Communications
raphy (n-pentane/diethyl ether 20:1) furnished
the thioether 6g as a yellow solid (220 mg,
75%).
Preparation of 7d: A dry and argon-
flushed 25-mL Schlenk flask, equipped with a
Table 2: Synthesis of tertiary amines of type 7 by the addition of magnesium amides 3 to benzyne
followed by the trapping of the intermediate Grignard reagent 5 with an electrophile.
Entry
3
Electrophile
7
Yield [%][a]
magnetic stirring bar and
a septum, was
charged with a solution of N-methylaniline
(107 mg, 1.0 mmol) in dry THF (3 mL). This
solution was cooled to À208C, iPrMgCl
(0.94 mL, 1.0 equiv, 1.07m in THF) was added
dropwise, and the reaction mixture was stirred
for 30 min. The reaction mixture was cooled to
À788C, and iPrMgCl (0.94 mL, 1.0 equiv,
1.07m in THF) was added. A solution of 1a
(394 mg, 1.0 mmol) in dry THF (2 mL) was
added, and the reaction mixture was stirred
vigorously for 30 min at the same temperature.
The resulting mixture was immediately
warmed to 08C and stirred for 10 min. Then,
the reaction mixture was cooled to À408C, and
DMF (0.20 mL, 2.5 equiv) was added. There-
after, the reaction mixture was warmed to
room temperature and stirred for 1 h. The
reaction was quenched with sat. aq. NH4Cl
solution and extracted with CH2Cl2 (3 ꢀ
40 mL). The combined organic phases were
dried over anhydrous Na2SO4 and filtered, and
the solvent was removed by evaporation in
vacuo. Purification by flash chromatography
(n-pentane/diethyl ether 250:1) furnished the
amino aldehyde 7d as a yellow oil (156 mg,
74%).
1
2
3
4
Ph(Me)NMgCl (3a)
7a: R=allyl
83
85
80
74
PhCOCl
PhCHO
DMF
7b: R=COPh
7c: R=CH(OH)OPh
7d: R=CHO
5
Ph(Bn)NMgCl (3b)
DMF
71
6
7
3c
3c
7 f: R=allyl
7g: R=COEt
66
62
EtCOCl
DMF
8
25
Received: February 5, 2005
Published online: June 7, 2005
Keywords: amination · arynes · Grignard
.
reagents · heterocycles · thioethers
9
10
3e
3e
DMF
EtCOCl
7i: R=CHO
7j: R=COEt
73
76
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benzyne.
added dropwise, and the reaction mixture was stirred for 10 min. A
solution of 1a (394 mg, 1.0 mmol) in dry THF (2 mL) was added, and
the reaction mixture was stirred vigorously for 30 min at the same
temperature. The resulting mixture was immediately warmed to 08C
and stirred for 10 min. Then the reaction mixture was cooled to
À408C, and DMF (0.20 mL, 2.5 equiv) was added. Thereafter, the
reaction mixture was warmed to room temperature and stirred for
1 h. The reaction was quenched with sat. aq. NH4Cl solution and
extracted with CH2Cl2 (3 ꢀ 40 mL). The combined organic phases
were dried over anhydrous Na2SO4 and filtered, and the solvent was
removed by evaporation in vacuo. Purification by flash chromatog-
[5] For excellent reviews, see: a) J. Sauer, R. Huisgen, Angew.
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4260
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2005, 44, 4258 –4261