Atom Efficient Magnesiation of N-Substituted Alkyl Indoles with a Mixed Sodium-Magnesium Base

Article abstract of DOI:10.1002/ejic.201701317

This study presents the alkali metal mediated magnesiation (AMMMg) of three N-alkylated indoles with the mixed Na/Mg base [(TMEDA)Na(TMP)₂Mg(CH₂SiMe₃)] 1 (TMEDA = N,N,N′,N′-tetramethylethylenediamine, TMP = 2,2,6,6-tetramethylpiperidine). All three magnesiated indoles have been successfully characterised by single-crystal X-ray diffraction and solution state NMR studies, whereas iodolysis and Pd-catalysed cross coupling have been investigated. The steric nature of the N-alkyl group changes the reactivity and efficiency of 1 to give either atom efficient disodium tetraindol-2-ylmagnesiates [(Na-TMEDA)₂Mg(α-C₉H₈N)₄] 2 and [(Na-TMEDA)₂Mg(α-C₁₀H₁₁N)₄] 3, or [(TMEDA)Na(TMP)(α-C₁₁H₁₂N)Mg(TMP)] 4, whereby only one indole molecule is selectively deprotonated.

Full text of DOI:10.1002/ejic.201701317

DOI: 10.1002/ejic.201701317
Full Paper
Magnesiation of Indoles | Very Important Paper |
Atom Efficient Magnesiation of N-Substituted Alkyl Indoles with
a Mixed Sodium-Magnesium Base
Michael A. Stevens[a] and Victoria L. Blair*[a]
Abstract: This study presents the alkali metal mediated mag- cross coupling have been investigated. The steric nature of the
nesiation (AMMMg) of three N-alkylated indoles with the mixed N-alkyl group changes the reactivity and efficiency of 1 to give
Na/Mg base [(TMEDA)Na(TMP)2Mg(CH2SiMe3)] 1 (TMEDA = either atom efficient disodium tetraindol-2-ylmagnesiates [(Na-
N,N,N′,N′-tetramethylethylenediamine, TMP = 2,2,6,6-tetrameth- TMEDA)2Mg(α-C9H8N)4] 2 and [(Na-TMEDA)2Mg(α-C10H11N)4] 3,
ylpiperidine). All three magnesiated indoles have been success- or [(TMEDA)Na(TMP)(α-C11H12N)Mg(TMP)] 4, whereby only one
fully characterised by single-crystal X-ray diffraction and solu- indole molecule is selectively deprotonated.
tion state NMR studies, whereas iodolysis and Pd-catalysed
Introduction
Recent studies by Mongin et al. focused on the room tem-
perature metalation of a diverse range of functionalised indole
and pyrrole species using a mixture of ZnCl2·TMEDA/LiTMP in
various ratios,[11,12] which report, after subsequent iodolysis,
predominately 2-iodo derivatives in excellent yields.
Mulvey and Hevia et al. also reported the direct magnesia-
tion and zincation of N-methylindole using the sodium magne-
siate and zincate reagents [(TMEDA)2Na2MgBu4] and
[(TMEDA)Na(tBu)(TMP)Zn(tBu)] at room temperature[13] reveal-
ing the first structurally characterised C-magnesiated [(Na-
TMEDA)2Mg(α-C9H8N)4] and C-zincated [(TMEDA)Zn(α-C9H8N)2]
examples of N-heterocyclic compounds.
In this study, we report the room temperature magnesiation
of a range of N-alkyl functionalised indoles (N-alkyl = Me, Et
and iPr) with the sodium magnesium base [(TMEDA)Na-
(TMP)(CH2SiMe3)Mg(TMP)][14] 1. Rapid reaction times (under
20 min) and atom-efficient metalation are defined by the steric
bulk of the N-alkyl substituent with X-ray crystallography and
solution NMR studies revealing different complex architectures.
Indoles and their derivatives play a prominent role in a large
number of biologically active compounds, as well as in many
diverse products across the entire chemical industry.[1] It is con-
sidered a “privileged structural scaffold”[2] present in many im-
portant natural products (such as serotonin, tryptamine, trypto-
phan),[1] pharmaceuticals (such as Sumatriptan and Rizatrip-
tan),[3] agrochemicals (such as auxins and Amisulbrom)[4] and
pigments and dyes (indigoid and cyanine).[4] With the majority
(88 %)[5] of active pharmaceutical drugs on the market contain-
ing aromatic heterocyclic components dominated by N-hetero-
cyclic compounds, the synthesis and functionalisation of ind-
oles and their derivatives is of significant interest to both syn-
thetic and medicinal chemists.[6]
Metalation reactions have proven indispensable in the con-
version of simple indole containing synthons into complex
functionalised indole-based products.[7] This has predominately
been achieved through the use of alkyllithium reagents
through direct metalation or metathesis and/or lithium second-
ary-amides. However, these methods commonly require low
temperatures, long reaction times and reagent excess to be em-
ployed to ensure selectivity.
In the last fifteen years, numerous research groups have de-
veloped mixed metal reagents as new tools to deprotometallate
sensitive aromatic compounds.[8] In the context of indoles,
Uchiyama et al. have studied both the direct ortho-cupration
and -alumination of N-boc-indoles using the lithium cuprate
[MeCu(TMP)(CN)Li2][9] and lithium aluminate [iBu3Al(TMP)Li] re-
agents achieving C2-selective outcomes.[10] However, both
mixed metal reagents required sub-ambient temperatures
(–40 °C or –78 °C) and/or an excess of metalating reagent.
Results and Discussion
Reaction of 1 with either N-methyl or N-ethyl-indole resulted in
the deposition of a yellow precipitate, which when re-crystal-
lised from n-hexane or toluene respectively afforded X-ray
quality single crystals, identified as the disodium tetraindol-
2-ylmagnesiates [(Na-TMEDA)2Mg(α-C9H8N)4][13] 2 and [(Na-
TMEDA)2Mg(α-C10H11N)4] 3 (Figure 1).
Using a different metalation route, complex 2 has been pre-
viously reported in the literature[13] and will not be discussed
in detail (see Supporting Information). Essentially isostructural
to 2, complex 3 contains a central distorted tetrahedral (mean
109.34°) magnesium atom [Mg(1)] bonded to four separate α-
[a] School of Chemistry, Monash University,
Clayton, Melbourne, VIC 3800 Australia
E-mail: Victoria.Blair@monash.edu
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ejic.201701317.
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Figure 1. Molecular structure of [(Na-TMEDA)2Mg(α-C10H10N)4] (3) with thermal ellipsoids at 40 % probability. Hydrogen atoms and one disordered TMEDA
molecule have been omitted for clarity. Selected bond lengths [Å]: Mg(1)–C(1), 2.2086(16); Mg(1)–C(11), 2.2120(18); Mg(1)–C(21), 2.2331(16); Mg(1)–C(31),
2.2377(17); Na(1)–C(1), 2.9184(17); Na(1)–C(2), 2.6993(17), Na(1)–C(11), 2.6905(18); Na(1)–C(12), 2.7420(18); Na(2)–C(21), 2.8580(17); Na(2)–C(22), 2.6159(17);
Na(2)–C(31), 2.6492(18); Na(2)–C(32), 2.7225(18); C(1)–Mg(1)–C(11), 102.76(6); C(1)–Mg(1)–C(21), 119.67(6); C(1)–Mg(1)–C(31), 116.16(6); C(11)–Mg(1)–C(21),
102.00(6); C(11)–Mg(1)–C(31), 112.06(7); C(21)–Mg(1)–C(31), 103.46(6).
metalated indole substituents [C(1), C(11), C(21) and C(31)] with and terminal TMP molecule and an α-deprotonated N-iso-
an average Mg–C bond length of 2.222 Å (mean 2.216 Å in propylindole [C(1)–Mg(1), 2.192(4) Å]. Similar to 3, the sodium
2
[13]). Each sodium atom in 3 makes electrostatic η2-interactions atom is interacting electrostatically with both the C(1) and C(2)
with the 2-C and 3-C atoms of each deprotonated indole unit atoms of the N-isopropylindole in a η2-manner, as indicated by
[range of lengths Na–C: 2.6159(17)–2.9184(17) Å]. Its coordina- the Na–C bond lengths of 2.857(4) and 2.646(4) Å respectively.
tion sphere is completed by a complexed bidentate molecule
of TMEDA making the Na atoms overall six coordinate.
The rational synthesis of both 2 and 3 was achieved by react-
ing NaTMP, Mg(CH2SiMe3)2, and TMEDA in a 2:1:2 ratio with four
equivalents of the respective indole (Scheme 1). In both cases
the desired product was isolated in a high crystalline yield (un-
optimised 81 % and 72 % respectively). The original synthesis is
likely to occur by a disproportionation reaction similar to that
which has been previously reported for 1 with thiophene[15]
and the mixed zincate bases [(TMEDA)Na(tBu)2Zn(TMP)] and
[Li(nBu)2Zn(TMP)(TMEDA)] and their reactivity towards indoles
and ferrocene respectively.[13,16]
When comparing complexes 2 and 3 to 4, although the
overall regioselectivity of 1 does not change, different complex
architectures are uncovered. The α-magnesiation of both N-
methyl and N-ethyl indole results in 1 or “[(TMEDA)2Na-
(TMP)2Mg(CH2SiMe3)2]” replacing all the available (potentially)
basic arms with α-magnesiated indole units, whereas in 4, only
one basic (CH2SiMe3) arm is lost. This makes 2 and 3 the prod-
ucts of a more atom efficient process. Complexes 2 and 3 are
obtained swiftly under ambient conditions (quantitative at
room temperature, 15 min), with no cooling or reflux conditions
(cf. lithiation of N-methylindole[21]) required to retain selectivity,
whereas 4 needs longer reaction times to achieve quantitation
Reaction of 1 with the more sterically encumbered N-iso- (16 h). Attempts to force 4 to be more atom-efficient and react
propylindole substrate at room temperature resulted in the faster unfortunately failed, even when an excess of N-isopropyl-
deposition of a yellow precipitate, which when recrystallised indole was employed under both room temperature and reflux
from n-hexane afforded X-ray quality single crystals. These conditions. It would therefore appear that the added steric bulk
were identified as [(TMEDA)Na(TMP)(α-C11H12N)Mg(TMP)] 4 of the N-isopropyl group in 4 inhibits the formation of a struc-
(Scheme 1 and Figure 2). Complex 4 adopts a familiar structural tural motif similar to 2 or 3. Examining the space filling diagram
motif,[17–20] whereby 1 has exhibited overall alkyl basicity, losing of 3 (Figure 3) demonstrates the steric congestion already
the CH2SiMe3 group and replacing it with an α-deprotonated present around the metal centres when an ethyl group is
N-isopropylindole unit. The molecular structure of 4 contains a present, most likely hindering the isolation of an isopropyl ana-
central trigonal planar magnesium atom, bonding to a bridging logue. To the best of our knowledge, structurally characterised
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Scheme 1. Reaction of 1 with methyl, ethyl and isopropyl N-alkyl indoles.
Figure 3. Space-filling diagram of compound 3.
1
Crystalline 2–4 were dissolved in C6D6 and analysed by H
and 13C NMR spectroscopy. The spectra indicate an α-substi-
tuted N-alkyl indole in a 2:1 ratio with TMEDA for 2 and 3 and
a 1:1 ratio for 4, with all three complexes preserving their solid
state composition in solution. The disappearance of the two
doublet signals (6.51 and 6.55 ppm for 2; 6.54 and 6.68 ppm
for 3; 6.57 and 6.88 ppm for 4) in the aromatic region corre-
sponding to the parent indole, and the appearance of a singlet
at δ = 6.53, 6.86 and 6.21 ppm respectively are indicative of an
α-magnesiated species. Large down field chemical shifts for the
2-C 13C resonance to 180.39, 181.49 and 178.79 ppm (parent
indole: 129.05, 126.5 and 123.0 ppm) in 2–4 respectively are
indicative of a magnesiation.
Figure 2. Molecular structure of [(TMEDA)Na(TMP)(α-C11H12N)Mg(TMP)] (4)
with thermal ellipsoids at 40 % probability. Hydrogen atoms are omitted for
clarity. Selected bond lengths [Å] and angles [°]: Mg(1)–C(1), 2.192(4); Mg(1)–
N(4), 2.070(3); Mg(1)–N(3), 2.009(3); Na(1)–N(4), 2.464(3); Na(1)–N(5), 2.499(4);
Na(1)–N(6), 2.457(4); Na(1)–C(1), 2.857(4); Na(1)–C(2), 2.646(4); C(1)–Mg(1)–
N(3), 121.72(15); N(3)–Mg(1)–N(4), 133.32(14); N(4)–Mg(1)C(1), 104.94(15).
Utilising the Mg–C bond in complexes 2–4, we examined
their potential use in both in situ iodolysis and Pd-catalysed
Mg–C or Mg–N bonded indole complexes are rare with only cross-coupling reactions[23] with iodobenzene. In a “one pot”
one previously reported Mg–C indole complex [(Na- procedure, all three complexes successfully gave their expected
TMEDA)2Mg(α-C9H8N)4][13] and two Mg–N bonded bis-indolyl 2-iodo-1-alkylindole or 2-phenyl-1-alkylindole products in un-
complexes [(C14H12SN)2Mg(THF)2] and [(C14H12ON)2Mg(THF)2] optimised high to moderate yields (I2 79–66 %; cross-coupling
reported in the literature.[22]
82–68 %, Scheme 2).
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Scheme 2. In situ iodolysis and cross coupling reactions of 2–4.
X-ray Data Collection, Reduction, Solution and Refinement
Conclusion
X-ray crystallographic data for 2 and 4 were obtained on a Bruker
X8 Nonius Kappa CCD diffractometer with graphite-monochro-
mated Mo-Kα (λ0 = 0.71073 Å) radiation at 123 K. All single crystals
were mounted on a glass fibre under oil. Data was collected and
processed using the Bruker Apex2 v.2012.2.0 software; Lorentz, po-
larisation and absorption corrections (multi-scan – SADABS)[27] were
applied. Crystallographic data of compound 3 was collected at the
MX1 beamline at the Australian Synchrotron, Melbourne, Victoria,
Australia (γ = 0.71070 A). All data was collected at 100 K, main-
tained using an open flow of nitrogen. The software used for data
collection and reduction of the data were BluIce[28] and XDS.[29]
Multi-scan absorption corrections (SADABS[27]) were applied. Com-
pounds 2, 3 and 4 were solved and refined with SHELX-2016[30] and
X-seed interface[31] or Olex2.[32] Compound 2 was modelled as a
two component twin (twin law –1 0 0 0 –1 0 0 0 1), BASF =
0.1492(19). Compound 3 had a disordered TMEDA molecule which
was modelled as disordered across two sites.
We have demonstrated that AMMMg with 1 can successfully α-
magnesiate three N-alkylated indoles selectively and under mild
reaction conditions. We have revealed, through X-ray crystallo-
graphic and solution characterisation, that the efficiency of 1 is
influenced by the steric nature of the N-alkyl group, leading to
a less atom efficient magnesiation as steric bulk is increased.
Utilising these selective indol-2-magnsiates in both in situ iodo-
lysis and Pd-catalysed cross-coupling reactions leads to the iso-
lation of the corresponding 2-iodo-1-alkylindole or 2-phenyl-1-
alkylindole products in high to moderate yields.
Experimental Section
General Experimental Details: All reactions (unless otherwise
stated) were completed under an atmosphere of dinitrogen and
anhydrous conditions using standard Schlenk-line techniques. Wa-
ter and oxygen were removed from n-hexane and diethyl ether
using a MBRAUN SPS-800 solvent purification system and were
stored over 4 Å molecular sieves under a dinitrogen atmosphere.
TMEDA was dried by reflux over CaH2 and stored over 4 Å molecular
sieves. TMP(H) was purchased from Oakwood Chemicals and stored
CCDC 1578143 (for 2), 1578142 (for 3), and 1578141 (for 4) contain
the supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre.
[(Na-TMEDA)2Mg(α-C9H8N)4] (2): N-Methylindole (0.13 mL,
1 mmol) was added to a stirred solution of GP1. A large quantity
of white precipitate was observed after roughly 10–15 min, which
was isolated by filtration and transferred to an argon glovebox for
storage. X-ray quality crystals were obtained upon recrystallisation
from n-hexane. Yield = 0.2 g, 24 % (max yield 25 % based on con-
sumption of N-methylindole). Rational synthesis of 2 was achieved
using GP2. N-methylindole (0.52 mL, 4 mmol) was added to a
stirred solution of GP2. This resulted in the immediate formation of
a clear solution. After approximately 10–20 min, a large quantity of
a white precipitate was observed, which was identified by NMR as
2. Isolated crystalline yield = 0.67 g, 81 % (quantitative by NMR). 1H
1
over 4 Å molecular sieves. H and 13C NMR spectra were recorded
on Bruker DRX 400 MHz or 600 MHz Cryo spectrometers with chem-
ical shifts internally referenced to C6D6 or CDCl3. Microanalysis were
carried out at the Science Centre, London Metropolitan University,
with samples prepared in air-tight sealed glass ampules. N-meth-
ylindole was purchased from Aldrich and stored over 4 Å molecular
sieves. N-ethylindole,[24] N-isopropylindole,[25] nBuNa,[26] and
[14]
Mg(CH2SiMe3)2
dures.
were prepared according to literature proce-
GP1: nBuNa (0.08 g, 1 mmol) was suspended in 10 mL of dry n-
hexane. To this suspension was added TMP(H) (0.34 mL, 2 mmol)
dropwise, and the reaction was stirred at room temperature for at NMR (400 MHz, C6D6, 300 K): δ = 7.68–7.60 (m, 1 H, H3), 7.27 (m, 1
4
least 30 min. Next, Mg(CH2SiMe3)2 (0.2 g, 1 mmol) was added with
subsequent addition of TMEDA (0.15 mL, 1 mmol), affording a pale
yellow, clear solution, which was used in situ. GP2: nBuNa (0.16 g,
2 mmol) was suspended in 10 mL of dry n-hexane. To this suspen-
H, H6), 7.21–7.16 (m, 2 H, H4/H5), 6.94 (d, JHH = 0.9 Hz, 1 H, H2),
4.15 (s, 3 H, CH3), 1.19 (s, 6 H, CH3-TMEDA), 1.06 (s, 2 H, CH2-TMEDA)
ppm. 13C NMR (101 MHz, C6D6, 300 K): δ = 180.39 (Mg-C2), 141.17,
131.79, 118.52 (C5/6), 117.97 (C4), 117.65 (C5/6), 109.71 (C3), 108.62
sion was added TMP(H) (0.34 mL, 2 mmol) dropwise, and the reac- (C7), 55.84 (CH2-TMEDA), 44.46 (CH3-TMEDA), 36.57 (CH3) ppm.
tion was stirred at room temperature for at least 30 min. Next C48H64MgN8Na2 (823.37): calcd. C 70.19, H 7.61, N 13.64; found C
Mg(CH2SiMe3)2 (0.2 g, 1 mmol) was added with subsequent addi-
tion of TMEDA (0.3 mL, 2 mmol). The resulting pale yellow, cloudy
solution was used in situ.
69.73, H 7.65, N 13.41. Crystal data for compound 2 C48H64MgN8Na2:
M = 823.38, colourless plates, 0.21 × 0.20 × 0.14 mm3, monoclinic,
space group P21/c, a = 17.6570(16), b = 16.8891(15), c = 15.9701(14),
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α = 90°, ꢀ = 90.628(4)°, γ = 90°, V = 4762.2(7) Å 3, Z = 4, Dc
1.148 g/cm3, F(000) = 1768, T = 123(2) K, 82061 reflections collected,
=
dropwise at room temperature. The resulting solution was stirred
overnight and quenched with saturated Na2S2O3 sodium thiosulfate
10691 unique (Rint = 0.1037), Final GooF = 1.022, R1 = 0.0794, wR2 = (20 mL). The solution was diluted with CH2Cl2, dried with MgSO4
0.2648, 545 parameters, 0 restraints. Lp and absorption corrections
applied, μ = 0.096 mm–1. Refined as a two-component twin (Twin
law –1 0 0 0 –1 0 0 0 1), BASF = [0.1492(19)].
and the solvent removed in vacuo. N-methyl-2-iodoindole was iso-
lated as a crystalline solid. N-ethyl-2-iodoindole and N-isopropyl-2-
iodoindole were isolated as pale yellow oils following purification
by flash chromatography (silica gel, n-hexane). N-methyl-2-iodoin-
dole: 0.81 g, 79 %: 1H NMR (400 MHz, CDCl3, 300 K): δ = 7.57 (d,
[(Na-TMEDA)2Mg(α-C10H11N)4] (3): N-Ethylindole (0.15 g, 1 mmol)
was added dropwise to a stirred solution of GP1. After approxi-
mately five minutes, formation of a white precipitate was observed.
The precipitate was isolated by filtration, washed with n-hexane and
dried in vacuo, before storage in an argon glove box. X-ray quality
crystals were obtained upon recrystallisation in toluene. Both the
crystalline material and the powder were found to be the same
product by NMR analysis. Yield = 0.2 g, 24 % (maximum yield 25 %
based on consumption of N-ethylindole). Rational synthesis of 3: To
a stirred suspension of GP2 was added N-ethylindole (0.58 g,
4 mmol) dropwise, resulting in the immediate formation of a clear
solution. After approximately 10–20 min, a large quantity of a white
precipitate was observed, which was identified by NMR as the title
species. Isolated crystalline yield: 0.586 g, 70 % (quantitative by
3
3JHH = 7.9 Hz, 1 H, H3), 7.34 (d, JHH = 8.3 Hz, 1 H, H6), 7.19 (d,
3
3JHH = 7.4 Hz, 1 H, H5), 7.11 (t, JHH = 7.4 Hz, 1 H, H4), 6.84 (s, 1 H,
H2), 3.79 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3, 300 K): δ = 138.19,
129.74, 121.96 (C4), 119.93 (C5), 119.62 (C6), 111.94 (C2), 109.82 (C7),
84.10 (C1), 34.19 (CH3) ppm. N-ethyl-2-iodoindole: 0.72 g, 66 %: 1H
NMR (600 MHz, CDCl3, 300 K): δ = 7.53 (dt, 3JHH = 7.9, 4JHH = 1.0 Hz,
3
4
1 H, H3), 7.33 (dd, JHH = 8.3, JHH = 0.9 Hz, 1 H, H6), 7.15 (ddd,
3JHH = 8.3, 7.1, JHH = 1.2 Hz, 1 H, H5), 7.06 (ddd, JHH = 7.9, 7.1,
4
3
4JHH = 1.0 Hz, 1 H, H4), 6.78 (d, JHH = 0.8 Hz, 1 H, H2), 4.23 (q,
4
3JHH = 7.2 Hz, 2 H, CH2), 1.35 (t, JHH = 7.2 Hz, 3 H, CH3) ppm. 13C
3
NMR (151 MHz, CDCl3, 300 K): δ = 137.01, 130.08, 121.87 (C5),
119.89 (C4), 119.76 (C3), 112.11 (C2), 109.74 (C6), 82.58 (C1), 42.25
(CH2), 15.35 (CH3) ppm. HRMS (ESI) ([M + H]+) calcd. for C10H10IN:
1
NMR). H NMR (400 MHz, C6D6, 300 K): δ = 7.63–7.56 (m, 1 H, H4),
271.9936, found 271.9925. IR: ν = (ax =) 3052 (w), 2939 (w), 1602
˜
7.29 (m, 1 H, H7), 7.17–7.08 (m, 2 H, H5/H6), 6.86 (s, 1 H, H3), 4.70
(w), 1512 (m), 1463 (s), 1420 (m), 1385 (m), 1316 (s), 1241 (s), 1205
(m) 1130 (m), 1075 (s), 1008 (s), 919 (m), 837 (m), 733 (s), 698 (s)
cm–1. N-isopropyl-2-iodoindole: 0.22 g, 78 %: 1H NMR (400 MHz,
CDCl3, 300 K): δ = 7.50–7.45 (m, 2 H, H4/7), 7.05–7.00 (m, 2 H, H5/
3
3
(q, JHH = 7.0 Hz, 2 H, CH2), 1.44 (t, JHH = 7.1 Hz, 3 H, CH3), 1.28 (s,
6 H, TMEDA-CH3), 1.21 (s, 3 H, TMEDA-CH2) ppm. 13C NMR (101 MHz,
C6D6, 300 K): δ = 181.49 (Mg-C2), 140.45, 132.73, 119.01 (C5/6),
118.58 (C5/6), 118.23 (C4), 109.88 (C7), 109.64 (C3), 56.79 (CH2-
TMEDA), 45.25 (CH3-TMEDA), 45.14 (CH2), 17.31 (CH3) ppm. Crystal
data for Compound 3 C52H72MgN8Na2: M = 1198.37, colourless
plates, 0.04 × 0.03 × 0.02 mm3, triclinic, space group Pbca, a =
16.682(3), b = 16.236(3), c = 38.216(8), α = 90°, ꢀ = 90°, γ = 90°, V =
10351(4) Å3, Z = 8, Dc = 1.129 g/cm3, F(000) = 3792.0, T = 100(2) K,
85955 reflections collected, 12826 unique (Rint = 0.706), Final
GooF = 1.056, R1 = 0.0706, wR2 = 0.1528, 612 parameters, 0 re-
3
3
6), 6.67 (d, JHH = 0.9 Hz, 1 H, H2),4.78 (septet, JHH = 7.1 Hz, 1 H,
CH), 1.56 (d, 3JHH = 7.1 Hz, 9 H, CH3) ppm. 13C NMR (101 MHz, CDCl3,
300 K): δ = 123.00 (C4/7), 120.91 (C5/6), 120.85 (C5/6), 119.68 (C4/
7), 111.19 (C3), 57.96 (CH), 21.12 (CH3) ppm. HRMS (ESI) ([M + H]+)
calcd. for C11H12IN: 286.0093, found 286.0082. IR: ν = (ax =) 2967
˜
(m), 2931 (m), 2440 (w), 1701 (w), 1457 (s), 1438 (s), 1400 (s), 1383
(m), 1336 (m), 1303 (s), 1260 (m), 1220 (s), 1087 (s), 1011 (s), 906
(m), 800 (m), 738 (s) cm–1
.
straints. Lp and absorption corrections applied, μ = 0.090 mm–1
.
Cross-Coupling Protocol: To a stirred solution of either 2, 3 or 4,
was added iodobenzene (5 equiv. for 2 and 3, 2 equiv. for 4), fol-
lowed by the addition of 4 mol-% of Pd(dbbf)Cl2. The reaction was
refluxed for 16 hours. After cooling to room temperature, the solu-
tion was quenched with saturated NH4Cl, extracted with dichloro-
methane, dried with anhydrous MgSO4 and the solvent was re-
moved in vacuo. N-methyl-2-phenylindole and N-ethyl-2-phenyl-
indole were isolated as crystalline solids, and N-isopropyl-2-phenyl-
indole was isolated as a pale yellow oil following flash chromatogra-
phy (silica gel, n-hexane). Compounds prepared were consistent
with literature values. N-methyl-2-phenylindole:[13] 0.68 g, 82 %:
[(TMEDA)Na(TMP)(α-C11H12N)Mg(TMP)] (4): N-Isopropylindole
(0.16 g, 1 mmol) was added dropwise to a stirred solution of GP1.
After stirring overnight, a white precipitate was observed and col-
lected via filtration, washed with n-hexane and dried in vacuo, be-
fore storage in a glovebox. X-ray quality single crystals were ob-
tained upon recrystallisation from n-hexane. Both the crystalline
material and the powder were found to be the same product by
1
NMR analysis. Yield: 0.35 g, 58 %. H NMR (400 MHz, C6D6, 300 K):
δ = 7.49 (m, 2 H, H3/6), 7.1–7.2 (m, 2 H, H4/5), 6.21 (d, 4JHH = 0.8 Hz,
3
3
1 H, H2), 5.16 (septet, JHH = 6.8 Hz, 1 H, CH), 1.69 (d, JHH = 6.8 Hz,
6 H, CH3), 1.88 (m, 4 H, γ-CH2 TMP), 1.59 [s (br), 24 H, CH3 TMP],
1.46 [s (br), 12 H, CH3, TMEDA], 1.44 [s (br), 4 H, CH2, TMEDA], 1.39
[s (br), 6 H, ꢀ-CH2 TMP] ppm. 13C NMR (100 MHz, C6D6, 300 K): δ =
178.79 (Mg-C2), 138.0, 133.4, 118.4 (C4), 117.8 (C7), 117.7 (C5), 111.1
(C6), 106.4 (C3), 56.4 (CH2 TMEDA), 54.1 (CH-isopropyl), 52.2 (TMP-
quaternary), 45.2 (CH3 TMEDA), 41.8 (ꢀ-CH2 TMP), 35.7 (CH3 TMP),
22.3 (CH3 isopropyl), 20.0 (γ-CH2 TMP) ppm. C70H122Mg2N10Na
(1175.40): calcd. C 69.80, H 10.71, N 11.63; found C 69.88, H 9.96, N
11.45. Crystal data for compound 4 C70H122Mg2N10Na2: M =
1198.37, colourless plates, 0.18 × 0.16 × 0.10 mm3, triclinic, space
3
1H NMR (600 MHz, CDCl3, 300 K): δ = 7.65 (d, JHH = 7.7 Hz, 1 H,
3
4
3
H4), 7.52 (dd, JHH = 8.3, JHH = 1.3 Hz, 2 H, ortho-H), 7.48 (t, JHH
=
3
7.6 Hz, 2 H, meta-H), 7.41 (t, JHH = 7.3 Hz, 1 H, para-H), 7.38 (d,
3JHH = 8.2 Hz, 1 H, H7), 7.28–7.23 (m, 2 H, H6), 7.18–7.13 (m, 1 H,
H5), 6.57 (s, 1 H, H3), 3.76 (s, 3 H, CH3) ppm. 13C NMR (151 MHz,
CDCl3, 300 K): δ = 141.79, 138.55, 133.07, 129.60 (meta-C), 128.70
(ortho-C), 128.17, 128.07 (para-C), 121.87 (C6), 120.68 (C5), 120.07
(C4), 109.81 (C7), 101.86 (C3), 31.40 (CH3) ppm. N-ethyl-2-phenyl-
indole:[33] 0.60 g, 68 %: H NMR (400 MHz, CDCl3, 300 K): δ = 7.63
(dt, JHH = 7.8, JHH = 1.0 Hz, 1 H, H4), 7.53–7.36 (m, 6 H, Ph + H7),
1
3
4
group P1, a = 11.5469(4), b = 16.3939(6), c = 20.4362(8), α =
¯
3
4
7.26–7.19 (m, 1 H, H6), 7.13 (ddd, JHH = 8.0, 7.0, JHH = 1.0 Hz, 1 H,
81.102(2)°, ꢀ = 85.116(2)°, γ = 72.647(2)°, V = 3644.9(2) Å3, Z = 2,
Dc = 1.092 g/cm3, F(000) = 1316, T = 123(2) K, 49988 reflections
collected, 14416 unique (Rint = 0.1065), Final GooF = 1.038, R1 =
0.0794, wR2 = 0.2291, 783 parameters, 0 restraints. Lp and absorp-
H5), 6.52 (d, 4JHH = 0.9 Hz, 1 H, H3), 4.18 (t, JHH = 7.2 Hz, 2 H, CH2),
3
1.32 (d, JHH = 7.2 Hz, 3 H, CH3) ppm. 13C NMR (101 MHz, CDCl3,
3
300 K): δ = 141.30, 137.31, 133.44, 129.59 (meta-C), 128.69 (ortho-
C), 128.53, 128.14 (para-C), 121.74 (C6), 120.80 (C4), 119.98 (C5),
110.08 (C7), 102.31 (C3), 38.96 (CH2), 15.59 (CH3) ppm. N-isopropyl-
2-phenylindole:[34] 0.17 g, 71 %: 7.64–7.59 (m, 2 H, H4/7), 7.5–7.4
(m, 5 H, phenyl-H), 7.20–7.15 (m, 2 H, H5/6), 6.45 (d, 1 H, J = 0.8,
tion corrections applied, μ = 0.090 mm–1
.
Iodolysis Protocol: To a stirred solution of 2, 3 or 4, was added a
solution of iodine in THF (10 mL for 2 and 3, 5 mL for 4)
1
M
Eur. J. Inorg. Chem. 2018, 74–79
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© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
H3), 4.68 (septet, 1 H, J = 7.0, CH), 1.6 (d, 1 H, J = 7.0, CH3). 13C NMR
(101 MHz, CDCl3, 300 K): δ = 141.41, 135.44, 133.81, 131.98, 129.64
(meta-C), 128.42 (ortho-C), 127.93 (para-C), 121.01 (C5/6), 120.85
(C5/6), 119.44 (C4/7), 112.40 (C4/7), 102.21 (C3), 47.90 (CH), 21.57
(CH3) ppm.
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Acknowledgments
We thank the Australian Research Council (DE140101137) and
Monash University for financial support. This research was sup-
ported by an Australian Government Research Training Program
(RTP) Scholarship. The authors acknowledge that part of this
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Received: November 9, 2017
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