synthesis and catalytic functionalization of biologically active indoles

1 Palladium-catalyzed Coupling Reactions of Indoles 48
the 2-alkynylindole derivative 153 in a yield of 78%. Under Sonogashira standard
conditions with Pd(PPh3)4, CuI and Et3N they got the key intermediate 153 for the
construction of the aspidosperma skeleton.
A further application in synthesis of natural structures is the study towards the
marine alkaloid chartelline C 161 by Magnus et al.. [121] The authors developed a
regioselective Sonogashira coupling of 2,6-dibromoindole at the 2-position with
simple acetylenic partners (Scheme 40). The authors were interested to see if a
2,6-dibromoindole 156 exhibited any selectivity in Songashira coupling reaction.
Scheme 40 shows the conversion of the dibrominated indole 156 with different
alkynes with complete regioselectivity to the 2-coupled indoles 157a-c in good
yields under standard Sonogashira coupling reaction conditions. Therefore the
choice of the protecting group on the indole nitrogen atom was essential for
achieving regioselectivity in Sonogashira coupling reaction.
Br
CN
CN
PdCl2(PPh3) 2
CuI, NEt3, 45 °C
Br
R
N
N
R
Br
Boc
Boc
156 157a-c
157a R = TIPS (92%)
157b R = iPr (67%)
157c R = -C6H4OMe-p (45%)
Scheme 40. Sonogashira coupling of 2,6-dibromoindole derivative.
The authors applied their findings in the synthesis of chartelline C analogue 160
subsequently. Scheme 41 outlined the development to the desired compound 160
in the presence of the dibrominated indole 156 and the complex alkyne 158. The
desired compound 159 was obtained in a yield of 67%. The regioselective
Sonogashira coupling reaction was used to synthesize the 2-isoprene-imidazole
chain whereas the imidazol was constructed after coupling reaction.