Palladium-Catalyzed Cross-Alkynylation of Aryl Bromides
TABLE 3. P a lla d iu m -Ca ta lyzed Cr oss-Alk yn yla tion of Som e P olybr om oa r en es by Com p lexes 1 a n d 2a
a
b
Reaction conditions as in Table 1 except that the amount of reagent was adjusted to the number of bromine atoms. Isolated yield.
mmol of PdCl2(PPh3)2 for 7 h at reflux. Thereafter, 7.5
mmol of [Me2AlOCH2CH2NMe2]2 and 0.38 mmol NiCl2-
(PPh3)2 were added. Heating at reflux for an additional
12 h gave 41% of 4-MeC6H4CtCPh.
suggests that the cross-alkynylation is not restricted to
aryl bromides alone.
Exp er im en ta l Section
The sodium tetraalkynylaluminates were also shown
to cross-couple with a variety of heteroaryl bromides.
Some typical experiments are listed in Table 2. This
observation is noteworthy, since other stable aluminum-
derived alkylating and alkynylating reagents such as R2-
Al(CH2)3NMe2 (R ) alkyl, alkynyl) studied in our labo-
ratory11 failed to cross-couple with nitrogen-containing
heterocycles.
Gen er a l P r oced u r e for Cr oss-Alk yn yla t ion of Ar yl
Br om id es. Typically, to a solution of 0.4 mmol of the ap-
propriate sodium tetraalkynylaluminate (either solution of the
isolated reagent or of the in situ prepared compound) in dry
degassed THF or DME (2 mL), was added under Ar atmo-
sphere, 1.2 mmol of the monobromoarene and 3.7 × 10-2 mmol
of PdCl2(PPh3)2 in an amount of solvent that gave a 0.1 M
solution of the substrate. The solution was heated at reflux
Entry 6 in Table 2 indicates that by using the exact
amount of NaAl(CtCR)4 required for the replacement of
one of the two bromine atoms of 2,5-dibromopyridine
(reagent/substrate ) 1:4) it is possible to obtain selec-
tively the 2-alkynyl-5-bromopyridine free of even traces
of the dialkynyl product. When excess reagent is em-
ployed, however, both halogen atoms are affected (see
Table 3, entry 2). In fact, the sodium tetraalkynylalumi-
nates are excellent reagents for complete cross-alkynyl-
ation of polybromoarenes. Several cross-coupling experi-
ments of di-, tri-, and tetrabromoarenes are summarized
in Table 3. Finally, it should be noted that under the
conditions of Table 1 reagent 1 couples with PhC(Br)d
CH2 to give within 12 h 47% of PhC(CtCPh)dCH2.16 This
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