Synthesis and transformation of [difluoro(phenylseleno)methyl]- trimethylsilane

Article abstract of DOI:10.1021/jo051119z

A novel and efficient strategy was developed to synthesize [difluoro(phenylseleno)methyl]trimethylsilane (PhSeCF₂-TMS, 2), which was further utilized as a nucleophilic difluoromethylating reagent to incorporate the difluoro-(phenylseleno)methyl (PhSeCF₂) group into carbonyl compounds in good yields. The resulting PhSeCF₂-containing alcohols 3 could be conveniently converted into corresponding difluoromethyl alcohols 4 by a radical deselenylation.

Full text of DOI:10.1021/jo051119z

pounds. In our opinion, [difluoro(phenylseleno)methyl]-
trimethylsilane (PhSeCF2TMS, 2) would be a versatile
nucleophilic difluoromethylating reagent although there
is no corresponding report on its synthesis. First, the
phenylseleno group is a useful reactive functionality,
which can be easily removed after the desired synthetic
steps and oxidative elimination of the phenylseleno
moiety have been successfully exploited for the introduc-
tion of the double bond into organic molecules.4 Second,
the oxidative deselenylation leading to olefins proceeds
relatively lower temperature than the corresponding
organosulfide.4a Finally, reduction of the phenylseleno
group to a hydrogen can be readily and directly achieved
by traditional treatment with Bu3SnH or by treatment
with Raney-nickel under hydrogen.5,6 These procedures
have the advantage over the corresponding phenylthio
group, which is removed by oxidation (H2O2 or CrO3)
followed by reductive desulfonylation (Na/Hg or Na/
EtOH).7
Synthesis and Transformation of
[Difluoro(phenylseleno)methyl]-
trimethylsilane
Ying-Ying Qin,† Xiao-Long Qiu,‡ Yan-Yan Yang,‡
Wei-Dong Meng,† and Feng-Ling Qing*,‡,†
College of Chemistry and Chemical Engineering, Donghua
University, 1882 West Yanan Lu, Shanghai 20051, China,
and Key Laboratory of Organofluorine Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of
Sciences, 354 Fenglin Lu, Shanghai 200032, China
flq@mail.sioc.ac.cn
Received June 3, 2005
We envisaged that silane 2 could react with carbonyl
compounds to give â-hydroxy selenides. Recently, the
synthesis of â-hydroxy selenides has gained extensive
attention due to its applications as the versatile building
blocks. The â-hydroxy selenides can be prepared either
by regioselective ring-opening of epoxides with nucleo-
philic benzeneselenolate or tributylstannyl phenylsele-
nolate (Bu3SnSePh) in the presence of BF3‚Et2O or by
treatment of benzaldehydes with phenylseleno methyl or
ethyl anion.8,9 Enolates derived from ketones could
condense with (phenylseleno)acetaldehyde, providing
another synthetic route to â-hydroxy selenides.10 The
unique chemical properties of â-hydroxy selenides have
been successfully employed for the introduction of double
bond by elimination of PhSeOH.9a,10 On the other hand,
the oxidation of â-hydroxy selenides with m-CPBA and
oxone can lead to a facile formation of epoxides.9b,11
A novel and efficient strategy was developed to synthesize
[difluoro(phenylseleno)methyl]trimethylsilane (PhSeCF2-
TMS, 2), which was further utilized as a nucleophilic
difluoromethylating reagent to incorporate the difluoro-
(phenylseleno)methyl (PhSeCF2) group into carbonyl com-
pounds in good yields. The resulting PhSeCF2-containing
alcohols 3 could be conveniently converted into correspond-
ing difluoromethyl alcohols 4 by a radical deselenylation.
The application of fluorinated organosulfur compounds
as useful synthetic intermediates has evoked a wide-
spread interest in the construction of fluorinated building
blocks. Prakash and co-workers have reported the prepa-
ration of difluoromethyl phenyl sulfone and its applica-
tions as a difluoromethyl anion equivalent, a selective
difluoromethylene dianion equivalent, as well as a dif-
luoromethylidene equivalent.1 In addition, bromodifluo-
romethyl phenyl sulfide (PhSCF2Br) has also been dem-
onstrated to be a highly versatile gem-difluoromethylene
building block via the reaction of difluorophenylsulfanyl
radical with olefins.2 However, very little attention has
been paid to the fluoroselenium compounds. It is well-
known that sulfur and selenium have similar chemical
reactivity, but differ in size, electronegativity, and nu-
cleophilicity.3 Based on the aforementioned cases, we are
very interested in the reactivity of fluoroselenium com-
(4) (a) Fuchigami, T.; Hayashi, T.; Konno, A. Tetrahedron Lett. 1992,
33, 3161-3164. (b) Choi, Y.; Choo, H.; Chong, Y.; Lee, S.; Olgen, S.;
Schinazi, R. F.; Chu, C. K. Org. Lett. 2002, 4, 305-307. (c) Chen, S.
H.; Wang, Q.; Mao, J.; King, I.; Dutschman, G. E.; Gullen, E. A.; Cheng,
Y. C.; Doyle, T. W. Bioorg. Med. Chem. Lett. 1998, 8, 1589-1594.
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1989, 111, 3728-3734. (b) Kang, Y. H.; Kim, K. Tetrahedron 1999,
55, 4271-4286. (c) Ternon, M.; Outurquin, F.; Paulmier, C. Tetrahe-
dron 2001, 57, 10259-10270. (d) Billimoria, A. D.; Cava, M. P. J. Org.
Chem. 1994, 59, 6777-6782. (e) Kamimura, A.; Omata, Y.; Mitsudera,
H.; Kakehi, A. J. Chem. Soc., Perkin Trans. 1 2000, 24, 4499-4504.
(6) (a) Wang, P. C.; Joullie´, M. M. J. Org. Chem. 1980, 45, 5359-
5363. (b) Blay, G.; Cardona, L.; Garca, B.; Garca, C. L.; Pedro, J. R.
Tetrahedron 1996, 52, 10507-10518. (c) Ley, S. V.; Murray, P. J.;
Palmer, B. D. Tetrahedron 1985, 41, 4765-4770. (d) Doherty, A. M.;
Ley, S. V.; Lygo, B.; Williams, D. J. J. Chem. Soc., Perkin Trans. 1
1984, 1371-1378. (e) Semple, J. E.; Wang, P. C.; Lysenko, Z.; Joulli,
M. M. J. Am. Chem. Soc. 1980, 102, 7505-7510.
(7) (a) Joglekar, B.; Miyake, T.; Kawase, R.; Shibata, K.; Muramatsu,
H.; Matsui, M. J. Fluorine Chem. 1995, 74, 123-126. (b) Stahly, G. P.
J. Fluorine Chem. 1989, 43, 53-66. (c) Boger, D. L.; Jenkins, T. J. J.
Am. Chem. Soc. 1996, 118, 8860-8870.
* To whom correspondence should be addressed. Fax: 86-21-
64166128.
† Donghua University.
‡ Shanghai Institute of Organic Chemistry.
(8) (a) Berlin, S.; Ericsson, C.; Engman, L. Org. Lett. 2002, 4, 3-6.
(b) Nishiyama, Y.; Ohashi, H.; Itoh, K.; Sonada, N. Chem. Lett. 1998,
159-160.
(1) (a) Prakash, G. K. S.; Hu, J.; Wang, Y.; Olah, G. A. Org. Lett.
2004, 6, 4315. (b) Prakash, G. K. S.; Hu, J.; Mathew, T.; Olah, G. A.
Angew. Chem., Int. Ed. 2003, 42, 5216-5219. (c) Prakash, G. K. S.;
Hu, J.; Wang, Y.; Olah, G. A. Angew. Chem., Int. Ed. 2004, 43, 5203-
5206. (d) Prakash, G. K. S.; Hu, J.; Wang, Y.; Olah, G. A. Eur. J. Org.
Chem. 2005, 2218-2223.
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101, 6638-6647. (b) Uemura, S.; Ohe, K.; Sugita, N. J. Chem. Soc.,
Perkin Trans. 1 1990, 1697-1703. (c) Uemura, S.; Ohe, K. J. Chem.
Soc., Perkin Trans. 1 1990, 907-910.
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7950-7951. (b) Clive, D. L. J.; Russell, C. G.; Suri, S. C. J. Org. Chem.
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(2) Reutrakul, V.; Thongpaisanwong, T.; Tuchinda, P.; Kuhakarn,
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(3) Arrica, M. A.; Wirth, T. Eur. J. Org. Chem. 2005, 395-403.
10.1021/jo051119z CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/22/2005
9040
J. Org. Chem. 2005, 70, 9040-9043

SCHEME 1
SCHEME 2
with sodium hydride, followed by sequential addition of
NaBH4 and CF2Br2. Just as anticipated, NaBH4 did pre-
vent the generation of PhSeSePh and our desired product
PhSeCF2Br was provided in 86% yield. Based on this
result, we considered that PhSeSePh could also be used
for the preparation of PhSeCF2Br. Treatment of Ph-
SeSePh with NaBH4 in THF followed by addition of CF2-
Br2 successfully furnished the desired product PhSeCF2-
Br in 61% yield, which further confirmed the important
role of NaBH4 in the reaction between PhSeH/NaH and
CF2Br2.
Trifluoromethyltrimethylsilane (CF3TMS) is a good
reagent to introduce a trifluoromethyl group into elec-
trophilic compounds.16 Therefore, [difluoro(phenylseleno)-
methyl]trimethylsilane (PhSeCF2TMS, 2) would also be
expected as a novel and efficient fluorination reagent to
incorporate PhSeCF2 group into organic compounds via
nucleophilic addition. To the best of our knowledge,
magnesium metal-mediated reductive fluoroalkylation of
halosilane is the efficient route for synthesis of fluoro-
alkyltrimethylsilane, just as the recent synthesis of
PhSCF2TMS by Prakash and co-workers.17 Thus, PhSeCF2-
TMS 2 was prepared in 81% yield by the reaction of
PhSeCF2Br, magnesium and chlorotrimethylsilane (TM-
SCl) (Scheme 2). In our experiment, we found that the
sequence of adding raw materials had a distinct influence
on the result. If TMSCl was added before PhSeCF2Br,
the reaction would be complicated. The proper procedure
was to treat PhSeCF2Br with Mg turnings at first in THF
at room temperature, followed by slow addition of TMSCl
via a syringe.
There are no corresponding synthetic procedures for
[difluoro(phenylseleno)methyl]trimethylsilane (PhSeCF2-
TMS, 2). We propose that it could be prepared from
halodifluoromethyl phenyl selenides. In 1995, Uneyama
and co-worker reported a new access to difluoromethylene
compounds by an electrochemical procedure, in which
bromodifluoromethyl phenyl selenide (PhSeCF2Br) was
furnished as a byproduct.12 However, there were no
detailed characterization data and synthetic procedure
of PhSeCF2Br in their report. Herein, we described a
novel and efficient preparation of PhSeCF2Br by the
reaction of selenophenol with CF2Br2 in the presence of
sodium borohydride. The difluoromethylating reagent
PhSeCF2TMS was then synthesized by the coupling
reaction of PhSeCF2Br and TMSCl. The transformation
of PhSeCF2TMS was studied with nucleophilic addition
to various aldehydes and ketones, and the resulting R,R-
difluoro-â-hydroxy selenides were also deselenylated to
give the corresponding difluoromethyl alcohol.
In 1981, Suda and Hino first reported the preparation
of bromodifluoromethyl phenyl sulfide (PhSCF2Br) in
58% yield by the reaction of thiophenol with CF2Br2 in
aprotic solvents, and they suggested that the difluoro-
carbene intermediate was involved in the formation of
PhSCF2Br.13 Later on, this reaction was improved by the
addition of dibenzo-18-crown-6 as a catalyst to increase
the yield.2,14 Inspired by their work,2,13,14 we attempted
to prepare fluoroselenide (PhSeCF2Br) by their methodol-
ogy. Selenophenol was first treated with sodium hydride
in THF followed by addition of CF2Br2 at -70 °C.
Unfortunately, the yield of the desired product 1 was
below 25%. Diphenyl diselenide (PhSeSePh) (major
byproduct), difluoromethyl phenyl selenide (PhSeCF2H),
and diphenylseleno compounds (PhSeCF2SePh) were
formed as the byproducts. Thus, how to improve the yield
of product 1 rendered us to investigate this reaction in
detail. Reduction of the byproducts was the key to
improve the yield of desired product 1. It was reported
that PhSeSePh was a common nucleophilic reagent, and
it could be easily transferred into phenylseleno anion
under the reduction of sodium borohydride.15 Thus, we
supposed that the addition of NaBH4 might prevent the
generation of PhSeSePh or convert the resulting Ph-
SeSePh into PhSe-, which could take part in the reaction
again (Scheme 1). Thus, selenophenol was first treated
With fluoroalkylated silane compound 2 in hand, we
first studied the reaction of PhSeCF2TMS with aldehydes
and ketones. The reaction was carried out with the
catalysis of TBAF to provide the corresponding R,R-
difluoro-â-hydroxy selenides 3. It was reported the exist-
ence of a small amount of water in TBAF did not pose
any serious problems in the trifluoromethylation of
aldehydes and ketones with CF3TMS, and use of anhy-
drous TBAF did not offer any advantages.16 However, the
existence of a small amount of water in TBAF lowered
the yield of the desired alcohols 3 and led to PhSeCF2H
as a byproduct in our experiments. This phenomenon was
attributed to the electron-donating property of PhSe
-
moiety, which resulted in more nucleophilic of PhSeCF2
-
than CF3 anion and perfluoroalkyl anion. Addition of
molecular sieves into the reaction mixture could success-
fully overcome this problem and the results were sum-
marized in Table 1. Reactions of aldehydes (aromatic and
aliphatic aldehydes, entries 1-4) with compound 2
proceeded well and gave the hydroxyl compounds 3a-e
in moderate to high yields. However, ketones provided
the corresponding compounds 3e,f in somewhat low
yields (entries 5 and 6) along with a large amount of
(11) Ceccherelli, P.; Curini, M.; Epifano, F.; Marcotullio, M. C.;
Rosati, O. J. Org. Chem. 1995, 60, 8412-8413.
(12) Asai, H.; Uneyama, K. Chem. Lett. 1995, 1123-1124.
(13) Suda, M.; Hino, C. Tetrahedron Lett. 1981, 22, 1997-2000.
(14) Li, X.-Y.; Jiang, X.; Gong, Y.; Pan, H.; Jiang, X. Huaxue Xuebao
1985, 43, 260-265.
(16) (a) Krishnamurti, R.; Bellew, D. R.; Prakash, G. K. S. J. Org.
Chem. 1991, 56, 984-989. (b) Singh, R. P.; Shreeve, J. M. Tetrahedron
2000, 56, 7613-7632.
(17) Prakash, G. K. S.; Hu, J.; Olah, G. A. J. Org. Chem. 2003, 68,
4457-5563.
(15) (a) Sharpless, K. B.; Lauer, R. F. J. Am. Chem. Soc. 1973, 95,
2697-2699. (b) Lucas, M. A.; Nguyen, O. T. K.; Schiesser, C. H.; Zheng,
S. L. Tetrahedron 2000, 56, 3995-4000.
J. Org. Chem, Vol. 70, No. 22, 2005 9041

TABLE 1. Nucleophilic
Experimental Section
(Phenylseleno)difluoromethylation of Carbonyl
Compounds with PhSeCF2-TMC 2
Bromodifluoromethyl Phenyl Selenide (1). Method A.
Under nitrogen atmosphere, phenylselenol (1.023 g, 6.5 mmol)
was added dropwise to a stirred suspension of sodium hydride
(303 mg, 7.6 mmol) in 10 mL of dry THF cooled in an ice bath.
Then NaBH4 (1.005 g, 26.5 mmol) was added to the yellow
suspension. After an exothermic reaction ceased, the mixture
was stirred at room temperature for 20 min and then cooled to
-70 °C in a dry ice-acetone bath. Dibromodifluoromethane (2.5
mL, 27.3 mmol) was slowly added to the stirred solution. The
reaction mixture was stirred for 10 min cooled in the dry ice-
acetone bath, and then for 30 min at room temperature. During
this period, the yellow suspension turned to a cream colored
suspension. Ether and saturated aqueous NH4Cl were added
slowly to the reaction mixture, and the resulting mixture was
partitioned. The aqueous layer was extracted with ether, and
the organic layer combined was washed with brine, dried over
Na2SO4, and concentrated under reduced pressure to leave an
oil, which was purified by column chromatography (n-pentane)
to give 1 (1.594 g, 86%) as a colorless oil.
Method B. Under nitrogen atmosphere, NaBH4 (100 mg, 2.64
mmol) was added to a stirred solution of diphenyl diselenide (103
mg, 0.33 mmol) in 2 mL of dry THF. Dry methanol (ca. 0.1 mL)
was added slowly to the reaction mixture cooled in an ice bath
until the bright yellow solution turned colorless. After an
exothermic reaction ceased, the mixture was stirred at room
temperature for 20 min and then cooled to -70 °C on a dry ice-
acetone bath. Dibromodifluoromethane (0.25 mL, 2.73 mmol)
was slowly added to the stirred solution. The reaction mixture
was stirred for 10 min cooled in a dry ice-acetone bath and then
stirred for 30 min at room temperature. Ether and saturated
aqueous NH4Cl were added slowly to the reaction mixture, and
the resulting mixture was partitioned. The aqueous layer was
extracted with ether, and the organic layer combined was
washed with brine, dried over Na2SO4, and concentrated under
reduced pressure to leave an oil, which was purified by column
chromatography (n-pentane) to give 1 (116 mg, 61%) as a
colorless oil: 1H NMR (300 MHz, CDCl3) δ 7.40-7.45 (2H, m),
7.49-7.51 (1H, m), 7.76-7.78 (2H, m); 13C NMR (75 MHz,
SCHEME 3
byproduct PhSeCF2H. In our opinion, the low yields of
3e,f were caused by the low reactivity of ketone carbonyl
group, which resulted in preferential reaction of fluoro-
alkylated silane 2 with water in TBAF.
R,R-Difluoro-â-hydroxy selenides can be further trans-
ferred into the corresponding difluoromethyl alcohols by
a traditional radical deselenylation procedure. As a
representative example, treatment of R,R-difluoro-â-
hydroxy selenide 3a with Bu3SnH in the catalysis of
AIBN provided the difluoromethyl alcohol 4 in 91% yield
(Scheme 3). The resulting difluoromethyl alcohol is a
highly useful compound for potential application.18
In conclusion, we described a novel and efficient syn-
thesis of bromodifluoromethyl phenyl selenide (PhSeCF2-
Br, 1) by the addition of NaBH4 to prevent the formation
of diphenyl diselenide. [Difluoro(phenylseleno)methyl]-
trimethylsilane (PhSeCF2TMS, 2) was conveniently pre-
pared by the coupling reaction of PhSeCF2Br and TMSCl.
The resulting fluoroalkylated silane 2, in the presence
of a fluoride initiator, could act as a “PhSeCF2-” equiva-
lent and reacted with a series of aldehydes and ketones
to furnish the corresponding R,R-difluoro-â-hydroxy se-
lenides 3, which could be deselenylated to afford difluo-
romethyl alcohols via a classical procedure. In our
opinion, difluoroalkylation of carbonyl compounds with
2 provided an optional method for the preparation of wide
ranges of R, R-difluoro-â-hydroxy selenides and difluo-
romethyl alcohols.
1
CDCl3) δ 108.6 (t, JCF ) 355 Hz), 126.1, 129.6, 130.6, 137.1;
19F NMR (282 MHz, CDCl3/CFCl3) δ -18.43 (2F, s); IR (neat) ν
1579, 1477, 1441, 1089, 1078, 1058 cm-1; MS (EI) m/z ) 286
(M+, 13), 207 (19), 157 (18), 127 (100), 77 (28); HRMS (EI) calcd
for C7H5F2BrSe 285.8708, found 285.8721.
[Difluoro(phenylseleno)methyl]trimethylsilane (2). To
a dry 25 mL Schlenk flask under nitrogen atmosphere were
added Mg turnings (30 mg, 1.25 mmol) and PhSeCF2Br (143 mg,
0.5 mmol) in 2.5 mL of THF at room temperature. Subsequently,
TMSCl (0.26 mL, 2.0 mmol) was added slowly via a syringe. The
reaction mixture was stirred at room temperature for 30 min,
and the starting substrate was completely consumed by TLC.
The reaction mixture was then transferred to a flask via a
syringe. Excess TMSCl was removed under reduced pressure.
The residue was purified by silica gel chromatography (n-
pentane) to give 2 (113 mg, 81%) as a pale yellow oil: 1H NMR
(300 MHz, CD3COCD3) δ 0.20 (9H, s), 7.40-7.43 (3H, m), 7.68-
2
7.71 (2H, m); 13C NMR (75 MHz, C6D6) δ -4.4, 124.3 (t, JCF
)
4.2 Hz), 128.9, 129.0, 133.3 (t, 1JCF ) 312.9 Hz), 137.3; 19F NMR
(282 MHz, CD3COCD3) δ -85.24 (2F, s); IR (neat) ν 3063, 2964,
1579, 1477, 1440, 1255, 1081, 1066 cm-1; MS (EI) m/z ) 280
(M+, 38), 261 (68), 230 (50), 169 (69), 77 (100), 73 (945); HRMS
(EI) calcd for C10H14F2SeSi 279.9997, found 280.0022; Anal.
Calcd for C10H14F2SeSi: C, 43.01; H, 5.05. Found: C, 43.38; H,
5.27.
2,2-Difluoro-2-phenylseleno-1-(4′-cynaophenyl)ethan-
ol (3a). A solution of PhSeCF2TMS (140 mg, 0.5 mmol) and
4-cynaobenzaldehyde (328 mg, 2.5 mmol) in 2.5 mL of THF was
dried over MS-4 Å, after which TBAF (0.1 mL, 1 M solution in
THF, containing ca. 5% water) was added. The resulting solution
was stirred at room temperature for 2 h. Then a substantial
amount of water was added, and stirring was continued for
another 1 h. The mixture was extracted with ether (3 × 20 mL),
and the combined extracts were washed with brine, dried over
(18) Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis, Reac-
tivity Application; Wiley-VCH: Weinheim, 2004.
9042 J. Org. Chem., Vol. 70, No. 22, 2005

Na2SO4, and evaporated. Purification of the residue with column
chromatography [petroleum ether/EtOAc, 5/1 (v/v)] gave the
corresponding alcohol 3a (154 mg, 91%) as a pale yellow solid:
mp 89 °C; 1H NMR (300 MHz, CDCl3) δ 3.05 (1H, d, J ) 3.0
Hz), 4.96-5.03 (1H, m), 7.32-7.68 (9H, m); 13C NMR (75 MHz,
to gave 4 (15 mg, 93%) as a pale yellow oil: 1H NMR (300 MHz,
CDCl3) δ 2.86 (1H, br), 4.93 (1H, m), 5.75 (1H, td, 2JFH ) 56 Hz,
3JHH ) 4.8 Hz), 7.57-7.59 (2H, m), 7.69-7.72 (2H, m); 13C NMR
(75 MHz, CDCl3) δ 72.9 (t, 2JCF ) 24.1 Hz), 115.2 (t, 1JCF ) 245
Hz), 112.8, 118.4, 127.9, 132.3, 140.8; 19F NMR (282 MHz, CDCl3)
δ -127.4 (1F, ddd, J ) 286 Hz, 56 Hz, 9.6 Hz), -128.0 (1F, ddd,
J ) 286 Hz, 56 Hz, 9.6 Hz); IR (neat) ν 3433, 2234, 1507, 1407,
1076 cm-1; MS (EI) m/z ) 184 (M+, 58), 132 (85), 104 (100), 77
(49); HRMS (EI) calcd for C9H7NOF2 183.0496, found 183.0507.
2
CDCl3) δ 75.9 (t, JCF ) 26 Hz), 112.9, 118.5, 123.2, 126.1 (t,
1JCF ) 299 Hz), 128.6, 129.4, 129.8, 132.0, 137.2, 140.1; 19F NMR
2
3
(282 MHz, CDCl3) δ -77.7 (1F, dd, JFF ) 213 Hz, JFH ) 6.9
2
3
Hz), -83.9 (1F, dd, JFF ) 213 Hz, JFH ) 15.8 Hz); IR (neat) ν
3433, 2963, 2235, 1578, 1475, 1440, 1056 cm-1; MS (EI) m/z )
339 (M+, 32), 208 (35), 132 (100), 127 (82), 77 (51); HRMS (EI)
calcd for C15H11NOF2Se 338.9973, found 338.9961.
Acknowledgment. We thank the National Natural
Science Foundation of China, Ministry of Education of
China, and Shanghai Municipal Scientific Committee
for funding this work.
2,2-Difluoro-1-(4′-cynaophenyl)ethanol (4). A mixture of
3a (30 mg, 0.09 mmol) and toluene (4 mL) was heated at 100
°C, followed by addition of a catalytic amount of AIBN (5 mg,
0.03 mmol) and tributyltin hydride (123 µL, 0.45 mmol). After
being kept at 100 °C for 30 min, the mixture was cooled to room
temperature and the solvent was evaporated, diluted with
saturated NaF solution (10 mL), and filtered. The aqueous layer
was extracted with EtOAc (3 × 10 mL). The combined organic
extracts were washed with water (3 × 10 mL) and brine (10 mL),
dried over Na2SO4, and evaporated. The residue was purified
by column chromatography [petroleum ether/EtOAc, 2/1 (v/v)]
Supporting Information Available: Characterization
data for compounds 3b-f, and 1H NMR and 13C NMR spectra
of all of the compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO051119Z
J. Org. Chem, Vol. 70, No. 22, 2005 9043