13C{1H} NMR (100.62 MHz, 300 K, D12-cyclohexane): d 172.0
(Cortho–Zn), 145.3 (Cipso), 140.8 (Cmeta), 129.0 (Cpara or Cmeta0), 126.8
(Cpara or Cmeta0), 125.2 (Cortho0), 84.2 (PhCH2), 59.1 (OCH3), 58.3
[NCH2 (TMEDA)], 53.4 [a-C (TMP)], 52.9 [a-C (TMP)], 46.2 [NCH3
(TMEDA)], 41.0 [b-CH2 (TMP)], 40.0 [b-CH2 (TMP)], 37.4 [CH3
(TMP)], 36.0 [CH3 (TMP)], 35.5 [CH3 (TMP)], 35.0 [CH3 (TMP)], 34.6
[CCH3 (tBu)], 20.5 [g-CH2 (TMP)], 20.1 [CCH3 (tBu)].
Synthesis of 1-iodo-2-(methyoxymethyl)benzene (3): an in situ
hexane solution of the previously reported4 zincate 1 (2 mmol) was
prepared as described above. Benzyl methyl ether (1 or 2 mmol) was
then added to the base. The yellow solution was allowed to stir at
ambient temperature for 48 h. The resultant orange solution was
treated with a freshly prepared solution of 1 M iodine in THF (4 mL,
4 mmol). Distilled water was then introduced. The organic phase was
washed three times before being dried over MgSO4. The NMR
spectrum of the crude material was obtained to determine the yield
of 3 relative to benzyl methyl ether. Yields of 3 were 88% and 59%
when 1 mmol and 2 mmol of benzyl methyl ether, respectively
were utilised. No other organic iodine-containing compounds were
detected. H NMR (400.13 MHz, 300 K, D6-benzene): d 7.62 (d, 1H,
Hmeta), 7.38 (d, 1H, Hortho0), 7.00 (t, 1H, Hmeta0), 6.56 (t, 1H, Hpara),
4.27 (s, 2H, PhCH2), 3.10 (s, 3H, OCH3).
Crystal data for 2: C27H52N3NaOZn, Mr = 523.08, monoclinic,
space group P21, a = 9.236(2), b = 16.527(2), c = 10.6095(19) A,
b = 114.39(3)1, V = 1475.0(5) A3, Z = 2, l = 0.71073 A,
m = 0.869 mmꢀ1, T = 123(2) K; 13 428 reflections, 7511 unique,
Rint = 0.0309; final refinement to convergence on F2 gave R = 0.0309
(F, 6567 obs. data only) and Rw = 0.0370 (F2, all data), GOF = 0.973,
Flack parameter 0.052(7).
Fig. 2 View of 2 along the Znꢂ ꢂ ꢂNa axis highlighting the non-
equivalent TMP Me groups.
1
ratio was 1 : 1, 59% of 1-iodo-2-(methyoxymethyl)benzene,
3 was prepared following standard electrophilic quenching
procedures. Increasing the base : ether ratio to 2 : 1 resulted
in the isolation of 3 in 88% yield. The need for an excess of
base in zincate metallations to achieve enhanced reaction
yields has been noted previously during the metallation of
alkylbenzoate and p-deficient heteroaromatic compounds
by a related lithium-containing zincate base.3a To further
emphasise the highly regioselective nature of the zincation
reaction, the NMR spectrum of a D6-benzene solution of 3
again showed no signs of any other iodinated products.
The successful isolation and characterisation of 2 has shown
that sodium-mediated zincation can be utilised to achieve pre-
viously unobtainable metallation regioselectivities using highly
favourable reaction conditions. Other key aromatic substrates,
including a range of primary and secondary alkyl ethers, which
have so far shown little or no promise in the classical DoM
reaction will be studied using alkali metal mediated zincation in
the future.
1 J. A. Wanklyn, Ann. Chem. Pharm., 1858, 107, 125.
2 R. E. Mulvey, F. Mongin, M. Uchiyama and Y. Kondo, Angew.
Chem., Int. Ed., 2007, 46, 3802.
3 (a) Y. Kondo, M. Shilai, M. Uchiyama and T. Sakamoto, J. Am.
Chem. Soc., 1999, 121, 3539; (b) M. Uchiyama, Y. Matsumoto,
D. Nobuto, T. Furuyama, K. Yamaguchi and K. Morokuma,
J. Am. Chem. Soc., 2006, 128, 8748; (c) R. E. Mulvey, Acc. Chem.
Res., 2009, 42, 743; (d) M. Mosrin, G. Monzon, T. Bresser and
P. Knochel, Chem. Commun., 2009, 5615.
4 P. C. Andrikopoulos, D. R. Armstrong, H. R. L. Barley, W. Clegg,
S. H. Dale, E. Hevia, G. W. Honeyman, A. R. Kennedy and
R. E. Mulvey, J. Am. Chem. Soc., 2005, 127, 6184.
´
5 D. R. Armstrong, J. Garcı
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a-Alvarez, D. V. Graham,
G. W. Honeyman, E. Hevia, A. R. Kennedy and R. E. Mulvey,
Chem.–Eur. J., 2009, 15, 3800.
The authors thank E. Hevia for helpful discussions and the
EPSRC for generously supporting this work.
6 (a) C. G. Hartung and V. Snieckus, in Modern Arene Chemistry,
ed. D. Astruc, Wiley-VCH, New York, 2002, p. 330;
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R. E. Mulvey, Angew. Chem., Int. Ed., 2006, 45, 2370;
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G. W. Honeyman and R. E. Mulvey, Angew. Chem., Int. Ed.,
2006, 45, 2374.
Notes and references
z All reactions were carried out under a protective argon atmosphere.
Synthesis of [(TMEDA)Na(m-TMP)(m-C6H4CH2OMe)Zn(tBu)] (2):
a solution of tBu2Zn (0.358 g, 2 mmol) in hexane (10 mL) was
transferred by cannula to a suspension of NaTMP in hexane [prepared
in situ by reaction of nBuNa (0.16 g, 2 mmol) with TMP(H) (0.34 mL,
2 mmol)]. TMEDA (0.30 mL, 2 mmol) was then added. The resultant
suspension was gently heated to produce a homogenous yellow
solution to yield an in situ mixture of 1.4 Benzyl methyl ether
(0.24 mL, 2 mmol) was added to the solution and the reaction mixture
was allowed to stir at ambient temperature for 12 h. The resulting
orange solution was concentrated in vacuo, preceding the growth of
large colourless crystals of 2 (0.51 g, 49%). Anal: actual C 61.99,
H 10.02, N 8.03; found C 61.04, H 10.00, N 7.74%. 1H NMR
(400.13 MHz, 300 K, D12-cyclohexane): d 7.59 (d, 1H, Hmeta), 7.01
(m, 2H, Hpara and Hmeta0), 6.90 (m, 1H, Hortho0), 4.48 (d, 1H, PhCH),
4.07 (d, 1H, PhCH), 3.43 (s, 3H, OCH3), 2.10 [br s, 4H, NCH2
(TMEDA)], 1.83 [br s, 12H, NCH3 (TMEDA)], 1.75 [m, 2H, g-CH2
(TMP)], 1.38 [m, 4H, b-CH2 (TMP) (observed by COSY NMR
spectroscopy)], 1.34 [s, 3H, CH3 (TMP)], 1.29 [s, 3H, CH3 (TMP)],
1.16 [s, 3H, CH3 (TMP)], 1.14 [s, 3H, CH3 (TMP)], 0.84 [s, 9H, CH3 (tBu)].
8 A. R. Kennedy, J. Klett, R. E. Mulvey and D. S. Wright, Science,
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9 (a) J. Clayden, in Organolithiums: Selectivity for Synthesis, Elsevier
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Science Ltd., Oxford, 2002, p. 56; (b) U. Schollkopf, Angew.
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ꢁc
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