synthesis and catalytic functionalization of biologically active indoles

1 Palladium-catalyzed Coupling Reactions of Indoles 59
Br
N
CH 3
CH 2
Ph
NH
Ph
Pd 2(dba) 3 (2 mol%)
ligand H (0.5 mol%)
tBuONa (3 equiv)
toluene, N 2, 100 °C, 24 h
O
O
183 184 185(99%)
iPr
iPr
ligand H
Scheme 47. Palladium-catalyzed amination of a 5-bromoindole derivative with benzophenone
imine.
Under optimized reaction conditions in the presence of 2 mol% Pd2(dba)3 and 1,8bisdiisopropylphosphinotriptycene
H as catalytic system, tert-BuONa as base, the
according product 185 was isolated in a yield of 99%. Fascinating compounds like
183 were effectively aminated by benzophenone imine 184 and led to interesting
new structures that represent important building blocks for construction of sensors
(anthracene-1,8-diamine) [134] and molecular switches (indole derivatives) [135] .
A further application of Buchwald-Hartwig coupling reaction was described by
Ganton and Kerr in total synthesis of the (±)-CC-1065 CPI subunit. [136] CC-1065
and the related compounds like duocarmycins are members of a structurally
unique family of naturally occurring molecules and remain some of the most
rigorously studied antitumor compounds to date. Their derivatives remain as some
of the strongest candidates for new exceptionally potent and highly selective
therapeutic agents against tumorigenic cells. Structurally CC-1065 consists of two
identical central and eastern pyrrolo[3,2-e] indole-4-one subunits linked together to
the western subunit by amide bonds through pyrrolidine nitrogen. The key steps of
the synthesis were a Diels-Alder reaction and a palladium-catalyzed intramolecular
aryl triflate amidation. Scheme 48 pictured two selected examples of the
intramolecular amidation.
Ph
Ph
N
N
CH 3
CH 3