Synthesis of six-membered silacycles by borane-catalyzed double sila-Friedel–Crafts reaction

We have developed a catalytic synthetic method to prepare phenoxasilins. A borane-catalyzed double sila-Friedel–Crafts reaction between amino group-containing diaryl ethers and dihydrosilanes can be used to prepare a variety of phenoxasilin derivatives in good to excellent yields. The optimized reaction conditions were also applicable for diaryl thioethers to afford their corresponding six-membered silacyclic products. The gram-scale synthesis of a representative bis(dimethylamino)phenoxasilin and the transformation of its amino groups have also been demonstrated.


Results and Discussion
A double sila-Friedel-Crafts reaction was initially investigated using diaryl ether 1a and dihydrodiphenylsilane (2a) as model substrates (Table 1). Under the optimized reaction conditions used for the synthesis of silafluorenes in our previous report [40] (B(C 6 F 5 ) 3 (5.0 mol %) and 2,6-lutidine (7.5 mol %) in chlorobenzene at 100 °C), the desired reaction between 1a with 2a proceeded to give phenoxasilin 3a in 60% yield (Table 1, entry 1). The structure of phenoxasilin 3a was confirmed using single-crystal X-ray crystallography (see Supporting Information File 1 for details) [42]. Upon increasing the reaction temperature to 140 °C, the yield of 3a was improved to 88% (Table 1, entry 2). Although the reaction in the presence of 3.0 mol % of the catalyst also proceeded efficiently (Table 1, entry 3, conditions A), the yield of 3a decreased when compared to that obtained using 1.5 mol % of the catalyst (Table 1, entry 4). The best result was obtained in the absence of 2,6-luti- dine by which phenoxasilin 3a formed in 99% yield (Table 1, entry 5, conditions B).
Next, the scope of the dihydrosilane starting materials used in the reaction was investigated (Scheme 2). The reactions of phenylmethylsilane (2b) and diethyldihydrosilane (2c) afforded their corresponding phenoxasilin derivatives 3b and 3c in 66 and 74% yield, respectively. The yields of 3b and 3c were improved to 83 and 91% in the presence of a catalytic amount of 2,6-lutidine, probably due to the acceleration of the deprotonation step by 2,6-lutidine [33]. In the case of phenylsilane (2d), the phenoxasilin product 3d was formed in 59% yield using conditions B and in 63% yield under conditions A. Di(4-bromophenyl)dihydrosilane (2e) was transformed successfully into phenoxasilin 3e in 83% yield without loss of the bromine substituent. The reaction system was also applicable for 9,9dihydro-5-silafluorene (2f), which gave the spiro-type phenoxasilin 3f in 96% yield.
We then investigated the scope of the starting biaryl ethers used in the reaction as well as related derivatives thereof using dihydrodiphenylsilane (2a, Scheme 3). Pyrrolidine-substituted diaryl ether 1b was transformed into phenoxasilin 3g in 80% yield.
Also, the chloro-substituted diaryl ether gave its corresponding phenoxasilin 3h in 94% yield without affecting the chlorine substituent. The methyl-substituted phenoxasilin derivatives 3i and 3j were formed in good yield despite of the steric hindrance of the methyl group in 3j. When one of the NMe 2 groups was replaced with a SMe group, a mixture of the corresponding phenoxasilin product (3k) and the hydrosilane compound (3k′) was obtained via a single sila-Friedel-Crafts reaction in 35% yield in the presence of 2,6-lutidine (3k:3k′ = 63:37). This result was probably due to the weaker electron-donating ability of the SMe group compared to that of NMe 2 . The double C-H silylation reaction proceeds efficiently upon increasing the temperature to 180 °C that afforded the mixture (3k:3k′ = 92:8) in 68% yield. The reaction system can also be applied to the synthesis of phenothiasilin 3l that was obtained in 93% yield starting from diaryl thioether 1g. N-(Benzyl)methylaminesubstituted diaryl thioether 1h was also transformed into phenothiasilin 3m in 58% yield. The corresponding six-membered silacycles were not formed using N-aryl-bridged biaryls as substrates.
To test the applicability of the method, a gram-scale synthesis of phenoxasilin 3a was carried out (Scheme 4). The reaction of Finally, the transformation of the amino groups in phenoxasilin 3a into phenyl groups was carried out (Scheme 5). First, the ammonium salt 4 was prepared by treating 3a with MeOTf fol-lowed by a palladium-catalyzed cross-coupling reaction with the Grignard reagent (PhMgBr) that afforded the desired diphenylated phenoxasilin 5 in 87% yield [43].

Conclusion
In summary, we have developed a new catalytic synthetic method to prepare six-membered silacyclic compounds, such as phenoxasilin and phenothiasilin derivatives, using a double sila-Friedel-Crafts reaction. The reaction system is applicable to diaryl ethers with halogen substituents or sterical hindrance. A gram-scale synthesis of phenoxasilins and transformation of the amino groups in the phenoxasilin product were also achieved. We hope that the developed protocol will prove to be a useful and efficient method to synthesize six-membered silacyclic compounds.