Borinic Acid Mediated Hydrosilylations: Reductions of Carbonyl Derivatives

Article abstract of DOI:10.1002/ejoc.201801528

4-Fluoro-2-chlorophenylborinic acid acts as a precatalyst in the presence of phenylsilane for the facile reduction of ketones, aldehydes and imines. Notably, synergistic mediation of a tertiary amine was found essential to trigger silicon to boron hydride transfer to generate a key amine–diarylhydroborane Lewis complex.

Full text of DOI:10.1002/ejoc.201801528

DOI: 10.1002/ejoc.201801528
Communication
Carbonyl Reduction
Borinic Acid Mediated Hydrosilylations: Reductions of Carbonyl
Derivatives
Aurélien Chardon,[a] Jacques Rouden,[a] and Jérôme Blanchet*[a]
Abstract: 4-Fluoro-2-chlorophenylborinic acid acts as a precat- of a tertiary amine was found essential to trigger silicon to
alyst in the presence of phenylsilane for the facile reduction of boron hydride transfer to generate a key amine–diarylhydro-
ketones, aldehydes and imines. Notably, synergistic mediation borane Lewis complex.
Introduction
philic activation to allow a productive silicon to boron hydride
transfer.
The reductions of C=C, C=O, and C=N bonds are commonly
achieved using alumino- or borohydrides.[1] Stability and chem-
oselectivity issues have increasingly shifted the interest for
these hydrides towards hydrosilanes, potent reducing agents
Results and Discussion
with high stability and low toxicity. The activation of the sili- During our previous investigations on amide reductions,[7a] late
con–hydrogen bond by a Lewis acid,[2] a Brønsted acid,[3] a nu- catalyst screening revealed a faster reaction with 5-fluoro-2-
cleophile[4] or a transition metal is well known.[2c] However, the chlorophenylborinic acid 1b. However, as observed with 1a, at-
use of a transition metal catalyst is not without drawbacks (cost, tempted reductions of ketones and imines led to the complete
toxicity) and bolstered intense research towards metal-free ca- recovery of starting materials (Scheme 2) and left unchanged
talysis. Piers early investigations showed that the tris(penta- borinic acids 1a and 1b. This puzzling result was in sharp con-
fluorophenyl)borane promoted hydrosilylation of aldehydes, trast with the accepted fact that ketone and imine groups are
ketones, esters and imines.[5] Since this important discovery, more easily reduced than amides.
boron-based catalysts were used as Si–H bond activators in
many chemical transformations.[6] Our group recently devel-
oped 2-chlorophenylborinic acid 1a for the challenging cataly-
sis of amide and phosphine oxide reductions.[7] Noticeable,
lower temperature was used and high chemoselectivity was
achieved when compared to B(C6F5)3 (Scheme 1). Preliminary
mechanistic investigations suggested the involvement of the
intermediate amine–diarylhydroborane complex 2a.
Scheme 2. Attempts to reduce ketone and imine with 1a or 1b.
The efficiency of 1a toward the reduction of amides sug-
gested a mandatory nucleophile activation for the reaction to
proceed. Accordingly, we investigated the hydride transfer from
silicon to boron using stoichiometric amount of boronic acid
1b and PhSiH3 (2 equivalents) in the presence of several amines:
with dimethylbenzylamine, formation of an amine–diaryl-
Scheme 1. Amides reduction using borinic acid 1a as precatalyst.
hydridoborane complex 2b was observed in less than 30 min-
utes (broad singlet, 11B NMR δ –0.51 ppm, 1H NMR δ =
The present report will detail our continuing effort to
broaden the scope of borinic acid-mediated hydrosilylations. In-
terestingly, NMR studies pointed out an indispensable nucleo-
3.97 ppm). A similar result was obtained with N-methylpyrrol-
idine (broad singlet, 11B NMR, δ –2.00 ppm, 1H NMR δ =
3.77 ppm) and boron hydride complex 2c was further character-
ized by a 1H-11B HMBC correlation (see supporting information).
Interestingly, triethylamine afforded an equimolar ratio (11B
NMR estimation) of an unproductive diborohydride 2e[7a] (trip-
let, δ –17.01 ppm, 1J = 84.1 Hz) and the expected amine–diaryl-
hydridoborane complex 2d (br. s, δ –3.01 ppm). Whereas with
secondary methylbenzylamine and primary benzylamine, only
[a] Laboratoire de Chimie Moléculaire et Thio-organique, Normandie Univ,
ENSICAEN, UNICAEN, CNRS, LCMT, 14000 Caen, France
E-mail: jerome.blanchet@ensicaen.fr.
https://www.lcmt.ensicaen.fr/groupe-jacques-rouden-2/
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201801528.
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Lewis complexes 2f and 2g were detected (11B NMR bs
+2.1 ppm and +3.6 ppm respectively) whose structures were
confirmed by comparative experiments in absence of phenyl-
silane.
Further experiments demonstrated the absence of silicon to
boron hydride transfer when triethylsilane or dimethylphenyl-
silane (6 equivalents) were substituted to phenylsilane.
These results strongly suggested that the hydride transfer
was dependent of the nitrogen Lewis basicity of the amine and
that the nucleophilicity of the silicon hydride was not a crucial
parameter (Scheme 3).[8]
Scheme 3. Effect of Lewis bases on the formation of amine–diarylhydro-
borane complexes.
Scheme 5. Mechanism proposal of ketone hydrosilylation.
Interestingly, control experiments showed that a stoichio-
metric amount of 2c failed to reduce 4-chloroacetophenone
while the reactivity was resumed in presence of excess PhSiH3
and a catalytic amount of 2c (5 mol-%) (Scheme 4). This result
illustrated that Lewis adduct 2c is not able to reduce directly
the ketone and requires the presence of excess phenylsilane.[9]
Additional control experiments using triethylsilane and dimeth-
ylphenylsilane left unchanged 4-chloroacetophenone, in line
with the absence of silicon to boron hydride transfer previously
observed with those reagents.
tion of 2c in the presence of twofold equivalent of N-methyl-
pyrrolidine (NMPI, Scheme 6) vs. 1b.[11] Good yields were ob-
tained chemoselectively with acetophenones to give alcohols
3b–3d bearing a nitro, a nitrile or an ester group (Scheme 6).
Fluorine substituent in para and ortho positions were also toler-
ated (3e and 3f).
Scheme 4. Reactivity of amine–diarylhydroborane complex 2c.
With this new insight in hands, a rationalization of the
ketone hydrosilylation mechanism is proposed as follow
(Scheme 5). In sharp contrast with the B(C6F5)3 mechanism in-
volving a concerted activation of the ketone and hydride trans-
fer from silicon to boron, the latter would take place in our case
in a distinct step ahead to the hydrosilylation of ketone.
The catalytic cycle would be initiated by the conversion of
Scheme 6. Substrates scope of ketones hydrosilylation. Isolated yields.
Cyclic chromanone and fluorenone also afforded the desired
the borinic acid 1 to an amine–borane complex 2 through the alcohols 3g and 3h with 89–76 % yields. Switching from aro-
putative equilibrium between PhSiH3 and 1 and a concerted matic to aliphatic ketones resulted in significantly slower reduc-
hydride abstraction.[10] At several instances, diphenyldisiloxane tions, leading to the corresponding alcohols with 56–74 %
1
was observed in H NMR, resulting from the silylation of tran- yields (3i–k). Gratefully, α,ꢀ-unsaturated ketone was selectively
sient monohydroxyphenylsilane. The absence of reactivity of reduced to allylic alcohol 3l in 76 % yield with no side-product
complex 2 in absence of PhSiH3 suggested that the hydrosilane resulting from a 1,4-addition of the hydride.
might polarize mildly the ketone, enough to initiate the addi-
tion of the hydride 2 that would be regenerated consecutively
by a rapid hydride transfer from pentavalent silicon to boron in
the salt A (Scheme 5).
With aldehydes a faster reaction was observed, therefore the
catalyst loading was successfully decreased to 1 mol-%. Inde-
pendently of the electron density, benzaldehyde derivatives
substituted with nitro, fluoro, methoxy or phenyl group af-
Next, the scope of the ketones and aldehydes hydrosilylation forded the corresponding alcohols 4a–4h in 74–98 % yields
was examined using reaction conditions allowing in situ forma- (Scheme 7).
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generally underinvestigated. Stephan recently developed effi-
cient fluorophosphonium salts and explored the reduction of
an imine in the presence of a ketone. However, side silyl enol
ether transformation of the ketone was obtained.[13] Therefore
we conducted a competitive reduction of a tosylimine in the
presence of a stoichiometric amount of 4-chloroacetophenone
(Scheme 9). In THF at room temperature, tosylamide 5b was
chemoselectivity obtained in 78 % yield with no trace of alcohol
3a being detected. However, another competitive experiment
involving 4-fluorobenzaldehyde instead of 4-choroacetophen-
one provided the corresponding primary alcohol as the major
reduction product (3:1).
Scheme 7. Substrate scope of aldehyde hydrosilylation. Isolated yields.
The reaction also tolerates heterocyclic aldehydes at the cost
of a slight decrease of reactivity for pyridine and thiophene
derivative 4i and 4j (Scheme 7). Finally, an aliphatic aldehyde
derived from phenylalanine was chemoselectively reduced in
91 % yield in the presence of a Boc nitrogen protecting group.
Our attention then turned out to the hydrosilylation of
imines (Scheme 8). Aldimines were underinvestigated sub-
Scheme 9. Competitive reduction of an imine in the presence of a ketone.
Conclusions
In this manuscript, we described a general methodology for the
reduction of a range of ketones, aldehydes and imines. Initial
experiments established an unprecedented Lewis base media-
tion of a silicon hydride transfer from a hydrosilane to a borinic
acid. The developed reaction conditions featured mild tempera-
tures and catalyst loading as low as 1 mol-%. Moreover, unusual
selective reduction of an imine in the presence of a ketone was
achieved.
strates for non-metal catalysed hydrosilylation with the excep-
[5b]
tion of Piers use of B(C6F5)3
and a single example reported
by Nikonov.[12]
Acknowledgments
The authors thank the Centre National de la Recherche Scientif-
ique (CNRS), Normandie université, Labex Synorg (ANR-11-
LABX-0029) for AC fellowship, the Conseil Régional de Nor-
mandie and the European FEDER fundings for financial support.
Keywords: Borinic acid · Reduction · Ketones ·
Aldehydes · Imines
Scheme 8. Substrate scope of imines hydrosilylation.
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Received: October 9, 2018
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Carbonyl Reduction
A. Chardon, J. Rouden,
J. Blanchet* .......................................... 1–5
Borinic Acid Mediated Hydrosilyl-
ations: Reductions of Carbonyl De-
rivatives
A facile hydride transfer from hydrosil- carbonyl derivatives by using phenyl-
ane to a borinic acid is efficiently me- silane and catalytic amount of borinic
diated by a tertiary amine. This led to acid and amine.
the development a mild reduction of
DOI: 10.1002/ejoc.201801528
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