synthesis and catalytic functionalization of biologically active indoles

1 Palladium-catalyzed Coupling Reactions of Indoles 18
The conversion of bromovindoline 57 with pinacol boronate (Table 4, entry 14) is
particularly interesting. With the availability of vindoline boronate, it should be
possible to use a vast array of commercially available aryl and vinyl halides to
prepare innumerable analogues of vindoline.
Indole alkaloids containing a pyrrolophenanthridinone core have been the subject
of many synthetic studies due to their interesting biological activities. [54] This family
of alkaloids is exemplified by hippadine 61 and pratosine 62 (Scheme 12).
Br
N
H
RO
X
OR
59 60a X = Br
60b X = I
CO 2Me
(i) one pot metalation
(ii) cross-coupling
(iii) lactamization
ligand C
PCy 2
Scheme 12. General reaction sequence to indole alkaloids.
N
O
RO
OR
61 Hippadine R = -CH2- 62 Pratosine R = Me
Previous synthesis of hippadine 61 required a series of additional synthetic
transformation either before or after the construction of the ring system. The total
synthesis of hippadine by a tandem metalation/cross-coupling/lactamization
strategy starting from 7-bromoindole 59 was investigated by T�nder and
colleagues. [55] As shown in Scheme 12, the pyrrolophenanthridinone ring system
was formed by a series of steps, (i) metalation, of either two coupling partners 59
or 60a, 60b, followed by (ii) a transition-metal-catalyzed cross-coupling, and finally
a base-mediated lactamization. Inspired by an elegant intermolecular tandem
palladium-catalyzed Suzuki-Miyaura coupling [56] and the corresponding
intramolecular Stille variant [57] , the metalation of 7-bromoindole 59 was
investigated. It was not possible to introduce zinc, magnesium or tin into the indole
7-position. They assumed that the unprotected indole nitrogen was responsible for
the problems so the magnesiation and stannylation were tested with benzylprotected
7-bromoindole without success again.