Angewandte
Chemie
(Eds.: Z. Rappoport, I. Marek), Wiley, New York, 2004, chap. 1,
ric amount of base 5b (1.1 equiv) in THF (À258C, 0.5 h)
leading regioselectively to the arylmagnesium species 30 and
31, which after reaction with electrophiles furnished the
polyfunctional aromatic derivatives 32 and 33 in 83–88%
yields. (Scheme 4)
In summary, we have prepared new mixed Mg/Li-bases of
the general type R2NMgCl·LiCl which have a high kinetic
activity because of the presence of LiCl which, we tentatively
propose, breaks up oligomeric aggregates of magnesium
amides. The use of TMPMgCl·LiCl, which has an excellent
solubility and is stable for more than 6 months as THF
solution at 258C, allows the regioselective functionalization of
various aromatic and heteroaromatic compounds. It provides
access to new magnesium species not readily available by Br/
Mg-exchange reactions or previously reported metalation
procedures. Extensions of this method are currently under-
way in our laboratories.
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Experimental Section
1) Synthesis of 5b: A dry and argon-flushed 250-mLSchlenk flask,
equipped with a magnetic stirring bar and a septum, was charged with
freshly titrated iPrMgCl·LiCl (100 mL, 1.2m in THF, 120 mmol).
TMPH (19.8 g, 126 mmol, 1.05 equiv) was added dropwise at room
temperature. The reaction mixture was stirred at room temperature
until gas evolution ceased (ca. 24 h).
2) Typical procedure: Synthesis of 7a: A dry and argon-flushed
10-mLSchlenk flask, equipped with a magnetic stirring bar and a
septum, was charged with 5b (5 mL, 1.2m in THF, 6.0 mmol).
Isoquinoline (703 mg, 5.45 mmol) in THF (5 mL) was added dropwise
at room temperature. During the addition the reaction mixture
became red, and the metalation was complete after 2 h. (The reaction
progress was checked by removal of reaction aliquots, which were
quenched with a solution of I2 in THF and analyzed by GC; the
conversion was more than 98%.) A solution of I2 in THF (6 mL, 1.0m
in THF, 6.0 mmol) was slowly added at À208C. The reaction mixture
was quenched with sat. aqueous solution of NH4Cl (10 mL). The
aqueous layer was extracted with diethyl ether (4 10 mL), and the
combined extracts were dried with Na2SO4 and concentrated in
vacuo. The crude residue was purified by filter column chromatog-
raphy (silica; CH2Cl2/pentane) affording 7a (1.33 g, 92%) as slightly
yellow crystals (m.p. 74–768C).
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Received: November 11, 2005
Published online: March 28, 2006
Keywords: amides · Ggrignard reagents · heterocycles
.
functionalization · lithium chloride · magnesium amides ·
mixed bases · regioselective metalation
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Angew. Chem. Int. Ed. 2006, 45, 2958 –2961ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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