University of Groningen
Carbon-carbon bond formations using organolithium reagents
Heijnen, Dorus
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Chapter 2: Palladium-Catalyzed Cross-Coupling
of (Trimethylsilyl)methyllithium with
(Hetero)-Aryl Halides
Abstract : The palladium-catalyzed direct cross-coupling of a range of organic chlorides and bromides with the bifunctional C(sp3)-(trimethylsilyl)methyllithium reagent is described in this chapter. The use of Pd-PEPPSI-IPent as the catalyst allows for the preparation of structurally diverse and synthetically versatile benzyl- and allylsilanes in high yields under mild conditions (room temperature) with short reaction times (1h).
Part of this chapter was published: D. Heijnen, V. Hornillos, B. P. Corbet, M. Giannerini, and B. L. Feringa. Org. Lett., 2015, 17 (9), pp 2262–2265.
2.1 Introduction
The development of new catalytic methods for carbon–carbon bond formation continues to present major challenges in organic synthesis.1 In particular, palladium-catalyzed cross-coupling of organometallic reagents with organic halides represents one of the most powerful methods for C–C bond formation.2 Several well established methods for this transformation are available using different organometallic partners including organozinc,3 organotin,4 organoboron,5 organosilicon,
6
and organomagnesium7 reagents. Murahashi and co-workers pioneered the use of highly reactive aryl- and alkyl-lithium reagents in catalytic cross-coupling reactions.8 Our group recently described methods for the palladium-catalyzed direct cross-coupling of organolithium reagents with (hetero)aryl- and alkenyl (pseudo)halides under mild conditions, avoiding side reactions such as lithium–halogen exchange or homocoupling.9,10 Additionally, we also reported the reaction of sp3 carbon nucleophiles with aryl bromides that allows a fast, selective, and high yielding coupling of primary and secondary alkyl groups with the notorious β-hydride elimination being suppressed in nearly all cases.9a,9e,11 Preliminary experiments showed the successful use of the functionalized C(sp3) nucleophile TMSCH2Li in metal-catalyzed cross-coupling reactions.9a,9e This bifunctional CH2 moiety
enables the preparation of stable ArCH2SiMe3 products that can further undergo a wide array of
possible transformations including Peterson olefination,12 photocatalyzed13 and gold catalyzed14 reactions, and oxidation to the corresponding acylsilanes15 (Scheme 1). Furthermore, the CH2 group can act as a nucleophile in fluoride-mediated processes giving rise to the formation of
saturated products.16a
Scheme 2.1. Pd-catalyzed cross-coupling of aryl halides employing TMSCH2Li and possible further
transformations at the TMSCH2 group.
Following our initial report,9a the use of this functionalized organolithium reagent recently attracted increasing attention in metal-catalyzed cross-coupling reactions, specifically using Ni catalysis.16 Considering the relevance of the (trimethylsilyl)methyllithium nucleophile, we wondered if readily available but less reactive organic chlorides17 could also be a precursors for the synthesis of highly versatile TMSCH2-functionalized compounds. Costs, waste production, and availability benefit
from the use of aryl chlorides as starting materials. However, due to their low reactivity, the use of high temperatures and long reaction times is usually required while the application of aryl chlorides in metal-catalyzed C(sp3)–C(sp2) cross-coupling reactions with organolithium reagents remains a challenge.18 Here, we report the development of a Pd-catalyzed cross-coupling reaction employing
aryl chlorides and TMSCH2Li that allows selective preparation of a variety of ArCH2TMS compounds in
high yields under mild conditions (rt) and short reaction times (1 h) (Scheme 2.1).
2.2 Catalyst optimization
The reaction between 4-methoxychlorobenzene 1a, a reluctant aryl chloride in coupling reactions, and TMSCH2Li was chosen as a model system since conditions for the successful coupling of this
substrate will enable access to a wide variety of other coupling partners. Under the optimized conditions for the cross-coupling of alkyllithium reagents with aryl bromides,9a using Pd(PtBu3)219 as a
catalyst (Table 1, entry 1), less than 5% conversion to the coupling product 2a was observed. The in situ prepared palladium complexes, using Pd2(dba)3 in combination with P(tBu)3 or dialkylbiaryl
phosphines,20 previously reported to be effective for the Pd-catalyzed cross-coupling with other aryl and alkyllithium reagents, led to similar results (Table 2.1, entries 2–4).
Table 2.1 Catalyst screening
entrya [Pd] ligand conv (%) 2a:3:4b
1 Pd(PtBu3)2 <5 2 Pd2(dba)3 L1, P( t Bu)3 c <5 3 Pd2(dba)3 L2, SPhos <5 4 Pd2(dba)3 L3, XPhos <5 5 Pd-PEPPSI-IPent full 98:<1<1 6 Pd-PEPPSI-IPr ~85 98:<1<1 a
Conditions: TMSCH2Li (0.72 mL, 1.0 M in pentane) was added to a solution of 4-bromoanisole (0.6 mmol) in toluene (2 mL). 1 h addition time. b2a:3:4ratio determined by GCMS analysis. c7.5 mol % was used. dba = dibenzylideneacetone.
We were delighted to find that the air stable Pd-PEPPSI-IPent catalyst, introduced by the group of Organ,21 afforded full conversion and nearly perfect selectivity toward the coupled product 2a at rt in 1 h, avoiding dehalogenation or homocoupling side products 3 and 4, respectively (entry 5, Table 1). It should be mentioned that, for the corresponding Pd-catalyzed cross-couplings of 1a with aryllithium reagents, higher temperatures (40 °C) and longer addition times (3 h) of the
organolithium reagent were necessary to reach full conversion and high selectivity.9c The structurally related Pd-PEPPSI-IPr complex also performed well in the reaction, although full conversion was not reached (entry 6).
2.3 Substrate scope with aryl chlorides
With Pd-PEPPSI-IPent as a highly efficient catalyst, we set out to investigate the cross-coupling between TMSCH2Li and different aryl chlorides (Scheme 2.2). The reactions employing other
electron-rich aryl chlorides such as 1b, 1c, or more sterically hindered 1d also proceed with full conversion and high selectivity without the need to increase the temperature or reaction time. Remarkably, highly deactivated amine-substituted aryl chlorides 1e and 1f, which did not perform well in the cross-coupling with aryllithium reagents,9c were also converted under the optimized reaction conditions to the desired product in good yields and with excellent selectivities (Scheme 2). It should be emphasized that benzyl alcohol 1g, as the Mg alkoxide, and 6-chloro-1H-indole 1h, as the Mg amide, were also tolerated, affording products 2g and 2h with high selectivity. The catalytic system also proved to be efficient in the reaction with 1- and 2-chloronaphthalene 1i and 1j, providing the corresponding trimethyl(naphthalenylmethyl)silanes 2i and 2j with no trace of regioisomers, indicating that benzyne intermediates via 1,2-elimination are not formed. Importantly, 2j was obtained quantitatively when the reaction was scaled up to 4.0 mmol. The electron-deficient 1-chloro-4-(trifluoromethyl)benzene 1k and 4-chloro-1-fluoro-2-methylbenzene 1l underwent clean coupling, giving high isolated yields of the fluorinated structures 2k and 2l. Pyridyl rings, which are susceptible to nucleophilic addition of alkyllithium reagents, also participated in the cross-coupling with high selectivity, albeit with lower yield after purification, as illustrated for substrate 1m. Facile multiple coupling is illustrated in the reaction of 1n with 2.1 equiv of TMSCH2Li providing bis-silylated product 2n in good yield.
Scheme 2.2aConditions: Aryl halide (0.6 mmol), TMSCH
2Li (0.72 mmol, 1.0 M in pentane). Toluene (2 mL). 1
h addition time. Selectivity >98%. Yield values refer to isolated yields after purification. biPrMgCl (1.0 equiv, 2
M in Et2O) was added over 5 min prior to the organolithium. c
TMSCH2Li (1.44 mmol).
2.4 Substrate scope with aryl bromides
After having established Pd-PEPPSI-IPent as a highly efficient catalyst for the cross-coupling of TMSCH2Li with aryl chlorides, we studied the scope of this catalyst in the reaction with challenging
organic bromides. Sterically hindered bromides, known for being more reluctant substrates for the coupling of alkyl units,22 were tested for the first time in combination with TMSCH2Li. As shown in
Scheme 2.3, a variety of bulky organic bromides (5a–d) could be coupled with excellent selectivity at room temperature within 1 h, indicating that the transmetalation step takes place rapidly, facilitating a fast coupling process. Notably, di-ortho-substituted tert-butyl aryl bromide 5d was tolerated, affording the TMS-functionalized product 6d at rt in high yield. Remarkably, bromofluorene was successfully employed, despite the acidity of the benzylic protons (pKa = 22). Alkenyl bromide 5f also undergoes this cross-coupling, leading to allyltrimethylsilane 6f with high selectivity with no presence of Fritsh–Butlenberg–Wiechell type rearrangement side products.23Fluorinated bromides 5g and 5h also underwent clean coupling without any traces of side products. Similar to the corresponding aryl chloride 1g, (4-bromophenyl)methanol 5i, bearing an unprotected hydroxyl group, could also be coupled with this organolithium reagent, provided the corresponding Mg
alkoxide was first generated. In the presence of an excess of TMSCH2Li, both the −OTf and −Cl groups
present in aryl bromides 5j and 5k were also coupled leading to products which contain two or three TMSCH2 functional groups
Scheme 2.3aConditions: Aryl halide (0.6 mmol), TMSCH
2Li (0.72 mmol, 1.0 M in pentane). Toluene (2 mL).
Selectivity >98%. Yield values refer to isolated yields after purification. bYield determined by 1H NMR using tetrachloroethane as internal standard. cModerate yield obtained after purification by column chromatography.
diPrMgCl (1.0 equiv, 2 M in Et
2O) was added over 5 min prior to the organolithium.eTMSCH2Li (1.44 mmol). fTMSCH
2Li (2.16 mmol).
2.5 Selectivity
As shown above, the Pd-PEPPSI-IPent complex has been shown to be an extremely efficient and versatile catalyst for the cross-coupling of (trimethylsilyl)methyllithium with (hetero)aryl chlorides, bromides, and triflates. However, the use of aryl chlorides presents additional advantages compared to the aforementioned, as they are less prone to undergo halogen–lithium exchange with the organolithium compound, preventing the formation of homocoupling or dehalogenated side products.24 We have recently shown that this different behavior is particularly evident in the Pd-catalyzed cross-coupling of 2-alkoxy-substituted bromo- and chloroarenes where the coordination of the ortho-methoxy group with the organolithium compound facilitates the Li–Br exchange and further stabilizes the resulting aryllithium compound.9f Here, the C(sp3) character of TMSCH2Li, when
compared with C(sp2) in aryl lithium reagents, could further enhance this effect. As shown in Scheme 2.4, this difference in reactivity was confirmed in the cross-coupling with
1-bromo-2-methoxybenzene 7a, where the TMSCH2 functionalized product was obtained along with a
homocoupling side product. However, the use of the corresponding aryl chloride 7b led to the desired silylated product 8 with nearly perfect selectivity and high yield, in accordance with the reduced tendency to undergo halogen–lithium exchange, and this enhanced selectivity will be beneficial in synthetic applications.
Scheme 2.4 Comparison between the Pd-catalyzed cross-coupling of TMSCH2Li with 1-chloro- and 1
bromo-2-methoxybenzene.
2.6 The sequential coupling of TMS-substituted toluene derivatives
Part of the unpublished work is the further functionalization of the benzylic TMS product by means of deprotonation (lithation) and a second cross-coupling reaction. (scheme 2.5) The facile deprotonation of the TMSCH2 coupled products has been previously described, and is performed in a
hexane/TMEDA mixture.26 The solid (insoluble) secondary organolithium reagent is easily separated from the solvent by removal of the supernatant, and washing with dry hexane. In preliminary experiments, we showed that sequential coupling gave the di-arylated TMS-methylene unit in moderate (40 % GC) yield. The synthetic applicability of this method however might be limited, since the products (the double benzylic methylene moiety) could easily be made by deprotonation of the relatively acidic proton and TMS-Cl quench. An enantioselective version might be investigated, but since most further functionalization steps yield achiral products we decided to not investigate this aspect any further.
2.7 Conclusions
In summary, we have shown the direct Pd-catalysed cross-coupling of TMSCH2Li with organic
(pseudo)halides, including reluctant but cheap and readily available organic chlorides, in high yields and excellent selectivity. The method is based on the use of commercially available Pd-PEPPSI-IPent catalyst. The reactions take place under mild conditions with broad substrate scope. The products formed are attractive stable α-C-activated systems,25 and precursors for various further transformations.
2.8 References
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(9) (a) Giannerini, M.; Fañ anas-Mastral, M.; Feringa, B. L. ́ Nat. Chem. 2013, 5, 667. (b) Giannerini, M.; Hornillos, V.; Vila, C.; Fañanas-Mastral, M.; Feringa, B. L. ́ Angew. Chem., Int. Ed. 2013, 52, 13329. (c) Hornillos, V.; Giannerini, M.; Vila, C.; Fañ anas-Mastral, M.; ́ Feringa, B. L. Org. Lett. 2013, 15, 5114. (d) Hornillos, V.; Giannerini, M.; Vila, C.; Fañ anas-Mastral, M.; Feringa, B. L. ́ Chem. Sci. 2015, 6, 1394. (e) Vila, C.; Hornillos, V.; Giannerini, M.; Fañ anas-Mastral, M.; ́ Feringa. Chem. Eur. J. 2014, 20,
13078. (f) Castello, L. M.; Hornillos, ́ V.; Vila, C.; Giannerini, M.; Fañ anas-Mastral, M.; Feringa, B. L. ́ Org. Lett. 2015, 17, 62.
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Patrocnio, A. F.; Moran, J. S. Braz. J. Chem. Soc. 2001, 12, 7. (d) Zhang, H.-J.; Priebbenow, D. L.; Bolm, C. Chem. Soc. Rev. 2013, 42, 8540.
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(17) For reviews on catalytic cross-coupling of aryl chlorides, see: (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176. (b) Noyori, S.; Nisihara, Y. In Applied Cross-Coupling Reactions; Nisihara, Y., Ed.; Springer-Verlag: Berlin Heidelberg, 2013; Chapter 7.
(18) For the corresponding Pd-catalyzed C(sp2 )−C(sp2 ) crosscoupling of aryl chlorides with aryllithium reagents, see ref 9c, f. For reviews about transition-metal-catalyzed cross-coupling reactions of alkylmetal reagents, see: (a) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011, 111, 1417. (b) Doucet, H. Eur. J. Org. Chem. 2008, 2013.
(19) Fu, G. C. Acc. Chem. Res. 2008, 41, 1555.
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Acknowledgements
Valentin Hornillos contributed to the overall process of the work, Brian Corbet contributed to the optimization of the catalyst, and the isolation of some of the reported products.
2.9 Experimental section
General methods: Chromatography: Grace Reveleris X2 flash chromatography system used with
Grace® Flash Cartridges, TLC: Merck silica gel 60, 0.25 mm. Components were visualized by UV and cerium/molybdenum or potassium permanganate staining. Progress, conversion and masses of the products in the reaction were determined by GC-MS (GC, HP6890: MS HP5973) with an HP1 or HP5 column (Agilent Technologies, Palo Alto, CA). 1H- and 13C-NMR were recorded on a Varian AMX400 (400 and 100.59 MHz, respectively) using CDCl3 as solvent. Chemical shift values are reported in ppm
with the solvent resonance as the internal standard (CHCl3: 7.26 for 1H, 77.0 for 13C). Data are
reported as follows: chemical shifts, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, br = broad, m = multiplet), coupling constants (Hz), and integration. Melting points were measured using a Büchi Melting Point B-545. All reactions were carried out under a nitrogen atmosphere using oven dried glassware and using standard Schlenk techniques. THF, Et2O and toluene were dried and
distilled over sodium. Pd-PEPPSI-Ipent was purchased from Aldrich and used without further purification. TMSCH2Li (1.0 M in pentane) and all the bromides and chlorides were commercially
available and were purchased from Aldrich and TCI Europe.
General procedure for cross coupling of TMSCH2Li with aryl halides.
The corresponding halide (0.6 mmol) and Pd-PEPPSI-IPent complex (5 mol %) were dissolved in toluene (4 ml) in a dried Schlenk flask under inert atmosphere, and the mixture stirred for 5 min. Subsequently, a solution of TMSCH2Li (0.72 mmol, 1.2 eq.) diluted to 2 ml (to reach a final
concentration of 0.36 M) with toluene was added over 1h by the use of a syringe pump. After complete addition, MeOH (1ml) was added to quench the remaining TMSCH2Li. The reaction mixture
was transferred to a round-bottom flask, Celite was added, and the solvents evaporated in vacuo. The remaining solid was directly loaded on a silica gel column.
General procedure for the lithiation and cross coupling of benzylic, trimethylsilyl compounds.
The corresponding Aryl-CH2-TMS (0.9 mmol, 1 eq.) was dissolved in dry hexane. Dry TMEDA (0.9
mmol, 1 eq.) was added. n-BuLi was added dropwise, resulting in a darkening of the solution. The mixture was stirred overnight, after which a solid had formed. The supernatant was carefully removed, and the solid washed with dry hexane (2 ml). THF (0.2 ml) and toluene (1.8 ml) were added, and 1 ml of this solution (0.45 mmol) was added to a stirred solution of aryl halide (0.3 mmol) and Pd-PEPPSI-IPent (5 mol %) catalyst as described above. The reaction was quenched, and an aliquot filtered and injected on a GC/MS.
(4-Methoxybenzyl)trimethylsilane (2a):1 Synthesized according to general method. The product was obtained after column chromatography as a yellow oil (SiO2, n-pentane). [99 mg, 85% yield].
1
H-NMR (400MHz, Chloroform-d) δ 6.93 (d, J = 8.69 Hz, 2H), 6.79 (d, J = 8.66 Hz, 2H), 3.78 (s, 3H), 2.02 (s, 2H), 0.01 (s, 9H) 13C-NMR (100MHz, Chloroform-d) δ 156.5, 132.3, 128.8, 113.6, 55.2, 25.7, 1.9. EI-MS m/z: 194, 179(100%), 121, 73.
(3-Methoxybenzyl)trimethylsilane (2b):2 Synthesized according to general method. The product was
obtained after column chromatography as a colorless liquid. (SiO2, n-pentane). [107 mg, 92% yield]. 1
H-NMR (400MHz, Chloroform-d) δ 7.15 (t, J = 7.88 Hz, 1H), 6.67-6.58 (m, 3H), 3.80 (s, 3H), 2.09 (s, 2H), 0.02 (s, 9H) 13C-NMR (100MHz, Chloroform-d) δ 160.0, 142.3, 129.1, 120.8, 113.9, 109.2, 55.1, 27.3, -1.7.EI-MS m/z: 194, 179, 73(100%).
(4-Butylbenzyl)trimethylsilane (2c): Synthesized according to general method. The product was
obtained after column chromatography as a colorless liquid (SiO2, n-pentane). [115 mg, 87% yield]. 1
H-NMR (400MHz, Chloroform-d) δ 7.08 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 2.60 (t, 2H), 2.09 (s, 2H), 1.63 (p, J = 7.5 Hz, 2H), 1.40 (dq, J = 14.6, 7.3 Hz, 2H), 0.98 (t, J = 7.3 Hz, 3H), 0.04 (s, 9H). 13CNMR (100 MHz, Chloroformd) δ 138.2, 137.4, 128.2, 127.9, 35.2, 33.8, 26.5, 22.5, 14.0, -1.8. EI-MS m/z: 220, 73 (100%).
(2,4-Dimethylbenzyl)trimethylsilane (2d): Synthesized according to general method. The product
was obtained after column chromatography as a colorless liquid. (SiO2, n-pentane). [90 mg, 78%
yield]. 1H-NMR (400MHz, Chloroform-d) δ 6.96 (s, 1H), 6.92 – 6.86 (m, 2H), 2.29 (s, 3H), 2.22 (s, 3H), 2.08 (s, 2H), 0.03 (s, 9H). 13C-NMR (100MHz, Chloroform-d) δ 135.8, 134.5, 133.4, 131.0, 128.8, 126.4, 26.3, 21.0, 20.4, -1.2.EI-MS m/z: 192, 177, 161, 73(100%).
N,N-Dimethyl-3-((trimethylsilyl)methyl)aniline (2e): Synthesized according to general method. The product was obtained after column chromatography as a colorless liquid. (SiO2, n-pentane). [107 mg,
86% yield]. 1H-NMR (400MHz, Chloroform-d) δ 7.11 (t, J = 8.04 Hz, 1H), 6.52 (m, 1H), 6.42 (m, 2H), 2.94 (s, 6H), 2.07 (s, 2H), 0.03 (s, 9H) 13C-NMR (100MHz, Chloroform-d) δ 150.6, 141.2, 128.7, 117.1, 112.8, 108.7, 40.8, 27.4, -1.7. EI-MS m/z: 207(100%), 192, 135, 133, 73
______________________________________
4-(4-((Trimethylsilyl)methyl)phenyl)morpholine (2f): Synthesized according to general method.
The product was obtained after column chromatography as a colorless liquid. (SiO2, n-pentane). [102
mg, 68% yield]. 1H-NMR (400MHz, Chloroform-d) δ 6.92 (d, J = 8.26 Hz, 2H), 6.81 (d, J = 8.26 Hz, 2H), 3.86 (t, J = 4.71 Hz, 4H), 3.10 (t, J = 4.86 Hz, 4H), 2.00 (s, 2H), 0.02 (s, 9H) 13C-NMR (100MHz, Chloroform-d 3) δ 148.0, 132.2, 128.7, 116.0, 67.0, 50.0, 25.7, -1.9. EI-MS m/z:
249(100%), 176, 73.
(4-((Trimethylsilyl)methyl)phenyl)methanol (2g):3 Synthesized according to general method with
the slow addition of 1.0 eq. of isopropylmagnesiumchloride (2.0 M in THF) prior to the addition of the catalyst. The product was obtained after column chromatography as a brown oil (SiO2, n-pentane). [75
mg, 65% yield]. 1H-NMR (400MHz, Chloroform-d) δ 7.18 (d, J = 7.9 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 4.58 (d, J = 4.6 Hz, 2H), 2.06 (s, 2H), 1.91 (s, 1H), -0.03 (s, 9H). 13C-NMR (101 MHz,
Chloroform-d) δ 140.0, 136.3, 128.2, 127.20, 65.3, 26.8, -1.9.EI-MS m/z: 194, 179, 104 (100%), 73.
6-((Trimethylsilyl)methyl)-1H-indole (2h): Synthesized according to general method. The product
was obtained after column chromatography as a colorless liquid. (SiO2, n-pentane). [84 mg, 69%
yield]. 1H-NMR (400MHz, Chloroform-d) δ 7.97 (s, 1H), 7.51 (d, J = 8.1Hz, 1H), 7.09-7.10 (m, 1H), 7.02 (s, 1H), 6.81-6.83 (m, 1H), 6.50-6.51 (m, 1H), 2.20 (s, 2H), 0.03 (s, 9H). 13C-NMR (100MHz, Chloroform-d) δ 136.6, 134.6, 124.8, 123.0, 121.4, 120.2, 109.8, 102.4, 27.2, -1.6. EI-MS m/z: 203, 130, 73(100%).
Trimethyl(naphtalen-2-ylmethyl)silane (2i):4 Synthesized according to general method. The product
was obtained after column chromatography as a white solid (SiO2, n-pentane). [110 mg, 89% yield]. 1
H-NMR: (400MHz, Chloroform-d) δ 7.82 - 7.73 (m, 3H), 7.46 - 7.38 (m, 3H), 7.20 (dd, J = 8.32, 1.69 Hz, 1H), 2.29 (s, 2H), 0.06 (s, 9H). 13C-NMR (100MHz, Chloroform-d) δ 138.2, 133.8, 131.0, 127.9, 124,5, 127.5, 127.0, 125.7, 125.1, 124.4, 27.3, -1.7. EI-MS m/z: 214, 141, 73(100%).
Trimethyl(naphthalen-1-ylmethyl)silane (2j):5 Synthesized according to general method. The product was obtained after column chromatography as a colorless oil. (SiO2, n-pentane). [116 mg,
90% yield]. 1H-NMR (400 MHz, Chloroform-d) δ 7.96 (d, J = 7.8 Hz, 1H), 7.84 (d, J = 7.4 Hz, 1H), 7.63 (d, J = 8.2 Hz, 1H), 7.47 (dd, J = 6.8, 2.9 Hz, 2H), 7.37 (t, J = 7.6 Hz, 1H), 7.18 (d, J = 7.1 Hz, 1H), 2.59 (s, 2H), 0.01 (s, 9H). 13C-NMR (100MHz, Chloroform-d) δ 137.2, 133.9, 131.7, 128.6, 125.5, 125.3, 125.2, 124.9, 124.8, 124.6, 23.4, -1.2. EI-MS m/z: 214, 141, 73(100%).
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Trimethyl(4-(trifluoromethyl)benzyl)silane (2k):6 Synthesized according to general method. The
product was obtained after column chromatography as a colorless liquid. (SiO2, n-pentane). [100 mg,
72% yield]. 1H-NMR (400MHz, Chloroform-d) δ 7.48 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 2.17 (s, 2H), 0.02 (s, 9H). 13C-NMR (100MHz, Chloroform-d) δ 145.1, 145.1, 128.0, 126.4, 126.1, 125.9, 125.0(q, J = 3.8 Hz), 123.2, 27.4, -2.1. 19F-NMR (376-MHz, Chloroform-d) δ -62.05 .EI-MS m/z: 232, 217, 140 (100%), 73.
(4-Fluoro-3-methylbenzyl)trimethylsilane (2l): Synthesized according to general method. The
product was obtained after column chromatography as a colorless liquid. (SiO2, n-pentane). [103 mg,
88% yield]. 1H-NMR (400MHz, Chloroform-d) δ 6.95 – 6.68 (m, 3H), 2.26 (s, 3H), 2.03 (s, 2H), 0.02 (s, 9H). 13C-NMR (100MHz, Chloroform-d) δ 160.0, 157.6, 135.6, 130.7, 130.7, 129.0, 128.2, 126.4, 124.2,124.0, 114.6, 114.3, 25.9, 14.6, -2.0. 19F-NMR (376MHz, Chloroform-d) δ -124.9. EI-MS m/z: 196, 181, 104 (100%), 73.
((2,5-Dimethyl-1,4-phenylene(bis(methylene))bis(trimethylsilane) (2n):7 Synthesized according to general method with the addition of 2.4 eq. of Li-CH2TMS. The product was obtained after column
chromatography as a colorless liquid. (SiO2, n-pentane). [147 mg, 88% yield]. 1
H-NMR (400MHz, Chloroform-d) δ 6.73 (s, 2H), 2.17 (s, 6H), 2.03 (s, 4H), 0.02 (s, 18H). 13C-NMR (100MHz, Chloroform-d) δ 134.1, 131.5, 130.5, 22.8, 19.9, -1.3.EI-MS m/z: 278(100%), 190, 175, 73.
3-((Trimethylsilyl)methyl)pyridine (2m):8 Synthesized according to general method. The product
was obtained after column chromatography as a yellow oil (SiO2, n-pentane). [Full conversion, 30 mg,
31% yield]. 1H-NMR (400 MHz, Chloroform-d) δ 8.31 (dd, J = 4.8, 1.5 Hz, 1H), 8.27 (d, J = 1.9 Hz, 1H), 7.32 – 7.26 (m, 1H), 7.12 (dd, J = 7.8, 4.8 Hz, 1H), 2.03 (s, 2H), -0.01 (s, 9H). 13C-NMR (100MHz, Chloroform-d) δ 149.2 , 145.4, 136.1, 135.0, 123.0, 23.9, -2.1. EI-MS m/z: 165, 150, 73(100%).
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(Anthracen-9-ylmethyl)trimethylsilane (6a)9: Synthesized according to general method. The product
was obtained after column chromatography as a yellow solid (SiO2, n-pentane). [143 mg, 90% yield]. 1
H-NMR (400MHz, Chloroform-d) δ 8.28 (s, 1H), 8.23 (d, J = 9.4 Hz, 2H), 8.03 (d, J = 9.7 Hz, 2H), 7.55 – 7.46 (m, 4H), 3.23 (s, 2H), 0.06 (s, 9H). 13C-NMR (100MHz, Chloroform-d) δ 134.3, 131.7, 129.2, 129.0, 125.5, 124.8, 124.5, 123.7, 19.0, -0.3.EI-MS m/z: 264(100%), 249, 191, 73.
(2-Isopropylbenzyl)trimethylsilane (6b): Synthesized according to general method. The product was obtained after column chromatography as a yellow oil. (SiO2, n-pentane). [105 mg, 85% yield]
1 H-NMR (400MHz, Chloroform-d) δ 7.27 (dd, J = 7.4, 1.7 Hz, 1H), 7.11 (dtd, J = 14.5, 7.2, 1.7 Hz, 2H), 7.01 (dd, J = 7.4, 1.7 Hz, 1H), 3.10 (hept, J = 6.9 Hz, 1H), 2.21 (s, 2H), 1.27 (dd, J = 6.8, 0.4 Hz, 6H), 0.07 (d, J = 0.5 Hz, 9H). 13C-NMR (100MHz, Chloroform-d) δ 145.1, 137.2, 129.2, 125.2, 124.9, 124.5, 29.1, 23.5, 23.2 , -1.4. EI-MS m/z: 206, 191, 117, 73(100%).
([1,1'-Biphenyl]-2-ylmethyl)trimethylsilane (6c):10 Synthesized according to general method. The
product was obtained after column chromatography as a colorless liquid. (SiO2, n-pentane). [133 mg,
92% yield]. 1H-NMR (400MHz, Chloroform-d) δ 7.46 – 7.13 (m, 9H), 2.26 (s, 2H), -0.13 (s, 9H). 13C NMR (101 MHz, Chloroform-d) δ 142.5, 140.7, 138.2, 130.3, 129.7, 129.2, 128.0, 127.0, 126.6, 124.1, 23.5, -1.3. EI-MS m/z: 240, 225, 165, 73(100%).
Trimethyl(2,4,6-tri-tert-butylbenzyl)silane (6d): Synthesized according to general method. The
product was obtained after column chromatography as a yellow oil. (SiO2, n-pentane). GC/MS
analysis showed 8% 2,4,6-tri-tert-butylbenzene. [182 mg, 85% yield]. 1H-NMR (400MHz,
Chloroform-d) δ 7.25 (d, J = 10.5 Hz, 2H), 7.16 (t, J = 1.8 Hz, 2H), 1.62 – 1.54 (m, 2H), 1.33 (d, J = 1.9 Hz, 20H), 1.28 (d, J = 1.9 Hz, 7H), 0.30 – 0.22 (m, 2H), -0.07 (d, J = 1.9 Hz, 9H). 13C-NMR (100MHz, Chloroform-d) δ 149.7, 149.3, 120.2, 119.0, 38.9, 38.4, 34.9, 31.6, 28.6, 10.9, -1.9. EI-MS m/z: 332, 274, 231(100%), 215, 73.
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((9H-Fluoren-2-yl)methyl)trimethylsilane (6e): Synthesized according to general method. The
product was obtained after column chromatography as a pale yellow solid (SiO2, n-pentane). [145 mg,
96% yield]. 1H-NMR (400MHz, Chloroform-d) δ 7.76 (d, J = 7.5 Hz, 1H), 7.68 (d, J = 7.8 Hz, 1H), 7.55 (d, J = 7.4 Hz, 1H), 7.39 (t, J = 7.5 Hz, 1H), 7.32 – 7.26 (m, 1H), 7.23 (s, 1H), 7.06 (d, J = 7.8 Hz, 1H), 3.89 (s, 2H), 2.21 (s, 2H), 0.07 (s, 9H). 13C-NMR (100MHz, Chloroform-d) δ 143.5, 142.9, 142.0, 139.4, 137.8, 126.6 (2x), 125.9, 124.9, 124.6, 119.5, 119.3, 36.8, 27.3, -1.8. EI-MS m/z: 252, 237, 179, 73(100%).
Trimethyl(2-(trifluoromethoxy)benzyl)silane (6h): Synthesized according to general method. The
product was obtained after column chromatography as a yellow oil. (SiO2, n-pentane). [80 mg, 54%
(100MHz, Chloroform-d) δ 146.7, 133.2, 130.4, 126.2, 125.2, 121.9, 119.9, 119.4, 20.8, -1.7. 19 F-NMR (376MHz, Chloroform-d) δ -56.9. EI-MS m/z: 248, 156, 90, 73(100%).
2,6-Bis((trimethylsilyl)methyl)naphthalene (6k): Synthesized according to general method. The
product was obtained after column chromatography as a white solid (SiO2, n-pentane). [120 mg, 66%
yield]. 1H-NMR (400MHz, Chloroform-d) δ 7.60 (d, J = 8.3 Hz, 1H), 7.38 (s, 1H), 7.12 (dd, J = 8.3, 1.5 Hz, 1H), 2.23 (s, 2H), 0.04 (s, 9H). 13C-NMR (100MHz, Chloroform-d) δ 136.5, 131.4, 127.8, 126.6, 124.9, 27.1, -1.8. EI-MS m/z: 300, 299, 212, 197, 73 (100%).
1,3,5-Tris((trimethylsilyl)methyl)benzene (6j):11 Synthesized according to general method with the
addition of 3.6 equiv. of TMS-CH2-Li. The product was obtained after column chromatography as a
colorless liquid. (SiO2, n-pentane). [165 mg, 82% yield]. 1H-NMR (400MHz, Chloroform-d) δ 6.39 (s,
1H), 1.99 (s, 2H), 0.01 (s, 9H). 13C-NMR (100MHz, Chloroform-d) δ 139.8, 123.7, 26.8, -1.6. EI-MS m/z: 336, 335, 320, 248(100%), 73, 141, 73(100%).
(2-Methoxybenzyl)trimethylsilane (8):2 Synthesized according to general method using 1-chloro-2-methoxybenzene. The product was obtained after column chromatography as a colorless liquid. (SiO2, n-pentane). [109 mg, 94% yield]. 1H-NMR (400MHz, Chloroform-d) δ 7.08 (td, J = 7.9, 1.7 Hz, 1H), 6.99 (dd, J = 7.4, 1.5 Hz, 1H), 6.89 – 6.77 (m, 2H), 3.79 (s, 3H), 2.11 (s, 2H), -0.01 (s, 9H). 13C-NMR (100MHz, Chloroform-d) δ 156.4, 129.4, 129.2, 124.9, 120.2, 109.8, 54.8, 20.5, -1.5. EI-MS m/z: 194, 179, 164, 149, 73(100%).
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