gem -Heterosubstituted (stannyl)methylsilanes as synthetic equivalents of functionalized  -stannyl(methyl) anions

 -Heterosubstituted silyl derivatives, such as phenylthio-, phenylseleno-and benzotriazolyl-stannyl silanes, react with aldehydes under tetra-n -butylammonium fluoride (TBAF) catalysis, leading to  -substituted-  - hydroxy stannanes, able to behave as precursors of Z - and E -olefins, generated by deoxystannylation. This reactivity shows the capability of such heterosubstituted silanes to act as masked carbanions through a mild functionalization of the carbon-silicon bond.


Introduction
The chemistry of organosilicon compounds has been studied over the years to search for new synthetic methodologies, able to develop chemical transformations under mild and selective conditions.In this context, their tolerance for various functional groups as well as their application as versatile intermediates in synthetic organic chemistry has been extensively demonstrated. 1,2In particular, the fluoride ion activation of a carbonsilicon bond has been commonly used to generate nucleophilic species, under milder conditions with respect to methods based on different organometallic species, such as lithium derivatives.Thus, organosilanes can be used as alternative and efficient reagents compatible with functional groups labile under strong basic conditions. 3,4In this context, more versatile compounds containing both a silicon and a tin moiety on position of heteroatoms may represent interesting structures for different chemical transformations (Figure 1).For instance, -thiosubstituted organosilicon and organotin compounds led to carbanions by transmetallation of the tin moiety with BuLi to afford ketones, 5 or through deprotonation with LDA (lithium diisopropylamide) or KDA (potassium diisopropylamide) in the presence of hexamethylphosphoramide (HMPA) to afford vinyl stannanes via a Peterson olefination. 6][9][10] Heteroatom compounds bearing silicon and tin on the same -carbon were subjected to selective electrochemical oxidation, using silicon and tin as electroauxiliaries, 11 and then reacted with nucleophiles, showing the versatility of this kind of polyfunctionalized molecules.
To the best of our knowledge, no direct functionalization of a C-Si bond in the presence of a tin moiety has ever been reported.On the other hand, as described above, phenylthio(methyl)stannanes can be metalated and further reacted with aldehydes to afford the corresponding -hydroxy adducts. 6,8,9us, due to the advantages of the fluoride induced reactivity of the C-Si bond, in terms of mildness and absence of toxic co-solvents like HMPA, we studied the possible selective functionalization of the silicon moiety of [(phenylthio)(stannyl)methyl]silanes 1a-c, bearing different stannylated groups.We initially performed the reaction of 1a with benzaldehyde in the presence of TBAF (tetra-n-butylammonium fluoride) (1 eq.) at room temperature (Scheme 1).Scheme 1. Reactivity of stannyl-silanes 1a-c with benzaldehyde.
The compound 1a reacted quite smoothly under these conditions leading to olefins 3a (cis:trans 1:2), together with the -hydroxy sulfide 4a and the phenylthio(methyl)stannane 5a, arising from protodesilylation (Scheme 1).To assess the scope of this approach, various aromatic, heteroaromatic and -unsaturated aldehydes were reacted with 1a-c under the same conditions (Table 1, entries 1-9).In all cases a similar distribution of products was observed.Alkenes 3a-d were always obtained and the trans-isomer was the major compound recovered (cis/trans 1:2 or 1:3, see Table 1).The formation of (phenylthio)methylstannane 5 was also observed (ca.20-30%, see Table 1).Interestingly, more hindered stannyl derivatives, such as [(phenylthio)(tributylstannyl)methyl]silane 1b and [(phenylthio)(triphenylstannyl)methyl]silane 1c, showed a similar behaviour when treated with different aldehydes under the same conditions (Table 1, entries 5-9).Although the reaction mixture seemed quite complicated, in our opinion such results were satisfactory, demonstrating the possibility to functionalize stannylsilanes 1 under mild conditions.The presence of olefins 3 can be indeed attributed to deoxystannylation of -phenylthio--hydroxy stannane intermediates 2. In fact, olefins arise from stereospecific elimination of R 3 SnOH from adducts 2, which are obtained as mixture of threo and erythro stereoisomers.Although a syn-or anti-elimination can occur, under the above described basic conditions, and based on the previously reported results, [8][9][10] olefins should be formed via a syn-elimination from the less hindered adduct threo-2, affording predominantly E-alkenes (Scheme 2).This reaction thus appears as a novel one-pot synthesis of alkenes via the tin-Peterson olefination.Scheme 2. Formation of olefins 3 from -hydroxy stannanes 2 via syn elimination.
In order to evaluate whether phenylthio--hydroxy stannanes 2a-c could be isolated, different reaction conditions were explored.Therefore, we sought to investigate the effect of the amount of TBAF and of the temperature.The tributylstannyl derivative 1b and PhCHO were chosen as model substrates and the reaction was initially carried out in the presence of 0.1 eq. of TBAF at ambient temperature.Under these conditions, the formation of the adduct 2e was evidenced for the first time as mixture of diastereoisomers, although olefins 3a and products 4 and 5 were observed in comparable amounts with respect to previous experiments (Table 1, entry 10).The reaction was then performed at lower temperature (0 °C) and the adduct 2e was recovered as major product (24%) (Table 1, entry 11), together with a minor amount of the olefins 3a (ca 10%).With the aim to verify whether a lower temperature could favour the formation of adducts 2, the reaction of the silylstannane 1b with PhCHO was carried out at -78 °C in the presence of a catalytic amount of TBAF (0.1 eq).Under these conditions, we were pleased to observe the formation of the -hydroxystannane 2e as the major product (64%), while only trace amounts of the olefin 3a (<10%) and of 5b were evidenced (Table 1, entry 12).The compound 2e was formed as an almost equimolar mixture of diastereoisomers.It is worth noting that an increased amount of olefins 3a, whose formation is favoured by the acidity of the medium, was recovered after purification of the crude mixture on silica gel.The reaction was efficiently extended to cinnamaldehyde and thiophene-2-carbaldehyde, enabling the synthesis of the corresponding -hydroxy tributylstannanes 2f,g (Table 1, entries 13 and 14), together with minor amounts of olefins 3b,d and phenylthio(methyl)stannane 5b.In order to further expand the scope of this study, -silyl stannanes 1a and 1c, bearing the trimethyl-and the triphenyl-stannyl moieties respectively, were reacted under the same conditions with benzaldehyde.The corresponding adducts 2a,h were achieved as predominant compounds (Table 1, entries 15 and 16), with minor amounts of olefins 3a.These results confirm that the temperature and the amount of TBAF play a key role in the distribution of the products.The so obtained results are in line with what reported by other authors on this kind of reactions.In fact, it has been observed [8][9][10] that the formation of olefins from -phenylthio--hydroxystannes occurs under acid conditions or by heating.In our procedure, taking advantage of the C-Si functionalization, we may state that room temperature was sufficient to promote the deoxystannylation, thus leading directly to the alkenylsulfides 3. On the contrary, the reaction performed at low temperatures (0 °C or -78 °C) allowed the formation of adducts 2. The results obtained in these reactions prompted us to further investigate the generality and the potentialities of the present fluoride ion induced functionalization, and we turned our attention to more intriguing substrates such as -phenylseleno(tributylstannyl)-methyltrimethylsilane 6, conveniently synthesized from trimethyl-phenylselanylmethyl-silane and tributyltin chloride.][22] Table 1.Influence of the reaction conditions on the transfer of 1a-c onto aldehydes a Yield refers to both diastereoisomers.b 5-15% of corresponding alcohols 4 was detected.c 20-30% of the corresponding desilylated derivatives 5 was detected.d 5-15% of the corresponding desilylated derivatives 5 was detected.e ca.10% of the -SiMe 3 protected alcohol was isolated.f cis/trans ratio not determined.
Organoselenides have been used as valuable synthetic intermediates, ligands, and catalysts.8][29][30][31] The development of novel routes towards organoselenium derivatives is, therefore, highly desirable. 16,32][35] However, despite the interest in the synthesis of organoselenium compounds, to the best of our knowledge, no reports are available on the -metalation of selenyl derivatives.][38][39] Preliminary results 40 showed that the TBAF-promoted (0.1 eq.) reaction of the selanylated compound 6 with benzaldehyde at room temperature led to the formation of -phenylseleno--hydroxy stannyl derivative 7a, even if in rather low yields, together with the protodesilylated compound 10 as major product and phenylvinyl selenide 8a, formed through deoxystannylation (Table 2, entry 1).Interestingly, also in the case of the selanylated alkenes, the trans isomer was always the major isomer (cis/trans 2:98), in a higher ratio with respect to vinyl sulfides.

Table 2. Reaction of trimethyl(phenylselanyl(tributylstannyl)methyl)silane 6 with aldehydes
Encouraged by these results, we moved to evaluate the effect of the temperature.Pleasingly, we found that when the silane 6 was treated with benzaldehyde at -78°C, the reaction proceeded smoothly affording phenylseleno--hydroxy stannanes 7a, as major product.The scope of this procedure was enlarged to include differently substituted aldehydes, enabling the formation of selenium-containing -hydroxy stannanes 7a-c, which were isolated in good yields as almost equimolar mixture of diastereoisomers (Table 2, entries 2-4), together with trace amounts of alcohols 9a-c and the selenide 10.Interestingly, after purification of the crude material on silica gel, olefins 8a-c and alcohols 9a-c were recovered as main products.On the contrary, purification on Florisil substantially reduced the deoxystannylation, enabling the isolation of the adducts 7a-c in good yields.Scheme 3. Functionalization of benzotriazolyl-stannyl-silane 11 with aldehydes.Yields refer to isolated products.Destannylated alcohols 13a-c were detected in 5-10% yields.
In order to further explore the scope of this methodology, we synthesized the benzotriazolyl(tributylstannyl)silylmethane 11 and evaluated its reactivity with aromatic and heteroaromatic aldehydes.Benzotriazolyl derivatives have been demonstrated valuable substrates in organic synthesis and have been widely applied as versatile intermediates. 41,42Pleasingly, the desired stannylated derivatives 12a-c were efficiently obtained in good yields through a selective fluoride-induced carbodesilylation reaction (Scheme 3).Amounts of desilylated (benzotriazolyl)stannylmethane 14 and alcohols 13a-c were recovered as well.Nevertheless, these findings highlight that also this heterosubstituted (stannyl)methylsilane is able to react as efficient nucleophile through a smooth functionalization of the carbon-silicon bond

Conclusions
The functionalization of a carbon-silicon bond under fluoride ion conditions affords the generation of heterosubstituted stannyl carbanionic species, able to act as nucleophiles toward different aldehydes leading to the corresponding -functionalized -hydroxy stannanes or olefins, depending on the reaction conditions.These showed that the C-Si bond could be efficiently and selectively functionalized in the presence of a stannyl moiety, as well as of other synthetically useful groups such as phenylthio-, phenylseleno-, and benzotriazolyl-derivatives.