Large-scale preparation and labelling reactions of deuterated silanes

Article abstract of DOI:10.1002/jlcr.1950

A catalytic synthesis of deuterated silanes SiEt₃D, SiMe ₂PhD and SiPh₂D₂ is reported that allows their facile generation in a 3-4g scale, utilizing D₂ (0.5bar) as the hydrogen isotope source and low

Full text of DOI:10.1002/jlcr.1950

Research Article
Received 29 August 2011,
Revised 25 October 2011,
Accepted 30 October 2011
Published online 21 November 2011 in Wiley Online Library
(wileyonlinelibrary.com) DOI: 10.1002/jlcr.1950
Large-scale preparation and labelling
reactions of deuterated silanes
*
Jesús Campos, Miguel Rubio, Ana C. Esqueda, and Ernesto Carmona
A catalytic synthesis of deuterated silanes SiEt3D, SiMe2PhD and SiPh2D2 is reported that allows their facile generation in a
3–4 g scale, utilizing D2 (0.5 bar) as the hydrogen isotope source and low catalyst loadings (0.01 mol%). The catalyst
precursor is the rhodium (III) complex 1, which contains a (h5-C5Me5)Rh cation stabilized by coordination to a cyclometallated
phoshine PMeXyl2 (Xyl = 2,6-C6H3Me2). The same complex is also an active catalyst for the hydrosilylation of the C==O and
CꢀN bonds of various ketones, aldehydes and a,b-unsaturated nitriles. Hence, combination of these two properties permits
development of a simple and proficient one-flask, two-step procedure for the deuterosilylation of these substrates.
Keywords: deuterium exchange; deuterium; silanes; deuterosilylation; catalysis; rhodium
bond of halosilanes with NaBD4, LiAlD4 or a similar deuteride
Introduction
agent as the more commonly used synthesis of deuterated
silanes.2a,16 For tritium, catalytic H/T exchange at carbon2d,e,3 is
The growing demand for deuterium-labelled and tritium-
labelled compounds stimulates the search for fast, selective,
preferred over the use of LiBT4, NaBT4 and LiT and related
catalytic methods that allow efficient isotopic incorporation.1 In
reagents.4,5 Indeed, the high potential of tritiated silanes such
as SiEt3T and SiPh2T2 was advanced by Saljoughian in 2002,17
but almost 10 years later, it does not seem to have been
accomplished, most likely because of unsolved problems in the
preparation of these tritiating reagents4,5 (see, e.g. the study by
Neu and Andres5 for difficulties in the preparation of SiEt3T).
We have recently communicated a very efficient, rhodium-
catalysed procedure for the synthesis of deuterated and tritiated
silanes.18a,b Subsequently, the catalytic properties of this
system to effect with great efficacy the deuterosilylation and
tritiosilylation of a variety of ketones and aldehydes, by using
SiEt3H under sub-atmospheric pressure of D2 or T2, have been
exploited.18c In this contribution, we provide details for the
synthesis in a several gramme scale of deuterated silanes
catalysed by complex 1 (Figure 2), by using SiEt3D, SiMe2PhD
and SiPh2D2 as representative examples. It is most probable that
the method can also be applied to the large-scale synthesis of
corresponding tritiated silanes with high specific activity.
Nevertheless, the lack of facilities in our laboratories to achieve
such goal has limited our work to the preparation of SiEt3T and
tritiated complex 1, in both cases with low specific activity.18 In
view of the efficacy of our method, microwave enhancement1b,19
of the labelling procedure has not been considered.
2
3
general, H-labelled and H-labelled molecules can be prepared
by the same basic procedures. In addition to H/D (or H/T)
exchange at carbon centres,2,3 a convenient labelling practice
is reduction of C-X multiple bonds (X==C, N, O) with a hydride
source such as a metal hydride derived from boron, aluminium
or tin.2a,4,5 However, use of these reagents, although common,
encounters substantial limitations by the chemistry required
(particularly for T-labelling) and by the generation of consider-
able amounts of waste products.
Hydrosilanes, SiR4ÀnHn (n = 1À3), are an extraordinarily
important class of reagents for chemical synthesis.6–12 They are
air and moisture stable and are viewed as environmentally
friendly reductants, therefore representing suitable alternatives
to the more toxic tin derivatives. Metal-catalysed hydrosilylation
is a very important industrial and laboratory method,7–10 widely
employed in chemical synthesis (Figure 1) for the reduction of
C-X (X==C, N, O) multiple bonds. Furthermore, hydrosilanes can
also be utilized for the catalytic reduction of carbon–halogen
bonds, including unreactive C-F bonds.11,12
Deuterated and tritiated commonly used silanes, for instance,
SiEt3D and SiEt3T, or SiPh2D2 and SiPh2T2, would therefore
offer significant advantages in the solution of chemical and
biochemical problems with the use of hydrogen isotopes. Thus,
catalytic deuterosilylation and tritiosilylation will reduce C-O
and C-N multiple bonds, placing the label at carbon while
simultaneously protecting the resulting alcohol or amine
moieties, allowing further multistep synthesis or the direct
introduction of a second D or T label. Despite this great potential,
deuterated and tritiated silanes have been hardly exploited as
isotopic labelling reagents. Most probably, this is due to the
scarcity of information on catalytic H/D (or H/T) exchanges at
Departamento de Química Inorgánica, Instituto de Investigaciones Químicas
(IIQ), Universidad de Sevilla, Consejo Superior de Investigaciones Científicas,
Avda. Américo Vespucio 49, 41092 Sevilla, Spain
*Correspondence to: Ernesto Carmona, Departamento de Química Inorgánica, Insti-
tuto de Investigaciones Químicas (IIQ), Universidad de Sevilla, Consejo Superior de
Investigaciones Científicas, Avda. Américo Vespucio 49, 41092 Sevilla, Spain.
silicon centres,13–15 which leaves reduction of the silicon–halogen E-mail: guzman@us.es
J. Label Compd. Radiopharm 2012, 55 29–38
Copyright © 2011 John Wiley & Sons, Ltd.

J. Campos et al.
heating at 50 ꢁC permits complete solubilization of the catalyst
into the neat silane and hence catalysis performance in the
absence of solvent. On the other hand, because an equilibrium
between reactants and products in Figure 2 is established, to
ensure complete deuteration of the silane (≥99%) in this 5-mL-
scale synthesis, the reaction was periodically stopped by cooling
at 0 ꢁC. The flask atmosphere was evacuated by application of
vacuum (0.1 bar for ~20 s) and the reaction vessel charged again
with 0.5 bar of D2. This cycle was repeated a total of five times
during the global reaction period and the pure SiEt3D then
obtained by trap-to-trap distillation. The same procedure was
utilized for the synthesis of SiMe2PhD and SiPh2D2. Pure
SiMe2PhD was separated by trap-to-trap distillation too, whereas
for SiPh2D2, a Kugelrohr vacuum distillation apparatus was
employed.
Si
C
Si
H
H
C
C
C
C
C
C
C
Si
Si
H
H
C
O
C
N
C
O
C
N
R
CF3
C
X
H
O
C
H
H
R
C
C
H
The course of the reaction was followed by 1H and 29Si{1H}
NMR spectroscopy and by IR spectroscopy to monitor the
hydrogen isotope exchange. The 1H NMR spectrum of SiEt3H
(CDCl3) exhibits a septet at d 3.68 ppm that corresponds to the
hydrogen atom bonded to silicon. Upon deuteration, this reso-
nance gradually disappears, and it is completely absent in the
1H NMR of the final product, which shows instead the
corresponding signal in the 2H NMR spectrum. Deuteration of
the silane ethyl substituents does not occur. As shown in Figure 3(a),
the 29Si{1H} NMR spectrum of SiEt3H is a singlet with d 0.8 p.p.
m. that experiences an isotopic displacement to d 0.4 p.p.m.
(1JSiD = 28 Hz) upon deuteration (Figure 3(c)). The spectrum of
Si
Si
O
O
C
H
C
H
Figure 1. Some synthetic applications of hydrosilanes.
Results and discussion
Catalytic synthesis of SiEt3D, SiMe2PhD and SiPh2D2
Figure 2 contains a general representation of the synthesis of an ~45:55 mixture of the two isotopologues has been included
deuterosilanes catalysed by compound 1. As already noted,18a in Figure 3(b). On the other hand, the IR spectrum of SiEt3H
this catalytic procedure is based on the following considerations: features a band at ~2100 cmÀ1 due to n(Si-H) (Figure 4) that
(a) there is no observable reaction between 1 and H2 or SiEt3H, shifts to about 1530 cmÀ1 in the spectrum of SiEt3D. The relative
but exposure of solutions of 1 to D2 yields 1(D11)+, as a intensities of these IR bands along the course of the H/D
consequence of fast exchange involving all sp3-hybridized C-H exchange match closely the results obtained from 1H and
+
bonds of the phosphine xylyl groups; (b) treatment of 1(D11
)
29Si{1H} NMR studies.
with an excess of SiEt3H exchanges the label and affords SiEt3D.
We have taken profit of this reactivity to effect the deuteration of
some common hydrosilane reagents, namely SiEt3H, SiMe2PhH
and SiPh2H2 in a large scale (3–4 g). In all probabilities, this
synthesis can be scaled up further and can also be applied
to other tertiary or secondary silanes, and even to primary
silanes.18a As a general precaution, water must be thoroughly
excluded, for compound 1 catalyses also with high efficiency
the production of H2 from H2O and hydrosilanes.20
Using SiEt3H as a representative example, we dissolved 4.2 mg
of compound 1 (3.1 Â 10À3 mmol) in 5 mL of SiEt3H (31.3 mmol;
catalyst concentration 0.01 mol%) in an ~220-mL flask and
stirred at 50 ꢁC, under 0.5 bar of D2, for a total time of 16 h.
Although the H/D exchange is fast at 20 ꢁC in CH2Cl2 solution,
-
F
CH2
3
3
2
2
2
2
2
3
3
Figure 2. Si-H/Si-D exchange catalysed by the rhodium(III) complex 1 (BArF = B
Figure 3. 29Si{1H} NRM spectrum of SiEt3H (a), SiEt3D (c) and an ~45:55 mixture of
[3,5-(CF3)2C6H3]).
the two isotopologues (b).
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J. Label Compd. Radiopharm 2012, 55 29–38

J. Campos et al.
1,2-addition of about 9:1, regardless of the use of SiEt3H or SiMe2PhH
as the reductant, although the corresponding silyl enols resulted as
comparable mixtures of their Z and E isomers. The more accessible
carbonyl group of cinnamaldehyde led to an almost 1:1 ratio of
1,2-addition and 1,4-addition products, although for the latter
reactivity almost only the E isomers of the silyl enols were obtained.
Less reactive carbonyl species like esters and amides were also
investigated. Reactions of several tertiary and secondary silanes
with esters ethylbenzoate and ethylbutyrate were unsuccessful,
even after prolonged heating at 60 ꢁC. Similarly, hydrosilylation
of benzamide and N,N-dimethylacetamide proved fruitless.
Nevertheless, a positive consequence of these results is that
selective reduction of the ketone functionality in a-ketoesters
and a-ketoamides should be feasible. In accord with expecta-
tions, SiEt3H added chemoselectively to the keto carbonyl group
of ethyl pyruvate (entry 16) to give the corresponding silyl ethers.
Thus, compound 1 seems to be a good candidate for the
selective hydrosilylation of aldehydes and ketones in the
presence of the less reactive ester and amide functional groups.
Hydrosilylation and deuterosilylation of C-N multiple bonds
Figure 4. IR spectra (neat silanes) of mixtures of SiEt3H (n(Si-H) = 2100 cmÀ1) and
SiEt3D (n(Si-D) = 1530 cmÀ1).
Reaction of N-benzylidene aniline with 2.2 eq of SiEt3H at 50 ꢁC
for 2 h, in the presence of 1 mol% concentration of 1, gave the
expected silylamine product in quantitative yield (Table 2,
entry 1). With the use of the procedure described previously for
Hydrosilylation and deuterosilylation of >C==O bonds
As an extension of previous work from our group in this area,18b direct deuterations, the D-isotopologue was generated also
we have studied the reduction of a common natural product quantitatively. In this case, to ensure full deuterosilylation, we
with biological activity, the (R)-camphor molecule that contains employed a non-optimized time of 12 h.
a sterically congested ketone functionality. Reduction of its
Imine hydrosilylation catalysed by 1 is very sensitive to steric
carbonyl group can give rise to exo or endo isomers. Entries 3–7 hindrance around the C==N bond. Thus, hydrosilylation of the
in Table 1 contain the results of this study that encompassed bulkier aldimine N-benzylidene-t-butylamine (entry 3), and
the use of SiEt3H, SiPh2H2, SiMe2PhH, SiEt3D and SiMe2PhD. ketimine (E)-N-(1-phenylethylidene)aniline (entry 4), occurred
For comparative purposes, entries 1 and
previous results obtained for acetophenone and SiEt3H and formation of the opposite regioselectivity product (entry 3).
SiEt3D.18b Both SiEt3H and SiPh2H2 led to little or no control of
Whereas well-known procedures are available for the hydrosi-
2
summarize with low conversion and, in the former case, with partial
diastereoselectivity, although the latter favoured formation of lylation of C==X bonds (X==C, N, O),7–10 hydrosilylation of CꢀN
the exo product (~7:3 ratio of exo : endo). This selectivity is bonds remains comparatively unexplored because the cyano
comparable with that reported when RhH(PPh3)4 was used as a group behaves as inert under common hydrosilylation condi-
catalyst21 for this reduction (1.8:1 ratio) but is opposite to tions.7e,22 Murai and co-workers used Co2(CO)8 as catalyst for
catalysis by the iridium cation [IrH(POCOP)(acetone)]+ (POCOP = 2, the reduction of nitriles by SiMe3H to N,N-disilylamines.23a Sub-
6-bis(di-tert-butylphosphinito)phenyl) that produced an approxi- sequently, a heterogeneous, Rh-catalysed process for the hydro-
mate 1:4 ratio of exo and endo isomers.8a Our reaction is less silylation of aromatic aldehydes was developed,23b and more
efficient than the latter process, which proceeds quantitatively recently, Gutsulyak and Nikonov have reported a very conve-
at 0 ꢁC.8a However, for our system, direct deuterosilylation was nient method for the selective monosilylation and disilylation
achieved by application of the one-flask, two-step procedure of nitriles, by action of a Ru catalyst.23c
described earlier,18b which makes use of D2 as the hydrogen
Whereas acetonitrile (Table 2, entry 2) underwent only partial
isotope source. Firstly, a dichloromethane solution of catalyst 1 conversion in the presence of 1 and SiEt3H (<40%, 50 ꢁC, 24 h)
and SiEt3H (entry 7) or SiMe2PhH (entry 8) was stirred in the and benzonitrile remained unaltered even under somewhat more
presence of D2 (0.5 bar) for 2–3 min, whereby D-incorporation to forcing conditions (entry 6), a,b-unsaturated nitriles experienced
SiEt3H and 1 took place. The gas atmosphere was then replaced facile hydrosilylation to produce vinylamines protected with two
by fresh D2 (0.5 bar) and the process repeated a total of three silyl groups (entries 7–9). This observation, which finds scarce
times, to ensure a D-content in the silane product of ≥99%. Then, literature precedent,23a,b allowed isolation of vinyl bis(silylamines)
camphor was added and the mixture stirred at 50 ꢁC for 24 h to as stable molecules. The parent vinylamines are usually unstable
yield the isotopically labelled silylborneols in good yields and decompose gradually even at low temperatures.24 The use of
(entries 7 and 8), with diastereoselectivity similar to that observed this method permitted also facile D-labelling of the amine resulting
for the non-labelled product.
from the double deuterosilylation of cinnamonitrile (Figure 5 and
To analyse competition between the 1,2-addition and 1,4- entry 8 of Table 2). At variance with previous reports,23a,b other
addition of the hydrosilane to a,b-unsaturated carbonyl possible products of this reaction, such as the protected aliphatic
compounds, we also employed benzylideneacetone (entries 8–10) amine or the protected allylic amine, were not observed (Figure 5).
and cinnamaldehyde (entries 11–14) for this study. For the former, Moreover, the double hydrosilylation of cinnamaldehyde by 1 is
there was a clear preference for the 1,4-addition with respect to the highly selective and gives exclusively the E isomer.
J. Label Compd. Radiopharm 2012, 55 29–38
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J. Campos et al.
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J. Campos et al.
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J. Campos et al.
Table 2. Hydrosilylation and deuterosilylation of C-N multiple bonds
Entry
1
Substrate
S/C
100
Silane
SiEt3H
T (ꢁC)
50
t (h)
2
%Conv
100
Product
2
3
100
100
SiEt3D
SiEt3H
50
50
12
24
100
15
4
100
SiEt3H
50
24
40
5
6
CH3CN
100
100
SiEt3H
SiEt3H
50
60
24
48
38
0
No reaction
7
8
100
100
SiEt3H
SiEt3D
50
50
6
100
100
36
9
100
SiEt3H
80*
7
95
Conditions: silane (2.2 eq for imines and 3 eq for nitriles) and solvent (CD2Cl2, 0.5 mL).
*Solvent ClCH2CH2Cl.
experiments where appropriate. Catalyst 1 was prepared as pre-
viously described.18 All substrates were purchased from commercial
sources and were distilled under vacuum from CaCl2 or MgSO4
before use. Silanes were purchased from commercial sources and
used without further purification. PMeXyl2 (Xyl = 2,6-C6H3Me2) was
prepared from PCl3, MeMgBr and XylMgBr.25a The rhodium dimer
and ZnCp*2 were also obtained using published procedures.25b,c
NaBArF can either be prepared25d or be obtained from commercial
sources.
Experimental
General
All operations were performed under an argon atmosphere by
using standard Schlenk techniques, employing dry solvents and
glassware. High Resolution Mass Spectrometry (HRMS) data were
obtained using a Jeol JMS-SX 102A mass spectrometer (JEOL Ltd.,
Tokyo, Japan) at the Analytical Services of the Universidad de Sevilla
(CITIUS). Infrared spectra were recorded on Bruker Vector 22 spec-
trometer (Bruker Biospin S.A.S, Wissembourg Cédex, France). The
NMR instruments used were Bruker DRX-500, DRX-400 and DRX-
300 spectrometers. Spectra were referenced to external SiMe4 (d
0 p.p.m.) by using the residual proton solvent peaks as internal stan-
dards (1H NMR experiments), or the characteristic resonances of the
solvent nuclei (13C NMR experiments). Spectral assignments were
made by routine one-dimensional and two-dimensional NMR
Synthesis of catalyst 118 (Figure 6)
Preparation of [(ꢀ5-C5Me5)Rh(Cl){PMe(2,6-CH2(Me)C6H3)(2,6-Me2C6H3)}]
(1-Cl)
A solution of PMe(Xyl)2 (131 mg, 0.5 mmol) in 2 mL of THF is
added, at À40 ꢁC, to a solution of [RhCl(C2H4)2]2 (100 mg,
3
3
3
3
3
3
3
Figure 5. Selective hydrosilylation of cynamonitrile with catalyst 1. Common by-products found in hydrosilylation of a,b-unsaturated nitriles have not been detected.
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J. Campos et al.
Figure 6. Synthesis of catalyst 1 (Xyl = 2,6-C6H3Me2; BArF = B[3,5-(CF3)2C6H3]).
0.25 mmol) in 3 mL of THF. The reaction mixture is stirred for 3 h [1-2H2]Diphenylsilane (SiPh2D2)
at this temperature. Then, a solution of ZnCp2* (84 mg,
The same procedure utilized to deuterate triethylsilane was
0.25 mmol) in 1 mL of THF is added, and the mixture is stirred
for 5 h while allowing the temperature to reach À25 ꢁC. The
solvent is removed under vacuum and the residue extracted
with diethyl ether and then evaporated to dryness. The crude
is dissolved in 5 mL of CH2Cl2 and stirred for 3 h at room tem-
perature. The solvent is removed under vacuum and the crude
product washed with pentane to yield complex 1-Cl as an
orange solid in 83% yield. Anal. calc. for C27H35ClPRh: C, 61.3;
employed but using diphenylsilane (5mL, 26.86 mmol) and
catalyst 1 (7.3mg, 5.4 Â 10À3 mmol). Deuterated diphenylsilane
was purified by Kugelrohr distillation to obtain SiPh2D2 as a
colourless oil (4.17 g, 84% yield; 99% D-incorporation). IR (Nujol):
1550 cmÀ1. 1H NMR (500 MHz, C6D6, 25 ꢁC) d: 7.30 (d, 4H, 3JHH = 7.8
Hz, o-Ph), 6.91 (m, 6H, m,p-Ph). 29Si{1H} NMR (99 MHz, C6D6)
d: –33.8 (quintet, 1JSiD = 30 Hz).
1
H, 6.7. Found: C, 61.2; H, 6.6. H, 13C and 31P NMR data can be
found in the study by Campos et al.18a
Determination of deuterium incorporation
The levels of deuteration exchange were checked by 1H NMR, 29Si
NMR and IR spectroscopy. The level of deuteration was
monitored by 1H NMR spectroscopy. Exchange reactions were
considered to be complete when no integrable 1H signal for the
Si-H atom could be detected. These results were confirmed by
the disappearance of the characteristic signals in the 29Si NMR
and IR spectra. Signals for the hydrosilane and deuterosilane
appear perfectly well resolved in the 29Si NMR spectra because
of the isotope effect on the chemical shift (Figure 3). The calcu-
lation of the deuterium percentage by 29Si NMR is totally in
accordance with the results obtained from the 1H NMR analysis.
The integration of the bands for n(Si-H) (~2100 cmÀ1) and n(Si-D)
Synthesis of [(ꢀ5-C5Me5)Rh{PMe(2,6-CH2(Me)C6H3)(2,6-Me2C6H3)}]+BArÀF , (1)
To a solid mixture of 1-Cl (150 mg, 0.28 mmol) and NaBArF
(252 mg, 0.28 mmol) was added 5 mL of CH2Cl2. The reaction
mixture was stirred for 10 min at room temperature, and after
this time, the solution was filtered and the solvent evaporated
under reduced pressure, to obtain an orange solid (350 mg,
95%). This complex can be crystallized from a 1:1 mixture of
CH2Cl2 : pentane. Anal. calc. for C59H47BF24PRh: C, 52.6; H, 3.5.
1
Found: C, 53.0; H, 3.3. H, 13C and 31P NMR data can be found
in the study by Campos et al.18a
1
(~1500 cmÀ1) match up with the results obtained by H and 29Si
High-scale synthesis of deuterosilanes
NMR (Figure 4).
[1-2H]Triethylsilane (SiEt3D)
Triethylsilane (5mL, 31.30 mmol) was added under nitrogen to a
pressure vessel (volume ~220 mL) containing catalyst 1 (4.2mg,
3.1 Â 10À3 mmol). The solution was cooled to 0ꢁC and nitrogen
pumped out. Then, the flask was charged with deuterium
(0.5bar), and the mixture was vigorously stirred at 50ꢁC for 16 h.
To exchange quantitatively the Si-H bond, we repeated the cooling
at 0 ꢁC/vacuum (0.1bar)/D2 (0.5bar) process five times. The solu-
tion was transferred to a Young’s ampoule and the deuterosilane
purified by trap-to-trap distillation to obtain SiEt3D as a colourless
liquid (3.49 g, 96% yield; 99% D-incorporation). IR (neat silane):
1530 cmÀ1. 1H NMR (500 MHz, C6D6, 25 ꢁC) d: 0.96 (t, 9H, 3JHH = 7.9
Hz, 3CH3), 0.53 (q, 6H, 3JHH = 7.9 Hz, 3CH2). 29Si{1H} NMR (99 MHz,
C6D6) d: 0.4 (t, 1JSiD = 28 Hz).
General method for the hydrosilylation of C-O and C-N
multiple bonds
In a typical experiment, a 2-mL screwcap glass vial was charged
with catalyst 1 (0.7 mg, 0.5 Â 10À3 mmol), the hydrosilane
(1.1 mmol), the organic substrate (0.5 mmol) and CD2Cl2
(0.5 mL) in a glove box. After stirring for 1 h, we transferred
the reaction mixture to a screwcap NMR tube and checked the
1
reaction progress by H NMR spectroscopy.
General method for the direct deuterosilylation of C-O and
C-N multiple bonds
In a typical experiment, a Young’s ampoule was charged with
[1-2H]dimethylphenylsilane (SiMe2PhD)
catalyst
1
(0.7 mg, 0.5 Â 10À3 mmol), triethylsilane (89 mL,
The same procedure utilized to deuterate triethylsilane was 0.55 mmol) and CD2Cl2. The solution was cooled to 0 ꢁC, argon
employed but using dimethylphenylsilane (5mL, 32.66 mmol) pumped out and replaced by D2 (0.5 bar). The solution was
and catalyst 1 (4.4mg, 3.2 Â 10À3 mmol). Deuterated dimethyl- stirred at room temperature for 10 min and then cooled at 0 ꢁC,
phenylsilane was purified by trap-to-trap distillation, and the gas atmosphere pumped out and replaced by D2 (0.5 bar).
SiMe2PhD was obtained as a colourless liquid (4.15 g, 93% yield; After repeating this cycle for a total of three times, the organic
99% D-incorporation). IR (neat silane): 1540 cmÀ1 1H NMR substrate (0.25 mmol) was added and the mixture transferred
.
(500MHz, C6D6, 25 ꢁC) d: 7.54 (m, 2H, Ph), 7.28 (m, 3H, Ph), 0.34 (s, to a screwcap NMR tube. The reaction progress was monitored
6H, 2CH3). 29Si{1H} NMR (99 MHz, C6D6) d: À17.2 (t, 1JSiD = 29Hz).
by 1H NMR spectroscopy.
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J. Campos et al.
Characterization of compounds
product). SiMe2PhH (entry 12, Table 1) 1H NMR (500 MHz,
CD2Cl2): characteristic signals, d 6.60 (d, 3JHH = 16.0 Hz; ==CH, 1,2-
addition product), 6.39 (dt, 3JHH = 12.0, 1.2 Hz; ==CH, E-1,4-addition
Hydrosilylation of (R)-camphor by hydrosilanes RnSiH4Àn (entries
3–7, Table 1)
3
product), 6.32 (dt, JHH = 16.0, 5.5 Hz; ==CH, 1,2-addition product),
3
Using the general procedure at 50 ꢁC, we hydrosilylated R-camphor
(0.015 g, 0.1 mmol). Spectroscopic data of the reaction mixture
were consistent with previously reported data for these
compounds.26
5.20 (dt, JHH = 12.0, 7.5 Hz; ==CH, E-1,4-addition product), 4.75
3
(m, ==CH, Z-1,4-addition product), 4.36 (dd, JHH = 5.5, 2.0 Hz;
CH2, 1,2-addition product), 3.20 (d, 3JHH = 7.5; CH2, E-1,4-addition
product).
1H NMR (500 MHz, CD2Cl2): SiEt3H (entry 3, Table 1; 46% endo,
54% exo): characteristic signals, d 3.94 (m, 1H, endo isomer), 3.57
(dd, 3JHH = 7.9, 3.5 Hz, 1H, exo isomer). SiPh2H2 (entry 4, Table 1;
30% endo, 70% exo): characteristic signals, d 4.26 (m, 1H, endo
Deuterosilylation of cinnamaldehyde (entries 13 and 14, Table 1)
Using the general procedure at 25 ꢁC, we deuterosilylated
cinnamaldehyde (13 mL, 0.1 mmol). Spectroscopic data of the prod-
ucts were consistent with those of the non-labelled compounds.
1H NMR (400 MHz, CD2Cl2): SiEt3D (entry 13, Table 1):
3
isomer), 3.85 (dd, JHH = 7.8, 3.2 Hz, 1H, exo isomer). SiMe2PhH
(entry 6, Table 1; 30% endo, 70% exo): characteristic signals, d
4.03 (m, 1H, endo isomer), 3.65 (dd, JHH = 7.5, 3.0 Hz; 1H, exo
isomer).
3
3
characteristic signals, d 6.60 (d, JHH = 16.0 Hz; ==CH, 1,2-addition
3
product), 6.39 (dd, JHH = 12.0, 1.2 Hz; ==CH, E-1,4-addition
product), 6.31 (dd, 3JHH = 16.0, 5.5 Hz; ==CH, 1,2-addition product),
Hydrosilylation of benzylideneacetone (entries 8 and 9, Table 1)
3
5.12 (dd, JHH = 12.0, 7.5 Hz; ==CH, E-1,4-addition product), 4.70
Using the general procedure at 50 ꢁC, we hydrosilylated
benzylideneacetone (0.015 g, 0.1 mmol). Spectroscopic data of
the 1,2-addition and 1,4-addition products were consistent with
previously reported data for these compounds.27
(m, ==CH, Z-1,4-addition product), 4.32 (bs, CH2, 1,2-addition
3
product), 3.21 (bd, JHH = 7.5; CH2, E-1,4-addition product).
SiMe2PhD (entry 14, Table 1): characteristic signals, d 6.60
3
3
(d, JHH = 16.0 Hz; ==CH, 1,2-addition product), 6.38 (dd, JHH
=
1H NMR (400 MHz, CD2Cl2): SiEt3H (entry 8, Table 1): character-
3
12.0, 1.2 Hz; ==CH, E-1,4-addition product), 6.32 (dd, JHH = 16.0,
5.5 Hz; ==CH, 1,2-addition product), 5.19 (dd, JHH = 12.0, 7.5 Hz;
istic signals, d 6.56 (d, 3JHH = 16.0 Hz; ==CH, 1,2-addition product),
3
3
6.27 (dd, JHH = 16.0, 6.0 Hz; ==CH, 1,2-addition product), 4.90
==CH, E-1,4-addition product), 4.74 (m, ==CH, Z-1,4-addition
3
3
3
(t, JHH = 7.5 Hz, ==CH, E-1,4-addition product), 4.64 (t, JHH = 7.0
Hz, ═CH, Z-1,4-addition product), 4.52 (m, CH, 1,2-addition pro-
product), 4.36 (bs, CH2, 1,2-addition product), 3.20 (d, JHH = 7.5;
CH2, E-1,4-addition product).
3
duct), 3.42 (d, JHH = 7.0 Hz, CH2, Z-1,4-addition product), 3.34
3
(d, JHH = 8.0 Hz, CH2, E-1,4-addition product). SiMe2PhH (entry
Hydrosilylation of ethyl pyruvate (entry 16, Table 1)
3
9, Table 1): characteristic signals, d 6.49 (d, JHH = 16.0 Hz; ==CH,
Using the general procedure at 50 ꢁC, we hydrosilylated ethyl
pyruvate (0.012 g, 0.1 mmol) by triethylsilane. Spectroscopic data
of the reaction mixture were consistent with previously reported
data for this compound.29
3
1,2-addition product), 6.25 (dd, JHH = 16.0, 6.0 Hz; ==CH, 1,2-
3
addition product), 4.88 (t, JHH = 7.5 Hz, ==CH, E-1,4-addition
3
product), 4.69 (d, JHH = 7.0 Hz, ==CH, Z-1,4-addition product),
3
4.53 (m, CH, 1,2-addition product), 3.39 (d, JHH = 7.0 Hz, CH2,
1H NMR (500 MHz, CD2Cl2): characteristic signals, d 4.30
Z-1,4-addition product), 3.30 (d, 3JHH = 7.5 Hz, CH2, E-1,4-addition
3
3
(q, JHH = 6.8 Hz, CH3CH), 4.13 (q, JHH = 7.0 Hz, OCH2CH3), 1.36
product).
3
3
(d, JHH = 6.8 Hz, CH3CH), 1.26 (t, JHH = 7.0 Hz, OCH2CH3).
Deuterosilylation of benzylideneacetone (entry 10, Table 1)
Using the general procedure at 25 ꢁC, we hydrosilylated
benzylideneacetone (0.015 g, 0.1 mmol) by [1-2H]-triethylsilane.
Spectroscopic data of the non-deuterated 1,2-addition27a and
1,4-addition products27b were consistent with previously
reported data for these compounds.
Hydrosilylation of N-benzylidene aniline (entry 1, Table 2)
Using the general procedure at 50 ꢁC, we hydrosilylated N-
benzylidene aniline (0.018 g, 0.1 mmol) by triethylsilane. Spectro-
scopic data of the reaction mixture were consistent with
previously reported data for this compound.18a
1H NMR (400 MHz, CD2Cl2): characteristic signals, d 6.53 (d,
1H NMR (500 MHz, CD2Cl2): characteristic signals, d 7.31
3JHH = 16.0 Hz; ==CH, 1,2-addition product), 6.25 (d, 3JHH = 16.0 Hz;
3
3
(d, JHH = 4.3 Hz, Ph), 7.22 (m, Ph), 7.17 (t, JHH = 7.9 Hz, Ph), 6.99
3
3
3
==CH, 1,2-addition product), 4.85 (d, JHH = 7.5 Hz, ==CH, E-1,4-
(d, JHH = 8.1 Hz, Ph), 6.83 (t, JHH = 7.3 Hz, Ph), 4.63 (s, CH2N),
3
3
3
addition product), 4.61 (d, JHH = 7.0 Hz, ==CH, Z-1,4-addition
1.04 (t, JHH = 7.8 Hz, SiCH2CH3), 0.89 (q, JHH = 7.8 Hz, SiCH2CH3).
3
product), 3.36 (bd, JHH = 7.0 Hz, CH2, Z-1,4-addition product),
3
3.29 (bd, JHH = 7.5 Hz, CH2, E-1,4-addition product).
Deuterosilylation of cinnamaldehyde (entry 2, Table 2)
Using the general procedure at 25 ꢁC, we deuterosilylated N-
benzylidene aniline (18 mg, 0.1 mmol) by [1-2H]-triethylsilane.
Spectroscopic data of the deuterosilylated product were
consistent with those of the non-labelled compound.
Hydrosilylation of cinnamaldehyde (entries 11 and 12, Table 1)
Using the general procedure at 25 ꢁC, we hydrosilylated
cinnamaldehyde (13 mL, 0.1 mmol). Spectroscopic data of the
1,2-addition and E-1,4-addition products were consistent with
previously reported data for these compounds.28
1H NMR (500 MHz, CD2Cl2): characteristic signals, d 7.28
3
3
(d, JHH = 4.3 Hz, Ph), 7.20 (m, Ph), 7.15 (t, JHH = 7.8 Hz, Ph), 6.96
SiEt3H (entry 11, Table 1) 1H NMR (400 MHz, CD2Cl2):
3
3
(d, JHH = 8.1 Hz, Ph), 6.80 (t, JHH = 7.5 Hz, Ph), 4.58 (br s, CHDN),
3
characteristic signals, d 6.63 (d, JHH = 16.0 Hz; ==CH, 1,2-addition
3
3
1.02 (t, JHH = 7.8 Hz), 0.86 (q, JHH = 7.8 Hz, 6H).
3
product), 6.39 (dt, JHH = 12.0, 1.2 Hz; ==CH, E-1,4-addition
product), 6.33 (dt, 3JHH = 16.0, 5.2 Hz; ==CH, 1,2-addition product),
Hydrosilylation of N-benzyliden-t-butylamine (entry 3, Table 2)
3
5.19 (dt, JHH = 12.0, 7.5 Hz; ==CH, E-1,4-addition product), 4.76
3
(m, ==CH, Z-1,4-addition product), 4.37 (dd, JHH = 5.2, 1.6 Hz; Using the general procedure at 50 ꢁC, we hydrosilylated N-
CH2, 1,2-addition product), 3.26 (d, 3JHH = 7.5; CH2, E-1,4-addition benzyliden-t-butylamine (18 mL, 0.1 mmol) by triethylsilane.
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Copyright © 2011 John Wiley & Sons, Ltd.
J. Label Compd. Radiopharm 2012, 55 29–38

J. Campos et al.
1H NMR (400 MHz, CD2Cl2): characteristic signals, d 4.14 (s, application to the catalytic deuterosilylation of some organic
t
N-CH-Si, C-Si isomer), 3.75 (s, CH2-NSi, C-N isomer), 1.22 (s, Bu, molecules containing C==O, C==N and CꢀN bonds.
C-Si isomer), 1.19 (s, tBu, C-N isomer).
Hydrosilylation of (E)-N-(1-phenylethylidene)aniline (entry 4,
Table 2)
Acknowledgements
Financial support (FEDER contribution) from the Spanish Ministry
Using the general procedure at 50 ꢁC, we hydrosilylated
of Science (projects CTQ2010-17476 and Consolider-Ingenio
2010 CSD2007-00006) and from the Junta de Andalucía (grant
FQM-119 and project P09-FQM-4832) is gratefully acknowl-
edged. J. C. thanks the Ministerio de Educación for a research
grant (ref. AP20080256), M. R. thanks CSIC for a JAE postdoctoral
contract (ref. JAEDoc107) and A. C. E. thanks CONACYT (Mexico)
for a research grant (ref. 22934).
ketimine (E)-N-(1-phenylethylidene)aniline (0.020 mg, 0.1 mmol)
by triethylsilane. Spectroscopic data of the reaction mixture were
consistent with previously reported data for this compound.30
1H NMR (300 MHz, CD2Cl2): characteristic signals, d 6.7
3
3
(d, JHH = 8.2 Hz, N-Ph(o)), 4.52 (q, JHH = 6.7 Hz, CH3CH-N), 1.62
3
(d, JHH = 6.7 Hz, CH3CH-N).
Hydrosilylation of (E)-N-(1-phenylethylidene)aniline (entry 5, Table 2)
Conflict of Interest
Using the general procedure at 50 ꢁC, acetonitrile (5 mL,
0.1 mmol) was hydrosilylated by triethylsilane.
The authors did not report any conflict of interest.
1H NMR (500 MHz, CD2Cl2): characteristic signals, d 2.88
3
3
(q, JHH = 7.4 Hz, CH3CH2N), 0.84 (t, JHH = 7.4 Hz, CH3CH2N).
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