Custom Hydrosilane Synthesis Based on Monosilane
Oestreich and colleagues present an approach to the chemoselective stepwise preparation of hydrosilanes with the general formula R 4-n SiH n where n = 1-3 and R can be different aryl and alkyl groups. The starting point is a bench-stable SiH 4 surrogate with two Si-H bonds masked as cyclohexa-2,5-dien-1-yl substituents. A sequence of palladium-catalyzed Si-H arylation and B(C 6 F 5 ) 3 -promoted deprotection and transfer hydrosilylation enables the programmable synthesis of hydrosilanes, even with three different substituents at the silicon atom.
INTRODUCTION<!>Si-H Arylation of SiH 4 Surrogates<!>B(C 6 F 5 ) 3 -Catalyzed Deprotection and Transfer Hydrosilylation of the Aryl-Substituted Surrogates<!>Further Diversification of the SiH 4 Platform<!>Concluding Remarks<!>SUPPLEMENTAL INFORMATION
<p>The silicon-carbon bond is not found in nature but is relevant to essentially any area of synthetic chemistry. Although there are numerous ways to reliably form that bond, methods are largely limited to silicon reagents with either one or more functional groups of strictly orthogonal reactivity. Selective decoration of the silicon atom with different carbon substituents in a controllable manner starting from simple building blocks such as trialkoxysilanes or tetrahalosilanes is one of the remaining challenges in silicon chemistry. The key problem is that nucleophilic displacements at either of those silicon electrophiles do not stop at monosubstitution, usually affording difficult-to-separate cocktails of the four possible silicon compounds (Fig- ure 1A). 1 This cannot be fully overcome with an excess of the silicon reagent. One known controlling factor is steric hindrance, thereby allowing for the selective preparation of di-or trisubstituted alkoxy-and halosilanes in selected cases, respectively. Another documented solution to the problem is stepwise transition-metal-catalyzed hydrosilylation of unsaturated hydrocarbons with dichlorosilane, obtainable in bulk quantities. [2][3][4][5] The accumulation of salt waste is another penalty often encountered when converting the aforementioned silanes into the corresponding hydrosilanes by hydride reduction, typically with LiAlH 4 (Figure 1A). What is missing is the custom synthesis of hydrosilanes R 4-n SiH n , where n = 3, 2, and 1, based on the simplest silicon molecule, i.e., monosilane, as a platform.</p><p>The enormous dangers associated with the handling of gaseous SiH 4 6 have deterred synthetic chemists from using it, [7][8][9] and hardly any synthetic chemistry makes use of it. In an effort to address this limitation, our laboratory recently introduced solid 1 as well as liquid 2 as bench-stable SiH 4 surrogates (Figure 1B), 10 and</p><p>The Bigger Picture tri(cyclohexa-2,5-dien-1-yl)silane ( 1) is now commercially available. The cyclohexa-2,5-dien-1-yl substituents in 1 and 2 serve as placeholders for the Si-H bonds, and these are set free by the action of the strong boron Lewis acid tris(pentafluorophenyl)borane, B(C 6 F 5 ) 3 . 11 As SiH 4 is almost insoluble in any solvent, the buildup of SiH 4 pressure becomes a potential risk. We therefore merged the above deprotection with the B(C 6 F 5 ) 3 -catalyzed hydrosilylation of alkenes 12 to directly and safely consume the in-situ-liberated monosilane. [13][14][15] The net reaction is an ionic transfer hydrosilylation, 16 providing access to alkyl-substituted dihydro-and monohydrosilanes R 4-n SiH n , where n = 2 and 1 and R = alkyl. 10 We were also able to demonstrate the compatibility of the cyclohexa-2,5-dien-1-yl units in 2 with platinum catalysis, and that allowed for the preparation of a small set of alkyl-substituted trihydrosilanes RSiH 3 , where R is the primary alkyl after B(C 6 F 5 ) 3 -promoted deprotection. 17 These contributions did indeed open the door to SiH 4 -based synthesis of alkyl-substituted hydrosilanes, but the installation of aryl groups at the silicon atom was not feasible. The present work closes this gap by palladium-catalyzed arylation of a SiH 4 surrogate followed by a series of silicon-carbon bond-forming events (Figure 1B). By this, the selective synthesis of more than 50 different silanes with various substitution patterns becomes accessible.</p><!><p>As an entry into the universal synthesis of R 4-n SiH n , we chose the transition-metalcatalyzed cross-coupling of the Si-H bond(s) in surrogates 1 and 2 and aryl halides. There are several palladium(0)- [18][19][20][21] and rhodium(I)-catalyzed 22,23 methods available, and they rely on either (EtO) 3 SiH 18,19,22 or R 2 SiH 2 20 and R 3 SiH 21,23 as the hydrosilane component. The big challenge in these reactions is competing hydrodehalogenation along with the formation of the corresponding halosilane. 24 Yamanoi and co-workers identified (tBu 3 P) 2 Pd together with a base as a catalyst system that would largely suppress that side reaction. 20,21 Applying their optimal setup and variations thereof to the coupling of tri(cyclohexa-2,5-dien-1-yl)silane (1) and 4-iodoanisole (3a), we always observed full conversion of both reactants to result in hydrodeiodination exclusively; the iodinated surrogate was also detected (Table S1). Conversely, less congested di(cyclohexa-2,5-dien-1-yl)silane (2) yielded the desired hydrosilane 4a with Yamanoi and co-workers' original procedure for dihydrosilanes ((tBu 3 P) 2 Pd [5 mol %], Et 3 N [3 equiv] in tetrahydrofuran at room temperature); 21 no 2-fold arylation was obtained, but anisole (5a) was still formed in substantial amounts. To force back hydrodeiodination, we performed an extensive optimization study (Table S2), and we were indeed able to minimize competitive formation of 5a by using iPr 2 NH as base and benzene as solvent at room temperature (Figure 2). Other coupling partners such as the respective aryl bromide and triflate showed partial or no conversion (Table S2). The cyclohexa-2,5-dien-1-yl  With an optimized setup in hand, we turned our attention toward the scope of the reaction with aryl iodides (Figure 2). Next to electron-rich 3a, iodobenzene 3b and several methyl-substituted derivatives 3c-3g reacted selectively in good yields (Figures S1-S21). However, 2-iodo-1,3-dimethylbenzene was most likely sterically too hindered, and no reaction happened (not shown). Interestingly, the selectivity was eroded for both iodonaphthalenes 3h and 3i, particularly for the sterically more hindered a-isomer 3h (Figures S22-S27). A broad range of electron-withdrawing functional groups as in 3j-3n was tolerated (Figures S28-S42). A free aniline as in 3o engaged in cross-coupling in moderate yield (Figures S43-S45), whereas a free phenol as in 3p reacted sluggishly. We then tested those heteroaryl groups that had worked in Yamanoi et al.'s case. 21 A thien-2-yl substituent as in 3q was introduced with excellent selectivity in high yield (Figures S46-S48), but the installation of a pyridin-4-yl group as in 3r failed. Separation of the desired aryl-substituted di(cyclohexa-2,5-dien-1-yl)silanes 4 from the hydrodeiodinated arene byproducts 5 by flash chromatography on silica gel was generally straightforward.</p><!><p>The two cyclohexa-2,5-dien-1-yl groups attached to the silicon atom in 4 are masked Si-H bonds, and we anticipated facile release of the aryl-substituted trihydrosilanes 6 by treatment with catalytic B(C 6 F 5 ) 3 (Figure 2). These trihydrosilanes 6 are highly important precursors, i.e., for the generation of oligo-and polysilanes. The usual way to prepare 6 is from trialkoxysilanes with LiAlH 4 as the hydride source; that step often furnishes low yields because of significant ligand redistribution. 25,26 Conversely, the B(C 6 F 5 ) 3 -catalyzed removal of the cyclohexa-2,5-dien-1-yl groups in 4 in CD 2 Cl 2 at room temperature enabled the rapid release of the trihydrosilanes 6 in quantitative yields (Figures 2 and S49-S75). Substrates containing Lewis-basic sites that coordinate to the B(C 6 F 5 ) 3 catalyst did not participate, e.g., derivatives 4a (OMe), 4l (CN), or 4o (NH 2 ).</p><p>After the successful release of the trihydrosilanes 6 from 4, we decided to directly subject 4 to the previously reported B(C 6 F 5 ) 3 -catalyzed transfer hydrosilylation of carbon-carbon multiple bonds (Figure 3A). 10,13,14,16 To achieve selective 1-fold hydrosilylation to arrive at dihydrosilanes 8, we used alkenes 7 as the limiting reagent, i.e., an excess of 3.0 equiv of 4. With 10 mol % of B(C 6 F 5 ) 3 as catalyst, these transfer hydrosilylations proceeded smoothly in CH 2 Cl 2 at room temperature, leaving the remaining two Si-H bonds intact. Four different types of disubstituted alkenes were exemplarily used, and isolated yields were good throughout (Figures S76-S93). It is virtually impossible to prepare dihydrosilanes 8 with one aryl and one alkyl substituent from SiX 4 with organometallic reagents. Simply reversing the ratio of the two reactants, i.e., increasing the amount of the alkene to 2.1 equiv on the basis of the aryl-substituted surrogate 4, allowed for 2-fold transfer hydrosilylation (Figure 3A). The monohydrosilanes 9 with one aryl and two identical alkyl groups formed selectively in high yields (Figures S94-S117). The results are in agreement with earlier observations. 10,13 We also attempted the 2-fold transfer hydrosilylation for internal triple bonds, and hex-3-yne (10a) and 1-phenylprop-1-yne (10b) were converted quantitatively into the tertiary hydrosilanes 11 in good yields (Figures 3A and S118-S123); the double bond geometries in 11ca and 11cb were determined to be Z, and this is in accordance with the assumed intermediacy of carbocations. 10,13 For the sake of completeness, we also tried a-olefins 7j and 7k but these always furnished mixtures of dihydro-and monohydrosilanes 8 and 9 as well as fully substituted silanes 12 under the above-described reaction conditions. Increasing the amount of these not hindered alkenes to 3.5 equiv afforded the tetraorganosilanes 12 cleanly (Figures 3B and S124-S127).</p><!><p>Transfer hydrosilylation cannot bring about the selective installation of linear alkyl chains. To realize this, we subjected selected aryl-substituted 4 to our platinumcatalyzed hydrosilylation, 17 and surrogates 4c and 4j were converted into 13ck and 13jk with oct-1-ene (7k) as solvent (Figures 4A and S128-S133). As before, the masked dihydrosilanes were easily deprotected with B(C 6 F 5 ) 3 to yield 8ck and Si H B(C 6 F 5 ) 3 (10 mol %) atom, we switched to Friedel-Crafts-type C-H silylation of electron-rich arenes (Figure 4B). 27 We as well as Hou and co-workers had recently found that B(C 6 F 5 ) 3 catalyzes the silylation of arene C-H bonds, 28,29 and we thought that this methodology would, in analogy to the transfer hydrosilylation, combine silicon-carbon bond formation and deprotection in a one-pot operation. Building block 4 reacted with anilines 15 in good yield to deliver dihydrosilanes 16 with two different aryl substituents (Figures S152-S160); indole derivatives were however not compatible (not shown).</p><!><p>This work demonstrates that the protected version of SiH 4 , di(cyclohexa-2,5-dien-1yl)silane ( 2), is a highly useful starting point for the on-demand synthesis of hydrosilanes with heteroleptic substitution patterns. The selective arylation of one of the available Si-H bonds in 2 leads to the central building block 4, the point of diversification. This is mainly achieved by B(C 6 F 5 ) 3 -catalyzed processes, namely deprotection and hydrosilylation or both (= transfer hydrosilylation) as well as Friedel-Crafts-type C-H silylation. Diverse sets of tri-, di-, and monohydrosilanes have been obtained. This approach overcomes the serious issues associated with traditional methods based on completely unselective nucleophilic substitution of SiCl 4 and related cheap starting materials with carbon nucleophiles.</p><!><p>Supplemental Information includes Supplemental Experimental Procedures, 160 figures, and 2 tables and can be found with this article online at https://doi.org/ 10.1016/j.chempr.2018.03.017.</p>