L Le ev ve el l 3 3 C Ca as se e 3 39 9
P Pe er ri io od di in na an ne e- -M Me ed di ia at te ed d C Cy yc cl li iz za at ti io on n o of f A An ni il li id de es s
K Ke ey y p po oi in nt t: : R Ra Ra Ra Ra Ra R Rad di di di d di di d dic ic ic ic i i a al l c cy cy cy yc yc y yc yc yc yc y y l li li li l li li l liz i iz i i iz i i a
za z za za za za z zat ti ti ti t ti ti t tio io io io i ion n r re re r re re re re r rea ac ct ti ti ti t ti ti t tio io io io i ion n. . S SE ET T
N
H
O
IBX
'
R
O
Me
N
THF/DMSO (10/1)
P Pe er ri io od di in na an ne e- -M Me ed di ia at te ed d C Cy yc cl li iz za at ti io on n o of f A An ni il li id de es s
Anilides 1 cyclize to J-lactams 2 by reaction with an hypervalent iodine reagent
y y
(1-hydroxy-1,2-benziodoxol-3(1H)-one-1-oxide, IBX) under the conditions shown
H H
in Scheme 39.1.
N
H
O
IBX
IBX
O
I
O
O
HO
'
R
N
O
Me
R
1
2
THF/DMSO (10/1)
Scheme 39.1
To explain these IBX-mediated ring closures, a stepwise radical mechanism has
been proposed. The first step consists of a single electron transfer (SET) process
from the substrate to the periodinane, leading to radical cation I which is converted into amidyl radical II after deprotonation. Cyclization of II in a 5-exo-trig
fashion provides a carbon-centered radical species III, which is quenched by the
transfer of a hydrogen radical in the termination step (Scheme 39.2).
P Pe er ri io od di in na an ne e- -M Me ed di ia at te ed d C Cy yc cl li iz za at ti io on n o of f A An ni il li id de es s
K Ke ey y p po oi in nt t: : R Ra Ra Ra Ra Ra R Rad di di di d di di d dic ic ic ic i i a al l c cy cy cy yc yc y yc yc yc yc y y l li li li l li li l liz i iz i i iz i i a
za z za za za za z zat ti ti ti t ti ti t tio io io io i ion n r re re r re re re re r rea ac ct ti ti ti t ti ti t tio io io io i ion n. . S SE ET T
N
H
O
IBX
'
R
O
Me
N
THF/DMSO (10/1)
P Pe er ri io od di in na an ne e- -M Me ed di ia at te ed d C Cy yc cl li iz za at ti io on n o of f A An ni il li id de es s
Anilides 1 cyclize to J-lactams 2 by reaction with an hypervalent iodine reagent
y y
(1-hydroxy-1,2-benziodoxol-3(1H)-one-1-oxide, IBX) under the conditions shown
H H
in Scheme 39.1.
N
H
O
IBX
IBX
O
I
O
O
HO
'
R
N
O
Me
R
1
2
THF/DMSO (10/1)
Scheme 39.1
To explain these IBX-mediated ring closures, a stepwise radical mechanism has
been proposed. The first step consists of a single electron transfer (SET) process
from the substrate to the periodinane, leading to radical cation I which is converted into amidyl radical II after deprotonation. Cyclization of II in a 5-exo-trig
fashion provides a carbon-centered radical species III, which is quenched by the
transfer of a hydrogen radical in the termination step (Scheme 39.2).