Sodium-Mediated Magnesiation
COMMUNICATION
was allowed to stir at ambient temperature for 18 h. NH4Cl (5 mL) was
added along with the addition of a saturated aqueous solution of Na2S2O3
until bleaching (6 mL) occurred and then CH2Cl2 (10 mL) was added.
The organic layer was separated from the aqueous layer and dried over
magnesium sulfate. The solvent was removed under vacuum to give a
yellow oil that was purified by column chromatography using CH2Cl2 as
eluent to afford 1-iodothiophene (0.2155 g, 86%). 1H NMR (500 MHz,
C6D6, 300 K): d=6.90 (dd, 1H; thiophene), 6.67 (dd, 1H; thiophene),
6.27 (m, 1H; thiophene).
philes under alternative reaction conditions, and indeed with
ꢀ
different types of C C bond formations in future work.
In summary, we have shown that when common sulfur-
containing heterocycles (thiophene and THT) are subjected
to sodium-mediated magnesiation, selective mono-a-depro-
tonation occurs. The structural chemistries of the isolated
metallo-compounds are remarkably different from those ob-
served previously with their closely related furan and THF
analogues.
Crystal data for 3: C24H41MgN4NaS3; Mr =529.09; monoclinic; space
group P21/c; a=10.1527(8), b=27.855(2), c=11.1678(8) ꢂ; b=
113.372(9)8; V=2899.2(4) ꢂ3; Z=4; m=0.311 mmꢀ1; 19264 reflections;
6494 unique; Rint 0.0757; final refinement to convergence on F2 gave R=
0.0451 (F, 3146 obs. data only) and Rw =0.0809 (F2, all data); GOF=
0.794.
Experimental Section
Crystal data for 4: C28H59MgN4NaS; Mr =531.15; triclinic; space group
General: All reactions and manipulations were carried out in an atmos-
phere of dry, pure argon gas, using standard Schlenk protocols. Hexane
was freshly distilled over Na/benzophenone. NMR spectroscopy samples
were prepared under a protective atmosphere inside a glove box using
C6D6 or [D8]THF as solvent (which was degassed by using freeze–pump–
thaw cycles, and pre-dried over 4 ꢂ molecular sieves). TMEDA was dis-
tilled over CaH2 and stored over 4 ꢂ molecular sieves. nBuLi in the form
¯
P1; a=10.3631(7), b=11.1764(8), c=15.5624(10) ꢂ; a=102.133(6), b=
107.474(6), g=98.968(6)8; V=1633.88(19) ꢂ3; Z=2; m=0.153 mmꢀ1
;
27027 reflections; 7702 unique; Rint 0.0286; final refinement to conver-
gence on F2 gave R=0.0519 (F, 5437 obs. data only) and Rw =0.1530 (F2,
all data); GOF=1.083.
of a 1.6m solution in hexane was purchased from Aldrich Chemicals and
[13]
used as received. n-Butylsodium[25] and Mg
ACHTUNGRTNE(UNG CH2SiMe3)2 were prepared
Acknowledgements
by using literature methods. All NMR spectra were measured on a
Bruker DPX500 spectrometer. For the X-ray structural determinations,
all data were collected with monochromated MoKa radiation (l=
0.71073 ꢂ) at 123 K and were measured on an Oxford Diffraction Xcali-
bur S instrument. CCDC-772560 (3) and 772561 (4) contain the supple-
mentary crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre via
The authors thank the EPSRC and Royal Society/Wolfson Foundation
(research merit award to R.E.M.) for generously supporting this work.
Keywords: magnesium
·
metalation
·
sodium
·
tetrahydrothiophenes · thiophenes
Synthesis of 3: nBuNa (0.08 g, 1 mmol) was suspended in dry n-hexane
(20 mL) in a dried Schlenk tube, and placed in an ultrasonic bath for
10 min. MgACHTUNGTRENNUNG(CH2SiMe3)2 (0.20 g, 1 mmol) was added along with TMEDA
[2] a) J. B. Sperry, D. L. Wright, Curr. Opin. Drug Discovery Dev. 2005,
8, 723; b) T. Eicher, S. Hauptmann, The Chemistry of Heterocycles,
2nd ed., Wiley-VCH, Weinheim, 2003.
(0.31 mL, 2 mmol) to this white suspension to give a colourless, homoge-
neous solution. Thiophene (0.24 mL, 3 mmol) was subsequently added
and the resultant pale yellow solution was allowed to stir at ambient tem-
perature for 3 h. The yellow solution was filtered and the solvent volume
was reduced by a quarter in vacuo. The solution was placed in a refriger-
ator operating at 58C. After two weeks, a crop of colourless plate crystals
was deposited (yield, 0.28 g, 53%). 1H NMR (500 MHz, C6D6, 300 K):
d=8.02 (brs, 1H; Ha), 7.94 (brs, 1H; Ha), 7.88 (brs, 2H; 2ꢃHg), 7.78
(brs, 1H; Hg), 7.77 (brs, 1H; Ha), 7.62 (brs, 1H; Hb), 7.53 (brs, 1H; Hb),
7.43 (brs, 1H; Hb), 2.01 (brs, 12H; CH3-TMEDA), 1.88 (brs, 4H; CH2-
TMEDA), 1.59 (brs, 12H; CH3-TMEDA), 1.53 ppm (brs, 4H; CH2-
TMEDA); 13C NMR (125 MHz, C6D6, 300 K): d=169.1 (q, C-Mg thio-
phene), 167.4 (q, C-Mg thiophene), 167.4 (C-Hg), 136.6 (3ꢃC-Ha), 130.9
(C-Hg), 128.5 (C-Hb), 128.0 (C-Hb), 127.9 (C-Hb), 56.6 (CH2-TMEDA),
46.5 (CH3-TMEDA), 45.1 (CH3-TMEDA).
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Lee, D. K. Tosh, A. Patel, K. K. Palaniappan, Z. G. Gao, K. A. Ja-
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Synthesis of 4: TMPH (0.34 mL, 2 mmol) was added to a suspension of
BuNa (0.08 g, 1 mmol) in dry n-hexane (20 mL) and the resultant mixture
was stirred at room temperature for 1 h. MgACHTUNRTGNE(UNG CH2SiMe3)2 (0.20 g, 1 mmol)
and TMEDA (0.15 mL, 1 mmol) were then introduced to give a pale
yellow solution. Tetrahydrothiophene, (0.08 mL, 1 mmol) was added and
the solution was allowed to stir at room temperature for 1 h. The pale
yellow solution was filtered and placed directly in a refrigerator operat-
ing at 58C. After one week colourless block crystals were obtained
(0.18 g, 34%).1H NMR (500 MHz, [D8]THF, 300 K): d=2.93 (m, 1H;
Hb’-THT), 2.62 (m, 1H; Ha’-THT), 2.49 (m, 1H; Ha’-THT), 2.18 (m, 1H;
Hb’-THT) 1.93 (brs, 4H; g-TMP), 1.77 (s, 13H; CH3-TMEDA+Hb-
THT), 1.71 (s, 4H; CH2-TMEDA), 1.58 (brs, 24H; CH3-TMP), 1.41 (m,
8H; b-TMP), 1.91 (m, 1H; Hb-THT), 0.93 (dd, 1H; Ha-THT); 13C NMR
(125 MHz, C6D6, 300 K): d=57.2 (CH2-TMEDA), 52.2 (q-TMP), 46.2
(CH3-TMEDA), 42.5 (C-Hbꢀ THT), 42.4 (b-CH2-TMP), 35.7 (CH3-TMP),
31.9 (C-Hb THT), 31.8 (C-Ha +Haꢀ THT), 20.3 (g-CH2 TMP).
and references therein.
Reaction of 3 with iodine: I2 (2 mL of 1m solution in THF) was added to
a solution of 3 (0.22 g, 0.4 mmol) in hexane (10 mL), and the solution
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Chem. Eur. J. 2010, 16, 8600 – 8604
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8603