General and Practical One-Pot Synthesis of Dihydrobenzosiloles from Styrenes

Abstract

A one-pot synthesis of dihydrobenzosiloles from styrenes has been developed. The reaction involves the nickel-catalyzed hydrosilylation of styrene with diphenylsilane, followed by the irridium-catalyzed dehydrogenative cyclization. This method is efficient for both electron rich and electron deficient styrenes, and exhibits good functional group tolerance, as well as excellent regioselectivity. The forming dihydrobenzosiloles can be efficiently converted into valuable benzosiloles or 2-hydroxyphenethyl alcohols.

Dehydrogenative coupling of the Si-H bond with aromatic C-H bonds is a powerful method for the synthesis of valuable aryl- and hetaryl silanes. In the last years, several methods for SiH - CH coupling have been developed (Figure 1). Thus, in 2005 Hartwig showed a possibility of the formation of dihydrobenzosilole from dimethylphenethylsilane via an intramolecular platinum-catalyzed dehydrogenative cyclization reaction (eq 1).¹ However, the reaction required harsh conditions; and the scope of this approach toward dihydrobenzosiloles was not established. Later, Falck reported² a milder iridium-catalyzed intermolecular silylation of electron rich aromatic heterocycles (eq 2). Then, Takai reported³ the rhodium-catalyzed synthesis of dibenzosiloles from biarylhydrosilanes (eq 3). Very recently, Hartwig showed⁴ that Falck’s conditions can efficiently be used for ortho- C-H silylation of benzyl alcohol derivatives (eq 4). In 2009, Kawashima reported⁵ the Lewis acid-mediated intramolecular sila-Friedel-Crafts reaction leading to dibenzosiloles (eq 5). Dihydrobenzosiloles hold a promise to become useful synthons for organic chemistry⁶ (vide infra), however, to date, there are no efficient methods for their synthesis exist.⁷ Herein, we wish to report a practical and general one-pot procedure for the synthesis of dihydrobenzosiloles 3 from styrenes 1 through the Ni-catalyzed hydrosilylation, followed by the Ir-catalyzed dehydrogenative cyclization (eq 6).

Figure 1.

Methods for SiH - CH Coupling

We aimed at developing a method for the synthesis of dihydrobenzosiloles via β-hydrosilylation of styrenes with dihydrosilanes, followed by dehydrogenative cyclization of the formed product. First, we turned our attention to hydrosilylation of styrenes, as the first step of the proposed sequence. Although several methods for hydrosilylation of styrene with diphenylsilane using Au,⁸ Zr,⁹ Yb,¹⁰ and Rh¹¹ complexes exist, methods employing cheap and readily available catalysts are still in demand. On the other hand, it is known that nickel (II) salts with phosphine ligands are effective catalysts for hydrosilylation of olefins.¹² Since there are no reports on nickel-catalyzed β-hydrosilylation of styrene with dihydrosilanes, we verified the possibility of hydrosilylation of styrene with diphenylsilane in the presence of nickel catalysts (Table 1). When 5 mol% NiCl₂•(PCy₃)₂ was employed, only triphenylsilane, a product of disproportionation of diphenylsilane,¹³ was formed (entry 1). Using 5 mol% NiCl₂•dppe, the desired hydrosilylated product 2a was obtained in 6% yield (entry 2). Other nickel catalysts, such as NiCl₂•dppf and NiCl₂•dppp, provided 2a in 10% and 55% yields, respectively (entries 3, 4). We were pleased to find that NiCl₂•(PPh₃)₂ and NiBr₂•(PPh₃)₂ gave 2a in high yield and high regioselectivity (entries 5–7). When NiBr₂ without triphenylphosphine was used, no hydrosilylated product was formed (entry 8). Employment of phosphine free Ni(cod)₂ resulted in the mixture of regioisomers (entry 9). However, a combination of triphenylphosphine with Ni(cod)₂ gave the desired hydrosilane 2a in high yield and regioselectivity (entry 10).

Table 1.

Optimization of the Reaction Conditions for Ni-Catalyzed Hydrosilylation of Styrene with Diphenysilane^a

		GC yield, %
entry	cat.	β -	α -	Ph3SiH
1	NiCl2•(PCy3)2	--	--	34
2	NiCl2•dppe	6	13	8
3	NiCl2•dppf	10	3	3
4	NiCl2•dppp	55	37	11
5	NiCl2•(PPh3)2	87	<2	<2
6	NiBr2•(PPh3)2	90	<2	<1
7b	NiBr2•(PPh3)2	92 (87)c	<1	<1
8	NiBr2	--	--	--
9	Ni(cod)2	53	30	6
10d	Ni(cod)2/PPh3	89	<2	<1

^aConditions: 5 mol % cat., 0.2 mmol of styrene, 0.22 mmol Ph₂SiH₂ in 0.2 mL THF were stirred at 80 °C for 6 h under N₂ atmosphere. The reaction was monitored by GC-MS analysis.

^b2 mol % cat. was used. The reaction was analyzed after 1 h.

^cIsolated yield is given in parenthesis.

^d5 mol % cat. and 20 mol % PPh₃ were used.

After a convenient method for beta-hydrosilylation of styrene with diphenylsilane was established, we searched for efficient conditions for intramolecular dehydrogenative cyclization. It was found that under Falck’s conditions,² the hydrosilane 2a underwent smooth dehydrogenative cyclization into the dihydrobenzosilole 3a. Moreover, it was found that the dehydrocyclization can be performed in a one-pot manner after completion of the hydrosilylation step to produce dihydrobenzosilole 3a in 86% overall yield.

Next we examined the scope of this one-pot transformation (Table 2). It was found that this method is quite general as diverse styrenes, possessing MeO, Me, F, Cl, and CO₂Me groups in ortho-, meta- and para-positions were well tolerated under the reaction conditions to give the corresponding dihydrobenzosiloles 3 in good yields. Generally, when meta-substituted styrenes were used, dehydrocyclization occurred at the least hindered para-position to the substituent. Only when small group, such as fluorine was employed, a 2:1 mixture of para- and ortho- cyclized products 3i was obtained. In the case of ortho-methylstyrene, 36 hours were required for the completion of the dehydrocyclization step toward 3g.

Table 2.

Scope of the One-Pot Hydrosilylation Dehydrocyclization Reaction^a

^aConditions: 2 mol % Ni cat., 0.50 mmol of styrene, 0.53 mmol Ph₂SiH₂ in 0.5 mL THF were stirred at 80 °C for 1 h under N₂ atmosphere. Then, 2 mol % Ir cat., 4 mol % dtbpy, 0.6 mmol norbornene, and 2.0 mL THF were added. Reaction was stirred at 80 °C for 12 h.

Next, we examined the possibility of employment of this one-pot method for synthesis of substituted dihydrobenzosiloles (Scheme 1). To this end, hydrosilylation of alpha-substituted styrenes was examined. Unfortunately hydrosilylation reaction of alpha-methyl- 1s and alpha-phenyl styrene 1t in the presence of NiBr₂•(PPh₃)₂ catalyst system was not effective. However, the corresponding hydrosilylated products were obtained in high yields employing Lewis acid catalyst, B(C₆F₅)₃.¹⁴ Subsequently, after removing B(C₆F₅)₃ and the solvent, the dehydrocyclization step was performed using standard dehydrogenative coupling conditions. Thus, 3-methylbenzosilole 3s and 3-phenyldehydrobenzosilole 3t were obtained using this semi one-pot procedure in 79% and 76% yields, respectively (Scheme 1).

Scheme 1.

Hydrosilylation-Dehydrocyclization Reaction of alpha-Substituted Styrenes

In order to get some insights on the mechanism of the dehydrocyclization reaction, we first performed intermolecular competitive cyclization study. It was found that the substrates possessing electron-withdrawing groups at the aromatic ring cyclized faster then those possessing electron-donating groups. Thus, the following reactivity trend was found for the rates of cyclization of meta-substituted styrenes: MeO<Me<H<Cl<CO₂Me. Likewise, intramolecular competitive cyclization experiments of 2u and 2v indicated similar reactivity trend (Scheme 2). Hence, cyclization of 2u, possessing Me- group in one of the aromatic rings, preferentially occurred at the unsubstituted ring, whereas there was slight preference of cyclization into Cl-substituted aromatic ring in 2v. Thus, in all cases, the reaction preferentially occurs at the electron-deficient C-H bond, thereby supporting the C-H activation path rather than electrophilic metalation pathway.⁴ Furthermore, the performed intermolecular kinetic isotope effect studies of 2a and 2a–d₅¹⁵ revealed k_H/k_D = 1.6, which suggests that the cleavage of the aromatic C-H bond may occur at the rate determining step.¹⁶

Scheme 2.

Intermolecular Competitive Cyclization

Based on the above mentioned observations, the following mechanistic pathways were proposed (Scheme 3). First, the iridium species undergo oxidative addition into the Si-H bond of hydrosilane 2 with a formation of iridium hydride A. Hydrometallation of the double bond of norbornene gives intermediate B, which then undergoes insertion into the aromatic C-H bond to give intermediate C (Path A, similar to the Falck’s mechanism²). The following reductive elimination of norbornane gives intermediate D. Alternatively (Path B), the concerted metallation-deprotonation of the intermediate B through the transition state E¹⁷ can occur to give the same intermediate D upon elimination of the norbornane. The reductive elimination from D leads to the cyclized product 3 and regenerates the iridium catalyst.

Scheme 3.

Proposed Mechanistic Pathways

After developing a practical method for the synthesis of dihydrobenzosiloles from styrenes, the initial studies of their synthetic utility were performed. It was found that compounds 3a, 3s, and 3t in the presence of DDQ can be effectively oxidized into valuable benzosiloles 4¹⁸ (Scheme 4). Expectedly, oxidation of 3-phenyl derivative 3t is more facile then that of 3-methyl derivative 3s, which in turn is more reactive then the unsubstituted dihydrobenzosilole 3a. It has also been shown that dihydrobenzosiloles 3a, 3s, and 3t can readily be converted into 2-hydroxyphenethyl alcohols 5 in 79–87% yield when treated with tert-butylperoxide and TBAF. Applying standard Mitsunobu-type reaction conditions, 2-hydroxyphenethyl alcohol 5a was smoothly transformed into dihydrobenzofuran 6a.

Scheme 4.

Further Transformations of Dihydrobenzosiloles

In summary, we have developed a general and practical method for a one-pot synthesis of synthetically valuable dihydrobenzosiloles from styrenes. The method implies nickel-catalyzed hydrosilylation reaction followed by the irridium-catalyzed dehydrogenative cyclization process. The obtained dihydrobenzosiloles can be readily converted into benzosiloles or 2-hydroxyphenethyl alcohols.