General Ambient Temperature Benzylic Metalations Using Mixed-Metal Li/K-TMP Amide

Article abstract of DOI:10.1021/acs.joc.5b01540

Highly regioselective benzylic metalations in hydrocarbon solvent have been achieved at rt and 0 °C using a mixed-metal Li/K-TMP amide comprised of KOtBu, BuLi, and 2,2,6,6,-tetramethylpiperidine (TMP(H)). Mixing of KOtBu, BuLi, and TMP(H) in heptane gave a solution of the base mixture which when used in deuterium labeling experiments confirmed the requirement of the three reagent components for both reactivity and selectivity. The reaction protocol is operationally straightforward and found to be applicable to a broad range of substrates. Upon generation of the metalated products, they are reacted in heptane at ambient temperature in a variety of synthetically useful ways. Illustrated examples include generation of the benzyltrimethylsilanes and α,α-bis(trimethylsilyl)toluenes reagents, which are bench-stable surrogates of benzyl anions and α-silyl carbanions utilized for nucleophilic addition and Peterson olefination reactions. Direct C-C couplings mediated by 1,2-dibromoethane provided entries into bibenzyls and [2.2]metacyclophanes. Comparison of reaction outcomes with the same reactions carried out in THF at -78 °C showed no negative effects for conducting the reactions under these milder more user-friendly conditions.

Full text of DOI:10.1021/acs.joc.5b01540

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Article
General Ambient Temperature Benzylic
Metalations Using Mixed-Metal Li/K-TMP Amide
Atul Manvar, Patricia Fleming, and Donal F. O'Shea
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b01540 • Publication Date (Web): 17 Aug 2015
Downloaded from http://pubs.acs.org on August 20, 2015
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General Ambient Temperature Benzylic Metalations Using Mixed-Metal
Li/K-TMP Amide
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Atul Manvar,† Patricia Fleming,† and Donal F. O’Shea* †‡
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†Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland,
Dublin 2, Ireland
‡School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4,
Ireland
EMAIL: donalfoshea@rcsi.ie
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ABSTRACT
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Highly regioselective benzylic metalations in hydrocarbon solvent have been achieved at
rt and 0 °C using a mixed-metal Li/K-TMP amide comprised of KOtBu, BuLi and 2,2,6,6,-
tetramethylpiperidine (TMP(H)). Mixing of KOtBu, BuLi and TMP(H) in heptane gave a
solution of the base mixture which when used in deuterium labelling experiments confirmed the
requirement of the three reagent components for both reactivity and selectivity. The reaction
protocol is operationally straightforward and found to be applicable to a broad range of
substrates. Upon generation of the metalated products they be reacted in heptane at ambient
temperature in a variety of synthetically useful ways. Illustrated examples include generation of
the benzyltrimethylsilanes and ,-bis(trimethylsilyl)toluenes reagents, which are bench-stable
surrogates of benzyl anions and α-silyl carbanions utilized for nucleophilic addition and Peterson
olefination reactions. Direct C-C couplings mediated by 1,2-dibromoethane provided entries into
bibenzyls and [2.2]metacyclophanes. Comparison of reaction outcomes with the same reactions
carried out in THF at -78 °C showed no negative effects for conducting the reactions under these
milder more user friendly conditions.
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INTRODUCTION
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The founding principles for the predictive use of organometallic bases for selective
kinetic proton abstraction were established in the work of Curtin, Gilman and Wittig1-3 and
expanded to the breadth of organic synthesis by the immense contributions of Schlosser,4 Beak,5
Snieckus5 and many others. The use of thermodynamic metalating conditions is often thought of
as less challenging technically, but does also pose significant selectivity challenges. For
example, substituted toluenes 1 are one group of substrates for which differentiation between
kinetic and thermodynamic metalation sites is often a challenging issue depending upon the
nature and position of the R substituent(s) on the aryl ring. Specifically, one or more directed
ortho metalation product(s) 2 can exist, restricting attainment of the benzylic metalated product 3
with high selectivity (Scheme 1).6 Numerous reports of lateral metalations (defined as
deprotonation of a benzylic position that is lateral, or flanked by, a heteroatom containing
substituent) have shown that they are highly substrate dependent leading to a myriad of
conditions used with high selectivities often unachievable.7
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Scheme 1. Competing Metalation Sites (M = metal)
In previously reported work we have shown that, in THF at -78 °C, the use of the triad of
reagents BuLi/KOtBu/TMP(H) was a general method to achieve benzylic metalations with
excellent selectivity, irrespective of whether the benzylic position is lateral (ortho) to a
heteroatom containing substituent or not (i.e. meta or para) (Scheme 2).8 This can be attributed
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to the enhanced reactivity of the in situ formed mixed Li/K metal TMP amide over LiTMP alone
and the ability of the TMP(H) to facilitate an anion migration from kinetic aryl to
thermodynamic benzylic position.8b The term LiNK was coined to describe the synergetic
combination of the mixed metal amide containing lithium (Li), nitrogen (N) from the TMP and
potassium (K). For simplicity the benzylic species generated from the LiNK metalation are
presented only as the K species based on the recent characterization of the PhLi/PhK/tBuOLi
mediated metalation of toluene as benzylpotassium, though it should be understood that the exact
nature of these organometallics could be substrate dependant and may be mixed metal species.9
The synthetic uses of these benzylic organometallics have included electrophile
reactions,8b direct Csp3-Csp3 coupling for bibenzyl,10 and [2.2]metacyclophane11 synthesis and
further transmetalation to Si by reaction with chlorotrimethylsilane providing access to the bench
stable benzyltrimethylsilane class 4 (Scheme 2).12 Alternative procedures for the synthesis of
benzyltrimethylsilanes require Pd or Ni catalyzed cross-coupling of the organo-lithium or -
magnesium substrates MCH2SiMe3, (M = Li or Mg) with aryl-halides, -methylethers or -
methylthioethers.13 The synthetic advantage of silanes 4 lies in the fact that they can act as
surrogates of benzyl anions and participated in nucleophilic addition reactions with mild
silyloxide or fluoride activation (Scheme 2).14
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Additionally, the utility of LiNK metalation (in THF at -78 °C) has been extended to
include the regioselective benzylic metalation of substituted benzyltrimethylsilanes 4 generating
the α-silyl carbanions 5, which upon chlorotrimethylsilane quench yields the α,α-
bis(trimethylsilyl)toluenes 6.15 The literature precedents for synthesis of reagents 6 using
organometallic deprotonation as the key step are few.16 Recently, the transition-metal catalyzed
cross-couplings of (Me3Si)2MgBr.LiCl or (Me3Si)2ZnCl.MgBrCl.LiCl with aryl halides has been
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reported as an additional route to this reagent class.17 The synthetic value of reagents 6 lie in
their bench stability, yet under mild activation conditions they can react as equivalents of the α-
silyl carbanions 5 in Peterson olefination reactions.15,17,18 The utility of reagents 6 for E-
selective Peterson olefination from N-phenyl imines has recently been reported.15
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Scheme 2. Selective Benzylic Metalation and Bench Stable Equivalents
The ability of LiNK to favour the thermodynamic over kinetic metalation product at –78 °C in
THF raised the possibility that this low temperature may not always be necessary to achieve
selective metalation. Recognising the instability of THF to strong bases at ambient temperature,
we chose to investigate the reactivity and selectivity in hydrocarbon solvents with the key goals
being to make the use of the base mixture as operationally straightforward as possible and
facilitate the generation of important silicon reagents.
Extensive studies of o-metalations in hydrocarbon solvents have been reported by Slocum and
co-workers, yet the literature precedents on thermodynamic benzylic metalation in hydrocarbons
are considerably less prevalent with poor selectivity and limited substrate scope often obtained.19
The kinetic versus thermodynamic o- and benzylic deprotonation of p-tolylsulfonamide, p-
tolylsulfonate and p-toluamide have previously been investigated in the literature.20 Arguably, a
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general ambient temperature method for benzylic metalation and electrophile reaction is
desirable due to the broad synthetic potential of this reaction as outlined above.
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RESULTS AND DISCUSSION
At the outset of our investigation into ambient temperature LiNK metalations in
hydrocarbon solvents, 2-methylanisole 1a was chosen as a model substrate. Previous reports
have shown that selective benzylic lithiation of 1a in hydrocarbons was challenging, for example
BuLi/cyclohexane (reflux, 10 h) gave bn/o ratio of 67/33,21a BuLi/TMEDA/cyclohexane (rt, 10
h) gave a 25/75 bn/o mixture,21b BuLi/KOtBu/heptane (reflux, 4.5 h) gave 49/25 for bn/o product
ratio with the remainding being rearrangement products,21b while LDA/KOtBu/hexane (25 °C,
10 h) provided 100/0: bn/o.21c
To gain a comparative understanding about the reactivity and selectivity of LiNK
metalation of 1a the following five reactions were carried out: (a) as per the previously
established LiNK conditions with the three reagents BuLi, KOtBu, TMP(H) at -78 °C in THF,
(b) with BuLi, KOtBu, TMP(H) at rt in cyclohexane (c) with BuLi, KOtBu, TMP(H) at rt in
heptane (d) with BuLi, KOtBu at rt in cyclohexane and (e) with BuLi/TMP(H) in cyclohexane at
rt (Scheme 3). Each reaction was stirred for 15 min and the resulting metalated mixture treated
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with CD3OD and the deuterated products analyzed by H and H NMR. As anticipated,
conditions (a) gave Bn-D-1a exclusively as product with good deuterium incorporation (>80%)
(Figure 1, NMR A) and gratifyingly, a similar exclusively benzylic deuterated product was
observed for both hydrocarbon reactions (b) and (c) at rt (>65% Bn-D) with no detectable o-D
incorporation (Figure 1, NMRs B and C). In contrast, when only the two components BuLi,
KOtBu were used, as in reaction (d), a complex mixture of deuterated isotopomers was obtained
showing complete loss of selectivity (Figure 1, NMR D).
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Scheme 3. Metalation of 2-Methylanisole Under Various Conditionsa
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aAll reaction times of 15 min, 1.2 equiv. of each reagent used.
2H NMR A: LiNK, THF -78 °C
*
2H NMR B: LiNK, C6H14, rt
*
2H NMR C: LiNK, C7H16, rt
*
2H NMR D: BuLi, KOtBu, C6H14, rt
Figure 1. 2H NMR spectra. (*CD2Cl2)
When the alternative two reagents BuLi and TMP(H) were used as in conditions (e), no
deuterium incorporation was detected showing that if LiTMP formed in situ22 it had insufficient
basic strength to deprotonate under these conditions. Taken together these experiments highlight
the significance of each component of the reagent mixture in delivering sufficient base strength
yet maintaining a high degree of selectivity for benzylic metalation.
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A further optimization was next conducted using TMSCl as electrophile. When
conducting these experiments, it was found easiest to first sequentially add the three LiNK
reagents (KOtBu, BuLi, and TMP(H)) to the flask and then subsequently add the substrate 1a,
followed by the electrophile. Reactions in both cyclohexane and heptane at rt gave the expected
TMS product 4a in 65% and 69% yields respectively (Scheme 4, entries 1, 2). Lowering the
reaction temperature to 0 °C gave a marginal improvement in the yields (entries 3 and 4), though
starting material was recovered after workup. Increasing the LiNK mixture to 2 equiv. in
heptane at 0 °C gave complete conversion, with the best yield of 86% (entry 5). Collectively,
these results suggest that 2.0 equiv. of the preformed base mix KOtBu/BuLi/TMP(H) in heptane
at 0 °C followed by addition of substrate would be the optimal general procedure.
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Scheme 4: Screening of Hydrocarbon Solventsa
Entry
Solvent
cyclohexane
heptane
T (°C) Yield (%)
1
2
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6
rt
rt
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70
73
86
86
cyclohexane
heptane
0
0
bheptane
bheptane
rt
Conditions: a 1a (1.0 mmol), BuLi (1.2 mmol), KOtBu
(1.2 mmol), TMP(H) (1.2 mmol), solvent (2.5 mL)
Me3SiCl (2.5 mmol). b 1a (1.0 mmol), BuLi (2.0 mmol),
KOtBu (2.0 mmol), TMP(H) (2.0 mmol), solvent (2.5 mL),
TMSCl (2.5 mmol).
Prior to exploring the generality of this method, a temperature profile analysis of the formation
and reaction of LiNK was undertaken (Figure 2). A stirred colorless suspension of KOtBu in
heptane was cooled in an ice-bath to 1 °C, and BuLi added dropwise giving a suspension of the
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Lochmann-Schlosser base with a 7 °C temperature rise.23 Upon the addition of TMP(H) a
temperature rise of 4 °C occurred with the formation of an orange-brown solution from which a
trace of precipitate formed over the 5 min time period before it was used. These results showed
that no large exotherm was associated with the formation of a 0.6 M solution of the LiNK
reagent generated for these experiments. Upon addition of the substrate 1a (1.0 mmol) no
change in temperature was detected and an immediate yellow suspension of 3a formed. Next,
upon addition of chlorotrimethylsilane electrophile a significant rise in temperature of 18 °C was
observed. Once the reaction mixture had cooled back to 2 °C (30 mins), 2M HCl was added
which also gave a significant temperature rise of 20 °C. Consequently, the electrophile quench
and reaction workup steps are critical in term of exotherms, confirming that it is advisable to
conduct these reactions at 0 °C for temperature control. Similar incremental increases in
temperature profile were observed when the reaction was carried out at rt (Figure S1, SI).
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aCondition: 1a (1.0 equiv), BuLi (2.0 equiv), KOtBu (2.0 equiv), TMP (2.0 equiv), Me3SiCl (2.5 equiv).
Figure 2. Temperature profile of benzylic metalation, TMSCl reaction and workupa
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As there is a growing interest in the use of bench stable organosilicon reagents as
carbanion equivalents, their synthesis was explored for a range of substrates using this
approach.12,13,14 Encouragingly, electron-rich toluenes such as 3-methylanisole 1b, 3,4,5-
trimethoxyanisole 1c and 2-N,N-trimethylaniline 1d each gave their corresponding
benzyltrimethylsilanes 4b-d with high yields 88%, 73%, 92% respectively (Scheme 5).
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Scheme 5. Synthesis of substituted benzyltrimethylsilane reagentsa
aCondition: Substrate (1.0 equiv), BuLi (2.0 equiv),
KOtBu (2.0 equiv), TMP(H) (2.0 equiv) and
Me3SiCl (2.5 equiv).b1.2 equiv of each
BuLi/KOtBu/TMP(H) used. 12 Reference for literature
reported yields in THF at -78 °C.
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Comparison of the results for 4b-e with those previously reported in THF at -78 °C showed
yields to be within small experimental error differences (Scheme 5, yields given in brackets).12
The electron deficient o/p amido and sulfonamido substituted toluenes were successfully
converted to their corresponding silanes 4e-g in 49-91% yields. For substrates containing more
than one methyl group such as m-xylene 1h, 3,5-dimethylanisole 1i, and 2,6-dimethylanisole 1j
the procedure was equally successful with yields for 4h-j ranging from 79 to 95% (Scheme 5).
Next, the set of aromatic hydrocarbons 1k-n was screened and found to be convertible to their
corresponding benzyltrimethylsilanes 4k-n in good yields, illustrating that heteroatom
substituent is not an essential factor. The heterocycle, α-picoline 1o, also reacted under the
established conditions with product 4o obtained in 87% yield. One substrate limitation
encountered was for halogenated toluenes, which were found to be incompatible with the
metalation conditions, leading to complex product mixtures.
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To further expand the repertoire of silicon reagents, the synthesis of ,,-
bis(trimethylsilyl)toluenes from benzyltrimethylsilanes was next addressed using 4b as the test
substrate. Pleasingly, following a 15 min LiNK metalation in heptane to form the -
silylcarbanion 5 and treatment with TMSCl the bis(silane) product 6a was selectively obtained in
a 88% yield (Scheme 6). Substrates 4c-e containing trimethoxy, o-dimethylamino and p-amido
substituents were also successfully converted to their corresponding di-TMS products 6b-d in
good to excellent yields (72-86%) which compared favorably with those previously reported in
THF at -78 °C.15 Notably, the presence of a competing methyl group in 4h did not interfere with
metalation regioselectivity, as product 6e was obtained in a 82% yield. Trimethylsilanes 4k-m,
which contain no heteroatom substituent, were also converted to products 6f, 6g and 6h with
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81%, 71% and 77% yields, respectively. Conveniently, a one-pot conversion of 2-picoline 1o
into bis-trimethylsilane 6i was directly achieved with 2.2 equiv of the LiNK reagent (Scheme 6).
Overall, a two-fold LiNK metalation / TMSCl quench procedure at ambient temperature appears
to be a routine general method for access to this class of Peterson olefination reagent.15
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Scheme 6: Synthesis of Peterson olefination reagents
aCondition: Substrate (1.0 equiv), BuLi (2.0 equiv),
KOtBu (2.0 equiv), TMP(H) (2.0 equiv) and
Me3SiCl (2.5 equiv). b 1o used as starting substrate
with BuLi (2.2 equiv), KOtBu (2.2 equiv), TMP(H)
(2.2 equiv) and Me3SiCl (2.5 equiv). 15Reference for
literature reported yields in THF at -78 °C.
Transition-metal free coupling of two carbon nucleophiles generated by direct
deprotonation is an atom-economical method for C-C bond formation.24 In a previous report it
was shown that LiNK metalation of toluenes in THF at -78 °C and treatment with 1,2-
dibromoethane was an effective method to produce 1,2-diarylethanes.10 As such, it was of
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interest to determine if this coupling was also achievable under ambient temperature heptane
conditions. Generality of the reaction sequence was established with toluene substrates 1b, c, d,
e, h, and i which were metalated and treated with 1,2-dibromoethane to provide the coupled
products 7a-e in moderate to excellent yields of 52 to 92% (Scheme 7, route A).
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Scheme 7: Csp3-Csp3 couplings and benzylbromide reactionsa
aConditions: 1 (1.0 equiv), BuLi (2.0 equiv),
KOtBu (2.0 equiv), TMP(H) (2.0 equiv).
(iv) 1,2-dibromoethane (4.0 equiv),
(v) ArCH2Br (4.0 equiv). 10Reference for
literature reported yields in THF at -78 °C.
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Comparison with previously reported results in -78 °C THF showed some marginally
higher and some lower yields but with only one example, 7d, showing a substantial difference.10
Notably, the natural product Brittonin A, 7f, was accessible with this approach in a single-step
showing that conducting these C-C bond forming reactions in hydrocarbon solvent had no
negative effect. Efficient synthesis of bibenzyls with two differing aryl rings is also appealing
and could be addressed by using substituted benzylbromides electrophiles (Scheme 7, route B).
As examples, 3-methoxytoluene 1b, 3,4,5-trimethoxytoluene 1c and 2-N,N-trimethylaniline 1d
were metalated with subsequent benzylbromide reaction to afford 7g-i in excellent yields (80-
85%) and dimethyl ether derivative of Aloifol I natural product 7j in 86%.
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Finally, the ambient temperature metalation approach was applied to the synthesis of
[2.2]metacylcyclophanes.11 A double LiNK metalation of bibenzyls 7d, e generated di-metalated
species 8 which upon treatment with dibromoethane effectively ring closed to produce
metacyclophanes 9a, and b in 29% and 31% yields, respectively (Scheme 8). This repetitive two
step synthesis of [2.2]metacyclophanes offers a straightforward entry into this strained cyclic
system.
Scheme 8: Synthesis of [2.2]metacyclophanes.
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CONCLUSION
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In summary, regioselective benzylic metalations of substituted toluenes, xylenes and
benzylsilanes can be successfully accomplished in hydrocarbon reaction media at 0 °C using the
LiNK reagent triad. Subsequent reaction of the generated metalated species with TMSCl gave
the corresponding benzyltrimethylsilanes and α,α-bis(trimethylsilyl)toluenes which are bench-
stable pro-nucleophiles for addition and Peterson olefination reactions. This new approach
provides routine access to these important Si-reagents which should find widespread use in
organic chemistry. Direct C-C couplings also allowed for atom efficient synthesis of bibenzyl
derivatives and [2.2]metacyclophane. Further synthetic and mechanistic studies involving the
LiNK reagent are ongoing.
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EXPERIMENTAL SECTION
General information. All of the reactions involving air-sensitive reagents were performed under
nitrogen either in oven- or flame-dried glassware using syringe-septum cap technique. All of the
solvents were purified and degassed before use. 2,2,6,6-Tetramethylpiperidine, TMP(H), was
distilled from CaH2 prior to use. Heptane and cyclohexane were purified under nitrogen from
CaH2. THF was purified on Na/benzophenone. BuLi was purchased as a 2.5 M solution in
hexanes. The exact concentration of the BuLi was determined by titration with diphenylacetic
acid in THF prior to use. KOtBu was sublimed prior to use. Chlorotrimethylsilane and CD3OD
was used as received. Chromatographic separations were carried out under pressure on Merck
silica gel 60 or aluminium oxide 60 using flash-column techniques. Reactions were monitored by
thin-layer chromatography (TLC) carried out on 0.25 mm silica gel coated aluminum plates with
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UV light (254 nm) as the visualizing agent. H and C NMR spectra were recorded at room-
temperature on a 400 and 600 MHz spectrometer. TOF mass analyzers were used for HRMS
measurements. The yields are after column chromatography.
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Metalation of 2-methylanisole under various conditions (Scheme 3)
Reaction (i): A solution of 2-methylanisole 1a (124 µL, 1.0 mmol) in THF (2.5 mL) at -78 °C
was treated with KOtBu (135 mg, 1.2 equiv). Subsequently, BuLi (512 µL, 2.35 M in hexanes,
1.2 equiv) and TMP(H) (202 µL, 1.2 equiv) was slowly added. The resulting solution was stirred
for 15 min at -78 °C. Methanol-d4 (203 µL, 5.0 equiv) was added and warmed it to rt and 2 M
HCl (10 mL) was slowly added. The residue was extracted with diethyl ether (3 × 15 mL) and
organic layers were combined, washed with water (2 × 10 mL) and brine (5 mL), dried over
Na2SO4, and concentrated to dryness gave crude 1-methoxy-2-deuteriomethylbenzene Bn-D-
1a8b. 1H NMR (600 MHz, CH2Cl2): δ 7.17–7.10 (m, 2.55 H), 6.86–6.81 (m, 2.20H), 3.81 (s, 3H),
2.21–2.17 (m, 2.64H). 2H NMR (92.07 MHz, CH2Cl2): 2.18 (t, 3H). (>75 % D incorporation).
Reaction (ii) and (iii): A solution of 2-methylanisole 1a (124 µL, 1.0 mmol) in heptane or
cyclohexane (2.5 mL) at rt was treated KOtBu (135 mg, 1.2 equiv). BuLi (512 µL, 2.35 M in
hexanes, 1.2 equiv) and TMP(H) (202 µL, 1.2 equiv) was slowly added. The resulting
suspension was stirred for 15 min at rt. Methanol-d4 (203 µL, 5.0 equiv) was added and stirred it
for 1 h and 2 M HCl (10 mL) was slowly added. The residue was extracted with diethyl ether (3
× 15 mL) and organic layers were combined, washed with water (2 × 10 mL) and brine (5 mL),
dried over Na2SO4, and concentrated to dryness gave crude 1-methoxy-2-deuteriomethylbenzene
1
Bn-D-1a8b. H NMR (600 MHz, CH2Cl2): δ 7.16–7.09 (m, 3.18H), 6.87–6.81 (m, 2.55H), 3.81
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(s, 3H), 2.20–2.15 (m, 2.90H). H NMR (92.07 MHz, CH2Cl2): 2.18 (t, 3H). (>65 % D
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incorporation).
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Reaction (iv): A mixture of 2-methylanisole 1a (124 µL, 1.0 mmol) and KOtBu (135 mg, 1.2
equiv) in heptane (2.5 mL) at rt was treated with BuLi (512 µL, 2.35 M in hexanes, 1.2 equiv).
The resulting suspension was stirred for 15 min at rt. Methanol-d4 (203 µL, 5.0 equiv) was added
and stirred it for 1 h at rt and 2 M HCl (10 mL) was slowly added. The residue was extracted
with diethyl ether (3 × 15 mL) and organic layers were combined, washed with water (2 × 10
mL) and brine (5 mL), dried over Na2SO4, and concentrated to dryness gave crude products. See
the complex 1H NMR in SI. 2H NMR (92.07 MHz, CH2Cl2): δ 6.95–6.77 (m, 0.70H), 3.85–3.75
(m, 0.15H), 3.63–3.50 (m, 0.05H), 2.30–2.10 (m, 3H), 2.05–1.87 (m, 0.30H), 1.30–1.11 (m,
0.25H).
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Reaction (v): 2-Methylanisole 1a (124 µL, 1.0 mmol) in heptane (2.5 mL) was treated with
TMP(H) (202 µL, 1.2 equiv) and BuLi (512 µL, 2.35 M in hexanes, 1.2 equiv) and was slowly
added. The resulting reaction mixture was stirred at rt for 15 min. Methanol-d4 (203 µL, 5.0
equiv) was added and stirred it for 1 h at rt and 2 M HCl (10 mL) was slowly added. The residue
was extracted with diethyl ether (3 × 15 mL) and organic layers were combined, washed with
water (2 × 10 mL) and brine (5 mL), dried over Na2SO4, and concentrated to dryness gave crude
1
product. H NMR (600 MHz, CH2Cl2): δ 7.21–7.12 (m, 2H), 6.90–6.82 (m, 2H), 3.83 (s, 3H),
2.24 (s, 2H). 2H NMR (92.07 MHz, CH2Cl2): No signals observed.
Screening of hydrocarbon solvents (Scheme 4)
Entries 1-3: A mixture of 2-methylanisole 1a (124 µL, 1.0 mmol) and sublimed KOtBu (135 mg,
1.2 equiv) in the corresponding solvent (2.5 mL) was treated with BuLi (512 µL, 1.2 equiv, 2.35
M in hexanes) at specified temperature in Scheme 4. TMP(H) (202 µL, 1.2 equiv) was added
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dropwise and it was stirred for 15 min. Chlorotrimethylsilane (317 µL, 2.5 equiv) was added and
stirred it for 1 h and 2 M HCl (10 mL) was slowly added. The residue was extracted with diethyl
ether (2 × 20 mL) and organic layers were combined, washed with brine (10 mL), dried over
Na2SO4, and concentrated to dryness. The product was purified by silica gel column
chromatography eluting with cyclohexane yielded 4a as colorless oil. The product yields are
depicted in Scheme 4.
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Entry 4: Sublimed KOtBu (135 mg, 1.2 equiv) in heptane (2.5 mL) was treated with BuLi (512
µL, 1.2 equiv, 2.35 M in hexanes) at 0 °C. TMP(H) (202 µL, 1.2 equiv) was added dropwise and
the resulting suspension was stirred for 5 min. A solution of 2-methylanisole 1a (124 µL, 1.0
mmol) in heptane (0.5 mL) was added dropwise and the reaction mixture was stirred for 15 min.
Chlorotrimethylsilane (317 µL, 2.5 equiv) was added and stirred it for 1 h and 2 M HCl (10 mL)
was slowly added. The residue was extracted with diethyl ether (2 × 20 mL) and organic layers
were combined, washed with brine (10 mL), dried over Na2SO4, and concentrated to dryness.
The product was purified by silica gel column chromatography eluting with cyclohexane yielded
4a12 (142 mg, 73%) as a colorless oil.
Entries 5 and 6: Sublimed KOtBu (224 mg, 2.0 equiv) in heptane (2.5 mL) was treated with BuLi
(851 µL, 2.0 equiv, 2.35 M in hexanes) at rt. TMP(H) (338 µL, 2.0 equiv) was added dropwise
and the resulting suspension was stirred for 5 min. A solution of 2-methylanisole 1a (124 µL, 1.0
mmol) in heptane (0.5 mL) was added dropwise and the reaction mixture was stirred for 15 min.
Chlorotrimethylsilane (317 µL, 2.5 equiv) was added, stirred for 1 h and 2 M HCl (10 mL) was
slowly added. The residue was extracted with diethyl ether (2 × 20 mL) and organic layers were
combined, washed with brine (10 mL), dried over Na2SO4, and concentrated to dryness. The
product was purified by silica gel column chromatography eluting with cyclohexane yielded 4a12
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as a colorless oil. The product yields are depicted in Scheme 4. H NMR (400 MHz, CDCl3): δ
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7.10–7.04 (m, 1H), 7.05–6.96 (m, 1H), 6.87–6.78 (m, 2H), 3.79 (s, 3H), 2.10 (s, 2H), -0.02 (s,
7
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9H). C NMR (100 MHz, CDCl3): δ 156.4, 129.4, 129.2, 124.9, 120.2, 109.8, 54.8, 20.5, -1.6.
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HRMS–EI [M]+: 194.1125, C11H18OSi requires 194.1127.
Exothermicity analysis in benzylic metalation of 1a (Figure 2)
Sublimed KOtBu (224 mg, 2.0 equiv) in heptane (2.5 mL) was cooled at 1 °C. BuLi (832 µL, 2.0
equiv, 2.4 M in hexanes) was added dropwise with internal temperature monitored with a Hanna
thermometer. The temperature of the reaction was increased from 1 °C to 7 °C. The reaction was
stirred for 5 min and cooled to 2 °C. TMP(H) (338 µL, 2.0 equiv) was added dropwise and the
temperature of the reaction was increased up to 6 °C. The reaction was stirred for 5 min and
cooled to 1 °C. A solution of 2-methylanisole 1a (124 µL, 1.0 mmol) in heptane (0.5 mL) was
added dropwise. The temperature was increased from 1 °C to 2 °C. The resulting precipitates
was stirred for 15 min and cooled to 1 °C. Chlorotrimethylsilane (317 µL, 2.5 equiv) was added
slowly and the temperature of the reaction was increased from 1 °C to 19 °C. The reaction mass
was stirred for 1 h and cooled to 2 °C. 2 M HCl (10 mL) was slowly added and the temperature
of the reaction was increased from 2 °C to 22 °C. The residue was extracted with diethyl ether (2
× 20 mL) and organic layers were combined, washed with brine (10 mL), dried over Na2SO4,
and concentrated to dryness. The product was purified by silica gel column chromatography
eluting with cyclohexane yielded 4a (173 mg, 85%) as a colorless oil.
(3-Methoxybenzyl)trimethylsilane, 4b12
Under inert atmosphere, a mixture of KOtBu (673 mg, 6.0 mmol) in heptane (7.5 mL) at 0 °C
was treated with BuLi (2.55 mL, 2.35 M in hexanes, 6.0 mmol), followed by TMP(H) (1.0 mL,
6.0 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
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of 3-methylanisole 1b (378 µL, 3.0 mmol) in heptane (1.0 mL) was added dropwise and stirred
for 15 min at 0 °C. Chlorotrimethylsilane (952 µL, 7.5 mmol) was added and stirred it for 1 h at
rt and 2 M HCl (20 mL) was slowly added. The residue was extracted with diethyl ether (3 × 20
mL) and organic layers were combined, washed with water (2 × 20 mL) and brine (10 mL), dried
over Na2SO4, and concentrated to dryness. The product was purified by silica gel column
chromatography eluting with cyclohexane yielded 4b (502 mg, 86%) as a colorless oil. 1H NMR
(400 MHz, CDCl3): δ 7.16–7.10 (m, 1H), 6.67–6.52 (m, 3H), 3.78 (s, 3H), 2.06 (s, 2H), 0.00 (s,
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9H). C NMR (100 MHz, CDCl3): δ 159.4, 142.2, 129.0, 120.7, 113.8, 109.1, 55.0, 27.2, -1.9
ppm. MS–EI [M]+: 194.6, C11H18OSi requires 194.3.
3,4,5-(Trimethoxybenzyl)trimethylsilane, 4c12
Under inert atmosphere, a mixture of KOtBu (673 mg, 6.0 mmol) in heptane (7.5 mL) at 0 °C
was treated with BuLi (2.55 mL, 2.35 M in hexanes, 6.0 mmol), followed by TMP(H) (1.0 mL,
6.0 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
of 3,4,5-trimethoxytoluene 1c (505 µL, 3.0 mmol) in heptane (1.0 mL) was added dropwise and
stirred for 15 min at 0 °C. Chlorotrimethylsilane (952 µL, 7.5 mmol) was added and stirred it for
1 h at rt and 2 M HCl (20 mL) was slowly added. The residue was extracted with diethyl ether (3
× 20 mL) and organic layers were combined, washed with water (2 × 20 mL) and brine (10 mL),
dried over Na2SO4, and concentrated to dryness. The product was purified by silica gel column
chromatography eluting with petroleum ether/ethylacetate (1/1) yielded 4c (560 mg, 73%) as a
colorless oil. 1H NMR (400 MHz, CDCl3): δ 6.20 (s, 2H), 3.82 (s, 6H), 3.81 (s, 3H), 2.02 (s, 2H),
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0.01 (s, 9H). C NMR (100 MHz, CDCl3): δ 154.7, 138.1, 136.7, 106.8, 62.7, 57.8, 29.2, -0.00
ppm. HRMS–ESI [M+H]+: 255.1411, C13H23O3Si requires 255.1416.
N,N-Dimethyl-2-[(trimethylsilyl)methyl]aniline, 4d12
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Under inert atmosphere, a mixture of KOtBu (673 mg, 6.0 mmol) in heptane (7.5 mL) at 0 °C
was treated with BuLi (2.55 mL, 2.35 M in hexanes, 6.0 mmol), followed by TMP(H) (1.0 mL,
6.0 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
of 2-N,N-trimethylaniline 1d (437 µL, 3.0 mmol) in heptane (1.0 mL) was added dropwise and
stirred for 15 min at 0 °C. Chlorotrimethylsilane (952 µL, 7.5 mmol) was added and stirred for 1
h at 0 °C and 2 M HCl (20 mL) was slowly added. The residue was extracted with diethyl ether
(3 × 20 mL) and organic layers were combined, washed with water (2 × 20 mL) and brine (10
mL), dried over Na2SO4, and concentrated to dryness. The product was purified on alumina
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eluting with cyclohexane/ethyl acetate (95/5) yielded 4d (540 mg, 86%) as a colorless oil. H
NMR (400 MHz, CDCl3): δ 7.09–7.05 (m, 2H), 7.02–6.98 (m, 1H), 6.96–6.91 (m, 1H), 2.62 (s,
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6H), 2.17 (s, 2H), -0.03 (s, 9H). C NMR (100 MHz, CDCl3): δ 152.0, 136.2, 129.7, 124.8,
123.3, 119.6, 44.8, 22.1, -1.2 ppm. MS–EI [M]+: 207.7, C12H21NSi requires 207.4.
N,N-Diisopropyl-4-[(trimethylsilyl)methyl]benzamide, 4e12
Under inert atmosphere, a mixture of KOtBu (673 mg, 6.0 mmol) in heptane (7.5 mL) at 0 °C
was treated with BuLi (2.55 mL, 2.35 M in hexanes, 6.0 mmol), followed by TMP(H) (1.0 mL,
6.0 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A
suspension of N,N-diisopropyl-4-methylbenzamide 1e (660 mg, 3.0 mmol) in heptane (3.0 mL)
was added dropwise and stirred for 15 min at 0 °C. Chlorotrimethylsilane (952 µL, 7.5 mmol)
was added and stirred for 1 h at 0 °C and 2 M HCl (20 mL) was slowly added. The residue was
extracted with ethyl acetate (3 × 20 mL) and organic layers were combined, washed with water
(2 × 20 mL) and brine (10 mL), dried over Na2SO4, and concentrated to dryness. The product
was purified by silica gel column chromatography eluting with cyclohexane/ethyl acetate (9/1)
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yielded 4e (772 mg, 88%) as a colorless solid, m.p. 53–54 °C. H NMR (400 MHz, CDCl3): δ
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7.17 (d, J = 8.4 Hz, 2H), 6.98 (d, J = 8.4 Hz, 2H), 4.25–3.25 (m, 2H), 2.08 (s, 2H), 1.75–0.75 (m,
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12H), -0.02 (s, 9H). C NMR (100 MHz, CDCl3): δ 171.4, 141.4, 134.5, 127.8, 125.8, 27.1,
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20.8, -2.0 ppm. MS–EI [M]+: 291.3, C17H29NOSi requires 291.2.
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N,N-Diisopropyl-2-[(trimethylsilyl)methyl]benzamide, 4f25
Under inert atmosphere, a mixture of KOtBu (673 mg, 6.0 mmol) in heptane (7.5 mL) at 0 °C
was treated with BuLi (2.55 mL, 2.35 M in hexanes, 6.0 mmol), followed by TMP(H) (1.0 mL,
6.0 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A
suspension of N,N-diisopropyl-2-methylbenzamide 1f (660 mg, 3.0 mmol) in heptane (3.0 mL)
was added dropwise and stirred for 15 min at 0 °C. Chlorotrimethylsilane (952 µL, 7.5 mmol)
was added and stirred for 1 h at 0 °C and 2 M HCl (20 mL) was slowly added. The residue was
extracted with ethyl acetate (3 × 20 mL) and organic layers were combined, washed with water
(2 × 20 mL) and brine (10 mL), dried over Na2SO4, and concentrated to dryness. The product
was purified by silica gel column chromatography eluting with cyclohexane/ethyl acetate (8/2)
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yielded 4f (429 mg, 49%) as a colorless oil. H NMR (400 MHz, CDCl3): δ 7.22–7.16 (m, 1H),
7.09–7.03 (m, 3H), 3.68 (m, 1H), 3.58 (m, 1H), 2.05 (s, 2H), 1.57–1.55 (m, 6H), 1.12 (d, J = 6.8
13
Hz, 3H), 1.04 (d, J = 6.8 Hz, 3H), 0.03 (s, 9H). C NMR (100 MHz, CDCl3): δ 170.7, 137.3,
136.8, 128.8, 127.7, 125.2, 124.1, 50.6, 45.5, 23.8, 20.9, 20.8, 20.6, 20.4, -1.10 ppm. MS–EI
[M]+: 291.7, C17H29NOSi requires 291.2.
N,N-Diethyl-4-[(trimethylsilyl)methyl]benzenesulfonamide, 4g20a
Under inert atmosphere, a mixture of KOtBu (673 mg, 6.0 mmol) in heptane (7.5 mL) at 0 °C
was treated with BuLi (2.55 mL, 2.35 M in hexanes, 6.0 mmol), followed by TMP(H) (1.0 mL,
6.0 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A
suspension of N,N-diethyl-4-methylbenzenesulfonamide 1g (682 mg, 3.0 mmol) in heptane (3.0
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mL) was added dropwise and stirred for 15 min at 0 °C. Chlorotrimethylsilane (952 µL, 7.5
mmol) was added and stirred for 1 h at 0 °C and 2 M HCl (20 mL) was slowly added. The
residue was extracted with ethyl acetate (3 × 20 mL) and organic layers were combined, washed
with water (2 × 20 mL) and brine (10 mL), dried over Na2SO4, and concentrated to dryness. The
product was purified by silica gel column chromatography eluting with cyclohexane/ethyl
acetate (8/2) yielded 4g (584 mg, 65%) as a colorless solid. m.p. 45–47 °C. 1H NMR (400 MHz,
CDCl3): δ 7.64 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 3.23 (q, 4H), 2.16 (s, 2H), 1.10 (t,
6H), -0.02 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 146.2, 135.8, 128.2, 127.0, 41.9, 27.7, 14.0, -
2.0 ppm. MS–EI [M]+: 299.2, C14H25NO2SSi requires 299.5.
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Trimethyl(3-methylbenzyl)silane, 4h26
Under inert atmosphere, a mixture of KOtBu (673 mg, 6.0 mmol) in heptane (7.5 mL) at 0 °C
was treated with BuLi (2.55 mL, 2.35 M in hexanes, 6.0 mmol), followed by TMP(H) (1.0 mL,
6.0 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
of m-xylene 1h (367 µL, 3.0 mmol) in heptane (1.0 mL) was added dropwise and stirred for 15
min at 0 °C. Chlorotrimethylsilane (952 µL, 7.5 mmol) was added and stirred for 1 h at 0 °C and
2 M HCl (20 mL) was slowly added. The residue was extracted with diethyl ether (3 × 20 mL)
and organic layers were combined, washed with water (2 × 20 mL) and brine (10 mL), dried over
Na2SO4, and concentrated to dryness. The product was purified by silica gel column
chromatography eluting with cyclohexane yielded 4h (502 mg, 94%) as a colorless oil. 1H NMR
(400 MHz, CDCl3): δ 7.13–7.08 (m, 1H), 6.91–6.86 (m, 1H), 6.84–6.78 (m, 2H), 2.30 (s, 3H),
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2.04 (s, 2H), -0.01 (s, 9H). C NMR (100 MHz, CDCl3): δ 140.4, 137.5, 128.9, 128.0, 125.1,
124.6, 26.9, 21.4, -1.9 ppm. HRMS–EI [M]+: 178.1179, C11H18Si requires 178.1178.
(3-Methoxy-5-methylbenzyl)trimethylsilane, 4i
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Under inert atmosphere, a mixture of KOtBu (673 mg, 6.0 mmol) in heptane (7.5 mL) at 0 °C
was treated with BuLi (2.55 mL, 2.35 M in hexanes, 6.0 mmol), followed by TMP(H) (1.0 mL,
6.0 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
of 3,5-dimethylanisole 1i (424 µL, 3.0 mmol) in heptane (1.0 mL) was added dropwise and
stirred for 15 min at 0 °C. Chlorotrimethylsilane (952 µL, 7.5 mmol) was added and stirred for 1
h at 0 °C and 2 M HCl (20 mL) was slowly added. The residue was extracted with diethyl ether
(3 × 20 mL) and organic layers were combined, washed with water (2 × 20 mL) and brine (10
mL), dried over Na2SO4, and concentrated to dryness. The product was purified by silica gel
column chromatography eluting with cyclohexane/ethyl acetate (95/5) yielded 4i (625 mg, 95%)
as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 6.60–6.40 (m, 2H), 6.39–6.27 (m, 1H), 3.76 (s,
3H), 2.28 (s, 3H), 2.02 (s, 2H), 0.00 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 159.5, 141.9, 138.9,
121.6, 110.8, 110.1, 55.0, 27.1, 21.6, -1.8 ppm. HRMS–EI [M]+: 208.1289, C12H20OSi requires
208.1283.
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(2-Methoxy-3-methylbenzyl)trimethylsilane, 4j
Under inert atmosphere, a mixture of KOtBu (673 mg, 6.0 mmol) in heptane (7.5 mL) at 0 °C
was treated with BuLi (2.55 mL, 2.35 M in hexanes, 6.0 mmol), followed by TMP(H) (1.0 mL,
6.0 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
of 2,6-dimethylanisole 1j (425 µL, 3.0 mmol) in heptane (1.0 mL) was added dropwise and
stirred for 15 min at 0 °C. Chlorotrimethylsilane (952 µL, 7.5 mmol) was added, stirred for 1 h at
0 °C and 2 M HCl (20 mL) was slowly added. The residue was extracted with diethyl ether (3 ×
20 mL) and organic layers were combined, washed with water (2 × 20 mL) and brine (10 mL),
dried over Na2SO4, and concentrated to dryness. The product was purified by silica gel column
chromatography eluting with cyclohexane/ethyl acetate (99/1) yielded 4j (495 mg, 79%) as a
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colorless oil. H NMR (400 MHz, CDCl3): δ 6.92–6.84 (m, 3H), 3.69 (s, 3H), 2.29 (s, 3H), 2.08
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(s, 2H), 0.00 (s, 9H). C NMR (100 MHz, CDCl3): δ 155.9, 133.5, 130.8, 127.6, 127.2, 123.5,
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59.5, 20.4, 16.3, -1.4 ppm. HRMS–EI [M]+: 208.1290, C12H20OSi requires 208.1283.
Benzyltrimethylsilane, 4k12
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Under inert atmosphere, a mixture of KOtBu (673 mg, 6.0 mmol) in heptane (7.5 mL) at 0 °C
was treated with BuLi (2.55 mL, 2.35 M in hexanes, 6.0 mmol), followed by TMP(H) (1.0 mL,
6.0 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
of toluene 1k (320 µL, 3.0 mmol) in heptane (1.0 mL) was added dropwise and stirred for 15
min at 0 °C. Chlorotrimethylsilane (952 µL, 7.5 mmol) was added, stirred for 1 h at 0 °C and 2
M HCl (20 mL) was slowly added. The residue was extracted with diethyl ether (3 × 20 mL) and
organic layers were combined, washed with water (2 × 20 mL) and brine (10 mL), dried over
Na2SO4, and concentrated to dryness. The product was purified by silica gel column
chromatography eluting with cyclohexane yielded 4k (351 mg, 72%) as a colorless oil. 1H NMR
(400 MHz, CDCl3): δ 7.23–7.20 (m, 2H), 7.07 (m, 1H), 7.03–6.98 (m, 2H), 2.08 (s, 2H), -0.01 (s,
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9H). C NMR (100 MHz, CDCl3): δ 140.5, 128.1, 128.0, 123.8, 27.0, -1.9 ppm. MS–EI [M]+:
164.6, C10H16 requires 164.3.
Trimethyl(naphthalen-1-ylmethyl)silane, 4l27
Under inert atmosphere, a mixture of KOtBu (673 mg, 6.0 mmol) in heptane (7.5 mL) at 0 °C
was treated with BuLi (2.55 mL, 2.35 M in hexanes, 6.0 mmol), followed by TMP(H) (1.0 mL,
6.0 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
of 1-methylnapthalene 1l (426 µL, 3.0 mmol) in heptane (1.0 mL) was added dropwise and
stirred for 15 min at 0 °C. Chlorotrimethylsilane (952 µL, 7.5 mmol) was added, stirred for 1 h at
0 °C and 2 M HCl (20 mL) was slowly added. The residue was extracted with diethyl ether (3 ×
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20 mL) and organic layers were combined, washed with water (2 × 20 mL) and brine (10 mL),
dried over Na2SO4, and concentrated to dryness. The product was purified by silica gel column
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chromatography eluting with cyclohexane yielded 4l (494 mg, 77%) as a yellow oil. H NMR
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(400 MHz, CDCl3): δ 7.96–7.93 (m, 1H), 7.85–7.82 (m, 1H), 7.64–7.51 (m, 1H), 7.50–7.42 (m,
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2H), 7.40–7.32 (m, 1H), 7.18–7.14 (m, 1H), 2.58 (s, 2H), 0.00 (s, 9H). C NMR (100 MHz,
CDCl3): δ 137.2, 133.9, 131.7, 128.6, 125.5, 125.3, 125.2, 125.0, 124.8, 124.6, 23.4, -1.2 ppm.
MS–EI [M]+: 214.6, C14H18Si requires 214.4.
[(1,1'-Biphenyl)]-4-ylmethyl]trimethylsilane, 4m28
Under inert atmosphere, a mixture of KOtBu (673 mg, 6.0 mmol) in heptane (7.5 mL) at 0 °C
was treated with BuLi (2.55 mL, 2.35 M in hexanes, 6.0 mmol), followed by TMP(H) (1.0 mL,
6.0 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
of 4-phenyltoluene 1m (505 mg, 3.0 mmol) in heptane (1.0 mL) was added dropwise and stirred
for 15 min at 0 °C. Chlorotrimethylsilane (952 µL, 7.5 mmol) was added, stirred for 1 h at 0 °C
and 2 M HCl (20 mL) was slowly added. The residue was extracted with diethyl ether (3 × 20
mL) and organic layers were combined, washed with water (2 × 20 mL) and brine (10 mL), dried
over Na2SO4, and concentrated to dryness. The product was purified by silica gel column
chromatography eluting with cyclohexane yielded 4m (633 mg, 88%) as a colorless solid, m.p.
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42–44 °C. H NMR (400 MHz, CDCl3): δ 7.65–7.61 (m, 2H), 7.51 (d, J = 7.6 Hz, 2H), 7.48–
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7.43 (m, 2H), 7.37–7.32 (m, 1H), 7.11 (d, J = 7.6 Hz, 2H), 2.17 (s, 2H), 0.07 (s, 9H). C NMR
(100 MHz, CDCl3): δ 141.2, 139.7, 136.7, 128.7, 128.4, 126.8, 126.8, 126.7, 26.7, -1.9 ppm.
MS–EI [M]+: 240.6, C16H20 requires 240.4.
(Anthracen-9-ylmethyl)trimethylsilane, 4n29
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Under inert atmosphere, a mixture of KOtBu (673 mg, 6.0 mmol) in heptane (7.5 mL) at 0 °C
was treated with BuLi (2.55 mL, 2.35 M in hexanes, 6.0 mmol), followed by TMP(H) (1.0 mL,
6.0 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
of 9-methylantracene 1n (576 mg, 3.0 mmol) in heptane (3.0 mL) was added dropwise and
stirred for 15 min at 0 °C. Chlorotrimethylsilane (952 µL, 7.5 mmol) was added, stirred it for 1 h
at 0 °C and 2 M HCl (20 mL) was slowly added. The residue was extracted with diethyl ether (3
× 20 mL) and organic layers were combined, washed with water (2 × 20 mL) and brine (10 mL),
dried over Na2SO4, and concentrated to dryness. The product was purified by silica gel column
chromatography eluting with cyclohexane yielded 4n (434 mg, 55%) as a yellow solid, m.p. 45–
47 °C. 1H NMR (400 MHz, CDCl3): δ 8.26 (s, 1H), 8.22–8.19 (m, 2H), 8.02–8.00 (m, 2H), 7.51–
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7.45 (m, 4H), 3.20 (s, 2H), 0.03 (s, 9H). C NMR (100 MHz, CDCl3): δ 134.6, 132.1, 129.5,
129.4, 125.8, 125.1, 124.9, 124.0, 19.3, 0.0 ppm. MS–EI [M]+: 264.5, C18H20 requires 264.4.
2-[(Trimethylsilyl)methyl]pyridine, 4o30
Under inert atmosphere, a mixture of KOtBu (135 mg, 1.2 mmol), in heptane (2.5 mL) at 0 °C
was treated with BuLi (501 µL, 2.4 M in hexanes, 1.20 mmol), followed by TMP(H) (203 µL,
1.2 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
of α-picoline 1o (99 µL, 1.0 mmol) in heptane (0.5 mL) was added dropwise and stirred for 15
min at 0 °C. Chlorotrimethylsilane (317 µL, 2.50 mmol) was added, stirred for 1 h at 0 °C and
NH4Cl (10 mL) was slowly added. The residue was extracted with diethyl ether (3 × 15 mL) and
organic layers were combined, washed with water (2 × 10 mL) and brine (10 mL), dried over
Na2SO4, and concentrated to dryness. The product was purified by silica gel column
chromatography eluting with cyclohexane yielded 4o (143 mg, 87%) as a colorless oil. 1H NMR
(400 MHz, CDCl3): δ 8.40–8.30 (m, 1H), 7.53–7.45 (m, 1H), 7.00–6.90 (m, 2H), 2.33 (s, 2H),
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0.01 (s, 9H). C NMR (100 MHz, CDCl3): δ 161.2, 148.9, 135.7, 122.1, 119.1, 30.2, -1.8 ppm.
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MS–EI [M]+: 165.8, C9H15NSi requires 165.3.
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[(3-Methoxyphenylmethylene)bis(trimethylsilane)], 6a15
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Under inert atmosphere, a mixture of KOtBu (56 mg, 0.50 mmol), in heptane (1.0 mL) at 0 °C
was treated with BuLi (213 µL, 2.35 M in hexanes, 0.50 mmol) followed by TMP(H) (84 µL,
0.50 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
of (3-methoxybenzyl)trimethylsilane 4b (49 mg, 0.25 mmol) in heptane (0.5 mL) was added
dropwise and stirred for 15 min at 0 °C. Chlorotrimethylsilane (79 µL, 0.63 mmol) was added,
stirred for 1 h at 0 °C and 2 M HCl (5 mL) was added. The residue was extracted with diethyl
ether (2 × 15 mL) and organic layers were combined, washed with water (2 × 5 mL) and brine (5
mL), dried over Na2SO4, and concentrated to dryness. The product was purified by silica gel
column chromatography eluting with cyclohexane yielded 6a (59 mg, 88%) as a colorless oil. 1H
NMR (400 MHz, CDCl3): δ 7.09 (t, 1H), 6.60–6.56 (m, 1H), 6.53–6.48 (m, 2H), 3.77 (s, 3H),
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1.47 (s, 1H), 0.03 (s, 18H). C NMR (100 MHz, CDCl3): δ 159.3, 144.7, 128.9, 121.5, 114.6,
108.3, 54.9, 29.8, 0.02 ppm. HRMS–EI [M]+: 266.1533, C14H26OSi2 requires 266.1522.
{[(3,4,5-Trimethoxyphenyl)methylene]bis(trimethylsilane)}, 6b15
Under inert atmosphere, a mixture of KOtBu (56 mg, 0.50 mmol), in heptane (1.0 mL) at 0 °C
was treated with BuLi (213 µL, 2.35 M in hexanes, 0.50 mmol) followed by TMP(H) (84 µL,
0.50 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
of trimethyl-(3,4,5-trimethoxybenzyl)silane 4c (64 mg, 0.25 mmol) in heptane (0.5 mL) was
added dropwise and stirred for 15 min at 0 °C. Chlorotrimethylsilane (79 µL, 0.63 mmol) was
added, stirred for 1 h at 0 °C and 2 M HCl (5 mL) was added. The residue was extracted with
ethyl acetate (2 × 15 mL) and organic layers were combined, washed with water (2 × 5 mL) and
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brine (5 mL), dried over Na2SO4, and concentrated to dryness. The product was purified by silica
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72%) as a colorless oil. H NMR (400 MHz, CDCl3): δ 6.13 (s, 2H), 3.81 (s, 3H), 3.80 (s, 6H),
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1.40 (s, 1H), 0.04 (s, 18H). C NMR (100 MHz, CDCl3): δ 152.7, 138.9, 134.4, 105.7, 61.0,
55.9, 29.9, 0.2 ppm. MS–EI [M]+: 326.7, C16H30O3Si2 requires 326.6.
2-[Bis(Trimethylsilyl)methyl]-N,N-dimethylaniline, 6c15
Under inert atmosphere, a mixture of KOtBu (56 mg, 0.50 mmol), in heptane (1.0 mL) at 0 °C
was treated with BuLi (213 µL, 2.35 M in hexanes, 0.50 mmol) followed by TMP(H) (84 µL,
0.50 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A solution
of N,N-dimethyl-2-[(trimethylsilyl)methyl]aniline 4d (52 mg, 0.25 mmol) in heptane (0.5 mL)
was added dropwise and stirred for 15 min at 0 °C. Chlorotrimethylsilane (79 µL, 0.63 mmol)
was added, stirred for 1 h at 0 °C and 2 M HCl (5 mL) was slowly added. The residue was
extracted with diethyl ether (2 × 15 mL) and organic layers were combined, washed with water
(2 × 5 mL) and brine (5 mL), dried over Na2SO4, and concentrated to dryness. The product was
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NMR (400 MHz, CDCl3): δ 7.10 (m, 1H), 7.06–6.92 (m, 3H), 2.58 (s, 6H), 2.49 (s, 1H), 0.03 (s,
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18H). C NMR (100 MHz, CDCl3): δ 152.1, 139.2, 129.0, 123.8, 123.4, 120.3, 45.1, 20.1, 0.4
ppm. MS–EI [M]+: 279.3, C15H29NSi2 requires 279.8.
4-[Bis(trimethylsilyl)methyl]-N,N-diisopropylbenzamide, 6d15
Under inert atmosphere, a mixture of KOtBu (56 mg, 0.50 mmol), in heptane (1.0 mL) at 0 °C
was treated with BuLi (213 µL, 2.35 M in hexanes, 0.50 mmol) followed by TMP(H) (84 µL,
0.50 mmol) was slowly added. The resulting suspension was stirred for 5 min at 0 °C. A
suspension of N,N-diisopropyl-4-[(trimethylsilyl)methyl] benzamide 4e (73 mg, 0.25 mmol) in
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