Potassium-Mediated Magnesiation of Anisole
COMMUNICATION
tube was then placed in the freezer (ꢀ288C) to yield colorless crystals
(0.41 g). 1H NMR (400.13 MHz, C6D12): d=7.53 (d, 1H; J=6.4 Hz, H of
anisole), 6.94 (t, 1H, J=7.6 Hz; H of anisole), 6.81 (t, 1H; J=6.5 Hz, H
of anisole), 6.58 (d, J=8.0 Hz 1H; H of anisole), 3.72 (s, 3H; OCH3 of
anisole), 2.23–2.27 (m, 8H; 4ꢅCH2 of PMDETA), 2.06 (s, 15H; 5ꢅCH3
of PMDETA), 1.72 (m, 2H; gCH2 of TMP), 1.35 (t, 4H, J=6.0 Hz; 2ꢅ
bCH2 of TMP), 1.22 (s, 12H; 4ꢅCH3 of TMP), ꢀ0.28 (s, 9H; 3ꢅCH3 of
This has established that the heteroleptic base reacts kineti-
cally through its TMP component to generate the first
ortho-magnesiated anisole product [(pmdeta)K
C6H4OMe)Mg(CH2SiMe3)], 2, which, in turn, reacts through
its alkyl component to yield the thermodynamic final ortho-
ACHTUNGTRENUN(NG m-tmp)(o-
ACHTUNGTRENNUNG
magnesiated
anisole
product
[(pmdeta)KACTHNGUETRNNU(G m-tmp)(o-
Me3Si), ꢀ1.60 ppm (s, 2H; Mg CH2 Si); 13C NMR (100.63 MHz, C6D12):
d=163.0 (ipso-C of anisole), 141.4 (aromatic C at Hd=7.53), 126.8 (aro-
matic C at Hd=6.94), 123.2 (aromatic C at Hd=6.81), 109.7 (aromatic C
at Hd=6.58), 57.9 (2ꢅCH2 of PMDETA), 56.5 (2ꢅCH2 of PMDETA),
56.3 (CH3 of anisole), 52.7 (2ꢅaC of TMP), 45.6 (4ꢅCH3 of PMDETA),
42.2 (CH3 of PMDETA), 41.4 (2ꢅbCH2 of TMP), 35.3 (4ꢅCH3 of TMP),
ꢀ
ꢀ
C6H4OMe)MgACHTUNGTRENNUNG(tmp)], 3, and Me4Si (R’H). This most com-
plete study of any alkali-metal-mediated metalation to date
has greatly improved our knowledge of how such reactions
work and will help towards the rational design of new syn-
thetic applications in the future. An important consideration
that this study brings out is that the timing of any subse-
quent electrophilic quench of the base–substrate reaction
mixture may be critical to the outcome given the presence
of different ortho-magnesiated products, though both should
yield the same functionalized anisole product on electrophil-
ic quenching. Studies aimed at exploring this factor are cur-
rently in progress in our laboratory.
ꢀ
ꢀ
20.9 (gCH2 of TMP), 4.3 (3ꢅCH3 of Me3Si), ꢀ3.8 ppm (Mg CH2 Si).
Synthesis of [(pmdeta)K(m-tmp)(o-C6H4OMe)Mg(tmp)] (3): Hexane
N
ACHTUNGTRENNUNG
(10 mL) was added to an oven-dried Schlenk tube followed by 1m
nBu2Mg (2 mL, 2 mmol) and TMP(H) (0.68 mL, 4 mmol). The reaction
mixture was placed under reflux conditions for 5 h, and was then trans-
ferred, through
a cannula, to a separate Schlenk tube containing
KCH2SiMe3 (0.24 g, 2 mmol). Next PMDETA (0.42 mL, 2 mmol) was
added to produce a clear yellow solution. Anisole (0.22 mL, 2 mmol) was
added to the reaction mixture, which was stirred for 4 days. The Schlenk
tube was then placed in the freezer (ꢀ288C) to yield colorless crystals
1
(0.44 g). H NMR (400.13 MHz, C6D12): d=7.47 (brd, 1H; H of anisole),
6.96 (t, 1H, J=7.2 Hz; H of anisole), 6.81 (t, 1H, J=6.4 Hz; H of ani-
sole), 6.52 (d, 1H, J=7.8 Hz; H of anisole), 3.60 (s, 3H; OCH3 of ani-
sole), 2.22–2.29 (m, 8H; 4ꢅCH2 of PMDETA), 2.09 (s, 3H; CH3 of
PMDETA), 2.02 (s, 12H; 4ꢅCH3 of PMDETA), 1.67 (m, 4H; 2ꢅgCH2
of TMP), 1.24 (s, 24H; 8ꢅCH3 of TMP), 1.06 ppm (m, 8H; 4ꢅbCH2 of
TMP); 13C NMR (100.63 MHz, C6D12): d=139.7 (aromatic C at Hd=
7.47), 126.1 (aromatic C at Hd=6.96), 122.8 (aromatic C at Hd=6.81),
109.1 (aromatic C at Hd=6.52), 58.2 (2ꢅCH2 of PMDETA), 56.9 (2ꢅ
CH2 of PMDETA), 55.2 (CH3 of anisole), 52.7 (4ꢅaC of TMP), 45.7 (4ꢅ
CH3 of PMDETA), 42.7 (4ꢅbCH2 of TMP), 42.5 (CH3 of PMDETA),
36.0 (8ꢅCH3 of TMP), 20.6 ppm (2ꢅgCH2 of TMP).
Experimental Section
Methods and materials: All reactions and manipulations were performed
by using standard Schlenk techniques under argon gas. Products were iso-
lated inside an argon-filled dry box. Solvents were freshly distilled from
sodium/benzophenone prior to use. TMP(H) was obtained from Aldrich,
distilled from CaH2 and stored over 4 ꢄ molecular sieves. All other
chemicals were obtained from Aldrich and used as supplied. 1H and
13C NMR spectra were proton decoupled. Correlations between protons
and carbon atoms were obtained through COSY and HSQC NMR spec-
troscopic methods. Single-crystal X-ray diffraction data were recorded on
an Oxford Diffraction Gemini S and A Ultra diffractometers and a
Nonius Kappa CCD diffractometer using MoKa (l=0.71073 ꢄ) or CuKa
(l=1.54184 ꢄ) radiation.[21] The structures were solved by direct meth-
ods (SHELX program family or SIR) and refined on all unique F2 values
(SHELX).[22] CCDC-737822, CCDC-737823, and CCDC-737824 contain
the supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Computational methods: The structure of 1 was obtained from the crys-
tallographic coordinates and the dislocations in the PMDETA ligand
were removed manually. The structure was optimized at the BP86-D/
def2-TZVP level of theory by using TurboMole.[23] The converged wave-
function file from the optimized structure was used for the subsequent
Bader and NBO analyses. The Bader analysis was performed with the
AIM2000[24] program and the NBO perturbation study was carried out
within the NBO5.0[18] program.
Synthesis of [(pmdeta)KACTHNUTRGENNUG(m-tmp)(m-CH2SiMe3)MgHCATUNGTRENN(UGN tmp)] (1): Hexane
(10 mL) was added to an oven-dried Schlenk tube followed by 1m
nBu2Mg (2 mL, 2 mmol) and TMP(H) (0.68 mL, 4 mmol). The reaction
mixture was placed under reflux conditions for 5 h, and was then trans-
ferred, through
a cannula, to a separate Schlenk tube containing
Acknowledgements
KCH2SiMe3 (0.24 g, 2 mmol). Next PMDETA (0.42 mL, 2 mmol) was
added to produce a clear yellow solution. The Schlenk tube was placed in
the freezer (ꢀ288C) to yield colorless crystals (0.65 g, 54% yield).
1H NMR (400.13 MHz, C6D12): d=2.36 (m, 8H; 4ꢅCH2 of PMDETA),
2.23 (s, 12H; 4ꢅCH3 of PMDETA), 2.22 (s, 3H; CH3), 1.72 (m, 4H; 2ꢅ
gCH2 of TMP), 1.25 (m, 24H; 8ꢅCH3 of TMP), 1.21 (t, 8H, J=6.1 Hz;
4ꢅbCH2 of TMP), 0.01 (s, 9H; 3ꢅCH3 of Me3Si), ꢀ2.11 ppm (s, 2H;
We thank the UK EPSRC for their generous sponsorship through grant
awards EP/D076889/1 and EP/F03637X/1 and the Royal Society/Wolfson
Foundation for a research merit award to R.E.M. This research was also
supported by a Marie Curie Intra European Fellowship within the 7th
European Community Framework Programme (for P.G.-A.). Our useful
discussions with Dr. E. Hevia and Dr. C. OꢀHara are also gratefully ac-
knowledged.
metal CH2 Si); 13C NMR (100.63 MHz, C6D12): d=57.1 (2ꢅCH2 of
PMDETA), 55.3 (2ꢅCH2 of PMDETA), 52.1 (4ꢅaC of TMP), 45.0 (4ꢅ
CH3 of PMDETA), 41.7 (CH3 of PMDETA), 41.1 (4ꢅbC of TMP), 34.9
ꢀ
ꢀ
ꢀ
ꢀ
(8ꢅCH3 of TMP), 19.9 (2ꢅgCH2 of TMP), 4.1 (metal CH2 Si), 4.0 ppm
(3ꢅCH3 of Me3Si).
Keywords: crystal structure · magnesiation · metalation ·
NMR spectroscopy · potassium
Synthesis of [(pmdeta)KACHTNURTGENNUG(m-tmp)(o-C6H4OMe)MgACHUTNTGERN(NUGN CH2SiMe3)] (2):
Hexane (10 mL) was added to an oven-dried Schlenk tube followed by
1m nBu2Mg (2 mL, 2 mmol) and TMP(H) (0.68 mL, 4 mmol). The reac-
tion mixture was placed under reflux conditions for 5 h, and was then
transferred, through a cannula, to a separate Schlenk tube containing
KCH2SiMe3 (0.24 g, 2 mmol). Next PMDETA (0.42 mL, 2 mmol) was
added to produce a clear yellow solution. Anisole (0.22 mL, 2 mmol) was
added to the reaction mixture, which was stirred for 2 h. The Schlenk
[1] For recent reviews on alkali-metal-magnesiates and their applica-
tions in deprotonative metalations, see: a) R. E. Mulvey, Organome-
Chem. Eur. J. 2009, 15, 10702 – 10706
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
10705