Facile preparation and synthetic applications of LiCH2C(CF3)2Oli

Article abstract of DOI:10.1016/S0022-1139(02)00154-9

Bromohydrin BrCH₂C(CF₃)₂OH readily reacts with two equivalents of n-BuLi at - 78 °C to produce the corresponding dilithium derivative LiCH₂C(CF₃)₂OLi in high yield. This dilithiated derivative reacts selectively, acting as a C-nucleophile, with a variety of electrophiles such as R₂PCl, carbonyl compounds, and epoxides, to give electron-deficient phosphines R₂PCH₂C(CF₃)₂OH, 1,3- and 1,4-diols, correspondingly.

Full text of DOI:10.1016/S0022-1139(02)00154-9

Journal of Fluorine Chemistry 117 (2002) 121–129
Facile preparation and synthetic applications of LiCH2C(CF3)2OLi$
Vladimir V. Grushin*, William J. Marshall, Gary A. Halliday,
Fredric Davidson, Viacheslav A. Petrov*
Central Research and Development, E.I. DuPont de Nemours & Co., Inc., Experimental Station, Wilmington, DE 19880-0328, USA
Received 22 April 2002; received in revised form 7 May 2002; accepted 10 May 2002
Dedicated to Professor Lev M. Yagupolskii on the occasion of his 80th Birthday.
Abstract
Bromohydrin BrCH2C(CF3)2OH readily reacts with two equivalents of n-BuLi at ꢀ78 8C to produce the corresponding dilithium derivative
LiCH2C(CF3)2OLi in high yield. This dilithiated derivative reacts selectively, acting as a C-nucleophile, with a variety of electrophiles such as
R2PCl, carbonyl compounds, and epoxides, to give electron-deficient phosphines R2PCH2C(CF3)2OH, 1,3- and 1,4-diols, correspondingly.
# 2002 Elsevier Science B.V. All rights reserved.
Keywords: Polyfluorinated phosphines; P,O-ligands; Dilithiation; Polyfluorinated dilos
1. Introduction
R2PCH2C(CF3)2OH via ring-opening with secondary phos-
phines R2PH. It has been recently demonstrated [6,7] that
1,1-bis(trifluoromethyl)oxirane readily reacts with nucleo-
philes in a highly selective manner, giving products of
nucleophilic attack on the unsubstituted carbon atom, i.e.
NuCH2C(CF3)2OH.
A somewhat sluggish reaction occurred between Ph2PH
and 1,1-bis(trifluoromethyl)oxirane in THF to give
Ph2PCH2C(CF3)2OH (LH-1) in 41% isolated yield at ca.
90% conversion of the oxirane after 2 days at 25 8C (Eq. (1)).
For our luminescent materials research program [1–4], we
were in the need of electron-deficient, monoanionic chelat-
ing P,O-ligands of the type R2PCH2C(CF3)2OH. To the best
of our knowledge, preparation of only one such ligand,
Ph2PCH2C(CF3)2OH (LH-1), has been reported [5]. As a
source of the –C(CF3)2OH moiety, the literature procedure
[5] employed hexafluoroacetone, a toxic gas. Our goal was
to develop a simple, efficient and general method for the
preparation of phosphinoalcohols R2PCH2C(CF3)2OH from
a more benign and easy-to-handle organofluorine source.
In this paper, we report dilithiation of the easily accessible
bromohydrin BrCH2C(CF3)2OH to produce LiCH2C(C-
F3)2OLi which selectively reacts with R2PCl to furnish
the desired P,O-ligands. Also described herein is the use
of LiCH2C(CF3)2OLi in the synthesis of polyfluorinated
diols via the reaction with various carbonyl compounds.
(1)
The moderate yield of LH-1 in Reaction (1) is due to the
formation of considerable quantities of the corresponding
phosphine oxide.1 Because we were interested in electron-
deficient P,O-ligands (see above), an attempt was made to
expand Reaction (1) to Ar2PH, where Ar ¼ 3,5-(CF3)2C6H3
[8,9]. In this case, however, no ring-opening took place after
a few days under similar conditions, likely due to the
2. Results and discussion
Easily accessible 1,1-bis(trifluoromethyl)oxirane [6]
seemed a suitable electrophile for the preparation of
$ Contribution no. 8310.
1 Since Reaction (1) and product isolation were conducted under
nitrogen, it is conceivable that the phosphine oxide formation may be
(partially) due to oxygen transfer from the oxirane to the LH-1 as
Reaction (1) occurs. Once isolated and purified, crystalline LH-1 is air-
stable at ambient temperature.
* Corresponding authors. Tel.: þ1-302-695-3534;
fax: þ1-302-695-8281; E-mail address: vlad.grushin-1@usa.dupont.com
(V.V. Grushin); Tel.: þ1-302-695-1958; fax: þ1-302-695-8281;
E-mail address: viacheslav.a.petrov@usa.dupont.com (V.A. Petrov).
0022-1139/02/$ – see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 0 2 ) 0 0 1 5 4 - 9

122
V.V. Grushin et al. / Journal of Fluorine Chemistry 117 (2002) 121–129
Scheme 1.
diminished nucleophilicity of the trifluoromethylated phos-
phine. Therefore, the secondary phosphine was converted to
its lithium salt which appeared reactive enough to furnish the
desired product (Eq. (2)).
aqueous HBr (see Section 3). We found that the resulting
bromohydrin undergoes a remarkably clean and facile reac-
tion with two equivalents of n-BuLi2 to give the desired
dilithiated derivative (1) which is stable at ꢀ78 8C and can
be used for the synthesis of various polyfluorinated mole-
cules (Schemes 1–4).
As shown in Scheme 1, intermediate 1 readily reacts with
diarylchlorophosphines Ar2PCl to give the desired P,O-
ligands (LH-1–4) upon acidification after the reaction.
The selectivity of the reaction is truly remarkable. In spite
of the high affinity of phosphorus for oxygen, no P–O bond
formation was observed (31P and 19F NMR) in the synthesis
of LH-1–3. As a result, these three products were isolated in
62–81% yield. In contrast, the isolated yield of LH-4 (23%)
was considerably lower. The formation of (C6F5)2POH (also
isolated) in that reaction indicated competition of the alk-
oxide and carbanionic centers of 1 for binding to the P atom,
likely due to the high electrophilicity of (C6F5)2PCl.
(2)
Chlorophosphines R2PCl are more readily available and
easier to handle than their secondary phosphine analogues
R2PH. Given that, it was highly desirable to develop an
alternative synthetic method for the phosphinoalcohols,
using R2PCl and a nucleophilic rather electrophilic synthetic
equivalent of the –CH2C(CF3)2OH building block. Keeping
in mind the Barluengo dilithiation of non-fluorinated
halohydrins [10], we attempted the synthesis of LiCH2-
C(CF3)2OLi from BrCH2C(CF3)2OH which was easily
prepared from 1,1-bis(trifluoromethyl)oxirane and 48%
2 The Barluenga procedure [10] involves the sequential treatment of a
non-fluorinated chlorohydrin with 1 equivalent of n-BuLi, followed by 1
equivalent of naphthyllithium for 3and 5 h, respectively. Our studies
of the reaction of BrCH2C(CF3)2OH with two equivalents of n-BuLi at
ꢀ78 8C indicated that the O-lithiation occurred within time of mixing,
whereas the Br/Li exchange took ca. 1 h to go to completion.

V.V. Grushin et al. / Journal of Fluorine Chemistry 117 (2002) 121–129
123
Scheme 2.
Phosphinoalcohols LH-1-4 may be regarded as proto-
nated forms of anionic analogues of hemilabile [11,12]
phosphine–phosphine oxide ligands [13] which have proven
usefulness in synthesis and catalysis [14]. All P,O-ligands
prepared in this work were fully characterized by elemental
reacted with 1 to produce trisubstituted diols 7a, 7b [15] and
7c [16].
The reaction of highly electrophilic 1,1-bis(trifluoro-
methyl)oxirane [6,7] with 1 readily occurred to furnish
1,1,4,4-tetrakis(trifluoromethyl)butanediol-1,4 (Eq. (3)).
1
analysis, H, 19F, and 31P NMR spectroscopical data (see
Section 3).
The dilithium derivative 1 was successfully used for
reactions with electrophiles, such as carbonyl compounds
to give a variety of polyfluorinated diols (Schemes 2–4).
Thus, 1 rapidly reacted with ketones, both fluorinated and
nonfluorinated, e.g. hexafluoroacetone (2a), 1,1,1-trifluoro-
acetone (2b) and acetone (2c) to produce, after acidification,
tetrasubstituted 1,3-diols 3a–c in 56–79% yield (Scheme 2).
Similarly, reactions of 1 with aromatic ketones, such as
octafluoroacetophenone (4a), a,a,a-trifluoroacetophenone
(4b) and acetophenone (4c) produced corresponding dioles
5a–c in up to 76% yield (Scheme 3). Both aromatic and
aliphatic aldehydes with different degrees of fluorination
were reactive toward 1 (Scheme 4). Pentafluorobenzalde-
hyde (6a), benzaldehyde (6b) and acetaldehyde (6c) rapidly
(3)
All diols prepared in this work, except for 7b [16], are
solids at ambient temperature. They are easily soluble in
THF and ether, somewhat soluble in chloroform and dichlor-
omethane, and poorly soluble in hydrocarbons. All new
compounds were characterized by elemental analysis and
NMR spectroscopical data. For compound 5a, a single-
crystal X-ray diffraction study was also carried out.
The 1H NMR spectra of symmetrical diols 3a and 8
exhibit a signal from the CH2 group at 2.7 and 2.3 ppm,
respectively, and a resonance from the OH group, normally
observed between 3.4 and 4.5 ppm. Due to the presence of
Scheme 3.

124
V.V. Grushin et al. / Journal of Fluorine Chemistry 117 (2002) 121–129
Scheme 4.
an asymmetric center in the molecules of 3b, 5b,c and 7a–c,
1
Unexpected solution behavior was observed for the pen-
1
their H NMR spectra exhibit two signals for the magneti-
tafluorophenyl diol 5a. Its H NMR spectrum in CDCl3 at
cally nonequivalent protons of the CH2 group at 2.5–
3.0 ppm. Also, two sharp resonances from the OH groups
are observed at 2–3 and 5–6 ppm for the less and more acidic
protons, respectively (see Table 1). It was noticed for all
diols that the chemical shift of the OH signal was dependent
on the amount of water present in the deuterated solvent used
(CDCl3). No NMR studies under rigorously anhydrous
conditions were undertaken.
20 8C contained two doublets at 2.8 ppm (sharp) and
3.3 ppm (slightly broadened) from the two magnetically
nonequivalent protons of the CH2 group, and a pair of 1:1
signals at 5.3 and 4.8 ppm. The two downfield resonances
were assigned to the OH protons of the C(CF3)2OH and
C(C6F5)CF3OH groups, respectively. While the signal at
5.3 ppm appeared as a sharp singlet, the OH resonance at
4.8 ppm displayed a well-resolved triplet of doublets with
Table 1
NMR data for compounds 3a–c, 5a–c, 7a–c, and 8a
Compound no.
1H NMR (d, ppm; J, Hz)
19F NMR (d, ppm; J, Hz)
13C NMR (d, ppm; J, Hz)b
3a
2.65 (2H, s), 4.45 (2H, s)
ꢀ78.9 (s)
27.15 (m), 76.5 (hept, 30.0), 123.2
(q; 288.0)
3b
1.7 (3H, m), 2.2 (1H, d; 15.9), 2.55
(1H, d; 15.9), 2.7 (1H, s), 5.35 (1H, s)
ꢀ77.6 (3F, q;11.0), ꢀ80.2
(3F, q;11), ꢀ85.2(3F, s)
20.3 (m), 31.2 (m), 74.0 (q;28.0), 76.5
(hept, 30.0), 123.1 (qm; 288.0),
126.5 (q;286.0)
3c
5a
1.5 (6H, s), 1.95 (1H, s), 2.15 (2H, s),
6.6 (1H, s)
ꢀ79.3 (s)
30.4 (m), 37.1 (s), 72.3 (s), 76.5
(hept, 29.0), 124.0 (qm; 287.0)
–
2.8 (1H, d; 16.0), 3.3 (1H, d; 16.0),
4.8 (1H, td; 8.2; 2.5), 5.0 (1H, s)
ꢀ76.0 (3F, qt, 11; 3.3),
ꢀ80 (3F, q; 11), ꢀ83.1 (3F, t; 10),
ꢀ134.1 (1F, br, s), ꢀ145.9 (1F, br, s),
ꢀ150.0 (1F, tt, 21.0; 4.8), ꢀ160.0
(2F, td; 21.0; 6.8)
5b
5c
7a
2.9 (2H, q; 16.8), 3.65 (1H, s), 4.75
(1H, s), 7.45 (3H, m), 7.55 (2H, m)
1.8 (3H, s), 2.4 (1H, d; 16.2), 2.5
(1H, d; 16.2), 6.5 (1H, s), 7.3–7.5 (5H, m)
2.3 (1H, d; 15.5), 2.8 (1H, d; 15.5), 2.9
(1H, s), 5.4 (1H, s), 5.7 (1H, ddd; 12.0;
5.3; 1.5)
ꢀ76.9 (3F, q; 10.0), ꢀ79.0 (3F, q; 10.0),
ꢀ81.6 (3F, s)
–
–
–
ꢀ78.3 (3F, q; 10.0), ꢀ79.4 (3F, q; 10.0)
ꢀ78.1 (3F, dq; 9.7; 1.3), ꢀ79.5
(3F, q; 9.7), ꢀ143.2 (2F, m), ꢀ152.3
(1F, m), ꢀ160.5 (2F, m)
7b
7c
8
2.2 (1H, dd; 15.5; 1.9), 2.4 (1H, ddq;
15.5; 11.3; 1.9), 2.9 (1H, br, s), 5.3
(1H, d; 11.3), 6.3 (1H, br, s), 7.4 (5H, m)
1.3 (3H, d; 6.1), 2.0 (1H, 17.0), 2.1
(1H, 17.0), 2.55 (1H, s), 4.5 (1H, m; 6.1),
6.45 (1H, s)
ꢀ75.7 (3F, q; 9.7), ꢀ75.6 (3F, q; 9.7)
–
ꢀ76.1 (3F, q; 9.7), ꢀ79.9 (3F, q; 9.7)
ꢀ77.4 (s)
24.2 (s), 35.1 (s), 65.3 (m, 2.1), 77.1
(hept; 29.1), 123.3 (qm; 285), 124.1
(q; 287)
2.3 (4H, s), 3.4 (2H, s)
23.5 (m), 76.1 (hept; 28), 124.0 (q; 287)
a In CDCl3, unless stated otherwise.
b In acetone-d6.

V.V. Grushin et al. / Journal of Fluorine Chemistry 117 (2002) 121–129
125
Fig. 1. An ORTEP drawing of 5a, showing intramolecular and intermolecular hydrogen bonding interactions.
J ¼ 8:2 and 2.5 Hz. The ambient temperature 19F NMR
spectrum of the same sample exhibited three resonances for
the CF3-groups, two sharp, well-resolved multiplets at
ꢀ150.0 (1F, p-C6F5) and ꢀ160.0 ppm (2F, m-C6F5) and
two very broad (Dn1=2 ¼ ca: 1000 Hz) signals at ꢀ134 and
ꢀ146 ppm (1F each, o-C6F5). Upon selective irradiation of
either one of the broad 19F NMR signals from the ortho
fluorines, loss of the 8.2 Hz coupling was observed in the 1H
NMR spectrum, and, as a result, the proton resonance at
4.8 ppm appeared as a doublet. These 1H-{19F} experiments
provided firm evidence for F Á Á Á H interactions between the
ortho-fluorines and the proximal OH group.
When the 19F NMR spectrum of 5a was re-run at 50 8C,
the broad resonances from the ortho fluorines collapsed into
one broad signal at ꢀ139.4 ppm. At ꢀ30 8C, the ortho-F
signals became noticeably sharper (Dn1=2 ¼ 60 Hz), the
para-F resonance broadened, and the signal from the
meta-fluorines split into two 1:1 peaks at ꢀ159.9 and
ꢀ159.5 ppm. The observed non-equivalence of all five
fluorines of the C6F5 group indicated restricted rotation
around the C–C6F5 bond. No NMR data was acquired at
lower temperatures, due to almost complete precipitation of
5a from the sample below ꢀ30 8C. The VT NMR data
indicated dynamic processes possibly involving the
OꢀH Á Á Á Fortho interactions (see above), and restricted rota-
tion around the C–C6F5 bond.
The unusual behavior of 5a in solution prompted us to
study this diol by X-ray diffraction. An ORTEP drawing of
the crystal structure of 5a is shown in Fig. 1, and selected
crystallographic data are presented in Section 3. As seen
from Fig. 1, in the solid state 5a forms an infinite hydrogen
bonded chain by translation along the c-axis. Hydrogen
atoms H10 and H30 form intramolecular bonds with O7
and O27, respectively. Both hydrogens H7 and H27 form
bifurcating contacts to an ortho-fluorine from the same
molecule (F6 or F22) and an oxygen atom from an adjacent
molecule (O30 or O10). The hydrogen bonding distances
and angles are given in Table 2, with all of the calculations
being from refined and not idealized hydrogen positions.
The hydrogen bonding pattern observed for 5a in the solid
Table 2
ꢁ
˚
Hydrogen bonds in diol 5a, with H Á Á Á X < rðAÞ þ 2:000 A and OꢀH Á Á Á X > 110
OꢀH Á Á Á X
O–H
H Á Á Á X
OꢀH Á Á Á X
O Á Á Á X
O7ꢀH7 Á Á Á F6
0.770
0.770
0.748
0.804
0.804
0.803
2.156
2.192
2.017
2.079
2.217
2.000
118.61
159.47
143.10
164.56
110.44
140.36
2.613
2.925
2.653
2.862
2.609
2.668
O7ꢀH7 Á Á Á O30
O10ꢀH10 Á Á Á O7
O27ꢀH27 Á Á Á O10
O27ꢀH27 Á Á Á F22
O30ꢀH30 Á Á Á O27

126
V.V. Grushin et al. / Journal of Fluorine Chemistry 117 (2002) 121–129
Fig. 2. An ORTEP drawing of 5a, showing the six-membered ring due to OꢀH Á Á Á O hydrogen bonding.
state (Fig. 1, Table 2) is unlikely to remain unchanged in
solution. Thus, the intermolecular hydrogen bonds are
probably too weak to exist in dilute solutions of 5a. How-
ever, the crystallographic data provides support for stronger
OꢀH Á Á Á Fortho intramolecular interactions which were also
observed in solution NMR experiments (see above). As seen
from Fig. 2, the O7 Á Á Á HꢀO10 contact results in the for-
mation of a six-membered ring with the pentafluorophenyl
group in the axial position. In solution, this six-membered
ring likely undergoes conformational changes which may
also contribute to the dynamic processes observed by NMR
spectroscopy.
It is believed that a combination of factors is involved in
the observed behavior of 5a in solution. The observed
restricted rotation around the C–C6F5 bond may be due to
both the steric bulk of the CF3 groups and the OꢀH Á Á Á Fortho
intramolecular interactions. Consistent with this explanation
is the fact that in 7a, a close analogue of 5a, the C6F5 group
freely rotates at room temperature in solution. Diols 5a and
7a differ in that the latter bears an H atom instead of the CF3
group in the a-position to C6F5. Therefore, rotation around
the C–C6F5 bond in 7a should be favored by both steric and
electronic factors, i.e. lower OH acidity translating into
weaker OꢀH Á Á Á Fortho interactions. It is still unknown,
however, to which extent each of the factors contributes
to the observed behavior of 5a.
reactions provides a simple and convenient route for the
introduction of the –CH2C(CF3)2OH fragment into organic
and organophosphorous molecules.
3. Experimental
NMR spectra were obtained with a Bruker Avance DPX
300 spectrometer, with TMS, CFCl3, and 85% H3PO4 used
as external standards for 1H, 19F, and 31P NMR runs.
Variable temperature spectra of 5a were obtained on a
400 MHz Varian Inova instrument. An HP 6890 instrument
equipped with an HP FFAP capillary column (30 m) and a
TC detector was used for GC analysis. Dry ether, acetone, n-
BuLi (1.6 M in hexane or 2 M in pentane), aqueous HBr,
Ph2PH, Ph2PCl, 2b, 4b and c, 6a–c (Aldrich), 2a, and 4a
(Synquest) were used as received. The fluorinated secondary
phosphine [8,9], 1,1-bis-(trifluoromethyl)oxirane [6], and
chlorophosphines [17–21] were prepared according to the
literature procedures.
3.1. Preparation of 1,1-bis(trifluoromethyl)-2-
bromoethanol, BrCH2C(CF3)2OH
1,1-bis(Trifluoromethyl)oxirane (100 g; 0.55 mol) was
added slowly (to maintain the temperature of the reaction
mixture at 30–40 8C) to vigorously stirring 47% aqueous
HBr (100 ml) in a round bottom glass flask equipped with a
dry-ice condenser and thermometer. The reaction mixture
was then stirred under reflux for 3 h. At that point the
temperature raised to 90 8C. After cooling to room tempera-
ture, the bottom layer was separated, dried over MgSO4, and
In conclusion, it has been demonstrated that the reaction
of BrCH2C(CF3)2OH with two equivalents of n-BuLi at low
temperature leads to the formation of LiCH2C(CF3)2OLi (1).
Intermediate 1 rapidly reacts with a variety of electrophiles,
such as chlorophosphines, ketones, aldehydes, and 1,1-bis-
(trifluoromethyl)oxirane. The high selectivity of these

V.V. Grushin et al. / Journal of Fluorine Chemistry 117 (2002) 121–129
127
distilled to give 104 g (72%) of BrCH2C(CF3)2OH, bp: 101–
103 8C. 1H NMR (CDCl3): 3.5 (br, s, 1H, –OH), 3.7 (s, 2H,
CH2). 19F NMR (CDCl3): ꢀ75.9 (s).
residue, followed by vacuum sublimation produced
(3,5-(CF3)2C6H3)2PCH2C(CF3)2OH (1.52 g; 73%).
Anal. Calcd. for C20H9F18OP, %: C, 37.6; H, 1.4.
1
Found, %: C, 37.5; H, 1.4. H NMR (CD2Cl2, 20 8C),
3.2. Preparation of LH-1
d: 8.0 (m, 6H, arom. H); 3.9 (br, s, 1H, OH); 2.9 (s, 2H,
CH2). 19F NMR (CD2Cl2, 20 8C), d: ꢀ63.9 (s, 12F,
(CF3)2C6H3); ꢀ77.8 (d, JFꢀP ¼ 19:4 Hz, 6F,
(CF3)2COH). 31P NMR (CD2Cl2, 20 8C), d: ꢀ22.1
(septet, JPꢀF ¼ 19:4 Hz).
(a) Under nitrogen, 1,1-bis(trifluoromethyl)oxirane (12 g;
0.066 mol) was added dropwise to a pre-cooled (10–
15 8C) solution of diphenylphosphine (10 g; 0.053 mol)
in dry THF (50 ml). The reaction mixture was stirred at
25 8C for 2 days, after which NMR analysis indicated
>90% conversion of oxirane. After evaporation of the
solvent, the residual viscous oil was distilled under
vacuum to give 8 g (41%) of a fraction (bp 110–114 8C
at 0.05 mmHg) which crystallized on standing. Both
the NMR data and mp (59–62 8C) of this material
(>95% purity) were consistent with those reported for
LH-1 [5]. 1H NMR (CDCl3, 20 8C), d: 7.3–7.8 (m,
10H, arom. H); 2.8 (br, s, 1H, OH); 2.2 (s, 2H, CH2).
19F NMR (CDCl3 , 20 8C), d: ꢀ77. 3 (d,
JFꢀP ¼ 15:5 Hz). 31P NMR (CDCl3, 20 8C), d: ꢀ24.4
(septet, JPꢀF ¼ 15:5 Hz).
(b) Under nitrogen, to a stirring solution of 1,1-bis(tri-
fluoromethyl)-2-bromoethanol (0.91 g) in dry ether
(20 ml) cooled to ꢀ78 8C, was added drop-wise
1.6 M n-BuLi in hexanes (Aldrich; 4.35 ml). After
1 h at ꢀ78 8C, (3,5-(CF3)2C6H3)2PCl (1.63 g) was
added drop-wise, at vigorous stirring, to the resulting
solution of the dilithiated derivative. After stirring for
2 h at ꢀ78 8C, the mixture was allowed to warm slowly
to room temperature and then stirred at room
temperature overnight. The solvents were removed
under vacuum. Dichloromethane (5 ml) and trifluor-
oacetic acid (0.26 ml) were added to the residue. Flash-
chromatography (silica gel, dichloromethane) of the
mixture produced solid Ar2PCH2C(OH)(CF3)2 (1.32 g;
62%) which was found to be identical with the material
prepared in method (a).
(b) Under nitrogen, to a stirring solution of 1,1-bis(tri-
fluoromethyl)-2-bromoethanol (5.64 g) in dry ether
(110 ml) cooled to ꢀ78 8C, was added drop-wise
1.6 M n-BuLi in hexanes (Aldrich; 27 ml). After 1 h
at ꢀ78 8C, chlorodiphenylphosphine (4.53 g) was
added drop-wise, at vigorous stirring, to the resulting
solution of the dilithiated derivative. After stirring the
mixture for 3 h 20 min at ꢀ78 8C, it was allowed to
warm slowly to room temperature and then stirred at
room temperature overnight. The solvents were re-
moved under vacuum. Dichloromethane (10 ml) and
trifluoroacetic acid (1.66 ml) were added to the residue,
and the mixture was chromatographed on a silica gel
column (5 cm ꢂ 25 cm) with dichloromethane. The
product was isolated as a colorless oil which crystal-
lized upon drying under vacuum. The yield of the
product as a white crystalline solid was 5.3 g (71%).
The compound was found identical with the material
synthesized according to method (a).
3.4. Preparation of LH-3
Under nitrogen, to a stirring solution of 1,1-bis(trifluor-
omethyl)-2-bromoethanol (2.28 g) in dry ether (46 ml)
cooled to ꢀ78 8C, was added drop-wise 1.6 M n-BuLi in
hexanes (Aldrich; 10.93 ml). After 1 h at ꢀ78 8C, (4-
CF3C6H4)2PCl (3.28 g) was added drop-wise, at vigorous
stirring, to the resulting solution of the dilithiated derivative.
After stirring for 2 h at ꢀ78 8C, the mixture was allowed to
warm slowly to room temperature and then stirred at room
temperature overnight. The solvents were removed under
vacuum. Dichloromethane (7 ml) and trifluoroacetic acid
(0.64 ml) were added to the residue. Flash-chromatography
(silica gel, dichloromethane) of the mixture, followed by
solvent evaporation and vacuum-drying produced (4-
CF3C6H4)2PCH2C(CF3)2OH (3.36 g; 81%) as a slightly
yellow oil. Anal. Calcd. for C18H11F12OP, %: C, 43.0; H,
2.2. Found, %: C, 42.8; H, 2.2. 1H NMR (CD2Cl2, 20 8C), d:
7.7 (m, 8H, arom. H); 3.6 (br, s, 1H, OH); 2.9 (s, 2H, CH2).
19F NMR (CD2Cl2, 20 8C), d: ꢀ63.5 (s, 6F, CF3C6H4);
ꢀ77.6 (d, JFꢀP ¼ 18:6 Hz, 6F, (CF3)2COH). 31P NMR
(CD2Cl2, 20 8C), d: ꢀ27.1 (septet, JPꢀF ¼ 18:6 Hz).
3.3. Preparation of LH-2
(a) Under nitrogen, a stirring solution of (3,5-(CF3)2C6H3)2-
PH (1.50 g; 3.27 mmol) in THF (30 ml) was cooled
to ꢀ78 8C and treated with a 1.6 M solution of
n-BuLi in hexanes (2.06 ml; 3.30 mmol) to produce a
deep-purple reaction mixture. To the latter was added,
at stirring, 1,1-bis(trifluoromethyl)ethylene oxide
(0.59 g; 0.453 ml; 3.27 mmol) and the mixture was
allowed to warm to room temperature. After stirring
at room temperature overnight, the solution was
treated with 0.3 ml of trifluoroacetic acid and eva-
porated to dryness. Flash-chromatography (silica
gel, methylene chloride–hexanes 1/1, v/v) of the
3.5. Preparation of LH-4
Under nitrogen, to a stirring solution of 1,1-bis(trifluor-
omethyl)-2-bromoethanol (3.43 g) in dry ether (70 ml)
cooled to ꢀ78 8C, was added drop-wise 1.6 M n-BuLi in
hexanes (Aldrich; 16.43 ml). After 30 min at ꢀ78 8C,
(C6F5)2PCl (5.0 g) was added drop-wise, at vigorous stirring,

128
V.V. Grushin et al. / Journal of Fluorine Chemistry 117 (2002) 121–129
Table 3
Reactions of 1 with C-electrophilesa
Entry
Bromohydrin
(mmol)
n-Butyl
lithium
(mmol)
Electrophile
(mmol)
Product
Boiling point,
8C/mmHg
(melting point)
Analysis found
(calcd.)
(yield %)
1
22
44
2a (50)
3a (56)
(78–79)
C, 23.94 (24.15), H, 1.13 (1.16),
F, 65.64 (65.50)
2
3
21
20
42
40
2b (20)
2c (34)
3b (60)
3c (79)
(68.5–69)
(60–61)
C, 28.49 (28.59), H, 2.14 (2.40)
C, 35.36 (35.01), H, 4.03 (4.20),
F, 47.29 (47.47)
4
5
16
16
35
32
4a (16)
4b (16)
5a (63)
5b (76)
(84–84.5)
C, 32.43 (32.31), H, 0.73 (0.90),
F, 59.72 (59.62)
67–68/0.3 (62–63)
C, 41.16 (40.46), H, 2.25 (2.55),
F, 47.80 (48.00)
6
7
20
30
40
60
4c (20)
6a (30)
5c (28)
7a (30)
82–83/0.5 (86–88)
C, 47.79 (47.69), H, 3.83 (4.00)
C, 34.83 (34.94), H, 1.16 (1.33),
F, 55.44 (55.27)
71/72/0.07 (87.5–88)
8
9
20
30
22
40
60
43
6b (20)
6c (30)
(22)d
7b (43)
7c (52)
8 (53)e
72–74/0.3b
89–90/46 (43–44)c
–
–
10
(97.5–98)
C, 26.26 (26.53), H, 1.09 (1.67)
a All reactions were carried out using 100 ml of dry ether as a solvent.
b bp: 104–106/2 mmHg [16].
c mp: 40–43 8C [16].
d 1,1-bis(Trifluoromethyl)oxirane.
e Formation of compound 8 among other products was observed in the photochemical reaction of hexafluoroacetone with ethane, however neither
analytical nor NMR data for 8 were reported. See ref. [22].
to the resulting solution of the dilithiated derivative. After
stirring for 5.5 h at ꢀ78 8C, the mixture was allowed to
warm slowly to room temperature and then stirred at room
temperature overnight. The solvents were removed under
vacuum. Dichloromethane (10 ml) and trifluoroacetic acid
(0.96 ml) were added to the residue. Flash-chromatography
(silica gel, dichloromethane) of the mixture, followed
by solvent evaporation and vacuum-drying produced
(C6F5)2PCH2C(OH)(CF3)2 (1.58 g; 23%) as a white solid.
Anal. Calcd. for C16H3F16OP, %: C, 35.2; H, 0.55. Found, %:
crystallized from hexane (compounds 3a–c, 5b, 8) or first
distilled under vacuum and than recrystallized from hexane
(compounds 5a and c, 7a and c). For the analytical and NMR
data, see Tables 1 and 3.
3.7. Single crystal X-ray diffraction study of 5a
Crystal data: C24H8F28O4, from CH2Cl2, colorless, irre-
gularblock,ꢃ 0:360 mm ꢂ 0:340 mm ꢂ 0:300 mm,triclinic,
˚
˚
˚
P-1, a ¼ 11:4517(7) A, b ¼ 13:4515(7) A, c ¼ 9:7316(4) A,
1
C, 35.1; H, 0.05. H NMR (CD2Cl2, 20 8C), d: 3.3 (s, 2H,
a ¼ 91:007(5)8, b ¼ 92:949(4)8, g ¼ 105:576(2)8, V ¼
3
CH2); 3.6 (br, s, 1H, OH). 19F NMR (CD2Cl2, 20 8C),
d: ꢀ77.8 (d, JFꢀP ¼ 20:5 Hz, 6F, CF3); ꢀ130.6 (m, 4F,
o-C6F5); ꢀ150.0 (t, JFꢀF ¼ 20 Hz; 2F, p-C6F5); ꢀ161.0
(m, 4F, m-C6F5). 31P NMR (CD2Cl2, 20 8C), d: ꢀ57.6 (m).
1441:35(13) A , Z ¼ 2, T ¼ ꢀ100 8C, formula weight ¼
˚
892:30, rcalcd: ¼ 2:056 g/cm3, mðMoÞ ¼ 0:26 mmꢀ1. Data
collection: a Rigaku RU300 diffractometer, R-AXIS image
plate area detector, Mo Ka radiation, filament size ¼
12:0 ꢂ 2:0 mm, anode power ¼ 55 kV ꢂ 220 mA, crystal
to plate distance ¼ 85:0 mm, 105 m pixel raster, number of
frames ¼ 30, oscillation range ¼ 6:08, exposure time ¼
8:0 min/frame, box sum integration, hkl min/max ¼
ðꢀ13; 13; ꢀ14; 15; ꢀ10; 10Þ, data input to shelx ¼ 7572,
unique data ¼ 4025, 2y range ¼ 3:14–48.228, completeness
to 2y 48:22 ¼ 87:70%, Rðint-xlÞ ¼ 0:0529, SADABS cor-
rection applied. Solution and refinement: Structure solved
using XS (Shelxtl), refined using shelxtl software package,
refinement by full-matrix least squares on F2, scattering
factors from Int. Tab. VolC Tables 4.2.6.8 and6.1.1.4, number
of data ¼ 4025, number of restraints ¼ 0, number of
parameters ¼ 522, data/parameter ratio ¼ 7:71, goodness-
of-fit on F2 ¼ 1:04, R indices [I > 4sðIÞ]: R1 ¼ 0:0357,
3.6. Preparation of polyfluorinated diols (typical
procedure; see Table 3 for specifics)
Under nitrogen, two equivalents of n-BuLi in hexanes
(0.04–0.08 mol) was added dropwise to a stirring solution of
1,1-bis(trifluoromethyl)-2-bromoethanol (0.02–0.04 mol) in
dry ether (100 ml) at ꢀ78 8C. After 1–1.5 h at ꢀ78 8C, a
solution of an electrophile (0.02–0.04 mol) in dry ether
(10 ml) was added slowly to keep the temperature within
the range of ꢀ78 to ꢀ60 8C. The reaction mixture was
allowed to warm up to ꢀ10 8C (ꢃ2 h) and poured into
500 ml of 10% aqueous HCl. The organic layer was sepa-
rated and the aqueous layer was extracted with ether
(3 ꢂ 75 ml). The combined organic solutions were dried
over MgSO4 and evaporated under vacuum. The residue was
wR2 ¼ 0:0963,
R
indices (all data): R1 ¼ 0:0406,
wR2 ¼ 0:0995, max difference peak and hole ¼ 0:244 and

V.V. Grushin et al. / Journal of Fluorine Chemistry 117 (2002) 121–129
129
3
˚
[7] V.A. Petrov, submitted for publication.
ꢀ0.237 e/A . All of the H atoms have been left in the final
refinement. Complete crystallographic data available from
the Cambridge Crystallographic Data Center (CCDC no.
184298).
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