Palladium-Catalyzed Carbonylative Coupling and C–H Activation - New Trends in Cross-Coupling: Theory and Applications - page 497

O

I

O

Pd(PPh 3 ) 4 (4 mol%)
anisole, 80 °C
CO (1 bar)

O

N
H

N

N

O

O

Scheme 10.41 Pd-catalysed carbonylative synthesis of indoxyls.

O

PdCl 2 (PPh 3 ) 2 (5 mol%)
Et 2 NH (3ml), 120 °C
CO (20 bar)

X

11 examples
55-95%

R

NH 2

N
H

R

X=I,Br

Scheme 10.42 Pd-catalysed carbonylative synthesis of quinolines.

O

Pd(PPh 3 ) 4 (2 mol%)
anisole, 80 °C
CO (1 bar)
MeCO 2 K

I

4 examples
15-75 %

R R

X

X

Scheme 10.43 Pd-catalysed carbonylative synthesis of indenones.

terminal alkynes. As early as 1990, Chiusoli and co-workers reported the
palladium-catalysed synthesis of indoxyl derivatives (Scheme 10.41). 52
Shortly afterwards, Torii and co-workers reported a novel methodology for
the synthesis of quinolines. 53a,b Quinolines were produced in good yields via
palladium-catalysed carbonylation of 2-haloaniline with terminal alkynes in
the presence of CO (Scheme 10.42).
When the amino group of the 2-haloaniline substrate is primary, the
cyclization proceeds without problems, but when using alkylated anilines
under the same conditions, the yield of the corresponding cyclization
product decreases dramatically. A similar methodology was reported in 1992
by Kalinin and co-workers using PdCl 2 (dppf) as palladium precusor. 53c This
cyclization was applied to synthesize the quinolone substructure of BILN
2061, a serine protease inhibitor. 53d In the same year, Chiusoli and co-
workers published an interesting methodology for indenone synthesis. 54
Sequential oxidative addition of o-alkoxycarbonylmethylene or alkylamido-
methylene-substituted aryl iodides, CO insertion, reductive coupling with
terminal alkynes, nucleophilic attack by the activated methylene group and
protonation with metal elimination afforded the indenones in high yields in
a one-pot process (Scheme 10.43).
In 2000, Miao and Yang reported a novel method for the preparation of
flavones. 55 Various flavones are easily synthesized via palladium-catalysed
carbonylative annulation of iodophenol acetates with terminal acetylenes in
high yields (Scheme 10.44). This novel reaction provides the possibility for a
combinatorial synthesis of flavones on solid supports.