Functionalization of Siloxanes with Arynes Generated from o-Triazenylarylboronic Acids

Abstract

Herein, we report the functionalization of polyhedral oligosilsesquioxanes (POSS) and related siloxanes with arynes. Using o-triazenylarylboronic acids as aryne precursors and silica gel as the activator, the transformation of siloxane bearing various arynophilic moieties on the side chains was achieved with high yields without touching the siloxane core. This method was applied to the conjugation of POSS and pharmaceutical cores using an aryne derived from the synthetic intermediate of cabozantinib. Furthermore, orthogonal dual functionalization of POSS was realized by combining the aryne reaction with Huisgen cyclization.

Introduction

Siloxanes, which are oligomers or polymers formed by the dehydrative condensation of R_nSi(OH)_4-n (n = 1–3), are an important class of organosilicon compounds with a wide range of applications in materials- and pharmaceutical sciences^1–3) (Chart 1a). For example, linear polysiloxanes (silicones) with an average molecular weight of less than 2000 are used as flame-retardant lubricating oils, whereas those with higher molecular weights are used as elastic and insulating resins. A remarkable feature of siloxanes is their biocompatibility. Linear and cyclic siloxanes are used in food as antifoaming agents and in cosmetics as lubricants. Furthermore, polydimethylsiloxane (dimethicone) has been approved as a medicine for bloated stomachs, and silicone resins have been used in surgery. Among siloxanes, polyhedral oligosilsesquioxanes (POSS) represented by cube-like POSS-T₈ have received much attention as organic–inorganic hybrid materials.^4–6) They are characterized by thermal stability and mechanical properties, similar to inorganic silica gel, and well-defined and divergent structures, of organic small molecules. Post-functionalization of side chains on the silicon atoms is an ideal method for realizing efficient structural divergence of POSS^7–14) (Chart 1b). Indeed, post-functionalization has been achieved by condensation,^7,8) nucleophilic substitution,^9,10) the Huisgen cyclization,¹¹⁾ hydrosilylation,¹²⁾ thiol–ene reaction,¹³⁾ and olefin metathesis,¹⁴⁾ among others.

Chart 1. (a) Structures of Organosilicon Compounds; (b) Reported Side Chain Transformations of POSS

Recently, we developed o-triazenylarylboronic acid 1 as a novel precursor of arynes^15–22) (Chart 2a). These precursors are readily available from the corresponding o-iodoanilines and are shelf-stable solids. Despite their stability, arynes can be generated under mild conditions using silica gel as the activator, making a broad range of arynophiles applicable to reactions with o-triazenylarylboronic acid 1. A salient feature of the proposed method is its compatibility with reactions of arynophiles with silyl ether moieties,¹⁹⁾ which is hardly possible with conventional methods using a combination of o-trimethylsilylaryl triflates and fluoride salts.^23–26) In this context, this study reports the functionalization of POSS and related siloxanes bearing arynophilic moieties with arynes using o-triazenylarylboronic acids as precursors (Chart 2b). These results are the first examples of POSS functionalization with arynes.

Chart 2. Silica Gel-Mediated Aryne Generation from o-Triazenylarylboronic Acid: (a) Previous Work; (b) This Work

Results and Discussion

POSS-T₈ 2 bearing arynophilic moieties were synthesized from commercially available 3-chloropropyl-POSS 2a or open-cage siloxane 4a (Chart 3). Following a procedure in the literature,⁹⁾ 3-azidopropyl-POSS 2b was synthesized by nucleophilic substitution of 2a with sodium azide (Chart 3a). The reaction of 2a with 2-furancarboxylic acid afforded ester 2c in 47% yield. Similarly, the reaction of 2a with phenylpropiolic acid afforded the corresponding phenylpropiolate, which was subsequently converted into β-enaminoester 2d through the Michael addition of diethylamine.²⁷⁾ The 3-aminopropyl-POSS 2e²⁸⁾ and f²⁹⁾ were prepared by the condensation of open-cage siloxane 4a with trimethoxysilanes 5a and 5b, respectively (Chart 3b). POSS 2g armed with a furan ring and terminal alkyne was obtained by the three-step conversion of primary amine 2f including reductive amination with 6, removal of the TMS group, and protection with a methoxycarbonyl group. Global silylation of 4a and subsequent azidation afforded open-cage siloxane 4c bearing three 3-azidopropyl groups. Linear siloxanes 8a and 8b were prepared from the corresponding silyl chlorides (7a, 7b) and furfuryl alcohol (Chart 3c).

Chart 3. Preparation of Siloxanes with Arynophilic Moieties

The POSS 2b–e thus obtained were subjected to aryne reactions using o-triazenylarylboronic acid 1a under silica gel-mediated conditions (Table 1). POSS 2b and 2c with azido and furan moieties underwent the addition of benzyne leaving the core structures of POSS untouched, and cycloadducts 3ab and 3ac were obtained in 86% and quantitative yields, respectively (entries 1 and 2). While small amount of 2b (<10%) was remained with 2.0 equivalent (equiv.) of 1a, full conversion of 2b was observed with 2.5 equiv. Benzyne also led to a formal C–C bond insertion into POSS 2d with a β-enaminoester moiety in 59% yield (entry 3).³⁰⁾ The nucleophilic addition of N-phenylamine 2e to benzyne afforded 3ae in quantitative yield (entry 4).

Table 1. Reactions of POSS 2 with o-Triazenylarylboronic Acid 1a

Subsequently, the reactions of POSS 2b with functionalized aryne precursors 1b–d were investigated (Chart 4). Precursor 1b with a chlorine atom at the C5 position uneventfully afforded 3bb in 84% yield as a 62 : 38 mixture of regioisomers. In contrast, the use of 2.5 equiv. of methoxy-functionalized precursor 1c led to the formation of 3cb in only 19% yield. Fortunately, adding the same amount of 1c in three parts to a suspension of 2b and silica gel improved the yield of 3cb to 55%. We consider that it is important to prevent the reaction between the arynes by keeping the concentration of the aryne low to achieve a high yield, since the reactivity of the POSS-conjugated arynophile is somewhat low. This protocol was also effective for aryne precursor 1d which was prepared from a synthetic intermediate of cabozantinib,^21,31) and 3db was obtained in 36% yield. This result demonstrates the potential applicability of the present method to the reactions of POSS derivatives with complex arynes.

Chart 4. Reactions of POSS 2b with Functionalized Aryne Precursors 1b–d

Next, the multiple-aryne reaction was investigated using the open-cage siloxane 4c and linear siloxanes 8a and 8b (Chart 5). The three azide groups of 4c completely reacted with 7.5 equiv. of 1a, and the triple aryne adduct 9 was obtained in 79% yield. With respect to linear siloxanes, dimethylsiloxane 8a, which is susceptible to hydrolysis, failed to produce the aryne adduct 10a. Meanwhile, the more stable diisopropylsiloxane 8b afforded the double aryne adduct 10b in 63% yield as a diastereomixture.

Chart 5. Reactions of Open-Cage Siloxane 4c and Linear Siloxanes 8a, b with Benzyne

Furthermore, the orthogonal dual functionalization of POSS 2g armed with a furan ring and a terminal alkyne was realized by combining an aryne reaction and Huisgen cyclization³²⁾ (Chart 6). Starting from 2g, the reaction with 1a followed by the Huisgen cyclization with ethyl azidoacetate afforded the desired product 11 in 48% yield in two steps (path A). Reversing the reaction order afforded 11 in a slightly higher yield (path B).

Chart 6. Orthogonal Functionalization of POSS 2g

Finally, the advantages of o-triazenylarylboronic acid 1 were demonstrated in comparisons with known aryne precursors such as o-iodophenyl triflate 12 or o-trimethylsilylphenyl triflate 13 (Table 2). As described above, azido-functionalized POSS 2b gave the adduct 3ab with 1a under silica gel-mediated conditions (entry 1). Conversely, combining 12 and TMSCH₂MgCl^33,34) afforded 3ab only in 5% yield (entry 2). Furthermore, no aryne adducts were obtained by the method using 13 as the aryne precursor and a fluoride or carbonate base³⁵⁾ as the activator (entries 3 and 4). For the transformation of linear siloxane 8b, although 10b was obtained in 30% yield with 12 (entry 6), a much higher yield was observed with 1a (entry 5). Again, the use of 13 as the aryne precursor was ineffective for the reaction with siloxane (entries 7 and 8). As well as silyl-substituted precursors, boryl-substituted aryne precursors are recently developed.^36–38) However, they usually require the use of base or fluoride salt similar to 13. Therefore, o-triazenylarylboronic acids complements the silyl- and boryl-substituted precursors. While benzenediazonium-2-carboxylates generate aryne upon heat, they are known to be explosive compounds.³⁹⁾ Therefore, o-triazenylarylboronic acids will be more practical in terms of safety.

Table 2. Comparison of Aryne Generation Methods

In summary, the side chain functionalization of POSS with arynes was realized for the first-time using o-triazenylarylboronic acids under silica gel mediated conditions. The present method allows the conjugation of the POSS backbone with a pharmaceutical core via the addition of a rather complex aryne. Therefore, the method will be applied to the design and synthesis of POSS derivatives for drug delivery and bioimaging in the future.⁴⁰⁾ Furthermore, the orthogonal dual functionalization of POSS was realized by combining an aryne reaction with the Huisgen cyclization. The present method is also applicable to siloxanes other than POSS. Open-cage siloxane and linear siloxanes bearing multiple arynophilic moieties undergo global transformations with arynes in high yields. Finally, the advantage of using o-triazenylarylboronic acid as an aryne precursor was demonstrated by much higher efficiencies than those observed with known aryne precursors, such as o-iodophenyl triflate or o-trimethylsilylphenyl triflate. As arynes exhibit both versatile reactivity with a range of arynophilic moieties and high chemoselectivity, the proposed method extends the range of accessible POSS derivatives. Therefore, this study contributes to the development of POSS derivatives with novel functionalities. Applications for functionalized POSS synthesis and extension of the present method to the transformation of other silicon-containing compounds are currently in progress.

Experimental

General Information

All melting points were measured on a Yanagimoto micro melting point apparatus. IR spectra were recorded on a JASCO FT/IR-4100 spectrometer and absorbance bands are reported in wavenumber (cm⁻¹). ¹H-NMR spectra were recorded on JEOL JNM-AL 300 (300 MHz) spectrometer or JEOL JNM-ECA 400 (400 MHz) spectrometer or JEOL JNM-ECZ 500 (500 MHz) spectrometer. Chemical shifts are reported relative to internal standard (tetramethylsilane at δ_Η 0.00, CDCl₃ at δ_Η 7.26). Data are presented as follows: chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), coupling constant and integration. ¹³C-NMR spectra were recorded on JEOL JNM-ECA 400 (100 MHz) spectrometer or JEOL JNM-ECZ 500 (125 MHz) spectrometer. Chemical shifts are reported relative to internal standard (CDCl₃ at δ 77.00). Mass spectra were recorded on JEOL JMS 700 (electron ionization (EI)) or JEOL JMS-T100LC (electrospray ionization (ESI)) instrument with a direct inlet system. Column chromatography was carried out on Kanto silica gel 60 N (spherical, neutral, particle size 40–50 mm). Analytical TLC was carried out on Merck Kieselgel 60 F₂₅₄ plates with visualization by ultraviolet, anisaldehyde stain solution or phosphomolybdic acid stain solution. All non-aqueous reactions were carried out in flame-dried glassware under Ar atmosphere unless otherwise noted. Reagents and solvents were used without purification. For aryne generation from o-triazenilarylboronic acids 1, silica gel, which was the same as that used for column chromatography, was used after dryness under vacuum at 200 °C. TMSCH₂MgCl (1.0 M in tetrahydrofuran (THF)) was purchased from FUJIFILM Wako Pure Chemical Corporation (Osaka, Japan). Siloxanes 2a, 4a, 7a, and 7b were purchased from Sigma-Aldrich (U.S.A.) (2a, 4a) and Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan) (7a, 7b). o-Triazenylphenylboronic acids 1a–d were synthesized by our previously reported method.^19,21) 3-Azidopropyl-POSS 2b,⁹⁾ 3-aminopropyl-POSS 2f²⁹⁾ were synthesized according to the literature procedures. See Supplementary Materials for the structures of compounds I through V.

Preparation of POSS 2b⁹⁾

To a solution of 3-chloropropyl-POSS 2a (447 mg, 0.500 mmol) in N,N-dimethylformamide (DMF)/THF (3 : 1, 10 mL) was added NaN₃ (163 mg, 2.50 mmol) at room temperature, and the solution was stirred at 70 °C for 24 h. After cooling, water was added to the reaction mixture and formed precipitates were collected by suction. The precipitates were recrystallized from THF/MeOH to afford 3-azidopropyl-POSS 2b (219 mg, 49%) as a colorless solid: ¹H-NMR (400 MHz, CDCl₃) δ: 0.60 (d, J = 6.8 Hz, 8H, SiCH₂CH(CH₃)₂), 0.61 (d, J = 6.8 Hz, 6H, SiCH₂CH(CH₃)₂), 0.66 (t, J = 8.0 Hz, 2H, SiCH₂CH₂CH₂N₃), 0.95 (d, J = 6.8 Hz, 24H, SiCH₂CH(CH₃)₂), 0.96 (d, J = 6.8 Hz, 18H, SiCH₂CH(CH₃)₂), 1.71 (quintet, J = 8.0 Hz, 2H, SiCH₂CH₂CH₂N₃), 1.86 (nonet, J = 6.8 Hz, 7H, SiCH₂CH(CH₃)₂), 3.25 (t, J = 8.0 Hz, 2H, SiCH₂CH₂CH₂N₃).

Preparation of POSS 2c

To a solution of 3-chloropropyl-POSS 2a (447 mg, 0.500 mmol) and 2-furancarboxylic acid (280 mg, 2.50 mmol) in DMF/1,4-dioxane (3 : 1, 10 mL) was added K₂CO₃ (346 mg, 2.50 mmol) and KI (415 mg, 2.50 mmol) at room temperature, and the solution was stirred at 100 °C for 24 h. After cooling, the reaction was quenched with water, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was purified by column chromatography (silica gel, 10 : 1 n-hexane/AcOEt, then 2 : 1 n-hexane/CH₂Cl₂) to give 2c (229 mg, 47%) as a colorless solid: mp 124–127 °C; IR (KBr) ν 2954, 1722, 1466, 1296, 1230, 1104, 741 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.60 (d, J = 6.8 Hz, 8H, SiCH₂CH(CH₃)₂), 0.61 (d, J = 6.8 Hz, 6H, SiCH₂CH(CH₃)₂), 0.70 (t, J = 8.0 Hz, 2H, SiCH₂CH₂CH₂O), 0.95 (d, J = 6.8 Hz, 18H, SiCH₂CH(CH₃)₂), 0.96 (d, J = 6.8 Hz, 24H, SiCH₂CH(CH₃)₂), 1.82–1.87 (m, 9H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂O), 4.27 (t, J = 8.0 Hz, 2H, SiCH₂CH₂CH₂O), 6.50–6.52 (m, 1H, ArH), 7.17 (d, J = 3.6 Hz, 1H, ArH), 7.57–7.58 (m, 1H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 8.3 (CH₂), 22.3 (CH₂), 22.4 (CH₂), 22.5 (CH₂), 23.8 (CH), 23.9 (CH), 25.6 (CH₃), 25.7 (CH₃), 66.8 (CH₂), 111.8 (CH), 117.6 (CH), 144.9 (C), 146.2 (CH), 158.8 (C=O); high resolution (HR)-MS (ESI) Calcd for C₃₆H₇₂O₁₅Si₈Na [M + Na]⁺ 991.2923. Found 991.2920.

Preparation of POSS 2d

To a solution of 3-chloropropyl-POSS 2a (447 mg, 0.500 mmol) and phenylpropiolic acid (365 mg, 2.50 mmol) in DMF/1,4-dioxane (3 : 1, 10 mL) was added K₂CO₃ (346 mg, 2.50 mmol) and KI (415 mg, 2.50 mmol) at room temperature, and the solution was stirred at 100 °C for 24 h. After cooling, the reaction was quenched with water, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was purified by column chromatography (silica gel, 10 : 1 n-hexane/AcOEt, then 3 : 1 n-hexane/CH₂Cl₂) to give corresponding phenylpropiolate I (378 mg, 75%, containing small amount of impurity) as a colorless solid.

A mixture of I (100 mg, 0.100 mmol), diethylamine (1.0 mL) and CuI (0.2 mg) was stirred at 70 °C overnight. After cooling, to the reaction mixture was added AcOEt and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was purified by column chromatography (silica gel, 4 : 1 n-hexane/AcOEt) to give POSS 2d (108 mg, quant.) as a colorless solid: mp 126–130 °C; IR (KBr) ν 2954, 1563, 1465, 1230, 1107, 838, 742 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.49 (t, J = 8.4 Hz, 2H, SiCH₂CH₂CH₂O), 0.59 (d, J = 6.8 Hz, 8H, SiCH₂CH(CH₃)₂), 0.59 (d, J = 6.8 Hz, 6H, SiCH₂CH(CH₃)₂), 0.95 (d, J = 6.4 Hz, 18H, SiCH₂CH(CH₃)₂), 0.96 (d, J = 6.8 Hz, 24H, SiCH₂CH(CH₃)₂), 1.10 (br, 6H, N(CH₂CH₃)₂), 1.49–1.53 (m, 2H, SiCH₂CH₂CH₂O), 1.84–1.89 (m, 7H, SiCH₂CH(CH₃)₂), 3.12 (br, 4H, N(CH₂CH₃)₂), 3.79 (t, J = 6.8 Hz, 2H, SiCH₂CH₂CH₂O), 4.82 (s, 1H, C=CH-CO₂), 7.18–7.20 (m, 2H, ArH), 7.37–7.39 (m, 3H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 8.3 (CH₂), 12.9 (CH₃), 22.3 (CH₂), 22.4 (CH₂), 22.5 (CH₂), 23.8 (CH), 25.7 (CH₃), 43.8 (CH₂), 64.6 (CH₂), 85.6 (CH), 128.0 (CH), 128.1 (CH × 2), 137.0 (C), 131.9 (C), 168.1 (C=O); HR-MS (ESI) Calcd for C₄₄H₈₅NO₁₄Si₈Na [M + Na]⁺ 1098.4022. Found 1098.4014.

Preparation of POSS 2e

To a solution of open-cage siloxane 4a (791 mg, 1.00 mmol) and trimethoxy[3-(phenylamino)propyl]silane (281 mg, 1.10 mmol) in THF (10 mL) was added tetrabutylammonium hydroxide (25.9 mg, 0.100 mmol) at room temperature. After stirring at the same temperature for 24 h, water was added, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was purified by column chromatography (silica gel, 10 : 1 n-hexane/AcOEt, then 3 : 1 n-hexane/CH₂Cl₂) to give 3-aminopropyl POSS 2e²⁸⁾ (489 mg, 51%) as a colorless solid: ¹H-NMR (400 MHz, CDCl₃) δ: 0.60 (d, J = 7.2 Hz, 14H, SiCH₂CH₂(CH₃)₂), 0.69 (t, J = 7.6 Hz, 2H, SiCH₂CH₂CH₂N), 0.95 (d, J = 6.4 Hz, 18H, SiCH₂CH₂(CH₃)₂), 0.96 (d, J = 6.4 Hz, 24H, SiCH₂CH₂(CH₃)₂), 1.72 (quintet, J = 7.6 Hz, 2H, SiCH₂CH₂CH₂N), 1.79–1.91 (m, 7H, SiCH₂CH(CH₃)₂), 3.12 (t, J = 7.6 Hz, 2H, SiCH₂CH₂CH₂N), 3.65 (br s, 1H, NH), 6.59 (dd, J = 1.2, 8.8 Hz, 2H, ArH), 6.67 (t, J = 7.2 Hz, 1H, ArH), 7.16 (dd, J = 7.2, 8.8 Hz, 2H, ArH).

Preparation of POSS 2f²⁹⁾

To a solution of open-cage siloxane 4a (791 mg, 1.00 mmol) and trimethoxy(3-aminopropyl)silane (197 mg, 1.10 mmol) in THF (10 mL) was added tetrabutylammonium hydroxide (25.9 mg, 0.100 mmol) at room temperature. After stirring at the same temperature for 24 h, water was added, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude precipitate, which was washed with MeOH to give 3-aminopropyl POSS 2f²⁹⁾ (804 mg, 92%) as a colorless solid: ¹H-NMR (400 MHz, CDCl₃) δ: 0.59–0.63 (m, 16H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂N), 0.95 (d, J = 6.8 Hz, 42H, SiCH₂CH(CH₃)₂), 1.53 (quintet, J = 7.2 Hz, 2H, SiCH₂CH₂CH₂N), 1.73 (brs, 2H, NH₂), 1.85 (nonet, J = 6.8 Hz, 7H, SiCH₂CH(CH₃)₂), 2.67 (t, J = 7.2 Hz, 2H, SiCH₂CH₂CH₂NH₂).

Preparation of 5-[4-(Trimethylsilylethynyl)phenyl]furan-2-carbaldehyde (6)

To a solution of 5-(4-bromophenyl)furan-2-carboxyaldehyde (1.00 g, 4.00 mmol), Pd(PPh₃)₄ (231 mg, 0.200 mmol, 5 mol%), and CuI (60.9 mg, 0.32 mmol, 8 mol%) in THF/Et₃N (1 : 1, 36 mL) was added trimethylsilylacetylene (1.66 mL, 12 mmol) at room temperature. After stirring at 80 °C overnight, the reaction mixture was filtered through a pad of Celite. Saturated aqueous NH₄Cl was added to the filtrate, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude product, which was purified by column chromatography (silica gel, 1 : 1 n-hexane/AcOEt) to give 6 (717 mg, 67%) as a colorless oil: IR (KBr) ν 2959, 2157, 1678, 1477, 1252, 1028, 843, 769 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.27 (s, 9H, Si(CH₃)₃), 6.86 (d, J = 3.6 Hz, 1H, ArH), 7.32 (d, J = 3.6 Hz, 1H, ArH), 7.53 (d, J = 8.0 Hz, 2H, ArH), 7.76 (d, J = 8.0 Hz, 2H, ArH), 9.66 (s, 1H, CHO); ¹³C-NMR (100 MHz, CDCl₃) δ: 0.0 (CH₃), 96.9 (C), 104.5 (C), 108.5 (CH), 123.6 (CH), 124.5 (C), 125.1 (CH), 128.8 (C), 132.6 (CH), 152.3 (C), 158.7 (C), 177.4 (C=O); HR-MS (EI) Calcd for C₁₆H₁₆O₂Si [M]⁺ 268.0920. Found 268.0917.

Preparation of POSS 2g

A mixture of 3-aminopropyl-POSS 2f (550 mg, 0.630 mmol) and aldehyde 6 (253 mg, 0.945 mmol), Et₃N (132 µL, 0.945 mmol), and MgSO₄ (47.5 mg) in MeOH/CHCl₃ (4 : 1, 19 mL) was stirred at room temperature. After stirring for 5 h, the reaction mixture was concentrated in vacuo. Then, water was added to the mixture and formed precipitate was collected by suction. Dried precipitate was dissolved in CH₂Cl₂/MeOH (1 : 1, 70 mL) and NaBH₄ (96.1 mg, 2.54 mmol) was added to the solution at room temperature. After stirring at the same temperature for 3 h, the reaction was quenched with saturated aqueous NaHCO₃, and the whole mixture was extracted with CH₂Cl₂. The combined organic layers were dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude product, which was purified by column chromatography (silica gel, 4 : 1 n-hexane/AcOEt) to give the reductive amination product II (417 mg, 59%, containing small amount of impurity) as a colorless solid.

To a solution of II (338 mg, 0.300 mmol) in THF (1.2 mL), TBAF (1.0 M in THF, 0.36 mL, 0.360 mmol) was added at room temperature. After stirring at the same temperature for 5 min, the reaction was quenched with water, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished terminal alkyne III (336 mg, quant.) as a colorless solid: mp 114–117 °C; IR (KBr) ν 2953, 1465, 1230, 1108, 742 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.59–0.65 (m, 16H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂N), 0.95 (d, J = 6.8 Hz, 18H, SiCH₂CH₂(CH₃)₂), 0.96 (d, J = 6.8 Hz, 24H, SiCH₂CH₂(CH₃)₂), 1.62 (quintet, J = 7.2 Hz, 2H, SiCH₂CH₂CH₂N), 1.80–1.89 (m, 7H, SiCH₂CH(CH₃)₂), 2.66 (t, J = 7.2 Hz, 2H, SiCH₂CH₂CH₂N), 3.12 (s, 1H C≡CH), 3.83 (s, 2H, NHCH₂Ar), 6.27 (d, J = 3.2 Hz, 1H, ArH), 6.61 (d, J = 3.2 Hz, 1H, ArH), 7.48 (d, J = 8.4 Hz, 2H, ArH), 7.60 (d, J = 8.4 Hz, 2H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 9.6 (CH₂), 22.4 (CH₂), 22.5 (CH₂), 23.0 (CH₂), 23.8 (CH), 23.9 (CH), 25.7 (CH₃), 46.1 (CH₂), 51.7 (CH₂), 77.7 (C), 83.7 (CH), 106.8 (CH), 109.1 (CH), 120.4 (C), 123.3 (CH), 131.1 (C), 132.4 (CH), 152.3 (C), 154.5 (C); HR-MS (ESI) Calcd for C₄₄H₈₀NO₁₃Si₈ [M + H]⁺ 1054.3784. Found 1054.3788.

To a solution of III (208 mg, 0.200 mmol) and Et₃N (31 µL, 0.360 mmol) in CH₂Cl₂ (1.0 mL) was added methyl chloroformate (23 µL, 0.300 mmol) at 0 °C. After stirring at the same temperature for 10 min and at room temperature for another 1 h, the reaction was quenched with saturated aqueous NaHCO₃, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was purified by column chromatography (silica gel, 3 : 1 n-hexane/AcOEt) to give 2g (186 mg, 84%) as a yellow oil: IR (KBr) ν 3300, 2953, 1709, 1466, 1120, 837, 741 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.59–0.61 (m, 16H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂N), 0.95 (d, J = 6.8 Hz, 18H, SiCH₂CH₂(CH₃)₂), 0.96 (d, J = 6.8 Hz, 24H, SiCH₂CH₂(CH₃)₂), 1.66 (quintet, J = 7.6 Hz, 2H, SiCH₂CH₂CH₂N), 1.80–1.91 (m, 7H, SiCH₂CH(CH₃)₂), 3.09 (s, 1H, C≡CH), 3.29 (t, J = 7.6 Hz, 2H, SiCH₂CH₂CH₂N), 3.73 (s, 3H, OCH₃), 4.47 (s, 2H, NCH₂Ar), 6.27 (br, 1H, ArH), 6.59 (d, J = 3.6 Hz, 1H, ArH), 7.47 (d, J = 8.4 Hz, 2H, ArH), 7.56 (d, J = 8.4 Hz, 2H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 9.2 (CH₂), 14.1 (CH₂), 22.4 (CH₂), 22.5 (CH₂), 23.8 (CH), 23.9 (CH), 25.6 (CH₃), 25.7 (CH₃), 43.7 (CH₂), 49.0 (CH₂), 52.7 (CH₃), 77.8 (C), 83.6 (CH), 106.9 (CH), 110.3 (CH), 120.6 (C), 123.3 (CH), 130.9 (C), 132.5 (CH), 151.8 (C), 152.7 (C), 156.9 (C=O); HR-MS (ESI) Calcd for C₄₆H₈₁NO₁₅Si₈Na [M + Na]⁺ 1134.3658. Found 1134.3663.

Preparation of Open-Cage Siloxane 4c

To a solution of open-cage siloxane 4a (396 mg, 0.500 mmol) and Et₃N (0.70 mL, 5.00 mmol) in THF (5.0 mL) was added chloro(3-chloropropyl)dimethylsilane (0.41 mL, 2.50 mmol) at 0 °C. After stirring at room temperature overnight, the reaction was quenched with water, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was purified by column chromatography (silica gel, n-hexane) to give 4b (501 mg, 84%, containing impurity) as a colorless oil.

To a solution of crude 4b (120 mg, 0.100 mmol) in DMF/THF (3 : 1, 2.0 mL) was added NaN₃ (97.5 mg, 1.50 mmol) at room temperature. After stirring at 70 °C for 24 h, the reaction was quenched with water, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was filtered through a pad of silica gel (4 : 1 n-hexane/AcOEt) to give 4c (116 mg, 96, 81% from 4a in 2 steps) as a colorless oil: IR (KBr) ν 2954, 2096, 1464, 1254, 1083, 838 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.15 (s, 18H, Si(CH₃)₂), 0.53–0.63 (m, 20H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂N₃), 0.96 (d, J = 6.8 Hz, 18H, SiCH₂CH(CH₃)₂), 0.97 (d, J = 6.8 Hz, 24H, SiCH₂CH(CH₃)₂), 1.59–1.67 (m, 6H, SiCH₂CH₂CH₂N₃), 1.79–1.87 (m, 7H, SiCH₂CH(CH₃)₂), 3.23 (t, J = 7.2 Hz, 6H, SiCH₂CH₂CH₂N₃); ¹³C-NMR (100 MHz, CDCl₃) δ: 0.2 (CH₃), 15.2 (CH₂), 22.4 (CH₂), 23.0 (CH₂), 23.7 (CH₂), 23.8 (CH), 24.0 (CH), 24.1 (CH), 25.0 (CH₂), 25.6 (CH₃), 25.8 (CH₃), 26.0 (CH₃), 54.3 (CH₂); HR-MS (ESI) Calcd for C₄₃H₉₉N₉O₁₂Si₁₀Na [M + Na]⁺ 1236.5004. Found 1236.5008.

Preparation of 1,5-Bis(furan-2-ylmethoxy)-1,1,3,3,5,5-hexamethyltrisiloxane (8a)

To a solution of furfuryl alcohol (2.33 mL, 27.1 mmol) and Et₃N (1.44 mL, 10.3 mmol) in THF (20 mL) was added 1,5-dichloro-1,1,3,3,5,5-hexamethyltrisiloxane (7a, 1.84 mL, 6.77 mmol) at 0 °C. After stirring at room temperature overnight, the reaction was quenched with water, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was filtered through a pad of silica gel (10 : 1 n-hexane/AcOEt, then 1 : 1 n-hexane/CH₂Cl₂) to give 8a (1.27 g, 47%) as a colorless oil: IR (KBr) ν 2962, 1504, 1372, 1260, 1151, 1039, 855, 802 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.09–0.14 (m, 18H, Si(CH₃)₂), 4.68 (s, 4H, OCH₂Ar), 6.24 (d, J = 3.2 Hz, 2H, ArH), 6.31 (dd, J = 2.0, 3.2 Hz, 2H, ArH), 7.37 (d, J = 2.0 Hz, 2H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 1.8 (CH₃), 57.8 (CH₂), 108.6 (CH), 111.2 (CH), 143.2 (CH), 154.7 (C); HR-MS (ESI) Calcd for C₁₆H₂₈O₆Si₃Na [M + Na]⁺ 423.1086. Found 423.1087.

Preparation of 1,3-Bis(furan-2-ylmethoxy)-1,1,3,3-tetraisopropyldisiloxane (8b)

To a solution of furfuryl alcohol (217 µL, 2.5 mmol) and Et₃N (347 µL, 2.5 mmol) in THF (10 mL) was added 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (7b, 320 µL, 1 mmol) at 0 °C. After stirring at 50 °C overnight, the reaction was quenched with water, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was filtered through a pad of silica gel (10 : 1 n-hexane/AcOEt) to give 8b (110 mg, 27%) as a colorless oil: IR (KBr) ν 2944, 1463, 1371, 1224, 1051, 884, 814, 739 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 1.02–1.07 (m, 28H, i-Pr), 4.76 (s, 4H, OCH₂Ar), 6.23 (dd, J = 0.8, 2.4 Hz, 2H, ArH), 6.31 (dd, J = 1.2, 2.4 Hz, 2H, ArH), 7.35 (dd, J = 0.8, 1.2 Hz, 2H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 13.0 (CH), 17.2 (CH₃), 57.5 (CH₂), 107.0 (CH), 110.1 (CH), 141.9 (CH), 154.2 (C); HR-MS (EI) Calcd for C₂₂H₃₈O₅Si₂ [M]⁺ 438.2258. Found 438.2252.

General Procedure for the Reactions of Siloxanes with o-Triazenylarylboronic Acids 1

To a suspension of the siloxane (5.00 × 10⁻² mmol) and silica gel (neutral, spherical, 40–50 µm, 2.00 g for 1.00 mmol of 1, used after heating under vacuum to dryness) in CH₂Cl₂ (1.0 mL) was added aryne precursor 1 (0.125–0.375 mmol, 2.5–7.5 equiv.). After stirring at room temperature for 16 h, silica gel was filtered off using CH₂Cl₂ as the eluent, and the eluent was concentrated in vacuo to furnish the crude product, which was purified by column chromatography to give the aryne adduct.

Aryne Adduct 3ab

The reaction was performed using 2b (45.0 mg, 5.00 × 10⁻² mmol) and 1a (31.1 mg, 0.125 mmol), and 3ab (42.2 mg, 86%) was obtained as a colorless solid after purification by column chromatography (silica gel, 10 : 1 n-hexane/AcOEt): mp 128–129 °C; IR (KBr) ν 2953, 1464, 1230, 1105, 838, 743 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.58 (d, J = 6.8 Hz, 6H, SiCH₂CH(CH₃)₂), 0.60 (d, J = 6.8 Hz, 8H, SiCH₂CH(CH₃)₂), 0.66 (t, J = 8.0 Hz, 2H, SiCH₂CH₂CH₂Ar), 0.92 (d, J = 6.8 Hz, 18H, SiCH₂CH(CH₃)₂), 0.94 (d, J = 6.8 Hz, 24H, SiCH₂CH(CH₃)₂), 1.83 (nonet, J = 6.8 Hz, 7H, SiCH₂CH(CH₃)₂), 2.11 (quintet, J = 8.0 Hz, 2H, SiCH₂CH₂CH₂Ar), 4.64 (t, J = 8.0 Hz 2H, SiCH₂CH₂CH₂Ar), 7.37 (t, J = 7.6 Hz, 1H, ArH), 7.45–7.52 (m, 2H, ArH), 8.07 (d, J = 8.4 Hz, 1H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 9.4 (CH₂), 22.3 (CH₂), 22.4 (CH₂), 23.5 (CH₂), 23.8 (CH), 23.9 (CH), 25.6 (CH₃), 25.7 (CH₃), 50.4 (CH₂), 109.3 (CH), 120.1 (CH), 123.7 (CH), 127.1 (CH), 132.9 (C), 146.1 (C); HR-MS (ESI) Calcd for C₃₇H₇₃N₃O₁₂Si₈Na [M + Na]⁺ 998.3240. Found 998.3251.

Aryne Adduct 3ac

The reaction was performed using 2c (48.5 mg, 5.00 × 10⁻² mmol) and 1a (31.1 mg, 0.125 mmol), and 3ac (52.1 mg, quant.) was obtained as a colorless solid after purification by column chromatography (silica gel, 10 : 1 n-hexane/AcOEt, then 1 : 1 n-hexane/CH₂Cl₂): mp 103–104 °C; IR (KBr) ν 2954, 1736, 1464, 1332, 1230, 1102, 837, 742 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.60 (d, J = 6.8 Hz, 8H, SiCH₂CH(CH₃)₂), 0.61 (d, J = 6.8 Hz, 6H, SiCH₂CH(CH₃)₂), 0.69 (t, J = 8.0 Hz, 2H, SiCH₂CH₂CH₂O), 0.94 (d, J = 6.8 Hz, 24H, SiCH₂CH(CH₃)₂), 0.95 (d, J = 6.8 Hz, 18H, SiCH₂CH(CH₃)₂), 1.81–1.91 (m, 9H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂O), 4.36 (t, J = 6.8 Hz 2H, SiCH₂CH₂CH₂O), 5.82 (s, 1H, OCH-CH = CH), 7.00–7.03 (m, 2H, ArH), 7.07–7.08 (m, 2H, OCH-CH = CH), 7.26–7.28 (m, 1H, ArH), 7.35 (dd, J = 2.0, 6.0 Hz, 1H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 8.2 (CH₂), 22.2 (CH₂), 22.4 (CH₂), 22.5 (CH₂), 23.8 (CH), 23.9 (CH), 25.6 (CH₃), 25.7 (CH₃), 67.8 (CH₂), 82.5 (CH), 90.4 (C), 119.9 (CH), 120.6 (CH), 125.2 (CH), 125.7 (CH), 142.6 (CH), 143.5 (CH), 147.4 (C), 147.9 (C), 167.7 (C=O); HR-MS (ESI) Calcd for C₄₂H₇₆O₁₅Si₈Na [M + Na]⁺ 1067.3236. Found 1067.3243.

Aryne Adduct 3ad

The reaction was performed using 2d (53.8 mg, 5.00 × 10⁻² mmol) and 1a (31.1 mg, 0.125 mmol), and 3ad (32.5 mg, 59%) was obtained as a colorless solid after purification by column chromatography (silica gel, 5 : 1 n-hexane/AcOEt, then 1 : 1 n-hexane/CH₂Cl₂): mp 97–99 °C; IR (KBr) ν 2953, 1737, 1665, 1464, 1230, 1099, 837, 742 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.52 (t, J = 8.0 Hz, 2H, SiCH₂CH₂CH₂O), 0.59 (d, J = 6.8 Hz, 6H, SiCH₂CH(CH₃)₂), 0.60 (d, J = 6.8 Hz, 8H, SiCH₂CH(CH₃)₂), 0.94 (d, J = 6.8 Hz, 18H, SiCH₂CH(CH₃)₂), 0.95 (d, J = 6.8 Hz, 24H, SiCH₂CH(CH₃)₂), 1.59–1.63 (m, 2H, SiCH₂CH₂CH₂O), 1.85 (nonet, J = 6.8 Hz, 7H, SiCH₂CH(CH₃)₂), 3.88 (s, 2H, COCH₂Ar), 3.93 (t, J = 6.8 Hz, 2H, SiCH₂CH₂CH₂O), 7.31–7.40 (m, 3H, ArH), 7.43–7.49 (m, 3H, ArH), 7.58 (t, J = 7.2 Hz, 1H, ArH), 7.80–7.82 (m, 2H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 8.2 (CH₂), 22.0 (CH₂), 22.4 (CH₂), 22.5 (CH₂), 23.8 (CH), 23.9 (CH), 25.6 (CH₃), 25.7 (CH₃), 38.7 (CH₂), 66.8 (CH₂), 126.4 (CH), 128.3 (CH), 129.9 (CH), 130.4 (CH), 130.8 (CH), 131.7 (CH), 132.9 (CH), 134.0 (C), 137.8 (C), 138.4 (C), 171.2 (C=O), 198.0 (C=O); HR-MS (ESI) Calcd for C₄₆H₈₀O₁₅Si₈Na [M + Na]⁺ 1119.3544. Found 1119.3550.

Aryne Adduct 3ae

The reaction was performed using 2e (47.5 mg, 5.00 × 10⁻² mmol) and 1a (31.1 mg, 0.125 mmol), and 3ae (51 mg, quant.) was obtained as a gray solid after purification by column chromatography (silica gel, 10 : 1 n-hexane/AcOEt): mp 111–113 °C; IR (KBr) ν 2953, 1590, 1497, 1230, 1105, 837, 746 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.56–0.62 (m, 16H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂N), 0.92 (d, J = 6.8 Hz, 18H, SiCH₂CH(CH₃)₂), 0.95 (d, J = 6.8 Hz, 24H, SiCH₂CH(CH₃)₂), 1.78–1.88 (m, 9H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂O), 3.66 (t, J = 8.0 Hz, 2H, SiCH₂CH₂CH₂N), 6.91–6.98 (m, 6H, ArH), 7.22–7.26 (m, 4H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 9.3 (CH₂), 20.5 (CH₂), 22.4 (CH₂), 22.5 (CH₂), 23.8 (CH), 23.9 (CH), 25.6 (CH₃), 25.7 (CH₃), 54.8 (CH₂), 120.8 (CH), 121.2 (CH), 129.2 (CH), 147.9 (C); HR-MS (ESI) Calcd for C₄₃H₈₀NO₁₂Si₈ [M + H]⁺ 1026.3835. Found 1026.3826.

Aryne Adduct 3bb

The reaction was performed using 2b (45.0 mg, 5.00 × 10⁻² mmol) and 1b (35.6 mg, 0.125 mmol), and 3bb (42.6 mg, 84%, 62 : 38 mixture of regioisomers) was obtained as a colorless solid after purification by column chromatography (silica gel, 10 : 1 n-hexane/AcOEt): IR (KBr) ν 2953, 1464, 1230, 1105, 837, 743 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.57–0.66 (m, 16H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂Ar for major isomer, and 16H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂Ar for minor isomer), 0.91–0.96 (m, 42H, SiCH₂CH(CH₃)₂ for major isomer, and 42H, SiCH₂CH(CH₃)₂ for minor isomer), 1.79–1.86 (m, 7H, SiCH₂CH(CH₃)₂ for major isomer, and 7H, SiCH₂CH(CH₃)₂ for minor isomer), 2.05–2.13 (m, 2H, SiCH₂CH₂CH₂Ar for major isomer, and 2H, SiCH₂CH₂CH₂Ar for minor isomer), 4.58–4.64 (m, 2H, SiCH₂CH₂CH₂Ar for major isomer, and 2H, SiCH₂CH₂CH₂Ar for minor isomer), 7.33 (dd, J = 1.6, 8.8 Hz, 1H, ArH for minor isomer), 7.43–7.44 (m, 2H, ArH for major isomer), 7.51 (dd, J = 0.4, 1.6 Hz, 1H, ArH for minor isomer), 7.98 (dd, J = 0.4, 8.8 Hz, 1H, ArH for minor isomer), 8.06 (dd, J = 1.2, 1.6 Hz, 1H, ArH for major isomer); HR-MS (ESI) Calcd for C₃₇H₇₂ClN₃O₁₂Si₈Na [M + Na]⁺ 1032.2856. Found 1032.2858.

Aryne Adduct 3cb

To a suspension of 2b (45.0 mg, 5.00 × 10⁻² mmol) and silica gel (250 mg) in CH₂Cl₂ (1.0 mL) was added 1c (11.6 mg, 4.20 × 10⁻² mmol). After stirring at room temperature for 2 h, 1c (11.6 mg, 4.20 × 10⁻² mmol) was added to the reaction mixture, and, after another 2 h, the same amount of 1c was added. After stirring at the same temperature for 2 h, silica gel was filtered off using CH₂Cl₂ as the eluent, and the eluent was concentrated in vacuo to furnish the crude product, which was purified by column chromatography (silica gel, 5 : 1 n-hexane/AcOEt, then 5 : 1 CH₂Cl₂/Et₂O) to give 3cb (27.7 mg, 55%, 59 : 41 mixture of regioisomers) was obtained as a colorless solid: IR (KBr) ν 2953, 1501, 1464, 1230, 1105, 837, 743 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.57–0.68 (m, 16H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂Ar for major isomer, and 16H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂Ar for minor isomer), 0.91–0.96 (m, 42H, SiCH₂CH(CH₃)₂ for major isomer, and 42H, SiCH₂CH(CH₃)₂ for minor isomer), 1.77–1.88 (m, 7H, SiCH₂CH(CH₃)₂ for major isomer, and 7H, SiCH₂CH(CH₃)₂ for minor isomer), 2.05–2.12 (m, 2H, SiCH₂CH₂CH₂Ar for major isomer, and 2H, SiCH₂CH₂CH₂Ar for minor isomer), 3.90 (s, 3H, OCH₃ for major isomer, and 3H, OCH₃ for minor isomer), 4.54–4.61 (m, 2H, SiCH₂CH₂CH₂Ar for major isomer, and 2H, SiCH₂CH₂CH₂Ar for minor isomer), 6.77 (d, J = 2.4 Hz, 1H, ArH for minor isomer), 6.99 (dd, J = 2.0, 9.2 Hz, 1H, ArH for major isomer), 7.13 (dd, J = 2.0, 9.2 Hz, 1H, ArH for major isomer), 7.36–7.39 (m, 1H, ArH for major isomer, and 1H, ArH for minor isomer), 7.91 (d, J = 9.2 Hz, 1H, ArH for minor isomer); HR-MS (ESI) Calcd for C₃₈H₇₆N₃O₁₃Si₈ [M + H]⁺ 1006.3532. Found 1006.3531.

Aryne Adduct 3db

To a suspension of 2b (45.0 mg, 5.00 × 10⁻² mmol) and silica gel (250 mg) in CH₂Cl₂ (1.0 mL) was added 1d (11.3 mg, 2.50 × 10⁻² mmol). After stirring at room temperature for 2 h, 1d (11.3 mg, 2.50 × 10⁻² mmol) was added to the reaction mixture, and, after another 2 h, the same amount of 1d was added. After stirring at the same temperature for 2 h, silica gel was filtered off using CH₂Cl₂ as the eluent, and the eluent was concentrated in vacuo to furnish the crude product, which was purified by column chromatography (silica gel, AcOEt) to give 3db (21.5 mg, 36%, 67 : 33 mixture of regioisomers) was obtained as a pale yellow solid: IR (KBr) ν 2954, 1479, 1230, 1111, 743 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.56–0.72 (m, 16H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂Ar for major isomer, and 16H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂Ar for minor isomer), 0.89–0.94 (m, 42H, SiCH₂CH(CH₃)₂ for major isomer, and 42H, SiCH₂CH(CH₃)₂ for minor isomer), 1.79–1.86 (m, 7H, SiCH₂CH(CH₃)₂ for major isomer, and 7H, SiCH₂CH(CH₃)₂ for minor isomer), 2.08–2.19 (m, 2H, SiCH₂CH₂CH₂Ar for major isomer, and 2H, SiCH₂CH₂CH₂Ar for minor isomer), 4.04 (s, 3H, OCH₃ for minor isomer), 4.07 (s, 6H, OCH₃ for major isomer, and 3H, OCH₃ for minor isomer), 4.59 (t, J = 6.8 Hz, 2H, SiCH₂CH₂CH₂Ar for minor isomer), 4.68 (t, J = 6.8 Hz, 2H, SiCH₂CH₂CH₂Ar for major isomer), 6.43 (d, J = 5.2 Hz, 1H, ArH for major isomer), 6.48 (d, J = 5.2 Hz, 1H, ArH for minor isomer), 7.21–7.26 (m, 1H, ArH for minor isomer), 7.32–7.36 (m, 1H, ArH for major isomer, and 1H, ArH for minor isomer), 7.46 (s, 1H, ArH for major isomer, and 1H, ArH for minor isomer), 7.55 (s, 1H, ArH for minor isomer) 7.59–7.60 (m, 2H, ArH for major isomer), 7.88 (s, 1H, ArH for major isomer), 8.13 (d, J = 8.8 Hz, 1H, ArH for minor isomer), 8.49 (d, J = 4.0 Hz, 1H, ArH for major isomer), 8.51 (d, J = 5.2 Hz, 1H, ArH for minor isomer); HR-MS (ESI) Calcd for C₄₈H₈₃N₄O₁₅Si₈ [M + H]⁺ 1179.4009. Found 1179.4014.

Aryne Adduct 9

The reaction was performed using 4c (39.5 mg, 3.30 × 10⁻² mmol) and 1a (62.3 mg, 0.250 mmol), and 9 (37.4 mg, 79%) was obtained as a pale brown oil after purification by column chromatography (silica gel, 10 : 1 n-hexane/AcOEt): IR (KBr) ν 2953, 1455, 1228, 1105, 838, 744 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.08 (s, 18H, Si(CH₃)₂), 0.51–0.53 (m, 14H, SiCH₂CH(CH₃)₂), 0.57 (t, J = 8.4 Hz, 6H, SiCH₂CH₂CH₂Ar), 0.89–0.94 (m, 42H, SiCH₂CH(CH₃)₂), 1.77 (nonet, J = 6.8 Hz, 7H, SiCH₂CH(CH₃)₂), 1.98–2.06 (m, 6H, SiCH₂CH₂CH₂Ar), 4.58 (t, J = 7.2 Hz, 6H, SiCH₂CH₂CH₂Ar), 7.33 (t, J = 8.0 Hz, 3H, ArH), 7.44 (t, J = 8.0 Hz, 3H, ArH), 7.51 (d, J = 8.0 Hz, 3H, ArH), 8.04 (t, J = 8.0 Hz, 3H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 0.0 (CH₃), 15.0 (CH₂), 22.1 (CH₂), 23.5 (CH₂), 23.6 (CH₂), 23.8 (CH), 23.9 (CH), 24.7 (CH₂), 25.4 (CH₃), 25.6 (CH₃), 25.8 (CH₃), 50.8 (CH₂), 109.2 (CH), 119.8 (CH), 123.5 (CH), 126.9 (CH), 132.8 (C), 145.8 (C); HR-MS (ESI) Calcd for C₆₁H₁₁₁N₉O₁₂Si₁₀Na [M + Na]⁺ 1464.5943. Found 1464.5951.

Aryne Adduct 10b

The reaction was performed using 8b (20.5 mg, 5.00 × 10⁻² mmol) and 1a (62.3 mg, 0.250 mmol), and 10b (18.5 mg, 63%, diastereomixture) was obtained as a colorless oil after purification by column chromatography (silica gel, 4 : 1 n-hexane/AcOEt): IR (KBr) ν 2944, 2866, 1454, 1055, 884, 807, 755, 689 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 1.09–1.15 (m, 4H, SiCH(CH₃)₂), 1.18–1.21 (m, 24H, SiCH(CH₃)₂), 4.63–4.66 (m, 2H, SiOCH₂C), 4.74–4.77 (m, 2H, SiOCH₂C), 5.33 (s, 2H, OCH-CH = CH), 6.60 (dd, J = 2.0, 5.6 Hz, 2H, ArH), 6.80 (t, J = 7.2 Hz, 2H, ArH), 6.83–6.87 (m, 2H, ArH), 6.90–6.93 (m, 4H, OCH-CH = CH), 7.32 (d, J = 6.8 Hz, 2H, ArH); HR-MS (ESI) Calcd for C₃₄H₄₆O₅Si₂Na [M + Na]⁺ 613.2782. Found 613.2776.

Procedure for Orthogonal Functionalization of POSS 2g (Path A of Chart 6)

To a suspension of 2g (55.6 mg, 5.00 × 10⁻² mmol) and silica gel (250 mg) in CH₂Cl₂ (1.0 mL) was added aryne precursor 1a (31.1 mg, 0.125 mmol). After stirring at room temperature for 16 h, silica gel was filtered off using CH₂Cl₂ as the eluent, and the eluent was concentrated in vacuo to furnish the crude product, which was purified by column chromatography (silica gel, 3 : 1 n-hexane/AcOEt) to give aryne adduct IV (35.8 mg, 60%) was obtained as a yellow solid: mp 93–94 °C; IR (KBr) ν 2954, 1753, 1703, 1464, 1109, 837, 744 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.50–0.61 (m, 16H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂N), 0.93 (d, J = 6.8 Hz, 18H, SiCH₂CH₂(CH₃)₂), 0.95 (d, J = 6.8 Hz, 24H, SiCH₂CH₂(CH₃)₂), 1.66 (br, 2H, SiCH₂CH₂CH₂N), 1.80–1.89 (m, 7H, SiCH₂CH(CH₃)₂), 3.12 (s, 1H, C≡CH), 3.27–3.34 (m, 1H, SiCH₂CH₂CHHN), 3.49–3.56 (m, 1H, SiCH₂CH₂CHHN), 3.74 (s, 3H, OCH₃), 3.98 (d, J = 15.2 Hz, 1H, NCHHC), 4.64 (d, J = 15.2 Hz, 1H, NCHHC), 6.93 (m, 2H, ArH), 7.00 (t, J = 7.2 Hz, 1H, ArH), 7.06 (d, J = 6.0 Hz, 1H, ArH), 7.13 (d, J = 5.6 Hz, 1H, ArH), 7.31 (d, J = 6.8 Hz, 1H, ArH), 7.55 (d, J = 7.6 Hz, 2H, ArH), 7.61 (d, J = 7.6 Hz, 2H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 9.2 (CH₂), 21.0 (CH₂), 22.4 (CH₂), 22.5 (CH₂), 23.8 (CH), 25.6 (CH₃), 25.7 (CH₃), 45.2 (CH₂), 50.3 (CH₂), 52.7 (CH₃), 77.7 (C), 83.3 (CH), 92.7 (C), 93.7 (C), 119.5 (CH), 119.6 (CH), 122.0 (CH), 125.1 (CH × 2), 126.4 (CH), 132.4 (CH), 136.7 (CH), 144.9 (C), 145.7 (C), 149.4 (C), 152.5 (C), 157.7 (C=O); HR-MS (ESI) Calcd for C₅₂H₈₅NO₁₅Si₈Na [M + Na]⁺ 1210.3971. Found 1210.3964.

A solution of IV (31.2 mg, 2.62 × 10⁻² mmol), ethyl azidoacetate (3.0 µL, 2.62 × 10⁻² mmol), (MeCN)₄CuBF₄ (0.4 mg, 1.31 × 10⁻³ mmol, 5 mol%), and Tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA, 0.7 mg, 1.31 × 10⁻³ mmol, 5 mol%) in CH₂Cl₂ (1.0 mL) was stirred at room temperature overnight. Then, water was added to the mixture, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was purified by column chromatography (silica gel, 3 : 1 n-hexane/AcOEt) to give 11 (26.5 mg, 80%) as a brown solid: mp 184–185 °C; IR (KBr) ν 2954, 1667, 1464, 1366, 1229, 1109, 838, 742 cm⁻¹; ¹H-NMR (500 MHz, CDCl₃) δ: 0.53–0.60 (m, 16H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂N), 0.94 (d, J = 6.8 Hz, 18H, SiCH₂CH₂(CH₃)₂), 0.95 (d, J = 6.8 Hz, 24H, SiCH₂CH₂(CH₃)₂), 1.33 (t, J = 7.2 Hz, 3H, OCH₂CH₃), 1.67 (br, 2H, SiCH₂CH₂CH₂N), 1.82–1.87 (m, 7H, SiCH₂CH(CH₃)₂), 3.29–3.35 (m, 1H, SiCH₂CH₂CHHN), 3.52–3.58 (m, 1H, SiCH₂CH₂CHHN), 3.74 (s, 3H, OCH₃), 3.98 (d, J = 12.4 Hz, 1H, NCHHC), 4.30 (q, J = 7.2 Hz, 2H, OCH₂CH₃), 4.65 (d, J = 12.4 Hz, 1H, NCHHC), 5.23 (s, 2H, ArCH₂CO₂), 6.96–7.00 (m, 3H, ArH), 7.07 (d, J = 4.4 Hz, 1H, ArH), 7.20 (d, J = 5.2 Hz, 1H, ArH), 7.31 (d, J = 6.0 Hz, 1H, ArH), 7.66 (d, J = 8.4 Hz, 2H, ArH), 7.96–7.98 (m, 3H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 9.2 (CH₂), 14.1 (CH₃), 21.0 (CH₂), 22.4 (CH₂), 22.5 (CH₂), 23.8 (CH), 25.6 (CH₃), 25.7 (CH₃), 45.1 (CH₂), 50.1 (CH₂), 51.0 (CH₂), 52.7 (CH₃), 62.5 (CH₂), 92.9 (C), 93.7 (C), 119.4 (CH), 119.8 (CH), 121.0 (C), 124.9 (CH), 125.0 (CH), 126.0 (CH), 127.1 (CH), 130.3 (CH), 135.9 (CH), 144.9 (C), 145.8 (C), 147.9 (CH), 149.6 (C), 152.7 (C), 157.8 (C=O), 166.2 (C=O); HR-MS (ESI) Calcd for C₅₆H₉₂N₄O₁₇Si₈Na [M + Na]⁺ 1339.4509. Found 1339.4510.

Procedure for Orthogonal Functionalization of POSS 2g (Path B of Chart 6)

A solution of 2g (46.8 mg, 4.21 × 10⁻² mmol), ethyl azidoacetate (5.0 µL, 4.21 × 10⁻² mmol), (MeCN)₄CuBF₄ (0.7 mg, 2.10 × 10⁻³ mmol, 5 mol%), and TBTA (1.1 mg, 2.10 × 10⁻³ mmol, 5 mol%) in CH₂Cl₂ (1.0 mL) was stirred at room temperature overnight. Then, water was added to the mixture, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was purified by column chromatography (silica gel, 3 : 1 n-hexane/AcOEt) to give V (33.3 mg, 66%) as a brown solid: mp 108–110 °C; IR (KBr) ν 2954, 1751, 1705, 1464, 1229, 1108, 838, 743 cm⁻¹; ¹H-NMR (400 MHz, CDCl₃) δ: 0.59–0.62 (m, 16H, SiCH₂CH(CH₃)₂ and SiCH₂CH₂CH₂N), 0.95 (d, J = 6.8 Hz, 18H, SiCH₂CH₂(CH₃)₂), 0.96 (d, J = 6.8 Hz, 24H, SiCH₂CH₂(CH₃)₂), 1.32 (t, J = 7.2 Hz, 3H, OCH₂CH₃), 1.67 (br, 2H, SiCH₂CH₂CH₂N), 1.82–1.90 (m, 7H, SiCH₂CH(CH₃)₂), 3.30 (br, 2H, SiCH₂CH₂CH₂N), 3.74 (s, 3H, OCH₃), 4.29 (q, J = 7.2 Hz, 2H, OCH₂CH₃), 4.49 (br s, 2H, NCH₂Ar), 5.19 (s, 2H, ArCH₂CO₂), 6.28 (br s, 1H, ArH), 6.60 (d, J = 3.2 Hz, 1H, ArH), 7.68 (d, J = 8.4 Hz, 2H, ArH), 7.85 (d, J = 8.4 Hz, 2H, ArH), 7.90 (s, 1H, ArH); ¹³C-NMR (100 MHz, CDCl₃) δ: 9.3 (CH₂), 14.1 (CH₃), 21.3 (CH₂), 22.5 (CH₂), 22.6 (CH₂), 23.8 (CH), 23.9 (CH), 25.6 (CH₃), 25.7 (CH₃), 43.7 (CH₂), 49.1 (CH₂), 51.1 (CH₂), 52.6 (CH₃), 62.5 (CH₂), 106.1 (CH), 110.0 (CH), 120.7 (CH), 124.1 (CH), 126.1 (CH), 129.3 (C), 130.7 (C), 148.0 (C), 151.5 (C), 153.2 (C), 156.9 (C=O), 166.1 (C=O); HR-MS (ESI) Calcd for C₅₀H₈₈N₄O₁₇Si₈Na [M + Na]⁺ 1263.4196. Found 1263.4189.

To a suspension of V (30 mg, 2.44 × 10⁻² mmol) and silica gel (122 mg) in CH₂Cl₂ (1.0 mL) was added aryne precursor 1a (15.2 mg, 6.10 × 10⁻² mmol). After stirring at room temperature for 16 h, silica gel was filtered off using CH₂Cl₂ as the eluent, and the eluent was concentrated in vacuo to furnish the crude product, which was purified by column chromatography (silica gel, 3 : 1 n-hexane/AcOEt) to give aryne adduct 11 (26.3 mg, 83%) was obtained as a yellow solid.

Procedure for the Reaction of Siloxanes with o-Iodophenyl Triflate (12) (Conditions B of Table 2)³³⁾

To a solution of siloxane 2b or 8b (5.00 × 10⁻² mmol) and o-iodophenyl triflate (12, 2.5 equiv. for 2b, 5 equiv. for 8b) in THF (1.0 mL) was added TMSCH₂MgCl (1.0 M in THF, 3.75 equiv. for 2b, 7.5 equiv. for 8b) at 0 °C. After stirring at the same temperature overnight, the reaction was quenched with saturated aqueous NH₄Cl, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was purified by column chromatography.

Procedure for the Reaction of Siloxanes with o-Trimethylsilylphenyl Triflate (13) Using KF (Conditions C of Table 2)

To a solution of siloxane 2b or 8b (5.00 × 10⁻² mmol) and o-trimethylsilylphenyl triflate (13, 2.5 equiv. for 2b, 5 equiv. for 8b) in THF (1.0 mL) was added KF (5 equiv. for 2b, 10 equiv. for 8b) and 18-crown-6 (5 equiv. for 2b, 10 equiv. for 8b) at room temperature. After stirring at the same temperature overnight, the reaction was quenched with water, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was analyzed by TLC and ¹H-NMR spectroscopy.

Procedure for the Reaction of Siloxanes with o-Trimethylsilylphenyl Triflate (13) Using Cs₂CO₃ (Conditions D of Table 2)³⁵⁾

To a solution of siloxane 2b or 8b (5.00 × 10⁻² mmol) and o-trimethylsilylphenyl triflate (13, 2.5 equiv. for 2b, 5 equiv. for 8b) in THF (1.0 mL) was added Cs₂CO₃ (5 equiv. for 2b, 10 equiv. for 8b) and 18-crown-6 (5 equiv. for 2b, 10 equiv. for 8b) at room temperature. After stirring at the same temperature overnight, the reaction was quenched with water, and the whole mixture was extracted with AcOEt. The combined organic layers were successively washed with brine and dried over anhydrous Na₂SO₄. Filtration and evaporation in vacuo furnished the crude mixture, which was analyzed by TLC and ¹H-NMR spectroscopy.

Acknowledgments

This study was financially supported by a Grant-in-Aid for Scientific Research (C) (No. 21K05077) from JSPS, Japan. We thank T. Koseki and S. Yamada of the Analytical Center of Meiji Pharmaceutical University for their assistance with high-resolution mass spectrometry (HRMS) and NMR spectra.

Conflict of Interest

The authors declare no conflict of interest.

Supplementary Materials

This article contains supplementary materials.

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