Activation of Si-Si bonds for copper(I)-catalyzed conjugate silylation

Article abstract of DOI:10.1002/ejoc.201200767

Several alkyl- and vinylsilanes were prepared through the copper(I)-catalyzed conjugate silylation of α,β-unsaturated compounds. Optimal reaction conditions were first investigated to realize the conjugate addition of a nucleophilic silicon species to poo

Full text of DOI:10.1002/ejoc.201200767

Job/Unit: O20767
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Date: 07-08-12 18:22:46
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SHORT COMMUNICATION
DOI: 10.1002/ejoc.201200767
Activation of Si–Si Bonds for Copper(I)-Catalyzed Conjugate Silylation
Laura Iannazzo[a] and Gary A. Molander*[a]
Keywords: Silanes / Copper / Nucleophilic addition / Alkenes / Silicon
Several alkyl- and vinylsilanes were prepared through the
copper(I)-catalyzed conjugate silylation of α,β-unsaturated
compounds. Optimal reaction conditions were first investi-
gated to realize the conjugate addition of a nucleophilic sili-
con species to poorly electrophilic acceptors such as phen-
ylvinyl sulfone by cleavage of the Si–Si bond of a disilane
reagent. The scope of this reaction was extended to various
electrophiles bearing different electron-withdrawing groups
and afforded the desired substituted alkyl- and vinylsilanes.
Among the wide range of commercially available disilanes,
the reactivities of alkyl-, aryl-, and ethoxydisilane were also
examined.
Introduction
Scheidt reported an extension of this method to α,β-unsatu-
rated esters, but that study was restricted to the case of
highly electrophilic alkylidene malonates.[6] This limitation
can be overcome by the use of silylboranes such as Sugino-
me’s dimethylphenylsilylpinacolatoboron.[7] Very recently,
Santos successfully applied this strategy to various α,β-un-
saturated compounds.[8] However, despite the efficiency of
the activation of the Si–B bond[9] by transition metals (Cu,
Rh)[10,11] or N-heterocyclic carbenes,[12] this approach suf-
fers from a lack of atom economy,[13] as these reagents re-
quired an additional step for their synthesis.[7]
New methods for the preparation of organosilicon com-
pounds have received increased attention owing to the ap-
plications of organosilicon compounds as reagents in or-
ganic synthesis and their interesting properties in functional
materials.[1] Among the different methods, the metal-medi-
ated conjugate addition of nucleophilic silicon is particu-
larly attractive, because it leads to the formation of func-
tionalized β-silyl carbonyl compounds.[2] Although the use
of commercially available disilanes has been studied, the
generation of nucleophilic silicon by activation of a Si–Si
bond[3] from disilanes is limited to Pd-[4] and Cu-catalyzed[5]
In connection with our recent efforts on the development
conjugate silylation of enones and enals. More recently, of Cu-catalyzed 1,4-additions[14] and on the use of organo-
Scheme 1. General route to β-silyl carbonyl compounds by 1,4-addition.
silicon reagents,[15] we report herein a general method for
the conjugate silylation of various α,β-unsaturated com-
pounds using disilanes (Scheme 1).
[a] Roy and Diana Vagelos Laboratories,
Department of Chemistry, University of Pennsylvania,
Philadelphia, PA 19104-6323, USA
Fax: +1-215-573-7165
E-mail: gmolandr@sas.upenn.edu
Results and Discussion
The catalytic system was first optimized on the model
reaction of commercially available diphenyltetramethyldi-
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L. Iannazzo, G. A. Molander
SHORT COMMUNICATION
silane (1a) with phenylvinyl sulfone in the presence of CuI
salts (5 mol-%) followed by an acidic workup. After screen-
ing the copper sources with the use of cataCXiumA as the
ligand in DMF at 100 °C (Table 1, Entries 1–3), (CuOTf)2·
[16]
C6H6
appeared as the most efficient salt, yielding 2a in
38% yield, whereas CuI gave a lower yield of 33%. Surpris-
ingly, no reaction occurred with CuCl. Subsequently, a wide
range of ligands (phosphanyl and amino ligands, Figure 1)
was explored (Table 1, Entries 4–9). CyJohnPhos and phen-
anthroline provided similar results, affording desired sil-
ylated compound 2a in 52 and 53% yield, respectively.
Given the low price of phenanthroline, it was selected as
the ligand of choice. Finally, the influence of the solvent
was found to be crucial to activate the disilane,[5] and we
were delighted to observe that, among the aprotic polar sol-
vents tested, N,NЈ-dimethyl-N,NЈ-propylene urea (DMPU;
Table 1, Entry 12) dramatically improved the yield of the
reaction, providing 2a in 80% yield.
Figure 1. Ligands utilized in optimization studies.
Table 1. Optimization of the reaction conditions.
Table 2. Scope of the α,β-unsaturated substrates.
Entry
[Cu]
Ligand
Solvent Yield
[%]
1
2
3
4
5
6
7
8
(CuOTf)2·C6H6
CuI
cataCXiumA
cataCXiumA
cataCXiumA
PBu3
SPhos
CyJohnPhos
2-ethylpyridine
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
HMPA
DMI
38
33
[a]
CuCl
–
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
40
47
52
47
43
53
54
40
80
(CuOTf)2·C6H6 di-tert-butylbipyridine
9
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
phenanthroline
phenanthroline
phenanthroline
phenanthroline
10
11
12
DMPU
[a] No reaction.
[a] No reaction.
Diphenyltetramethyldisilane (1a) was subjected to the
previously optimized cleavage conditions by using CuI salts
Interestingly, the designed conditions could be extended
[(CuOTf)2·C6H6 (5 mol-%), phenanthroline (7 mol-%), in to the use of alkynes, leading to a new route for the prepa-
DMPU at 100 °C, overnight, followed by acidic workup ration of vinylsilanes (Table 3).[17] Hence, phenylbutynone
using p-toluenesulfonic acid in water] to generate a nucleo- allowed the formation of the corresponding silylated com-
philic silicon species, which was then trapped with several pound 6a in 74% yield (Table 3, Entry 1). Less-reactive alk-
1,4-acceptors such as sulfono, cyano, amido, and phos- ynyl esters also proved to be suitable partners, and methyl
phonato groups (Table 2, Entries 1–4). Phenyl vinyl sulfone and ethyl propiolates afforded desired 6b and 6c in 51 and
emerged as a very efficient acceptor for this reaction, as 41% yield, respectively (Table 3, Entries 2 and 3). A mixture
previously reported, yielding the corresponding silylated of two inseparable isomers was obtained with a predomi-
product in 80% yield (Table 2, Entry 1). Acrylonitrile was nant E configuration, as determined by 1H NMR spec-
also found to be a suitable partner for this transformation, troscopy. The same trend was observed for the other alkyl-
affording desired 3a in 60% yield (Table 2, Entry 2). In the substituted alkynes, which led to the formation of function-
case of less electrophilic substrates such as amides and alized vinylsilanes 6d–g in moderate yields with various
phosphonates, more limited results were obtained. A mod- E/Z ratios (Table 3, Entries 4–7). Complete stereoselectivity
erate yield of 38% was observed with unsaturated amide in favor of the E isomer was only observed in the cases of
4a (Table 2, Entry 3), and no reaction occurred with α,β- phenyl-substituted alkynes, albeit in a reduced yield in the
unsaturated diethylvinylphosphonate 5a (Table 2, Entry 4).
case of the propiolate (Table 3, Entries 1 and 8).
2
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Activation of Si–Si Bonds for Copper(I)-Catalyzed Conjugate Silylation
Table 3. Scope of the alkynes.
1
[a] Isomeric ratio determined by H NMR spectroscopy. [b] Mixture of 6d and silane (trace amounts).
Finally, owing to the ability of diphenyltetramethyldisil- complex mixture of unidentified products, and no reaction
ane (1a) to generate a nucleophilic silicon species in the 1,4 occurred with hexaethoxydisilane (1e), as the starting mate-
addition reactions, we decided to expand the scope of our rials were recovered.
method to other commercially available disilanes by using
phenyl vinyl sulfone as the acceptor (Scheme 2). We started
Conclusions
our investigation with hexamethyldisilane (1b), and ex-
pected alkylsilane 2b was detected in a low yield of 12%,
probably because of the volatility of the disilane reagent.
Tetraphenyldimethyldisilane (1c) emerged as a suitable part-
ner for this transformation, leading to 2c in 60% yield. Un-
fortunately, the use of hexaphenyldisilane (1d) only led to a
In summary, we have demonstrated that the copper-cata-
lyzed conjugate silylation by using disilanes can be applied
to a good range of α,β-unsaturated compounds. Various
electrophiles bearing different electron-withdrawing groups
were successfully used, and this method appears as a useful
and direct route for the preparation of substituted alkyl-
and vinylsilanes.
Experimental Section
Procedure for Silylation: Cu(OTf)2·C6H6 (0.025 mmol, 12.5 mg)
and phenanthroline (0.035 mmol, 6.3 mg) were placed in a Biotage
microwave vial under an atmosphere of argon and DMPU (1 mL)
was added. After stirring for 5 min at room temperature, the α,β-
unsaturated compound (0.5 mmol) and disilane (0.6 mmol) were
added, and the reaction mixture was heated conventionally to
Scheme 2. Variation of disilanes.
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L. Iannazzo, G. A. Molander
SHORT COMMUNICATION
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(Na2SO4), concentrated in vacuo, and purified by flash column
chromatography (hexanes/EtOAc).
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Supporting Information (see footnote on the first page of this arti-
cle): General considerations, characterization data, and copies of
1
the H NMR and 13C NMR spectra.
Acknowledgments
This research was supported by the National Institutes of Health
(GM R01 081376). We acknowledge Dr. Rakesh Kohli (University
of Pennsylvania) for obtaining HRMS data. We also thank Dr.
Nicolas Fleury-Brégeot (University of Pennsylvania) for his kind
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Received: June 8, 2012
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Published Online: ᭿
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Activation of Si–Si Bonds for Copper(I)-Catalyzed Conjugate Silylation
Conjugate Addition
L. Iannazzo, G. A. Molander* .......... 1–5
Activation of Si–Si Bonds for Copper(I)-
Catalyzed Conjugate Silylation
Alkyl- and vinylsilanes were prepared
through copper(I)-catalyzed conjugate ad-
dition through activation of Si–Si bonds.
Electrophilic substrates such as activated
alkenes containing sulfono, cyano, and
amido groups were used as acceptors for
Keywords: Silanes / Copper / Nucleophilic
addition / Alkenes / Silicon
this transformation, and ester-substituted
alkynes also emerged as suitable partners,
leading to a new method for the generation
of vinylsilanes.
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