Thiolated Janus Silsesquioxane Tetrapod: New Precursors for Functional Materials

Herein, we report synthetic strategies for the development of a bifunctional Janus T4 tetrapod (Janus ring), in which the orthogonal silsesquioxane and organic faces are independently functionalized. An all-cis T4 tetrasilanolate was functionalized to introduce thiol moieties on the silsesquioxane face and naphthyl groups on the organic face to introduce luminescent and self-organization properties. The stepwise synthesis conditions required to prepare such perfectly defined oligomers via a suite of well-defined intermediates and to avoid polymerization or reactions over all eight positions of the tetrapod are explored via 29Si, 13C and 1H NMR, FTIR and TOF-ESI mass spectroscopy. To the best of our knowledge, this is one of the few reports of Janus T4 tetrapods, with different functional groups located on both faces of the molecule, thus expanding the potential range of applications for these versatile precursors.


Introduction
Silsesquioxane compounds, defined by the general formula (RSiO 1.5 ) n where R is an organic group, extend from simple molecular systems to complex material architectures [1]. Random networks [2] together with well-defined molecules [3] can be obtained from the hydrolysis and condensation of trialkoxy-or trichloro-silanes. In 1965, Brown and Vogt first described a range of well-defined oligomeric silsesquioxanes, together with some of their precursors, including the T 4 tetrasilanols [4]. T 4 tetrasilanols/silanolates have been demonstrated to be versatile precursors for producing a variety of oligomeric silsesquioxanes such as cages [4,5], Janus cages [6][7][8][9], ladder silsesquioxanes [9,10] and in particular silsesquioxane tetrapods [11].
Herein, we report the development of a new bifunctional Janus T4 tetrapod, in the orthogonal silsesquioxane and organic faces are independently functionalized ( Using this functionalization approach, several functional Janus tetrapod silsesquioxanes have now been reported, together with details of their synthesis in some cases ( Figure 2) [11,23,24,[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]. To the best of our knowledge, these T 4 compounds have all been functionalized on the silanol/silanolate face of the precursor molecule via condensation reactions with commercially available chlorosilanes, to yield a Janus tetrapod silsesquioxane. However, post-functionalization can be realized either on the Si-O-SiMe 2 R face, mainly by hydrosilylation [37][38][39][41][42][43]50,51] or by the Piers-Rubinsztajn reaction [23,24]; or on the Si-C face using a wide range of standard reactions including Suzuki [44], Sonogashira [11,45] and Heck coupling reactions [11,45,47], etc. The resulting tetrapodal compounds have a range of applications, including self-organizing systems [37][38][39]; chromophores [44][45][46][47][48] and photoexcitation [44]; flame-retardant and water-repelling applications [40]; liquid crystals [11,37,38,41]; or as a fluorescent dye [43]. In some of the applications, the inherent geometrical constraints associated with the T 4 cycles conferred interesting properties on the tetrapods. These include the formation of tetrapodal excimers [44,48] from organic monomers that do not exhibit such properties. However, it is important to note that, in all of these cases, only one face of the Janus tetrapod silsesquioxane confers these properties on the molecule. on the organic Si-O-Si(Me)2-R face (R 1 ). The design of the stepwise synthesis employed, which enables well-defined intermediates and oligomers to be obtained, is explored, extending the scope of potential applications for this interesting family of molecular precursors. Naphthyl-and thiol-functionalized groups were chosen for this proof-of-concept study due to the luminescence and self-organization properties of the former, and the potential for modification of the latter via thiol-ene click reactions or binding to metal nanoparticles such as Au.

Results and Discussion
In our work, a T4 silanolate (tetravinylcyclotetrasilanolate, potassium salt [32]) was chosen as the precursor from which to prepare the Janus T4 tetrapod, because of its more facile synthesis and relatively good stability compared to T4 tetrasilanols. The approach involved the use of an all-cis tetravinylcyclotetrasilanolate, to take advantage of the many different reactions available for the functionalization of the vinyl C=C bond, including metathesis, Heck coupling, hydrosilylation and thiol-ene click reaction. Further functionalization of the silanolate precursor, by the condensation of a chlorosilane on the silanolate face, was then envisaged. However, as previously mentioned, the variety of commercially available chlorosilanes is limited. The organic groups are generally restricted to moieties such as aliphatics (methyl, t-Bu, octadecyl), C6F5, etc., which are difficult to post-functionalize. Chlorosilanes with nucleophilic substituents (chloromethyl, cyanopropyl) or phenyl derivatives are also available, but these can induce unwanted side reactions during different post-functionalization steps. Chlorodimethylsilane and vinyl derivatives were also discounted, as orthogonal functions are required between the silanolate and the Si-C face to prevent polymerization or reaction over all eight positions of the tetrapod. Accordingly, a tailor-made chlorosilane was synthesized from an ethoxysilane precursor, as described below, to avoid the issues of pronounced reactivity, sensitivity to air and water as well as Figure 2. Existing functional Janus tetrapod silsesquioxanes [11,23,24,[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51].
Herein, we report the development of a new bifunctional Janus T 4 tetrapod, in which the orthogonal silsesquioxane and organic faces are independently functionalized (R 1 and R 2 , respectively, in Figure 2). All-cis T 4 tetrasilanolates were functionalized to introduce (a) four thiol moieties on the silsesquioxane Si-C face (R 2 ); and (b) four naphthyl groups on the organic Si-O-Si(Me) 2 -R face (R 1 ). The design of the stepwise synthesis employed, which enables well-defined intermediates and oligomers to be obtained, is explored, extending the scope of potential applications for this interesting family of molecular precursors. Naphthyl-and thiol-functionalized groups were chosen for this proof-of-concept study due to the luminescence and self-organization properties of the former, and the potential for modification of the latter via thiol-ene click reactions or binding to metal nanoparticles such as Au.

Results and Discussion
In our work, a T 4 silanolate (tetravinylcyclotetrasilanolate, potassium salt [32]) was chosen as the precursor from which to prepare the Janus T 4 tetrapod, because of its more facile synthesis and relatively good stability compared to T 4 tetrasilanols. The approach involved the use of an all-cis tetravinylcyclotetrasilanolate, to take advantage of the many different reactions available for the functionalization of the vinyl C=C bond, including metathesis, Heck coupling, hydrosilylation and thiol-ene click reaction. Further functionalization of the silanolate precursor, by the condensation of a chlorosilane on the silanolate face, was then envisaged. However, as previously mentioned, the variety of commercially available chlorosilanes is limited. The organic groups are generally restricted to moieties such as aliphatics (methyl, t-Bu, octadecyl), C 6 F 5 , etc., which are difficult to post-functionalize. Chlorosilanes with nucleophilic substituents (chloromethyl, cyanopropyl) or phenyl derivatives are also available, but these can induce unwanted side reactions during different post-functionalization steps. Chlorodimethylsilane and vinyl derivatives were also discounted, as orthogonal functions are required between the silanolate and the Si-C face to prevent polymerization or reaction over all eight positions of the tetrapod. Accordingly, a tailor-made chlorosilane was synthesized from an ethoxysilane precursor, as described below, to avoid the issues of pronounced reactivity, sensitivity to air and water as well as limited purification options associated with direct modification of a commercial chlorosilane.

Synthesis of Ethoxydimethyl(2-naphthylethyl)silane
Initial scoping studies employed a commercially-available dimethylvinylethoxysilane, ViMe 2 SiOEt, which was reacted with 2-bromonaphthalene to obtain a conjugated ethoxysilane by Heck coupling [52,53]. However, both Eand Z-stereoisomers were identified in the crude reaction product, which was obtained in low yield (14%). Subsequent attempts to purify the mixture and separate the isomers by column chromatography were unsuccessful.
The hydrosilylation reaction [54,55] was thus performed with ethoxydimethylsilane and 2-vinylnaphthalene using Karstedt's catalyst ( Figure 3). The 1 H NMR spectrum of the crude product revealed the absence of signals associated with the vinylic protons of the vinylnaphthalene, indicating completion of the reaction. Although the Karstedt's catalyst generally leads to the product of β-addition, both regioisomers could be identified in the crude reaction product in a ratio of 25/75 αto β-addition products. Following the purification of the crude mixture by flash column chromatography to isolate the pure β-addition product (recovered with 40% yield), the corresponding 1 H NMR spectrum ( Figure S1) exhibited CH 2 signals at 2.84 and 1.07 ppm arising from the hydrosilylation of the double bond. The ethoxy signals are also present at 3.72 and 1.20 ppm and the methyl groups bonded to the silicon are attributed at 0.16 ppm. No impurities were evident in the spectrum. In addition, the integrations are consistent with the expected product. Similarly, all signals observed in 13 C NMR are consistent with the formation of the β-addition product ( Figure S2). In the 29 Si NMR spectrum ( Figure S3), a single signal is observed at 16.70 ppm, consistent with that usually observed for compounds similar to ethoxydimethyl(alkyl)silane [56,57]. The product was confirmed by ESI-MS with a measured mass of 213.1 (M after OEt loss) + for an expected 213.1 m/z. The FTIR spectrum of the product also exhibits the characteristic band at 3055 cm −1 arising from ν(C Napht -H), together with the antisymmetric and symmetric ν(Si-O-C) modes at 1077 and 942 cm −1 , respectively [58,59]. limited purification options associated with direct modification of a commercial chlorosilane.

Synthesis of Ethoxydimethyl(2-naphthylethyl)silane
Initial scoping studies employed a commercially-available dimethylvinylethoxysilane, ViMe2SiOEt, which was reacted with 2-bromonaphthalene to obtain a conjugated ethoxysilane by Heck coupling [52,53]. However, both E-and Z-stereoisomers were identified in the crude reaction product, which was obtained in low yield (14 %). Subsequent attempts to purify the mixture and separate the isomers by column chromatography were unsuccessful.
The hydrosilylation reaction [54,55] was thus performed with ethoxydimethylsilane and 2-vinylnaphthalene using Karstedt's catalyst ( Figure 3). The 1 H NMR spectrum of the crude product revealed the absence of signals associated with the vinylic protons of the vinylnaphthalene, indicating completion of the reaction. Although the Karstedt's catalyst generally leads to the product of β-addition, both regioisomers could be identified in the crude reaction product in a ratio of 25/75 α-to β-addition products. Following the purification of the crude mixture by flash column chromatography to isolate the pure β-addition product (recovered with 40 % yield), the corresponding 1 H NMR spectrum ( Figure  S1) exhibited CH2 signals at 2.84 and 1.07 ppm arising from the hydrosilylation of the double bond. The ethoxy signals are also present at 3.72 and 1.20 ppm and the methyl groups bonded to the silicon are attributed at 0.16 ppm. No impurities were evident in the spectrum. In addition, the integrations are consistent with the expected product. Similarly, all signals observed in 13 C NMR are consistent with the formation of the β-addition product ( Figure S2). In the 29 Si NMR spectrum ( Figure S3), a single signal is observed at 16.70 ppm, consistent with that usually observed for compounds similar to ethoxydimethyl(alkyl)silane [56,57]. The product was confirmed by ESI-MS with a measured mass of 213.1 (M after OEt loss) + for an expected 213.1 m/z. The FTIR spectrum of the product also exhibits the characteristic band at 3055 cm −1 arising from ν(CNapht-H), together with the antisymmetric and symmetric ν(Si-O-C) modes at 1077 and 942 cm −1 , respectively [58,59]. Triethoxysilanes, when involved in condensation reaction with silanolates, are not as reactive as chlorosilanes and can release basic ethanolates, which can interfere with the reaction. Indeed, attempts to directly graft the ethoxydimethyl(2-naphthylethyl)silane onto the T4 silanolate were unsuccessful. In contrast, chlorosilanes, which form neutral chloride salts as a byproduct during condensation, avoid this side reaction. Consequently, the ethoxydimethyl(2-naphthylethyl)silane was chlorinated using acetyl chloride as a chlorinating agent, as previously described [60] (Figure 3), yielding S1. The 1 H NMR spectrum ( Figure S4) demonstrates the disappearance of the ethoxy-group signals, as well as a shift of the dimethyl signals toward the lower field due to the proximity of the more electronegative chlorine atom. Similarly, the CH2 signals are displaced downfield to 2.97 and 1.33 ppm. No significant impurities can be observed in the spectrum. The 13 C NMR Triethoxysilanes, when involved in condensation reaction with silanolates, are not as reactive as chlorosilanes and can release basic ethanolates, which can interfere with the reaction. Indeed, attempts to directly graft the ethoxydimethyl(2-naphthylethyl)silane onto the T 4 silanolate were unsuccessful. In contrast, chlorosilanes, which form neutral chloride salts as a byproduct during condensation, avoid this side reaction. Consequently, the ethoxydimethyl(2-naphthylethyl)silane was chlorinated using acetyl chloride as a chlorinating agent, as previously described [60] (Figure 3), yielding S1. The 1 H NMR spectrum ( Figure S4) demonstrates the disappearance of the ethoxy-group signals, as well as a shift of the dimethyl signals toward the lower field due to the proximity of the more electronegative chlorine atom. Similarly, the CH 2 signals are displaced downfield to 2.97 and 1.33 ppm. No significant impurities can be observed in the spectrum. The 13 C NMR spectrum is also consistent with the chlorination, as evidenced by the disappearance of the ethoxy signals around 18 and 58 ppm and by the shift of the dimethyl signal from −1.95 to 1.77 ppm ( Figure S5). Moreover, in 29 Si NMR ( Figure S6), the silicon signal is shifted to 31.61 ppm, characteristic of the chlorosilane [56]. The ESI-MS data were also consistent with the target compound, with a 248.1 m/z corresponding to the expected value for S1.

Synthesis of Bifunctional T 4 Janus Tetrapod
The chlorosilane described above was subsequently grafted onto the all-cis T 4 tetrasilanolate [32] via condensation. This significantly enhances the solubility of the resulting T 4 in common solvents such as chloroform, dichloromethane, tetrahydrofuran and toluene, thus facilitating functionalization on the Si-C face ( Figure 4). The target Janus T 4 tetrapod was then obtained via a three-step reaction: (1) condensation to graft the naphthyl chlorosilane onto the silanolates; (2) thiol-ene click reaction with thioacetic acid at the vinyl site to introduce a protected thiol moiety; and (3) deprotection of the latter to release the thiol function. Other recent reports of the synthesis of functional Janus tetrapods with thioacetate [49] or naphthalene groups [24,50] have yielded products which either bear functional groups on only one face; have vinyl moieties on both faces (thus preventing a selective functionalization of one face of the cycle); or were not further functionalized. In contrast, our approach enables the orthogonal faces to be independently functionalized. spectrum is also consistent with the chlorination, as evidenced by the disappearance of the ethoxy signals around 18 and 58 ppm and by the shift of the dimethyl signal from -1.95 to 1.77 ppm ( Figure S5). Moreover, in 29 Si NMR ( Figure S6), the silicon signal is shifted to 31.61 ppm, characteristic of the chlorosilane [56]. The ESI-MS data were also consistent with the target compound, with a 248.1 m/z corresponding to the expected value for S1.

Synthesis of Bifunctional T4 Janus Tetrapod
The chlorosilane described above was subsequently grafted onto the all-cis T4 tetrasilanolate [32] via condensation. This significantly enhances the solubility of the resulting T4 in common solvents such as chloroform, dichloromethane, tetrahydrofuran and toluene, thus facilitating functionalization on the Si-C face ( Figure 4). The target Janus T4 tetrapod was then obtained via a three-step reaction: (1) condensation to graft the naphthyl chlorosilane onto the silanolates; (2) thiol-ene click reaction with thioacetic acid at the vinyl site to introduce a protected thiol moiety; and (3) deprotection of the latter to release the thiol function. Other recent reports of the synthesis of functional Janus tetrapods with thioacetate [49] or naphthalene groups [24,50] have yielded products which either bear functional groups on only one face; have vinyl moieties on both faces (thus preventing a selective functionalization of one face of the cycle); or were not further functionalized. In contrast, our approach enables the orthogonal faces to be independently functionalized. Firstly, the all-cis T4 vinyl silanolate was reacted with the chlorosilane S1 in the presence of triethylamine as an HCl scavenger to avoid isomerization of the T4 structure [35]. A small excess of S1 was used to ensure complete substitution on the four silanolate sites. The resulting oil was purified via flash column chromatography to remove the main impurity, namely, the disiloxane formed by the hydrolysis of the excess S1. The 1 H NMR spectrum of the pure J1 ( Figure S7) shows signals arising from both naphthyl (7.33 to 7.80 ppm) and vinyl protons (5.99 to 6.01 ppm). In addition, the signals from CH2 associated with the chlorosilane are shifted upfield to 1.10 (CH2-Si) and 2.86 ppm (CH2-CH2-Si) due to the substitution of the chlorine by an oxygen atom. The dimethyl groups of the silane experience a similar effect and are seen at 0.25 ppm. In addition, the small signals observed on the base of the main signals are due to the presence of small quantities of some isomers, which could not be separated by column chromatography. In the 29 Si NMR spectrum of J1 ( Figure 5, left), two signals can be seen at 10.30 and −80.19 ppm. The former corresponds to the dimethyl(2-naphthylethyl)silane linked to an oxygen atom, while the latter is consistent with the signals typically obtained for T 3 silsesquioxane species linked to an unsaturated organic group. Both chemical shifts are consistent with the literature [37]. It is noteworthy that no additional signals associated with the chlorosilane or its hydrolysis/self-condensation products are observed. In addition, FTIR ( Figure S8) and mass spectrum is also consistent with the chlorination, as evidenced by the disappearance of the ethoxy signals around 18 and 58 ppm and by the shift of the dimethyl signal from -1.95 to 1.77 ppm ( Figure S5). Moreover, in 29 Si NMR ( Figure S6), the silicon signal is shifted to 31.61 ppm, characteristic of the chlorosilane [56]. The ESI-MS data were also consistent with the target compound, with a 248.1 m/z corresponding to the expected value for S1.

Synthesis of Bifunctional T4 Janus Tetrapod
The chlorosilane described above was subsequently grafted onto the all-cis T4 tetrasilanolate [32] via condensation. This significantly enhances the solubility of the resulting T4 in common solvents such as chloroform, dichloromethane, tetrahydrofuran and toluene, thus facilitating functionalization on the Si-C face (Figure 4). The target Janus T4 tetrapod was then obtained via a three-step reaction: (1) condensation to graft the naphthyl chlorosilane onto the silanolates; (2) thiol-ene click reaction with thioacetic acid at the vinyl site to introduce a protected thiol moiety; and (3) deprotection of the latter to release the thiol function. Other recent reports of the synthesis of functional Janus tetrapods with thioacetate [49] or naphthalene groups [24,50] have yielded products which either bear functional groups on only one face; have vinyl moieties on both faces (thus preventing a selective functionalization of one face of the cycle); or were not further functionalized. In contrast, our approach enables the orthogonal faces to be independently functionalized. Firstly, the all-cis T4 vinyl silanolate was reacted with the chlorosilane S1 in the presence of triethylamine as an HCl scavenger to avoid isomerization of the T4 structure [35]. A small excess of S1 was used to ensure complete substitution on the four silanolate sites. The resulting oil was purified via flash column chromatography to remove the main impurity, namely, the disiloxane formed by the hydrolysis of the excess S1. The 1 H NMR spectrum of the pure J1 ( Figure S7) shows signals arising from both naphthyl (7.33 to 7.80 ppm) and vinyl protons (5.99 to 6.01 ppm). In addition, the signals from CH2 associated with the chlorosilane are shifted upfield to 1.10 (CH2-Si) and 2.86 ppm (CH2-CH2-Si) due to the substitution of the chlorine by an oxygen atom. The dimethyl groups of the silane experience a similar effect and are seen at 0.25 ppm. In addition, the small signals observed on the base of the main signals are due to the presence of small quantities of some isomers, which could not be separated by column chromatography. In the 29 Si NMR spectrum of J1 ( Figure 5, left), two signals can be seen at 10.30 and −80.19 ppm. The former corresponds to the dimethyl(2-naphthylethyl)silane linked to an oxygen atom, while the latter is consistent with the signals typically obtained for T 3 silsesquioxane species linked to an unsaturated organic group. Both chemical shifts are consistent with the literature [37]. It is noteworthy that no additional signals associated with the chlorosilane or its hydrolysis/self-condensation products are observed. In addition, FTIR ( Figure S8) and mass refers to the Si4O4 ring, as il-lustrated in Figure 1).
Firstly, the all-cis T 4 vinyl silanolate was reacted with the chlorosilane S1 in the presence of triethylamine as an HCl scavenger to avoid isomerization of the T 4 structure [35]. A small excess of S1 was used to ensure complete substitution on the four silanolate sites. The resulting oil was purified via flash column chromatography to remove the main impurity, namely, the disiloxane formed by the hydrolysis of the excess S1. The 1 H NMR spectrum of the pure J1 ( Figure S7) shows signals arising from both naphthyl (7.33 to 7.80 ppm) and vinyl protons (5.99 to 6.01 ppm). In addition, the signals from CH 2 associated with the chlorosilane are shifted upfield to 1.10 (CH 2 -Si) and 2.86 ppm (CH 2 -CH 2 -Si) due to the substitution of the chlorine by an oxygen atom. The dimethyl groups of the silane experience a similar effect and are seen at 0.25 ppm. In addition, the small signals observed on the base of the main signals are due to the presence of small quantities of some isomers, which could not be separated by column chromatography. In the 29 Si NMR spectrum of J1 ( Figure 5, left), two signals can be seen at 10.30 and −80.19 ppm. The former corresponds to the dimethyl(2-naphthylethyl)silane linked to an oxygen atom, while the latter is consistent with the signals typically obtained for T 3 silsesquioxane species linked to an unsaturated organic group. Both chemical shifts are consistent with the literature [37]. It is noteworthy that no additional signals associated with the chlorosilane or its hydrolysis/self-condensation products are observed. In addition, FTIR ( Figure S8) and mass spectrometry corroborate the results obtained by NMR. In particular, the ESI-MS exhibits a strong peak at 1201.41 m/z (M+H) + for an expected m/z of 1201.40. In the FTIR spectrum, the naphthyl group can be observed through the C-C and C-H stretching modes at 1600 and 3056 cm −1 , respectively [59]. The CH in-plane bending mode of the alkene [61] can be seen at 1366 cm −1 and the Si-Me stretching mode of the dimethylsilane [37] at 841 cm −1 . Furthermore, the Si-O-Si stretching mode of the silsesquioxane is observed at 1043 cm −1 , which is higher than that of the T 4 tetrasilanolate (952 cm −1 ). This shift is consistent with a more constrained T 4 ring than that of the unfunctionalized tetrasilanolate. The sharpness of the Si-O-Si peak also confirms that the product obtained is not a polymer, but a well-defined cyclic oligomer, consistent with the formation of J1. To release the thiol function, the deprotection of the J2 thioacetate is required. Due to the possibility that the released thiol would oxidize, all reactions were carried out in solvent outgassed by freeze-pump-thaw cycles. As silsesquioxanes are generally sensitive to basic and nucleophilic media, the deprotection was first performed under acidic conditions with 35% hydrochloric acid solution [65] or with in situ acid generated from acetyl chloride [66]. In both cases, the thiol was successfully deprotected, but isomerization and/or polymerization was observed via the broadening of the NMR signals. Additional trials involved the use of potassium carbonate [67] as a weak base and weak nucleophile, but no reaction occurred even after three days. Finally, the successful deprotection was achieved under reducing conditions using LiAlH4. The crude J3 product obtained after completion of the reaction was purified by flash column chromatography to remove small quantities of isomeric impurities. The 1 H NMR spectrum of J3 ( Figure S10) illustrates the disappearance of the acetate signal associated with the thioacetate at 2.29 ppm, together with the sharp dimethyl signal at 0.17 ppm expected for the pure compound. In addition, signals arising from the CH2 in the α-position of the silicon atoms are present at 1.03 ppm, while those in the α-position of the thiol at 2.75 ppm (similar shift to that of the thioacetate) and the α-position of the naphthyl group at 2.62 ppm are also observed. Similarly, the 29 Si NMR spectrum of J3 ( Figure 5, right) shows two signals: one at 10.42 ppm corresponding to the dimethylsilane, and a second at −71.87 ppm corresponding to the T4 cycle (T 3 silsesquioxane species linked to saturated moieties). The sharp signals observed in 29 Si NMR confirm that the degradation and isomerization by-products were successfully removed. In addition, the FTIR spectrum ( Figure S8) shows the disappearance of the thioacetate C=O mode (1687 cm −1 ) [63]. The weak thiol S-H stretching mode [68] appears at 2570 cm −1 , confirming successful deprotection. The characteristic bands of naphthyl are also observed, with the C-C and C-H stretching modes observed at 1600 and 3051 cm −1 , respectively [59]. A sharp Si-O-Si stretching band of the silsesquioxane T 3 species is still seen at 1047 cm −1 , suggesting that the cyclic system remained intact following the treatment with LiAlH4, although the peaks appear slightly broader in the latter case. The ESI-MS data were also consistent with the formation of J3, with a peak observed at 1354.38 m/z (M+NH4) + (expected value 1354.39 m/z).
These data confirm the successful synthesis of the target Janus T4 tetrapod in an all-cis configuration, as shown in Figure 6. This constitutes one of the few reports of the synthesis The grafting of the chlorosilane onto the T 4 tetrasilanolate significantly increases its solubility, thus facilitating the functionalization of the T 4 on the opposite Si-C face. Accordingly, J1 was subjected to a thiol-ene click reaction with thioacetic acid to introduce a thiol function in its protected form (J2, Figure 4), following a procedure previously developed by our group [62]. The 1 H NMR spectrum of the crude product indicated the completion of the reaction, together with the presence of impurities. After purification by silica column chromatography, the 1 H NMR spectrum of J2 ( Figure S9) was consistent with the complete functionalization of the four vinyl groups of J1, as shown by the disappearance of the vinyl signal at 6.00 ppm. A new CH 2 signal at 2.98 ppm, which corresponds to the expected chemical shift of the CH 2 group in the α-position of the sulfur atom, was observed. Indeed, the electronegativity of the sulfur atom leads to lower field shifts. In addition, the signal at 1.04 ppm appears as a complex multiplet after grafting. Due to the proximity of the silicon atoms of the T 4 ring, the two CH 2 protons in the α-position of the silicon atoms on each face of the ring can appear together and thus be nearly superimposed. The signal corresponding to the thioacetate is observed at 2.29 ppm. In addition, it should be noted that column chromatography enables some of the isomers generated during the condensation step to be removed. Indeed, the signal associated with the dimethylsilane is very sharp and the signals near the base of the main signal, observed in the spectrum of J1 ( Figure S7), were not evident in Figure S9. The changes in polarity between the naphthylvinyl T 4 silsesquioxane and naphthylthioacetate T 4 silsesquioxane may have facilitated the improved separation. The 29 Si NMR spectrum also exhibits a major change in the silicon chemical shifts (Figure 5, middle). In particular, the silicon linked to the organic group of the T 3 silsesquioxane species shifts from −80.19 ppm in the case of the vinyl substituent (unsaturated) to −71.58 ppm in the case of the ethylthioacetate substituent (saturated). This result is consistent with the expected chemical shift of the T 3 silsesquioxane linked to a saturated organic group, which is expected at around −70 ppm [32]. Furthermore, the FTIR spectrum ( Figure S8) is consistent with the NMR data. The thioacetate C=O stretching mode appears at 1687 cm −1 and the (C=O)-S stretching mode at 624 cm −1 [63]. The characteristic naphthyl bands are also visible, including the C-C and C-H stretching modes at 1600 and 3055 cm −1 , respectively [59]. The Si-Me stretching mode of the dimethylsilane [37] is still visible at 842 cm −1 . The Si-O-Si stretching mode of the silsesquioxane [64] is observed at 1053 cm −1 as a sharp peak, consistent with a well-defined T 3 silicon species such as J2. The ESI-MS data also confirm the formation of J2, with a peak observed at 1527.42 m/z (M+Na) + for an expected value of 1527.38 m/z.
To release the thiol function, the deprotection of the J2 thioacetate is required. Due to the possibility that the released thiol would oxidize, all reactions were carried out in solvent outgassed by freeze-pump-thaw cycles. As silsesquioxanes are generally sensitive to basic and nucleophilic media, the deprotection was first performed under acidic conditions with 35% hydrochloric acid solution [65] or with in situ acid generated from acetyl chloride [66]. In both cases, the thiol was successfully deprotected, but isomerization and/or polymerization was observed via the broadening of the NMR signals. Additional trials involved the use of potassium carbonate [67] as a weak base and weak nucleophile, but no reaction occurred even after three days. Finally, the successful deprotection was achieved under reducing conditions using LiAlH 4 . The crude J3 product obtained after completion of the reaction was purified by flash column chromatography to remove small quantities of isomeric impurities. The 1 H NMR spectrum of J3 ( Figure S10) illustrates the disappearance of the acetate signal associated with the thioacetate at 2.29 ppm, together with the sharp dimethyl signal at 0.17 ppm expected for the pure compound. In addition, signals arising from the CH 2 in the α-position of the silicon atoms are present at 1.03 ppm, while those in the α-position of the thiol at 2.75 ppm (similar shift to that of the thioacetate) and the α-position of the naphthyl group at 2.62 ppm are also observed. Similarly, the 29 Si NMR spectrum of J3 ( Figure 5, right) shows two signals: one at 10.42 ppm corresponding to the dimethylsilane, and a second at −71.87 ppm corresponding to the T 4 cycle (T 3 silsesquioxane species linked to saturated moieties). The sharp signals observed in 29 Si NMR confirm that the degradation and isomerization by-products were successfully removed. In addition, the FTIR spectrum ( Figure S8) shows the disappearance of the thioacetate C=O mode (1687 cm −1 ) [63]. The weak thiol S-H stretching mode [68] appears at 2570 cm −1 , confirming successful deprotection. The characteristic bands of naphthyl are also observed, with the C-C and C-H stretching modes observed at 1600 and 3051 cm −1 , respectively [59]. A sharp Si-O-Si stretching band of the silsesquioxane T 3 species is still seen at 1047 cm −1 , suggesting that the cyclic system remained intact following the treatment with LiAlH 4 , although the peaks appear slightly broader in the latter case. The ESI-MS data were also consistent with the formation of J3, with a peak observed at 1354.38 m/z (M+NH 4 ) + (expected value 1354.39 m/z).
These data confirm the successful synthesis of the target Janus T 4 tetrapod in an all-cis configuration, as shown in Figure 6. This constitutes one of the few reports of the synthesis of such bifunctional compounds and is, to the best of our knowledge, the first report of a Janus T 4 silsesquioxane bearing reactive thiol ligands on one face of the molecule. As demonstrated in previous reports, such ligands attached to both ring and cage silsesquioxanes can be readily post-functionalized using standard reactions such as thiol-ene click chemistry [62]. Such strategies involving J3 will be explored in a future study.

Chemicals
All-cis T4 vinyl silanolate (tetravinylcyclotetrasilanolate, potassium salt) was prepared as described previously [32]. Azobisisobutyronitrile (AIBN) was recrystallized prior to use. 2-vinylnaphthalene and ethoxydimethylsilane were purchased from Alfa Aesar; Karstedt's catalyst and triethylamine from Sigma Aldrich; and thioacetic acid and acetyl chloride from Acros. Lithium aluminum hydride was provided by TCI. All chemicals were used without any purifications. Toluene and THF were obtained from VWR and dried prior to use.
The products were purified by flash chromatography in a Buchi Reveleris X2 flash chromatography system, equipped with a silica column, evaporative light-scattering detection (ELSD) and 254-nm light source, using a mixture of dichloromethane (DCM)/cyclohexane (VWR, technical grade) as eluents.

Synthesis of Ethoxydimethyl(2-naphthylethyl)silane
In a rotaflo ® Schlenk flask flamed-dried three times, 2-vinylnaphthalene (39 mmol, 6.0 g, 1 eq) was dissolved in toluene (20 mL) under an argon atmosphere. Ethoxydimethylsilane (58 mmol, 8.0 mL, 1.5 eq) was then added. The vessel was placed in a water bath to dissipate the heat generated by the highly exothermic reaction and avoid evaporation of the volatile ethoxydimethylsilane. Karstedt's catalyst (2% Pt in xylene, 0.195 mmol, 2.2 mL, 0.5 mol% Pt with respect to vinylnaphthalene) was added dropwise. The completion of the reaction was verified by 1 H NMR after 10 min. The solvent and excess silane were evaporated under reduced pressure after 1 h of reaction. Finally, the crude product was purified by flash column chromatography with a cyclohexane/DCM gradient up to 80/20. After separation and solvent evaporation, the product was recovered as a colorless oil.

Chemicals
All-cis T 4 vinyl silanolate (tetravinylcyclotetrasilanolate, potassium salt) was prepared as described previously [32]. Azobisisobutyronitrile (AIBN) was recrystallized prior to use. 2-vinylnaphthalene and ethoxydimethylsilane were purchased from Alfa Aesar; Karstedt's catalyst and triethylamine from Sigma Aldrich; and thioacetic acid and acetyl chloride from Acros. Lithium aluminum hydride was provided by TCI. All chemicals were used without any purifications. Toluene and THF were obtained from VWR and dried prior to use.
The products were purified by flash chromatography in a Buchi Reveleris X2 flash chromatography system, equipped with a silica column, evaporative light-scattering detection (ELSD) and 254-nm light source, using a mixture of dichloromethane (DCM)/cyclohexane (VWR, technical grade) as eluents.

Synthesis of Ethoxydimethyl(2-naphthylethyl)silane
In a rotaflo ® Schlenk flask flamed-dried three times, 2-vinylnaphthalene (39 mmol, 6.0 g, 1 eq) was dissolved in toluene (20 mL) under an argon atmosphere. Ethoxydimethylsilane (58 mmol, 8.0 mL, 1.5 eq) was then added. The vessel was placed in a water bath to dissipate the heat generated by the highly exothermic reaction and avoid evaporation of the volatile ethoxydimethylsilane. Karstedt's catalyst (2% Pt in xylene, 0.195 mmol, 2.2 mL, 0.5 mol% Pt with respect to vinylnaphthalene) was added dropwise. The completion of the reaction was verified by 1 H NMR after 10 min. The solvent and excess silane were evaporated under reduced pressure after 1 h of reaction. Finally, the crude product was purified by flash column chromatography with a cyclohexane/DCM gradient up to 80/20. After separation and solvent evaporation, the product was recovered as a colorless oil. Yield: 40% (C 16

Synthesis of Tetrakis(dimethyl(2-naphthylethyl)silyloxy)tetravinylcyclotetrasiloxane (J1)
In a flame-dried Schlenk flask, T 4 tetravinylcyclotetrasilanolate (0.87 mmol, 440 mg, 1 eq) was suspended in dry THF (4.4 mL) under an inert atmosphere. Distilled triethylamine (3.87 mmol, 540 µL, 4.4 eq) was then added, followed by the dropwise addition of the chlorodimethyl(2-naphthylethyl)silane (3.83 mmol, 955 mg, 4.4 eq). During the addition, a large quantity of salts was produced. The reaction mixture was held overnight at 25 • C. After reaction completion, the crude product was evaporated, dissolved in pentane to precipitate the triethylammonium salts formed and filtered on a celite ® pad. The evaporated filtrate was then purified by silica column chromatography with a cyclohexane/DCM gradient from 90/10 to 70/30 (by volume). Finally, the solvent was evaporated, and the pure J1 product was recovered as a colorless oil. In a flame-dried Schlenk flask, J1 (0.5 mmol, 600 mg, 1 eq) was dissolved in dry toluene (3.6 mL) under an inert atmosphere. AIBN (0.1 mmol, 16 mg, 5 mol%/vinyl) was added and the reaction mixture was heated to 40 • C. Once this temperature was reached, thioacetic acid (3.0 mmol, 215 µL, 6 eq) was injected and the temperature was further increased to 60 • C and left reacting overnight. The reaction mixture was evaporated under vacuum and the crude product was purified via silica column chromatography with a gradient of cyclohexane/ethyl acetate eluent (up to 10%). The solvent was evaporated under reduced pressure and the J2 product was recovered as a colorless oil. The THF used in this reaction was dried and outgassed with three freeze/pump/thaw cycles prior to use. In a first flame-dried Schlenk flask, a solution of LiAlH 4 (0.42 mmol, 16 mg, 4 eq) in THF (3.2 mL) was prepared under an argon atmosphere. In another flamedried Schlenk flask, J2 (106 µmol, 160 mg, 1 eq) was dissolved in THF (8.0 mL). The second Schlenk flask was placed in an ice bath at 0 • C, and then the LiAlH 4 solution was slowly added to the solution of J2. The reacting mixture was kept at 0 • C for 1 h and then returned to room temperature for 1 h. The reaction was neutralized with a HCl solution at pH=6 and DCM was added. The solvent was evaporated, and the crude product was re-dissolved in DCM to wash the organic phase with water. After drying over Na 2 SO 4 , the solvent was evaporated under reduced pressure. The product was purified by column chromatography with ethyl acetate/cyclohexane with a gradient of 10/90 and the product was recovered as an opaque oil. Yield: 28 % (C 64

Characterization Methods
Liquid 1 H, 13 C and 29 Si NMR spectra were obtained on a Bruker Advance 400 MHz spectrometer in CDCl 3 at 25 • C and at concentrations of around 10 mg/mL. 29 Si and 13 C spectra were proton decoupled. High-resolution TOF-ESI mass spectra were obtained using a Waters Synapt G2-S spectrometer. FTIR spectra were measured on a Perkin Elmer Spectrum 100 apparatus equipped with a Gladia attenuated total reflectance (ATR) accessory. The spectrum of chlorodimethyl(2-naphthylethyl)silane was not obtained due to the corrosive characteristics of the compound, and the possibility of damaging the apparatus.

Conclusions
Herein, we describe a new strategy for synthesizing all-cis bifunctional Janus cyclotetrasiloxanes, in which the orthogonal silsesquioxane and organic faces are independently functionalized. In a first step, an all-cis tetravinylcyclotetrasilanolate was modified on the silanolate face via condensation with a functional chlorosilane. In addition to introducing a functional moiety on all four sites on the silanolate face, this step significantly enhances the solubility of the resulting T 4 molecule, facilitating the use of conventional organic synthesis approaches for modifying the vinyl site on the Si-C face. A thiol-ene click reaction was subsequently used to graft an alkylthiol moiety onto the Si-C face, thus generating an all-cis Janus tetrapod. To the best of our knowledge, this is the first report of a Janus T 4 silsesquioxane bearing reactive thiol ligands on one face of the molecule.
This synthetic strategy enables a variety of all-cis bifunctional Janus cyclotetrasiloxanes to be envisaged, with the silsesquioxane and Si-C faces being independently functionalized.
In particular, the availability of a wide range of vinyl-functionalized moieties provides access to a correspondingly broad palette of chlorosilanes, which can be used to introduce different functional groups on four corners of the silsesquioxane face. This feature, together with the proximity of the different organic groups, opens up a range of potential applications for this interesting family of molecular precursors in such areas as imaging, self-organization and sensing. The investigation of these properties, together with the synthesis of new Janus-type T 4 tetrapod architectures, will be explored in future studies.