Exploring Silyl Protecting Groups for the Synthesis of Carbon Nanohoops

Abstract

The synthesis of topological molecular nanocarbons, such as hoop-like [n]cycloparaphenylenes, requires the use of spatially prearranged, pro-aromatic units to overcome a build-up of large molecular strain in their curved structures. The used cyclohexadienyl units, however, contain tertiary alcohols that need protection to prevent side reactions until the aromatization step that affords the final curved hydrocarbon. Although alkyl and triethylsilyl groups have been successfully applied as protecting groups for this purpose, each suffers from specific drawbacks. Here, we explore the potential of sterically more crowded silyl groups, namely, tert-butyldimethylsilyl and triisopropylsilyl, as alternatives to the established protection strategies. We show that tert-butyldimethylsilyl can be easily installed and removed under mild conditions, displaying markedly higher resistance towards acids or bases than the triethylsilyl group used to date. Unlike in the case of alkyl groups, tert-butyldimethylsilyl also preserves a high stereoselectivity during the nucleophilic additions of ArLi. Furthermore, we demonstrate that both tert-butyldimethylsilyl and triethylsilyl groups can be installed on the same substrate, and that the latter be selectively deprotected. Thus, the high stereoselectivity, improved stability, and easy deprotection make tert-butyldimethylsilyl an excellent protecting group for the synthesis of carbon nanohoops.

Key words

topological molecular nanocarbons - carbon nanohoops - cycloparaphenylenes - protecting groups - silyl ethers - tert-butyldimethylsilyl - macrocycles - orthogonality

Protecting groups are an indispensable tool to control the selectivity of chemical transformations in modern natural product synthesis or the synthesis of organic materials. An ideal protecting group needs to match several criteria, such as high-yielding introduction and removal steps, sufficient stability and highly specific deprotection conditions to afford orthogonality towards other protecting groups. Particularly useful types of scaffolds bearing tertiary alcohols, which require protection, are A and B (Figure [1]). For example, compounds 1 and 2 (Figure [2]), that contain scaffolds A and B, are important building blocks for the synthesis of topological molecular nanocarbons that involve carbon nanohoops, such as [n]cycloparaphenylenes ([n]CPPs).[1] Carbon nanohoops exhibit unique size-dependent optoelectronic properties[2] and host–guest chemistry,[3] giving rise to applications in bioimaging, optoelectronic materials and supramolecular carbon-rich nanomaterials.[4] Although envisioned decades ago, the first synthesis of these strained molecules was accomplished only in 2008 by Jasti and Bertozzi.[5] Their strategy relies on masking a p-phenylene unit as a 1,4-dimethoxycyclohexa-2,5-diene-1,4-diyl moiety. Here, the two tertiary alcohols prearrange the geometry in scaffold B with cis configuration for an effective macrocyclization. The reductive aromatization of the cyclohexa-2,5-diene unit then provides the necessary driving force to build up the strain in the final step.

Figure 1 Protection of important structural scaffolds A and B in the synthesis of carbon nanohoops

Figure 2 Topological molecular nanocarbons based on cycloparaphenylene nanohoops (top) and their synthesis using scaffolds A and B (bottom)[1i] [5]

The exergonicity of the aromatization, however, requires that the tertiary alcohols be protected throughout the multistep synthesis to avoid side reactions. The electronic nature and the size of the methyl group used originally, however, result in a poor diastereoselectivity of the addition of organolithium reagents, typically ArLi, to ketone scaffold A.[5] [6] Moreover, their removal during the aromatization often necessitates the use of harsh reagents, such as lithium/sodium naphthalide. Although the diastereoselectivity of the addition was found to be mostly dictated by electrostatics,[7,8] Yamago and co-workers[9,10] proposed the use of bulkier triethylsilyl (TES) as the protecting group for the tertiary alcohols in A or B. TES improves the stereoselectivity of ArLi addition and the exclusive formation of the cis-diastereomer of B is typically observed. TES is also relatively straightforward to deprotect with tetra-n-butylammonium fluoride (TBAF) before the aromatization of the ensuing 1,4-dihydroxycyclohexa-2,5-diene-1,4-diyl, performed under mild conditions with H₂SnCl₄.[8]

In our own experience, however, the sensitivity of the TES group towards acids compromises the stability of compounds that contain the structural motif B. Such compounds are prone to decomposition, either during the purification step after their synthesis or when stored, even at low temperatures, although such negative results are rarely reported in the literature.[1k] [4d] [11] Because of the individual drawbacks of the methyl and TES groups, we decided to search for an alternative protecting group that would (a) be easy to introduce, (b) would undergo stereoselective addition of ArLi to ketones A, (c) would be significantly more stable than TES, and (d) would be easy to remove to allow for a mild aromatization. Such a protecting group could introduce additional orthogonality to the synthesis of topological molecular nanocarbons.

Scheme 1 Introduction of silyl protecting groups to scaffolds A and B using two model alcohols 1a and 2a

The steric bulk around the silicon determines the stabi­lity of a silyl protecting group and permits selective protection/deprotection in the presence of another silyl ether.[12] [13] [14] The stability of the TES ethers used in A and B is relatively low in comparison to other silyl ethers in the presence of both acids and bases. For example, the half-lives of TES-protected p-cresol in the presence of 1% hydrochloric acid or 5% sodium hydroxide are <1 minute, while the half-lives of tert-butyldimethylsilyl (TBDMS)-protected p-cresol are 273 minutes and 3.5 minutes, respectively.[13] In general, the relative stability of different silyl groups to acids increase in the following order: trimethylsilyl (TMS) (1) < TES (64) < TBDMS (20,000) < triisopropylsilyl (TIPS) (700,000) < tert-butyldiphenylsilyl (TBDPS) (5,000,000), while to bases the order is: TMS (1) < TES (10–100) < TBDMS ~ TBDPS (20,000) < TIPS (100,000).[14] Therefore, protecting groups with additional steric bulk, such as TBDMS or TIPS, represent great candidates as considerably more stable protecting groups. In addition, the extra steric bulk of the silyl ether in A is expected to display excellent diastereoselectivity for an ArLi nucleophilic addition to form the motif B. Protection of a tertiary alcohol, however, becomes more challenging with increasing steric bulk of the silyl protecting group.[15]

We selected model alcohols 1a and 2a (Scheme [1]) as proxies for the motifs A and B, respectively. In fact, these two alcohols are frequently used in the synthesis of carbon nanohoops, including CPPs,[1] ^, [5] [6] [7] [8] ^, [16] and their protection with TES to give 1b and 2b can be achieved in 92%[1f] and ≥82%[8] yields, respectively, in a clean transformation.

We first tested the standard silylation of 1a with tert-butyldimethylsilyl chloride (TBDMSCl) and imidazole[17] in CH₂Cl₂ at room temperature (Table [1], entry 1; see also Table S1, entry 1 in the Supporting Information) and obtained full conversion of 1a. However, we observed the formation of a complicated mixture of unknown products. We assumed that the steric bulk slows down the nucleophilic substitution of the chloride in TBDMSCl, allowing other reactions to compete. We thus exchanged CH₂Cl₂ for significantly more polar DMF, which we expected to stabilize the alcoholate that would be generated from 1a and imidazole in a very small amount. Such attempts resulted only in a slow conversion of 1a into an unknown product, even when larger amounts of the reagents and an elevated temperature were used (Table [1], entry 2). Diol 2a was completely inert under the same reaction conditions (Table [1], entry 5). Similarly, alcohol 1a turned unreactive when bulkier 2,6-lutidine with a similar basicity was used (Table [1], entry 3). Likely, the observed side reactions are catalyzed by a general base. To accelerate the nucleophilic substitution at silicon, we decided to replace the chloride in TBDMSCl for triflate, which is an excellent nucleofuge. The combination of 2,6-lutidine with tert-butyldimethylsilyl trifluoromethanesulfonate (TBDMSOTf) in CH₂Cl₂, however, afforded a full conversion of 1a into 3c and 4c (Table S1, entry 4). Product 3c is most probably formed through a rearrangement involving a 1,2-aryl shift (Scheme [2]), while 4c ensues from the excess TBDMSOTf reacting with 3c. The observed transformation nicely illustrates the power of aromatization to drive rearrangements of cyclohexadienones.[18] To our satisfaction, we observed the formation of 1c when the reaction was repeated under the same conditions but in polar DMF, albeit the reaction appeared significantly slower (Table S1, entry 5).

Table 1 Optimization of the Reaction Conditions to Introduce Silyl Ethers to 1a and 2a

Entry	Reagent (equiv.)	Base (equiv.)	Solvent	Temp (°C)	Ratioa	Yield (%)b
Reaction A					1a:1c:3c:4c	1c	3c	4c
1	TBDMSCl (2)	imidazole (3)	CH2Cl2	RTc	0:0:0:0d	–	–	–
2	TBDMSCl (5)	imidazole (6)	DMF	60	<100:0:0:0d,e	–	–	–
3	TBDMSCl (5)	2,6-lutidine (6)	DMF	70	n.c.f	–	–	–
4	TBDMSOTf (2.5)	2,6-lutidine (4)	DMF	70	0:82:0:18	63 (71)g	0	14 (17)g
Reaction B					2a:2c:6c:5c	2c	6c	5c
5	TBDMSCl (5)	imidazole (6)	CH2Cl2	RTc	n.c.f	–	–	–
	TBDMSCl (5)	imidazole (6)	DMF	70	n.c.f	–	–	–
6	TBDMSOTf (5)	2,6-lutidine (6)	DMF	70	0:52:0:48	–	–	–
7	TBDMSOTf (5)	2,6-lutidine (6)	DMF	50	0:98:0:2	70	0	<5h
Reaction A					1a:2d:3d:4d	1d	3d	4d
8	TIPSOTf (5)	2,6-lutidine (6)	DMF	70	–i	3	0	34j
Reaction B					2a:2d:6d:5d	2d	6d	5d
9	TIPSOTf (5)	2,6-lutidine (6)	DMF	50	46:0:49:5	0	39	6k

^a Ratio of products determined by ¹H NMR in CDCl₃ after 18 h.

^b Yield of the isolated product after 18 h.

^c RT = room temperature.

^d Formation of unidentified product(s).

^e Product ratio determined after 38 h.

^f n.c. = no conversion.

^g Performed on 1.00 g (3.77 mmol) scale.

^h Compound 5c was isolated along with a minor unidentified product.

ⁱ Determination of the ratio was not successful due to overlap of the ¹H resonances.

^j Compound 1a was recovered in 36% yield.

^k Compound 2a was recovered in 35% yield.

Increasing the amounts of the TBDMSOTf and 2,6-lutidine and increasing the temperature provided a faster reaction, which was, however, accompanied by the formation of 4c (Table S1, entries 6–10). The optimal temperature was found to be 70 °C because it resulted in a full conversion of 1a in 18 hours (incomplete at 60 °C) and a lower yield of 4c compared to the reaction at 80 °C. The reaction at 70 °C afforded 1c and 4c in 58% and 8% isolated yields, respectively, after an easy separation by column chromatography. Finally, reducing the amounts of the reagents and the solvent (Table S1, entries 11–17) provided the optimal conditions that allowed us to isolate 1c in 71% yield on one-gram scale (Table [1], entry 4). We also tested different bases in combination with TBDMSOTf (Table S1, entries 18–23), however, the reaction was slower or no significant improvement of the 1c:4c ratio or the isolated yield of 1c could be achieved.

We next attempted the protection of diol 2a with TBDMSOTf (Scheme [1], Reaction B). The optimal conditions found for the protection of 1a led to a full conversion of 2a (Table [1], entry 6). In addition to the desired product 2c, however, formation of a significant portion of 5c was observed. Similar to the formation of 3c, this rearrangement involves a 1,2-aryl shift aromatizing the cyclohexa-2,5-diene-1,4-diyl unit (Scheme [2]). Increasing the amount of TBDMSOTf and 2,6-lutidine improved the relative yield of 2c (see Table S2, entry 3 in the Supporting Information). In analogy to our experiments with 1a, we hypothesized that the rate-limiting step in the rearrangement has a higher barrier. We noticed almost exclusive formation of 5c at 100 °C, while the reaction at 40 °C showed the opposite effect and provided mostly 2c (Table S2, entries 4 and 5). At room temperature, however, a small amount of the monoprotected compound 6c was observed (Table S2, entry 6). Finally, the reaction performed at 50 °C with reduced amounts of TBDMSOTf and 2,6-lutidine provided the best result (Table [1], entry 7). Compounds 2c and 5c are relatively nonpolar with similar retention factors. Nevertheless, we achieved their full separation by column chromatography and isolated 2c in 70% yield. Although the isolated yields upon protection with TBDMS are somewhat lower than those with TES, the optimized protocols provide satisfactory results that improve with the reaction scale and allow for using TBDMS protection in a multistep synthesis of hoop-like molecular nanocarbons.

Scheme 2 Proposed mechanisms for the observed rearrangements of 1a and 2c. LA = Lewis acid.

We were then interested whether the steric bulk on silicon could further be increased. We thus attempted protecting 1a with TIPSOTf by employing the base and solvent used in the case of TBDMSOTf (Table [1], entry 4). We reached an incomplete conversion after 18 hours and isolated the desired TIPS-protected 1d in only 3% yield along with the rearranged product 4d in 34% yield (Table [1], entry 8). A similar unsatisfactory result was obtained when 2a was reacted with TIPSOTf (Table [1], entry 9). In this case, no formation of doubly protected 2d was observed. Instead, the reaction afforded the monoprotected product 6d in 39% isolated yield, together with 6% of the rearranged product 5d. Although increasing the amounts of TIPSOTf and the base and elevating the temperature allowed us to improve the conversion (see Table S3, entries 3 and 4 in the Supporting Information), heating favored the formation of 5d, the exclusive product at 100 °C. Clearly, the bulkiness of the TIPS group leads to its relatively difficult introduction to 1a, and precludes installing two TIPS protecting groups on 2a due to their proximity in 2d.

The nearly exclusive formation of 5c at 100 °C (see Table S2, entry 4 in the Supporting Information) was rather intriguing because we expected the formation of 2c and 5c in similar amounts if the protection and the rearrangement were parallel processes. Instead, the result suggests that it is compound 2c that is transformed into 5c in a subsequent reaction. We thus conducted a series of experiments to determine the conditions that promote the rearrangement and that may have a detrimental effect on the stability of 2c (Table [2]).

Table 2 Stability of 2b and 2c under Different Conditions

Entry	Conditions	Substrate	Resulta
1	no additive, 100 °C	2c	n.c.b
2	2,6-lutidine (12 equiv.), 100 °C	2c	n.c.
3	TBDMSOTf (10 equiv.), 100 °C	2c	2c:5c = 0:100c
4	TBDMSCl (10 equiv.), 100 °C	2c	n.c.
5	TfOH (10 mol%), 100 °C	2c	2c:5c = 0:100d
6	TFA (10 mol%), 35 °Ce	2b	2b:6b = 83:17
		2c	n.c.
7	HCl (1 mol%), 35 °C	2b	n.c.
		2c	n.c.
8	HCl (10 mol%), 35 °C	2b	2b:2a:6b = 63:8:29
		2c	n.c.
9	TfOH (10 mol%), 35 °C	2b	unknown product(s) and traces of 2a
		2c	2c:5c = 83:17

^a Ratio of products determined by ¹H NMR in CDCl₃ after 18 h.

^b n.c. = no conversion.

^c Compound 5c was isolated in 83% yield.

^d Compound 5c was isolated in 84% yield.

^e Temperature required to dissolve 2c in DMF.

When a DMF solution of 2c was stirred at 100 °C, with or without addition of 2,6-lutidine, no conversion of 2c was observed (Table [2], entries 1 and 2). An excess of TBDMSOTf in the absence of base converted 2c fully into 5c, which we isolated in 83% yield (Table [2], entry 3). Using an excess of TBDMSCl, a weaker Lewis acid, did not show any sign of rearrangement (Table [2], entry 4). This indicates that TBDMSOTf may act in the rearrangement as a Lewis acid.[11] We suspected that TBDMSOTf may contain traces of triflic acid (TfOH) that could catalyze the rearrangement. Indeed, a catalytic amount (10 mol%) of TfOH led to a clean rearrangement of 2c at 100 °C to furnish 5c, which we isolated in 84% yield (Table [2], entry 5). It is worth noting that the second TBDMS group in 5c was not cleaved during the reaction. The TBDMS group is known to be more resistant to acidic conditions than the TES group,[14] which motivated us to compare their stabilities in 2b and 2c in the presence of acids such as TFA, HCl, and TfOH. In a typical experiment, a DMF solution of 2b or 2c was stirred with a catalytic amount of the selected acid at 35 °C for 18 hours, and the reaction progress was monitored by ¹H NMR spectroscopy (Table [2], entries 6–9). Compound 2c was inert to the presence of TFA (pK _a = 0.52 in water[19]), while partial deprotection of one of the TES groups in 2b was observed. The much stronger acid HCl (pK _a = –5.9[20]) affected neither 2b nor 2c when only 1 mol% was used. Increasing the amount of HCl to 10 mol%, however, promoted deprotection of the TES groups, while the TBDMS was inert. No rearrangement was observed in any of these attempts. Both 2b and 2c reacted in the presence of 10 mol% of the very strong acid TfOH (pK _a = –14.7[20]). Only a partial conversion of 2c was reached after 18 hours at 35 °C compared to the full rearrangement into 5c at 100 °C (Table [2], entries 5 and 9), and no TBDMS deprotection could be detected. On the other hand, compound 2b was fully transformed into a mixture of unknown products. These results indicate that 2c is considerably more resistant to acids than 2b. In our experience, some TES-protected moieties similar to 2b (see 2 in Figure [2]) are surprisingly labile.[11] Their stability is influenced by the solvent and traces of impurities. For example, we even observed a rearrangement analogous to 2c → 5c in the presence of Mg²⁺ ions in one specific case.[21] We thus expect that many issues associated with the stability of the building blocks (1 and 2 in Figure [2]) used in the synthesis of hoop-like molecular nanocarbons that rely on the strategy employing triethylsilyl protecting groups (TES) can now be avoided by using TBDMS. Clearly, the 1,2-aryl shift of TBDMS-protected 2c in DMF requires a very strong Lewis or Brønsted acid and an elevated temperature to proceed on a reasonable timescale (see Scheme [2] for the proposed mechanism). However, we cannot exclude that the formation of 5c first involves the rapid formation of 6c, although our results with HCl indicate that this process is likely not particularly facile.

We next aimed to demonstrate that the TBDMS protecting group in 1c preserves the high stereoselectivity of ArLi addition to the carbonyl group and that both TBDMS and TES groups could be installed on a single 1,4-dihydroxycyclohexa-2,5-diene-1,4-diyl moiety, as in compound 2e (Scheme [3]), with the latter being selectively removed in a subsequent step. The addition was accomplished via the reaction­ of monolithiated 1,4-dibromobenzene with 1c at –78 °C, followed by protection of the resulting alcohol with a TES group to provide 2e (1.7 g, 78% yield). We noticed the formation of a single cis diastereomer, which confirms that TBDMS displays the same high stereoselectivity as observed for 1b bearing a TES group. We fully deprotected both silyl groups with TBAF at room temperature, isolating 2a in 83% yield. Similarly, both TBDMS groups in 2c could be cleaved in 73% yield. When the temperature was decreased to –45 °C, we successfully achieved the selective deprotection of TES in 2e to afford 6c in 76% yield. Similarly, the selective deprotection of TES could also be accomplished in 82% yield when 2e was stirred with an excess of K₂CO₃ in refluxing methanol. The selective deprotection of the TES group can thus be easily achieved under mild conditions with two complementary methods. As such, combination of both silyl groups represents an attractive strategy to construct versatile building blocks that may prove useful beyond the synthesis of macrocycles found in topological molecular nanocarbons.

Scheme 3 Synthesis of 2e and its selective deprotection to 2a or 6c

Finally, we evaluated the effect of the steric bulk of the protecting groups on the ‘bite’ angle defined by the two phenylenes attached to the central cyclohexadienyl unit in 2. Building blocks such as 2 are key intermediates in the synthesis of a variety of carbon nanohoops and the size of the bite angle may affect the efficiency of the macrocyclization step. The steric hindrance between two bulky protecting groups, such as TBDMS, could decrease this angle and prevent macrocycle formation if a wider bite angle is required. Therefore, we compared the impact of the size of the protecting group (Me, TMS, TBDMS) in 2 on the bite angle using DFT calculations. We found that the value of the bite angle in 2 (65° ± 5°) is not particularly sensitive to the type of the protecting group (see Table S4 in the Supporting Information). Analysis of the few reported[16b] [22] crystal structures of compounds analogous to 2 (see Figures S1–S3 and Table S4) to validate the accuracy of the selected DFT functionals confirmed that our calculations reproduce the bite angles well. In addition, analysis of the crystal structures further revealed that the phenylenes can adopt surprisingly acute bite angles (47°). As a result, it can be expected that 2c with bulky TBDMS protecting groups can be used in place of 2b (or Me-protected 2a) in the synthesis of carbon nanohoops. However, in cases where the TES introduction or removal steps prevent successful synthesis of a carbon nanohoop, the use of TBDMS will likely lead to the same outcome.

In conclusion, we have demonstrated that tert-butyldimethylsilyl is a versatile protecting group in the preparation of important building blocks used in the synthesis of topological molecular nanocarbons, such as hoop-like CPPs. We developed the methodology to install and cleave tert-butyldimethylsilyl under mild conditions, minimizing undesired rearrangements driven by aromatization of cyclohexa-2,5-diene-1,4-diyl units. The tested tert-butyldi­methylsilyl ethers were substantially more stable towards acids and bases than the corresponding triethylsilyl groups frequently used to date. The steric bulk in the tert-butyldimethylsilyl group preserves the high stereoselectively of ArLi additions to afford spatially prearranged building blocks used in CPP synthesis. We also explored the conditions that trigger the undesired rearrangements involving 1,2-aryl shifts. In addition, we successfully prepared a compound with both tert-butyldimethyl and triethylsilyl ethers, and identified conditions that permit removing the triethylsilyl chemoselectively. We anticipate that the strategies developed in this work will not only find applications in the synthesis of carbon nanohoops, such as CPPs and their derivatives, but also of other macrocycles, e.g., unprecedented macrocyclic drugs that incorporate a biphenyl or a terphenyl moiety.

Unless otherwise stated, all glassware used to perform moisture-sensitive reactions was oven-dried at 120 °C overnight, assembled hot and allowed to cool to room temperature under a stream of argon, or flame-dried under high vacuum and filled with argon. All reactions that require heating were conducted in an oil bath and the indicated temperature corresponds to the temperature of the oil bath. To obtain a temperature of –78 °C or –45 °C, a bath of acetone or acetonitrile, respectively, was cooled with dry ice. All commercially available reagents and solvents were used directly without purification unless stated otherwise. Flash column chromatography was performed using silica gel 60 Å (230–400 mesh particle size) from Supelco^®. Thin-layer chromatography (TLC) was performed on silica gel plates F₂₅₄ 60 (aluminum-supported) from Supelco^® using UV (254 nm) visualization. ¹H and ¹³C NMR spectra were recorded on a Bruker Avance II 400 or a Bruker Avance III HD 400 spectrometer (¹H: 400 MHz, ¹³C: 101 MHz), or a Bruker Avance III HD 300 spectrometer (¹H: 300 MHz, ¹³C: 75 MHz). Chemical shifts (δ) are reported in parts per million (ppm) referenced to the residual solvent peak (¹H: 7.26 ppm for CDCl₃, 5.32 ppm for CD₂Cl₂; ¹³C: 77.16 ppm for CDCl₃, 53.84 ppm for CD₂Cl₂). Multiplicities are given as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), and br (broad). High-resolution mass spectra (HRMS) were recorded on a ThermoScientific LTQ Orbitrap XL mass instrument using nanoelectrospray (NSI-MS) or electron ionization (EI-MS). Elemental analysis was performed in triplicate on a Thermo Scientific Flash 2000 Series instrument using the CHN method with sulfanilamide or cyclohexanone as the reference. Melting points were determined on a Büchi B-545 apparatus and are uncorrected.

4′-Bromo-1-hydroxy-[1,1′-biphenyl]-4(1H)-one (1a)

We modified a literature procedure for the synthesis of 1a.[6] To a solution of 4′-bromo-(1,1′-biphenyl)-4-ol [CAS Reg. No. 29558-77-8] (20.00 g, 80.3 mmol, 1 equiv.) and imidazole [CAS Reg. No. 288-32-4] (8.75 g, 128.0 mmol, 1.6 equiv.) in CH₂Cl₂ (210 mL) was added chlorotrimethylsilane [CAS Reg. No. 75-77-4] (14.0 mL, 128.0 mmol, 1.6 equiv.) at 0 °C. The reaction mixture was allowed to warm to room temperature and stirred for 19 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (60 mL) and extracted with CH₂Cl_2­ (3 × 50 mL). The organic layers were combined, washed with saturated aqueous NaHCO₃ solution (100 mL) and brine (100 mL), dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo to afford a beige solid that was used in the next step without further purification.

(Diacetoxyiodo)benzene [CAS Reg. No. 3240-34-4] (33.62 g, 104.4 mmol, 1.3 equiv.) was added portionwise to a solution of the above solid in THF (300 mL), distilled H₂O (130 mL) and MeCN (75 mL) over 30 min. The reaction mixture was stirred at room temperature for 21.5 h. The solvents were then removed in vacuo to afford an orange solid. The crude product was purified by flash chromatography (SiO₂, EtOAc/n-pentane = 1:4 → EtOAc/n-pentane = 1:0, then MeOH/EtOAc = 1:19) to afford 1a as a pale orange solid (17.26 g, 65.1 mmol, 81%). The spectral data match the literature-reported values.[6]

Pale orange solid; R_f = 0.27 (SiO₂, EtOAc/n-pentane = 3:7); mp 176–177 °C.

¹H NMR (300 MHz, CDCl₃): δ = 7.51 (d, J = 8.7 Hz, 2 H), 7.35 (d, J = 8.7 Hz, 2 H), 6.85 (d, J = 10.1 Hz, 2 H), 6.25 (d, J = 10.0 Hz, 2 H), 2.39 (s, 1 H).

¹³C NMR (101 MHz, CDCl₃): δ = 185.44, 150.20, 137.90, 132.20, 127.37, 127.27, 122.74, 70.88.

HRMS (NSI): m/z [M – H]⁺ calcd for C₁₂H₈O₂Br: 262.9713; found: 262.9706.

Anal. Calcd for C₁₂H₉O₂Br: C, 54.37; H, 3.42. Found: C, 54.52; H, 3.46.

4′-Bromo-1-((triethylsilyl)oxy)-[1,1′-biphenyl]-4(1H)-one (1b)

According to a literature procedure,[1f] chlorotriethylsilane [CAS Reg. No. 994-30-9] (0.475 mL, 2.83 mmol, 3 equiv.) was added to a solution of 1a (500.0 mg, 1.89 mmol, 1 equiv.) and imidazole (257.0 mg, 3.77 mmol, 2 equiv.) in DMF (10 mL). The reaction mixture was stirred at 40 °C for 15 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (10 mL) and extracted with EtOAc (3 × 15 mL). The organic layers were combined, washed with saturated aqueous NaHCO₃ solution (50 mL), H₂O (2 × 50 mL) and brine (50 mL), dried over anhydrous Na₂SO₄, filtered and concentrated in vacuo to afford an orange oil. The crude product was purified by flash chromatography (SiO₂, EtOAc/n-pentane = 1:99 → EtOAc/n-pentane = 3:97) to afford 1b as a yellow oil (539.8 mg, 1.42 mmol, 75%). The spectral data match the literature-reported values.[1f]

Yellow oil; R_f = 0.30 (SiO₂, EtOAc/n-pentane = 1:19).

¹H NMR (400 MHz, CDCl₃): δ = 7.46 (d, J = 8.6 Hz, 2 H), 7.31 (d, J = 8.7 Hz, 2 H), 6.78 (d, J = 10.1 Hz, 2 H), 6.22 (d, J = 10.0 Hz, 2 H), 0.97 (t, J = 7.9 Hz, 9 H), 0.65 (q, J = 7.9 Hz, 6 H).

¹³C NMR (101 MHz, CDCl₃): δ = 185.73, 151.62, 139.29, 131.95, 127.35, 126.89, 122.23, 72.96, 7.02, 6.35.

HRMS (NSI): m/z [M + H]⁺ calcd for C₁₈H₂₄O₂BrSi: 379.0723; found: 379.0721.

Anal. Calcd for C₁₈H₂₃O₂BrSi: C, 56.99; H, 6.11. Found: C, 56.89; H, 5.99.

4′-Bromo-1-((tert-butyldimethylsilyl)oxy)-[1,1′-biphenyl]-4(1H)-one (1c)

To a solution of 1a (200.0 mg, 0.754 mmol, 1 equiv.) in DMF (10 mL) was added 2,6-lutidine [CAS Reg. No. 108-48-5] (0.351 mL, 3.02 mmol, 4 equiv.), followed by tert-butyldimethylsilyl trifluoromethanesulfonate [CAS Reg. No. 69739-34-0] (0.433 mL, 1.89 mmol, 2.5 equiv.). The reaction mixture was stirred at 70 °C for 18 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (10 mL) and extracted with EtOAc (3 × 10 mL). The organic layers were combined, washed with H₂O (2 × 30 mL) and concentrated in vacuo to afford a dark orange oil. The crude product was purified by flash chromatography (SiO₂, EtOAc/n-pentane = 1:99 → EtOAc/n-pentane = 1:19) to afford 4c as a white solid (36.8 mg, 0.075 mmol, 10%) and 1c as a white solid (197.8 mg, 0.521 mmol, 69%).

White solid; R_f = 0.29 (SiO₂, EtOAc/n-pentane = 1:19); mp 88–89 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.46 (d, J = 8.6 Hz, 2 H), 7.31 (d, J = 8.6 Hz, 2 H), 6.79 (d, J = 10.0 Hz, 2 H), 6.23 (d, J = 10.1 Hz, 2 H), 0.97 (s, 9 H), 0.12 (s, 6 H).

¹³C NMR (101 MHz, CDCl₃): δ = 185.66, 151.67, 139.34, 131.96, 127.31, 126.92, 122.23, 73.15, 25.86, 18.54, –2.49.

HRMS (NSI): m/z [M + H]⁺ calcd for C₁₈H₂₄O₂BrSi: 379.0723; found: 379.0707.

Anal. Calcd for C₁₈H₂₃O₂BrSi: C, 56.99; H, 6.11. Found: C, 57.10; H, 6.18.

4′-Bromo-5-((tert-butyldimethylsilyl)oxy)-[1,1′-biphenyl]-2-ol (3c)

To a solution of 1a (200.0 mg, 0.754 mmol, 1 equiv.) in CH₂Cl₂ (10 mL) was added 2,6-lutidine (0.263 mL, 2.26 mmol, 3 equiv.), followed by tert-butyldimethylsilyl trifluoromethanesulfonate (0.346 mL, 1.51 mmol, 2 equiv.). The reaction mixture was stirred at room temperature for 18 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (10 mL) and extracted with CH₂Cl₂ (3 × 10 mL). The organic layers were combined, washed with brine (50 mL), dried over anhydrous Na₂SO₄, filtered and concentrated in vacuo to afford an orange solid. The crude product was purified by flash chromatography (SiO₂, EtOAc/n-pentane = 1:19) to afford 4c as a white solid (194.7 mg, 0.392 mmol, 52%) and 3c as a pale orange solid (49.3 mg, 0.130 mmol, 17%).

Pale orange solid; R_f = 0.32 (SiO₂, EtOAc/n-pentane = 1:9); mp 77–78 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.60 (d, J = 8.4 Hz, 2 H), 7.35 (d, J = 8.4 Hz, 2 H), 6.81 (d, J = 8.5 Hz, 1 H), 6.74 (dd, J = 8.5, 2.9 Hz, 1 H), 6.71 (d, J = 2.9 Hz, 1 H), 4.74 (s, 1 H), 0.99 (s, 9 H), 0.19 (s, 6 H).

¹³C NMR (101 MHz, CDCl₃): δ = 149.58, 146.71, 136.34, 132.29, 130.89, 127.74, 122.08, 121.35, 120.76, 116.88, 25.85, 18.32, –4.31.

HRMS (NSI): m/z [M + H]⁺ calcd for C₁₈H₂₄O₂BrSi: 379.0723; found: 379.0721.

Anal. Calcd for C₁₈H₂₃O₂BrSi: C, 56.99; H, 6.11. Found: C, 57.06; H, 6.16.

((4′-Bromo-[1,1′-biphenyl]-2,5-diyl)bis(oxy))bis(tert-butyldimethylsilane) (4c)

See compound 1c or 3c for the synthetic procedure.

White solid; R_f = 0.69 (SiO₂, EtOAc/n-pentane = 1:99); mp 78–79 °C.

¹H NMR (300 MHz, CDCl₃): δ = 7.49 (d, J = 8.5 Hz, 2 H), 7.36 (d, J = 8.5 Hz, 2 H), 6.76 (d, J = 8.7 Hz, 1 H), 6.75 (d, J = 3.0 Hz, 1 H), 6.69 (dd, J = 8.7, 3.0 Hz, 1 H), 0.98 (s, 9 H), 0.82 (s, 9 H), 0.18 (s, 6 H), –0.09 (s, 6 H).

¹³C NMR (101 MHz, CDCl₃): δ = 150.01, 146.78, 138.12, 132.70, 131.53, 131.09, 121.82, 121.16, 121.02, 119.91, 25.86, 25.78, 18.32, 18.19, –4.29, –4.43.

HRMS (NSI): m/z [M + H]⁺ calcd for C₂₄H₃₈O₂BrSi₂: 493.1588; found: 493.1584.

Anal. Calcd for C₂₄H₃₇O₂BrSi₂: C, 58.40; H, 7.56. Found: C, 58.29; H, 7.59.

4′-Bromo-1-((triisopropylsilyl)oxy)-[1,1′-biphenyl]-4(1H)-one (1d)

To a solution of 1a (200.0 mg, 0.754 mmol, 1 equiv.) in DMF (10 mL) was added 2,6-lutidine (0.527 mL, 4.52 mmol, 6 equiv.), followed by triisopropylsilyl trifluoromethanesulfonate [CAS Reg. No. 80522-42-5] (1.01 mL, 3.77 mmol, 5 equiv.). The reaction mixture was stirred at 70 °C for 18 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (10 mL), extracted with EtOAc (3 × 10 mL), washed with H₂O (2 × 30 mL) and concentrated in vacuo to afford an orange oil. The crude product was purified by flash chromatography (SiO₂, n-pentane → EtOAc/n-pentane = 3:97) to afford 4d as a pale yellow solid (148.0 mg, 0.256 mmol, 34%), 1a as a beige solid (72.7 mg, 0.274 mmol, 36%) and an impure material that was further purified by flash chromatography (SiO₂, n-pentane → EtOAc/n-pentane = 1:49) to afford 1d as a yellow oil (8.4 mg, 0.020 mmol, 3%).

Yellow oil; R_f = 0.33 (SiO₂, EtOAc/n-pentane = 1:19).

¹H NMR (400 MHz, CDCl₃): δ = 7.47 (d, J = 8.7 Hz, 2 H), 7.35 (d, J = 8.7 Hz, 2 H), 6.82 (d, J = 10.1 Hz, 2 H), 6.23 (d, J = 10.1 Hz, 2 H), 1.11–1.05 (m, 21 H).

¹³C NMR (101 MHz, CDCl₃): δ = 185.68, 151.53, 139.46, 131.99, 127.47, 126.88, 122.25, 73.22, 18.36, 13.43.

HRMS (EI): m/z [M]⁺ calcd for C₂₁H₂₉O₂BrSi: 420.1115; found: 420.1123.

Elemental analysis was not performed due to an insufficient amount of the material.

((4′-Bromo-[1,1′-biphenyl]-2,5-diyl)bis(oxy))bis(triisopropylsilane) (4d)

See compound 1d for the synthetic procedure.

Pale yellow solid; R_f = 0.57 (SiO₂, EtOAc/n-pentane = 1:99); mp 49–50 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.49 (d, J = 8.5 Hz, 2 H), 7.37 (d, J = 8.4 Hz, 2 H), 6.79 (d, J = 2.7 Hz, 1 H), 6.77 (d, J = 8.5 Hz, 1 H), 6.72 (dd, J = 8.5, 2.7 Hz, 1 H), 1.26–1.21 (m, 3 H), 1.11–1.06 (m, 21 H), 0.94 (d, J = 7.2 Hz, 18 H).

¹³C NMR (101 MHz, CDCl₃): δ = 150.10, 147.18, 138.28, 132.24, 131.48, 131.02, 121.81, 120.92, 120.14, 119.71, 18.08, 17.96, 13.02, 12.76.

HRMS (EI): m/z [M]⁺ calcd for C₃₀H₄₉O₂BrSi₂: 576.2449; found: 576.2467.

Anal. Calcd for C₃₀H₄₉O₂BrSi₂: C, 62.36; H, 8.55. Found: C, 62.24; H, 8.65.

4,4′′-Dibromo-[1,1′:4′,1′′-terphenyl]-1′,4′-diol (2a)

From p-Benzoquinone

We modified a literature procedure for the synthesis of 2a.[16i] N-Butyllithium [CAS Reg. No. 109-72-8] (2.5 M in hexanes, 14.5 mL, 36.1 mmol, 2.6 equiv.) was added dropwise to a solution of 1,4-dibromobenzene [CAS Reg. No. 106-37-6] (9.18 g, 38.9 mmol, 2.8 equiv.) in THF (92 mL) at –78 °C. The reaction was stirred at this temperature for 30 min, before a solution of p-benzoquinone [CAS Reg. No. 106-51-4] (1.50 g, 13.9 mmol, 1 equiv.) in THF (32 mL) was added via cannula. The resulting reaction mixture was stirred at –78 °C for 1 h and then at room temperature for 15 h. The reaction was quenched with H₂O (50 mL), diluted with Et₂O (100 mL) and extracted with Et₂O (3 × 50 mL). The organic layers were combined, washed with brine (150 mL), dried over anhydrous Na₂SO₄, filtered and concentrated in vacuo to afford a dark oil. The crude product was purified by flash chromatography (SiO₂, EtOAc/n-pentane = 1:9 → EtOAc/n-pentane = 1:1) to afford 2a as a beige solid (2.95 g, 7.0 mmol, 50%). The spectral data match the literature-reported values.[23]

From Compound 2c

Tetrabutylammonium fluoride [CAS Reg. No. 429-41-4] (1 M solution in THF, 0.161 mL, 0.161 mmol, 2.5 equiv.) was added to a solution of 2c (42.0 mg, 0.065 mmol, 1 equiv.) in THF (1 mL). The reaction mixture was stirred at room temperature for 2.5 h. The reaction was quenched with H₂O (5 mL), extracted with EtOAc (3 × 5 mL) and concentrated in vacuo to afford a yellow oil. The crude product was purified by flash chromatography (SiO₂, EtOAc/n-pentane = 3:7 → EtOAc/n-pentane = 2:3) to afford 2a as a white solid (19.8 mg, 0.047 mmol, 73%).

From Compound 2e

Tetrabutylammonium fluoride (1 M solution in THF, 0.384 mL, 0.384 mmol, 2.5 equiv.) was added to a solution of 2e (100.0 mg, 0.154 mmol, 1 equiv.) in THF (2.5 mL). The reaction mixture was stirred at room temperature for 2.5 h. The reaction was quenched with H₂O (5 mL), extracted with EtOAc (3 × 5 mL) and concentrated in vacuo to afford a colorless oil. The crude product was purified by flash chromatography (SiO₂, EtOAc/n-pentane = 1:9 → EtOAc/n-pentane = 1:1) to afford 2a as a white solid (53.6 mg, 0.127 mmol, 83%).

Beige solid; R_f = 0.34 (SiO₂, EtOAc/n-pentane = 1:1); mp 141–142 °C.

¹H NMR (300 MHz, CDCl₃): δ = 7.48 (d, J = 8.6 Hz, 4 H), 7.29 (d, J = 8.6 Hz, 4 H), 6.04 (s, 4 H), 2.25 (s, 2 H).

¹H NMR (300 MHz, CD₂Cl₂): δ = 7.48 (d, J = 8.6 Hz, 4 H), 7.31 (d, J = 8.6 Hz, 4 H), 6.03 (s, 4 H), 2.34 (s, 2 H).

¹³C NMR (101 MHz, CD₂Cl₂): δ = 143.46, 132.34, 131.97, 127.81, 121.94, 69.32.

HRMS (NSI): m/z [M – H]⁺ calcd for C₁₈H₁₃O₂Br₂: 418.9288; found: 418.9275.

Anal. Calcd for C₁₈H₁₄O₂Br₂: C, 51.22; H, 3.34. Found: C, 51.46; H, 3.36.

((4,4′′-Dibromo-[1,1′:4′,1′′-terphenyl]-1′,4′-diyl)bis(oxy))bis(triethylsilane) (2b)

We adapted a literature procedure for the synthesis of 2b.[1f] Chlorotriethylsilane (2.1 mL, 12.8 mmol, 3 equiv.) was added to a solution of 2a (1.80 g, 4.3 mmol, 1 equiv.) and imidazole (1.16 g, 17.0 mmol, 4 equiv.) in DMF (16 mL). The reaction mixture was stirred at 40 °C for 12 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (15 mL) and extracted with EtOAc (3 × 30 mL). The organic layers were combined, washed with saturated aqueous NaHCO₃ solution (100 mL), H₂O (2 × 100 mL) and brine (100 mL), dried over anhydrous Na₂SO₄, filtered and concentrated in vacuo to afford an orange oil. The crude product was purified by flash chromatography (SiO₂, n-pentane → EtOAc/n-pentane = 1:19) to afford 2b as a white solid (2.14 g, 3.3 mmol, 77%). The spectral data match the literature-reported values.[16i]

White solid; R_f = 0.35 (SiO₂, n-pentane); mp 63–64 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.39 (d, J = 8.6 Hz, 4 H), 7.18 (d, J = 8.7 Hz, 4 H), 5.96 (s, 4 H), 0.93 (t, J = 7.9 Hz, 18 H), 0.60 (q, J = 7.9 Hz, 12 H).

¹³C NMR (101 MHz, CDCl₃): δ = 145.11, 131.56, 131.41, 127.76, 121.46, 71.25, 7.15, 6.57.

HRMS (EI): m/z [M]⁺ calcd for C₃₀H₄₂O₂Br₂Si₂: 648.1085; found: 648.1103.

Anal. Calcd for C₃₀H₄₂O₂Br₂Si₂: C, 55.38; H, 6.51. Found: C, 55.35; H, 6.47.

4,4′′-Dibromo-4′-((triethylsilyl)oxy)-[1,1′:4′,1′′-terphenyl]-1′(4′H)-ol (6b)

n-Butyllithium (2.5 M in hexanes, 0.221 mL, 0.553 mmol, 1.95 equiv.) was added dropwise to a solution of 1,4-dibromobenzene (134.0 mg, 0.567 mmol, 2 equiv.) in THF (1 mL) at –78 °C. The reaction was stirred at this temperature for 30 min, before a solution of 1b (107.6 mg, 0.284 mmol, 1 equiv.) in THF (1 mL) was added via cannula. The resulting reaction mixture was stirred at –78 °C for 2 h. The reaction was quenched with EtOH (1 mL) and after the addition of H₂O (5 mL), the organic phases were extracted with EtOAc (3 × 10 mL). The organic layers were combined and concentrated in vacuo to afford an orange oil. The crude product was purified by flash chromatography (SiO₂, EtOAc/n-pentane = 1:19) to afford 6b as a colorless oil (93.6 mg, 0.175 mmol, 62%).

Colorless oil; R_f = 0.16 (SiO₂, EtOAc/n-pentane = 1:19).

¹H NMR (400 MHz, CDCl₃): δ = 7.48 (d, J = 8.6 Hz, 2 H), 7.42 (d, J = 8.6 Hz, 2 H), 7.31 (d, J = 8.6 Hz, 2 H), 7.22 (d, J = 8.6 Hz, 2 H), 5.99 (d, J = 10.5 Hz, 2 H), 5.97 (d, J = 10.5 Hz, 2 H), 0.99 (t, J = 7.9 Hz, 9 H), 0.68 (q, J = 7.9 Hz, 6 H).

¹H NMR (400 MHz, CD₂Cl₂): δ = 7.49 (d, J = 8.6 Hz, 2 H), 7.43 (d, J = 8.6 Hz, 2 H), 7.32 (d, J = 8.6 Hz, 2 H), 7.25 (d, J = 8.7 Hz, 2 H), 6.00 (s, 4 H), 0.99 (t, J = 7.9 Hz, 9 H), 0.69 (q, J = 8.0 Hz, 6 H).

¹³C NMR (101 MHz, CD₂Cl₂): δ = 145.29, 143.91, 133.36, 131.95, 131.66, 131.10, 127.97, 127.83, 121.95, 121.45, 71.52, 69.36, 7.20, 6.81.

HRMS (EI): m/z [M]⁺ calcd for C₂₄H₂₈O₂Br₂Si: 534.0220; found: 534.0232.

Anal. Calcd for C₂₄H₂₈O₂Br₂Si: C, 53.74; H, 5.26. Found: C, 53.79; H, 5.26.

((4,4′′-Dibromo-[1,1′:4′,1′′-terphenyl]-1′,4′-diyl)bis(oxy))bis(tert-butyldimethylsilane) (2c)

To a solution of 2a (100.0 mg, 0.237 mmol, 1 equiv.) in DMF (4 mL) was added 2,6-lutidine (0.166 mL, 1.42 mmol, 6 equiv.), followed by tert-butyldimethylsilyl trifluoromethanesulfonate (0.272 mL, 1.18 mmol, 5 equiv.). The reaction mixture was stirred at 50 °C for 18 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (5 mL) and extracted with EtOAc (3 × 10 mL). The organic layers were combined, washed with H₂O (2 × 30 mL) and concentrated in vacuo to afford a white solid. The crude product was purified by flash chromatography (SiO₂, n-pentane) to afford 2c as a white solid (108.1 mg, 0.166 mmol, 70%).

White solid; R_f = 0.36 (SiO₂, n-pentane); mp 161–162 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.40 (d, J = 8.6 Hz, 4 H), 7.20 (d, J = 8.6 Hz, 4 H), 5.96 (s, 4 H), 0.94 (s, 18 H), 0.04 (s, 12 H).

¹³C NMR (101 MHz, CDCl₃): δ = 145.05, 131.51, 131.44, 127.75, 121.48, 71.34, 26.00, 18.50, –2.17.

HRMS (EI): m/z [M]⁺ calcd for C₃₀H₄₂O₂Br₂Si₂: 648.1085; found: 648.1107.

Anal. Calcd for C₃₀H₄₂O₂Br₂Si₂: C, 55.38; H, 6.51. Found: C, 55.35; H, 6.47.

tert-Butyl((4,4′′-dibromo-[1,1′:3′,1′′-terphenyl]-4′-yl)oxy)dimethylsilane (5c)

From compound 2a

To a solution of 2a (25.0 mg, 0.059 mmol, 1 equiv.) in DMF (1 mL) was added 2,6-lutidine (0.083 mL, 0.710 mmol, 12 equiv.), followed by tert-butyldimethylsilyl trifluoromethanesulfonate (0.136 mL, 0.592 mmol, 10 equiv.). The reaction mixture was stirred at 100 °C for 18 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (5 mL), extracted with EtOAc (3 × 10 mL), washed with H₂O (2 × 30 mL) and concentrated in vacuo to afford a brown solid. The crude product was purified by flash chromatography (SiO₂, n-pentane → EtOAc/n-pentane = 1:99) to afford 5c as a white solid (23.3 mg, 0.045 mmol, 76%).

From Compound 2c with TBDMSOTf

tert-Butyldimethylsilyl trifluoromethanesulfonate (0.177 mL, 0.768 mmol, 10 equiv.) was added to a solution of 2c (50.0 mg, 0.077 mmol, 1 equiv.) in DMF (2 mL). The reaction mixture was stirred at 100 °C for 18 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (5 mL), extracted with EtOAc (3 × 10 mL), washed with H₂O (2 × 30 mL) and concentrated in vacuo to afford a colorless waxy solid. The crude product was purified by flash chromatography (SiO₂, n-pentane) to afford 5c as a white solid (32.1 mg, 0.064 mmol, 83%).

From Compound 2c with TfOH

Triflic acid [CAS Reg. No. 1493-13-6] (0.08 M in DMF, 0.096 mL, 0.1 equiv.) was added to a solution of 2c (50.0 mg, 0.077 mmol, 1 equiv.) in DMF (2 mL). The reaction mixture was stirred at 100 °C for 18 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (5 mL), extracted with EtOAc (3 × 10 mL), washed with H₂O (2 × 30 mL) and concentrated in vacuo to afford a white solid. The crude product was purified by flash chromatography (SiO₂, n-pentane → EtOAc/n-pentane = 1:19) to afford 5c as a white solid (32.4 mg, 0.065 mmol, 84%).

White solid; R_f = 0.26 (SiO₂, n-pentane); mp 101–102 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.54 (d, J = 8.6 Hz, 2 H), 7.53 (d, J = 8.5 Hz, 2 H), 7.46–7.39 (m, 6 H), 6.97 (d, J = 8.4 Hz, 1 H), 0.85 (s, 9 H), 0.02 (s, 6 H).

¹³C NMR (101 MHz, CDCl₃): δ = 152.59, 139.65, 137.93, 133.62, 132.74, 131.99, 131.56, 131.21, 129.30, 128.50, 127.23, 121.28, 121.20, 120.96, 25.73, 18.26, –4.29.

HRMS (EI): m/z [M]⁺ calcd for C₂₄H₂₆OBr₂Si: 516.0114; found: 516.0118.

Anal. Calcd for C₂₄H₂₆OBr₂Si: C, 55.61; H, 5.06. Found: C, 55.73; H, 5.26.

4,4′′-Dibromo-4′-((tert-butyldimethylsilyl)oxy)-[1,1′:4′,1′′-terphenyl]-1′(4′H)-ol (6c)

With TBAF

Tetrabutylammonium fluoride (1 M solution in THF, 0.231 mL, 0.231 mmol, 1.5 equiv.) was added to a solution of 2e (100.0 mg, 0.154 mmol, 1 equiv.) in THF (5 mL) at –45 °C. The reaction mixture was stirred at this temperature for 2.5 h. The reaction was quenched with H₂O (5 mL), extracted with EtOAc (3 × 5 mL) and concentrated in vacuo to afford a colorless oil. The crude product was purified by flash chromatography (SiO₂, EtOAc/n-pentane = 1:19 → EtOAc/n-pentane = 1:9) to afford 6c as a white solid (62.9 mg, 0.117 mmol, 76%).

With K₂CO₃

A solution of 2e (100.0 mg, 0.154 mmol, 1 equiv.) and K₂CO₃ [CAS Reg. No. 584-08-7] (212.0 mg, 1.54 mmol, 10 equiv.) in MeOH (3 mL) was stirred at 65 °C for 18 h. After cooling to room temperature, the reaction mixture was diluted with H₂O (10 mL), extracted with EtOAc (3 × 10 mL) and concentrated in vacuo to afford a colorless oil. The crude product was purified by flash chromatography (SiO₂, EtOAc/n-pentane = 1:9) to afford 6c as a white solid (67.7 mg, 0.126 mmol, 82%).

White solid; R_f = 0.15 (SiO₂, EtOAc/n-pentane = 1:19); mp 63–64 °C.

¹H NMR (300 MHz, CDCl₃): δ = 7.49 (d, J = 8.6 Hz, 2 H), 7.42 (d, J = 8.6 Hz, 2 H), 7.31 (d, J = 8.6 Hz, 2 H), 7.22 (d, J = 8.7 Hz, 2 H), 6.00 (d, J = 10.1 Hz, 2 H), 5.96 (d, J = 10.1 Hz, 2 H), 2.06 (s, 1 H), 0.96 (s, 9 H), 0.17 (s, 6 H).

¹H NMR (400 MHz, CD₂Cl₂): δ = 7.49 (d, J = 8.6 Hz, 2 H), 7.43 (d, J = 8.6 Hz, 2 H), 7.32 (d, J = 8.7 Hz, 2 H), 7.25 (d, J = 8.6 Hz, 2 H), 6.01 (d, J = 10.5 Hz, 2 H), 5.99 (d, J = 10.5 Hz, 2 H), 2.18 (s, 1 H), 0.96 (s, 9 H), 0.18 (s, 6 H).

¹³C NMR (101 MHz, CD₂Cl₂): δ = 145.30, 143.96, 133.40, 131.96, 131.68, 131.08, 127.97, 127.84, 121.97, 121.46, 71.73, 69.44, 25.99, 18.68, –2.14.

HRMS (EI): m/z [M – H₂O]⁺ calcd for C₂₄H₂₆OBr₂Si: 516.0114; found: 516.0127.

Anal. Calcd for C₂₄H₂₈O₂Br₂Si: C, 53.74; H, 5.26. Found: C, 53.65; H, 5.24.

((4,4′′-Dibromo-[1,1′:3′,1′′-terphenyl]-4′-yl)oxy)triisopropylsilane (5d)

See compound 6d for the procedure. Alternatively, 5d was obtained in a higher purity and yield according to the procedure below.

To a solution of 2a (49.8 mg, 0.118 mmol, 1 equiv.) in DMF (2 mL) was added 2,6-lutidine (0.110 mL, 0.944 mmol, 8 equiv.), followed by triisopropylsilyl trifluoromethanesulfonate (0.222 mL, 0.826 mmol, 7 equiv.). The reaction mixture was stirred at 100 °C for 16.5 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (5 mL), extracted with EtOAc (3 × 10 mL), washed with H₂O (2 × 30 mL) and concentrated in vacuo to afford a yellow oil. The crude product was purified by flash chromatography (SiO₂, n-pentane) to afford 5d as a colorless oil (56.3 mg, 0.100 mmol, 85%).

Colorless oil; R_f = 0.24 (SiO₂, n-pentane).

¹H NMR (400 MHz, CDCl₃): δ = 7.53 (d, J = 8.7 Hz, 2 H), 7.52 (d, J = 8.5 Hz, 2 H), 7.46–7.38 (m, 6 H), 6.98 (d, J = 8.4 Hz, 1 H), 1.19–1.14 (m, 3 H), 1.00 (d, J = 7.3 Hz, 18 H).

¹³C NMR (101 MHz, CDCl₃): δ = 153.05, 139.62, 138.05, 133.01, 132.27, 131.96, 131.50, 131.11, 129.32, 128.41, 127.15, 121.18, 121.09, 119.88, 18.00, 13.10.

HRMS (EI): m/z [M]⁺ calcd for C₂₇H₃₂OBr₂Si: 558.0584; found: 558.0602.

Anal. Calcd for C₂₇H₃₂OBr₂Si: C, 57.86; H, 5.76. Found: C, 57.82; H, 5.58.

4,4′′-Dibromo-4′-((triisopropylsilyl)oxy)-[1,1′:4′,1′′-terphenyl]-1′(4′H)-ol (6d)

To a solution of 2a (100.0 mg, 0.237 mmol, 1 equiv.) in DMF (4 mL) was added 2,6-lutidine (0.166 mL, 1.43 mmol, 6 equiv.), followed by triisopropylsilyl trifluoromethanesulfonate (0.318 mL, 1.18 mmol, 5 equiv.). The reaction mixture was stirred at 50 °C for 18 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (5 mL), extracted with EtOAc (3 × 10 mL), washed with H₂O (2 × 30 mL) and concentrated in vacuo to afford a yellow oil. The crude product was purified by flash chromatography (SiO₂, n-pentane → EtOAc/n-pentane = 1:1) to afford 5d as a colorless oil (8.1 mg, 0.015 mmol, 6%), 6d as a colorless oil (53.0 mg, 0.092 mmol, 39%) and 2a as a white solid (35.0 mg, 0.083 mmol, 35%).

Colorless oil; R_f = 0.53 (SiO₂, EtOAc/n-pentane = 1:9).

¹H NMR (300 MHz, CDCl₃): δ = 7.48 (d, J = 8.6 Hz, 2 H), 7.42 (d, J = 8.6 Hz, 2 H), 7.29 (d, J = 8.7 Hz, 2 H), 7.26 (d, J = 9.4 Hz, 2 H), 6.01 (d, J = 10.1 Hz, 2 H), 5.99 (d, J = 10.1 Hz, 2 H), 1.19–1.12 (m, 3 H), 1.09 (d, J = 5.0 Hz, 18 H).

¹H NMR (300 MHz, CD₂Cl₂): δ = 7.48 (d, J = 8.7 Hz, 2 H), 7.43 (d, J = 8.7 Hz, 2 H), 7.30 (d, J = 8.7 Hz, 2 H), 7.28 (d, J = 8.7 Hz, 2 H), 6.05 (d, J = 10.3 Hz, 2 H), 6.00 (d, J = 10.2 Hz, 2 H), 2.14 (s, 1 H), 1.19–1.12 (m, 3 H), 1.09 (d, J = 5.2 Hz, 18 H).

¹³C NMR (101 MHz, CD₂Cl₂): δ = 145.41, 143.73, 133.33, 131.93, 131.65, 131.07, 128.02, 127.95, 121.95, 121.49, 71.68, 69.34, 18.63, 13.78.

HRMS (EI): m/z [M – H₂O]⁺ calcd for C₂₇H₃₂OBr₂Si: 558.0584; found: 558.0602.

Anal. Calcd for C₂₇H₃₄O₂Br₂Si: C, 56.06; H, 5.92. Found: C, 56.06; H, 5.86.

tert-Butyl((4,4′′-dibromo-4′-((triethylsilyl)oxy)-[1,1′:4′,1′′-terphenyl]-1′(4′H)-yl)oxy)dimethylsilane (2e)

n-Butyllithium (2.5 M in hexanes, 2.62 mL, 6.55 mmol, 1.95 equiv.) was added dropwise to a solution of 1,4-dibromobenzene (1.58 g, 6.72 mmol, 2 equiv.) in THF (13 mL) at –78 °C. The reaction was stirred at this temperature for 30 min, before a solution of 1c (1.27 g, 3.36 mmol, 1 equiv.) in THF (13 mL) was added via cannula. The resulting reaction mixture was stirred at –78 °C for 2 h. The reaction was quenched with MeOH (20 mL) and the solvents were removed in vacuo. To the residue was added H₂O (15 mL) and the organic phases were extracted with CH₂Cl₂ (3 × 20 mL). The organic layers were combined and concentrated in vacuo to afford an orange oil that was used in the next step without further purification.

Chlorotriethylsilane (1.69 mL, 10.10 mmol, 3 equiv.) was added to a solution of the obtained oily crude product and imidazole (0.686 g, 10.10 mmol, 3 equiv.) in DMF (13 mL). The reaction mixture was stirred at room temperature for 17 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (10 mL) and extracted with EtOAc (3 × 20 mL). The organic layers were combined, washed with H₂O (2 × 50 mL), brine (50 mL), dried over anhydrous Na₂SO₄ and concentrated in vacuo to afford a yellow oil. The crude product was purified by flash chromatography (SiO₂, n-pentane) to afford 2e as a white solid (1.71 g, 3.36 mmol, 78%).

White solid; R_f = 0.32 (SiO₂, n-pentane); mp 68–69 °C.

¹H NMR (400 MHz, CDCl₃): δ = 7.41 (d, J = 8.7 Hz, 2 H), 7.39 (d, J = 8.7 Hz, 2 H), 7.20 (d, J = 8.7 Hz, 2 H), 7.17 (d, J = 8.7 Hz, 2 H), 5.98 (d, J = 10.2 Hz, 2 H), 5.94 (d, J = 10.2 Hz, 2 H), 0.96–0.92 (m, 18 H), 0.62 (q, J = 7.9 Hz, 6 H), 0.01 (s, 6 H).

¹³C NMR (101 MHz, CDCl₃): δ = 145.11, 145.06, 131.63, 131.45, 131.41, 131.41, 127.82, 127.69, 121.52, 121.41, 71.30, 71.28, 25.96, 18.50, 7.17, 6.57, –2.27.

HRMS (EI): m/z [M]⁺ calcd for C₃₀H₄₂O₂Br₂Si₂: 648.1085; found: 648.1105.

Anal. Calcd for C₃₀H₄₂O₂Br₂Si₂: C, 55.38; H, 6.51. Found: C, 55.57; H, 6.56.

Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

We are grateful to the NMR and Mass Spectrometry Services at the Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern for their support.

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Publication History

Received: 01 November 2022

Accepted after revision: 06 January 2023

Accepted Manuscript online:
06 January 2023

Article published online:
09 February 2023