Reactions of CF3-substituted boranes with α-diazocarbonyl compounds

Article abstract of DOI:10.1016/j.tetlet.2011.07.141

Boranes substituted with a CF₃-group can be generated from methyl boronic esters RB(OMe)₂ and Me₃SiCF₃/KF followed by treatment with Me₃SiCl. These boranes are stable only in coordinating solvents, and due to the increased Lewis acidity of boron, react rapidly with α-diazocarbonyl compounds to give the products of transfer of the organic group from boron. Alkyl, aryl, vinyl, and alkynyl boronic esters can be used in this reaction.

Full text of DOI:10.1016/j.tetlet.2011.07.141

Tetrahedron Letters 52 (2011) 5259–5263
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Reactions of CF3-substituted boranes with
a-diazocarbonyl compounds
Pavel K. Elkin a, Vitalij V. Levin a, Alexander D. Dilman a, , Marina I. Struchkova a, Pavel A. Belyakov a,
⇑
Dmitry E. Arkhipov b, Alexander A. Korlyukov b, Vladimir A. Tartakovsky a
a N.D. Zelinsky Institute of Organic Chemistry, Leninsky Prosp. 47, 119991 Moscow, Russian Federation
b A.N. Nesmeyanov Institute of Organoelement Compounds, Vavilov Str. 28, 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Boranes substituted with a CF3-group can be generated from methyl boronic esters RB(OMe)2 and
Me3SiCF3/KF followed by treatment with Me3SiCl. These boranes are stable only in coordinating solvents,
and due to the increased Lewis acidity of boron, react rapidly with a-diazocarbonyl compounds to give
the products of transfer of the organic group from boron. Alkyl, aryl, vinyl, and alkynyl boronic esters
can be used in this reaction.
Received 2 June 2011
Revised 14 July 2011
Accepted 29 July 2011
Available online 6 August 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Trifluoromethylation
Boranes
Boronic esters
Diazocarbonyl compounds
The reaction of organoboranes with diazo compounds consti-
tutes an attractive process for C–C bond formation. Though discov-
ered more than forty years ago,1 only in recent times has this
transformation begun evolving into an efficient synthetic method.2,3
The reaction mechanism involves the equilibration of a borane
with a diazo group to generate zwitterionic intermediate A which
undergoes migration of a substituent from boron accompanied by
competing transfer of chlorine with the formation of chloroketones
was observed.4
It is well known that the Lewis acidity of boron can be increased
dramatically by the introduction of perfluorinated substituents,
and pentafluorophenyl boranes have been employed extensively
as Lewis acids.5 We reasoned that a perfluoroalkyl group would
exert an even stronger electron-depleting effect.6 Herein we report
on the generation of the CF3-substituted boranes7 and their subse-
the elimination of nitrogen (Scheme 1). The a-boryl carbonyl com-
pound then readily tautomerizes to a boron enol ether, and the lat-
quent reactions with a-diazocarbonyl compounds.
ter is hydrolyzed on work-up to give the product.
In order to introduce the trifluoromethyl group, methyl boronic
ester 1a was treated with Me3SiCF3 and potassium fluoride in 1,2-
dimethoxyethane (DME) at room temperature8,9 (Eq. 1). The corre-
sponding borate 2a was isolated and its structure verified by NMR
spectroscopy and X-ray analysis (Fig. 1).10 This salt was an air
-stable solid, which was stored in a tightly closed flask at room
temperature for several months without any noticeable changes,
and it could be safely handled in air.
The efficiency of this reaction depends strongly on the ease of
formation of species A, and therefore, the Lewis acidity of boron
is an important factor. Thus, the reaction works well with trialkyl
boranes,1 but only one group is used. The use of aryl-BBN has re-
cently been reported for the transfer of an aryl group, but for some
diazo compounds migration of a borabicyclononane ring was ob-
served.3 On the other hand, conventional boronic acids and their
esters, in which two oxygen atoms decrease the boron Lewis acid-
ity, typically do not couple with diazoesters. However, recently, an
example involving the reaction of excess 4-methoxyphenylboronic
acid at 110 °C with ethyl diazoacetate was described.2a In another
report, more reactive boroxines taken in stoichiometric amount
(3 equiv of organic group) were employed at elevated tempera-
tures (60–100 °C). Furthermore, the latter process was applied only
for aryl and vinyl boroxines.2b In earlier publications, aryl- and
alkyldichloroboranes were exploited at low temperatures, but
Me3SiCF3 (1.25 equiv)
KF (1.0 equiv)
OMe
OMe
B
OMe
Ph
Ph
1a
B
ð1Þ
ð2Þ
CF3
OMe
DME, 18 h, rt
K
2a 97%
solvent
OMe
Me3SiCl
solvent
– Me3SiOMe, KCl
2a
Ph
3a
B
dec.
CF3
solvent
⇑
Corresponding author. Fax: +7 499 1355328.
E-mail address: adil25@mail.ru (A.D. Dilman).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.07.141

5260
P. K. Elkin et al. / Tetrahedron Letters 52 (2011) 5259–5263
When borate 2a was treated with chlorotrimethylsilane in
nate borane may be associated with the facile generation of
difluorocarbene.11
donating solvents such as acetonitrile, DME or THF, complex 3a
was formed, which could be identified in solution by 1H, 13C, 19F,
and 11B NMR spectroscopy (Eq. 2). However, concentration of the
solution under vacuum, which was expected to cause decomplex-
ation of the solvent molecule, led to decomposition. A similar
intractable mixture was observed on treatment of salt 2a with Me3-
SiCl in non-coordinating CDCl3. Decomposition of the three-coordi-
The solution of 3a in donating solvents was treated with ethyl
diazoacetate (EDA, 1.1 equiv) under various conditions (Table 1).
The evolution of nitrogen gas was typically observed at tempera-
tures between ꢀ20 and 0 °C, and the mixture was kept for an addi-
tional one hour at room temperature. Though the starting
compounds were consumed, only complex mixtures were formed
after aqueous work-up (entries 1–5). We surmised that the initially
formed boron ketene acetal 4 containing both an electron-rich
double bond and a Lewis acidic boron center could readily decom-
pose. It was rewarding to find that simple addition of a stoichiom-
etric amount of methanol (1.1 equiv) prior to the diazo ester
afforded ethyl phenylacetate (5a) as the sole product (entry 7). It
is believed that methanol rapidly protonates species 4 preventing
its decomposition. The reaction of 2a with Me3SiCl and EDA/MeOH
proceeded well in 1,2-dimethoxyethane, the same solvent used for
the formation of starting 2a, hence isolation of the borate salt was
not necessary.
N2
R2
N2
BY2
Y
Y
R1
B
Y
H
O
+
O
O
Y
B
R1
R1 R2
A
R2
OBY2
O
R1
R1
R2
R2
It is worthy of note that of the two organic substituents on bor-
on (Ph and CF3), only the phenyl group undergoes migration. This
phenomenon is in accord with the previously reported decrease
in the migratory aptitude of a fluorinated group from boron.12
Besides methyl boronic ester, other esters were subjected to tri-
fluoromethylation followed by the reaction with EDA (Table 2). Tri-
fluoromethylation of neopentyl glycol and pinacol esters was
noticeably slower, and the decreased yields of 5a were due to
incomplete conversion during the formation of salt 2. With cate-
chol ester, again the trifluoromethylation step was problematic,
affording a complex mixture. Reactions of the trifluoroborate salt,
PhBF3K, which upon treatment with Me3SiCl generated dif-
luorophenylborane,13 gave under various conditions less than
10% of the product. Methyl boronic esters proved to be superior
substrates, and they were used for further studies.
Scheme 1.
While methyl esters can be obtained from widely available
boronic acids, we encountered a practical problem at this point.
Since some methyl boronic esters are sensitive to chromatography
and even to moisture present in the air, they have to be prepared
on large scale and purified by distillation. Moreover, for some boro-
Figure 1. X-ray structure of salt 2a (thermal ellipsoids at 50% probability, ORTEP
drawing). The potassium cation is omitted for clarity.
Table 1
Reaction of borate 2a with EDA
Table 2
Variation of the boronic ester
O
N2
OMe
OMe
B
solvent
OMe
B
CF3
Me3SiCl
solvent
OEt
conditions
additive
OR
Ph
2a
Ph
3a
i
ii
OR
Ph
B
CF3
Ph B(OR)2
K
Ph
CO2Et
time
CF3
2
1
5a
K
(– solvent)
i: Me3SiCF3, KF, DME, rt
ii: Me3SiCl, EDA, MeOH, DME
CF3
MeO
N2
B
O
MeO
O
Ph
5a
CO2Et
C
B
F3
Ph
aqueous
work-up
Ph OEt
OEt
4
Entry
1
Substrate
Time
Yield of 5a (%)a
O
Entry
Solvent
Temp.
rt
ꢀ25 °C?rt
Additive
Yield of 5a (%)
Ph
B
18 h
18 h
60
O
O
a
a
a
a
a
1
2
3
4
5
6
7
MeCN
DME
DME
DME
Et2O
THF
—
—
—
—
—
MeOH
MeOH
Ph
Ph
B
B
2
33
ꢀ60?ꢀ10 °C
ꢀ20 °C?rt
ꢀ20 °C?rt
ꢀ20 °C?rt
ꢀ20 °C?rt
O
O
82b
93c
3
4
12 h
—
<10
<10
O
DME
PhBF3Kb
a
b
c
Complex mixture.
NMR yield.
Isolated yield.
Determined by 1H NMR spectroscopy of the crude material.
The trifluoroborate salt was used instead of salt 2.
a
b

P. K. Elkin et al. / Tetrahedron Letters 52 (2011) 5259–5263
5261
nic acids (e.g., 4-iodophenylboronic acid), Brown’s procedure with
methanol/hexane14 was found to be inapplicable. We proposed an-
other protocol for generation of the methyl esters. Thus, the ester-
ification of phenylboronic acid with trimethyl orthoformate was
effected in the presence of catalytic amounts of trifluoroacetic acid
Substrates with the boron attached to sp3, sp2, or sp carbon
atoms reacted successfully with EDA. Importantly, alkyl boronates
gave good yields of products (entries 1–3). Of particular note is that
the reaction proceeded when using a boronic ester containing a ke-
tone group (entry 6), which suggests that nucleophilic trifluorom-
ethylation at boron proceeds faster.15 Vinyl boronates were also
coupled with EDA (entries 7 and 8), though in the case of boronate
1i, the desired product 5i was accompanied by a small amount of
by-product 5ii (entry 8, shown in parentheses). The latter sub-
stance may originate either during protonation of the intermediate
boron enol ether, or upon isomerization of the product on work-up.
Bromo-substituted boronate 1h also underwent the reaction point-
ing to the stability of the intermediate borate salt.
When 3-bromopropylboronic ester (1k) was subjected to stan-
dard conditions, a complex mixture was formed containing 9% of
MeO-substituted product 5k along with another species bearing
an unreacted CH2B fragment (Scheme 2). It seems likely that in this
case, formation of borate salt 2k was accompanied by intramolec-
ular displacement of the bromine by the methoxy group at a rate
comparable to the formation of 2k, leading to borane 3k.16 With
chlorinated derivative 1l the expected product 5l was produced
in 43% yield; this reflects the poorer leaving group ability of chlo-
rine compared to bromine.
(10 lL per 1 mmol of boronic acid). The esterification was com-
plete within 15 min, and subsequent evaporation of volatile mate-
rials under vacuum gave the pure boronic ester in quantitative
yield (Eq. 3). The methyl ester obtained was suitable for further
transformations, and this procedure was interchangeable with that
using presynthesized material.
i
PhB(OH)2
PhB(OMe)2
Ph
CO2Et
rt, 15 min
ð3Þ
1a
5a 93%
i: CH(OMe)3 (2.5 equiv), cat. CF3CO2H
A variety of boronic esters 1 were employed in the coupling
reaction with EDA under optimized conditions. After the trifluo-
romethylation in 1,2-dimethoxyethane, simple addition of chloro-
trimethylsilane followed by methanol and EDA, and brief stirring at
room temperature gave product 5 (Table 3).
Table 3
Reactions of boronic esters 1
i-iii
R
B(OMe)2
R
CO2Et
5
1
i: Me3SiCF3 (1.25 equiv), KF (1.0 equiv), DME, rt, 18 h
ii: Me3SiCl (1.0 equiv), -20 → -10 °C, 20 min
iii: MeOH (1.1 equiv), EDA (1.1 equiv), -20 → 0 °C, 1 h; rt 1 h
Entry
Boronate
Product
Yield (%)a
B(OMe)2
B(OMe)2
1
2
1b
5b
5c
79
70
Ph
Ph
CO2Et
Ph
Ph
B(OMe)2
1c
CO2Et
CO2Et
3
4
1d
5d
5e
80
85
CO2Et
1eb
1f
I
B(OMe)2
I
B(OMe)2
5
5f
83
63
CO2Et
O
O
CO2Et
6
7
1g
5g
B(OMe)2
S
S
Br
Br
1hb
5h
5i
75
72
B(OMe)2
Ph
Ph
Ph
Ph
CO2Et
CO2Et
B(OMe)2
8
1i
1j
5ii
5j
(12)c
73
CO2Et
CO2Et
Ph
Ph
Ph
B(OMe)2
9
a
b
c
Isolated yield.
The boronic ester was obtained from boronic acid using trimethyl orthoformate.
Ethyl (2E)-3-phenylbut-2-enoate (5ii) was obtained as a by-product.

5262
P. K. Elkin et al. / Tetrahedron Letters 52 (2011) 5259–5263
X = Br
X = Cl
this particular case the intermediate boron enol ether is suffi-
ciently stable.
In summary, we have demonstrated that boranes possessing tri-
fluoromethyl, methoxy and various organic groups can be readily
generated starting from the methyl boronic esters and Me3SiCF3.
These boranes are stable only in donating solvents, and due to
CO2Et
MeO
Cl
5k 9%
i
X
B(OMe)2
1k, X = Br
CO2Et
5l 43%
1l, X = Cl
the increased Lewis acidity of boron, react with
a-diazocarbonyl
i: Me3SiCF3, KF; Me3SiCl; MeOH, EDA
compounds under very mild conditions.17
MeO
Acknowledgments
MeO
CF3
solvent
OMe
B
CF3
B
solvent
EDA
MeO
5k
This work was supported by the Russian Foundation for Basic
Research (project 11-03-00362), the Ministry of Science (project
MD-1151.2011.3), the Russian Academy of Sciences (program
#7), and the Federal program ‘‘Scientific and Educational Personnel
of Innovative Russia’’.
Br
K
3k
Scheme 2.
2k
Table 4
Supplementary data
Reaction of borate salt 2a with various diazocarbonyl compounds
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.07.141.
O
O
OMe
OMe
B
Me3SiX, MeOH
Ph
R2
N2
Ph
2a
R2
+
R1
CF3
R1
References and notes
-20 → -10 °C, 1 h;
then rt, time
K
6
7
1. (a) Hooz, J.; Linke, S. J. Am. Chem. Soc. 1968, 90, 5936–5937; (b) Hooz, J.; Linke,
S. J. Am. Chem. Soc. 1968, 90, 6891–6892; (c) Hooz, J.; Gunn, D. M. Tetrahedron
Lett. 1969, 10, 3455–3458; (d) Hooz, J.; Gunn, D. M. J. Am. Chem. Soc. 1969, 91,
6195–6196.
2. (a) Barluenga, J.; Tomas-Gamasa, M.; Aznar, F.; Valdes, C. Nat. Chem. 2009, 1,
494–499; (b) Peng, C.; Zhang, W.; Yan, G.; Wang, J. Org. Lett. 2009, 11, 1667–
1670.
Entry
X
Time Product
Yield
(%)a
Ad
N2
3. Luan, Y.; Schaus, S. E. Org. Lett. 2011, 13, 2510–2513.
Ph
7a
80
4. (a) Hooz, J.; Bridson, J. N.; Calzada, J. G.; Brown, H. C.; Midland, M. M.; Levy, A. B.
J. Org. Chem. 1973, 38, 2574–2576; (b) Brown, H. C.; Midland, M. M.; Levy, A. B.
J. Am. Chem. Soc. 1972, 94, 3662–3664.
5. (a) Piers, W. E.; Chivers, T. Chem. Soc. Rev. 1997, 26, 345–354; (b) Piers, W. E.
Adv. Organomet. Chem. 2004, 52, 1–76; (c) Ishihara, K.; Yamamoto, H. Eur. J. Org.
Chem. 1999, 527–538; (d) Chivers, T. J. Fluorine Chem. 2002, 115, 1–8; (e)
Stephan, D. W.; Erker, G. Angew. Chem., Int. Ed. 2010, 49, 46–76.
6. For calculated fluoride ion affinities of various perfluorinated boranes, see: (a)
Abo-Amer, A.; Frohn, H.-J.; Steinberg, C.; Westphal, U. J. Fluorine Chem. 2006,
O
1
6a Cl
12 h
O
Ad
7aa (9)b
Cl
O
Ad
N2
Ph
2
3
6a OTf 12 h
6b OTf 2 h
7a
7b
70
85
O
O
127, 1311–1323; For
a recent review on perfluorinated boranes, see: (b)
O
Adonin, N. Yu.; Bardin, V. V. Russ. Chem. Rev. 2010, 79, 757–785.
7. For reviews on CF3-substituted boranes, see: (a) Pawelke, G.; Bürger, H. Appl.
Organomet. Chem. 1996, 10, 147–174; (b) Finze, M.; Bernhardt, E.; Willner, H.
Angew. Chem., Int. Ed. 2007, 46, 9180–9196.
8. An analogous reaction of B(OMe)3 with Me3SiCF3/KF has been reported, see: (a)
Molander, G. A.; Hoag, B. P. Organometallics 2003, 22, 3313–3315; (b)
Kolomeitsev, A. A.; Kadyrov, A. A.; Szczepkowska-Sztolcman, J.; Milewska,
M.; Koroniak, H.; Bissky, G.; Barten, J. A.; Röschenthaler, G.-V. Tetrahedron Lett.
2003, 44, 8273–8277.
O
N2
Ph
Ph
O
Ph
O
4
5
6c Cl
2 h
7c
7c
65
N2
N2
Ph
Ph
O
O
6c OTf 2 h
60c
O
O
9. For recent applications of KCF3B(OMe)3, see: (a) Levin, V. V.; Dilman, A. D.;
Belyakov, P. A.; Struchkova, M. I.; Tartakovsky, V. A. Tetrahedron Lett. 2011, 52,
281–284; (b) Knauber, T.; Arikan, F.; Röschenthaler, G.-V.; Gooßen, L. J. Chem.
Eur. J. 2011, 17, 2689–2697.
6d
6d Cl
12 h
7d
60
N2
Ph
EtO
EtO
10. The crystal of 2a (C9H11BF3KO2) was monoclinic at 120 K, space group P21/c,
a
b
c
Isolated yield unless mentioned otherwise.
a = 13.289(3), b = 6.8369(14), c = 12.765(3) Å, b = 102.833(4)°, V = 1130.8(4) Å3,
(1-Adamantyl)chloromethyl ketone (7aa) was formed as a by-product.
Z = 4, M = 258.09, dcalc = 1.516 g cmꢀ3 ) = 0.490 cmꢀ1, F(0 0 0) = 528.
, l(MoKa
Determined by 1H NMR spectroscopy.
10030 reflections were collected using a Smart 1000 diffractometer, 2470
d
reflections were unique. R1 = 0.0604 was calculated against F2 for 1629
No methanol was added.
reflections with I >2r(I). Crystallographic data (excluding structure factors)
have been deposited with the Cambridge Crystallographic Data Centre (CCDC
827611) and are available free of charge on application from the CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (Fax: +44(0)-1223-336033 or e-mail:
deposit@ccdc.cam.ca.uk).
Variation of the diazocarbonyl partner in reactions with borate
salt 2a is presented in Table 4. In reactions of diazoketones under
typical conditions, the formation of small amounts of -chloroke-
11. Such a decomposition pattern is typical for highly Lewis acidic CF3-substituted
a
boranes. For
a discussion, see Ref. 7b On the other hand, analogous
tones occurred, which proved difficult to separate from the desired
products (entry 1). Apparently, this by-product is produced upon
protonation of diazoketones with methanol complexed with the
CF3-substituted borane followed by a chloride anion attack. The
dimethylamino boranes Alk-B(CF3)NMe2 and (CF3)2NAlk2 have been well-
characterized in the individual state, see: (a) Brauer, D. J.; Bürger, H.; Dittmar,
T.; Pawelke, G. J. Organomet. Chem. 1995, 493, 167–173; (b) Bürger, H.;
Grunwald, M.; Pawelke, G. J. Fluorine Chem. 1986, 31, 89–98.
12. (a) Stoddard, J. M.; Shea, K. J. Organometallics 2003, 22, 1124–1131; (b)
Stoddard, J. M.; Shea, K. J. Thermochim. Acta 2004, 424, 149–155.
13. Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.; Schrimpf, M. R. J. Org. Chem.
1995, 60, 3020–3027.
14. Brown, H. C.; Bhat, N. G.; Somayaji, V. Organometallics 1983, 2, 1311–1316.
15. In the crude sample no product arising from trifluoromethylation of the
carbonyl group was detected.
formation of
a-chloroketones can be avoided by using a silyl tri-
flate instead of chlorotrimethylsilane. Reaction with ethyl
a-diazo-
propionate (6d) gave a complex mixture. However, a reasonable
yield of the product could be obtained by performing the reaction
without methanol (entry 6). This observation may signify that in

P. K. Elkin et al. / Tetrahedron Letters 52 (2011) 5259–5263
5263
16. The boronic ester 1k itself can interact with KF which complicates the reaction
mixture. Indeed, stirring 1k with KF in 1,2-dimethoxyethane for 18 h gave a
milky suspension; 1H and 19F NMR spectra showed the formation of several
unidentified products.
General procedure for the synthesis of methyl boronic esters. TFA (10
l
L) was
added to a mixture of boronic acid (1.0 mmol) and trimethyl orthoformate
(273 L, 2.5 mmol) and the resulting mixture stirred vigorously at room
l
temperature for 15 min. The volatile materials were evaporated under vacuum
to give virtually pure methyl boronic esters, which could be used in
trifluoromethylation reactions and reactions with EDA.
17. General procedure for the trifluoromethylation of boronates and subsequent
reaction with EDA. KF (58.1 mg, 1.0 mmol) and Me3SiCF3 (148 lL, 1.25 mmol)
were added to a solution of boronate 1 (1.0 mmol) in 1,2-DME (1.5 mL), and
General procedure for the reactions of borate 2a with diazo compounds 6. TMSCl
the mixture stirred overnight at room temperature. The mixture was cooled to
(140 lL, 1.1 mmol) or TMSOTf (200 lL, 1.1 mmol) was added to a solution of
ꢀ20 °C, TMSCl (128
allowed to warm to ꢀ10 °C over 20 min. The mixture was again cooled to
L, 1.1 mmol) and EDA (116 L, 1.1 mmol) were added, and
the temperature was allowed to warm to 0 °C over 1 h. The cooling bath was
removed, and the mixture was stirred for an additional 1 h at room
temperature. For the work-up, H2O (5 mL) was added with stirring, and the
organic phase was extracted with hexanes (3 ꢁ 3 mL). The combined organic
extracts were filtered through Na2SO4, concentrated, and the residue flash
chromatographed on silica gel.
l
L, 1.0 mmol) was added, and the temperature was
borate 2a (284 mg, 1.1 mmol) in 1,2-DME (1.5 mL) at ꢀ20 °C, and the
temperature was allowed to warm to ꢀ10 °C over 20 min. The mixture was
ꢀ20 °C, MeOH (45
l
l
again cooled to ꢀ20 °C, diazo compound
6 (1 mmol) and MeOH (49 lL,
1.2 mmol) were added [in the case of ethyl diazopropionate (6d) the reaction
was carried out without MeOH], and the temperature was allowed to warm to
0 °C over 1 h. The cooling bath was removed, and the mixture stirred at room
temperature for the time indicated in Table 4. The work-up was the same as
that used in the procedure with EDA.