Metal-free ring-opening of epoxides with potassium trifluoroborates

Article abstract of DOI:10.1039/c3cc47360k

The ring-opening of epoxides with potassium trifluoroborates proceeds smoothly in the presence of trifluoroacetic anhydride under metal-free conditions. The reactions are regioselective and afford a single diastereomer. Both electron-rich and electron-poor aryltrifluoroborates are tolerated.

Full text of DOI:10.1039/c3cc47360k

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Metal-free ring-opening of epoxides with
potassium trifluoroborates†
Cite this: Chem. Commun., 2014,
50, 454
Silvia Roscales and Aurelio G. Csaky*
´
¨
Received 26th September 2013,
Accepted 1st November 2013
DOI: 10.1039/c3cc47360k
www.rsc.org/chemcomm
The ring-opening of epoxides with potassium trifluoroborates pro-
Herein, we report our initial studies towards the ring-opening
ceeds smoothly in the presence of trifluoroacetic anhydride under of epoxides with potassium aryl- and alkenyltrifluoroborates under
metal-free conditions. The reactions are regioselective and afford a metal-free conditions to afford the corresponding 2-arylethanols or
single diastereomer. Both electron-rich and electron-poor aryltri- homoallylic alcohols, respectively. Under optimum conditions,
fluoroborates are tolerated.
these reactions are promoted by trifluoroacetic anhydride (TFAA),
and they are completely regioselective (eqn (1)), giving rise to the
Epoxides are one of the essential functional groups in organic formation of a single diastereomer with retention of the configu-
chemistry, readily accessible from alkenes and from carbonyl ration at the reacting centre of the epoxide.
compounds. The strained ring system of this class of ethers
confers a distinctive type of reactivity which makes them highly
(1)
versatile as synthetic intermediates.1 Regioselective and stereo-
defined ring-opening reactions performed using nucleophiles
3-Arylglycidates were chosen as initial substrates because of
their easy availability9,10 and proven utility as electrophiles in
ring-opening reactions with electron-rich arenes.11,12 On the
basis of recent studies on conjugate addition reactions of
alkenylboronic acids catalyzed by acylating reagents,13 we first
examined the reaction of trans ethyl 3-phenylglycidate (1a) and
(E)-styrenylboronic acid (2) in the presence of AcCl or TFAA
(eqn (2)). However, no reaction was observed.
are some of the most characteristic transformations, useful in
the synthesis of a wide variety of alcohols. With regard to the use
of carbon nucleophiles, reported examples have been limited to
the use of stabilized carbanions, strong organometallic reagents,
and p-rich aromatics.2 Boronic acids3 and potassium trifluoro-
borates4 are important reagents for the synthesis of complex
molecules due to their low toxicity, thermal stability, and wide
compatibility with functional groups. Many of these compounds
are commercially available, and an ample variety of synthetic
methods have been developed for their preparation. Due to the
relatively low nucleophilicity of these aryl- and alkenylboron
compounds, most of their reactions are catalyzed by transition
metal complexes. Comparatively, synthetic transformations under
metal-free conditions remain scarce and have been limited to
Mannich-type reactions,5 conjugate additions,6 and reactions with
oxonium cations.7 The finding of reaction conditions which could
enable the ring-opening of epoxides with these boron-based
carbon nucleophiles under metal-free conditions, an unprece-
dented reaction,8 would be a highly attractive addendum to the
synthetic arsenal.
(2)
Instituto Pluridisciplinar, Universidad Complutense, Campus de Excelencia
Internacional Moncloa, 28040-Madrid, Spain. E-mail: csaky@ucm.es;
Tel: +34 913943280
In light of these results, we switched to the more nucleophilic
potassium (E)-styrenyltrifluoroborate (3a).14 We were pleased to
find that in TFAA-promotion, the ring-opening reaction took place
regioselectively by the addition of the styrenyl moiety at the
b-position of the glycidic epoxide in a completely stereocontrolled
† Electronic supplementary information (ESI) available: Synthesis of starting
materials, experimental details and characterization data. See DOI: 10.1039/
c3cc47360k
454 | Chem. Commun., 2014, 50, 454--456
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Table 1 Ring-opening of trans and cis ethyl 3-phenylglycidates with
phenyltrifluoroborate (Table 1, entry 4), an electron-rich aryltri-
fluoroborate (Table 1, entry 5) and aryltrifluoroborates endowed
with electron-withdrawing substituents (Table 1, entries 6 and 7)
performed well in the ring-opening reaction. This is in sharp
contrast to the Friedel–Crafts type ring opening of epoxides, a
process which gives rise to similar products, but is limited only
to electron-rich aromatics.11,12 Only one diastereomer (4-I) was
obtained in all cases (Table 1, entries 1–7). On the other hand, the
reactions of cis ethyl 3-phenylglycidate (1b) (Table 1, entries 8–10)
afforded exclusively diastereomers 4-II. Again, this behavior is
different to the Friedel–Crafts type ring-opening of epoxides,
which is well known to give rise to mixtures of diastereomers.11,12
Secondly, we extended the results to other epoxides and repre-
sentative trifluoroborates (Table 2). We observed that other 3-aryl-
glycidates with either electron-releasing or electron-withdrawing
substituents on the aryl moiety (Table 2, entries 1–4) were also good
substrates. Additionally, the reaction allowed the construction of
various trifluoroboratesa
Entry 1 R-BF3K (2)
Product (3)
Yieldb (%)
82
1
1a
(3b)
(4b-I)
2
1a
71
(3c)
(4c-I)
3
4
1a
78
76
(3d)
(4d-I)
1a Ph-BF3K (3e)
Table 2 Ring-opening of various epoxides with representative trifluoroboratesa
(4e)
5
6
7
1a
79
81
82
(3f)
(4f-I)
1a
1a
1b
(3g)
Entry Epoxide (5)
3
6 (% yield)b
(4g-I)
1
3f
(3h)
(5a)
(5a)
(4h-I)
(6a, 70)
8
80
83
75
(3a)
(4a-II)
2
3
4
3a
3a
3a
9
1b
1b
(3b)
(4b-II)
(6b, 74)
10
(3c)
(4c-II)
(5b)
a
Reaction conditions: epoxide (1.0 equiv.), R-BF3K (1.25 equiv.), TFAA
(6c, 78)
(6d, 80)
(0.5 equiv.), CH2Cl2 (6 mL mmolÀ1 epoxide), rt, 3 h. Isolated yield
obtained after column chromatography.
b
fashion to give the (2RS,3SR) product 4a-I exclusively. After some
optimization of the reaction parameters (eqn (2)), we found that the
use of a slight excess of the boron nucleophile (1.25 equiv.) together
with a substoichiometric amount of TFAA (0.5 equiv.) in CH2Cl2
solution at rt were optimal conditions for this transformation.15 On
the other hand, no addition was observed with 3 when Ac2O was
used as a promoter, and in the presence of BF3OEt2 at 0 1C, the
ring-opening reaction took place only with very modest yield.
In order to investigate the scope of this transformation, first we
examined the ring-opening of trans and cis ethyl 3-phenylglycidates
(1a and 1b) with different potassium trifluoroborates (Table 1). We
observed that this reaction could be extended to other alkenyltri-
fluoroborates with preservation of the CQC bond geometry of the
nucleophile (Table 1, entries 1 and 2).
(5c)
5
6
7
3a
3a
3a
(5d)c
(6e, 78)d
(6f, 65)
(5e)
—
—
(5f)
(5g)
8
9
3a
3a
(6g, 52)
(5h)
a
Reaction conditions: epoxide (1.0 equiv.), R-BF3K (1.25 equiv.), TFAA
The reaction also included substitution at the a-carbon of
the alkenyltrifluoroborate (Table 1, entry 3). Furthermore, the
process was not restricted to alkenyltrifluoroborates, as potassium epoxides. 1 : 1 mixture of syn and anti diastereomers.
(0.5 equiv.), CH2Cl2 (6 mL mmolÀ1 epoxide), rt, 3 h. Isolated yield
b
c
obtained after column chromatography. 1 : 1 mixture of cis and trans
d
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tertiary stereocentres (Table 2, entry 5). A similar result to that for Notes and references
esters was obtained with an a,b-epoxyketone (Table 2, entry 6).
1 For reviews, see: (a) Aziridines and Epoxides in Organic Synthesis, ed. A. Yudin,
Wiley-VCH, Weinheim, 2006; (b) J. B. Johson, Sci. Synth., 2011, 3, 759.
2 For reviews, see: (a) J. G. Smith, Synthesis, 1984, 629; (b) M. Pineschi,
Eur. J. Org. Chem., 2006, 4979.
3 Boronic Acids: Preparation and Applications in Organic Synthesis,
Medicine and Materials, ed. D. G. Hall, Wiley-VCH, Weinheim, 2011.
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(b) S. Darses and J.-P. Genet, Chem. Rev., 2008, 108, 288; (c) G. A. Molander
However, no reaction was observed for a b-unsubstituted-a,b-
epoxyester (Table 2, entry 7). Apart from a,b-epoxycarbonyl com-
pounds, we tested other types of synthetically relevant epoxides.
Thus, we observed that the reaction did not work for styrene oxide
(Table 2, entry 8).16 Finally, the reaction with the phenyl ether of
glycidol17 afforded the ring-opening reaction products which
resulted from the attack to the less hindered position (Table 2,
entry 9).
The stereochemistry of compounds 4 was determined by
transformation of 4b-I and 4b-II respectively, into the cyclic
derivatives18 7-I and 7-II (eqn (3)), and by comparison of the
NMR data of 6a with those previously reported for the anti
diastereomer.12 Assignments for the other products are based
on analogy.
´
and L. Jean-Gerard, Boronic Acids: Preparation and Applications in Organic
Synthesis, Medicine and Materials, ed. D. G. Hall, Wiley-VCH, Weinheim,
2011, vol. 2, p. 507.
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(3)
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8 For other reactions of trifluoroborates with epoxides, see: (a) C. Che and
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9 T. Rosen, Comprehensive Organic Synthesis, ed. B. M. Trost, I. Fleming
and C. H. Heathcock, Pergamon, Oxford, 1991, vol. 2, p. 409.
10 All compounds used were racemic.
To account for these results, we suggest the transient formation
of an organodifluoroborane19,20 by the reaction of the starting
potassium trifluoroborate with TFAA.21 As exemplified for a trans-
epoxide (eqn (4)), coordination of the highly electrophilic boron of
this newly generated species to the oxygen of the epoxide would
enable the operation of a borderline SNi type mechanism, favoring
the transfer of the carbon backbone of the starting trifluoroborate
to the most electrophilic position of the epoxide with retention of
configuration.22,23 This proposal encompasses both the regio- and
stereochemical experimental observations.24
11 (a) J. H. van der Westhuizen, D. Ferreira and D. G. Roux, J. Chem. Soc., Perkin
Trans. 1, 1980, 2856; (b) R. F. C. Brown, W. R. Jackson, T. D. McCarthy and
G. D. Fallon, Aust. J. Chem., 1992, 45, 1833; (c) F. Bertolini, P. Crotti,
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12 D. Wilcke and T. Bach, Org. Biomol. Chem., 2012, 10, 6498.
´
´
13 (a) S. Roscales, A. Rincon, E. Buxaderas and A. G. Csak¨y, Tetrahedron Lett.,
´
2012, 53, 4721; (b) S. Roscales and A. G. Csak¨y, Org. Lett., 2012, 14, 1187.
(4)
14 G. Berionni, V. Morozova, M. Heiniger, P. Mayer, P. Knochel and
H. Mayr, J. Am. Chem. Soc., 2013, 135, 6317.
15 Variable ratios of mono- and bis-trifluoroacylated 1,2-diols were
obtained as subproducts.
16 A mixture of mono- and bis-trifluoroacylated 1-phenyl-1,2-ethanediols
were obtained as the only reaction products.
´
´
`
17 (a) R. Marcos, C. Rodrıguez-Escrich, C. I. Herrerıas and M. Pericas, J. Am.
Chem. Soc., 2008, 130, 16838. For a review, see: (b) R. M. Hanson, Chem.
Rev., 1991, 91, 437.
In summary, we have developed the ring-opening of epoxides
with potassium aryl- and alkenyltrifluoroborates in the presence
of trifluoroacetic anhydride (TFAA) under metal-free conditions, 18 S. D. Burke, R. A. Ng, J. A. Morrison and M. J. Alberti, J. Org. Chem.,
1998, 63, 3160.
following a very simple experimental procedure. The reaction is
highly regioselective, thus allowing for the synthesis of either syn
19 For the generation of organodifluoroboranes using a variety of Lewis acids,
see: R. A. Batey, A. N. Thadani, D. V. Smil and A. J. Lough, Synthesis, 2000, 990.
or anti 2-arylethanols or homoallylic alcohols starting from trans 20 Styrene was detected as a subproduct in the reactions using 3a. This
may arise from protodeborylation of the RBF2 intermediate upon
TFA formation in work-up.
21 To the best of our knowledge, this is the first example of TFAA being
or cis epoxides. In the case of alkenyltrifluoroborates, the E- or
Z-stereochemistry of the CQC bond is preserved. In the case of
aryltrifluoroborates, the use of either electron-poor or electron-
rich compounds is well tolerated. Further studies toward enhan-
cing the scope of the reaction to other epoxides will be reported
in due course.
We thank grant CTQ-2010-16170 from the Spanish govern-
ment (MICINN). S. Roscales is thankful to the government of
Spain and for FPU predoctoral grant No. AP20090051.
utilized as a fluorophile.
22 R. E. Parker and N. C. Isaacs, Chem. Rev., 1959, 59, 737.
23 For the ring-opening of epoxides by thiols with retention of configu-
ration at the reaction center, see: A. Schwartz, P. B. Madan, E. Mohacsi,
J. P. O’Brien, L. J. Todaro and D. L. Coffen, J. Org. Chem., 1992, 57, 851.
24 Independent essays carried out with 3a and the mono- or bis-
trifluoromethylated derivatives of 2,3-dihydroxy-3-phenyl-propionic
acid ethyl ester in the presence or absence of TFAA put forward that
these were not intermediates in the formation of 4a-I.
456 | Chem. Commun., 2014, 50, 454--456
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