After-effects of lithium-mediated alumination of 3-iodoanisole: Isolation of molecular salt elimination and trapped-benzyne products

Article abstract of DOI:10.1039/c2dt11893a

Gaining a deeper understanding of the modus operandi of heterometallic lithium aluminate bases towards deprotonative metallation of substituted aromatic substrates, we have studied the reactions and their aftermath between our recently developed bis-amido

Full text of DOI:10.1039/c2dt11893a

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PAPER
After-effects of lithium-mediated alumination of 3-iodoanisole: isolation of
molecular salt elimination and trapped-benzyne products†
Elaine Crosbie, Alan R. Kennedy, Robert E. Mulvey* and Stuart D. Robertson*
Received 7th October 2011, Accepted 21st November 2011
DOI: 10.1039/c2dt11893a
Gaining a deeper understanding of the modus operandi of heterometallic lithium aluminate bases
towards deprotonative metallation of substituted aromatic substrates, we have studied the reactions and
their aftermath between our recently developed bis-amido base ‘iBu2Al(m-TMP)2Li’ 3 and
3-halogenated anisoles. Ortho-metallation of 3-iodoanisole with 3 results in a delicately poised
heterometallic intermediate whose breakdown into homometallic species and benzyne cannot be
suppressed, even at low temperature or in a non-polar solvent (hexane). Homometallic components
[LiI·TMP(H)]4 (5) and iBu2Al(TMP)·THF (6) have been isolated while the reactive benzyne
intermediate has been trapped via Diels–Alder cyclization with 1,3-diphenylisobenzofuran yielding
1-methoxy-9-10-diphenyl-9-10-epoxyanthracene (7). In polar THF solution, nucleophilic addition of
LiTMP across the benzyne functionality followed by electrophilic quenching with iodine yields the
trisubstituted aromatic species 1-(2-iodo-3-methoxyphenyl)-2,2,6,6-tetramethylpiperidide (8).
Compounds 5–8 have been characterized by single-crystal X-ray diffraction in the solid state and
multinuclear NMR spectroscopy in solution. By considering these collated results, a plausible reaction
mechanism has been proposed for the breakdown of the aforementioned intermediate bimetallic
framework. Interestingly, the metallation reaction can be controlled by changing to 3-chloroanisole
with an excess of base 3, as evidenced by electrophilically trapping the deprotonated aromatic with
iodine to give 2-iodo-3-chloroanisole (9).
Introduction
Alkali-Metal Mediated Metallation (AMMM) is a recent ad-
vance in deprotonative metallation (C–H to C–metal exchange)
which shows considerable promise for the synthetic chemistry
community.1 Involving the juxtaposition of a typically powerful,
sometimes indiscriminate metallating reagent such as an alkali-
Fig. 1 Generic synthesis of a typical mixed-metal base.
metal alkyl or amido compound (R–MI or R2N–MI) with a
weaker yet more discriminate metallating reagent (RxMx, x >
polydeprotonations of multi-C–H containing substrates.4 While
this field has been dominated largely by MgII and ZnII as the
reactivity enhanced ex-subordinate metal, the concept has been
2
1) into a single ligand-shared molecular compound (which
seemingly displays the reactivity of the alkali-metal coupled
with the selectivity/functional group tolerance of the subordinate
metal—see Fig. 1 for a general example where x = 2), this method
is attractive due to its utility in relatively cheap, non-polar solvents
without the need for non-ambient temperature regimes.
Economic advantages aside, AMMM is also attractive from a
fundamental chemistry standpoint since not only can it outper-
form many homometallic reagents, it can also lead to deprotona-
tion of poorly acidic substrates (with high pKa values) typically
considered inert towards metal–hydrogen exchange,3 or to unusual
extended recently to include other metals such as FeII,5 MnII
6
and CdII,7 amongst others.8 One of the key recent advances
has involved the extension to a metal which is in the +3
oxidation state, namely AlIII.9 This has resulted in a myriad of
novel chemistry being developed, including a-C–H-deprotonation
of typically unreactive (towards metallation) polyamine Lewis
donors such as TMEDA 10 or PMDETA,10b a-C–H-deprotonation
of the cyclic ethers THF and THP,11 and even the astonishing
generation and trapping of a TMP2- dianion from the C,N-
bisdeprotonation of TMP(H).12 A particularly attractive facet
of Alkali-Metal Mediated Alumination (AMMAl) is the high
halogen tolerance which has been documented by the bases
(TMP)3Al·3LiCl (1, Knochel),13 iBu3Al(TMP)Li (2, Uchiyama—
WestCHEM, Department of Pure and Applied Chemistry, University of
Strathclyde, Glasgow, G1 1XL. E-mail: r.e.mulvey@strath.ac.uk
† CCDC reference numbers 815746, 847968–847970. For crystallographic
data in CIF or other electronic format see DOI: 10.1039/c2dt11893a
i
the first reported base of this type),14 and Bu2Al(TMP)2Li (3,
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our own group);15 heterometallic alkali-metal aluminate bases will
carry out directed ortho metallation (metal–hydrogen exchange)
reactions of halo-substituted aromatic molecules in preference to
metal–halogen exchange. While alkyl-amido bases 2 and 3 are
clearly constitutionally very similar, they can display markedly
different reactivity; 2 is stable in THF, a solvent in which
it is routinely utilized, while 3 deprotonates a stoichiometric
amount of THF in bulk hexane solution. With this in mind
and inspired by Uchiyama’s recent report of thermally controlled
ortho-deprotonation of 3-bromo-N,N-diisopropylbenzamide with
mono-TMP base 2,16 we investigated whether bis-TMP base
3 can likewise ortho-deprotonate 3-halogenated ortho-directing
substituted aromatics. Focusing on 3-haloanisoles, as reported
herein, we learn much about the fate of the different metals and
different ligands following their ortho-alumination.
Fig. 2 Molecular structure of tetrameric 5. Thermal ellipsoids are drawn
at the 50% probability level and all carbon bound H atoms have been
removed for clarity. Primed atom labels represent symmetry generated
atoms via symmetry operation -x, y, 0.5 - z.
Results and discussion
The attempted deprotonation of 3-iodoanisole by THF solvated
lithium aluminate base 3 to give complex 4 was carried out in bulk
hexane solution as depicted by eqn (1).17
gallium or indium species.23 Like its predecessors mentioned
above, 5 consists of interpenetrating Li4 and I4 tetrahedra, with
lone pair donation from the TMP(H) nitrogen atoms to the
Lewis acidic lithium cations giving Li a distorted tetrahedral
environment overall. From the ring-stacking principle developed
by Snaith, which is widely applicable throughout lithium structural
chemistry, 5 could be alternatively described as a face-to-face stack
of two dimeric (LiI)2 rings.24 Secondary amine TMP(H) is not
a common Lewis donor towards electron deficient metals, with
most crystallographically authenticated examples involving either
late transition metals25 or group 13 metals.26 However, TMP(H)
(1)
◦
Even at a temperature as low as -78 C, the mixture instantly
precipitated a white solid. This solid was removed by vacuum
filtration and the resulting solution was kept overnight at -35 ◦C,
yielding a decent crop of colourless crystals. A single crystal
structural determination revealed that this crystalline product was
in fact the C2 symmetric amine solvated lithium iodide cubane
[LiI·TMP(H)]4, 5 (Fig. 2, see Table 1 for selected bond parameters).
Since Snaith first reported a HMPA solvated LiCl cubane
tetramer in 1984,18 examples of Lewis donor-solvated (LD) alkali-
metal halide cubanes [(MX·LD)4] have sporadically graced the
literature. Surprisingly, only lithium examples with alkali-metal
bound Lewis donors are known, including those of Et2O,19 Et3N,20
27
solvation of lithium is precedented, with both base 2 and a
dilithium zincate28 having been stabilized via a Li ◊ ◊ ◊ N(TMPH)
interaction. The two distinct TMP(H) ligands in 5, which both
reside in the more typical chair conformation, lie tilted towards
one of the adjacent iodide anions as displayed by their one smaller
(mean 101.7◦) and two larger N–Li–I bond angles (mean 125.6◦).
The NH bond (the H atom was located and independently refined
in the crystallographic study) lies almost parallel to the Li–I bond
representing the smaller angle (H–N–Li–I torsion angle = 5.8/2.2◦
for Li1 and Li2 respectively) with an N(H) ◊ ◊ ◊ I distance of 3.42(3)
HN = PR3 (R = Bu, Ph)21 and O = PH(tBu)2.22 While heavier alkali-
metal halide cubanes such as those of KF or CsF are known, these
are stabilized via halide–Lewis acid interactions involving trisalkyl
t
˚
and 3.34(2) A for H1–I1 and H2–I2 respectively. The cubane itself
is high◦ly distorted [I–Li–I, 97.1(3)–102.3(2)◦; Li–I–Li, 77.1(2)–
˚
81.8(2) ] with Li–I bond lengths [range 2.799(9)–2.907(7) A; mean
◦
˚
˚
Table 1 Selected bond lengths (A) and angles ( ) of complex 5
2.847 A] in accord with those in previously reported LiI cubanes,
as are the dative Li ◊ ◊ ◊ N distances when compared to those in the
tertiary amine solvated [LiI·NEt3]4.
Li–I
Li–N
To the best of our knowledge, somewhat surprisingly complex 5
represents the first example of a secondary amine stabilized alkali-
metal halide cubane. Lack of solubility in common non-donating
NMR solvents was a problem, precluding us from obtaining such
spectra. Polar THF-d8 was used but this displaced TMP(H) as
the donor, giving a spectrum of free secondary amine. Infra-
red characterization to confirm the presence of the secondary
amine functionality was also attempted; however this proved
uninformative due to either the hygroscopic nature of the product
resulting in peaks masking the region of interest or the inherently
weak absorptions of the functionality in question.
Li1–I1
Li1–I1¢
Li1–I2
2.879(8) Li2–I1
2.843(7) Li2–I2
2.907(7) Li2–I2¢
2.843(7) Li1–N1
2.799(9) Li2–N2
2.814(7)
2.111(9)
2.097(6)
I–Li–I
Li–I–Li
N–Li–I
I1–Li1–I1¢ 102.3(2) Li1–I1–Li1¢ 77.1(2)
I1–Li1–I2 98.4(2)
I1¢–Li1–I2 97.7(2)
I1–Li2–I2 101.9(2) Li1–I2–Li2
I1–Li2–I2¢ 99.9(2)
I2–Li2–I2¢ 97.1(3)
N1–Li1–I1 102.4(3)
N1–Li1–I1¢ 126.0(4)
N1–Li1–I2 124.9(3)
N2–Li2–I1 101.1(3)
N2–Li2–I2 125.1(3)
N2–Li2–I2¢ 126.6(3)
Li1–I1–Li2
Li1¢–I1–Li2 80.4(2)
79.3(2)
Li1–I2–Li2¢ 79.8(2)
Li2–I2–Li2¢ 81.8(2)
79.0(2)
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Table 2 Crystallographic data and refinement details for compounds 5–8
5
6·THF
7
8
Empirical formula
Mr
C36H76I4Li4N4
1100.37
Monoclinic
C2/c
25.5194(9)
10.7301(2)
19.8807(6)
118.682(4)
4775.9(2)
4
1.530
11422
5807
4687
C21H44AlNO
353.55
Orthorhombic
Pbca
10.4710(2)
12.1167(2)
35.1416(2)
90
4458.55(14)
8
1.053
16838
5203
3858
C27H20O2
376.43
Monoclinic
P21/n
10.7897(3)
17.0361(4)
11.4052(3)
110.652(3)
1961.72(9)
4
1.275
9138
4795
3789
C16H24INO
373.26
Orthorhombic
Fdd2
12.8821(5)
59.0714(18)
8.4330(4)
90
6417.2(4)
16
1.545
15680
4065
3931
Crystal system
Space group
˚
a/A
˚
b/A
˚
c/A
b (◦)
3
˚
V/A
Z
rc/g cm-3
Reflns measured
Unique reflns
Observed reflns
Rint
0.0354
1.082
0.0294
1.092
0.0217
1.017
0.0335
1.083
GooF
R [on F , obs rflns only]
0.0409
0.0794
1.070/-0.600
0.0559
0.1126
0.308/-0.238
0.0460
0.1044
0.327/-0.237
0.0212
0.0473
0.444/-0.388
wR [on F2,all data]
-3
˚
Largest diff. peak/hole/e A
All attempts at a rational synthesis of 5 were unsuccessful.
For example, LiI would not dissolve in non-polar solvents in the
presence of stoichiometric amounts of TMP(H) or even in neat
TMP(H) while in situ generated LiI (either from Me3SiI + MeLi or
NH4I + nBuLi) immediately precipitated from the mixture. When
polar THF was used as a solvent, TMP(H) failed to displace this
with the only tangible product identified being the known solvate
LiI·3THF.29
quantities it is conceivable that the less sterically bulky donor
(THF) will bind preferentially to the more sterically encumbered
stronger Lewis acidic metal (in this case Al), leaving only TMP(H)
available to solvate the electron-poor lithium.
1
This pathway was further supported by a H NMR spectrum
of the residues left over after 5 had been isolated which showed
resonances consistent with the neutral dialkylaluminium amide
6·THF. We recently reported the synthesis of 6 as an oil which
was shown by DOSY NMR spectroscopy to exist as a monomer,
almost certainly because of the short Al–NTMP distance, coupled
with the steric bulk around the TMP nitrogen, which meant
that dimerization to give four-coordinate Al centres could not
occur.15,33 Consequently we prepared an authentic sample of
6·THF by simply adding a molar equivalent of THF to pre-
prepared 6 in hexane. Upon cooling to -34 ◦C, the resultant
crystals were confirmed as being the desired product via a
An NMR spectroscopic study on both the white precipitate
isolated initially and the subsequently grown crystals of 5 suggest
that these two products are identical. This result implies that the
putative metallated product 4 must rapidly decompose, almost
certainly via a benzyne mechanism, and that unlike Uchiyama’s
protocol with base 2, the suppression of this decomposition is not
possible since it cannot be stopped even at -78 ◦C. The fact that a
product containing a Li–I fragment is produced, even though it is
almost certain that alumination occurs ortho to the halide, allows
us to propose a potential pathway by which the decomposition of
the putative aluminated intermediate occurs (eqn (2)—our recent
report of a variety of ortho-aluminated substituted aromatics
provides us with confidence that it is an alumination, that is,
formation of 4, which first occurs here).
While there are many documented examples of complexes
of general formula “Li(m-anion)2Al(anion)2”, from a search of
the Cambridge Structural Database30 surprisingly none involve
a mixed organic anion/iodide anion bridging set,31 perhaps in
part due to the appreciably different M–I and M–C/M–N bond
lengths which would lead to a severely distorted M–I–M–C/N
four atom ring. It is therefore highly likely that putative Li(m-I)(m-
TMP)AliBu2 rapidly disproportionates to 5 and 6·THF.32 Since the
Lewis donors TMP(H) and THF are only present in stoichiometric
1
combination of X-ray crystallography (Fig. 3), and H and 13C
NMR spectroscopy.
To verify that benzyne formation is a key step during this pro-
cess, we repeated this reaction and then attempted to trap any ben-
zyne formed via a Diels–Alder cyclization by adding a diene (1,3-
diphenylisobenzofuran) at -78 ◦C, before allowing the reaction to
naturally warm to room temperature (Fig. 4). After work up and
purification (see experimental section for full details) crystals of 1-
methoxy-9-10-diphenyl-9-10-epoxyanthracene (7) were obtained
1
in near quantitative yield. H and 13C NMR spectroscopy (see
Fig. 5 for the assigned 13C spectrum) plus elemental analysis
established that 7 was the final product. In particular, the 13C
NMR spectrum displayed all 23 expected resonances which could
be easily assigned to one of five environments—methyl (orange),
quaternary aliphatic (red), aromatic C–H (green), ortho/meta
(2)
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An interesting parallel can be drawn here with alkali-
metal mediated zincations. Bisalkyl TMP zincates formulated as
“R2Zn(TMP)Li”34 (which are also adept at chemoselective de-
protonations in both typical34a,35 and atypical36 positions) display
contrasting reactivity in the zincation of 3-halogenated substituted
aromatic molecules; with the metallated product extruding ben-
t
zyne when R = Me but not when R = Bu, suggesting steric bulk is
critical in preventing benzyne formation (Fig. 6a).37 It is pertinent
to note that dual alkyl/amido alkali-metal zincates depend on the
identity of the alkali-metal and Lewis donor for their reactivity
and can operate via a two step mechanism whereby the initial
deprotonation occurs via TMP basicity [generating TMP(H)];
this amine is subsequently deprotonated by an alkyl group of
the deprotonated substrate containing intermediate resulting in
re-integration of TMP into the framework and loss of alkane
(Fig. 6b).38 This however relies on the accessibility of the zinc
centre by the Lewis donating TMP(H) and is prevalent in lighter
alkali-metal congeners (Li, Na) which tend to be monomeric with
coordinatively unsaturated 3-coordinate Zn as opposed to heavier
potassium zincates which oligomerize and have 4-coordinate
inaccessible Zn centres of diminished Lewis acidity.39
Fig. 3 Molecular structure of 6·THF. Thermal ellipsoids are drawn at
the 50% probability level and all H atoms◦have been removed for clarity.
˚
Selected bond lengths (A) and angles ( ): Al1–N1 1.865(1), Al1–O1
1.951(1), Al1–C10 1.992(2), Al1–C14 2.011(2); N1–Al1–O1 100.99(6),
N1–Al1–C10 122.11(7), N1–Al1–C14 119.67(7), O1–Al1–C10 99.45(7),
O1–Al1–C14 101.98(7), C10–Al1–C14 107.80(7).
An analogous two step mechanism can be ruled out for the
lithium aluminates 2 and 3 discussed thus far since apart from
deprotonated substrate, the only other anions present when 2
i
executes a deprotonation are Bu groups, and if alkyl induced
deprotonation were to occur at any stage then volatile Bu–H
i
Fig. 4 Diels–Alder cyclization with the methoxy-substituted benzyne
intermediate to give the polycycle 7.
would be permanently lost from the system before it could re-
enter. The presence of a TMP anion bound to a coordinatively
saturated (4 coordinate) Al centre in our system here would thus
appear to be key to the high reactivity of this intermediate and
may explain why this breaks down with extrusion of a benzyne.
However, while it is tempting at this stage to unequivocally assign
the reactivity to anionic effects, it is important to remember that
solvent (polar THF versus non-polar hexane) in the zincate systems
above plays a highly important role. Likewise, 2 is routinely used
as a THF solution, while 3 is used in hexane as it a-deprotonates
C–H (blue) and aromatic C (black). The identity of the product was
corroborated by a single crystal molecular structure determination
(see inset of Fig. 5).
The results described thus far show that bases 2 and 3
display a completely different reactivity towards 3-halogenated
substituted aromatic substrates, since Uchiyama et al. utilized a
low temperature regime to sedate their aluminated product prior
to electrophilic quenching.
1
Fig. 5 13C { H} NMR spectrum of 7 with molecular structure inset (thermal ellipsoids at 50% probability level and H atoms omitted for clarity. Oxygen
atoms are shaded red).
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Fig. 6 (a) contrasting reactivity of bisalkyl lithium TMP zincates and (b) two-step mechanism of bisalkyl alkali-metal TMP zincate displaying overall
alkyl basicity. R = ortho directing group, X = halide.
THF, vide supra. Consequently, we decided to repeat the attempted
synthesis of complex 4 in THF at -78 ◦C, anticipating firstly
that the low temperature would suppress THF deprotonation and
secondly that the more acidic 3-iodoanisole would be preferentially
deprotonated. In practice, no white precipitate was witnessed when
3-iodoanisole was introduced to a stirring solution of pre-prepared
3 in THF at -78 ◦C. After stirring for two hours, a stoichiometric
solution of elemental iodine in THF was introduced in an attempt
to prepare 2,3-diiodoanisole.40 After work-up and purification via
column chromatography, a crystalline product (8) was obtained.
NMR spectroscopy and a molecular structure determination (Fig.
7) showed the identity of 8 to in fact be the hitherto unknown N-
substituted TMP compound 1-(2-iodo-3-methoxyphenyl)-2,2,6,6-
tetramethylpiperidide.
The 1H NMR spectrum of 8 suggests that the TMP chair is
conformationally locked since the methyl, b and g environments
are all resolved into twice the number of resonances typically
anticipated for a TMP compound. This cascade of metallation
of meta-halogenated substituted aromatics, elimination of metal
halide/formation of benzyne and then LiTMP addition across
the benzynyl functionality has previously been documented by
Mortier41 amongst others.42
It should be noted here that prior to column purification, a 1H
NMR spectrum of the crude product was obtained whose aromatic
region showed product 8 to be present in about an equimolar
amount to the starting substrate, 3-iodoanisole. This result allows
us to propose a final hypothesis for the fate of the benzyne
generated once LiI is expelled from the putative metallated
product 4. If the benzyne reacts with the LiTMP component
of the base 3·THF quicker than the base can deprotonate the
remaining substrate, then additional iBu2Al(TMP)·THF (6·THF)
will be generated along with 1-(2-lithio-3-methoxyphenyl)-2,2,6,6-
tetramethylpiperidide (which itself is simply quenched with io-
dine). As a consequence of the base being consumed this way,
50% of the 3-iodoanisole will remain unreacted, as seen here. This
allows us to propose a modification of eqn (2) showing the fate of
all the intermediate products (eqn (3)).
At this juncture we speculated that perhaps the relatively weak
C–I bond was responsible for the failure to ortho deprotonate
the substrate without causing further decomposition reactions,
so consequently we turned our attention to the 3-bromo- and
3-chloroanisole congeners. However, on moving to the bromo
congener an analogous reactivity was witnessed. The chloro-
substituted derivative however yielded 2-iodo-3-chloroanisole (9)43
in only 25% yield after being subjected to metallation with
one molar equivalent of base 3 at -78 ◦C for 2 h followed by
electrophilic quenching with iodine. A longer reaction time (8 h)
had no significant effect on the yield, however, using a four fold
excess of base 3 furnished a near-quantitative yield of 98% of 9.
Fig. 7 Molecular structure of N-substituted TMP derivative 8. Thermal
ellipsoids are drawn at the 50% probability level and all H atoms have
◦
˚
been removed for clarity. Selected bond lengths (A) and angles ( ): C1–O1
13.71(3), C2–I1 2.107(2), C3–N1 1.436(3); O1–C1–C2 116.4(2), C1–C2–I1
117.6(2), C3–C2–I1 120.7(2), C2–C3–N1 119.6(2).
Tri-substituted benzene 8 can be logically considered as the
product of Li–TMP addition across the benzyne functionality,
followed by replacement of the lithium atom via an iodine quench.
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(3)
TMP(H) solvate 5 precipitated immediately as a white pow-
der and was collected by vacuum filtration. The filtrate was
left overnight at -35 ◦C yielding a batch of X-ray quality
crystals of 5 (combined yield of powder and crystals 0.45 g,
82%).
Conclusion
We have shown that seemingly innocuous changes to a bimetal-
lic framework [in this case switching from the alkyl rich
iBu3(TMP)AlLi to the amide rich Bu2(TMP)2AlLi] can dramat-
i
ically alter the pathway that a metallation reaction will follow.
While ortho-deprotonation at the 2-position of 3-halogenated
anisoles is facile with the former, the increased reactivity of the
latter (due to the presence of a TMP anion in the deprotonated
intermediate not present in the former) causes breakdown of the
trapped deprotonated intermediate complex resulting in a series
of different homometallic and organic products due to competing
reactions. By mapping these products we have shed new light
on the processes and potential pitfalls one may encounter when
embarking on a deprotonative journey using such heterometallic
low-polarity metallators. While factors such as solvent and
temperature play an important role in controlling these reactions,
what is clear is that aluminium TMP bases are generally highly
tolerant of halogeno functionality, preferring metal—hydrogen
exchange over metal—halogen exchange.
El. analysis calc. for C36H76I4Li4N4 (Mr = 1100.40) C, 39.29; H,
6.96; N, 5.09; found: C, 39.73; H, 7.22; N, 4.24.
Synthesis of iBu2Al(TMP)·THF (6·THF)
Pre-prepared iBu2Al(TMP) (0.28 g, 1 mmol) was added to hexane
(5 mL) and THF (0.08 mL, 1 mmol) was introduced via syringe.
This solution was left overnight at -34 ◦C to yield the final product
as colourless crystals (0.25 g, 71%).
1H NMR (400.13 MHz, 298 K, C6D6): d = 0.28 [4H, d, 3J(H,H) =
3
6.40 Hz, Al–CH2], 1.15 [4H, m, THF], 1.25 [12H, d, J(H,H) =
6.40 Hz, iBu CH3], 1.36 [12H, s, TMP CH3], 1.48 [4H, t, 3J(H,H) =
6.29 Hz, TMP b], 1.76 [2H, m, TMP g], 2.08 [2H, sept, 3J(H,H) =
6.53 Hz, iBu CH], 3.57 ppm [4H, m, THF].
1
13C { H} (100.62 MHz, 298 K, C6D6): d = 18.7 [TMP g], 24.9
[THF], 26.8 [iBu CH], 28.5 [iBu CH2], 28.9 [iBu CH3], 34.5 [TMP
CH3], 41.6 [TMP b], 51.9 [TMP a], 69.7 ppm [THF].
El. analysis calc. for AlC21H44NO (Mr = 353.56) C, 71.34; H,
12.54, N, 3.96; found: C, 70.98; H, 13.21, N 4.15.
Experimental
General experimental
All reactions and manipulations were carried out under a protec-
tive argon atmosphere using either standard Schlenk techniques
or a glove box. All solvents were dried over Na/benzophenone
and freshly distilled prior to use. iBu2Al(m-TMP)2Li·THF (3) and
iBu2Al(TMP) were prepared by literature methods.15 3-iodoanisole
and 1,3-diphenylisobenzofuran were purchased from Aldrich and
used as received. 1H and 13C NMR spectra were recorded on
a Bruker AV400 MHz spectrometer (operating at 400.03 MHz
for 1H and 100.58 MHz for 13C). All 13C NMR spectra were
proton decoupled. Elemental (C, H, N) analyses were performed
by Denise Gilmour, University of Strathclyde Elemental Analysis
Service.
Synthesis of Diels–Alder product (1-methoxy-9-10-diphenyl-
9-10-epoxyanthracene) (7)
3-Iodoanisole (0.24 mL, 2 mmol) was added to a prepared solution
of 3 in hexane at -78 ◦C. 1,3-Diphenylisobenzofuran (0.54 g,
2 mmol) was added after a few minutes and the mixture was
allowed to stir and to warm to room temperature overnight.
Saturated aq. NH4Cl (40 mL) was added to quench the reaction
and the mixture was extracted with CHCl3 (30 mL ¥ 3). The
mixture was dried over MgSO4 and the solvent evaporated under
reduced pressure. The residue was purified by SiO2 column
chromatography using petroleum ether (100%), diethyl ether–
petroleum ether (1 : 10) and diethyl ether–petroleum ether (1 : 5) as
an eluent to give 1-methoxy-9-10-diphenyl-9-10-epoxyanthracene
(0.69 g, 92%).
Synthesis of [LiI·TMP(H)]4 (5)
A pre-prepared solution of 3 in hexane was cooled to -78 ◦C
and 3-iodoanisole was added via syringe. Lithium iodide
1H NMR (400.13 MHz, 298 K, C6D12): d = 3.66 [3H, s, OCH3],
3
6.66 [1H, d, J(H,H) = 7.46 Hz], 7.02–7.12 [4H, m], 7.37 [1H, d,
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3J(H,H) = 7.05 Hz], 7.47–7.58 [7H, m], 7.92 [2H, m], 8.01 ppm
Acknowledgements
[2H, m].
1
13C { H} (100.62 MHz, 298 K, C6D12): d = 55.6 [OCH3], 90.4
This work was generously sponsored by the U.K. Engineering and
Physical Sciences Research Council (award no. EP/F063733/1)
and the Royal Society via a Wolfson research merit award to
R.E.M.
[quaternary C], 91.8 [quaternary C], 111.4 [aromatic CH], 113.6
[aromatic CH], 120.5 [aromatic CH], 121.2 [aromatic CH], 125.4
[aromatic CH], 125.7 [aromatic CH], 127.1 [2C, phenyl CH], 127.8
[2C, phenyl CH], 128.0 [aromatic CH], 128.2 [aromatic CH], 128.5
[aromatic CH], 128.6 [2C, phenyl CH], 129.4 [2C, phenyl CH],
134.7 [aromatic C], 135.0 [aromatic C], 136.4 [aromatic C], 150.0
[aromatic C], 151.5 [aromatic C], 153.6 [aromatic C], 153.8 ppm
[aromatic C].
References
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2 Lewis donor identity and stoichiometry is clearly important as to
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a contacted ion-pair (CIP) structure: S. Merkel, D. Stern, J. Henn and
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Synthesis of
3 For the meta deprotonation of toluene see: (a) P. C. Andrikopolous, D.
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1-(2-iodo-3-methoxyphenyl)-2,2,6,6-tetramethylpiperidide (8)
LiTMP was prepared from TMP(H) (0.17 mL, 1 mmol) and
nBuLi (0.63 mL, 1.6 M in hex◦anes, 1 mmol) in THF (5 mL)
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i
4 For the bisdeprotonation of benzene and toluene see: (a) D. R.
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THF (5 mL) was added via cannula to give an in situ solution
of 3. 3-Iodoanisole (0.12 mL, 1 mmol) in THF at -78 ◦C was
added and this was stirred for 2 h. I2 (5 mL of a 1 M solution,
5 mmol) in dry THF was added to the reaction mixture and stirred
overnight. The mixture was diluted with saturated aq. NaHS2O3
(20 mL) and saturated aq. NH4Cl (40 mL) and extracted with
CHCl3 (30 mL ¥ 3). The organic layer was dried over MgSO4 and
solvent removed under reduced pressure. The residue was purified
by SiO2 column chromatography using hexane (100%) as an eluent
to give 1-(2-iodo-3-methoxyphenyl)-2,2,6,6-tetramethylpiperidide
(0.36 g, 48%).
´
5 P. Albore´s, L. M. Carrella, W. Clegg, P. Garc´ıa-Alvarez, A. R. Kennedy,
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6 V. L. Blair, W. Clegg, R. E. Mulvey and L. Russo, Inorg. Chem., 2009,
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7 For excellent work on deprotonative cadmation utilizing a mixed metal
approach see the following paper and references cited therein: K.
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8 An alternative concept for direct metallation involves introduction of
the alkali-metal as a halide salt rather than an organo-lithium reagent.
For an excellent review of this approach by one of its leading proponents
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1H NMR (400.13 MHz, 298 K, CDCl3): d = 0.93 [6H, s, 2 ¥
CH3 of TMP], 1.30 [6H, s, 2 ¥ CH3 of TMP], 1.54–1.58 [2H, m, 1 ¥
bCH2 of TMP], 1.63–1.69 [1H, m, 1 ¥ gCH of TMP], 1.81–1.98
[2H, m, 1 ¥ bCH2 of TMP] and [1H, m, 1 ¥ gCH of TMP], 3.89
[3H, s, OCH3], 6.71 [1H, d, 3J(H,H) = 8.16 Hz, 1 ¥ aromatic C–H],
7.07 [1H, d, 3J(H,H) = 7.94 Hz, 1 ¥ aromatic C–H], 7.22 ppm [1H,
t, 3J(H,H) = 8.02 Hz, 1 ¥ aromatic C–H].
1
13C { H} (100.62 MHz, 298 K, CDCl3): d = 18.7 [1 ¥ gCH of
9 H. Naka, J. V. Morey, J. Haywood, D. J. Eisler, M. McPartlin, F. Garc´ıa,
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TMP], 25.7 [1 ¥ CH3 of TMP], 31.4 [1 ¥ CH3 of TMP], 41.2 [1 ¥
bCH2 of TMP], 56.1 [1 ¥ gCH of TMP], 56.5 [1 ¥ OCH3], 106.2
[1 ¥ aromatic C], 108.6 [1 ¥ aromatic CH], 124.3 [1 ¥ aromatic
CH], 127.9 [1 ¥ aromatic CH], 150.9 [1 ¥ aromatic C], 159.3 ppm
[1 ¥ aromatic C].
´
10 (a) J. Garc´ıa-Alvarez, D. V. Graham, A. R. Kennedy, R. E. Mulvey and
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´
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6.48; N, 3.75; found: C, 52.13; H, 6.85; N, 3.76.
´
11 E. Crosbie, P. Garc´ıa-Alvarez, A. R. Kennedy, J. Klett, R. E. Mulvey
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´
12 B. Conway, A. R. Kennedy, R. E. Mulvey, J. Garc´ıa-Alvarez and S. D.
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X-ray crystallography
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˚
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17 It should be noted that at no time did we ever witness deprotonation
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reaction always occurs at the site mutually ortho to both substituents.
To the best of our knowledge none of the other experts cited within
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Diffraction Diffractometers with Mo-Ka (l = 0.71073 A) radi-
ation. Structures were solved using SHELXS-97,44 and refined to
convergence on F2 against all independent reflections by the full-
matrix least-squares method using the SHELXL-97 program.44
CCDC 815746 and 847968–847970 contain the supplementary
crystallographic data for this paper. These can be obtained free
of charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
1838 | Dalton Trans., 2012, 41, 1832–1839
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The Royal Society of Chemistry 2012
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´
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The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 1832–1839 | 1839
©