Nucleophilic difluoromethylation of epoxides with PhSO(NTBS)CF2H by a preorganization strategy

Article abstract of DOI:10.1002/chem.201402506

Unlike the facile synthesis of β-monofluoromethyl alcohols by nucleophilic monofluoromethylation of epoxides, the synthesis of β-difluoromethyl alcohols by nucleophilic difluoromethylation of epoxides still remains a challenge. Herein, studies on tackling this problem with PhSO(NTBS)CF₂H (2; TBS=tert-butyldimethylsilyl) are reported. The preorganization of 2 and epoxides with BF₃Et₂O was found to be crucial for the reaction. The reaction shows excellent regioselectivity and has a broad substrate scope. The facile transformation of the ring-opened products to β-difluoromethyl, γ-difluoromethyl, and β-difluoromethylenyl alcohols demonstrates the synthetic utility of the reaction.

Full text of DOI:10.1002/chem.201402506

DOI: 10.1002/chem.201402506
Full Paper
&
Fluoroalkylation
Nucleophilic Difluoromethylation of Epoxides with
PhSO(NTBS)CF2H by a Preorganization Strategy**
Xiao Shen, Qinghe Liu, Tao Luo, and Jinbo Hu*[a]
Abstract: Unlike the facile synthesis of b-monofluoromethyl
alcohols by nucleophilic monofluoromethylation of epox-
ides, the synthesis of b-difluoromethyl alcohols by nucleo-
philic difluoromethylation of epoxides still remains a chal-
lenge. Herein, studies on tackling this problem with PhSO-
(NTBS)CF2H (2; TBS=tert-butyldimethylsilyl) are reported.
The preorganization of 2 and epoxides with BF3·Et2O was
found to be crucial for the reaction. The reaction shows ex-
cellent regioselectivity and has a broad substrate scope. The
facile transformation of the ring-opened products to b-di-
fluoromethyl, g-difluoromethyl, and b-difluoromethylenyl al-
cohols demonstrates the synthetic utility of the reaction.
Introduction
fully reacted with epoxides to give b-monofluoromethyl alco-
hols.[8] The difficulty of the ring-opening reaction between the
À
In recent years, selective incorporation of fluorine or fluoroalkyl
groups into organic compounds has become a routine and
powerful strategy in the design of pharmaceuticals, agrochemi-
cals, and materials.[1] Among various fluoroalkyl groups, the di-
fluoromethyl (CF2H) and 1,1-difluoromethylenyl (=CF2) func-
tionalities have attracted particular interest. The former group
(CF2H) has been used not only as an isostere to an OH or SH
unit, but also as a hydrogen donor to form hydrogen bond-
ing.[2] The 1,1-difluoromethylidene functionality (=CF2), which
can act as a biostere of the carbonyl group, has also been
used in the design of mechanism-based enzyme inhibitors.[3]
Therefore, developing methods for the synthesis of difluoro-
methyl- or 1,1-difluoromethylenyl-substituted compounds is
highly desirable.
epoxides and PhSO2CF2 was attributed to the “negative fluo-
rine effect”, that is, fluorine substitution on the carbanion
center reduces the thermal stability (lifetime) of the carbanion
as well as its nucleophilicity toward epoxides.[8–10] In 2007, we
reported that when 1,2-cyclic sulfates (more electrophilic epox-
ide equivalents) were used as substrates, the difluoromethyla-
tion with PhSO2CF2H (1) could be achieved (Scheme 1a).[9a] Al-
Over the past decades, nucleophilic fluoroalkylation, typically
involving the transfer of a-fluoro carbanions or their equiva-
lents to electrophiles, has proved to be a powerful strategy for
the synthesis of fluorinated compounds.[4,5] In this respect, flu-
orinated sulfones have been widely used as the precursors of
a-fluoro carbanions in synthetic organofluorine chemistry.[4]
For example, a-difluoromethyl alcohols were easily obtained
Scheme 1. Strategies for the synthesis of b-difluoromethyl and b-difluorome-
thylenyl alcohols.
by nucleophilic difluoromethylation of carbonyl compounds
though this reaction provides facile access to b-difluoromethy-
lated or b-difluoromethylenated alcohols, it is associated with
some drawbacks: 1) it is not suitable for more sterically hin-
À [5]
with PhSO2CF2
.
However, the synthesis of b-difluoromethyl
alcohols by the corresponding nucleophilic difluoromethyla-
tion of epoxides is more challenging.[6,7] In our previous study,
dered
1,2-disubstituted
1,2-cyclic
sulfates
such
as
À
the reaction between PhSO2CF2 and 2-methyloxirane was un-
hexahydrobenzo[d][1,3,2]dioxathiole 2,2-dioxide;[9b] 2) the sub-
strates (1,2-cyclic sulfates) themselves often require multi-step
syntheses.[9] Therefore, a new, efficient, and direct ring-opening
difluoromethylation of epoxides is highly desired. Herein, we
disclose our recent success in addressing this issue with sulfox-
imine PhSO(NTBS)CF2H (2) by means of preorganization of ep-
oxides and 2 with BF3·Et2O (Scheme 1b). To the best of our
knowledge, this preorganization strategy has not previously
been used in the ring-opening reactions between epoxides
and carbanions.
successful, although (PhSO2)2CFÀ and PhSO2CHFÀ were success-
[a] Dr. X. Shen, Q. Liu, T. Luo, Prof. Dr. J. Hu
Key Laboratory of Organofluorine Chemistry
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
345 Ling-Ling Road, Shanghai 200032 (P. R. China)
E-mail: jinbohu@sioc.ac.cn
[**] TBS=tert-butyldimethylsilyl.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402506.
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As monoaza analogues of sulfones, sulfoximines have been
widely used in organic synthesis due to their diverse chemical
and biological properties.[11] Recently, various fluorinated sul-
foximines have been designed, synthesized, and used as pow-
erful fluoroalkylation reagents.[12,13] In our previous study, it
was found that (R)-PhSO(NTBS)CF2H ((R)-2) can serve as a di-
fluoromethyl anion precursor and react with aryl ketones and
aldehydes to give optically enriched a-difluoromethyl alco-
hols.[12a] In this article, we report the application of reagent 2
in the synthesis of b-difluoromethyl, g-difluoromethyl, and b-
difluoromethylenyl alcohols, which has not been achieved by
the reaction of epoxides with any other difluoromethylation re-
agents (Scheme 1b).
Ring-opening difluoromethylation of epoxides
Encouraged by the above results, we started to investigate the
possibility of ring-opening difluoromethylation of epoxides
using sulfoximine 2. 2-Methyloxirane (4a) was chosen as
a model substrate to first test and then optimize the reaction
conditions. To our disappointment, the reaction of PhSO-
À
(NTBS)CF2 with 4a was not successful and no ring-opening di-
fluoromethylation product 5 was found, even though PhSO-
À
À
(NTBS)CF2 is more stable than PhSO2CF2 (Scheme 4a). We as-
Results and Discussion
Preparation of PhSO(NTBS)CF2H (2)
Firstly, we developed a new procedure for the synthesis of
compound 2 on a relatively large scale. Sulfoximine 3 was
readily synthesized according to the reported procedure.[13c]
Sulfoximine 2 was obtained in 90% yield (13.5 g) by treatment
of compound 3 with TBSCl and imidazole in DMF, overnight
(Scheme 2).
Scheme 4. Survey of reaction conditions. 4a (1.5 equiv), LiHMDS (2 equiv),
BF3·Et2O (2.5 equiv) were used, and the yield was determined by 19F NMR
with PhCF3 as the internal standard.
À
sumed that the nucleophilicity of PhSO(NTBS)CF2 towards the
epoxide was not high enough and that activation of 4a would
be needed to achieve the ring-opening difluoromethylation re-
action. Previously, BF3·Et2O has often been used as a Lewis acid
to activate epoxides in their reactions with carbanions.[6b,8,14]
Two traditional procedures have been applied: 1) adding the
epoxide to mixtures of BF3·Et2O and carbanions;[14] 2) adding
BF3·Et2O immediately after the addition of the epoxide to a so-
lution of the carbanion.[6b,8] As discussed by Ganem et al.,[14]
these successful reactions would indicate that combinations of
such carbanions and BF3·Et2O are reasonably stable under cer-
tain reaction conditions, allowing them to react independently
as potent nucleophile and strong Lewis acid, respectively.[6b,8,14]
However, in the case of sulfoximine 2, compound 5 was not
obtained by using either of these two procedures (Scheme 4b,
c). Moreover, in neither case was any of the desired product 5
obtained, even when the reaction mixture was allowed to
warm to room temperature after being stirred at À788C for
30 min. 19F NMR experiments showed that PhSO(NTBS)CF2H (2)
was completely deprotonated by LiHMDS, and new 19F NMR
peaks at d=À111.30–111.38 ppm were observed (see the Sup-
porting Information). We surmised that these signals might
Scheme 2. Preparation of PhSO(NTBS)CF2H (2).
À
À
Thermal stabilities of PhSO(NTBS)CF2 and PhSO2CF2
With compound 2 in hand, we examined the stability of PhSO-
(NTBS)CF2À, since the low thermal stability of PhSO2CF2 has
À
been considered as one of the major reasons for the previous
failure of its ring-opening difluoromethylation reaction with
epoxides. It was found that PhSO2CF2H (1) completely decom-
posed upon treatment with lithium hexamethyldisilazide
(LiHMDS; 2 equiv) at À788C for 5 min (Scheme 3a). In contrast,
50% recovery was observed for PhSO(NTBS)CF2H (2) under the
same conditions (Scheme 3b), indicating a higher thermal sta-
À
À
bility of PhSO(NTBS)CF2 than that of PhSO2CF2
.
result from the reaction between BF3·Et2O and PhSO-
À [15,16]
(NTBS)CF2
.
We presumed that the nucleophilicity of the
newly formed species toward epoxides was still not high
enough.[17]
À
À
Scheme 3. Investigation of the stability of PhSO2CF2 and PhSO(NTBS)CF2
.
Based on these experimental results, we considered that in
order to achieve a successful ring-opening reaction between
epoxide 4a and sulfoximine 2, the following prerequisites
À
should be met: 1) PhSO(NTBS)CF2 should be generated in
situ, because it will slowly decompose after formation; 2) the
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epoxide should be activated before the formation of PhSO-
successfully difluoromethylated by reagent 2 (Scheme 5). The
reaction showed excellent regioselectivity, and the substitution
took place at the less hindered carbon atoms of the epoxides.
For monosubstituted epoxides, the reaction worked well,
giving products 6a–f in good yields (70–87%), although the
diastereoselectivities were low (53:47–58:42 d.r.). Optically
pure b-difluoromethylated alcohols could be readily obtained
when enantiomerically pure epoxides were used as substrates.
When compound (S)-4a was subjected to the reaction with
sulfoximine (R)-2, product (2R, SR)-6a was obtained in 77%
yield. The reaction could be easily scaled-up, and a 78% yield
of product 6 f was obtained on a 1.5 g scale. More importantly,
1,2-disubstituted oxiranes 4g–i also proved to be suitable sub-
strates for the current difluoromethylation reaction, giving
compound 6g in 70% yield with 63:37 d.r., 6h in 65% yield
with 67:33 d.r., and 6i in 65% yield with 63:37 d.r., respective-
ly. It is worth noting that the previous reactions between
PhSO2CF2H and cyclic sulfates did not proceed with sterically
À
(NTBS)CF2À; 3) the reaction between PhSO(NTBS)CF2 and the
activated epoxide should be faster than that between PhSO-
À
(NTBS)CF2 and the activator. With these considerations in
mind, we surmised that adding BF3·Et2O (activator) to a mixture
of 2 and 4a before the addition of LiHMDS should be the best
choice. To our satisfaction, a 95% yield of product 5 was ob-
served by 19F NMR using this new “preorganization” procedure
(Scheme 4d). Subsequently, several parameters, including base,
solvent, and reactant ratio, were further investigated (for de-
tails, see the Supporting Information). THF was found to be
a better solvent than Et2O, PhCH3, DME, or CH2Cl2, and LiHMDS
proved to be a better base than NaHMDS, KHMDS, TMPLi,
tBuOK, or tBuONa. Eventually, with a 4a/2/LiHMDS/BF3·Et2O
ratio of 1.5:1:2:2.5, THF as the solvent, and 12m aqueous HCl
to quench the reaction and remove the TBS group of the ring-
opened product, compound 6a was isolated in 82% yield
(Scheme 5).
Having optimized the reaction conditions, the substrate
scope of the reaction between epoxides 4 and sulfoximine 2
was investigated. Various structurally diverse epoxides were
hindered
1,2-disubstituted
substrates
such
as
hexahydrobenzo[d][1,3,2]dioxathiole 2,2-dioxide, which high-
lights the potency of our current difluoromethylation
method.[9] Moreover, the current reaction could also be per-
formed with four-membered oxacycles 4j and 4k, giving g-di-
fluoromethylated alcohols 6j and 6k in 68% and 85% yield,
respectively.
After achieving reactions of difluoromethyl sulfoximine 2
with three-membered and four-membered oxacycles, we
tested the possibility of the difluoromethylation of five-mem-
bered oxacycles such as tetrahydrofuran (THF). However, the
anticipated product 6l was not obtained when LiHMDS was
used as the base. Interestingly, however, when LiHMDS was re-
placed by KHMDS, compound 6l was formed in 50% yield
(Scheme 6).
Scheme 6. Reaction of THF with sulfoximine 2.
To demonstrate the synthetic utility of the current difluoro-
methylation reaction, compounds 6 f and 6k were further
transformed to b-difluoromethyl alcohol 7 and g-difluorometh-
yl alcohol 8, respectively. Under conditions of Mg/BrCH2CH2Br
(cat.)/MeOH, the sulfonimindoyl groups of compounds 6 f and
6k were easily removed, affording products 7 and 8 in 90%
and 89% yield, respectively (Scheme 7a, b). When saturated
aqueous NH4Cl was added to quench the ring-opening reac-
tion, the TBS group was preserved, and compound 9 was ob-
tained in 81% yield (Scheme 8). Compound 9 was transformed
to compound 10 in 92% yield using TMSCl as a silylating
agent. b-Difluoromethylenyl alcohol 11 was obtained in 86%
yield after successive treatment of compound 10 with LiHMDS
and 3m aqueous HCl.
Scheme 5. Regioselective difluoromethylation of epoxides. Typical proce-
dure: under a N2 atmosphere, BF3·Et2O (0.3 mL, 2.5 mmol) was added to a so-
lution of (S)-4a (87 mg, 1.5 mmol) and (R)-2 (305 mg, 1 mmol) in THF (6 mL),
at À78oC. Three minutes later, LiHMDS (1.0 m in THF, 2.0 mL, 2 mmol) was
added slowly at À78oC. After 30 min, HCl aqueous solution (12 m, 1.5 mL)
was added to quench the reaction. Yield and d.r. are based on the isolated
product. [a] (R)-2 was used as the reagent. [b] 1.5 g scale of 2.
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Scheme 9. Reaction between 4a and 1.
Conclusion
Scheme 7. Synthesis of b-difluoromethyl alcohol 7 and g-difluoromethyl al-
cohol 8 by reductive desulfoximination.
In summary, an efficient and highly regioselective nucleophilic
difluoromethylation of epoxides has been achieved by using
an unprecedented preorganization strategy. The reaction is
amenable to three-, four-, and five-membered oxacycles. Steri-
cally hindered 1,2-disubstituted oxiranes are also suitable sub-
strates for the reaction. The facile transformation of the ring-
opened products to b-difluoromethyl, g-difluoromethyl, and b-
difluoromethylenyl alcohols shows the potential synthetic utili-
ty of this reaction. The preorganization strategy is likely to be
applicable to other ring-opening reactions between epoxides
and carbanions of low thermal stability and weak nucleophilici-
ty, as demonstrated by the successful reaction between 2-
methyloxirane and PhSO2CF2H (Scheme 9).
Scheme 8. Synthesis of b-difluoromethylenyl alcohol 11.
Since the nitrogen atom in a sulfoximine is a coordination
site, many sulfoximines have been used as chiral ligands in
metal-catalyzed reactions.[11a,b,18] Penta- and hexacoordinate hy-
pervalent boron species have also been reported, some of
which have been synthesized in THF or Et2O.[19] It was found
that the ring-opening difluoromethylation reaction only pro-
ceeded well when the base was added after mixing 2, 4a, and
BF3·Et2O (Scheme 4), indicating the crucial influence of the pre-
organization of the three components in this reaction. Al-
though the details of the reaction mechanism need further in-
vestigation, we propose that BF3 probably holds sulfoximine 2
and the epoxide in close proximity through complexation, as
shown in A. After deprotonation of 2, the in-situ generated
carbanion should immediately attack the activated epoxide,
with a reaction rate much faster than those of its decomposi-
tion or side reaction with BF3.
Experimental Section
Preparation of N-tert-butyldimethylsilyl-S-difluoromethyl-S-
phenylsulfoximine (2)
Under N2 atmosphere, imidazole (10.2 g, 150 mmol) was added to
a solution of PhSO(NH)CF2H (9.55 g, 50 mmol) in dry DMF (100 mL)
at RT. After 5 min, the solution was cooled to 08C and TBSCl
(11.25 g, 75 mmol) was added in two portions. The mixture was al-
lowed to warm to RT and stirred, overnight. The reaction was then
quenched by adding an excess of water, and the mixture was ex-
tracted with diethyl ether. The organic phase was washed with
brine and dried over anhydrous MgSO4. It was then filtered, the
solvent was evaporated under vacuum, and the residue was sub-
jected to column chromatography on silica gel eluting with petro-
leum ether/ethyl acetate (50:1, v/v) to give 2 (13.5 g, 90%) as a col-
orless oil.
This preorganization strategy
might also be useful for the reac-
tions of epoxides with other carb-
anions of low thermal stability and
weak nucleophilicity. As a proof of
Typical procedure for the ring-opening difluoromethylation
of epoxides 4 with sulfoximine 2
concept, we set up the reaction
between
epoxide
4a
and
PhSO2CF2H (1). Previously, it was
found that when no BF3·Et2O was
Under N2 atmosphere, BF3·Et2O (0.3 mL, 2.5 mmol) was added to
a solution of (S)-2-methyloxirane (S)-4a (87 mg, 1 mmol) and sulf-
oximine (R)-2 (305 mg, 1 mmol) in THF (6 mL) at À788C. After
3 min, LiHMDS (1.0m in THF, 2.0 mL, 2 mmol) was slowly added at
À788C. After a further 30 min, aqueous HCl solution (12m, 1.5 mL,
18 mmol) was added to quench the reaction. The resulting mixture
was stirred for 30 min, basified with 20% aqueous NaOH, and then
extracted with ethyl acetate. The organic phase was washed with
brine and dried over anhydrous MgSO4. It was then filtered, the
solvent was evaporated under vacuum, and the residue was sub-
jected to column chromatography on silica gel eluting with petro-
leum ether/ethyl acetate (3:1, v/v) to give (2R, SR)-6a (191 mg,
77%) as a colorless oil.
added or when BF3·Et2O was added after the formation of
PhSO2CF2À, none of the desired product 12 was obtained.[8] In-
terestingly, by using this preorganization strategy, ring-opened
product 12 was formed in 38% yield (Scheme 9). The relatively
low yield of 12 compared to that of compound 6a (76%,
entry 6, Table S1 in the Supporting Information) might be at-
À
tributed to the relatively lower stability of PhSO2CF2 com-
À
pared with that of PhSO(NTBS)CF2 and/or the lower coordi-
nating ability of a sulfonyl group compared with a sulfoximinyl
group.
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Typical procedure for the reductive desulfoximination of
compound 6 f
Umemoto (Visiting Professor at Shanghai Institute of Organic
Chemistry) for helpful discussions.
BrCH2CH2Br (2 mL) was added to Mg chips (144 mg, 6 mmol) in dry
MeOH (2 mL) at RT. When gas evolution was observed (after about
3 min), compound 6 f (141 mg) and dry MeOH (2.5 mL) were
added. After 3 h, most of the MeOH was removed under reduced
pressure. Saturated aqueous NH4Cl solution was added and the re-
sulting mixture was extracted with diethyl ether. The organic
phase was washed with saturated aqueous NaCl and dried over an-
hydrous MgSO4. It was then filtered, the solvent was evaporated
under vacuum, and the residue was subjected to column chroma-
tography on silica gel eluting with petroleum ether/ethyl acetate
to give 7 (69 mg, 90%) as a colorless oil.
Keywords: alcohols
substitution · preorganization · sulfoximines
·
difluoromethylation
·
nucleophilic
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Preparation of compound 9
Under N2 atmosphere, BF3·Et2O (1.5 mL, 12.5 mmol) was added to
a solution of 2-phenethyloxirane (1.11 g, 7.5 mmol) and sulfoximine
2 (1.51 g, 5 mmol) in dry THF (20 mL) at À788C. After 3 min,
LiHMDS (1.0m in THF, 10 mL, 10 mmol) was slowly added at
À788C. After a further 30 min, the reaction was quenched by
adding an excess of saturated aqueous NH4Cl solution and the re-
sulting mixture was extracted with diethyl ether. The organic
phase was washed with brine and dried over anhydrous MgSO4. It
was then filtered, the solvent was evaporated under vacuum, and
the residue was subjected to column chromatography on silica gel
eluting with petroleum ether/ethyl acetate to give 9 (1.83 g, 81%)
as a colorless oil.
Preparation of compound 10 from compound 9
Under N2 atmosphere, TMSCl (143 mL, 1.125 mmol) was added to
a solution of compound 9 (335 mg, 0.74 mmol) and imidazole
(130 mg, 1.875 mmol) in dry DMF (3 mL) at RT and the mixture was
stirred for 4 h. The reaction was then quenched by adding an
excess of water, and the resulting mixture was extracted with di-
ethyl ether. The organic phase was washed with brine and dried
over anhydrous MgSO4. It was then filtered, the solvent was evapo-
rated under vacuum, and the residue was subjected to column
chromatography on silica gel eluting with petroleum ether/ethyl
acetate (PE/EA, 200:1) to give 10 (359 mg, 92%) as a colorless oil.
Preparation of compound 11 from compound 10
[7] The ring-opening reaction of 2-methyloxirane with stable C2F5Li has
been reported, see: O. Kazakova, G.-V. Rçschenthaler, in Efficient Prepa-
rations of Fluorine Compounds (Ed.: H. W. Roesky), John Wiley & Sons,
Hoboken, 2012, p. 207.
Under N2 atmosphere, LiHMDS (1m in THF, 0.3 mL, 0.3 mmol) was
added to a solution of compound 10 (105 mg, 0.2 mmol) in dry
DMF (2 mL) at 08C. The mixture was stirred at RT for 1 h, and then
aqueous HCl solution (3m, 1 mL) was added. The resulting mixture
was further stirred at RT for 1 h, and then extracted with diethyl
ether. The organic phase was washed with brine and dried over an-
hydrous MgSO4. It was then filtered, the solvent was evaporated
under vacuum, and the residue was subjected to column chroma-
tography on silica gel eluting with petroleum ether/ethyl acetate
to give 11 (34 mg, 86%) as a colorless oil.
[8] C. Ni, Y. Li, J. Hu, J. Org. Chem. 2006, 71, 6829.
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Acknowledgements
Support of our work by the National Basic Research Program
of China (2012CB215500 and 2012CB821600), the NNSFC
(21372246), the Shanghai QMX program (13QH1402400), the
Chinese Academy of Sciences, and the Syngenta PhD Student-
ship (to X.S.) is gratefully acknowledged. We thank Prof. Teruo
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doret, J.-C. Blazejewski, E. Magnier, Eur. J. Org. Chem. 2011, 4862;
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[15] After quenching the reaction with aqueous NH4Cl, the peaks at d=
À111.30–111.38 ppm disappeared and compound 2 was recovered in
44% yield.
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À
[16] (EtO)2P(O)CF2BF3 Li+ was reported to be the main product of the reac-
tion of (EtO)2P(O)CF2Li with 2-methyloxirane (4a) in the presence of
BF3·Et2O, see ref. [6c].
[17] 13C NMR and 1H NMR experiments showed that the epoxide 4a did not
decompose after the addition BF3·Et2O at À708C in THF; see the Sup-
porting Information.
Received: March 7, 2014
Published online on && &&, 0000
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FULL PAPER
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Fluoroalkylation
X. Shen, Q. Liu, T. Luo, J. Hu*
&& – &&
Nucleophilic Difluoromethylation of
Epoxides with PhSO(NTBS)CF2H by
a Preorganization Strategy
New preorganization strategy: Preor-
ganization of difluoromethyl sulfoximine
and epoxide with BF3 has been found
to facilitate the success of the title nu-
cleophilic difluoromethylation. The reac-
tion shows excellent regioselectivity and
a broad substrate scope. The facile
transformation of the ring-opened prod-
ucts to b-difluoromethyl, g-difluoro-
methyl, and b-difluoromethylenyl alco-
hols (see scheme) demonstrates the
synthetic utility of the reaction.
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
7
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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These are not the final page numbers! ÞÞ