New reactivity and structural insights of alkali-metal-mediated alumination in directed ortho-alumination of a tertiary aromatic amide

Article abstract of DOI:10.1039/b606080c

The first reported sodium alkyl(TMP)aluminate reagent to be synthesised and crystallographically characterised, [TMEDA·Na(μ-TMP)(μ- ⁱBu)Al(ⁱBu)₂], reacts as an amido base towards phenylacetylene to form crystalline [(TMEDA)₂·Na(μ-CCPh) (μ-ⁱBu)Al(ⁱBu)₂]; whereas the congeneric TMEDA-stabilised lithium (TMP)aluminate exhibits dual alkyl/amido basicity in its reaction with N,N-diisopropylbenzamide to form a novel heterobimetallic- heterotrianionic crystalline complex [{PhC(=O)N(ⁱPr) ₂}·Li{2-[1-C(=O)N(ⁱPr)₂]C ₆H₄}{Me₂NCH₂CH₂N(Me) CH₂}Al(ⁱBu)₂], which, in addition to having an ortho-deprotonated benzamide ligand, also contains a methyl-deprotonated TMEDA ligand and a neutral benzamide molecule ligated to lithium. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b606080c

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COMMUNICATION
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New reactivity and structural insights of alkali-metal-mediated
alumination in directed ortho-alumination of a tertiary aromatic amide
´
Joaqu´ın Garc´ıa-Alvarez, David V. Graham, Alan R. Kennedy, Robert E. Mulvey* and Susan Weatherstone
Received (in Cambridge, UK) 28th April 2006, Accepted 26th May 2006
First published as an Advance Article on the web 19th June 2006
DOI: 10.1039/b606080c
neutral amide molecule to lithium [prompting thoughts of the
‘‘complex-induced proximity effect’’ (CIPE)]5 and methyl-alumina-
tion of TMEDA (Me2NCH2CH2NMe2, N,N,N9,N9-tetramethy-
lethylenediamine).
The first reported sodium alkyl(TMP)aluminate reagent to be
synthesised and crystallographically characterised, [TMEDA?
Na(m-TMP)(m-iBu)Al(iBu)2], reacts as an amido base towards
phenylacetylene to form crystalline [(TMEDA)2?Na(m-
CCPh)(m-iBu)Al(iBu)2]; whereas the congeneric TMEDA-sta-
bilised lithium (TMP)aluminate exhibits dual alkyl/amido
basicity in its reaction with N,N-diisopropylbenzamide to form
a novel heterobimetallic-heterotrianionic crystalline complex
[{PhC(LO)N(iPr)2}?Li{2-[1-C(LO)N(iPr)2]C6H4}{Me2NCH2-
CH2N(Me)CH2}Al(iBu)2], which, in addition to having an
ortho-deprotonated benzamide ligand, also contains a
methyl-deprotonated TMEDA ligand and a neutral ben-
zamide molecule ligated to lithium.
The new sodium TMP-aluminate reagent [TMEDA?Na(m-
TMP)(m-iBu)Al(iBu)2] (1) can be synthesised simply by mixing
i
together its component parts NaTMP, Bu3Al and TMEDA in a
bulk hydrocarbon solution. Avoiding THF (used as the bulk
solvent in the preparation of the aforementioned lithium TMP-
aluminate) enabled 1 to be obtained in a crystalline form suitable
for a X-ray crystallographic study.{ The molecular structure of 1
(Fig. 1) features a planar, four-element NaCAlN ring with a mixed
iBu-TMP bridging ligand set, and is completed by two terminal
iBu ligands on Al and a chelating TMEDA (N,N-attached) on Na.
The Al displays a distorted tetrahedral geometry (subtending bond
angles from 99.85(11) (C9–Al1–C5) to 120.57(10)u (N1–Al1–C9))
and bridging/terminal Al–C bonds that are indistinguishable in
length (2.038(2) and (mean) 2.037 s, respectively). Lying only
0.293(2) s out of the N1N2N3 basal plane, the Na geometry is
best described as trigonal-pyramidal, with C1 at the apex (Na–C1
bond length 2.680(2) s, cf. 2.468 s (mean) for Na–N bonds). The
bridge is stronger at the Na–N(TMP)–Al span, with lengths of
2.4368(19) and 1.9712(19) s, respectively. A search of the
Cambridge Structural Database6 scored only 3 hits for other
structures of general formula [Na(NR2)Al(R)3?¡donor], but none
of them adopt a discrete NaCAlN ring motif.
Heterometallic and heteroleptic in composition, alkali metal alkyl-
TMP-ates (where TMP is 2,2,6,6-tetramethylpiperidide) are
currently being developed as an exciting new class of organome-
tallic reagent. The few studies carried out thus far1 have established
that these new additions to one of the oldest dynasties in
organometallic chemistry can offer unique (synergic) reactivities,
and often improved regio- and chemoselectivities in their reactions,
in comparison to the classical homometallic/homoleptic reagents
(e.g., lithium alkyls, lithium TMP) from which they are descended.
Most of these studies have focused on TMP-zincates2 or TMP-
magnesiates.3 To date, there has only been one communication on
TMP-aluminates,4 in which Uchiyama et al. reported the new
reagent lithium triisobutyl(TMP)aluminate, empirically formulated
as ‘‘iBu3Al(TMP)Li’’. Opening-up a new means of approach to
aromatic aluminum compounds, this reagent can effect the direct
alumination of a wide range of functionalized aromatics. However,
the structure of the reagent itself and those of the arylaluminated
intermediates it generates (prior to electrophilic interception) are
unknown, nor indeed have these important compounds been
isolated from solution and characterized in their own right, though
an in situ (in THF solution) NMR study of an anisole
alumination4 points to the TMP function as being the active base
within this mixed alkyl-amido reagent. In this paper, by
introducing a sodium TMP-aluminate reagent and reporting its
reaction with phenylacetylene, we present unprecedented structural
information on both the reagent itself and the aluminated
acetylene intermediate. We also describe a remarkable reaction
between the congeneric lithium TMP-aluminate and a tertiary
aromatic amide, which affords a product that uniquely combines
ortho-alumination of the amide, complexation of a non-metallated
To establish the ligand transfer reactivity of 1 in a deprotonative
application, we tested it in
a 1 : 1 stoichiometry with
phenylacetylene in hexane solution. Unexpectedly, the crystalline
WestCHEM, Department of Pure and Applied Chemistry, University of
Strathclyde, Glasgow, UK G1 1XL. E-mail: r.e.mulvey@strath.ac.uk;
Fax: +44 (0)141 552 0876
Fig. 1 Molecular structure of 1 with 30% probability displacement
ellipsoids. H atoms have been omitted for clarity.
3208 | Chem. Commun., 2006, 3208–3210
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product [(TMEDA)2Na(m-iBu)(m-CMCPh)Al(iBu)2] (2) contains
two molecules of TMEDA. The reaction was therefore repeated
by adding an extra equivalent of TMEDA, this increasing the yield
of 2. On this evidence, 1 mimics the reactivity of ‘‘iBu3Al(TMP)Li’’
by functioning as a TMP base. Heavily donor-solvated with
respect to Na, the molecular structure of 2{ (Fig. 2) is strictly a
contacted ion pair, but the contact (Na1–C1 (of CMCPh) =
3.013(2) s) is extremely loose. The Na–C(iBu) bridge in 1 is
2.680(2) s in length, whereas in 2 it is significantly elongated
(Na1–C(9), 3.250(3) s). Other notable features of 2 include the
contrast between the near-linearity of the CMC–Al bond angle
(163.85(19)u) and the near-perpendicularity of the CMC–Na bond
angle (94.75(15)u). This resembles the signature s/p distinction of
the metal (Mg or Zn/alkali metal)–deprotonated substrate bonding
found in alkali metal magnesiates or zincates.1 Also, while the
geometry at Al is definitely tetrahedral, though distorted (range of
C–Al–C bond angles 103.65(9)–118.44(10)u), the sodium coordina-
tion is less clear cut, as aside from the loose contact to
[Al(CMCPh)(iBu)3]2, the TMEDA ligands both bind asymmetri-
cally (i.e., N1: 2.539(2) cf. N2: 2.723(2) s; N3: 2.628(2) cf. N4:
2.526(2) s).
Fig. 3 Molecular structure of 3 with 30% probability displacement
This success with 1 prompted us to investigate its lithium
congener, that is a TMEDA-stabilised variant of Uchiyama et al.’s
‘‘iBu3Al(TMP)Li’’. However, by following the same synthetic
procedure as that for 1, but substituting LiTMP for NaTMP, gave
only a white oily product. As no useful structural information
could be gleaned from this oil, we decided to utilise it in situ with
N,N-diisopropylbenzamide in anticipation of a Directed ortho
Alumination (DoAl), reaction. This was indeed realised, but in a
most unexpected manner. Thus, remarkably, the solid product of
the reaction was the heterobimetallic-heterotrianionic complex
[{PhC(LO)N(iPr)2}?Li{2-[1-C(LO)N(iPr)2]C6H4}{Me2NCH2CH2-
N(Me)CH2}Al(iBu)2] (3), obtained in an isolated crystalline
yield of 43%. Amenable to X-ray crystallographic study,{ 3
provides not just the first structural insight into alkali-metal-
mediated alumination (AMMA) but also reveals other
surprising facts about the reaction.
ellipsoids. H atoms have been omitted for clarity.
i
C atoms, two Bu a-carbons and one CH2 from ‘‘TMEDA’’,
complete the distorted tetrahedral Al coordination. Secondly,
closer inspection discloses that this CH2 (C1) belongs to a methyl-
deprotonated TMEDA, while, more normally, TMEDA’s two N
atoms (N1 and N2) chelate the Li in a five-membered LiNCCN
ring. Thirdly, also bonded to O1 of the aluminated benzamide, the
Li coordination sphere is completed by O2 of a second but non-
metallated benzamide molecule. Overall, the Al and Li centres are
held together in an irregularly-shaped undeca LiNCCNCAlCCCO
ring. Based on the precedent of the conversion of 1 to 2, a reaction
sequence can be proposed (Scheme 1) to rationalise the formation
of 3.
In the first step, the benzamide is ortho-aluminated by TMP,
with elimination of the amine TMPH. In the second step, a second
benzamide molecule, by complexing to Li through its highly basic
O,7 appears to induce an intramolecular deprotonation of a
TMEDA Me group via an Al-attached iBu base, with concomitant
Firstly, DoAl is confirmed since the Al bonds to the ortho-
carbon (C15) of the deprotonated benzamide (Fig. 3). Three other
i
i
elimination of BuH. On its own, Bu3Al is not a strong enough
base to metallate a tertiary aromatic amide or TMEDA,8,9 so the
Fig. 2 Molecular structure of 2 with 30% probability displacement
ellipsoids. H atoms have been omitted for clarity.
Scheme 1 Proposed stepwise reaction pathway for the formation of 3.
Chem. Commun., 2006, 3208–3210 | 3209
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0.29 (d, 6 H, CH2–Al-iBu). 13C{H} NMR (100.63 MHz, d6-benzene,
300 K): 132.47 (i-C6H5), 129.13 (o-C6H5), 128.39 (m-C6H5), 127.90
(p-C6H5), 126.64 (CMCPh), 109.58 (CMCPh), 57.81 (CH2-TMEDA), 46.18
(CH3-TMEDA), 30.01 (CH3-iBu), 29.01 (CH-iBu) and 26.31 (CH2–Al-iBu).
Synthesis of [{PhC(LO)N(iPr)2}?Li{2-[1-C(LO)N(iPr)2]C6H4}{Me2NCH2-
CH2N(Me)CH2}Al(iBu)2] (3): In a Schlenk tube, 2 mmol of TMEDA
(0.3 mL) was added to a hexane solution of LiTMP (prepared freshly from
a mixture of nBuLi (2 mmol, 1.25 mL of a 1.6 M solution in hexane) and
TMPH (2 mmol, 0.34 mL)) to give a slightly opaque yellow solution. After
the solution had been stirred for 30 min, iBu3Al (2 mmol, 2 mL of a 1.0 M
solution in hexane) was introduced, and the mixture further stirred for 1 h.
Addition of N,N-diisopropylbenzamide (4 mmol, 0.82 g) caused the
precipitation of a colourless solid. This solid dissolved upon addition of hot
toluene. Standing the solution on the bench afforded colourless crystals of 3
(0.58 g, 43%). Note that adding only 1 molar equivalent of the benzamide
also produced 3, but in a smaller yield. This suggests that the intermediate
reacts more quickly with the benzamide than does the starting reagent. FT-
IR (nujol): 1621 and 1614 cm21 (nCLO). 1H NMR (400.13 MHz, d4-THF,
300 K): 7.98 (m, 1 H, m-C6H4), 7.33 (m, 3 H, 2 H m-C6H5 and 1 H
p-C6H5), 7.26 (m, 2 H, o-C6H5), 7.08 (m, 1 H, p-C6H4), 6.97 (m, 2 H, 1 H,
m*-C6H4 and 1 H o-C6H4), 4.09, 3.67, 2.04 and 1.86 (m, 1 H each, CH-iPr),
3.08 and 2.77 (m, 1 H each, CH-iBu), 2.31 (s, 6 H, 2CH3-TMEDA), 2.25 (s,
4 H, CH2-TMEDA), 2.13 and 1.97 (br s, 1 H each, N(CH2)Al-TMEDA),
1.77 (s, 3 H, CH3-TMEDA), 1.72, 1.57, 1.32, 1.26, 1.03 and 0.99 (d, 3 H
each, CH3-iPr), 0.93 (d, 6 H, 2CH3-iPr), 0.85 and 0.83 (d, 6 H each,
CH3-iBu), 0.23, 0.11, 20.12 and 20.24 (m, 1 H each, CH2–Al-iBu). 13C{H}
NMR (100.63 MHz, d4-THF, 300 K): 177.98 (2 C, CLO), 169.81 (o-C6H4),
146.07 (i-C6H4), 141.08 (m-C6H4), 139.71 (i-C6H5), 128.05 (3 C, m-C6H5
and p-C6H5), 126.24 (p*-C6H4), 125.59 (2 C, o-C6H5), 122.90 (m*-C6H4),
122.86 (o*-C6H4), 62.03 (CH3-TMEDA), 69.58 and 51.36 (CH-iPr), 56.78
(CH2-TMEDA), 48.46 (N(CH2)Al-TMEDA), 45.63 (2CH3-TMEDA),
28.79 (CH3-iBu), 27.83 (CH-iBu), 20.09, 19.83, 19.68 and 19.36
(CH3-iPr). The signal for the Al–CH2 of iBu was not observed. 7Li
NMR (155.50 MHz, d4-THF, 300 K, reference LiCl in D2O at 0.00 ppm):
20.05.
two distinct deprotonations of this reaction are synergic in origin,
as the contacted Li appears to activate the Al-attached TMP and
iBu bases. This work thus establishes that TMP-aluminates can
function as dual TMP/alkyl bases. It also establishes that normal
patterns of reactivity can be reversed using AMMA, for although
N,N-diisopropylbenzamide is significantly more acidic than
TMEDA, TMEDA deprotonation is favoured over that of a
second benzamide molecule. Finally, it further establishes that the
extra stability inherent in these mixed-metal composites can allow
normally ‘‘hot’’ interactions, such as the (neutral benzamide) O–Li
donor–acceptor contact (of a type thought to be the foundation of
the suspected pre-metallation complexes in the CIPE),5 to be
‘‘frozen out’’, thus facilitating their direct study.
We thank the EPSRC (grant award no. GR/T27228/01) and the
Royal Society/Leverhulme Trust (Fellowship to R. E. M.) for
generously sponsoring this research.{
Notes and references
{ Crystal data for 1: C27H61AlN3Na, Mr = 477.76, orthorhombic, space
group P212121, a = 10.3767(2), b = 16.9980(4), c = 17.8197(4) s, V =
3143.09(12) s3, Z = 4, l = 0.71073 s, m = 0.096 mm21, T = 150 K, 35650
reflections, 6929 unique (Rint = 0.045), final refinement to convergence on
F2 gave R = 0.0509 (F, 5768 obs. data only) and Rw = 0.1212 (F2, all data),
GOF = 1.059. CCDC 606350. Crystal data for 2: C32H64AlN4Na, Mr =
554.84, triclinic, space group P1, a = 9.4085(4), b = 9.7578(4), c =
10.5611(4) s,
a = 102.489(2), b = 102.940(2), c = 91.186(2)u,
V = 920.16(6) s3, Z = 1, l = 0.71073 s, m = 0.090 mm21, T = 123 K,
23628 reflections, 9674 unique (Rint 0.050), final refinement to convergence
on F2 gave R = 0.0537 (F, 7563 obs. data only) and Rw = 0.1163 (F2, all
data), GOF = 1.044. CCDC 606351. Crystal data for 3: C40H70AlLiN4O2,
Mr = 672.92, monoclinic, space group P21/c, a = 11.3307(3), b = 20.5770(5),
c = 18.5945(5) s, b = 100.5393(14)u, V = 4262.20(19) s3, Z = 4, l =
0.71073 s, m = 0.082 mm21, T = 123 K, 17709 reflections, 9860 unique
(Rint 0.040), final refinement to convergence on F2 gave R = 0.0477 (F, 6609
obs. data only) and Rw = 0.1101 (F2, all data), GOF = 1.025. CCDC
606352. For crystallographic data in CIF or other electronic format see
DOI: 10.1039/b606080c
{ All reactions were carried out under a protective argon atmosphere.
Synthesis of [TMEDA?Na(m-TMP)(m-iBu)Al(iBu2)] (1): In a Schlenk tube,
3 mmol of BuNa (0.24 g) was suspended in 10 mL of hexane and a molar
equivalent of (H)TMP (3 mmol, 0.51 mL) added via syringe. The resultant
1 R. E. Mulvey, Organometallics, 2006, 25, 1060.
2 (a) M. Uchiyama, T. Miyoshi, Y. Kajihara, T. Sakamoto, Y. Otani,
T. Ohwada and Y. Kondo, J. Am. Chem. Soc., 2002, 124, 8514; (b)
T. Imahori, M. Uchiyama, T. Sakamoto and Y. Kondo, Chem.
Commun., 2001, 2450; (c) Y. Kondo, M. Shilai, M. Uchiyama and
T. Sakamoto, J. Am. Chem. Soc., 1999, 121, 3539.
3 (a) H. Awad, F. Mongin, F. Tre´court, G. Que´guiner and F. Marsais,
Tetrahedron Lett., 2004, 45, 7873; (b) H. Awad, F. Mongin, F. Tre´court,
G. Que´guiner, F. Marsais, F. Blanco, B. Abarca and R. Ballesteros,
Tetrahedron Lett., 2004, 45, 6697; (c) D. V. Graham, E. Hevia,
A. R. Kennedy, R. E. Mulvey, C. T. O’Hara and C. Talmard, Chem.
Commun., 2006, 417.
i
creamy white suspension was allowed to stir for 1 h, after which Bu3Al
(3 mmol, 3 mL of a 1.0 M solution in hexane) was added at room
temperature. The suspension changed from creamy white to a slightly
cloudy, pale yellow solution. This was followed by the addition of a molar
equivalent of TMEDA (3 mmol, 0.45 mL) to yield a clearer solution. The
storage of this solution in a freezer (227 uC) resulted in the precipitation of
colourless crystals (0.47 g, 33%), which were isolated and dried in the form
of a white powder. Reduction of the filtrate volume yielded only a pale
yellow oil, from which no further solid precipitated. Recrystallisation of a
portion of the solid from toluene yielded colourless crystals, suitable for
solution and solid state analysis. 1H NMR (400.13 MHz, d6-benzene,
300 K): 2.45 (sept, 3 H, CH-iBu), 1.75 (s overlapping m, 16 H, 12 H of
CH3-TMEDA and 4 H of b-TMP), 1.64 (s overlapping m, 6 H, 4 H of
CH2-TMEDA and 2 H of c-TMP), 1.49 (s br, 12 H, CH3-TMP), 1.43 (d,
18 H, CH3-iBu) and 0.21 (6 H, d, CH2–Al-iBu). 13C{H} NMR
(100.63 MHz, d6-benzene, 300 K): 56.95 (CH2-TMEDA), 52.49
(a-TMP), 46.29 (b-TMP), 45.93 (CH3-TMEDA), 30.5–31.5 (br, CH3-
TMP), 29.88 (CH3-iBu), 27.94 (CH-iBu) and 18.81 (c-TMP). The signal for
the Al–CH2 was not observed. Synthesis of [(TMEDA)2?
Na(m-iBu)(m-CMCPh)Al(iBu)2] (2): Following the method above for 1, but
adding two molar equivalents of TMEDA (6 mmol, 0.9 mL), produced a
cloudy yellow solution. PhCMCH (3 mmol, 0.33 mL) was then introduced
to give a transparent solution. Freezer cooling of this solution at 227 uC
afforded colourless crystals of 2 (0.35 g, 21%). Note that adding only
1 molar equivalent of TMEDA also produced 2, but in a smaller yield. 1H
NMR (400.13 MHz, d6-benzene, 300 K): 7.34 (m, 2 H, o-C6H5), 6.96 (m,
3 H, 1 H p-C6H5 and 2 H m-C6H5), 2.46 (sept, 3 H, CH–iBu), 1.84 (s, 12 H,
CH3-TMEDA), 1.83 (s, 4 H, CH2-TMEDA), 1.44 (d, 18 H, CH3-iBu) and
4 M. Uchiyama, Y. Naka, Y. Matsumoto and T. Ohwada, J. Am. Chem.
Soc., 2004, 126, 10526.
5 For an authoritative review, see: M. C. Whisler, S. MacNeil, V. Snieckus
and P. Beak, Angew. Chem., Int. Ed., 2004, 43, 2206.
6 (a) F. H. Allen, Acta Crystallogr., Sect. B: Struct. Sci., 2002, 58, 380; (b)
Cambridge Structural Database, version 5.25 with updates to March
2006; (c) For an example, see: M. Schiefer, H. Hatop, H. W. Roesky,
H.-G. Schmidt and M. Noltemeyer, Organometallics, 2002, 21, 1300.
7 For an example of a structure where this amide is complexed to a lithium
zincate reagent, see: W. Clegg, S. H. Dale, E. Hevia, G. H. Honeyman
and R. E. Mulvey, Angew. Chem., Int. Ed., 2006, 45, 2370.
8 TMEDA has recently been lithiated during the ortho-dilithiation of
thiophenol or 2-trimethylsilylthiophenol, see: A. Hildebrand, P. Lo¨nnecke,
L. Silaghi-Dumitrescu, I. Silaghi-Dumitrescu and E. Hey-Hawkins,
Dalton Trans., 2006, 967.
9 For examples of alumino-TMEDA derivatives made by transmetallation
as opposed to direct metallation see: X. Tian, R. Fro¨hlich, T. Pape and
N. W. Mitzel, Organometallics, 2005, 24, 5294.
3210 | Chem. Commun., 2006, 3208–3210
This journal is ß The Royal Society of Chemistry 2006