Synthesis of formylsilanes through oxidative cleavage of α-silyl glycols

Article abstract of DOI:10.1021/jo402123j

A convenient method for the synthesis and isolation of highly reactive formylsilanes by oxidative cleavage of α-silyl glycols is presented. The mild conditions provide an entry to acid- and heat-sensitive members of this theoretically intriguing class of compounds. The utility of the method is demonstrated through the isolation and subsequent diastereoselective derivatization of t-BuMe₂- and t-BuPh₂-formylsilanes, previously not reported in isolated form.

Full text of DOI:10.1021/jo402123j

Note
pubs.acs.org/joc
Synthesis of Formylsilanes through Oxidative Cleavage of α‑Silyl
Glycols
Henrik von Wachenfeldt and Daniel Strand*
Centre for Analysis and Synthesis, Department of Chemistry, Lund University, PO Box 124, S-221 00 Lund, Sweden
S
* Supporting Information
ABSTRACT: A convenient method for the synthesis and isolation of highly reactive
formylsilanes by oxidative cleavage of α-silyl glycols is presented. The mild conditions
provide an entry to acid- and heat-sensitive members of this theoretically intriguing class
of compounds. The utility of the method is demonstrated through the isolation and
subsequent diastereoselective derivatization of t-BuMe2- and t-BuPh2-formylsilanes, previously not reported in isolated form.
he simplest acylsilanes,1 formylsilanes, are a class of highly
reactive species that are in principle synthetically
Scheme 1. Preparative Synthesis of Formylsilanes
T
equivalent to prostereogenic formaldehyde.2 While higher
acylsilanes are frequently employed in synthesis,3 applications
of formylsilanes are surprisingly rare. This paucity is likely a
reflection of their challenging synthesis and very high inherent
reactivity. When exposed to limited amounts of oxygen,
formylsilanes rapidly rearrange to the correponding silanols
with loss of carbon dioxide,4 and exposure to the atmosphere
has been reported to cause spontaneous ignition.5 To advance
the chemistry of these potentially useful compounds, general,
mild, and operationally convenient procedures that enable
isolation of the products are of particular interest.
In a pioneering study, Swern oxidation of trimethylsilylme-
thanol was used to generate Me3-formylsilane, which was
trapped in situ by reactions with Wittig ylides to produce
vinylsilanes.6a,7 This procedure was later extended also to
reactions with hydrazines and organometallics.6b More recently,
(1,3-dioxolan-2-yl)silanes8 and benzotriazol(1-yl)carbazol(9-
yl)-silylmethane derivatives9 have been used in transacetaliza-
tion reactions with hydrazines and the latter also to generate
the electrophile in an aldol condensation.
For more elaborate applications of formylsilanes in synthesis,
preparative scale access to such compounds in isolated form is
likely a prerequisite. To this end, only two procedures are
currently available (Scheme 1): (i) insertion of carbon
monoxide into the Zr−Si bond of TMS3Si− and Ph3Si−Zr
complexes to generate the corresponding η2-complexes, which
upon exposure to HCl produces the thermally stable Ph3- and
(Me3Si)3-formylsilanes,5a,b and (ii) hydrolysis of (dimethox-
ymethyl)-triisopropylsilane under carefully controlled condi-
tions to form i-Pr3-formylsilane.10 Importantly, the i-Pr3-
formylsilane was in the latter work shown to participate in
highly diastereoselective Wittig and aldol reactions.
we present an operationally simple procedure for the syntheses
of formylsilanes by oxidative cleavage of readily available α-silyl
glycols.12 On a 3 mmol scale, the formylsilane products were
obtained in good isolated yields with homogenities adequate for
synthetic applications as demonstrated by diastereoselective
aldol and HWE reactions.
The principal byproducts of the reaction, formaldehyde and
sodium iodate, are water soluble and can thus be conveniently
removed by partitioning the reaction mixture against pentane
under an inert atmosphere. The mild conditions (i.e., neutral
pH and ambient temperature) enabled the synthesis of t-
BuMe2-formylsilane and t-BuPh2-formylsilane, previously not
reported in isolated form.
The possibility of using oxidative diol cleavage for
formylsilane synthesis was first evaluated by a screening of
standard conditions and reagents using α-silyl glycol 1a13 as the
substrate (Table 1). NaIO4 in a mixture of acetonitrile and
water (2:1) gave complete consumption of the starting
materials within one hour, and the desired formylsilane 2a
was formed in 61% yield along with minor amounts of the
corresponding silanol 3a.14 Longer reaction times, use of excess
NaIO4, or a more concentrated reaction mixture under
The potential of using formylsilanes, and by extension their
imine derivatives, as homologues to their nonenolizable
aliphatic counterparts in multicomponent reactions,11 together
with the operational drawbacks of current procedures (high-
pressure carbon monoxide and strong acid or elevated
temperature and stochiometric use of mercury) prompted us
to investigate alternative methods for their prepration. Herein
Received: September 25, 2013
© XXXX American Chemical Society
A
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Table 1. Reagents and Conditions for Oxidative Cleavage of
α-Silyl Glycol 1a
Scheme 2. Synthesis of α-Silyl Glycols 1a−d
a
b
yield (%)
entry oxidant (equiv)
solvent
time
2a; 3a; 4a
b
1
2
3
4
5
NaIO4 (1.0)
NaIO4 (1.0)
NaIO4 (1.0)
MeCN/H2O
(2:1)
30 min
49; 5; 0
b
b
b
b
MeCN/H2O
(2:1)
1 h
61; 8; 0
60; 13; 0
1; 10; 0
3; 33; 0
MeCN/H2O
(2:1)
2 h
a
Table 2. Preparative Synthesis of Formylsilanes 2a−c
NaIO4/silica
(1.0)
DCM
22 h
22 h
NaIO4 (1.0)
EtOAc/H2O
(2:1)
b
c
c
c
6
7
8
9
H5IO6 (1.2)
PIDA (1.2)
THF
10 min
10 min
10 min
5 h
0; 67; 0
0; 0; 38
0; 0; 69
0; 0; 37
DCM
Pb(OAc)4 (1.2) MeCN
Mn(OAc)3 (4.0) MeCN
a
General conditions: Diol 2a (0.1 mmol), organic solvent (1 mL),
b
water (0.5 mL), rt. Yield determined by 13C NMR using
c
triisopropylsilane as internal standard. Yield determined by 1H
NMR using mesitylene as internal standard.
otherwise identical conditions gave lower yields due to
increased overoxidation.
Silica-supported NaIO4,15 or a two-phase solvent system
(EtOAc/water), gave very slow conversion and only trace
amounts of product. Periodic acid gave a fast consumption of
the starting material, even at 0 °C, but no formylsilane
formation was detected. Oxidants like PIDA,16 Pb(OAc)4,17
a
b
Isolated yields are corrected for silanol content. Mol % of silanol in
isolated product (1H NMR).
18
and Mn(OAc)3 did not give detectible amounts of product
volatile product and silanol during solvent removal accounts for
the somewhat reduced isolated yield in Table 2, entry 3. In
contrast to diols 1a−c, cleavage of α-(TMS3Si)-glycol (1d)
gave only unspecific decomposition. This result is attributed, at
least in part, to the propensity of TMS3-silanes to be oxidized at
the Si−Si bond.27
2a; instead acyl-silyl acetal 4a, formed via a radical Brook
rearrangement,19 was obtained (yields are unoptimized).20 The
formation of 4a with hypervalent iodine and Mn(OAc)3 is
noteworthy as these reagents have potential as less toxic
alternatives to Pb(OAc)4 for the generation of α-silyloxy carbon
radicals in this context.
The successful cleavage of diol 1a with NaIO4 prompted an
investigation of the scalability and substrate scope of these
conditions. Multigram preparation of α-silyl glycols 1a−c for
this study was performed via a two-step procedure starting with
a partial hydrogenation of alkynylsilanes 5a−c with Lindlar
catalyst.21 Upjohn-dihydroxylation of the resulting vinylsilanes
6a−c22 then gave the corresponding α-silyl glycols 1a−c in
good yields over two steps. In contrast, the attempted
dihydroxylation of (TMS3Si)-vinylsilane 6d gave only a
complex mixture with OsO4/NMO. The desired α-(TMS3Si)-
glycol 1d could, however, be efficiently formed by dihydrox-
ylation with AD-mix β (Scheme 2).23,24
When conducting the cleavage of α-silyl glycol 1a on a
preparative scale (3 mmol), the reaction was complete in just
20 min, enabling the isolation of formylsilane 2a in good yield
together with only trace amounts of silanol (5%) (Table 2).
The same conditions translated well also to the synthesis and
isolation of the new t-BuPh2- and t-BuMe2-formylsilanes 2b and
2c. Access to these compounds is particularly attractive, as
nucleophilic addition to t-BuMe2-formylsilane (2b) constitutes
an entry to α-(t-BuMe2Si)-alcohols, a motif previously
exploited as a chiral primary alcohol equivalent,25 and
derivatives carrying a t-BuPh2-group have added value as a
masked hydroxyl group.26 Partial evaporation of the semi-
In agreement with the literature data for known formylsi-
lanes, t-BuPh2-formylsilane (2b) and t-BuMe2-formylsilane (2c)
display properties characteristic of a highly polarized CO
bond (2b: 13C NMR δ = 243 (CO) ppm, IR νCO = 1650 cm−1;
2c: 13C NMR δ = 246 (CO) ppm, IR νCO = 1648 cm−1).
Molecular ions of the fragile structures were not detected by
MS-ESI. For analytical purposes, the isolated formylsilanes were
instead converted into their corresponding known 2,4-
dinitrophenylhydrazones 8a−c (Scheme 3).8,9 Noteworthy in
this context is the essentially quantitative formation of t-BuPh2-
derivative 8b from 2b. Recrystallization of the hydrazones from
MeOH gave single crystals from which the solid-state structures
were solved by X-ray crystallography.28 In agreement with the
apparent stability of these compounds, virtually no elongation
of the CN bonds (1.27−1.28 Å) were found compared to
that of related hydrazone derivatives of aliphatic aldehydes
(typically ranging from 1.25 to 1.26 Å).29
The usefulness of the title conditions to provide
formylsilanes for applications in synthesis was investigated by
subjecting i-Pr-formylsilane (2a) to the known syn-selective
aldol reaction with a Z-enolate of propiophenone.30 The yield
and selectivity of this reaction (64%; syn:anti > 98:2) followed
that previously reported for this substrate (65%, syn:anti >
97:3).10a Formylsilanes 2b and 2c were also investigated as
substrates in this reaction and were both found to give the
B
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enable access to formylsilanes in isolated form with good to
moderate isolated yields. The mildness of the protocol is
highlighted by synthesis, isolation, and characterization of the
sensitive t-BuMe2- and t-BuPh2-formylsilanes 2b and 2c. The
formylsilane products derived from this procedure were shown
to efficiently participate in diastereoselective aldol and HWE
reactions with up to excellent levels of diastereoselectivity.
Studies on expanding this methodology as well as investigations
of the properties and applications of these potentially very
useful compounds in synthesis are currently under way.
Scheme 3. Synthesis and Crystal Structures of Hydrazones
8a−c
a
EXPERIMENTAL SECTION
■
Optimization Study for Oxidative Cleavage of α-Silyl Glycol
1a. For details, see Table 1. To a vial charged with oxidant and a
magnetic stir-bar (for entries 1−3 and 5, dissolved in degassed water,
0.5 mL) was added a solution of α-silyl glycol 1a (21.8 mg, 0.1 mmol)
in the solvent indicated (1 mL, degassed). The resulting mixture was
stirred for the time and temperature indicated, after which pentane (3
mL, degassed) and water (3 mL, degassed) were added sequentially.
The aqueous layer was removed by syringe, and the organic layer was
concentrated under reduced pressure and then backfilled with
nitrogen. The yields were determined by quantitative 13C NMR32
1
for entries 1−6 and H NMR for entries 7−9 using triisopropylsilane
and mesitylene, respectively, as internal standard.
a
2-Hydroxy-1-((triisopropylsilyl)oxy)ethyl acetate (4a). The
NMR sample used in Table 1 entry 7 was concentrated and purified by
silica-gel chromatography eluting with EtOAc/petroleum ether (0−
20% EtOAc) to yield acyl-silyl acetal 4a (8.3 mg, 30%) as a clear oil,
>95% pure by NMR spectroscopy and a single spot by TLC: Rf = 0.53
in 1:3 EtOAc:petroleum ether; 1H NMR (400 MHz, C6D6) δ 6.31 (t, J
= 4.7 Hz, 1H), 3.57 (t, J = 5.3 Hz, 2H), 1.68 (s, 3H), 1.52 (t, J = 6.3
Hz, 1H), 1.12−1.04 (m, 21H) ppm; 13C NMR (101 MHz, C6D6) δ
169.8, 92.4, 65.7, 20.9, 18.1, 18.0, 12.5 ppm; IR (CHCl3 film) 3020
(m), 2948 (w), 2869 (m), 1734 (s), 1464 (m), 1375 (m) cm−1;
HRMS-ESI (m/z) [M + K]+ calcd for C13H28KO4Si, 315.1400, found
315.1394.
Thermal ellipsoid plots at 30% probability; hydrogen atoms are
omitted for clarity.
corresponding aldols with complete diastereoselectivities and
moderate isolated yields (Scheme 4). The propensity of the t-
Scheme 4. Diastereoselective Derivatization of
Formylsilanes 2b and 2c
a b
,
General Procedure for the Oxidative Cleavage of α-Silyl
Glycols 1a−c. To a gently stirred solution of diol (1 equiv) in MeCN
(10 mL/mmol diol, degassed) was added NaIO4 (1 equiv) dissolved in
water (5 mL/mmol diol, degassed) under a nitrogen atmosphere.
Within a few minutes the mixture turned yellow, and a white
precipitate started to form. After stirring for a total of 20 min (1a) or
30 min (1b and 1c), pentane (20 mL/mmol diol, degassed) and water
(10 mL/mmol diol, degassed) were added sequentially. The aqueous
layer was removed by syringe, and the remaining organic layer was
concentrated in the reaction vessel under reduced pressure (house
vacuum 20 mbar), after which it was backfilled with nitrogen to leave
the corresponding formylsilanes as yellow oils (2a,b) or a yellow
amorphous solid (2c).
a
b
Isolated yields. The selectivities were quantified by 1H NMR
Formyltriisopropylsilane (2a).10a Scale: 3.0 mmol of diol 1a. Yield:
c
1
spectroscopy of the crude reaction mixtures. No minor diastereomer
detected. The relative configuration was assigned by analogy: see ref
10a and references therein.
556 mg, 88% (5% silanol), isolated as a yellow oil; H NMR (400
MHz, C6D6) δ 12.07 (s, 1H), 1.09−1.05 (m, 3H), 0.99 (d, J = 6.5 Hz,
18H) ppm; 13C NMR (101 MHz, C6D6) δ 246.7, 18.5, 10.4 ppm; IR
(CHCl3 film) 1647 (νCO) cm−1.
Formyl-tert-butyldiphenylsilane (2b). Scale: 3.0 mmol of diol 1b.
Yield: 743 mg, 88% (5% silanol), isolated as a yellow oil; H NMR
1
BuPh2 group to migrate after addition of the enolate leading to
a reduced yield could be suppressed by quenching the reaction
immediately after addition of the enolate. The library of
available transformations for formylsilanes was also expanded to
include E-selective olefinations by reacting silanes 2b and 2c
under Horner−Wadsworth−Emmons (HWE) conditions.31 In
this reaction t-BuMe2 formylsilane (2c) gave a good geometric
selectivty (E:Z = 93:7), whereas t-BuPh2-formylsilane (2b) gave
only a fair selectity (E:Z = 61:39) but a higher isolated yield.
In conclusion, an operationally convenient procedure for the
synthesis of formylsilanes by oxidative cleavage of readily
available α-silyl glycols with NaIO4 is described. The conditions
(400 MHz, C6D6) δ 12.14 (s, 1H), 7.62−7.53 (m, 4H), 7.16−7.09 (m,
6H), 1.09 (s, 9H) ppm; 13C NMR (101 MHz, C6D6) δ 242.5, 136.5,
131.1, 130.4, 128.5, 27.4, 18.9 ppm; IR (CHCl3 film) 1650 (νCO
)
cm−1.
Formyl-tert-butyldimethylsilane (2c). Scale: 5.0 mmol of diol 1c.
Yield: 459 mg, 61% (4% silanol), isolated as a yellow amorphous solid;
1H NMR (400 MHz, C6D6) δ 11.89 (s, 1H), 0.81 (s, 9H), −0.08 (s,
6H) ppm; 13C NMR (101 MHz, C6D6) δ 245.7, 26.4, 16.9, −8.8 ppm;
IR (CHCl3 film) 1648 (νCO) cm−1.
General Procedure for the Hydrazone Formation. To 2,4-
dinitrophenylhydrazine (1.48 g, 5.0 mmol, 33% in H2O) was added
formylsilane (3.05−4.10 mmol) in MeCN (50 mL, degassed) under a
C
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nitrogen atmosphere. The resulting mixture was stirred at ambient
temperature for 20 h, and then concentrated, suspended in CHCl3 (50
mL), and filtered. The filtrate was concentrated and purified by silica-
gel chromatography eluting with EtOAc/petroleum ether (0−10%
EtOAc) to yield the corresponding hydrazones 8a−c.
1-(Triisopropylsilyl)ethane-1,2-diol (1a).13 Yield: 67% (60% from
crystallization and 7% from chromatography), isolated as a white solid,
>95% pure by NMR spectroscopy and a single spot by TLC; Rf = 0.36
in 1:3 EtOAc:petroleum ether; 1H NMR (400 MHz, CDCl3) δ 3.96−
3.74 (m, 3H), 2.01 (bs, 2H), 1.19−1.06 (m, 21H) ppm; 13C NMR
(101 MHz, CDCl3) δ 66.6, 66.0, 19.1, 19.0, 10.7 ppm; IR (CHCl3
film) 3364 (s, br), 2943 (s), 2866 (s), 1434 (m), 1050 (m), 882 (m)
cm−1; HRMS-ESI (m/z) [M + Na]+ calcd for C11H26NaO2Si,
241.1600, found 241.1599; mp 52.5−52.8 °C (recrystallized from
pentane at −78 °C).
(E)-1-(2,4-Dinitrophenyl)-2-((triisopropylsilyl)methylene)-
hydrazine (8a).9,10a Scale: 3.34 mmol of formylsilane 2a. Yield: 1.19 g,
89%, isolated as a yellow solid, >95% pure by NMR spectroscopy and
1
a single spot by TLC; Rf = 0.74 in 1:10 EtOAc:petroleum ether; H
NMR (400 MHz, CDCl3) δ 11.10 (s, 1H), 9.14 (d, J = 2.6 Hz, 1H),
8.34 (ddd, J = 9.6, 2.6, 0.6 Hz, 1H), 7.99 (d, J = 9.6 Hz, 1H), 7.82 (d, J
= 1.1 Hz, 1H), 1.35−1.25 (m, 3H), 1.15 (d, J = 7.2 Hz, 18H) ppm; IR
(CHCl3 film) 3301 (m), 3021 (m), 2867 (m), 1618 (s), 1595 (m),
1517 (m), 1338 (s), 1317 (s) cm−1; mp 112.1−112.5 °C (recrystal-
lized from warm MeOH by slow cooling).
1-(tert-Butyldiphenylsilyl)ethane-1,2-diol (1b). Yield: 61% (20%
from crystallization and 41% from chromatography), isolated as a
white solid, >95% pure by NMR spectroscopy and a single spot by
1
TLC; Rf = 0.32 in 1:3 EtOAc:petroleum ether; H NMR (400 MHz,
CDCl3) δ 7.75−7.69 (m, 2H), 7.69−7.62 (m, 2H), 7.47−7.30 (m,
6H), 4.23 (dd, J = 10.5, 3.1 Hz, 1H), 3.83−3.63 (m, 2H), 2.09 (bs,
2H), 1.16 (s, 9H) ppm; 13C NMR (101 MHz, CDCl3) δ 136.6, 136.3,
133.2, 132.8, 129.71, 129.69, 128.0, 66.4, 65.7, 28.4, 18.5 ppm. The
spectra contain a signal overlap in the aromatic region; IR (CHCl3
film) 3376 (s, br), 3072 (w), 3013 (w) 2859 (m), 1427 (m), 1105
(m), 1053 (m), 882 (m) cm−1; HRMS-ESI (m/z) [M + Na]+ calcd for
C18H24NaO2Si, 323.1443, found 323.1444; mp 86.6−87.1 °C
(recrystallized from pentane at −78 °C).
(E)-1-((tert-Butyldiphenylsilyl)methylene)-2-(2,4-dinitrophenyl)-
hydrazine (8b).9 Scale: 4.10 mmol of formylsilane 2b. Yield: 1.75 g,
95%, isolated as a yellow solid, >95% pure by NMR spectroscopy and
1
a single spot by TLC; Rf = 0.34 in 1:10 EtOAc:petroleum ether; H
NMR (400 MHz, CDCl3) δ 11.27 (s, 1H), 9.14 (d, J = 2.5 Hz, 1H),
8.33 (dd, J = 9.5, 2.0 Hz, 1H), 8.10 (d, J = 1.1 Hz, 1H), 7.95 (d, J = 9.5
Hz, 1H), 7.74−7.64 (m, 4H), 7.51−7.36 (m, 6H), 1.22 (s, 9H) ppm;
IR (CHCl3 film) 3300 (m), 3019 (m), 2861 (w), 1618 (s), 1596 (m),
1515 (m), 1339 (s), 1317 (s) cm−1; mp 128.2−128.5 °C (recrystal-
lized from warm MeOH by slow cooling).
1-(tert-Butyldimethylsilyl)ethane-1,2-diol (1c). To a stirred sol-
ution of tert-butyldimethylsilylacetylene (4.94 g, 35.2 mmol, 1 equiv)
and quinoline (207 μL, 1.76 mmol, 5%) in t-BuOH (35.2 mL) was
added Lindlar catalyst (5% Pd on CaCO3 poisoned with lead, 225 mg,
0.105 mmol, 3%), under a nitrogen atmosphere. The atmosphere was
changed to H2 (purged three times using H2 from a balloon). After 3 h
the mixture was filtered trough a plug of Celite. t-BuOH (17.6 mL),
water (17.6 mL), NMO (50% in water, 14.6 mL, 70.4 mmol, 2 equiv),
and OsO4 (2.5% in t-BuOH, 1.78 mL, 0.176 mmol, 0.5%) were added.
After stirring at ambient temperature for 1 h the reaction was
quenched by addition of Na2SO3 (10 g) and stirred for additionally 30
min. The mixture was diluted with water (200 mL), extracted with tert-
butyl methylether (2 × 200 mL), and concentrated. Purification by
silica-gel chromatography eluting with EtOAc/petroleum ether (0−
25% EtOAc) yielded diol 1c (4.02 g, 65%) as a white solid, >95% pure
by NMR spectroscopy and a single spot by TLC: Rf = 0.18 in 1:3
(E)-1-((tert-Butyldimethylsilyl)methylene)-2-(2,4-dinitrophenyl)-
hydrazine (8c).9 Scale: 3.05 mmol of formylsilane 2c. Yield: 809 mg,
82%, isolated as a yellow solid, >95% pure by NMR spectroscopy and
1
a single spot by TLC; Rf = 0.50 in 1:10 EtOAc:petroleum ether; H
NMR (400 MHz, CDCl3) δ 11.09 (s, 1H), 9.13 (d, J = 2.6 Hz, 1H),
8.33 (ddd, J = 9.6, 2.6, 0.7 Hz, 1H), 8.01 (d, J = 9.6 Hz, 1H), 7.82 (d, J
= 1.1 Hz, 1H), 1.00 (s, 9H), 0.23 (s, 6H) ppm; IR (CHCl3 film) 3302
(m), 3020 (m), 2862 (w), 1618 (s), 1595 (m), 1517 (m), 1338 (s),
1317 (s) cm−1; mp 135.1−136.9 °C (recrystallized from warm MeOH
by slow cooling).
General Procedure for the Partial Hydrogenation to Alkenes
6a,b. To a stirred solution of silylacetylene (1.0 equiv) and quinoline
(0.05 equiv) in methanol (0.8 M) was added Lindlar catalyst (5% Pd
on CaCO3 poisoned with lead, 0.3%), under a nitrogen atmosphere.
The atmosphere was changed to H2 (H2 from a balloon) and purged
three times. Upon complete consumption of the alkyne (TLC
control), the mixture was filtered trough a plug of Celite and
concentrated. The crude mixture was redissolved in petroleum ether,
filtered trough a plug of silica, and concentrated to yield the
corresponding vinyl silanes 6a,b.
1
EtOAc:petroleum ether; H NMR (400 MHz, CDCl3) δ 3.83−3.68
(m, 2H), 3.63 (dd, J = 9.4, 3.2 Hz, 1H), 2.05 (s, 2H), 0.94 (s, 9H),
0.05 (s, 3H), −0.03 (s, 3H) ppm; 13C NMR (101 MHz, CDCl3) δ
66.1, 66.0, 27.0, 16.8, −7.4, −8.0 ppm; IR (CHCl3 film) 3377 (s, br),
2954 (m), 2858 (m), 1464 (m), 1057 (m) cm−1; HRMS-ESI (m/z)
[M + Na]+ calcd for C8H20NaO2Si, 199.1130, found 199.1136; mp
65.8−66.3 °C (from EtOAc:petroleum ether).
Triisopropyl(vinyl)silane (6a).33 Yield: 98%, isolated as a clear oil,
>95% pure by NMR spectroscopy and a single spot by TLC; Rf = 0.96
Tri(trimethylsilyl)(vinyl)silane (6d).35 To chlorotris(trimethylsilyl)-
silane (8.39 g, 30 mmol) was added vinyl magnesium bromide (0.7 M
in THF, 64.3 mL, 45 mmol) at 0 °C under a nitrogen atmosphere.
The resulting mixture was stirred for 20 min and then quenched by
addition of NH4Cl (aq., sat.). The resulting mixture was diluted with
water (50 mL) and extracted with CH2Cl2 (×2). The organic layer was
dried using a phaseseparator and concentrated to yield alkene 6d (8.27
g, 100%) as a white waxy solid, >95% pure by NMR spectroscopy and
1
in petroleum ether; H NMR (400 MHz, CDCl3) δ 6.10−5.98 (m,
2H), 5.71 (dd, J = 17.5, 7.1 Hz, 1H), 1.07−1.02 (m, 21H) ppm.
tert-Butyldiphenyl(vinyl)silane (6b).34 Yield: 89%, isolated as a
clear oil, >95% pure by NMR spectroscopy and a single spot by TLC;
1
Rf = 0.48 in petroleum ether; H NMR (400 MHz, CDCl3) δ 7.67−
7.62 (m, 4H), 7.45−7.36 (m, 6H), 6.60 (dd, J = 20.3, 14.8 Hz, 1H),
6.30 (dd, J = 14.8, 3.8 Hz, 1H), 5.74 (dd, J = 20.3, 3.8 Hz, 1H), 1.12
(s, 9H) ppm.
1
a single spot by TLC: Rf = 0.91 in 1:10 EtOAc:petroleum ether; H
General Procedure for Dihydroxylation of Vinyl Silanes
6a,b. To a stirred solution of alkene (1.0 equiv) and NMO (2.0 equiv)
in t-BuOH, THF, and water (ratio 1.0:1.4:1.0, 0.6 M) was added OsO4
(0.005 equiv, 2.5% in t-BuOH) under a nitrogen atmosphere. After
stirring at ambient temperature for 26 h, the reaction was quenched by
addition of Na2SO3 (0.3 g/mmol alkene), and the resulting mixture
was stirred for an additional 30 min. The reaction was then extracted
with petroleum ether (4 mL/mmol alkene), washed with water (2 × 4
mL/mmol alkene), and concentrated under reduced pressure. The
resulting crude product was dissolved in Et2O (2 mL/mmol alkene),
filtered trough a plug of silica, and concentrated. Crystallization from
pentane (0.5 M) at −78 °C gave the corresponding diols 1a,b. The
mother liquor was concentrated and purified by silica-gel chromatog-
raphy, eluting with EtOAc/petroleum ether (0−25% EtOAc), to
increase the yield.
NMR (400 MHz, CDCl3) δ 6.08 (dd, J = 19.8, 14.0 Hz, 1H), 5.93 (dd,
J = 14.0, 3.8 Hz, 1H), 5.66 (dd, J = 19.8, 3.8 Hz, 1H), 0.17 (s, 27H)
ppm.
(Tri(trimethylsilyl)silyl)ethane-1,2-diol (1d). To a solution of
K3Fe(CN)6 (0.98 g, 3.0 mmol), K2CO3 (0.41 g, 3.0 mmol), and
(DHQD)2-PHAL (78 mg, 0.1 mmol) in t-BuOH:water 1:1 (14 mL)
was added K2OsO2(OH)2 (7.4 mg, 0.02 mmol). The resulting yellow
mixture was cooled to 0 °C (some precipitation was observed). Vinyl
silane 6d (250 mg, 0.91 mmol) was added in one portion dissolved in
t-BuOH (1.5 mL) followed by addition of water (1.5 mL). The
resulting mixture was stirred at 0 °C for 20 h and then quenched by
addition of Na2SO3 (0.5 g) followed by stirring for an additional 30
min. The organic layer was separated, and the aqueous phase was
extracted with CH2Cl2. The combined organic layers were dried with
Na2SO4, filtered, and concentrated under reduced pressure.
D
dx.doi.org/10.1021/jo402123j | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Purification by silica-gel chromatography, eluting with EtOAc/
petroleum ether (3.13−12.5% EtOAc), yielded diol 1d (204 mg,
73%) as a white solid, >95% pure by NMR spectroscopy and a single
spot by TLC: [α]2D5 +7.9 (c = 0.7, CH2Cl2); Rf = 0.59 in 1:3
silica-gel chromatography, eluting with EtOAc/petroleum ether (5%
EtOAc), yielded the vinyl silane.
(E)- and (Z)-Ethyl 3-(tert-butyldimethylsilyl)acrylate (10a). Yield:
57%, (E):(Z) = 93:7, isolated as a clear oil, >95% pure by NMR
spectroscopy and two spots by TLC; Rf major = 0.54; minor = 0.51 in
1
EtOAc:petroleum ether; H NMR (400 MHz, CDCl3) δ 4.06−3.95
1
1:20 EtOAc:petroleum ether; H NMR (400 MHz, CDCl3) δ (E-
(m, 1H), 3.81−3.68 (m, 2H), 2.01 (bs, 1H), 1.76 (bs, 1H), 0.21 (app.
d, J = 2.6 Hz, 27H) ppm; 13C NMR (101 MHz, CDCl3) δ 68.5, 67.1,
1.7 ppm; IR (CHCl3 film) 3401 (s, br), 2949 (m), 2893 (m), 1397
(m), 1059 (m) cm−1; HRMS-ESI (m/z) [M + Na]+ calcd for
C11H32NaO2Si4, 331.1377, found 331.1376; mp 102.0−103.5 °C
(from EtOAc:petroleum ether).
isomer) 7.27 (d, J = 18.9 Hz, 1H), 6.26 (d, J = 18.9 Hz, 1H), 4.21 (q, J
= 7.2 Hz, 2H), 1.31 (t, J = 7.1 Hz, 3H), 0.90 (s, 9H), 0.09 (s, 6H)
ppm. (Z-isomer) 6.59 (d, J = 14.9 Hz, 1H), 6.54 (d, J = 14.9 Hz, 1H),
4.21 (q, J = 7.2 Hz, 2H), 1.30 (t, J = 7.1 Hz, 3H), 0.92 (s, 9H), 0.17 (s,
6H) ppm; 13C NMR (101 MHz, CDCl3) δ (E-isomer) 165.8, 147.4,
135.2, 60.5, 26.4, 16.5, 14.3, −6.5 ppm; IR (CHCl3 film) 2954 (m),
29.24 (s), 2855 (m), 1721 (m), 1463 (m), 997 (m) cm−1; HRMS-ESI
(m/z) [M + H]+ calcd for C11H23O2Si, 215.1467, found 215.1472.
(E)- and (Z)-Ethyl 3-(tert-butyldiphenylsilyl)acrylate (10b). Yield:
69%, (E):(Z) = 61:39, isolated as a clear oil, >95% pure by NMR
spectroscopy and two spots by TLC; Rf major = 0.43; minor = 0.41 in
General Procedure for Aldol Reaction with Formylsilanes.
To a stirred solution of diisopropylamine (2 equiv) in THF (0.2 M)
was added n-BuLi (1.6 M in hexanes, 1.5 equiv) at −78 °C under a
nitrogen atmosphere. The temperature was raised to 0 °C over 20 min
and then reduced back to −78 °C. Propiophenone (1.5 equiv) was
added dropwise over 1 min, and the resulting mixture was stirred for
20 min. The resulting enolate solution was then transferred by cannula
to a solution of freshly prepared formylsilane (1 equiv, corrected for
silanol) in THF (0.2 M) at −78 °C. After complete consumption of
the formylsilane (5 s for 2a,b and 2 h for 2c) the reaction was
quenched by addition of AcOH (10% v/v, in MeOH) or NH4Cl (aq.
sat.), diluted with water (50 mL/mmol formylsilane), extracted with
Et2O (2 × 50 mL/mmol formylsilane), dried with Na2SO4, filtered,
and concentrated. Purification of the crude product by silica-gel
chromatography, eluting with EtOAc/petroleum ether (0−10%
EtOAc), yielded the aldol adduct.
1
1:20 EtOAc:petroleum ether; H NMR (400 MHz, CDCl3) δ (E)-
isomer 7.68 (d, J = 18.8 Hz, 1H), 7.60−7.54 (m, 4H), 7.45−7.30 (m,
6H), 6.23 (d, J = 18.8 Hz, 1H), 4.22 (q, J = 7.1 Hz, 2H), 1.30 (t, J =
7.1 Hz, 3H), 1.11 (s, 9H) ppm; (Z)-isomer 7.70−7.66 (m, 4H), 7.45−
7.30 (m, 6H), 6.94 (d, J = 14.9 Hz, 1H), 6.89 (d, J = 14.9 Hz, 1H),
3.40 (q, J = 7.1 Hz, 2H), 0.99 (s, 9H), 0.58 (t, J = 7.1 Hz, 3H) ppm;
13C NMR (101 MHz, CDCl3) δ (E)-isomer 165.8, 143.8, 138.8, 136.4,
133.1, 129.8, 128.0, 60.9, 27.8, 18.5, 14.4 ppm; (Z)-isomer 166.1,
142.1, 140.7, 135.5, 133.9, 129.1, 127.6, 60.1, 27.3, 18.5, 13.5 ppm; IR
(CHCl3 film) 2959 (m), 2929 (m), 2858 (m), 1720 (s), 1427 (m),
999 (m) cm−1; HRMS-ESI (m/z) [M + Na]+ calcd for C21H26NaO2Si,
361.1600, found 361.1599.
(2R*,3R*)-3-(tert-Butyldimethylsilyl)-3-hydroxy-2-methyl-1-phe-
nylpropan-1-one (9a). Yield: 55%, isolated as a clear oil, >95% pure
by NMR spectroscopy and a single spot by TLC; Rf = 0.24 in 1:20
1
ASSOCIATED CONTENT
EtOAc:petroleum ether; H NMR (400 MHz, CDCl3) δ 7.95−7.90
■
(m, 2H), 7.62−7.56 (m, 1H), 7.52−7.46 (m, 2H), 4.01 (dd, J = 3.3,
1.9 Hz, 1H), 3.57 (qd, J = 7.2, 1.9 Hz, 1H), 2.84 (d, J = 3.4 Hz, 1H),
1.32 (d, J = 7.2 Hz, 3H), 0.96 (s, 9H), 0.15 (s, 3H), 0.05 (s, 3H) ppm;
13C NMR (101 MHz, CDCl3) δ 206.4, 135.8, 133.5, 129.0, 128.6, 63.3,
S
* Supporting Information
1H and 13C NMR spectra, X-ray diffraction structures, and
crystallographic data for compounds 8a−c in CIF format. This
material is available free of charge via the Internet at http://
pubs.acs.org
42.6, 26.9, 16.9, 12.9, −6.5, −7.2 ppm; IR (CHCl3 film) 3516 (m, br),
2952 (m), 2928 (m), 1666 (s), 1449 (m), 972 (m) cm−1; HRMS-ESI
(m/z) [M + Na]+ calcd for C16H26NaO2Si, 301.1600, found 301.1598.
(2R*,3R*)-3-(tert-Butyldiphenylsilyl)-3-hydroxy-2-methyl-1-phe-
nylpropan-1-one (9b). Yield: 58%, isolated as a white solid, >95%
pure by NMR spectroscopy and a single spot by TLC; Rf = 0.59 in
AUTHOR INFORMATION
Corresponding Author
*E-mail: daniel.strand@chem.lu.se.
■
1
1:10 EtOAc:petroleum ether; H NMR (400 MHz, C6D6) δ 8.13−
Notes
8.07 (m, 2H), 7.75−7.69 (m, 2H), 7.59−7.55 (m, 2H), 7.24−7.13 (m,
6H), 7.03−6.98 (m, 1H), 6.93−6.87 (m, 2H), 4.70 (dd, J = 2.8, 1.5
Hz, 1H), 3.60 (d, J = 2.8 Hz, 1H), 3.39 (qd, J = 7.2, 1.3 Hz, 1H), 1.22
(s, 9H), 1.19 (d, J = 7.2 Hz, 3H) ppm; 13C NMR (101 MHz, C6D6) δ
206.4, 137.7, 136.6, 135.9, 134.7, 134.2, 133.2, 129.74, 129.72, 128.8,
128.7, 128.3, 127.8, 65.8, 41.7, 28.6, 18.8, 13.5 ppm; IR (CHCl3 film)
3510 (w, br), 3017 (m), 2951 (m), 2862 (m), 1665 (s), 1428 (m),
1106 (m) cm−1; HRMS-ESI (m/z) [M + Na]+ calcd for
C26H30NaO2Si, 425.1913, found 425.1913; mp 105.8−107.7 °C
(from EtOAc:petroleum ether).
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Swedish Research Council and the Royal
Physiographical Society for financial support.
REFERENCES
■
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1
EtOAc:petroleum ether; H NMR (400 MHz, CDCl3) δ 7.96−7.91
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E
dx.doi.org/10.1021/jo402123j | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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F
dx.doi.org/10.1021/jo402123j | J. Org. Chem. XXXX, XXX, XXX−XXX