Radical Silyldifluoromethylation of Electron-Deficient Alkenes

Article abstract of DOI:10.1021/acs.orglett.7b01334

A reaction of bromo- and iododifluoromethyl-substituted silanes with electron-deficient alkenes in the presence of an N-heterocyclic carbene borane complex is described. The reaction is performed under irradiation with light-emitting diodes and proceeds v

Full text of DOI:10.1021/acs.orglett.7b01334

Letter
pubs.acs.org/OrgLett
Radical Silyldifluoromethylation of Electron-Deficient Alkenes
†
†
†
‡
Vyacheslav I. Supranovich, Vitalij V. Levin, Marina I. Struchkova, Alexander A. Korlyukov,
,†
and Alexander D. Dilman*
†
N. D. Zelinsky Institute of Organic Chemistry, Leninsky prosp. 47, 119991 Moscow, Russian Federation
A. N. Nesmeyanov Institute of Organoelement Compounds, Vavilov str. 28, 119991 Moscow, Russian Federation
‡
*
S Supporting Information
ABSTRACT: A reaction of bromo- and iododifluoromethyl-substituted
silanes with electron-deficient alkenes in the presence of an N-
heterocyclic carbene borane complex is described. The reaction is
performed under irradiation with light-emitting diodes and proceeds via a
radical chain mechanism. The resulting products, the functionalized
silicon reagents, can undergo chemoselective transformations involving
either the silyldifluoromethyl fragment or the functional group.
1
2
idespread applications of organofluorine compounds in
applying various boron hydrides. The reactions were irradiated
using 400 nm light-emitting diodes with the temperature
maintained around 25 °C by external cooling (Table 1). With
1
W
drug development have spurred the elaboration of
2
methods for their synthesis. Fluorinated silicon reagents have
become valuable tools for the direct introduction of a
3
4
perfluorinated or a partially fluorinated fragment into organic
molecules. The reactions with these silanes are, typically,
performed under Lewis basic conditions, which are required to
effect cleavage of the Si−C bond. In these processes, the silane3s
serve as sources of either the corresponding carbanionic species
Table 1. Reaction of Silanes with Benzyl Acrylate
5
or difluorocarbene (Scheme 1). Herein, we report the use of
a
Scheme 1. Application of Fluorinated Silanes
no.
X
reagent
time, h
yield of 3a (%)
1
2
3
4
5
6
Br
Br
Br
Br
Br
I
NaBH CN
3
3
3
3
3
2
42
27
3
Bu N·BH CN
4
3
py·BH3
Me N·BH3
3
b
NHC·BH3
NHC·BH3
57 (57)
b
89 (85)
a
b
Determined by NMR or GC analysis of reaction mixtures. Isolated
yield.
a cyanoborohydride anion, product 3a was formed in moderate
yields (entries 1 and 2). Variation of hydride source allowed us to
identify N-heterocyclic carbene borane complex (N,N′-dime-
bromo- and iodo-substituted difluorinated silanes 1 in free-
radical coupling with electron-deficient alkenes, affording
products of hydrofluoroalkylation. We also demonstrate that
products of the silyldifluoromethylation reaction can be further
functionalized selectively at the Si−C bond or at the terminal
group.
12b,13
thylimidazolydene borane, NHC·BH )
as a suitable reagent,
3
6
,7
providing product 3a in 57% yield. Further increase in yield was
achieved by switching to more reactive iodo-substituted silane
1
b.
Under the optimized conditions, a series of electron-deficient
alkenes were silyldifluoromethylated using NHC-borane com-
plex. As iodo-substituted silane 1b is obtained from 1a by a
Homolytic cleavage of the carbon−halogen bond is usually
effected using toxic tin hydride or expensive tris(trimethylsilyl)-
14
8
tedious protocol, reactions were, typically, first evaluated with
silane 1a (Table 2). As a rule, products 3 were formed in
reasonable yields with esters and N,N-disubstituted amides. For
silane. In 2008, it was reported that alkyl iodides react with
electron-deficient alkenes in the presence of sodium cyanobor-
9
ohydride under irradiation with a powerful xenon arc lamp. In
our work, as a starting point, we evaluated a reaction of
commercially available (bromodifluoromethyl)-
Received: May 3, 2017
1
0,11
trimethylsilane
(Me SiCF Br, 1a) with benzyl acrylate,
3
2
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b01334
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 2. Silyldifluoromethylation of alkenes 2
product was observed, presumably due to the reduction of the
enone system with NHC-borane.
15
Silanes 3 are air-stable liquid or solid compounds, which can be
purified by conventional column chromatography on silica gel.
The structure of silane 3g was verified by X-ray diffraction
analysis.
Concerning the mechanism, we believe that the reaction
proceeds via a radical chain process (Scheme 2). Silyldifluor-
Scheme 2. Proposed Mechanism
omethyl radical 4 attacks the double bond, generating radical 5,
which abstracts hydrogen from NHC-borane, leading to boryl-
16
centered radical 6. The latter species abstracts the halogen
atom from silanes 1, regenerating radical 4 along with formation
of haloborane byproduct 7. The scheme would be successful if
NHC-borane reacts faster with radical 5 than with radical 4. This
assumption is supported by earlier calculations of B−H bond
cleavage by a radical, suggesting much greater reactivity of an
9b
ester-substituted radical compared to that of an alkyl radical.
Nevertheless, in our case, the reduced silane Me SiCHF is
3
2
observed in reaction mixtures in small amounts (less than 10%).
An alternative mechanism for the formation of product 3 would
be a SET reduction of radical 5 followed by abstraction of a
proton from the solvent. However, when the reaction of 1a with
tert-butyl acrylate (2b) and NHC-borane was performed in
CD CN, no incorporation of the deuterium in the product was
3
observed (NMR and GC-MS control).
The reaction is completely blocked if TEMPO (1.5 equiv) is
added, thereby corroborating the involvement of radical
intermediates. The progress of the NHC-borane-mediated
reaction of bromo-substituted silane 1a with tert-butyl acrylate
(
2b) was monitored in a light/dark sequence (Figure 1). The
a
b
Reaction time: for 1a, X = Br, 3 h; for 1b, X = I, 2 h. Isolated yield.
reaction proceeds during periods when the light is turned off,
which supports the chain mechanism.
c
d
Isolated yield is decreased due to product volatility. Determined by
e
NMR analysis of reaction mixture. 2 equiv of 1a was used.
A challenging question for this reaction is how it is initiated. In
a report on a cyanoborohydride-mediated process, it was
proposed that the carbon−iodine bond of alkyl iodides is
amide bearing an N−H bond, silane 1b must be used to achieve
efficient reaction (entries 9 and 10). At the same time, for
Weinreb amide, bromo-substituted silane 1a gave higher yield of
the product compared to that of the iodinated counterpart
9a
homolytically cleaved with UV light. However, homolysis of
the carbon−bromine bond of 1a with 400 nm light seems less
17
likely. At the same time, light is important for reaction
efficiency. Thus, in the absence of light, the reaction of silane 1a
with tert-butyl acrylate 2b performed under typical conditions
(argon atmosphere) gave product in 36% yield (Scheme 3). The
same dark reaction but under air atmosphere proceeded
similarly. In an attempt to exclude oxygen, the starting mixture
was degassed by triple freeze−thaw cycles followed by filling the
vessel with argon, and the product was formed in 14% yield.
To evaluate the effect of fluorine, silane 1a was compared with
nonfluorinated analogue 8 under the same conditions (Scheme
(
entries 16 and 17). Interestingly, in reactions of allyl and
homopropargyl acrylates, only expected products 3e,f were
formed (entries 5 and 6), and no cyclization products were
observed. Phenyl vinyl sulfone and acrylonitrile reacted
successfully, furnishing corresponding products (entries 18−
2
0). Di- and trisubstituted acrylates were markedly less reactive.
Thus, in reactions of methyl crotonate and methyl (E)-2-
methylbut-2-enoate with silane 1a, less than 20% of expected
products were formed. For methyl vinyl ketone, no addition
B
DOI: 10.1021/acs.orglett.7b01334
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 5. Reactions at the C−Si Bond
Figure 1. Light/dark sequence for the reaction of 1a, 2b, and NHC-
borane. Dark periods are shown in gray.
Scheme 3. Mechanistic Experiments
Scheme 6. Reactions at the Functional Group
3
, bottom equation). In reaction with tert-butyl acrylate 2b,
difluorinated silane 1a was notably more reactive. Given that C−
Br bond dissociation energies are similar for fluorinated and
nonfluorinated bromides, the observed accelerating effect of
fluorine is remarkable.
18
22
in situ generation of borane was employed. Finally, compound
On the basis of available observations, we may propose the
formation of a complex between the silane and the borane
3
n bearing a Weinreb amide fragment was converted to the
corresponding ketone upon reaction with phenyl magnesium
bromide. These transformations provide access to new function-
alized fluorinated silicon reagents 13−15.
(Scheme 4). Two fluorine atoms provide greater stability to this
Scheme 4. Proposed Initiation Step
In summary, a convenient method for the silyldifluoromethy-
lation of electron-deficient alkenes is described. The use of NHC-
borane in combination with irradiation is important for the
reaction efficiency. The method provides straightforward access
to a family of functionalized gem-difluorinated silanes, which can
further undergo chemoselective transformations.
ASSOCIATED CONTENT
Supporting Information
■
1
9
*
S
species featuring attractive halogen−hydride interaction.
Under the action of light, the complex can undergo homolytic
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b01334.
fragmentation, generating radicals 4 and 6, which can lead a chain
2
0,21
reaction.
Experimental procedures, compound characterization
data, copies of NMR spectra for all compounds (PDF)
X-ray data for 3g (CIF)
Compounds 3 contain two reactive sitesthe carbon
silicon bond and a functional group, and it would be interesting
to develop conditions for chemoselective transformations. The
fragment of gem-difluorinated silane can be reacted with N-tosyl
imine or aldehyde in the presence of fluoride anion (Scheme 5).
Protodesilylation of silane proceeded cleanly when water was
added in the reaction mixture, furnishing product 12 bearing the
difluoromethyl group.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: adil25@mail.ru.
ORCID
Reactions at the functional group without affecting the
Me SiCF fragment are shown in Scheme 6. Reduction of the
Alexander D. Dilman: 0000-0001-8048-7223
Notes
3
2
ester group was cleanly performed using lithium aluminum
hydride. For deoxygenation of amide 3h, a procedure involving
The authors declare no competing financial interest.
C
DOI: 10.1021/acs.orglett.7b01334
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Fensterbank, L.; Malacria, M.; Laco
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■
5
(
8
This work was supported by the Russian Science Foundation
project 17-13-01041).
(
(
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DOI: 10.1021/acs.orglett.7b01334
Org. Lett. XXXX, XXX, XXX−XXX