Periodinane-Mediated Cyclization of Anilides 265
Cyclization step as rate-determining
N
O
II
N
O
CH 2
R
slow ?
Before making a decision, it would be necessary to confirm whether cyclization
step II to III is sensitive or not to the electronic effects of the substituents in the
aromatic ring.
In this case, the information was taken from the study of the n-Bu 3 SnH-mediated cyclization of substituted N-(phenylthio)amides N N
8, detailed in Scheme 39.6.
The reaction is a radical process in which the nitrogen-centered radical 11 formed
in the first instance, cyclizes onto the C=C double bond to give carbon-centered
radical species 13 which, after quenching, yields cyclized compound 9. The cyclization step follows the exo-mode in agreement with the Baldwin rules (5-exo-trig).
R
PhSN
O
AIBN
R
N
O
N
R
O
H
H
H
N
R
O
H
H
5-exo-trig
8
R
relative rates
H
0.66
MeO 0.30
F
0.40
COMe >0.40
CF 3
—
9
11
13
n-Bu 3 SnH
Scheme 39.6
From the comparison of the relative cyclization rate values of substituted anilides 8, it is clear that there is no relationship between the electronic character of
the substituents and the reaction rate. Both electron-donating and electronwithdrawing substituents decrease the rate of the cyclization of 8 relative to that of
the unsubstituted substrate. Since the opposite trend is experimentally observed in
Cyclization step as rate-determining
N
O
II
N
O
CH 2
R
slow ?
Before making a decision, it would be necessary to confirm whether cyclization
step II to III is sensitive or not to the electronic effects of the substituents in the
aromatic ring.
In this case, the information was taken from the study of the n-Bu 3 SnH-mediated cyclization of substituted N-(phenylthio)amides N N
8, detailed in Scheme 39.6.
The reaction is a radical process in which the nitrogen-centered radical 11 formed
in the first instance, cyclizes onto the C=C double bond to give carbon-centered
radical species 13 which, after quenching, yields cyclized compound 9. The cyclization step follows the exo-mode in agreement with the Baldwin rules (5-exo-trig).
R
PhSN
O
AIBN
R
N
O
N
R
O
H
H
H
N
R
O
H
H
5-exo-trig
8
R
relative rates
H
0.66
MeO 0.30
F
0.40
COMe >0.40
CF 3
—
9
11
13
n-Bu 3 SnH
Scheme 39.6
From the comparison of the relative cyclization rate values of substituted anilides 8, it is clear that there is no relationship between the electronic character of
the substituents and the reaction rate. Both electron-donating and electronwithdrawing substituents decrease the rate of the cyclization of 8 relative to that of
the unsubstituted substrate. Since the opposite trend is experimentally observed in