Ruthenium-Catalyzed Dehydrogenative Intermolecular O-H/Si-H/C-H Silylation: Synthesis of (E)-Alkenyl Silyl-Ether and Silyl-Ether Heterocycle

Selective dehydrogenative silylation is one of the most valuable tools for synthesizing organosilicon compounds. In this study, a regio- and stereoselective ruthenium-catalyzed dehydrogenative intermolecular silylation was firstly developed to access (E)-alkenyl silyl-ether derivatives and silyl-ether heterocycles with good functional group tolerance. Furthermore, two pathways for RuH2(CO)(PPh3)3/NBE-catalyzed dehydrogenative intermolecular silylation of alcohols and alkenes as well as intermolecular silylation of naphthol derivatives were investigated with H2SiEt2 as the hydrosilane reagent.

In spite of the significant progress in the direct dehydrogenative silylation of alke HSiEt3 and HSiMe(OSiMe3)2 as the hydrosilane reagents are always used, whereas H2S has still not been developed in dehydrogenative silylation of alkenes mainly beca H2SiEt2 is more difficult to control and easily generates other silane-byproducts during catalytic reaction.In addition, H2SiEt2 constitutes two Si-H bonds, which could pro more possibilities and molecule diversity to produce organosilicon compounds.Rece Hartwig demonstrated efficient synthetic methods to afford five-membered silyl ether erocycles via Rh or Ir-catalyzed dehydrogenative silylation of alcohols or ketones w H2SiEt2 (Scheme 1c) [27,28].

Results
To attempt the alkenyl silyl-ether, a two-step sequential ruthenium-catalyzed d drogenative intermolecular silylation of 1-phenylpropan-1-ol (1a) with styrene (3a) been evaluated.Based on our previous experience and literature on dehydrogenativ lylation of O-H/Si-H bonds [32], full conversion of intermediate silyl-ether (2a) was tained from the reaction of 1-phenylpropan-1-ol (1a) with H2SiEt2 in the presence mol% of RuCl2(PPh3)3 in toluene at 60 °C under N2 (more details see Table S1).After the reaction conditions of the in situ-generated silyl-ether (2a) with styrene (3a) were timized and shown in Table 1.Firstly, 88% yield of (E)-alkenyl silyl-ether 4a was obser by using 10 mol% of RuHCl(CO)(PPh3)3 as catalyst, 6 equiv. of norbornene (NBE) as In spite of the significant progress in the direct dehydrogenative silylation of alkenes, HSiEt 3 and HSiMe(OSiMe 3 ) 2 as the hydrosilane reagents are always used, whereas H 2 SiEt 2 has still not been developed in dehydrogenative silylation of alkenes mainly because H 2 SiEt 2 is more difficult to control and easily generates other silane-byproducts during the catalytic reaction.In addition, H 2 SiEt 2 constitutes two Si-H bonds, which could provide more possibilities and molecule diversity to produce organosilicon compounds.Recently, Hartwig demonstrated efficient synthetic methods to afford five-membered silyl ether heterocycles via Rh or Ir-catalyzed dehydrogenative silylation of alcohols or ketones with H 2 SiEt 2 (Scheme 1c) [27,28].
We next studied the tolerance and selectivity of the reaction of alkene derivatives (Scheme 3).(E)-Alkenyl silyl-ethers with a 4-methoxyphenyl group could be easily prepared through this sequential ruthenium-catalyzed dehydrogenative intermolecular silylation.The corresponding alkenyl silyl-ethers bearing substituents, including -OMe, -Me, -tBu, -F, -Cl, and -Br at the para or meta position on the styrene ring, could be produced in 63-87% yields under similar conditions (5b-5h).Analogously, the pyridine ring instead of the phenyl ring also proceeded well via this sequential ruthenium-catalyzed dehydrogenative intermolecular silylation.We next studied the tolerance and selectivity of the reaction of alkene derivatives (Scheme 3).(E)-Alkenyl silyl-ethers with a 4-methoxyphenyl group could be easily prepared through this sequential ruthenium-catalyzed dehydrogenative intermolecular silylation.The corresponding alkenyl silyl-ethers bearing substituents, including -OMe, -Me, -tBu, -F, -Cl, and -Br at the para or meta position on the styrene ring, could be produced in 63-87% yields under similar conditions (5b-5h).Analogously, the pyridine ring instead of the phenyl ring also proceeded well via this sequential ruthenium-catalyzed dehydrogenative intermolecular silylation.Then, the above-described catalytic system was evaluated for dehydrogenative C-H silylation of naphthol with styrene, however, an important silyl-ether heterocycle 7a product was observed, which indicated that styrene did not play a role in this dehydrogenative intermolecular silylation.After our evaluation, an 88% yield of silyl-ether heterocycle 7a was isolated in the presence of 10 mol% of RuH 2 (CO)(PPh 3 ) 3 and 6 equiv. of NBE at 120 • C for 12 h under N 2 (Scheme 4).Then, some naphthols bearing -OMe, -Cl, and -Br substituents were also successfully transferred to the corresponding silyl-ether heterocycles 7b-7d in 59-82% yields.Interestingly, this dehydrogenative intermolecular C-H silylation catalytic system could also be applied to synthesize pyren silyl-ether 7e at a good yield.Moreover, when this reaction reacted with 1-naphthaldehyde, the C-H bond at position eight of the naphthalene ring was not activated, whereas position two of the C-H bond was activated and generated silyl-ether heterocycle 9a at an 88% yield (Scheme 5).This result indicated that the five-membered silyl-ether heterocycle is easier to produce than the six-membered silyl-ether heterocycle.
intermolecular silylation.After our evaluation, an 88% yield of silyl-ether hetero was isolated in the presence of 10 mol% of RuH2(CO)(PPh3)3 and 6 equiv. of NB °C for 12 h under N2 (Scheme 4).Then, some naphthols bearing -OMe, -Cl, and stituents were also successfully transferred to the corresponding silyl-ether hete 7b-7d in 59-82% yields.Interestingly, this dehydrogenative intermolecular C-H si catalytic system could also be applied to synthesize pyren silyl-ether 7e at a goo Moreover, when this reaction reacted with 1-naphthaldehyde, the C-H bond at eight of the naphthalene ring was not activated, whereas position two of the Cwas activated and generated silyl-ether heterocycle 9a at an 88% yield (Scheme result indicated that the five-membered silyl-ether heterocycle is easier to produ the six-membered silyl-ether heterocycle.To gain further insight into the reaction mechanism, several controlled expe were performed (Scheme 6).Two H/D exchange reactions were conducted in the p of D2O (0.2 mL) under the above conditions for 3 h.A 90% H/D exchange took pla C-H bonds of 4-methoxystyrene 3b.In the H/D exchange reaction of naphthol 6a the H/D exchange took place at position two, and a 92% H/D exchange was obse position eight.These results indicated that C-H bonds at both position two and eight in naphthol could be reactive.However, the ruthenium-catalyzed intermole lylation was performed at position eight in naphthol, not at position two, mainly the four-membered ruthenacycle activated at position two is more difficult to g and unstable during the catalytic cycle.In addition, the KIE value of the C-H ac in this dehydrogenative silylation of 3b and 3b-D with 1i and Et2SiH2 was 1.43, re intermolecular silylation.After our evaluation, an 88% yield of silyl-ether hetero was isolated in the presence of 10 mol% of RuH2(CO)(PPh3)3 and 6 equiv. of NB °C for 12 h under N2 (Scheme 4).Then, some naphthols bearing -OMe, -Cl, and stituents were also successfully transferred to the corresponding silyl-ether heter 7b-7d in 59-82% yields.Interestingly, this dehydrogenative intermolecular C-H si catalytic system could also be applied to synthesize pyren silyl-ether 7e at a goo Moreover, when this reaction reacted with 1-naphthaldehyde, the C-H bond at p eight of the naphthalene ring was not activated, whereas position two of the Cwas activated and generated silyl-ether heterocycle 9a at an 88% yield (Scheme result indicated that the five-membered silyl-ether heterocycle is easier to produ the six-membered silyl-ether heterocycle.To gain further insight into the reaction mechanism, several controlled expe were performed (Scheme 6).Two H/D exchange reactions were conducted in the p of D2O (0.2 mL) under the above conditions for 3 h.A 90% H/D exchange took plac C-H bonds of 4-methoxystyrene 3b.In the H/D exchange reaction of naphthol 6a the H/D exchange took place at position two, and a 92% H/D exchange was obse position eight.These results indicated that C-H bonds at both position two and p eight in naphthol could be reactive.However, the ruthenium-catalyzed intermole lylation was performed at position eight in naphthol, not at position two, mainly the four-membered ruthenacycle activated at position two is more difficult to g and unstable during the catalytic cycle.In addition, the KIE value of the C-H ac in this dehydrogenative silylation of 3b and 3b-D with 1i and Et2SiH2 was 1.43, re Scheme 5. Ru-catalyzed dehydrogenative intermolecular silylation of 1-naphthaldehyde.
To gain further insight into the reaction mechanism, several controlled experiments were performed (Scheme 6).Two H/D exchange reactions were conducted in the presence of D 2 O (0.2 mL) under the above conditions for 3 h.A 90% H/D exchange took place at the C-H bonds of 4-methoxystyrene 3b.In the H/D exchange reaction of naphthol 6a, 90% of the H/D exchange took place at position two, and a 92% H/D exchange was observed at position eight.These results indicated that C-H bonds at both position two and position eight in naphthol could be reactive.However, the ruthenium-catalyzed intermolecular silylation was performed at position eight in naphthol, not at position two, mainly because the four-membered ruthenacycle activated at position two is more difficult to generate and unstable during the catalytic cycle.In addition, the KIE value of the C-H activation in this dehydrogenative silylation of 3b and 3b-D with 1i and Et 2 SiH 2 was 1.43, revealing that the C-H cleavage is not the rate-determining step.No dehydrogenative silylated compound 3b was detected and full conversion of reductive product 4-ethylanisole was obtained from the reaction of 4-methoxystyrene 3b with H 2 SiEt 2 in the presence of RuH 2 (CO)(PPh 3 ) 3 and NBE, which indicated that the silyl ether would reduce the reactivity of the Si-H bond and play an important role for dehydrogenative silylation.Furthermore, Murai described a complex Ru(H)(o-C 6 H 4 PPh 2 )(PPh 3 ) 2 (CO), which could be easily synthesized from the reaction with RuH 2 (CO)(PPh 3 ) 3 with trimethylsilane [33].With this important result, the reaction of RuH 2 (CO)(PPh 3 ) 3 with NBE was performed at 120 • C for 3 h, and a mixture with the major Ru complex A Ru(H)(o-C 6 H 4 PPh 2 )(PPh 3 )(CO) was obtained and detected by HR-MS (See in Supplementary Materials).Then, Ru complex A could be successfully applied to dehydrogenative intermolecular silylation and give 95% GC-yield of alkenyl silyl-ether 5b.These results indicated that the Ru(H)(o-C 6 H 4 PPh 2 )(PPh 3 )(CO) may be the active ruthenium catalyst for the dehydrogenative intermolecular silylation.
that the C-H cleavage is not the rate-determining step.No dehydrogenative silylated compound 3b was detected and full conversion of reductive product 4-ethylanisole was obtained from the reaction of 4-methoxystyrene 3b with H2SiEt2 in the presence of RuH2(CO)(PPh3)3 and NBE, which indicated that the silyl ether would reduce the reactivity of the Si-H bond and play an important role for dehydrogenative silylation.Furthermore, Murai described a complex Ru(H)(o-C6H4PPh2)(PPh3)2(CO), which could be easily synthesized from the reaction with RuH2(CO)(PPh3)3 with trimethylsilane [33].With this important result, the reaction of RuH2(CO)(PPh3)3 with NBE was performed at 120 °C for 3 h, and a mixture with the major Ru complex A Ru(H)(o-C6H4PPh2)(PPh3)(CO) was obtained and detected by HR-MS (See in Supplementary Materials).Then, Ru complex A could be successfully applied to dehydrogenative intermolecular silylation and give 95% GC-yield of alkenyl silyl-ether 5b.These results indicated that the Ru(H)(o-C6H4PPh2)(PPh3)(CO) may be the active ruthenium catalyst for the dehydrogenative intermolecular silylation.

Scheme 6. Controlled experiments.
On the basis of the above results and previous studies [29,[33][34][35] in the literature, we proposed mechanisms for the RuH2(CO)(PPh3)3/NBE-catalyzed silylation of alkene with alcohol and the silylation of naphthol through the intermolecular pathway, as illustrated Scheme 6. Controlled experiments.
On the basis of the above results and previous studies [29,[33][34][35] in the literature, we proposed mechanisms for the RuH 2 (CO)(PPh 3 ) 3 /NBE-catalyzed silylation of alkene with alcohol and the silylation of naphthol through the intermolecular pathway, as illustrated in Scheme 7. In the Ru-catalyzed intermolecular silylation cycle of alkene with alcohol, the active Ru(H)(o-C 6 H 4 PPh 2 )(PPh 3 )(CO) species A was generated in situ after the release of one PPh 3 and cyclometallation from the reaction of RuH 2 (CO)(PPh 3 ) 3 with NBE [29,33,34].Then, the oxidative addition of the above-generated ROSi(Et 2 )H compound led to "Ru-Si" intermediate B [36].Next, following the insertion of the Ru-Si bond to styrene [18] and β-elimination of Ru, intermediate C led to Ru intermediate D. Finally, (E)-alkenyl silyl-ether product 4 was produced via the decoordination of Ru intermediate D, and RuH 2 (CO)(PPh 3 ) 3 was regenerated with the previous release of PPh 3 for the next catalytic cycle.On the other hand, in the Ru-catalyzed dehydrogenative intermolecular silylation cycle of naphthol, the active Ru(H)(o-C 6 H 4 PPh 2 )(PPh 3 )(CO) species A reacted with the in situ generated "O-Si-H" compound to afford "Ru-Si" intermediate E.Then, a six-membered "Ru-Si-O" intermediate F was generated via C-H bond deprotonation and cycloruthenation.The silyl-ether heterocycle 7a was finally obtained by reductive elimination and released RuH 2 (CO)(PPh 3 ) 3 for the next catalytic cycle.in Scheme 7. In the Ru-catalyzed intermolecular silylation cycle of alkene with alcohol, the active Ru(H)(o-C6H4PPh2)(PPh3)(CO) species A was generated in situ after the release of one PPh3 and cyclometallation from the reaction of RuH2(CO)(PPh3)3 with NBE [29,33,34].Then, the oxidative addition of the above-generated ROSi(Et2)H compound led to "Ru-Si" intermediate B [36].Next, following the insertion of the Ru-Si bond to styrene [18] and β-elimination of Ru, intermediate C led to Ru intermediate D. Finally, (E)-alkenyl silylether product 4 was produced via the decoordination of Ru intermediate D, and RuH2(CO)(PPh3)3 was regenerated with the previous release of PPh3 for the next catalytic cycle.On the other hand, in the Ru-catalyzed dehydrogenative intermolecular silylation cycle of naphthol, the active Ru(H)(o-C6H4PPh2)(PPh3)(CO) species A reacted with the in situ generated "O-Si-H" compound to afford "Ru-Si" intermediate E.Then, a six-membered "Ru-Si-O" intermediate F was generated via C-H bond deprotonation and cycloruthenation.The silyl-ether heterocycle 7a was finally obtained by reductive elimination and released RuH2(CO)(PPh3)3 for the next catalytic cycle.Scheme 7. Proposed mechanism.

General Information
All reagents were obtained from commercial sources and used as received.Ethanol (anhydrous) was used as received.Technical grade petroleum ether (40-60 °C bp.) and ethyl acetate were used for chromatography column.
1 H NMR spectra were recorded in CDCl3 at ambient temperature on Bruker AVANCE I 400 or 500 spectrometers at 400.1 or 500.1 MHz, using the solvent as internal standard (7.26 ppm). 13C NMR spectra were obtained at 100 MHz or 125 MHz and referenced to the internal solvent signals (central peak is 77.2 ppm).Chemical shift (δ) and coupling constants (J) are given in ppm and in Hz, respectively.The peak patterns are indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; and br. for broad.
The following GC conditions were used: Method A: initial temperature 100 °C for 1.7 min, then rate 10 °C/min until 250 °C and 250 °C for 13 min.Method B: initial temperature 120 °C for 2 min, then rate 10 °C/min until 280 °C and 280 °C for 15 min.

General Information
All reagents were obtained from commercial sources and used as received.Ethanol (anhydrous) was used as received.Technical grade petroleum ether (40-60 • C bp.) and ethyl acetate were used for chromatography column.
1 H NMR spectra were recorded in CDCl 3 at ambient temperature on Bruker AVANCE I 400 or 500 spectrometers at 400.1 or 500.1 MHz, using the solvent as internal standard (7.26 ppm). 13C NMR spectra were obtained at 100 MHz or 125 MHz and referenced to the internal solvent signals (central peak is 77.2 ppm).Chemical shift (δ) and coupling constants (J) are given in ppm and in Hz, respectively.The peak patterns are indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; and br. for broad.
The following GC conditions were used: Method A: initial temperature 100  (10 mol%), and norbornene (3 mmol) were introduced in a tube under N 2 and stirred at 120 • C for 12 h; then the conversion of the reaction was analyzed by gas chromatography.The solvent was then evaporated under vacuum, and the desired product was purified by using a silica gel chromatography column and a mixture of petrol ether/ethyl acetate as eluent.Naphthalen-1-ol derivative (0.5 mmol), RuH 2 (CO)(PPh 3 ) 3 (10 mol%), norbornene (3 mmol), H 2 SiEt 2 (0.55 mmol), and toluene (2 mL) were introduced in a tube under N 2 , equipped with magnetic stirring bar and stirred at 120 • C for 12 h; then the conversion of the reaction was analyzed by gas chromatography.The solvent was then evaporated under vacuum, and the desired product was purified by using a silica gel chromatography column and a mixture of petrol ether/ethyl acetate as eluent.