Copper-catalyzed 1,2-addition of nucleophilic silicon to aldehydes: Mechanistic insight and catalytic systems

Article abstract of DOI:10.1002/chem.201102367

Activation of the Si-B inter-element bond with copper(I) alkoxides produces copper-based silicon nucleophiles that react readily with aldehydes to yield α-silyl alcohols (that is, α-hydroxysilanes) after hydrolysis. Two independent protocols were develope

Full text of DOI:10.1002/chem.201102367

DOI: 10.1002/chem.201102367
Copper-Catalyzed 1,2-Addition of Nucleophilic Silicon to Aldehydes:
Mechanistic Insight and Catalytic Systems
Christian Kleeberg,*[a] Evgenia Feldmann,[a] Eduard Hartmann,[b]
Devendra J. Vyas,[b, c] and Martin Oestreich[b]
ꢀ
Abstract: Activation of the Si B inter-
element bond with copper(I) alkoxides
produces copper-based silicon nucleo-
philes that react readily with aldehydes
to yield a-silyl alcohols (that is, a-hy-
droxysilanes) after hydrolysis. Two in-
dependent protocols were developed,
catalytic experiments as well as NMR
spectroscopic measurements. The pri-
mary reaction product of the addition
acterized crystallographically. Based on
these data, a reasonable catalytic cycle
ꢀ
is proposed. The NHC CuOtBu cata-
ꢀ
of the Si B reagent and the aldehyde
lytic setup performs nicely at elevated
temperature. A more reactive catalytic
system is generated from CuCN–
NaOMe, showing fast turnover at a sig-
nificantly lower temperature. Both aro-
matic and aliphatic aldehydes are
transformed into the corresponding a-
silyl alcohols in good to very good
yields under these mild reaction condi-
tions.
(a boric acid ester of the a-silyl alco-
hol) and also the “dead-end” inter-
mediate, formed in the competing
[1,2]-Brook rearrangement, were char-
ꢀ
one employing a well-defined NHC
CuOtBu complex and one using the
simple CuCN–NaOMe combination
without added ligand. The mechanism
of the aldehyde addition was investi-
gated in detail by stoichiometric and
Keywords: aldehydes · copper · nu-
cleophilic addition · silicon · trans-
metalation · X-ray diffraction
Introduction
tion of imines and proposed a catalytic cycle involving a
[5]
ꢀ
Cu Si complex as the silyl transfer reagent. The active cat-
The copper-catalyzed transfer of silicon nucleophiles[1] onto
various electrophiles, for example, a,b-unsaturated carbonyl
and carboxyl compounds,[2–4] imines,[5] alkynes,[6] allylic[7] and
alyst in this system is generated in situ from CuCN–NaOMe
ꢀ
in the presence of an Si B compound. We now decided to
apply the same strategy in carbonyl addition reactions as it
might provide a convenient direct route to a-silyl alcohols
(that is, a-hydroxysilanes) from commercially available alde-
hydes.
propargylic[8,9] chlorides, involving the Si B interelement
ꢀ
linkage[10] as the source of nucleophilic silicon, has recently
gained considerable attention. The actual nucleophile is as-
ꢀ
sumed to be a Cu Si complex that transfers the silicon
moiety onto the acceptor, followed by its regeneration
Aside from the retro-[1,2]-Brook rearrangement of transi-
ent a-silyloxy-substituted lithium carbanion pairs,[12] the ma-
jority of literature-known methods[13] for the preparation of
a-silyl alcohols are based on the (asymmetric) reduction of
acyl silanes,[14–19] or the hydrogenation of enolsilanes.[20]
However, the synthesis of the acyl silanes usually requires
several steps.[21] An alternative but lesser used approach is
ꢀ
through transmetalation of an intermediate Cu O complex
and the Si B reagent. The new methodology is particularly
ꢀ
attractive as it provides a facile access to copper-based sili-
con reagents without using strongly basic precursors. These
are necessary in the established chemistry of silicon-based
cuprates as stoichiometric reagents.[11] We recently reported
an efficient catalytic system for the copper-catalyzed silyla-
the addition of
a silicon nucleophile to a carbonyl
group.[22–25] Hiyama et al. had introduced a fluoride-cata-
ꢀ
lyzed Si Si bond cleavage followed by the addition of the
thus released silicon nucleophile to aldehydes.[22] Yields
were, however, found to be diminished by partial [1,2]-
Brook rearrangement.[23] Barrett and Hill then elaborated a
practical procedure that is based on the addition of easy-to-
make Me2PhSiLi to aliphatic and aromatic aldehydes.[24a]
Neither a-deprotonation (high chemoselectivity for enoliza-
ble aldehydes) nor Brook rearrangement were competing
with the 1,2-addition. Despite these efforts, the use of
strongly basic lithium silicon nucleophiles is not without
problems for functionalized aldehydes, and there is a note-
worthy report that the stoichiometric use of a silicon-based
cuprate overcomes that issue.[24c] The copper-mediated mild
[a] Dr. C. Kleeberg, E. Feldmann
Institut fꢀr Anorganische und Analytische Chemie
Technische Universitꢁt Carolo-Wilhelmina zu Braunschweig
Hagenring 30, 38106 Braunschweig (Germany)
Fax : (+49)0531-3915387
E-mail: ch.kleeberg@tu-braunschweig.de
[b] E. Hartmann, D. J. Vyas, Prof. Dr. M. Oestreich
Organisch-Chemisches Institut
Westfꢁlische Wilhelms-Universitꢁt Mꢀnster
Corrensstrasse 40, 48149 Mꢀnster (Germany)
[c] D. J. Vyas
NRW Graduate School of Chemistry
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201102367.
ꢀ
generation of nucleophilic silicon from Si B com-
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FULL PAPER
pounds[1–3,5–8] might therefore be useful in a catalytic one-
step access to a-silyl alcohols from aldehydes. We report
here two independent protocols for the catalytic 1,2-addition
of a silicon nucleophile to aromatic and aliphatic aldehydes
ꢀ
by employing either a well-defined NHC CuOtBu complex
or the CuCN–NaOMe combination without added ligand.
We also present insight into the mechanism of the former
catalysis for the first time.[26]
Results and Discussion
ꢀ
The nucleophilic attack of the Cu Si on the electrophile,
that is, the formal insertion of the electrophilic moiety into
ꢀ
the Cu Si bond, is supposed to be crucially involved in cata-
lytic silylation reactions.[1–3,5–8] To study this essential step in
Figure 1. Molecular structure of 6a. Thermal ellipsoids are given at the
50% probability level. 2,6-Diisopropylphenyl units are represented by
the ipso carbon atom only (spheres); hydrogen atoms are omitted for
clarity. Selected bond lengths [ꢃ] and angles [8]: Cu(1)–C(9) 1.904(2);
Cu(1)–C(1) 1.955(2); C(1)–O(1) 1.473(2); O(1)–Si(1) 1.633(2); C(9)–
Cu(1)–C(1) 169.64(8).
ꢀ
detail, we employed the complex [(iPrNHC)Cu SiMe2Ph]
(3; iPrNHC=1,3-bis(2,6-diisopropylphenyl)imidazol-2-yli-
dene) in stoichiometric reactions with an aldehyde. This
complex is readily generated by the reaction of the alcohola-
[27]
ꢀ
ꢀ
to complex [(iPrNHC)Cu OtBu] (1) and Me2PhSi Bpin
(2) (pin=pinacolato).[3,26a] An exemplary aldehyde, 4-tolyl
Table 1. Selected crystallographic data for 6a and 7a.[31]
ꢀ
aldehyde (4a), inserts cleanly into the Cu Si bond upon re-
6a
7a
action with 3 under mild conditions, leading to the forma-
tion of the benzyl complex 6a isolated in 53% yield
(Scheme 1). Complex 6a was characterized by a single X-
formula
C43H55CuN2OSi
707.52
C22H31BO3Si
382.37
Mr [gmolꢀ1
]
crystal system
space group
a[ꢃ]
b[ꢃ]
c[ꢃ]
a [8]
b [8]
g [8]
triclinic
P1 (no. 2)
monoclinic
P21/c (no. 14)
6.4823(5)
34.692(3)
10.8310(7)
90
117.782(7)
90
100(2)
2154.9(2)
1.179, 4
0.47ꢄ0.14ꢄ0.11
colorless, column
0.127 (0.71073 ꢃ)
4.4–54.0
¯
9.8343(3)
10.7270(3)
20.1244(6)
74.770(3)
83.437(2)
85.444(3)
100(2)
2032.3(1)
1.156, 2
0.36ꢄ0.35ꢄ0.27
colorless, block
0.599 (0.71073 ꢃ)
4.5–60.0
T [K]
V[ꢃ3]
1calcd [gcmꢀ3], Z
crystal dimensions [mm3]
color, shape
m [mmꢀ1] (l)
2q limits [8]
no. of reflns:
measured
86039
31671
independent
11639
8891
4682
4066
observed[a]
completeness
98.1% to 2q=60.08 99.6% to 2q=54.08
parameter/restraints
R1 (obs. reflns)[b]
wR2 (all reflns)[c]
GOF on F2
444/0
251/0
0.0518
0.0709
0.1158[d]
1.044
0.1606[e]
1.200
max./min. electron density
ꢀ0.563/1.267
ꢀ0.326/0.705
[eꢃꢀ3
]
[a] Observation criterion: I>2s(I). [b] R1 =Sj jFo jꢀjFcj j/SjFo j.
2
2
2
[c] wR2 ={S[w
1.5631P]ꢀ1 in which P=(Fo2 +2Fc2)/3. [e] w=[q2
3.5959P]ꢀ1, in which P=(Fo2 +2Fc2)/3.
G
E
[d] w=[q2
ACHTUNGTRENNUNG
ꢀ
Scheme 1. Stoichiometric experiment: Aldehyde insertion into the Cu Si
bond, followed by [1,2]-Brook rearrangement.
2
,
(Fo )+(0.0446P)2 +
ray diffraction study as well as by NMR spectroscopy and
its connectivity was unambiguously established. Compound
6a crystallized as racemate in the centrosymmetric triclinic
ic ligand. The copper is approximately linearly coordinated
with bond length and angles comparable to the closely relat-
ꢀ
ed
complex
[(iPrNHC)Cu CH(2,4,6-trimethylphenyl)-
¯
space group P1 with one molecule in the asymmetric unit.
(OBpin)] (adopted numbering scheme): Cu(1)–C(9)
The molecular structure of 6a (Figure 1 and Table 1, left
column) is typical for a (iPrNHC)Cu complex with a benzyl-
1.898(2) ꢃ, Cu(1)–C(1) 1.947(2) ꢃ, C(9)–Cu(1)–C(1)
175.46(8)8.[28a] The slightly larger deviation from linearity
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13539

C. Kleeberg et al.
might be attributed to the increased steric encumbrance of
the complex. The formation of 6a seems to suggest a nucle-
ophilic attack of the copper atom on the carbonyl carbon
atom in 4a. This regioselectivity would be more than sur-
prising as 3 and related complexes are supposed to transfer
the silicon nucleophile onto the electrophilic carbon atoms
of a,b-unsaturated carbonyl and carboxyl compounds,[2–4]
and imines[5] under formation of a C Si bond. On the other
ꢀ
hand, the formation of an analogous benzyl complex is re-
ported for the closely related reaction of complex
[28]
ꢀ
[(iPrNHC)Cu Bpin] with aldehydes. A DFT study on this
reaction substantiates the initial formation of the alcoholato
ꢀ
complex [(iPrNHC)Cu OCHR
Brook-like rearrangement to yield [(iPrNHC)Cu CHR-
G
ACHTUNGTRENNUNG
(OBpin)].[28] This suggests a similar pathway to 6a and,
hence, 5a rearranges to isomeric 6a, which is corroborated
by the known [1,2]-Brook rearrangement of a-silyl-substitut-
ed alkoxides.[29] To confirm the formation of 5a as an inter-
mediate, the reaction of 3 and 4a (excess) was monitored by
1H NMR spectroscopy (Figure 2). It is evident from the
Figure 3. Molecular structure of 7a. Thermal ellipsoids are given at the
50% probability level. Hydrogen atoms are omitted for clarity. Selected
bond lengths [ꢃ]: C(1)–O(1) 1.458(4); O(1)–B(1) 1.352(3); C(1)–C(2)
1.504(3); C(1)–Si(1) 1.909(3).
plex 5a is indeed an intermediate in the formation of 6a
and likewise 7a. Moreover, we also conclude that the trans-
metalation reaction of 5a and 2 generating 7a and 3 is sig-
nificantly faster than the competing rearrangement of 5a to
6a. Compound 7a was isolated in 50% yield by crystalliza-
tion from the reaction mixture upon addition of n-pentane
at ꢀ208C. It crystallized as racemate in the centrosymmetric
monoclinic space group P21/c with four molecules in the
unit cell. The molecular structure (Figure 3 and Table 1,
right column) is comparable to the closely related com-
ꢀ
pound pinB CH(2,4,6-trimethylphenyl)ACHTNUTRGNEUNG(OBpin) (adopted
numbering scheme): C(1)–O(1) 1.456(2) ꢃ, O(1)–B(1)
1.358(2) ꢃ, C(1)–C(2) 1.518(2) ꢃ.[28a] The formation of 7a
was also monitored by time-dependent H NMR spectrosco-
Figure 2. Relevant segments of the 1H NMR spectra (300 MHz, C6D6,
RT) of 3 and 6a, as well as the reaction mixture of 3 and 4a after 1 h at
ambient temperature (+6a in bottom spectrum).
1
py, using 3 (10 mol%), silyl boronic ester 2 (0.90 equiv), and
excess aldehyde 4a (1.0 equiv). Clean formation of 7a from
4a and 2 is seen at ambient temperature (Figure 4), the only
identified copper complex is 3 until 2 is largely consumed.
Complex 6a, being the “dead-end” copper complex, is only
formed from 5a when 2 is essentially completely consumed.
A reaction performed as described above (but in the ab-
sence of 3) proved that no uncatalyzed background reaction
1H NMR data obtained that complex 6a is formed as single
product, whereas unreacted 3 and 4a are still present after
1 h at ambient temperature. This clearly indicates that the
rearrangement step 5a!6a is considerably faster than the
insertion step 4a!5a (Scheme 1). The reaction of a catalyt-
ic amount of 3 (10 mol%) with 2 and 4a at ambient temper-
ature resulted in the formation of
a new compound
(Scheme 2), which was identified by NMR spectroscopy and
single crystal X-ray diffraction analysis as C-silylated and O-
borylated 7a (Figure 3). This is strong evidence that com-
Figure 4. Relevant segments of the time-dependent 1H NMR spectra
(300 MHz, C6D6, RT) of the copper-catalyzed 1,2-addition of 4a with 2
[3 (10 mol%), 2 (0.90 equiv), and 4a (1.0 equiv); *denotes an unassigned
signal].
Scheme 2. Catalytic experiment: Isolation of the non-rearranged O-
borylated a-silyl alcohol.
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Copper-Catalyzed 1,2-Addition
FULL PAPER
Table 2. Copper-catalyzed 1,2-addition to aldehydes employing
(NHC)CuOtBu (1): Optimization of the reaction conditions.
Entry
Catalyst 1
[mol%]
Solvent
T
[8C]
t
Yield
[%][b]
G
[h][a]
1
2
3
4
5
10
PhMe
PhMe
PhMe
PhMe
THF
RT
RT
60
90
60
32
74
16
16
16
75
81
80
54
85
5.5
5.5
5.5
5.5
[a] Full consumption of aldehyde as monitored by GLC analysis. [b] Iso-
lated product yield after flash chromatography on silica gel.
reaction conditions, we screened catalyst loading, reaction
temperature, and solvent in the reaction of test substrate 4a
(Table 2 with selected data): 5.5 mol% of 1 and 608C in tol-
uene were found to be the optimal conditions (Table 2, en-
tries 1–3). At higher reaction temperature (908C), unidenti-
fied by-products were detected by GLC analysis (Table 2,
entry 4). The catalysis worked equally well in THF (Table 2,
entry 5). This reaction setup was then applied to a series of
aromatic and aliphatic aldehydes 4 (Table 3). With respect
Scheme 3. Catalytic cycle of a typical 1,2-addition of nucleophilic silicon
ꢀ
using a preformed (NHC)Cu Si complex.
is present.[30] Although no quantitative kinetic data have
been obtained, the data available allows a catalytic cycle to
be proposed for the copper-catalyzed addition of silicon nu-
cleophiles to aldehydes (Scheme 3). It is particularly note-
worthy that during the catalytic process complex 3 is identi-
fied in the reaction mixture, thereby indicating that 3 is the
copper complex with the longest lifetime. We therefore con-
Table 3. Copper-catalyzed 1,2-addition to aldehydes employing
(iPrNHC)CuOtBu (1): Substrate scope.
ꢀ
clude that the insertion of the aldehyde into the Cu Si bond
is the rate-determining step. The regeneration of 3 by trans-
metalation of 5a and 2 accompanied by the release of the
7a is supposed to be faster. The same step must also be con-
siderably faster than the competing rearrangement of 5a to
6a, which is not formed until 2 is not available for the re-
generation of 3. Moreover, the reaction of isolated 6a with
2 does not lead to the formation of 7a and, for that reason,
we are convinced that 6a is not involved in the catalysis,
and that 5a and 6a are not in rapid equilibrium.[30] All these
data amount to the catalytic cycle depicted in Scheme 3. It
must be emphasized that the outlined catalytic cycle is re-
markably similar to the catalytic cycle proposed for the
copper-catalyzed 1,2-bisboration of aldehydes on basis of
DFT calculations, indicating a closely related mechanism for
the 1,2-bisboration and C-silyl-O-boration of aldehydes.[28b]
The reaction leading to 7a represents a procedure for the
chemoselective preparation of pinacol boric esters of a-silyl
alcohols (see Scheme 2). To make it synthetically useful,
these primary products must be hydrolyzed to the a-silyl al-
cohols. An exemplary experiment showed that 7a hydrolyz-
es readily in the presence of D2O.[30] The hydrolysis also
occurs readily during the purification by flash chromatogra-
phy on silica gel. After these mechanistic investigations
using stoichiometric and catalytic amounts of preformed
Entry
Aldehyde
R
t
a-Silyl
alcohol
Yield
[%][b]
[h][a]
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4 f
4g
4-MeC6H4
16
120
84
8a
8b
8c
8d
8e
8 f
8g
80
78
74
85
86[c]
68
50
2,4,6-Me3C6H4
4-(MeO)C6H4
4-CF3C6H4
16
16
16
16
U
G
[a] Full consumption of aldehyde as monitored by GLC analysis. [b] Iso-
lated product yield after flash chromatography on silica gel. [c] Reaction
at ambient temperature.
to aromatic aldehydes, both electron-donating as well as
electron-withdrawing groups were tolerated and isolated
product yields were generally good (Table 3, entries 1–4).
Reaction times were, however, much longer with a sterically
bulky (Table 3, entry 2) or an electron-rich aryl group
(entry 3). Conversely, an activated, electron-deficient alde-
hyde reacted in shorter reaction time (Table 3, entry 4).
These results reflect the importance of the electrophilicity
of the carbonyl carbon atom in the rate-determining silyl
transfer. To our delight, we found that also aliphatic (that is,
enolizable) aldehydes performed well (Table 3, entries 5 and
6). Functionalized aromatic aldehydes with reactive func-
ꢀ
complex [(iPrNHC)Cu SiMe2Ph] (3), we turned toward the
elaboration of a general procedure employing [(iPrNHC)-
CuOtBu] (1) as the catalyst precursor. To establish suitable
Chem. Eur. J. 2011, 17, 13538 – 13543
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13541

C. Kleeberg et al.
tional groups in the para-position (NO2 and OH groups) or
pyridine-4-carboxaldehyde did not yield the desired a-silyl
alcohols but only unidentified products (not shown). The re-
lated CN-substituted aldehyde afforded the product in mod-
erate yield (Table 3, entry 7). Based on our recent imine ad-
dition,[5] we anticipated that a more reactive catalytic system
might be generated from CuCN–NaOMe without added
ligand. As shown in Table 4, aromatic and aliphatic alde-
Table 4. Copper-catalyzed 1,2-addition to aldehydes employing CuCN–
NaOMe without added ligand: Substrate scope.
Scheme 4. General catalytic cycle of the 1,2-addition of nucleophilic sili-
con using a CuCN–NaOMe as the pre-catalyst.
Entry
Aldehyde
R
t
a-Silyl
alcohol
Yield
[%][b]
[h][a]
to be immediately protonated (V!VI).The catalysis also
works without added MeOH, presumably through another
s-bond metathesis of intermediate V with 2 resulting in the
1
2
3
4
5
6
7
8
9
4b
4c
4d
4e
4h
4i
4j
4k
4l
2,4,6-Me3C6H4
4-(MeO)C6H4
4-CF3C6H4
2
2
2
2
2
2
2
2
2
8b
8c
8d
8e
8h
8i
8j
8k
8l
58[c]
83
89
A
73[d]
50[d]
82
ꢀ
formation of VIII and Cu Si reagent III (V!VII!VII).
cyclohexyl
1-naphthyl
C6H5
4-ClC6H4
4-BrC6H4
Final hydrolysis during the aqueous work-up affords the a-
silyl alcohols VI (VIII!VI).
87
93
87
Conclusion
[a] Full consumption of aldehyde as monitored by GLC analysis. [b] Iso-
lated product yield after flash chromatography on silica gel. [c] CuCN
(10 mol%) and NaOMe (20 mol%) were used. [d] 2 (2.0 equiv) was
used.
Stoichiometric experiments on the insertion of aldehydes
into the Cu Si bond of a well-defined NHC–copper silyl
ꢀ
complex led to the development of a catalytic system for the
a-silylation of aldehydes. On the basis of experimental data
and NMR spectroscopy, we propose a catalytic cycle and
relative reaction rates of the reactions involved. Another
protocol for the a-silylation of aldehydes, employing a not
yet characterized catalyst prepared in situ from CuCN and
NaOMe, shows comparable performance at a significantly
lower temperature. Both protocols are well-suited for the a-
silylation of aromatic and aliphatic aldehydes under mild
conditions. Although the NHC-based catalytic system is syn-
thetically more elaborate, it provides valuable mechanistic
insight into copper-catalyzed transfer reactions of nucleo-
philic silicon. In turn, the CuCN–NaOMe-based system is
preparatively straightforward and performs exceedingly well
under mild conditions. However, functionalized aldehydes
remain challenging substrates for both catalytic systems.
Further combined computational and kinetic investigations
to gain a deeper insight into the mechanism of the a-silyla-
tion of aldehydes are subject of ongoing research.
hydes 4 are efficiently transformed into a-silyl alcohols 8
under these reaction conditions (MeOH–THF). Reaction
times are short, even at 08C. A trend similar to that found
for the NHC-based catalyst is observed. Steric hindrance is
detrimental, and double the amount of catalyst is required
to obtain a reasonable yield (Table 4, entry 1). Electron-de-
ficient, non-hindered aldehydes perform best (Table 4, en-
tries 2, 8, and 9). Aliphatic aldehydes afforded only decent
yields when using excess 2 (Table 4, entries 4 and 5). It is im-
portant to note that the order of reagent is crucial (see gen-
eral procedure 2 (GP2) in the Experimental Section). Any
changes to that led to inconsistent results. Compared with
the NHC-based system, the present setup is superior in
terms of practicability and reactivity as no pre-prepared
copper complex and no heating are required. The latter
aspect might be beneficial for sensitive substrates. The cata-
lytic cycle for the CuCN–NaOMe–MeOH system
(Scheme 4) is likely to be similar to the one investigated in
ꢀ
ꢀ
detail for [(iPrNHC)Cu OtBu] (1) and [(iPrNHC)Cu
SiMe2Ph] (3), respectively, (see Scheme 3). It begins with
ꢀ
the boron-to-copper transmetalation of in situ-formed Cu
OMe and 2 (I!III), the formal s-bond metathesis through
Experimental Section
ꢀ
II. Thus formed Cu Si reagent III adds to aldehyde IV to
arrive at intermediate V (IV!V) but we do not know
whether the 1,2-addition is rate-determining as with the
NHC ligand (see Scheme 3). With added MeOH, V is likely
General: Detailed experimental procedures (6a and 7a), detailed charac-
terization and experimental data (6a,7a, and 8a–8l), and crystallographic
data are provided in the Supporting Information.
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Copper-Catalyzed 1,2-Addition
FULL PAPER
General procedure for the a-silylation of aldehydes employing
ACHTUNGTRENNUNG[(iPrNHC)CuOtBu] (1) as precatalyst (GP1 for Table 3): In a glove box,
[11] For a review of silicon-based cuprate chemistry catalytic in copper,
see: A. Weickgenannt, M. Oestreich, Chem. Eur. J. 2010, 16, 402–
412.
[12] For a general retro-[1,2]-Brook rearrangement approach, see: R. J.
Linderman, A. Ghannam, J. Am. Chem. Soc. 1990, 112, 2392–2398.
[13] J. M. Aizpurua, C. Palomo in Science of Synthesis Vol. 4 (Ed.: I.
Fleming), Thieme, Stuttgart, 2002, 595–632.
[14] For the reduction of acyl silanes with the Itsuno reagent, see: J. D.
Buynak, J. B. Strickland, T. Hurd, A. Phanm, J. Chem. Soc. Chem.
Commun. 1989, 89–90.
a Schlenk tube was charged with 1 (11 mg, 0.021 mmol, 5.5 mol%) and
the indicated dried and degassed solvent (5 mL). After addition of the in-
dicated aldehyde 4 (0.38 mmol, 1.0 equiv) and Me2PhSiBpin (2, 110 mg,
0.42 mmol, 1.1 equiv) under inert conditions, the reaction was maintained
at 608C until full conversion (GLC monitoring). After removal of solvent
in vacuo, the residue was subjected to flash column chromatography on
silica gel using n-hexane/diethyl ether as eluent affording analytically
pure 8.
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General procedure for the a-silylation of aldehydes employing CuCN–
NaOMe as precatalyst (GP2 for Table 4): A flame-dried Schlenk tube
was successively charged with CuCN (0.020 mmol, 5.0 mol%), and
NaOMe (0.040 mmol, 10 mol%) under an inert atmosphere. After addi-
tion of THF (1 mL), the reaction mixture is maintained at RT for 1 h. At
08C, the indicated aldehyde 4 (0.40 mmol, 1.0 equiv), Me2PhSiBpin (2,
0.48 mmol, 1.2 equiv), MeOH (1.6 mmol, 4.0 equiv), and THF (1 mL)
were added in this order. The reaction was subsequently maintained at
08C until full conversion (TLC and GLC monitoring). Filtration through
a small pad of silica gel using tert-butyl methyl ether (10 mL) and evapo-
ration of the solvents under reduced pressure afforded the corresponding
a-silyl alcohol 8 as the crude product. Purification by flash column chro-
matography on silica gel using cyclohexane/tert-butyl methyl ether as the
eluent affords analytically pure 8.
Acknowledgements
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The research was supported by the Fonds der Chemischen Industrie
(Liebig fellowship to C.K., 2010–2013 as well as predoctoral fellowship to
E.H., 2009–2011) and the Deutsche Forschungsgemeinschaft (Oe 249/3–
2). D.J.V thanks the NRW Graduate School of Chemistry for a predoc-
toral fellowship (2008–2011).
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[30] For details, see the Supporting Information.
[31] Crystallographic data (excluding structure factors) for the structures
reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary crystallographic
data: CCDC-836714 and 836715. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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[10] For a recent summary of Si B chemistry, see: T. Ohmura, M. Sugi-
Received: July 29, 2011
Published online: October 24, 2011
nome, Bull. Chem. Soc. Jpn. 2009, 82, 29–49.
Chem. Eur. J. 2011, 17, 13538 – 13543
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
13543