"Front Matter". In: Organosilanes in Radical Chemistry - Index of

Application to Tandem and Cascade Radical Reactions 177
The plan for a tandem cyclization as the key step in the synthesis of morphine
alkaloids has been successfully performed [95]. Three examples are given in
Scheme 7.10. Specifically, the initially formed aryl radical, generated by bromine
abstraction from compound 74, underwent a tandem cyclization to construct
the desired carbocyclic skeleton. Depending on the nature of the Z
substituent to the double bond, the product radicals either abstracted hydrogen
from silane (Z ¼ CO2Me or CN) or eliminated thiyl radical (Z ¼ SPh).
MeO
O
H
H
H Z
(TMS) 3SiH
MeO
AIBN, 125 �C
Z = CO2Me or CN
O
Br
74
Z
(TMS) 3SiH
AIBN, 125 �C
Z = SPh
MeO
45% 85%
Scheme 7.10 Examples of tandem radical cyclizations
Novel bridged spirolactones have been synthesized via tandem radical cyclizations
of enol ether radical. In Reaction (7.85) the first 5-exo spirocyclization
is followed by a 6-endo cyclization to give the bridged derivative as a single
diastereoisomer [96].
O
O
Br
(TMS) 3SiH
AIBN, 80 �C
O O H
Me
O
76%
O
O
H
H
H
(7.85)
Tandem strategies have been successfully applied to synthesis of indole
alkaloids, starting from aryl radical generation [97–99]. Iodoarylazides have
been thoroughly used in protocols where the aryl radical formation is coupled
with radical addition to alkenes and eventually a further cyclization onto an
azide, with the elimination of nitrogen gas, as a driving force. The skeletons of
( )-horsfiline, ( )-aspidospermidine and ( )-vindoline have been achieved by
this route. For example, cyclization of the iodoarylazide, such as 75, mediated
by (TMS) 3SiH under standard experimental conditions, produced the
N w Si(TMS) 3 protected alkaloid 76, which after washing with dilute acid
afforded the amine 77 in an overall 83 % yield from 75 (Reaction 7.86). The