Contrasting reactivity of mono- versus Bis-2,2,6,6-tetramethylpiperidide lithium aluminates towards polydentate lewis bases: Co-complexation versus deprotonation

Article abstract of DOI:10.1071/CH13157

Two closely related lithium alkylaluminium amides LiAl(TMP)2iBu2 and LiAl(TMP)iBu3 (TMP: 2,2,6,6-tetramethylpiperidide) have been compared in their reactivity towards six polydentate Lewis bases containing either N or O donor atoms or a mixed N,O donor set. Seven of the twelve potential organometallic products of these reactions, which were carried out in hexane solution, have been crystallographically characterised. Three of these structures, [Li(-Me2NCH2CHCH2CH2CHO)(-TMP)Al(iBu)2], [Li(-Me2NCH2CH2OCH2)(-TMP)Al(iBu)2], and [Li(-Me2NCH2CH2OCHCH2NMe2)(-TMP)Al(iBu)2] reveal that the bis-amide LiAl(TMP)2iBu2 deprotonates (aluminates) the multifunctional Lewis base selectively at the carbon atom adjacent to oxygen with the anion generated captured by the residue of the base. In contrast, the mono-amide LiAl(TMP)iBu3 in general fails to deprotonate the Lewis bases but instead forms co-complexes with them as evidenced by the molecular structures of [Me2NCH2CHCH2CH2CH2O·Li(-iBu)(-TMP)Al(iBu)2], [Me2NCH2CH2OMe·Li(- iBu)(-TMP)Al(iBu)2], and [MeOCH2CH2OMe·Li(-iBu)(-TMP)Al(iBu)2]. Providing an exception to this pattern, the mono-amide reagent deprotonates chiral R,R,-N,N,N′,N′-tetramethylcyclohexanediamine to afford [Li(-CH2NMeC6H10NMe2)2Al(iBu)2], the final complex to be crystallographically characterised. All new products have been spectroscopically characterised through 1H, 7 Li, and 13C NMR studies. Reaction mixtures have also been quenched with D2O and analysed by 2D NMR spectroscopy to ascertain the full metallation versus co-complexation picture taking place in solution.

Full text of DOI:10.1071/CH13157

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem. 2013, 66, 1189–1201
Full Paper
http://dx.doi.org/10.1071/CH13157
Contrasting Reactivity of Mono- versus Bis-2,2,6,6-
tetramethylpiperidide Lithium Aluminates Towards
Polydentate Lewis Bases: Co-Complexation Versus
Deprotonation
A
A
A
Ross Campbell, Elaine Crosbie, Alan R. Kennedy,
A B
,
A
A B
,
Robert E. Mulvey,
Rachael A. Naismith, and Stuart D. Robertson
A
WestCHEM, Department of Pure and Applied Chemistry,
University of Strathclyde, Glasgow, G1 1XL, UK.
Corresponding authors. Email: r.e.mulvey@strath.ac.uk;
stuart.d.robertson@strath.ac.uk
B
i
Two closely related lithium alkylaluminium amides LiAl(TMP)2 Bu2 and LiAl(TMP)iBu3 (TMP: 2,2,6,6-tetramethyl-
piperidide) have been compared in their reactivity towards six polydentate Lewis bases containing either N or O donor
atoms or a mixed N,O donor set. Seven of the twelve potential organometallic products of these reactions, which
were carried out in hexane solution, have been crystallographically characterised. Three of these structures, [Li(m-
Me2NCH2CHCH2CH2CHO)(m-TMP)Al(iBu)2], [Li(m-Me2NCH2CH2OCH2)(m-TMP)Al(iBu)2], and [Li(m-Me2NCH2
i
CH2OCHCH2NMe2)(m-TMP)Al(iBu)2] reveal that the bis-amide LiAl(TMP)2 Bu2 deprotonates (aluminates) the multi-
functional Lewis base selectively at the carbon atom adjacent to oxygen with the anion generated captured by the residue of
the base. In contrast, the mono-amide LiAl(TMP)iBu3 in general fails to deprotonate the Lewis bases but instead forms
co-complexes with them as evidenced by the molecular structures of [Me2NCH2CHCH2CH2CH2OꢀLi(m-iBu)(m-TMP)Al
(iBu)2], [Me2NCH2CH2OMeꢀLi(m-iBu)(m-TMP)Al(iBu)2], and [MeOCH2CH2OMeꢀLi(m-iBu)(m-TMP)Al(iBu)2]. Provid-
ing an exception to this pattern, the mono-amide reagent deprotonates chiral R,R,-N,N,N0,N0-tetramethylcyclohexane-
diamine to afford [Li(m-CH2NMeC6H10NMe2)2Al(iBu)2], the final complex to be crystallographically characterised. All
1
7
new products have been spectroscopically characterised through H, Li, and 13C NMR studies. Reaction mixtures
2
have also been quenched with D2O and analysed by D NMR spectroscopy to ascertain the full metallation versus
co-complexation picture taking place in solution.
Manuscript received: 5 April 2013.
Manuscript accepted: 27 May 2013.
Published online: 3 July 2013.
subordinate metal.[9] Organoaluminium chemistry, both in its
þ3 oxidation state, and more recently in its þ1 state[10–12] has
been comprehensively studied for many years. As a tri-valent
metal, this opens up alternative potential reaction pathways
when compared with the more often studied bi-valent metals
mentioned above due to either the electronic effect of using a
formal 3þ metal or the steric effects of introducing a further
anion to saturate this increase in positive charge. In particular,
our interest has focussed on the bis-amido/bis-alkyl heterobi-
Introduction
Ubiquitous in synthetic chemistry for priming molecules for
their subsequent functionalisation, the metallation reaction
has traditionally been the domain of polar, highly reactive
alkali-metals, notably lithium.[1–5] However, this discipline has
evolved recently such that the place vacated on the molecule by
the departing hydrogen atom can be directly taken by a less
polar, less reactive metal such as magnesium, zinc, or manga-
nese(II).[6–8] This is achieved by pairing such a metal with a
polar alkali-metal within a discrete molecular bimetallic ‘ate’
framework, the result being that the alkali-metal in effect
imparts its reactivity onto the subordinate metal which ulti-
mately performs the deproto-metallation reaction. Since the
subordinate metal cannot typically perform the metallation
reaction by itself, the term ‘alkali-metal-mediated metallation’
was coined to reflect the subsidiary but mandatory role played
by the group 1 metal in activating the less reactive metal.
Due to the high natural abundance, low toxicity, and
relative inexpensiveness of aluminium, we have recently taken
an interest in developing and understanding its role as the
i
metallic aluminate of general formula DꢀLiAl(TMP)2 Bu2
(1, where D ¼ a neutral Lewis donor molecule and TMP ¼
2,2,6,6-tetramethylpiperidide), which is generated in a facile
manner by simply mixing equimolar quantities of Li(TMP) with
(TMP)AliBu2 in hexane.[13] Aluminate 1 has been shown to act
as an excellent chemoselective, halogen tolerant base towards
functionalised aromatic substrates.[14,15]
Our studies have run in parallel with the excellent work of
Uchiyama, Wheatley and coworkers who pioneered and
have concentrated on the more alkyl-rich lithium aluminate
LiAl(TMP)iBu3 (2), which is also accessed through the
Journal compilation Ó CSIRO 2013
www.publish.csiro.au/journals/ajc

1190
R. Campbell et al.
(a)
THF
O
TMP
Al
Li
TMP
iBu
iBu
iBu
iBu
1
2
THF
Li
Al
O
ꢀTMP(H)
iBu
CH
A
1A
2A
1 ꢁ Li(TMP) ꢂ (TMP)AliBu2
2 ꢁ Li(TMP) ꢂ AliBu3
(b)
1B
N
TMP
Li
iBu
all reactions carried out in hexane
Al
N
iBu
CH2
TMEDA
ꢀTMP(H)
X
1
ꢀTMP(H)
CH2
iBu
N
Me2N
Me2N
2
N
N
Li
Al
CH2
2B
ꢀTMP(H)
ꢀiBuH
B
iBu
N
N
iBu
Al
Li
iBu
N
iBu
CH2
2B′
Scheme 1. Contrasting reactivity of aluminate bases 1 and 2 towards (a) THF and (b) N,N,N0,N0-tetramethylethylene-
diamine (TMEDA).
co-complexationofhomometallicstartingmaterialsLi(TMP) and
AliBu3.[16–18] What has consistently been clear throughout the
studyofthesetwocloselyrelatedbimetallicbasesisthedifference
in their reactivity upon the substitution of one of the alkyl groups
in 2 by another equivalent of the bulky secondary amide in 1.
While both bases can operate in a ‘conventional’ manner with
respect to functionalised aromatic molecules – that is they are
potent direct aluminators (C–H to C–Al exchangers) of such
molecules by the well established and understood principles of
directed ortho-metallation (DoM)[19–21] – they display marked
differences in their reactivity towards non-aromatic, heteroatom
containing molecules. This is best displayed by their respective
reactivities towards the most common cyclo-ether tetrahydro-
furan (THF, donor A; Scheme 1a). Thus 2 can be stabilised as a
THF solvate (2A)[22] and is routinely utilised in this medium;[17]
while in contrast 1 will deprotonate THF at the methylene group
adjacent to the heteroatom by TMP basicity, sedating the
resulting highly sensitive cyclic anion (in 1A)[23] without the
ether cleavage typically witnessed when a monometallic
approach to THF a-deprotonation is attempted.[24–26] Another
pertinent example of the contrasting reactivity of aluminates
1 and 2 involves the common bidentate donor N,N,N0,N0-
tetramethylethylenediamine (TMEDA, donor B).[27] While
both bases will directly aluminate this diamine at one methyl
group adjacent to the nitrogen atom, 2 will actually metallate
a second equivalent to give 2B as depicted in Scheme 1b. This
distinction suggests that the first deprotonation event carried out
i
by 2 must occur through TMP and not Bu basicity to give
intermediate 2B9 (which cannot be isolated), since if the latter
situation was operative then this would generate complex 1B,
which is inert towards a further equivalent of TMEDA.
Interestingly, the solvent plays an important role in any
reaction of a base such as 2 as demonstrated by its reaction
with N,N-diisopropylbenzamide (Scheme 2). In hexane, a sim-
ple donor adduct (2ꢀbenzamide) is produced with no
deprotonation;[28] whereas in THF ortho-deprotonation of the
aromatic substrate results in a 94 % yield of 2-iodo-N,N-
diisopropylbenzamide after iodination.[16] When the hexane
reaction is repeated in the presence of stoichiometric THF only
a negligible amount of ortho-deprotonation occurs, while
stoichiometric TMEDA yields a product which contains both
deprotonated TMEDA and benzamide bridges as well as
a ligating neutral benzamide.[29] Furthermore, 2ꢀbenzamide will
cleave 1,4-dioxan and capture the resulting highly sensitive
alkoxy vinyl ether anion;[28] while 2 (in the absence of benza-
mide) produces the segregATE (solvent-separated ate)
[Li(dioxan)4]þ [Al(iBu)4]ꢁ, presumably from a dismutation
process (Scheme 2).[30]
The captivating reactivity of alkali-metal aluminates is not
limited to lithium derivatives, as exposed by the potassium

Lithium Aluminate Chemistry
1191
Me2N
N
CH2
Al
Li
iBu
iBu
benzamide
O
iPr2N
TMEDA
benzamide
hexane
iPr2N
O
iBu
iBu
iBu
hexane
THF
2
benzamide
Li
Al
I
benzamide
benzamide
I2
TMP
4 equiv.
dioxan
2 equiv.
dioxan
hexane
hexane
94 %
ꢂ
O
O
O
AliBu3
O
Li
benzamide
ꢀ
iBu
iBu
iBu
iBu
O
O
O
O
O
O
O
Li
O
Li
O
Al
benzamide
iBu3Al
O
Scheme 2. Reactivity of aluminate 2 in hexane or THF with benzamide and dioxane.
i
aluminate congener KAl(TMP)2 Bu2 which, rather than attack-
ing a neutral Lewis donor through TMP basicity, actually attacks
the other TMP anion at a flanking methyl position to give
an unprecedented N,C-bis-deprotonated TMP dianion, essen-
tially inverting the TMP anion from a potent Brønsted base to
a Brønsted acid.[31]
Intrigued by the vagaries in reactivity displayed by the two
closelyrelatedlithiumaluminates1and2, wehave systematically
studied their reactivity with a series of multidentate nitrogen and
oxygen containing donor molecules C–H (shown in Fig. 1) that
offer a variety of donor ligation and/or deprotonation possibilities
in an attempt to further understand these important heterometallic
reagents and now present our findings herein.
NMe2
O
MeO
NMe2
N,N-dimethyltetrahydro
furfurylamine (Me2TFA)
1-methoxy-2-dimethyl
aminoethane (MDAE)
C
D
Me2N
O
NMe2 MeO
OMe
Bis[2-(N,N-dimethylamino)
ethyl]ether (Me4AEE)
1,2-dimethoxyethane
(DME)
E
F
NMe2
NMe2
Experimental
N
General Experimental
All reactions and manipulations were carried out under a
protective argon atmosphere using either standard Schlenk
techniques or a glove box. All solvents were dried over Na/
Me2N
NMe2
Me2N
i
benzophenone and freshly distilled before use. Bu2Al(TMP)
Tris(N,N-dimethyl-2-amino
ethyl)amine (Me6TREN)
R,R-N,N,Nꢃ,Nꢃ-tetramethylcyclo
hexanediamine (TMCDA)
and Li(TMP) were prepared in situ; N,N-dimethyltetra-
hydrofurfurylamine (Me2TFA),[32] 1-methoxy-2-dimethyl-
aminoethane (MDAE),[32] tris(N,N-dimethyl-2-aminoethyl)
amine (Me6TREN),[33] and R,R,N,N,N0,N0-tetramethylcyclo-
hexanediamine (TMCDA)[34] were prepared by literature
methods. Bis[2-(N,N-dimethylamino)ethyl]ether (Me4AEE),
iBu3Al (1.0 M in hexane), and 1,2-dimethoxyethane (DME) were
H
G
Fig. 1. Neutral heteroatom containing molecules employed in this study.
and 155.50 MHz for Li). All 13C NMR spectra were proton
decoupled. Ligands containing a * next to their name indicate that
they have been deprotonated and are in an anionic form. The high
sensitivityof theorganometallicspecies1and2preventedusfrom
7
1
7
purchased from Aldrich and used as received. H, 13C, and Li
NMR spectra were recorded on a Bruker AV400 MHz spectro-
1
meter (operating at 400.03 MHz for H, 100.58 MHz for 13C,

1192
R. Campbell et al.
1
obtaining satisfactory elemental analyses. H NMR spectra are
provided in the Supplementary Material to confirm purity.
Synthesis of [Me2TFAꢀLi(m-TMP)(m-iBu)Al(iBu)2] 2C
Hexane (10 mL) was introduced to an oven-dried Schlenk tube.
Next, 1.6 M nBuLi (1.25 mL, 2 mmol) was added, followed by
TMP(H) (0.34 mL, 2 mmol) at room temperature. The reaction
Synthesis of [Li(m-TMP)(m-Me2TFA*)Al(iBu)2] 1C
i
Hexane (10 mL) was injected into an oven-dried Schlenk tube.
Next, 1.6 M nBuLi (1.25 mL, 2 mmol) was added, followed by
TMP(H) (0.34 mL, 2 mmol) at room temperature. The reaction
mixture was left to stir for 10 min and then iBu2AlCl (0.38 mL,
2 mmol) was introduced, producing a white suspension almost
immediately. The reaction was left to stir for 1 h and was then
filtered through Celite and glass wool, which was then washed
with more hexane (10 mL). To a separate Schlenk tube con-
taining a solution of freshly prepared LiTMP in hexane (10 mL)
(from a mixture of nBuLi (1.25 mL, 2 mmol) and TMP(H)
mixture was left to stir for 10 min and then Bu3Al (2 mL,
2 mmol) was injected into it. Finally, Me2TFA (0.28 mL,
2 mmol) was added and the reaction mixture was left to stir
overnight. The solution was left to stand at ꢁ308C. A crop of
colourless crystals formed (0.58 g, 61 %) in solution, which
were successfully studied by X-ray crystallographic analysis.
dH (400.13 MHz, THF-D8, 298 K) ꢁ0.34 (1H, m, CH2 of
iBu), ꢁ0.20 (5H, d, 3J(H, H) 6.3, CH2 of iBu), 0.84 (15H, d, 3J(H,
H) 6.4, CH3 of iBu), 0.89 (3H, d, 3J(H, H) 6.4, CH3 of iBu), 1.22
(4H, m, bCH2 of TMP), 1.22 (12H, s, CH3 of TMP), 1.52 (2H, m,
gCH2 of TMP), 1.54 (1H, m, OCHCH2 of Me2TFA), 1.81 (2H,
m, OCH2CH2 of Me2TFA), 1.89 (3H, m, CH of iBu), 1.93 (1H,
m, OCHCH2 of Me2TFA), 2.20 (6H, s, NCH3 of Me2TFA), 2.30
(2H, m, CH2NMe2 of Me2TFA), 3.64 (1H, m, aCH2 of
Me2TFA), 3.78 (1H, m, aCH2 of Me2TFA), 3.90 ppm (1H, m,
aCH of Me2TFA).
i
(0.34mL, 2 mmol)), the solution of Bu2Al(TMP) was added
through a cannula. Finally, Me2TFA (0.28 mL, 2 mmol) was
added by injection and the reaction mixture was left to stir over-
night. The solution was then left to stand in the freezer at ꢁ308C.
A crop of colourless crystals (0.24 g, 29%) formed in solution,
which were successfully studied by X-ray crystallographic
analysis. Two diastereoisomers were observed by 1H NMR
spectroscopy in a ratio of 2 : 1 (diastereomer A : diastereomer B).
Diastereomer A: dH (400.13 MHz, THF-D8, 298 K) ꢁ0.17
dC (100.62 MHz, THF-D8, 298 K) 20.2 (gCH2 of TMP), 26.2
(OCH2CH2 of Me2TFA), 30.0 (CH2 of iBu), 28.7 (CH of iBu),
i
30.2 (CH3 of Bu), 30.8 (OCHCH2 of Me2TFA), 34.6 (Me of
TMP), 45.3 (bCH2 of TMP), 46.5 (NMe2 of Me2TFA), 52.5
(CMe2 of TMP), 64.8 (CH2NMe2 of Me2TFA), 68.4 (OCH2 of
Me2TFA), 78.7 (OCH of Me2TFA).
(1H, d, 3J(H, H) 6.5, CH2 of Bu), ꢁ0.08 (3H, d, 3J(H, H) 6.3, CH2
i
of iBu), 0.92 (12H, m, CH3 of Bu), 1.23 (1H, m, gCH2 of TMP),
i
1.25 (6H, s, CH3 of TMP), 1.27 (1H, m, AlCHCH2 of Me2TFA*),
1.30 (6H, s, CH3 of TMP), 1.51 (1H, m, AlCHCH2CH2 of
Me2TFA*), 1.64 (1H, m, gCH2 of TMP), 1.79 (1H, m,
d
Li (155.50 MHz, THF-D8, 298 K) ꢁ0.43.
i
AlCHCH2CH2 of Me2TFA*), 1.90 (2H, m, CH of Bu), 1.92
Synthesis of [Li(m-TMP)(m-MDAE*)Al(iBu)2] 1D
(1H, m, AlCHCH2 of Me2TFA*), 2.06 (1H, m, CH2NMe2 of
Me2TFA*), 2.24 (6H, s, CH3 of Me2TFA*), 2.33 (1H, m,
CH2NMe2 of Me2TFA*), 3.26 (1H, dd, 3J(H, H) 13.0, 4J(H, H)
5.9, AlCH of Me2TFA*), 3.94 (1H, m, CHCH2N of Me2TFA*).
Diastereomer B: dH (400.13 MHz, THF-D8, 298 K) 0.00 (4H,
m, CH2 of iBu)], 0.89 (12H, m, CH2 of iBu), 1.22 (6H, s, CH3 of
TMP), 1.24 (6H, s, CH3 of TMP), 1.27 (1H, m, gCH2 of TMP),
1.28 (1H, m, AlCHCH2CH2 of Me2TFA*), 1.29 (1H, m,
AlCHCH2 of Me2TFA*), 1.58 (1H, m, gCH2 of TMP), 1.85
(2H, m, CH of iBu), 1.95 (1H, m, AlCHCH2CH2 of Me2TFA*),
2.05 (1H, m, AlCHCH2 of Me2TFA*), 2.17 (1H, m, CH2NMe2
of Me2TFA*), 2.23 (6H, s, CH3 of Me2TFA*), 2.43 (1H, m,
CH2NMe2 of Me2TFA*), 3.37 (1H, dd, 3J(H, H) 12.6, 4J(H, H)
5.8, AlCH of Me2TFA*), 3.98 (1H, m, CHCH2N of Me2TFA*).
Due to the presence of several overlapping signals the bCH2 of
TMP could not be identified.
This was prepared as per complex 1C but with MDAE (0.25 mL,
2 mmol) injected to the in situ generated lithium aluminate base.
The solution was left to stand in the freezer at ꢁ308C. A crop of
colourless crystals (0.63 g, 81 %) formed in solution, which
were successfully studied by X-ray crystallographic analysis.
dH (400.13 MHz, THF-D8, 298 K) ꢁ0.12 (4H, m, CH2 of
iBu), 0.88 (6H, d, 3J(H, H) 6.4, CH3 of iBu), 0.90 (6H, d, 3J(H, H)
6.4, CH3 of iBu), 1.25 (4H, m, bCH2 of TMP), 1.25 (12H, s, CH3
of TMP), 1.59 (2H, m, gCH2 of TMP), 1.86 (2H, m, CH of iBu),
2.26 (6H, s, NMe2 of MDAE*), 2.46 (2H, m, Me2NCH2 of
MDAE*), 3.20 (2H, s, AlCH2 of MDAE*), 3.57 (2H, m,
AlCH2OCH2 of MDAE*).
dC (100.62 MHz, THF-D8, 298 K) 19.6 (gCH2 of TMP), 28.3
(CH of iBu), 29.2 (CH3 of iBu), 30.0 (CH3 of iBu), 30.8 (CH2 of
iBu), 33.9 (CH3 of TMP), 45.0 (bCH2 of TMP), 45.5 (NMe2 of
MDAE*), 52.6 (CMe2 of TMP), 60.0 (Me2NCH2 of MDAE*),
71.7 (AlCH2OCH2 of MDAE*), 78.0 (AlCH2 of MDAE*).
Diastereomer A: dC (100.62 MHz, THF-D8, 298 K) 19.2
i
i
(gCH2 of TMP), 28.0 (CH of Bu), 28.1 (CH of Bu), 32.8
(AlCHCH2CH2 of Me2TFA*), 33.7 (CH3 of TMP), 44.6
(AlCHCH2 of Me2TFA*), 46.3 (CH3 of Me2TFA*), 52.7
(CMe2 of TMP), 66.7 (CHCH2NMe2 of Me2TFA*), 76.1
(CHCH2NMe2 of Me2TFA*), 84.3 (AlCH of Me2TFA*).
Diastereomer B: dC (100.62 MHz, THF-D8, 298 K) 19.6
(gCH2 of TMP), 28.2 (CH of Bu), 28.3 (CH of Bu), 33.0
(AlCHCH2 of Me2TFA*), 34.4 (CH3 of TMP), 34.6 (CH3 of
TMP), 44.2 (AlCHCH2 of Me2TFA*), 46.1 (CH3 of Me2TFA*),
52.5 (CMe2 of TMP), 65.8 (CHCH2NMe2 of Me2TFA*), 76.5
(CHCH2NMe2 of Me2TFA*), 84.5 (AlCH of Me2TFA*).
Diastereomer A/B dC (100.62 MHz, THF-D8, 298 K) 30.4
(CH2 of iBu), 29.9 (CH2 of iBu), 29.0 (CH2 of iBu), 28.7 (CH2
of iBu). Due to a complex 1H NMR spectrum the CH3 of iBu and
bCH2 of TMP could only be assigned to 29.4, 29.7, 30.1, and
31.2 ppm and could not be differentiated.
d
Li (155.50 MHz, THF-D8, 298 K) 0.19.
Synthesis of [MDAEꢀLi(m-TMP)(m-iBu)Al(iBu)2] 2D
This was prepared as per complex 2C but with MDAE (0.25 mL,
2 mmol) injected to the in situ generated lithium aluminate base.
The solution was left to stand in the freezer at ꢁ308C. A crop of
colourless crystals (0.30 g, 33 %) formed in solution, which
were successfully studied by X-ray crystallographic analysis.
i
i
3
dH (400.13 MHz, 298 K, C6D6) 0.27 (6H, d, J(H, H) 6.50,
3 ꢂ CH2 of iBu), 1.40 (2H, m, 1 ꢂ bCH2 of TMP), 1.42 (15H, d,
i
3
3J(H, H) 6.50, 5 ꢂ CH3 of Bu), 1.46 (3H, d, J(H, H) 6.50,
i
1 ꢂ CH3 of Bu), 1.50 (12H, broad s, 4 ꢂ CH3 of TMP), 1.70
(6H, s, N(CH3)2 of MDAE), 1.76 (2H, t, 3J(H, H) 5.18, NCH2
of MDAE), 2.43 (3H, m, 3 ꢂ CH of iBu), 2.64 (2H, s, OCH2 of
MDAE), 2.93 (3H, s, OCH3 of MDAE).
d
Li (155.50 MHz, THF-D8, 298 K) 0.33.

Lithium Aluminate Chemistry
1193
dC (100.62 MHz, 298 K, C6D6) 18.8 (gCH2 of TMP), 27.7
CH3 of iBu), 1.52 (12H, br s, CH3 of TMP), 2.40 (3H, m, CH of
iBu), 2.68 (4H, s, CH2 of DME), 2.86 (6H, s, CH3 of DME).
dC (100.62 MHz, C6D6, 298 K) 18.9 (gCH2 of TMP), 27.8
(CH3 of iBu), 27.8 (CH of iBu), 29.7 (CH3 of TMP), 44.8 (bCH2
of TMP), 52.8 (CMe2 of TMP), 59.0 (CH3 of DME), 69.7 (CH2
of DME).
i
(CH of Bu), 27.8 (bCH2 of TMP), 28.6 (CH3 of TMP), 29.4
(CH3 of TMP), 29.7 (CH3 of iBu), 29.9 (CH2 of iBu), 45.0 (bCH2
of TMP), 45.1 (NCH3 of MDAE), 52.8 (CMe2 of TMP), 57.8
(NCH2 of MDAE), 59.4 (OCH3 of MDAE), 68.2 (OCH2 of
MDAE).
d
Li (155.50 MHz, 298 K, C6D6) ꢁ0.34.
dLi (155.50 MHz, C6D6, 298 K) ꢁ0.45.
Synthesis of [Li(m-TMP)(m-Me4AEE*)Al(iBu)2] 1E
Synthesis of [Li(Me2NC6H10NMeCH2)2Al(iBu)2] 2H
This was prepared as per complex 1C but with Me4AEE
(0.38 mL, 2 mmol) injected to the in situ generated lithium
aluminate base, producing a white precipitate which dissolved
on gentle heating. A crop of colourless crystals (0.38 g, 42 %)
formed in solution while cooling to room temperature.
This aluminate was prepared analogously to complex 2C but
with TMCDA (0.38 mL, 2 mmol) injected to the in situ gener-
ated lithium aluminate base. The Schlenk tube was left in the
freezer at ꢁ308C. A crop of colourless crystals (0.27 g, 28 %)
formed in solution that were suitable for X-ray crystallographic
analysis. The rational synthesis of 2H was attempted using two
molar equivalents of the Lewis base (0.76 mL, 4 mmol of
TMCDA), however, an oil formed in solution and no crystals
could be grown.
dH (400.13 MHz, 298 K, C6D6) 0.48–0.54 (4H, m, 2 ꢂ CH2
i
of Bu), 1.34 (1H, m, gCH of TMP), 1.36–1.46 (12H, m, 4 ꢂ
i
CH3 of Bu), 1.51 (12H, br s, CH3 of TMP), 1.55 (1H, m,
OCH2CH2 of Me4AEE*), 1.60 (6H, s, N(CH3)2 of Me4AEE*),
1.84 (1H, m, gCH of TMP), 2.02 (1H, m, OCH2CH2
of Me4AEE*), 2.25 (6H, s, N(CH3)2 of Me4AEE*), 2.35 (2H,
Attempts to prepare 1G, 1H, 2E, and 2G were made by
combining the appropriate lithium aluminate base and donor,
however, in each case no tangible products were obtained.
i
3
m, 2 ꢂ CH of Bu), 2.66 (1H, d, J(H, H) 14.4, OCHCH2 of
Me4AEE*), 3.15 (1H, m, OCH2 of Me4AEE*), 3.28 (1H, m,
OCH of Me4AEE*), 3.50 (1H, d, 3J(H, H) 11.1Hz, OCHCH2 of
Me4AEE*), 4.48 (1H, m, OCH2 of Me4AEE*).
Synthesis of [Me2NCH2CH2OCH
(C6H4OCH3)CH2NMe2] 3E
dC (100.62 MHz, 298 K, C6D6) 18.3 (gCH2 of TMP), 27.6
(CH of iBu), 27.8 (CH of iBu), 29.0 (CH2 of iBu), 28.6 (CH3 of
iBu), 29.4 (CH3 of iBu), 29.6 (CH3 of iBu), 35.7 (CH3 of TMP),
Compound 1E was synthesised on a 2 mmol scale as described
above. Hexane was removed under vacuum and 10 mL of dry
THF was added. Four molar equivalents of Zn(OAc)2 (8 mmol,
1.48 g) was added and the mixture allowed to stir overnight. In
aseparateSchlenktube2 mol-% (0.009 g)of Pd(OAc)2 wasadded
together with 4 mol-% (0.03 g) of 2-dicyclohexylphosphino-
20,60-dimethoxybiphenyl to give Pd(OAc)2/SPhos. THF (5 mL)
was added and the solution was allowed to stir until the solid had
completely dissolved. Three equivalents of 4-iodoanisole was
added and this solution was added to the first solution through a
cannula. This combined solution was left to stir overnight.
A saturated solution of ammonium chloride (20 mL) was added
and the organic layer was separated from the aqueous layer,
washing twice with ethyl acetate. Ammonia solution and ethyl
acetate were added to the aqueous layer and the organic layer
was once again separated from the aqueous layer. The organic
layer was concentrated under vacuum to leave 3E and TMP(H)
as a crude product. The TMP(H) was removed under vacuum to
give 3E in 62 % (0.27 g) yield.
i
30.2 (CH3 of Bu), 43.2 (CH3 of Me4AEE*), 45.4 (CH3 of
Me4AEE*), 46.1 (CH3 of Me4AEE*), 60.1 (OCH2CH2
of Me4AEE*), 68.2 (OCHCH2 of Me4AEE*), 69.7 (OCH2 of
Me4AEE*), 82.0 (OCH of Me4AEE).
d
Li (155.50 MHz, 298K, C6D6) 1.34.
Synthesis of DMEꢀ[Li(m-TMP)(m-DME*)Al(iBu)2]2 1F
This was prepared as per complex 1C but with DME (0.21 mL,
2 mmol) injected to the in situ generated lithium aluminate base,
producing a white precipitate which dissolved on gentle heating.
A crop of colourless crystals (0.45 g, 64 %) formed in solution
while cooling to room temperature.
dH (400.13 MHz, C6D6, 298 K) 0.42–0.70 (8H, m, 4 ꢂ CH2 of
iBu), 1.09 (8H, br t, 2 ꢂ bCH2 of TMP), 1.35 (12H, d, 3J(H, H)
6.4, 4 ꢂ CH3 of iBu), 1.41 (12H, d, 3J(H, H) 6.4, 4 ꢂ CH3 of iBu),
1.42 (24H, s, 8 ꢂ CH3 of TMP), 1.56 (4H, m, gCH2 of TMP),
i
2.32 (4H, sept, 3J(H, H) 6.4, 4 ꢂ CH of Bu), 2.58 (6H, s,
dH (400.13 MHz, CDCl3, 298 K) 2.23 (6H, s, N{CH3}2), 2.31
(6H, s, N{CH3}2), 2.29 (1H, m, CH of CH2), 2.43 (1H, m, CH of
CH2), 2.55 (1H, m, CH of CH2), 2.76 (1H, m, CH of CH2), 3.35
(2H, m, CH2), 3.79 (3H, s, OCH3), 4.38 (1H, dd, 3J(H, H) 9.04,
3.51, CH next to O), 6.86 (2H, d, 3J(H, H) 8.7, 2 ꢂ CH aromatic),
7.22 ppm (2H, d, 3J(H, H) 8.7, 2 ꢂ CH aromatic).
2 ꢂ CH3 of DME*), 2.61 (4H, t, 3J(H, H) 5.0, OCH2 of
DME*), 2.95 (4H, t, 3J(H, H) 5.0, OCH2 of DME*), 3.00
(6H, s, CH3 of DME), 3.03 (4H, s, CHꢁ2 of DME*), 3.37 (4H,
s, OCH2 of DME).
d
Li (155.50 MHz, C6D6, 298 K) 0.77.
When left to stir for 24 h, a second crystalline material was
also deposited in a low yield along with 1F (DMEꢀLi(m-TMP)
(m-OMe)Al(iBu)2, 1FA). This material could not be isolated in
pure form for NMR spectroscopic analysis.
dC (100.62 MHz, CDCl3, 298 K) 45.5 (N{CH3}2), 45.8
(N{CH3}2), 55.2 (OCH3), 59.0 (CH2), 65.9 (CH2), 66.4 (CH2),
79.9 (CH next to O), 113.9 (2 ꢂ CH of aromatic), 127.9 (2 ꢂ CH
of aromatic), 133.9 (quaternary para C of aromatic), 159.2
(quaternary C of aromatic next to OMe).
Synthesis of [DMEꢀLi(m-TMP)(m-iBu)Al(iBu)2] 2F
Deuterium Studies
This was prepared as per complex 2C but with DME (0.21 mL,
2 mmol) injected to the in situ generated lithium aluminate
base. The Schlenk tube was left to stand at 08C where a crop of
colourless crystals (0.42 g, 48 %) formed in solution, which
were successfully studied by X-ray crystallographic analysis.
One millilitre of D2O was added by syringe to an in situ generated
solution of complexes 1 and 2 and this was allowed to stir for
15 min. This was then dried with MgSO3, filtered, and concen-
trated under vacuum. The resulting mixtures were analysed for
deuterium uptake by 2D NMR spectroscopy in CHCl3 (see
Table 1), with the resulting spectra referenced to the solvent.
i
dH (400.13 MHz, C6D6, 298 K) 0.21 (1H, m, CH2 of Bu),
0.29 (5H, d, 3J(H, H) 6.1, CH2 of iBu), 1.40 (18H, d, 3J(H, H) 6.6,

1194
R. Campbell et al.
Crystallographic Analysis
of an equimolar quantity of each of the six neutral Lewis base
molecules (C–H) displayed in Fig. 1. Of the twelve potential
organometallic products, seven were prepared in crystalline
form suitable for single crystal X-ray diffraction analysis. The
molecular structure results of these analyses are displayed in
Figs 2–8. What is instantly clear is, mirroring the THF examples
shown in Scheme 1a, the fully intact donor molecules simply
coordinate datively to base 2 (this could be regarded as
‘co-complexation’), contributing to the four-coordinate, dis-
torted tetrahedral lithium environments shown in Figs 5–7. In
marked contrast the di-TMP base 1 C–H deprotonates all of
the involved donors by TMP basicity to complete three-
coordinate lithium centres and five-membered Li–N–Al–C–O
Crystallographic data was collected at 123(2) K on Oxford
˚
Diffraction instruments with MoKa (l 0.71073 A) radiation.
Structures were solved using the SHELXS-97 program[35] and
were refined to convergence against F2 against all independent
reflections by the full-matrix least-squares method using the
SHELXL-97 program.[35] The quality of the structure of 1C was
adversely affected by disorder in the deprotonated Me2TFA
ligand. Selected crystallographic and refinement parameters
are given in Table S1. CCDC 932147–932153 contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Results and Discussion
Solid State Studies
The experimental protocol followed was simply to stir the
lithium aluminate bases 1 or 2 in hexane solution in the presence
C1
N1
AI1
Table 1. Deuterium NMR studies on in situ prepared bases
Li1
C5
In situ prepared base
2D NMR(d)
Assignment
N3
1C
2C
1D
2D
1E
2E
1F
2F
1G
2G
1H
2H
3.85, 3.71
OCHD, OCDH
C22
O2
3.85, 3.71, 2.26
OCHD, OCDH, NCH2D
3.41
OCH2D
H2
H1
–
–
3.53, 2.26
OCHD, NCH2D
–
–
Fig. 3. Molecular structure of deprotonated 1-methoxy-2-dimethyl-
aminoethane (MDAE) compound 1D [Li(m-Me2NCH2CH2OCH2)(m-TMP)
Al(iBu)2]. Ellipsoids are drawn at 50 % probability level and hydrogen
atoms, except those on the metallated carbon, are omitted for clarity.
3.38
–
OCH2D
–
2.26
–
NCH2D
–
2.29
2.29
NCH2D
NCH2D
N1
C1ꢃ
AI1
Li1
N1
C1
Li1
O2
O2
N3
N3
C1
AI1
C22
C5
H1
C22
H1
N4
Fig. 2. Molecular structure of a-deprotonated N,N-dimethyltetrahydrofur-
furylamine (Me2TFA) compound 1C [Li(m-Me2NCH2CHCH2CH2CHO)
(m-TMP)Al(iBu)2]. Ellipsoids are drawn at 50 % probability level and
hydrogen atoms, except that on the metallated carbon, are omitted for
clarity. The Me2TFA and one iBu group were modelled as disordered in a
76 : 24 and 51 : 49 ratio respectively, only the major components are
displayed for clarity.
Fig. 4. Molecular structure of deprotonated bis[2-(N,N-dimethylamino)
ethyl]ether (Me4AEE) compound 1E [Li(m-Me2NCH2CH2OCHCH2NMe2)
(m-TMP)Al(iBu)2]. Ellipsoids are drawn at 50 % probability level and
hydrogen atoms, except that on the metallated carbon, are omitted for
i
clarity. Me4AEE and Bu groups were modelled as disordered in a 50 : 50
ratio. Only one component is shown for clarity.

Lithium Aluminate Chemistry
1195
rings (Figs 2–4 for 1C, 1D, and 1E, respectively). The one
exception to this trend is seen in the reaction of base 2 with
TMCDA (2H, Fig. 8) because two molecules of this chiral donor
are deprotonated by dual iBu/TMP basicity. Such a scenario has
been witnessed before using the similar but achiral bidentate
N,N-donor TMEDA (Scheme 1b) and therefore the arguments
presented previously for TMEDA are applicable also to this
case.
occurs selectively on one of the methylene groups adjacent to
oxygen rather than at a terminal methyl arm, with the ligand then
coordinating to lithium in a hypodentate N,O fashion leaving
one CH2NMe2 limb uncoordinated and swinging free (Fig. 4).
The three aluminates [Li(m-Me2NCH2CHCH2CH2CHO)
(m-TMP)Al(iBu)2] 1C, [Li(m-Me2NCH2CH2OCH2)(m-TMP)
Al(iBu)2] 1D, and [Li(m-Me2NCH2CH2OCHCH2NMe2)
As shown in Figs 2–4, base 1 preferentially deprotonates
(aluminates) selectively at the carbon atom adjacent to oxygen
rather than nitrogen when given the choice of either position.
With the potentially tridentate N,O,N-donor Me4AEE (isoelec-
tronic to the common tridentate N,N,N-donor PMDETA,
N,N,N0,N00,N00-pentamethyldiethylenetriamine), deprotonation
N1
O3
Li1
C1
AI1
O2
N1
C9
C5
N3
Li1
C1
C5
AI1
O2
C9
Fig. 7. Molecular structure of solvated 1,2-dimethoxyethane (DME)
compound 2F [DMEꢀLi(m-iBu)(m-TMP)Al(iBu)2]. Ellipsoids are drawn at
50 % probability level and hydrogen atoms are omitted for clarity.
Fig. 5. Molecular structure of solvated N,N-dimethyltetrahydrofurfuryl-
amine (Me2TFA) compound 2C [Me2TFAꢀLi(m-iBu)(m-TMP)Al(iBu)2].
Ellipsoids are drawn at 50 % probability level and hydrogen atoms are
omitted for clarity. Part of the Me2TFA molecule was modelled as disor-
dered in an 88 : 12 ratio. Only the major component is displayed for clarity.
N3
H2
H1
N2
C22
C1
Li1
N1
AI1
N3
Li1
C5
AI1
C5
N4
N5
C32
O2
H3
H4
C9
C1
Fig. 6. Molecular structure of solvated 1-methoxy-2-dimethylaminoethane
(MDAE) compound 2D [MDAEꢀLi(m-iBu)(m-TMP)Al(iBu)2]. Ellipsoids are
drawn at 50% probability level and hydrogen atoms are omitted for clarity.
The crystal structure contained two independent molecules, only one is
displayed for clarity.
Fig. 8. Molecular structure of deprotoaluminated bis-N,N,N0,N0-tetra-
methylcyclohexanediamine (TMCDA) compound 2H
CH2NMeC6H10NMe2)2Al(iBu)2]. Ellipsoids are drawn at 50 % probability
level and hydrogen atoms, except those on metallated carbon atoms, are
omitted for clarity.
[Li(m-

1196
R. Campbell et al.
H2C
AI
O
iBu
iBu
g
O
h
[∗1e6]
Li
j
h
c
N
O
O
iBu
N
a
Li
AI
i
e
f
O
25
20
k
O
CH2
b
d
d
e
i
c
15
10
a
b
5
0
d
d
j
k
k
g
f
[ppm]
3.5
3.0
2.5
2.0
1.5
1.0
0.5
Fig. 9. 1H NMR spectrum of crystalline material from the reaction of base 1 with 1,2-dimethoxyethane (DME) showing full assignment.
the donor ligand with all its hydrogen atoms attached simply
solvates the now spirocyclic Li atom. The lack of deprotonation
of these chelating donor ligands is further backed up by the 1H
NMR spectroscopic data which confirms the presence of an
intact donor ligand.
iBu
iBu
N
O
O
O
Al
Li
A crystalline product was also obtained from the reaction in
hexane of bis-TMP base 1 with the bis-oxygen donor molecule
DME; however, crystals of 1F proved not to be of X-ray quality
precluding us from obtaining a suitable X-ray crystal structure.
However, the 1H NMR spectrum of 1F in C6D6 (Fig. 9) shows
that deprotonation at one terminal methyl group has occurred
as two triplets are observed at 2.61 and 2.95 ppm resulting from
loss of symmetry of the CH2–CH2 backbone. The signals for
the two terminal Al-bound isobutyl groups can be seen as a
multiplet at 0.42–0.70 ppm for the CH2 protons, two doublets at
1.35 and 1.41 ppm for the CH3 protons, and a septet at 2.32 ppm
for the CH protons. TMP methyl protons can be seen at
1.42 ppm. The integration of the two singlets at 2.58 and
3.03 ppm are consistent with the methyl and CH2 hydrogen
atoms of a methyl deprotonated DME ligand. The two remain-
ing singlets at 3.00 and 3.37 ppm are consistent with the
CH3 and CH2 hydrogen atoms of a second, fully intact DME
molecule. The integration of the intact DME against the
deprotonated DME indicates a 1 : 2 ratio. As these signals
are shifted compared with free DME (methyl, 3.40; methylene,
3.55 ppm) it can be proposed that the structure might contain
one donor DME bridging two typical deprotonated motifs to
give [(iBu)2Al(m-TMP)(m-CH3OCH2CH2OCH2)Li(DME)Li
(m-CH2OCH2CH2OCH3)(m-TMP)Al(iBu)2] (Fig. 9, inset).
Such a structure clearly has similarities with the lithium
aluminate dioxan complex (see above) which also contains a
neutral molecule acting as a bridging ligand with deprotonated
versions of the same ligand bridging between lithium and
aluminium.
Fig. 10. Proposed structure of cleaved 1,2-dimethoxyethane (DME)
product 1FA.
(m-TMP)Al(iBu)2] 1E with the mono-deprotonated donor
ligands are made up of two terminal iBu groups on Al, resulting
in a distorted tetrahedral geometry, with one TMP bridging Li
and Al. The donor ligands are deprotonated in an intramolecular
fashion at the most acidic C–H site adjacent to the O atom after
prior coordination to Li. The ligand forms the second bridging
anion and as a result the deprotonated C and adjacent O
complete the central five-element five-membered Al–N–Li–
O–C ring. In addition to this multi-element ring, each structure is
made up of another one or two rings fused onto the central ring.
Compounds 1D and 1E are made up of an additional four-
element five-membered N–Li–O–C–C ring, the only major
difference between these structures is the pendant CH2NMe2
arm attached to the deprotonated C of compound 1E. Aluminate
1C has two additional fused rings due to the cyclic substituted-
THF component of the ligand and NMe2 dative coordination to
Li from the pendant arm which forms an additional four-element
five-membered N–Li–O–C–C ring.
Compound 2H [Li(m-CH2NMeC6H10NMe2)2Al(iBu)2] dif-
fers only in the replacement of the bridging TMP anion with
another deprotonated TMCDA ligand which now occupies the
bridging site. The compound contains a central four-element
six-membered N–C–Al–C–N–Li ring with two fused three-
element five-membered N–C–C–N–Li rings while solvated
lithium compounds [Me2TFAꢀLi(m-iBu)(m-TMP)Al(iBu)2] 2C,
[MDAEꢀLi(m-iBu)(m-TMP)Al(iBu)2] 2D, and [DMEꢀLi(m-iBu)
(m-TMP)Al(iBu)2] 2F adopt a similar motif to compounds 1C,
1D, and 1E, however, this time the second bridging anion is an
isobutyl ligand rather than a deprotonated donor molecule and
When a solution of 1 containing DME was allowed to stir for
longer (24 h) a second product in addition to 1F was found to
co-crystallise within the solution. The 1H NMR spectrum shows
a mixture of the proposed compound shown above (1F) and a
second product 1FA. The X-ray crystal data of 1FA is of
insufficient quality to discuss in any detail, however, these data

Lithium Aluminate Chemistry
1197
[rel]
40
(a)
30
20
10
0
(b)
(c)
4
3
2
1 [ppm]
Fig. 11. (a) 1H NMR spectrum of free N,N-dimethyltetrahydrofurfurylamine (Me2TFA), (b) 2D NMR spectra for the
deuterium quench of Me2TFA after reaction with base 2 or (c) base 1.
[rel]
(a)
150
(b)
100
50
(c)
0
[ppm]
8
7
6
5
4
3
2
Fig. 12. (a) 1H NMR spectrum of free 1-methoxy-2-dimethylaminoethane (MDAE), (b) 2D NMR spectra for the deuterium
quench of MDAE after reaction with base 2 or (c) base 1.
suggest that the product contains a trapped OMe group in the
bridging position between Li and Al and a fully intact donor
DME on Li instead of a deprotonated diether DME giving
DMEꢀLi(m-TMP)(m-OMe)Al(iBu)2 (Fig. 10). This suggests that
after time the deprotonated DME[36–39] cleaves at the MeO–CH2
junction with the resulting methoxy group subsequently becom-
ing trapped, although the mechanism through which this occurs
is unclear.[40] Reactions of this type have been discussed in
terms of ‘cleave and capture chemistry’ as recently described in
a perspective article.[41]
Solution State Studies
A solution state NMR spectroscopic study was initiated on
the highly soluble crystalline material obtained from these
1
reactions (see above). H and 13C NMR spectra in C6D6 or
D8-THF were consistent with the molecular structures discussed

1198
R. Campbell et al.
[rel]
(a)
(b)
3000
2000
1000
0
(c)
[ppm]
4.0
3.5
3.0
2.5
2.0
Fig. 13. (a) 1H NMR spectrum of free bis[2-(N,N-dimethylamino)ethyl]ether (Me4AEE), (b) 2D NMR spectra for the deuterium
quench of Me4AEE after reaction with base 2 or (c) base 1.
[rel]
100
(a)
80
60
(b)
40
20
(c)
0
6
5
4
3
2
[ppm]
Fig. 14. (a) 1H NMR spectrum of free 1,2-dimethoxyethane (DME), (b) 2D NMR spectra for the deuterium quench of DME after
reaction with base 2 or (c) base 1.
previously, with complexes 1 each displaying a 2 : 1 : 1 iBu/TMP/
deprotonated-donor ratio and complexes 2 each displaying a
3 : 1 : 1 Bu/TMP/intact-donor ratio in their H resonance inte-
grations. The one exception to this was found in 2H, which
displays a 1 : 1 iBu/deprotonated-TMCDA ratio. In the case of
1C, resonances representing two diastereomers were witnessed
(in a 2 : 1 ratio) as a consequence of deprotonation of the
methylene group adjacent to oxygen (C22 in Fig. 2) in the
substituted THF ring generating a stereogenic carbon centre.
This is noteworthy as no distinction between diastereomers was
evident when a chiral carbon centre was generated in 1E or when
THF was the substrate.[23] The most informative resonances
i
1

Lithium Aluminate Chemistry
1199
[rel∗1e3]
(a)
50
40
(b)
30
20
(c)
10
0
[ppm]
3.0
2.5
2.0
1
2
Fig. 15. (a) H NMR spectrum of free tris(N,N-dimethyl-2-aminoethyl)amine (Me6TREN), (b) D NMR spectra for the deuterium
quench of Me6TREN after reaction with base 2 or (c) base 1.
[rel]
(a)
6000
5000
4000
(b)
3000
2000
(c)
1000
0
[ppm]
3.0
2.5
2.0
1.5
1.0
1
Fig. 16. (a) H NMR spectrum of free R,R,N,N,N0,N0-tetramethylcyclohexanediamine (TMCDA), (b) 2D NMR spectra for the
deuterium quench of TMCDA after reaction with base 2 or (c) base 1.
were those of the hydrogen atoms bonded to the metallated
carbon atom as well as the metallated carbon atoms themselves.
Specifically, resonances at 3.26/3.37 (diastereomer A/B), 3.20,
and 3.28 ppm were witnessed in the H NMR spectra of com-
plexes 1C, 1D, and 1E, respectively (compare with 3.75/3.86,
3.37, and 3.45 ppm for the corresponding resonances in the free
donor ligands). In the 13C NMR spectra, the resonances of the
metallated carbon atom were located downfield at 84.3/84.5,
78.0, and 82.0 ppm for 1C, 1D, and 1E, while the non-metallated
derivatives 2C and 2D showed these carbon resonances at 68.4
and 59.4 ppm, respectively. Meanwhile, the NMR spectra of 2F
suggested no deprotonation of the donor ligand had occurred due
1

1200
R. Campbell et al.
1 LiAl(TMP)2(iBu)2
OMe
ꢂ
N
iBu
iBu
THF
4 equiv. Zn(OAc)2
Al
N
Li
hexane
O
N
N
N
N
O
O
OMe
1E
N
3 equiv.
62 %
3E
I
2 mol-%
Pd(OAc)2/SPhos
Scheme 3. Deprotonation of bis[2-(N,N-dimethylamino)ethyl]ether (Me4AEE) with base 1, transmetallation with Zn(OAc)2
and subsequent cross-coupling in THF with 2 mol-% Pd(OAc)2/SPhos and three equivalents of 4-iodoanisole to give
compound 3E.
to the resonances indicating its symmetrical chemical makeup
remained. Complex 2H gave a highly complicated NMR spec-
trum, in part we believe due to the formation of stereogenic
centres, which could not be satisfactorily assigned due to
overlap of a forest of peaks.
Aware that the NMR spectrum of a crop of isolated crystals is
not necessarily representative of the whole in situ generated
reaction mixture from which the crystals grew, we also carried
out a series of electrophilic quenches on these mixtures to
ascertain if the reactivity of 1 and 2 was consistent towards
the other donor molecules. Specifically, a deuterium quench
(using D2O) was carried out with the resulting 2D NMR
spectrum consequently compared with the 1H spectrum of
the parent donors to ascertain whether the base had abstracted
a proton from them or not.
incorporation into the organic donor ligands has occurred.
Overall, aside from the NMe2 deprotonation of Me2TFA and
Me4AEE and the aCH2-deprotonation of Me2TFA, the D2O
quenches corroborate that the reaction of base 1 or 2 with each
ligand follows the same general trend, stronger base 1 deproto-
nates the donor ligand; whereas the intact ligand simply solvates
lithium in the weaker base 2.
As a representative example Me4AEE (E) was reacted with a
variety of electrophiles to determine whether it was possible to
selectively functionalise ligands such as these. The best proce-
dure was found to be cross-coupling deprotonated compound 1E
with 4-iodoanisole using a Pd(OAc)2/SPhos[42] catalyst after
transmetallation with zinc acetate [Zn(OAc)2] in THF solution
(Scheme 3). Due to the presence of three sp3 carbanionic carbon
i
centres (1 ꢂ Me4AEE and 2 ꢂ Bu) three equivalents of
The deuterium studies reveal some interesting results which
cannot be gleaned from the crystal structures in isolation.
4-iodoanisole were necessary. The new compound 3E was
synthesised in a 62 % yield. To the best of our knowledge this
is the first example of the preparation of 3E.
1
A comparison of the H NMR spectrum of Me2TFA with the
2D NMR spectra of the product formed after it was reacted with
base 2 (giving 2C in the solid state) and then quenched with D2O
(Fig. 11) shows that some deprotonation at the CH2 group
adjacent to oxygen has indeed occurred. There is also a reso-
nance consistent with some NMe2 deprotonation after reaction
with base 2. The amount of deprotonation must be negligible as a
1H NMR spectrum of the filtrate solution after the crystals were
removed confirms that the major product in solution is consis-
tent with the crystal structure which contains the donor molecule
intact, with no evidence of a deprotonation having taken place.
Moving to MDAE, as shown in Fig. 12 the deuterium quench
resulted in no 2D incorporation into the ligand after reaction with
base 2 while there was clearly 2D now present on the OMe arm
when the more reactive base 1 was used, consistent with this
base deprotonating the bidentate ligand. The 2D NMR spectrum
of 1 with Me4AEE reveals that a small amount of NMe2
deprotonation has also occurred in addition to the crystallo-
graphically determined deprotonation adjacent to oxygen
(Fig. 13). The D NMR spectrum of 1 with DME (Fig. 14)
confirms that deprotonation has occurred at the methyl group
1
adjacent to O as observed in the H NMR spectrum of the
crystals (Fig. 9).
Although crystal structure determinations were not success-
fully obtained for the products 1G and 1H, the D2O quench
experiment performed upon the in situ mixtures revealed that
deprotonation at the methyl NMe2 sites has occurred to some
extent (Figs 15 and 16). However, the 2D NMR spectra for the
reaction of 2E or 2G with D2O confirm that no deuterium
Due to the amine nitrogen atoms of Me4AEE the 4-isobutyl-
anisole by-product could be easily removed from the desired
product by working up the solution using ammonium chloride
and then removing the organic layer. Ammonia solution and
ethyl acetate were then added to the aqueous layer leaving only
3E and TMP(H) as the crude products in the organic layer.
Compound 3E was purified by removing ethyl acetate and
TMP(H) under vacuum then characterising by 1H and 13C
NMR spectroscopy in CDCl3 solution. In future work we will
investigate quenching procedures and electrophiles for the
functionalisation of deprotonated compounds 1C, 1D, and 2H.
Conclusions
i
This study has demonstrated that the bis-amide LiAl(TMP)2 Bu2
is a far superior deprotonating agent to the mono-amide ana-
logue LiAl(TMP)iBu3 and that the deprotonations achieved can
be carried out in hexane solution. The aluminium–hydrogen
exchanges take place selectively adjacent to the O centre in the
mixed N,O ligand sets. In most cases under the conditions
studied the mono-amide does not bring about deprotonation but
simply engages in a Lewis acid–Lewis base complex with the
polydentate donor molecule. A surprising exception to this
pattern is that the chiral diamine TMCDA is deprotonated by the
weaker aluminating agent at one methyl arm of an NMe2 group,
while the solution investigation shows that the stronger base
does this too. Such deprotonations a to a nitrogen atom are
relatively challenging so this points to possible energetically
favourable intramolecular processes. Although the relative
2

Lithium Aluminate Chemistry
1201
deprotonating ability of these synergic lithium–aluminium
reagents is made clearer through this study, some uncertainty
still remains as to the actual constitutions of these reagents in
their own right both in hexane and in THF solution. Detailed
solution studies using a battery of NMR techniques, as well as
theoretical calculations, will be used in future work to shed light
on this issue.
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these component parts are bound to one another by a simple Lewis
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Supplementary Material
1H NMR spectra and table of crystallographic data for com-
plexes 1C, 1D, 1E, 2C, 2D, 2F, and 2H are available on the
Journal’s website.
Acknowledgements
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[23] E. Crosbie, P. Garc´ıa-Alvarez, A. R. Kennedy, J. Klett, R. E. Mulvey,
This work was generously supported by the UK Engineering and Physical
Science Research Council (award no. EP/F063733/1), the Royal Society
(Wolfson research merit award to REM), a University of Strathclyde
RDF award (REM and SDR), and a Royal Society of Edinburgh/BP Trust
Fellowship award (SDR).
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