at 100 8C under N2. After the addition was complete, the
reaction mixture was stirred for 40 min. Excess Zn was
removed by filtration and washed with CH2Cl2. The filtrate
was poured into acidic water. Lower layer was separated and
washed with water aqueous NaCl solution and dried over
MgSO4. After removal of CH2Cl2, residue was distilled
to give 125.6 g (69%) of the desired product, bp 77–
78 8C/40 mmHg. 19F NMR: ꢀ114.3 (t, J ¼ 18:3 Hz, 2F),
ꢀ120.3 (s, 2F). IR: 1775 (vs), 1648 (w), 1246 (vs), 1167 (s).
Anal: calcd for C8H10F4O2: C, 44.87; H, 4.71; F, 35.48.
Found: C, 44.78; H, 4.66; F, 35.79.
Acknowledgements
I wish to thank R.E. Smith Jr. for technical assistance.
References
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Typical procedure for 5: To a stirred mixture of 110 g
(1.1 mol) of allyl acetate and 300 g (0.99 mol) of ICF2CF2-
CO2Et Et was added 0.8 g of benzoyl peroxide at 100 8C in
N2. Exothermic reaction occurred and the temperature raised
to 165 8C. After cooling to 110 8C, additional 0.6 g of
benzoyl peroxide was added and the reaction mixture was
stirred for 30 min. Three grams of benzoyl peroxide was
added in a fraction of 1.0 g for every 30 min. GC indicated
the formation of 95% of adduct, and the mixture was distilled
to give 350.6 g (89%) of adduct, bp 104–105 8C/0.8 mmHg.
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